Miracle-dz/UniFAR-FTUs huggingface dataset:
Pulmonary retention of free and liposome-encapsulated tobramycin after intratracheal administration in uninfected rats and rats infected with Pseudomonas aeruginosa

The pulmonary residence time of free and liposome-encapsulated tobramycin was studied with uninfected rats and rats infected with Pseudomonas aeruginosa. Chronic infection in lungs was established by intratracheal administration of 10(8) CFU of P. aeruginosa PA 508 prepared in agar beads. After 3 days, a single dose (300 micrograms) of free or liposome-encapsulated tobramycin was given intratracheally to both infected and uninfected rats. At various time intervals (0.25 to 16 h) after drug instillations, the remaining tobramycin was evaluated in blood, lungs, and kidneys by a microbiological assay. Intratracheal instillation of liposome-encapsulated tobramycin resulted in high and sustained levels of tobramycin in lungs of uninfected and infected rats over the 16-h period studied; however, the tobramycin levels were two times higher in uninfected rats. There was no tobramycin detected in the blood or kidneys from these animals. In contrast, the intratracheally instilled free tobramycin was cleared within 3 and 1 h from the lungs of uninfected and infected animals, respectively. These data suggest that the encapsulation of tobramycin in liposomes can result in a significant increase of its residence time within lungs. This study also shows that pulmonary infection was associated with a lowering of tobramycin levels in lungs.
Salivary cortisol in panic attacks.

OBJECTIVE Documentation of hypothalamic-pituitary-adrenal (HPA) axis disturbance in panic disorder has been inconsistent. Increased cortisol levels have been associated with altered HPA function due to stress. The authors examined salivary cortisol levels in spontaneously occurring, unprovoked panic attacks. METHOD Patients with panic disorder (N=25) collected saliva samples when panic attacks occurred. Levels of cortisol in the saliva samples were determined and were compared with levels in comparison samples of saliva obtained 24 hours after the panic attack occurred. RESULTS During spontaneous panic attacks there was a subtle but significant elevation of cortisol levels, compared with levels obtained 24 hours later. No significant correlations were found between the cortisol elevations during panic attacks and the severity of the attack as measured by using the Acute Panic Inventory or the severity of illness as measured by using the Panic and Agoraphobia Scale. CONCLUSIONS Saliva sampling may be a useful method for investigating neuroendocrine parameters during spontaneously occurring panic attacks.
Adnexal torsion during pregnancy: Report of four cases and review of the literature

Adnexal torsion is a rare cause of acute abdominal pain during pregnancy. It is frequently associated with ovarian stimulation for in vitro fertilization (IVF) or with ovarian masses, mainly of functional origin. The clinical, laboratory and imaging findings are non‐specific. The authors present four cases with adnexal torsion diagnosed during the first trimester of pregnancy. The clinical picture, the mode of diagnosis, and the therapeutic approach are discussed. In two cases, the adnexa was removed, because there was extensive hemorrhage and ischemia. In the other two cases, unwinding of the adnexa was carried out and the ovary was preserved. The diagnosis of adnexal torsion is difficult, especially during pregnancy, and occasionally remains a diagnostic dilemma. It necessitates a prompt surgical intervention, because any delay leads to irreversible ovarian necrosis, so that adnexectomy is ultimately required.
Gender Diversity on Boards and Firms’ Environmental Policy

This paper tests the relationship between gender diversity on boards and firms’ environmental policy. Based on prior research, we predict that gender diversity on boards of directors should have a positive relationship with firms’ environmental policy. Moreover, firm character in terms of pollution creation likelihood moderates the relationship between gender diversity on boards and firms’ environmental policy. Analyzing data from 865 publicly listed firms in the United States, we found direct and significant empirical evidence for our predictions. According to the findings, we highlight the importance of gender diversity for the development of good firm environmental policy as well as for the improvement of corporate governance. Moreover, the more likely firms in a given industry are to cause environmental pollution, the more salient will be the beneficial effect of gender diversity on boards on firms’ environmental policy in the industry. Copyright © 2016 John Wiley & Sons, Ltd and ERP Environment
Development and Application of Different Methods for the Detection of Toxoplasma gondii in Water

