Monitoring the biodegradability of bisphenol A and its metabolic intermediates by manometric respirometry tests.
As a result of its wide usage in the production of polycarbonate plastics and epoxy resins, bisphenol A (BPA) is commonly detected in wastewaters. Recently, BPA became a major concern because its adverse effects as an endocrine disruptor. In this work, the biodegradation kinetics of BPA and its metabolic intermediates 4-hydroxyacetophenone (4HAP), 4-hydroxybenzaldehyde (4HB) and 4-hydroxybenzoic acid (4HBA) by BPA-acclimated activated sludge was studied using manometric respirometry (BOD) tests. For all the tested compounds, BOD curves exhibited two phases. In the first one, a fast increase of the oxygen consumption (OC) due to the active oxidation of the substrate was obtained. Then, when the substrate was exhausted, the endogenous respiration produced a slower increase of OC. A standard Monod-model with biomass growth was used to represent the OC profiles as a function of time. For all the tested compounds, a good agreement between the proposed model and the experimental data was obtained. According to their biodegradation rates, the tested compounds can be ordered as follows: BPA < 4HAP ≪ 4HB < 4HBA. Because the oxidation rate of BPA by BPA-acclimated activated sludge limits the rate of the whole biodegradation pathway, the accumulation of metabolic intermediates 4HAP, 4HB, and 4HBA would be negligible. To calculate the dissolved oxygen (DO) concentration (C) during the BOD tests, the oxygen transfer coefficient (kLa) of the BOD bottles was obtained using the sulfite method. Finally, a simple procedure to calculate the minimum DO concentration (Cmin) based on BOD data was developed. Calculation results demonstrated that under the tested conditions, C values were high enough as not to be the limiting substrate for the microbial growth.


Altered retrograde axonal transport of nerve growth factor after single and repeated doses of acrylamide in the rat.
The retrograde axoplasmic transport of iodinated nerve growth factor (125I-NGF) was markedly altered by systemic acrylamide treatment. Single doses of acrylamide (25 to 100 mg/kg, ip) inhibited the retrograde transport of 125I-NGF in a dose-dependent manner within 12 hr after administration. A dose of acrylamide (15 mg/kg, ip) which did not alter retrograde transport when given as a single dose, markedly inhibited retrograde transport when given repeatedly. Alterations in retrograde transport appeared prior to detectable alterations in peripheral nerve function and correlated with cumulative dose of acrylamide. These data suggest that single doses of acrylamide produce a biochemical lesion which accumulates to produce neuropathy. Altered retrograde axoplasmic transport may reflect the primary biochemical event responsible for the induction of neuropathy by acrylamide.


[Acupuncture in the treatment of locomotive disorders - status of research and situation regarding clinical application].
Acupuncture has been used for over 2000 years for a wide variety of complaints with minimal side effects. Based on the experience in Chinese medicine and the anticipated positive effects, acupuncture has been widely accepted in Western medicine as well. Some clinical evidence supports the efficacy of acupuncture treatment, but randomized controlled trials have been conducted for only a few of all possible locomotive disorder indications, and the results have been equivocal. Other indications have not yet been systematically studied, and application is based on clinical experience and consensus among practitioners. One of the outcomes on which consensus appears to exist is that 10-20 sessions are generally necessary, and that initial improvement can be expected to occur by the 10th treatment. Rigorous trials should be conducted to improve clinical validity and provide scientific proof of the efficacy of acupuncture. Clinical trials like the German Acupuncture Trials (gerac), funded by the German health insurance companies, have been launched with the aim of furthering knowledge in this area.


