Miracle-dz/UniFAR-FTUs huggingface dataset:
Mode-of-action analysis for induction of rat liver tumors by pyrethrins: relevance to human cancer risk

High doses of pyrethrins have been shown to produce liver tumors in female rats. Pyrethrins are not genotoxic agents. Pyrethrins produce liver tumors in rats by a mode of action (MOA) involving induction of hepatic xenobiotic metabolising enzymes, hypertrophy, increased cell proliferation, and the development of altered hepatic foci. The relevance of pyrethrins-induced rat liver tumors to human health was assessed by using the 2006 International Programme on Chemical Safety Human Relevance Framework. The postulated rodent tumor MOA was tested against the Bradford Hill criteria and was found to satisfy the conditions of dose and temporal concordance, biological plausibility, coherence, strength, consistency, and specificity that fit with an established mode of action for rodent liver tumor formation by phenobarbital and related compounds, which are activators of the constitutive androstane receptor. Other possible MOAs including mutagenicity, cytotoxicity, hepatic peroxisome proliferation, porphyria, and hormonal pertubation were excluded. The proposed MOA is considered not to be plausible in humans because pyrethrins, like phenobarbital, do not induce cell proliferation in human hepatocytes. Moreover, epidemiological studies with phenobarbital demonstrate that such compounds do not increase the risk of liver tumors in humans. It is concluded that pyrethrins do not pose a hepatocarcinogenic hazard for humans.
Normalization rates of compression ultrasonography in patients with a first episode of deep vein thrombosis of the lower limbs : association with DVT recurrence and new thrombosis

Background and Objectives. Delayed thrombus regression after a first episode of deep vein thrombosis (DVT) of the inferior limbs has been implicated in the development of the post-thrombotic syndrome. Whether normalization of vein segments involved in the index DVT has prognostic significance with respect to the probability of DVT recurrence or new thrombosis is currently unknown. In this study, we prospectively monitored thrombus regression in consecutive patients with symptomatic and asymptomatic DVT. Factors affecting normalization rates and the relationship between previous normalization and DVT recurrence or new thrombosis were explored.
Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy.

PURPOSE To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.
Comparison of Middle Ear Visualization With Endoscopy and Microscopy

Introduction: The primary goal of chronic ear surgery is the creation of a safe, clean dry ear. For cholesteatomas, complete removal of disease is dependent on visualization. Conventional microscopy is adequate for most dissection, but various subregions of the middle ear are better visualized with endoscopy. Objective: The purpose of the present study was to quantitatively assess the improved visualization that endoscopes afford as compared with operating microscopes. Methods: Microscopic and endoscopic views were simulated using a three-dimensional model developed from temporal bone scans. Surface renderings of the ear canal and middle ear subsegments were defined and the percentage of visualization of each middle ear subsegment, both with and without ossicles, was then determined for the microscope as well as for 0-, 30-, and 45-degree endoscopes. Using this information, we analyzed which mode of visualization is best suited for dissection within a particular anatomical region. Results: Using a 0-degree scope provides significantly more visualization of every subregion, except the antrum, compared with a microscope. In addition, angled scopes permit visualizing significantly more surface area of every subregion of the middle ear than straight scopes or microscopes. Conclusions: Endoscopes offer advantages for cholesteatoma dissection in difficult-to-visualize areas including the sinus tympani and epitympanum.
INSTRUCTIONAL DESIGN AND ASSESSMENT Evaluation of an Online Tobacco Cessation Course for Health Professions Students