ABSTRACT Two methods, centrifugation and flocculation, were evaluated to determine their efficiencies of recovery of Toxoplasma gondii oocysts from contaminated water samples. Demineralized and tap water replicates were inoculated with high numbers of sporulated or unsporulated T. gondii oocysts (1 × 105 and 1 × 104 oocysts). The strain, age, and concentration of the seeded oocysts were recorded. Oocysts were recovered either by centrifugation of the contaminated samples at various g values or by flocculation with two coagulants, Fe2(SO4)3 and Al2(SO4)3. The recovery rates were determined with the final pellets by phase-contrast microscopy. Sporulated oocysts were recovered more effectively by flocculation with Al2(SO4)3 (96.5% ± 21.7%) than by flocculation with Fe2(SO4)3 (93.1% ± 8.1%) or by centrifugation at 2,073 × g (82.5% ± 6.8%). For the unsporulated oocysts, flocculation with Fe2(SO4)3 was more successful (100.3% ± 26.9%) than flocculation with Al2(SO4)3 (90.4% ± 19.1%) or centrifugation at 2,565 × g (97.2% ± 12.5%). The infectivity of the sporulated oocysts recovered by centrifugation was confirmed by seroconversion of all inoculated mice 77 days postinfection. These data suggest that sporulated Toxoplasma oocysts purified by methods commonly used for waterborne pathogens retain their infectivity after mechanical treatment and are able to induce infections in mammals. This is the first step in developing a systematic approach for the detection of Toxoplasma oocysts in water.
Evidence for a Disequilibrium pH in the Proximal Tubule of Rat Kidney.∗

Reabsorption of filtered HCO3 - by the kidney is thought to be mediated by secretion of cellular H+(1,2), resulting in the following intratubular reaction: Since dehydration of H2CO3 is not instantaneous, excess H2CO3 would accumulate in tubular fluid and would not be in equilibrium with plasma CO2. Consequently, intratubular pH would be lower than that calculated by the Henderson-Hasselbalch equation using plasma pCO2 and luminal concentration of HCO3 -(3). An opposing view postulates that HCO3 - ions per se are reabsorbed directly (4). Were this the mechanism involved, excess H2CO3 would not be generated, H2CO3 and CO2 would be in continuous equilibrium, and the intratubular pH would be equal to that predicted by the Henderson-Hasselbalch equation. In the present experiments the in vivo intratubular pH of single proximal tubules perfused with a solution containing 60 mM NaHCO3 was 6.3, or 1.5 pH units below the calculated equilibrium pH of 7.8. These results afford the first direct evidence that HCO3 - reabsorption in the proximal tubule is mediated via H+ secretion. Methods. Sprague-Dawley rats were anesthetized and prepared for micropuncture as previously described (5). The exposed surface of the kidney was covered with Ringer's bicarbonate solution continuously equilibrated with 5% CO2-95% O2. Single proximal tubules were perfused by first injecting a drop of silicone oil into the lumen through a micropipette. The oil drop was then split by injecting with a second micropipette a solution containing 90 mM NaCl and 60 mM NaHCO3. The pH of this solution when equilibrated with 5% CO2 was 7.8. The in vivo intratubular pH was estimated by adding various acid-base indicators to the perfusion fluid in a concentration of 100 mg %. The color changes in the column of injected fluid were observed by direct microscopic visualization.
Characterisation of genomic translocation breakpoints and identification of an alternative TCF3/PBX1 fusion transcript in t(1;19)(q23;p13)‐positive acute lymphoblastic leukaemias

The t(1;19)(q23;p13), one of the most common translocations in childhood and adult acute lymphoblastic leukaemias (ALLs), usually results in fusion of exons 1–16 of TCF3 (previously E2A) and exons 3–9 of PBX1. However, some t(1;19)‐positive ALLs are negative for this chimaera. We here report an alternative TCF3/PBX1 transcript, fusing exon 17 of TCF3 with exon 5 of PBX1, in a paediatric t(1;19)‐positive ALL. The different breakpoints made this hybrid undetectable by reverse transcription polymerase chain reaction using standard TCF3 and PBX1 primers. Hence, ALLs with t(1;19) that test negative for TCF3/PBX1 should be analysed further before excluding this alternative fusion. Furthermore, we have characterised the genomic translocation breakpoints in eight TCF3/PBX1‐positive ALLs; four cases with a balanced t(1;19) and four with an unbalanced der(19)t(1;19). It has previously been suggested that the breakpoints are clustered, particularly in TCF3, and that N‐nucleotides are frequently present in the fusion junctions. Three of seven investigated TCF3 intron 16 breakpoints were within the previously described 14 base pair‐cluster, and all but two junctions harboured N‐nucleotides. The PBX1 breakpoints were more dispersed, although still clustered in two regions. This confirms that most t(1;19) rearrangements may arise by a combination of illegitimate V(D)J recombination and non‐homologous end joining.
Effect of ketamine on pro- and anti-inflammatory cytokine response in paediatric cardiac surgery: A prospective randomised controlled study