Bone marrow mesenchymal stem cells stabilize already-formed aortic aneurysms more efficiently than vascular smooth muscle cells in a rat model.
Abdominal aortic aneurysms (AAAs) expand because of aortic wall destruction. Enrichment in Vascular Smooth Muscle Cells (VSMCs) stabilizes expanding AAAs in rats. Mesenchymal Stem Cells (MSCs) can differentiate into VSMCs. We have tested the hypothesis that bone marrow-derived MSCs (BM-MSCs) stabilizes AAAs in a rat model. Rat Fischer 344 BM-MSCs were isolated by plastic adhesion and seeded endovascularly in experimental AAAs using xenograft obtained from guinea pig. Culture medium without cells was used as control group. The main criteria was the variation of the aortic diameter at one week and four weeks. We evaluated the impact of cells seeding on inflammatory response by immunohistochemistry combined with RT-PCR on MMP9 and TIMP1 at one week. We evaluated the healing process by immunohistochemistry at 4 weeks. The endovascular seeding of BM-MSCs decreased AAA diameter expansion more powerfully than VSMCs or culture medium infusion (6.5% ± 9.7, 25.5% ± 17.2 and 53.4% ± 14.4; p = .007, respectively). This result was sustained at 4 weeks. BM-MSCs decreased expression of MMP-9 and infiltration by macrophages (4.7 ± 2.3 vs. 14.6 ± 6.4 mm(2) respectively; p = .015), increased Tissue Inhibitor Metallo Proteinase-1 (TIMP-1), compared to culture medium infusion. BM-MSCs induced formation of a neo-aortic tissue rich in SM-alpha active positive cells (22.2 ± 2.7 vs. 115.6 ± 30.4 cells/surface units, p = .007) surrounded by a dense collagen and elastin network covered by luminal endothelial cells. We have shown in this rat model of AAA that BM-MSCs exert a specialized function in arterial regeneration that transcends that of mature mesenchymal cells. Our observation identifies a population of cells easy to isolate and to expand for therapeutic interventions based on catheter-driven cell therapy.


A chaotic map-based authentication scheme for telecare medicine information systems.
With the development of Internet, patients could enjoy health-care delivery services through telecare medicine information systems (TMIS) in their home. To control the access to remote medical servers' resources, many authentication schemes using smart cards have been proposed. However, the performance of these schemes is not satisfactory since modular exponential operations are used in these schemes. In the paper, we propose a chaotic map-based authentication scheme for telecare medicine information systems. The security and performance analysis shows our scheme is more suitable for TMIS.


Spatial dynamic metabolomics identifies metabolic cell fate trajectories in human kidney differentiation.
Accumulating evidence demonstrates important roles for metabolism in cell fate determination. However, it is a challenge to assess metabolism at a spatial resolution that acknowledges both heterogeneity and cellular dynamics in its tissue microenvironment. Using a multi-omics platform to study cell-type-specific dynamics in metabolism in complex tissues, we describe the metabolic trajectories during nephrogenesis in the developing human kidney. Exploiting in situ analysis of isotopic labeling, a shift from glycolysis toward fatty acid β-oxidation was observed during the differentiation from the renal vesicle toward the S-shaped body and the proximal tubules. In addition, we show that hiPSC-derived kidney organoids are characterized by a metabolic immature phenotype that fails to use mitochondrial long-chain fatty acids for energy metabolism. Furthermore, supplementation of butyrate enhances tubular epithelial differentiation and maturation in cultured kidney organoids. Our findings highlight the relevance of understanding metabolic trajectories to efficiently guide stem cell differentiation.


Study on the thermal stability of alpha-amylase modified by maleic anhydride copolymer.
The thermal inactivation of mesophilic Bacillus subtilis alpha-amylase modified by maleic anhydride/vinyl acetate copolymer has been studied at different polymer/enzyme ratios in the pH range of relevance to enzymatic catalysis. Enzymatic activity measurements combined with circular dichroism measurements were used to determine the enzyme thermostability. The apparent first-order rate constants and activation energies of thermo-inactivation affected by addition of Ca2+ ions as well as by modification have been calculated. The modified alpha-amylase exhibited sufficiently high catalytic activity with enhanced resistance to the thermal unfolding process.


A qualitative evaluation of the process of creating and implementing an interprofessional care pathway for patients treated with oral anticancer drugs.
To investigate factors affecting the co-creation and implementation of care pathways for patients treated with oral anticancer drugs. An explorative qualitative process evaluation was performed at four Belgian hospitals, co-creating and implementing a care pathway for patients on oral anticancer drugs. Semistructured interviews and focus groups were performed by a) local coordinators leading an interprofessional project team during the co-creation and implementation stage, b) external implementation coaches, and c) teams of healthcare professionals with a role in the care pathway. In total, 47 stakeholders were interviewed. Interviews were audio-taped, transcribed verbatim, and analyzed thematically. We found four factors affecting co-creation and implementation of care pathways for patients on oral anticancer drugs. Developing an adequate supporting context using motivated interprofessional project teams of clinical and management staff led by competent coordinators is one important facilitator. Leadership of local coordinators and oncologists is crucial for progressing the co-creation. Other factors included the complexity of the oral anticancer drug intervention, the interprofessional character of the care pathway, and involving primary care. External coaching during co-creation proved an important facilitator. Prior investigation of willingness and motivation to change in clinical and management staff, competent coordinators, and leadership of oncologists are needed. In addition, external support determines the success of co-creating and implementing care pathways for patients on oral anticancer drugs.