Objective. To implement and evaluate the impact of a semester-long, online, 1-credit elective course designed to promote tobacco cessation counseling proficiency among health professions students. Design. Online technology was used to create an elective course devoted to tobacco cessation, modeled closely after the Rx for Change curriculum. Students from pharmacy, nursing, and other health disciplines enrolled in the course. Assessment. Students completed pretraining and posttraining survey instruments that assessed their self-reported skills and ability to counsel patients for tobacco cessation. Overall ability to counsel for tobacco cessation and each of the ‘‘5 A’s’’ approach for comprehensive counseling (ask, advise, assess, assist, arrange) increased significantly from pretraining to posttraining (p , 0.001). Self-efficacy also increased from 2.2 to 4.1 (p , 0.001; on a 5-point scale). Conclusion. This study demonstrated that an online tobacco cessation course improved studentreported ability and skills to counsel patients on tobacco cessation.
Broad T cell immunity to the LcrV virulence protein is induced by targeted delivery to DEC‐205/CD205‐positive mouse dendritic cells

There is a need for a more efficient vaccine against the bacterium Yersinia pestis, the agent of pneumonic plague. The F1‐LcrV (F1‐V) subunit vaccine in alhydrogel is known to induce humoral immunity. In this study, we utilized DC to investigate cellular immunity. We genetically engineered the LcrV virulence protein into the anti‐DEC‐205/CD205 mAb and thereby targeted the conjugated protein directly to mouse DEC‐205+ DC in situ. We observed antigen‐specific CD4+ T cell immunity measured by intracellular staining for IFN‐γ in three different mouse strains (C57BL/6, BALB/c, and C3H/HeJ), while we could not observe such T cell responses with F1‐V vaccine in alhydrogel. Using a peptide library for LcrV protein, we identified two or more distinct CD4+ T cell mimetopes in each MHC haplotype, consistent with the induction of broad immunity. When compared to nontargeted standard protein vaccine, DC targeting greatly increased the efficiency for inducing IFN‐γ‐producing T cells. The targeted LcrV protein induced antibody responses to a similar extent as the F1‐V subunit vaccine, but Th1‐dependent IgG2a and IgG2c isotypes were observed only after anti‐DEC‐205:LcrV mAb immunization. This study sets the stage for the analysis of functional roles of IFN‐γ‐producing T cells in Y. pestis infection.
Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia.

BACKGROUND The diagnosis and treatment of bacterial pneumonia in patients who are receiving mechanical ventilation remain a difficult challenge. The triggering receptor expressed on myeloid cells (TREM-1) is a member of the immunoglobulin superfamily, and its expression on phagocytes is specifically up-regulated by microbial products. The presence of soluble TREM-1 (sTREM-1) in bronchoalveolar-lavage fluid from patients receiving mechanical ventilation may be an indicator of pneumonia. METHODS We conducted a prospective study of 148 patients receiving mechanical ventilation in whom infectious pneumonia was suspected. A rapid immunoblot technique was used to measure sTREM-1 in bronchoalveolar-lavage fluid. Two independent intensivists who were unaware of the results of the sTREM-1 assay determined whether community-acquired pneumonia and ventilator-associated pneumonia were present or absent. RESULTS The final diagnosis was community-acquired pneumonia in 38 patients, ventilator-associated pneumonia in 46 patients, and no pneumonia in 64 patients. The presence of sTREM-1 by itself was more accurate than any clinical findings or laboratory values in identifying the presence of bacterial or fungal pneumonia (likelihood ratio, 10.38; sensitivity, 98 percent; specificity, 90 percent). In multiple logistic-regression analysis, the presence of sTREM-1 was the strongest independent predictor of pneumonia (odds ratio, 41.5). CONCLUSIONS In patients receiving mechanical ventilation, rapid detection of sTREM-1 in bronchoalveolar-lavage fluid may be useful in establishing or excluding the diagnosis of bacterial or fungal pneumonia.
Laparoscopic donor nephrectomy: effect of perirenal fat upon donor operative time.