Background and Aims: Paediatric cardiac surgery with cardiopulmonary bypass (CPB) is associated with a marked inflammatory response and triggers release of inflammatory cytokines. The aim of this study was to study the effect of ketamine on the inflammatory response during correction of congenital cyanotic heart diseases. Methods: Sixty-six patients with congenital cyanotic heart diseases scheduled for cardiac surgery were randomised into three groups. Group A patients did not receive ketamine (control group), Group B patients received 2 mg/kg ketamine intravenous (IV) and Group C patients received ketamine 2 mg/kg IV and an IV infusion of ketamine (50 μg/kg/min). Interleukin (IL) levels for IL-6, IL-8, IL-10, C-reactive protein (CRP) and tumour necrosis factor-α (TNF-α) levels were examined in the three groups at four timings: pre-operative (baseline), intraoperative (after weaning off the CPB) and post-operative (6 and 24 h after weaning off CPB). Paired sample t-test and ANOVA test were used for statistical analysis and P< 0.05 was considered statistically significant. Results: Within each group, the intra- and post-operative serum levels of IL-6, IL-8, IL-10 and CRP were significantly elevated from the baseline, however, TNF-α was not significantly elevated. There were no statistically significant differences in the IL, CRP or TNF-α levels between the three groups. Conclusion: Paediatric cardiac surgery for congenital cyanotic heart disease is a triggering factor for the inflammatory response, yet we could not detect any beneficial effect of ketamine on that response whether given either as an IV induction dose or continued as an IV infusion.
Targeting the pregnane X receptor in liver injury

Introduction: The nuclear receptor pregnane X receptor (PXR) is a well-characterized hepatic xenobiotic sensor whose activation by chemically diverse compounds results in the induction of drug clearance pathways that rid the body of potentially toxic substances, thus conferring protection from foreign chemicals and endobiotics. Areas covered: PXR activities are implicated in drug–drug interactions and endocrine disruption. Recent evidence supports a hepatoprotective role for PXR in chronic liver injury, inhibiting liver inflammation through suppression of the NF-κB pathway. However, PXR-mediated induction of CYP3A enhances APAP-induced acute liver injury by generating toxic metabolites. While these observations implicate PXR as a therapeutic target for liver injury, they also caution against PXR activation by pharmaceutical drugs. Expert opinion: While evidence of PXR involvement in acute and chronic liver injuries identifies it as a possible therapeutic target, it raises additional concerns for all drug candidates. The in vitro and in vivo tests for human PXR activation should be incorporated into the FDA regulations for therapeutic drug approval to identify potential liver toxicities. In addition, PXR pharmacogenetic studies will facilitate the prediction of patient-specific drug reactivities and associated liver disorders.
Real-Time Determination of Credit Cycle Phases in Emerging Markets

We test the ability of early warning indicators that appear in the literature to predict credit cycle peaks in a cross-section of emerging markets. Our results confirm that the standard credit gap indicator performs satisfactorily. The robustness of real-time credit cycle determination may potentially (and with a risk of overfitting the data) be improved by simultane-ously monitoring GDP growth, banks’ non-core liabilities, the financial sector’s value added and (to a lesser extent) the change in the debt service ratio.
Combining kallistatin gene therapy and meloxicam to treat hepatocellular carcinoma in mice