Global longitudinal strain may identify preserved systolic function of the systemic right ventricle.
Assessment of systemic right ventricle (RV) function is a key point in the follow-up of patients with dextroposition of the great arteries (D-TGA) after the atrial switch procedure. Cardiac magnetic resonance (CMR) is considered the reference standard but is not feasible for a considerable number of patients. Experience with the application of 2-dimensional speckle tracking echocardiography for the assessment of systemic RV function in such patients is very limited, and the cutoff strain value differentiating normal and subnormal RV function is missing. We prospectively examined, with echocardiography and CMR, 40 patients with D-TGA (mean age, 25.6 ± 5 years; 25 men; 33 after the Senning, 7 after the Mustard procedure) who attended a tertiary adult congenital heart disease centre. There was a linear correlation between global longitudinal strain (GLS) and CMR systemic RV ejection fraction (EF) values (r = 0.4; P = 0.01), systemic RV fractional area change and CMR systemic RV EF (r = 0.41; P = 0.008). There was no correlation between systemic RV s', tricuspid annular plane systolic excursion or the rate of change of the systemic RV pressure with time and CMR systemic RV EF. Only 1 of 19 patients with GLS < -14.2% had CMR systemic RV EF < 45%. The GLS cutoff value of -14.2% predicted the CMR systemic RV EF of ≥ 45% with 90% specificity and 83% sensitivity. Its positive predictive value was 96%. The systemic RV GLS is able to discriminate between D-TGA patients after the atrial switch with, and those without, a CMR systemic RV EF of at least 45%.


Variables predictive of adherence to diet and physical activity recommendations in the treatment of obesity and overweight, in a group of Spanish subjects.
To assess the factors that could predict a successful completion of a weight loss program. A single-centered, cross-sectional, prospective study conducted over 4 y. Data were obtained on 1018 overweight subjects (788 women, 230 men) aged 14.8-76.3 y (mean 38.4) and body mass index (BMI) of 31.7 (range 25.03-57.1) seeking help to lose weight at a specialist obesity clinic. A program involving a hypocaloric, Mediterranean diet was prescribed plus recommendations for free-time exercise and day-to-day activity. Follow-up was weekly until the desired weight loss was achieved ('successful completion') or the patient dropped-out of the program ('failure'). Cox's regression analysis was used to evaluate success and the variables included were compliance with the program, age, gender, initial BMI, physical activity, alcohol consumption, smoking habit, hypertension, diabetes, hypercholesterolemia, cardiovascular disease, previous dietary programs, cause of obesity, age at which excessive weight was first noted and parental obesity. Factors predictive of completion were: gender (males responded better), previous dietary programs (predictive of dropout), initial BMI (higher index, lower completion), and age (younger age, poorer outcome). There was an interaction between parental obesity and offspring childhood obesity. Absence of parental obesity and adult-onset obesity had a higher probability of program completion. In a standard weight reduction program the recommendations of dietary restriction and moderate exercise seems less effective for women, persons with high BMI, younger age groups and those who have had other attempts at weight loss. Poorest outcomes applied to those subjects with childhood obesity and who had obese parents.