PURPOSE Previous attempts to correlate preoperative patient characteristics with operative complexity and operative time prior to laparoscopic donor nephrectomy have found few consistent relationships. The purpose of this study is to determine the effect of abdominal and perirenal fat measured with preoperative computerized tomography (CT) upon subsequent operative time and complexity during hand-assisted laparoscopic donor nephrectomy. MATERIALS AND METHODS A retrospective chart, database, and CT angiogram review was conducted on 103 consecutive patients who underwent a hand-assisted laparoscopic donor nephrectomy. Perirenal fat and abdominal wall fat were correlated with a variety of parameters including operative time. Univariate and multivariate regression analysis was performed and p values<0.05 were considered significant. RESULTS There was no correlation between operative time and body mass index (BMI), abdominal fat measurements, or spleno-renal distance. There was a significant positive correlation between operative time and anterior perirenal fat (r=0.28, p=0.005), posterior perirenal fat (r=0.20, p=0.05), and donor CPK levels (r=0.53, p<0.001). Men had greater perirenal fat, while women had greater abdominal fat. A multivariate model including anterior perirenal fat measurement accounted for 20% of the variance in operative time. CONCLUSION This is the first study to demonstrate that increased perirenal fat increases operative complexity as measured by operative time. This information may potentially be used to help predict operative complexity based upon measurable preoperative variables and help improve operating room efficiency and donor and recipient outcomes.
Retinopathy of prematurity in a south Australian neonatal intensive care unit.

PURPOSE To establish the incidence and severity of retinopathy of prematurity (ROP) in an Australian population of premature infants, and define risk factors for this population. METHODS A survey of neonates born weighing less than 1501 g and/or with gestational age below 33 weeks, was undertaken at a neonatal intensive care unit in South Australia. RESULTS ROP was diagnosed in 16.0% of the 94 neonates who were screened until retinal vascularisation was complete. Threshold disease occurred in 4.2%. Logistic regression identified three significant risk factors for the development of ROP: days of mechanical ventilation, multiple birth and female sex. CONCLUSIONS The incidence of ROP was relatively low when compared with figures recently published for two large populations studied in the United States and England. This difference was due to a lower incidence of mild forms of the disease. Days of mechanical ventilation, multiple birth and female sex were independently predictive of the occurrence of ROP. As small numbers of infants with ROP are managed at individual Australian centres each year, a national ROP register is recommended to facilitate the study of the disease in this country.
Vitamin E Decreases the Occurrence of Malformations in the Offspring of Diabetic Rats

An association between excess oxygen radical activity and disturbed embryogenesis in diabetic pregnancy has been suggested. In the present study, the protective capacity of vitamin E with different treatment regimens was investigated in early and late pregnancy of streptozotocin-induced diabetic rats. Daily gavaging of 0.2 g/kg or 0.8 g/kg of vitamin E exerted moderate protective effects. In contrast, treatment with a diet enriched with 2% (wt/wt) of vitamin E, yielding an approximate daily dosage of 2 g/kg of vitamin E, clearly restored both embryonic and fetal morphology. Highperformance liquid chromatography measurement showed that maternal diabetes decreased embryonic content of vitamin E. When pregnant diabetic animals were supplemented with vitamin E, increased concentrations of the vitamin were found in maternal, embryonic, and fetal tissues. Thus, despite marked accumulation of vitamin E in maternal tissues, the compound apparently reached the conceptus. Thiobarbituric acid reactive substances (TBARS) were estimated as a measure of lipid peroxidation, and no changes were observed in maternal tissue, embryonic tissue, placenta, and fetal brain in the untreated diabetic group. In contrast, a fivefold increase of TBARS was found in fetal liver, a rise that was reduced with vitamin E treatment of the diabetic pregnant rats and completely normalized with 2% vitamin E in the diet. Congenital malformations caused by experimental diabetes can be prevented by antioxidants in vivo. These findings further corroborate the notion that an imbalance in the metabolism of free oxygen radicals is involved in the embryonic maldevelopment of diabetic pregnancy, and suggest a direction for prophylactic treatment in the future.
Formulation and evaluation of sustained release enteric-coated pellets of budesonide for intestinal delivery