Hepatocellular carcinoma (HCC) is one of the most common cancer‐related causes of death, and conventional treatments offer unsatisfactory response. We have previously reported that kallistatin gene therapy suppressed the growth of HCC tumors by its anti‐angiogenic activity, and meloxicam, a selective COX‐2 inhibitor, inhibited proliferation and induced apoptosis of human HCC cells in vitro. The aim of this study was to determine whether combining kallistatin gene therapy and meloxicam could offer a better therapeutic effect to combat HCC in mice. A kallistatin expression plasmid was constructed and its expression was detected after intratumoral gene transfer. Both kallistatin gene therapy and meloxicam suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, and the combinational therapy showed a stronger effect in suppressing tumor growth, tumor angiogenesis and cell proliferation, and increasing cell apoptosis, than the respective monotherapies. Gene transfer of kallistatin inhibited tumor angiogenesis, and slightly inhibited cell proliferation and increased cell apoptosis in situ, but had no effect on expression of vascular endothelial growth factor, basic fibroblast growth factor, proliferating cell nuclear antigen, Bcl‐2, Bax, or activation of caspase‐3. Meloxicam therapy inhibited cell proliferation, induced cell apoptosis, reduced expression of proliferating cell nuclear antigen, increased activation of caspase‐3, and upregulated Bax. Meloxicam also slightly inhibited tumor angiogenesis with no effect on the expression of vascular endothelial growth factor or basic fibroblast growth factor. Combining two novel anticancer agents, kallistatin targeting tumoral vascularization and meloxicam targeting cell proliferation and apoptosis, warrants investigation as a therapeutic strategy to combat HCC. (Cancer Sci 2009)
Noninvasive evaluation of intrarenal oxygenation with BOLD MRI.

BACKGROUND The countercurrent arrangement of capillary blood flow in the medulla of mammalian kidneys generates a gradient of oxygen tension between the renal cortex and the papillary tip that results in a state of relative hypoxia within the renal medulla. Exploration of the pathophysiological implications of medullary hypoxia has been hampered by the absence of a noninvasive technique to estimate intrarenal oxygenation in different zones of the kidney. In the present study, we demonstrate the feasibility of such a method on the basis of blood oxygenation level-dependent (BOLD) MRI, which allows sequential measurements in humans in response to a variety of physiological/ pharmacological stimuli in health and disease. METHODS AND RESULTS BOLD MRI measurements were obtained in healthy young human subjects (n = 7), and the effects of three different pharmacological/physiological maneuvers that induce diuresis were studied. Spin-spin relaxation rate, R2*, was measured, which is directly related to the amount of deoxyhemoglobin in blood and in turn to tissue PO2. Furosemide but not acetazolamide (n = 6 each) increased medullary oxygenation (delta R2* = 7.62 Hz; P < .01), consistent with the separate sites of action of these diuretics in the nephron and with previous direct measurements of their effects in anesthetized rats with oxygen microelectrodes. A new finding is that water diuresis improves medullary oxygenation (delta R2* = 6.43 Hz; P < .01) in young human subjects (n = 5). CONCLUSIONS BOLD MRI can be used to monitor changes in intrarenal oxygenation in humans in a noninvasive fashion.
Effect of Microwave Electromagnetic Field on Skeletal Muscle Fibre Activity

The aim of the present study was to investigate the influence of microwave irradiation on fatiguing activity of isolated frog skeletal muscle fibres. The changes in the electrical and mechanical activity were used as criteria for the exposure effects. Repetitive suprathreshold stimulation with interstimu-lus interval of 200ms for 3min was applied. Intracellular (ICAP) and extracellular (ECAP) action potentials and twitch contractions (Tw) of muscle fibres after 1 hour microwave exposure (2.45GHz, 20mW/cm 2 power density) were compared with those recorded after one hour sham exposure (control). The duration of uninterrupted activity in the trial (endurance time; ET) was not significantly affected by microwave field exposure. After microwave irradiation, the ICAP amplitude was higher, the rising time was shorter, and the resting membrane potential was more negative compared to controls. There was a slower rate of parameters changes during ET in potentials obtained from irradiated fibres. Microwave exposure increased the propagation velocity of excitation, the ECAP and Tw amplitudes, as well as shortened their time parameters. We concluded that a 2.45GHz microwave field possesses a stimulating effect on muscle fibre activity, which is in part due to its specific, non-thermal properties. The microwave induced-changes in muscle fibre activity may reduce development of skeletal muscle fatigue.
G‐CSF Priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm

Prior study of the combination of clofarabine and high dose cytarabine with granulocyte colony‐stimulating factor (G‐CSF) priming (GCLAC) in relapsed or refractory acute myeloid leukemia resulted in a 46% rate of complete remission despite unfavorable risk cytogenetics. A multivariate analysis demonstrated that the remission rate and survival with GCLAC were superior to FLAG (fludarabine, cytarabine, G‐CSF) in the relapsed setting. We therefore initiated a study of the GCLAC regimen in the upfront setting in a multicenter trial. The objectives were to evaluate the rates of complete remission (CR), overall and relapse‐free survival (OS and RFS), and toxicity of GCLAC. Clofarabine was administered at 30 mg m−2 day−1 × 5 and cytarabine at 2 g m−2 day−1 × 5 after G‐CSF priming in 50 newly‐diagnosed patients ages 18–64 with AML or advanced myelodysplastic syndrome (MDS) or advanced myeloproliferative neoplasm (MPN). Responses were assessed in the different cytogenetic risk groups and in patients with antecedent hematologic disorder. The overall CR rate was 76% (95% confidence interval [CI] 64–88%) and the CR + CRp (CR with incomplete platelet count recovery) was 82% (95% CI 71–93%). The CR rate was 100% for patients with favorable, 84% for those with intermediate, and 62% for those with unfavorable risk cytogenetics. For patients with an antecedent hematologic disorder (AHD), the CR rate was 65%, compared to 85% for those without an AHD. The 60 day mortality was 2%. Thus, front line GCLAC is a well‐tolerated, effective induction regimen for AML and advanced myelodysplastic or myeloproliferative disorders. Am. J. Hematol. 90:295–300, 2015. © 2014 Wiley Periodicals, Inc.
Treatment of Amanita phalloides intoxication by fractionated plasma separation and adsorption (Prometheus®).

OBJECTIVE To investigate the effectiveness and safety of extracorporeal detoxification using the fractionated plasma separation and adsorption system (FPSA, Prometheus® 4008H, Fresenius Medical Care, Germany) in patients suffering from acute liver failure due to intoxication with Amanita phalloides (AP) toxin. METHODS The study population consisted of 20 patients with proven AP intoxication (FPSA treatment group n=9, control group n=11). Urinary amanitin toxin concentration was measured by the Amanitin ELISA Kit (Bühlmann Laboratories, Germany, cut off level 1.5 ng/ml). All patients received standard medical treatment with activated charcoal, i.v. crystalloid fluids, silibinine and N-acetylcysteine. Additionally 9 patients underwent treatment with FPSA until undetectable amanitin levels. RESULTS Mean urinary amanitin levels were significantly reduced by FPSA with 42.5 +/- 21.9 ng/ml before and 1.2 +/- 0.31 ng/ml after treatment (p=0.04). No hemodynamic, respiratory or hematological complications were observed. None of the patients had to undergo liver transplantation. All patients in the treatment group survived and were discharged fully recovered. One patient in the control group died due to shock and lactic acidosis; one patient remained dialysis dependent. Mean duration of hospital stay was 7.1 days in the treatment group and 11.7 days in the control group (p=0.30). CONCLUSIONS Use of liver support therapy by fractionated plasma separation and adsorption (Prometheus®) offers a safe way for elimination of Amanita toxin with the potential to avoid the need for liver transplantation.
Anesthesiologists at work: an increase in pro‐inflammatory and Th2 cytokine production, and alterations in proliferative immune responses

Background: Anesthesiologists are a population at high risk of alcohol and drug abuse, depression, suicide, and psychiatric hospitalization. The impact of their working milieu on specific immune indices has scarcely been studied, and it is assumed that immune perturbations may contribute to some of the above risks. This study took advantage of an unplanned, 3‐month long strike of anesthesiologists, and explored its relations to specific immune measures.
The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development.

The decapentaplegic (dpp) gene of Drosophila melanogaster encodes a polypeptide of the transforming growth factor‐beta family of secreted factors. It is required for the proper development of both embryonic and adult structures, and may act as a morphogen in the embryo. In wing imaginal discs, dpp is expressed and required in a stripe of cells near the anterior‐posterior compartment boundary. Here we show that viable mutations in the segment polarity genes patched (ptc) and costal‐2 (cos2) cause specific alterations in dpp expression within the anterior compartment of the wing imaginal disc. The interaction between ptc and dpp is particularly interesting; both genes are expressed with similar patterns at the anterior‐posterior compartment boundary of the disc, and mis‐expressed in a similar way in segment polarity mutant backgrounds like ptc and cos2. This mis‐expression of dpp could be correlated with some of the features of the adult mutant phenotypes. We propose that ptc controls dpp expression in the imaginal discs, and that the restricted expression of dpp near the anterior‐posterior compartment boundary is essential to maintain the wild‐type morphology of the wing disc.