Cataract surgery in eyes with nanophthalmos and relative anterior microphthalmos.
To compare the refractive outcome and postoperative complications of cataract surgery among nanophthalmos and relative anterior microphthalmos and the normal control eyes. Retrospective case-control series. Seventeen eyes with nanophthalmos, 29 eyes with relative anterior microphthalmos, and 54 normal control eyes were enrolled in this study. The subjects were divided into 3 diagnostic subgroups according to the following: nanophthalmos with an axial length <20.5 mm and without morphologic malformation; relative anterior microphthalmos with a corneal diameter (CD) ≤ 11 mm, an anterior chamber depth (ACD) ≤ 2.2 mm, and an axial length (AL) ≥ 20.5 mm; and normal control group eyes defined as an AL ≥ 20.5 mm with a CD >11 mm or an ACD >2.2 mm. The implanted intraocular lens (IOL) power was used to calculate the predicted postoperative refraction error according to 4 IOL power formulas: SRK II, SRK/T, Hoffer Q, and Holladay 1. With each formula, the mean numeric error and mean absolute error were calculated. At postoperative 2 months, the endothelial cell count and the complications were analyzed. As measured by mean numeric error or mean absolute error, there was a significant difference among the 3 groups based on SRK II, SRK/T, and Hoffer Q, with less predictability in the nanophthalmic eyes. In eyes with nanophthalmos, the Holladay 1 produced the best refractive results as measured by mean numeric error (P < .001). A higher occurrence rate of posterior capsule rupture (11.7%) was shown in the nanophthalmic eyes. The difference among the 3 groups for the postoperative endothelial cell loss was not significant (P = .421). The refractive predictability and postoperative outcome was poorer in the eyes with nanophthalmos compared to the eyes with relative anterior microphthalmos or normal control.


Messenger ribonucleic acid vaccines for severe acute respiratory syndrome coronavirus-2 - a review.
The mRNA therapeutics have been studied since the 1970s and the currently available mRNA vaccines against COVID-19 are the culmination of decades of scientific research. The mRNA vaccines BNT162b2 and mRNA-1273 have played a key role in our global response to the COVID-19 pandemic as they have demonstrated significant advantages over conventional vaccines and have proven to be highly effective against COVID-19 associated hospitalization and severe illness in large clinical trials and studies using real-world data.


Characterization of 3H-GABA receptor binding to rat brain synaptosomal membranes: effect of non GABAergic compounds.
Characteristics of 3H-GABA binding to rat brain synaptic membranes in vitro have been investigated. The specific binding of 3H-GABA displays saturation kinetics. Only one single population of receptor sites was found (Km = 31.3 nM) with a concentration of 2.09 pmol/mg protein. Only GABA agonists show inhibitory effect on the binding, whereas GABA antagonists, GABA-uptake inhibitors, and inhibitors of GAD and GABA-T are without effect. The order of potencies for GABA agonists are: Muscimol greater than GABA greater than or equal to 4,5-dihydromuscimol greater than 3-aminoproprane sulphonic acid greater than isoguvacine greater than THIP greater than 3-hydroxy-GABA greater than imidazol-4-acetic acid. Agonists and antagonists from other neurone systems as well as neuroleptics and benzodiazepines had no or only a very slight potency in the binding test.


Diagnostic accuracy of conventional and cholangioscopy-guided sampling of indeterminate biliary lesions at the time of ERCP: a prospective, long-term follow-up study.
The diagnostic accuracy of cholangioscopy-guided sampling has not been rigorously evaluated. To prospectively evaluate the accuracy of cholangioscopy-guided mini-forceps sampling and compare it with standard cytology brushings and forceps biopsies for the tissue diagnosis of indeterminate biliary lesions. Prospective, long-term follow-up, paired design cohort study. Tertiary center. Patients undergoing cholangioscopy for the evaluation of indeterminate biliary lesions. Each patient underwent triple sampling with cholangioscopy-guided mini-forceps, cytology brushing, and standard forceps. Diagnostic accuracy of each sampling method compared with the patient final status (cancer vs no cancer). A total of 26 patients (17 cancer positive/9 cancer negative) were enrolled. The mean follow-up in the patients with no cancer was 21.78 (SD ±6.78) months. The procedure was technically successful in all cases (100%). Sample quality was adequate in 25 of 26 (96.2%) of the cytology brushings, in 26 of 26 (100%) of the standard forceps biopsies, and in 25 of 26 (96.2%) of the mini-forceps biopsies. The sensitivity, accuracy, and negative predictive values were 5.9%, 38.5%, and 36% for standard cytology brushings; 29.4%, 53.8%, and 42.8% for standard forceps biopsies; and 76.5%, 84.6%, and 69.2% for mini-forceps biopsies, respectively. When comparing the 3 methods of sampling, mini-forceps biopsy provided significantly better sensitivity and overall accuracy compared with standard cytology brushing (P < .0001) and standard forceps biopsy (P = .0215). Potential for selection bias. Cholangioscopy-guided biopsies of indeterminate biliary lesions have significantly higher accuracy compared with ERCP-guided cytology brushings and standard forceps biopsies, but negative findings on mini-forceps biopsy cannot rule out malignancy with a high degree of certainty. ( NCT01227382.).