Introduction: The aim of present work was to develop intestinal-targeted pellets of Budesonide, a potent glucocorticoid, used for the treatment of ulcerative colitis and Crohn's disease by extrusion and spheronization method. Current available oral formulations of Budesonide have low efficacy because of the premature drug release in the upper part of the gastrointestinal tract. In this study, a pH-controlled intestinal-targeted pellet of budesonide was established using 32 full factorial design by giving an enteric coating with Eudragit S100. Materials and Methods: Budesonide-sustained release pellets were prepared by extruder and spheronization technique using a combination of water-soluble and permeable polymers by applying 32 full factorial design. The pellets were coated by spray coating technique using Eudragit S100 as an enteric polymer. The pellets were characterized for its flowability, sphericity, friability, and in vitro drug release. Release behaviour was studied in different pH media. The release profile was studied for the mechanism of drug release. Result: The optimized formulation showed negligible drug release in the stomach followed by release for 12 h in the intestinal pH. Differential scanning calorimetry and Fourier Transform Infrared Spectroscopy studies indicated no interaction between drug and polymer. Scanning Electron Microscopy image of coated pellets suggested a uniform and smooth coat over the surface of pellets. Accelerated stability studies showed a stable nature of drug in the formulation. All evaluation parameter showed that pellets were good in spherocity and flowability. Conclusion: Sustained release pellets of Budesonide could be prepared by extrusion and spheronization which released the drug in intestinal pH for an intestine to treat inflammatory bowel disease. A ratio of polymer combination could be decided using a full factorial design.
Using Severity-adjusted Mortality to Compare Performance in a Veterans Mffairs Hospital and in Private-sector Hospitals

The objective of this study was to compare hospital mortality in Veterans Affairs (VA) and private-sector patients. The study included 5016 patients admitted to 1 VA hospital. Admission severity of illness was measured using a commercial methodology that was developed in a nation-wide database of 850,000 patients from 111 private-sector hospitals. The method uses data abstracted from patients' medical records to predict the risk of death in individual patients, based on the normative database. Analyses compared actual and predicted mortality rates in VA patients. VA patients had higher (P < .05) severity of illness than private-sector patients. The observed mortality rate in VA patients was 4.0% and was similar (P = .09) to the predicted risk of death (4.4%; 95% confidence interval 4.0-4.9%). In subgroup analyses, actual and predicted mortality rates were similar in medical and surgical patients and in groups stratified according to severity of illness, except in the highest severity stratum, in which actual mortality was lower than predicted mortality (57% vs 73%; P < .001). We found that in-hospital mortality in 1 VA hospital and a nationwide sample of private-sector hospitals were similar, after adjusting for severity of illness. Although not directly generalizable to other VA hospitals, our findings nonetheless suggest that the quality of VA and private-sector care may be similar with respect to one important and widely used measure.
Lifestyle related factors & impact of metabolic syndrome on quality of life, level of functioning & self-esteem in patients with bipolar disorder & schizophrenia

Background & objectives: Though studies have reported high prevalence rates of metabolic syndrome among patients with bipolar disorder (BPAD) and schizophrenia, there is lack of data on the impact of the same on the patients’ life. This study was aimed to assess the lifestyle related factors associated with metabolic syndrome (MetS) and to study the impact of MetS on functioning and quality of life (QOL) in patients with BPAD and schizophrenia. Methods: A total of 102 patients with BPAD and 72 patients with schizophrenia attending the output unit of a tertiary care hospital in north India were evaluated for MetS. These patients were assessed on Health Promoting Lifestyle Profile scale II (HPLP II), World Health Organization QOL -Bref Version (WHOQOL-Bref), Impact of Weight on Quality of Life- Lite version (IWOQOL -Lite), Body weight, Image and Self-esteem Evaluation questionnaire (BWISE), Obesity-related Problem scale (OP scale) and Global Assessment of Functioning (GAF) scale. Results: MetS was associated with lower scores on domains of health responsibility and nutrition habit domain on HPLP-II scale in both groups, and additionally on physical activity and stress management domain in BPAD group. On WHOQOL-Bref, MetS was associated with lower scores on the domains of physical and psychological health in both groups. On IWQOL–Lite, scores on personal distress and self esteem domains were higher in those with obesity in both groups and also on physical activity domain in schizophrenia group. Those with MetS had lower level of functioning as measured by GAF in schizophrenia group. Fulfillment of higher number of criteria of MetS correlated with poorer quality of life and higher problems in both groups. Interpretation & conclusions: Many modifiable lifestyle factors increase the risk of MetS. MetS was found to be associated with poorer QOL in patients with BPAD and schizophrenia; in addition, obesity led to poor self-esteem and excessive personal distress.
Dual role of IL-21 in megakaryopoiesis and platelet homeostasis

Gene profiling studies have indicated that in vitro differentiated human megakaryocytes express the receptor for IL-21 (IL-21R), an immunostimulatory cytokine associated with inflammatory disorders and currently under evaluation in cancer therapy. The aim of this study was to investigate whether IL-21 modulates megakaryopoiesis. We first checked the expression of IL-21 receptor on human bone marrow and in vitro differentiated megakaryocytes. We then investigated the effect of IL-21 on the in vitro differentiation of human blood CD34+ progenitors into megakaryocytes. Finally, we analyzed the consequences of hydrodynamic transfection-mediated transient expression of IL-21, on megakaryopoiesis and thrombopoiesis in mice. The IL-21Rα chain was expressed in human bone marrow megakaryocytes and was progressively induced during in vitro differentiation of human peripheral CD34+ progenitors, while the signal transducing γ chain was down-regulated. Consistently, the STAT3 phosphorylation induced by IL-21 diminished during the later stages of megakaryocytic differentiation. In vitro, IL-21 increased the number of colony-forming unit megakaryocytes generated from CD34+ cells and the number of megakaryocytes differentiated from CD34+ progenitors in a JAK3- and STAT3-dependent manner. Forced expression of IL-21 in mice increased the density of bi-potent megakaryocyte progenitors and bone marrow megakaryocytes, and the platelet generation, but increased platelet clearance with a consequent reduction in blood cell counts. Our work suggests that IL-21 regulates megakaryocyte development and platelet homeostasis. Thus, IL-21 may link immune responses to physiological or pathological platelet-dependent processes.
Evaluation of candida albicans biofilm formation on various dental restorative material surfaces

Aims: Candida adhesion to any oral substrata is the first and essential stage in forming a pathogenic fungal biofilm. In general, yeast cells have remarkable potential to adhere to host surfaces, such as teeth or mucosa, and to artificial, nonbiological surfaces, such as restorative dental materials. This study compared the susceptibility of six dental restorative materials to Candida albicans adhesion. Materials and methods: Cylindrical samples of each material were made according to the manufacturersa instructions. The antifungal effect of the samples on C. albicans was determined with the disc-diffusion method. The samples were put in plates with sterile Mueller Hinton and Sabouraud dextrose agar previously seeded with C. albicans. After the incubation period, the inhibition zone around each sample was evaluated. To evaluate the biofilm formation, the XTT technique and scanning electron microscopy (SEM) were used. Results: No inhibition zone was observed around the samples. According to the XTT assays, the amalgam samples revealed the lowest quantity of biofilm formation (P > 0.001). The highest median XTT values, significantly higher than the other materials (P < 0.001), were found for the composite and the compomer samples. Within the SEM examination, the amount of candidal growth was significantly lower on the resin-modified glass ionomer and glass-ionomer cement samples. The compomer and the composite samples showed more candidal adhesion. Conclusion: This finding emphasizes the use of glass ionomer restorative cements and amalgam to reduce C. albicans adhesion to dental restorative materials especially in people with weakened immune systems, neutropenia, and cancer.