In vitro evaluation of polymeric micelles based on hydrophobically-modified sulfated chitosan as a carrier of doxorubicin.
Four types of doxorubicin (DOX)-loaded polymeric micelles based on hydrophobically-modified sulfated chitosan (SCTS) were prepared. The hydrophobic group was composed of glycyrrhetinic acid (GA), cholic acid, stearic acid (SA) or lauric aldehyde. DOX encapsulation depended on several parameters, including the degree of substitution of the sulfate group and the hydrophobic group, and the type of hydrophobic group. Of these micelles, GA-SCTS micelles had the best capability to solubilize DOX. In addition, GA-SCTS micelles had the ability to target HepG(2) cells, and the IC50 for DOX-loaded GA-SCTS micelles was 54.7 ng/mL, which was much lower than that of the other micelles. Further studies on the DOX-loaded GA-SCTS micelles showed that they were stable in salt and protein solutions, in cell culture media, and during long-term storage (6 months). Based on these results, these micelles may be a promising DOX-encapsulated formulation, particularly, GA-SCTS as a potential vehicle for liver-targeted delivery.


Development, characterization and clinical validation of new sensitive immunofluorometric assay for the measurement of serum thyroglobulin.
In the last decade, data published stressed the role of highly-sensitive thyroglobulin (Tg) assays in the follow-up of differentiated thyroid carcinoma (DTC) patients. The present study describes a new, highly-sensitive Tg assay, compares it with an available commercial assay, and validates it in the follow-up of DTC patients. The immunofluorometric high-sensitivity Tg assay is based on monoclonal and polyclonal antibodies produced at our laboratories. It was validated in 100 samples of 87 patients with DTC submitted to total thyroidectomy, 87% of whom also received radioiodine. For correlation, all samples were also tested using a commercial Tg assay (Beckman Access) with functional sensitivity (FS) of 0.1 ng/mL. The new method showed FS of 0.3 ng/mL. The correlation between the two methods was good (r = 0.74; p < 0.0001). The diagnostic sensitivity was 88.9%, and it was increased to 100% when combined with neck US. This new, high-sensitivity Tg assay presented a good correlation with Beckman Access assay and with the clinical outcome of the patients. The continuous availability of a validated assay is an additional advantage for long term follow-up of DTC patients.


Development of a FTIR-ATR based model for typing clinically relevant Acinetobacter baumannii clones belonging to ST98, ST103, ST208 and ST218.
In this work we developed and validated a FTIR-ATR (Fourier transform infrared spectroscopy with attenuated total reflectance) based model for typing Acinetobacter baumannii clinical isolates belonging to ST98, ST208 and ST218 included into the worldwide spread clonal complex (CC) 92 and ST103. FTIR-ATR spectra of seventy-seven previously characterized isolates (Multi Locus Sequence Type-MLST, Pulsed-Field Gel Electrophoresis-PFGE and carbapenem-hydrolyzing class D β-lactamase-CHDL) were acquired and modeled by partial least squares discriminant analysis (PLSDA). The model was tested and successfully validated with a diverse collection of isolates (n=148) recovered from different countries and periods of time belonging to modeled and non-modeled STs.


Distribution-free estimation of age-related centiles.
A method is described for calculating age-related centiles which makes no assumption about the nature of the distribution of the measurement at a fixed age.


Deep Neural Networks for QSAR.
Quantitative structure-activity relationship (QSAR) models are routinely applied computational tools in the drug discovery process. QSAR models are regression or classification models that predict the biological activities of molecules based on the features derived from their molecular structures. These models are usually used to prioritize a list of candidate molecules for future laboratory experiments and to help chemists gain better insights into how structural changes affect a molecule's biological activities. Developing accurate and interpretable QSAR models is therefore of the utmost importance in the drug discovery process. Deep neural networks, which are powerful supervised learning algorithms, have shown great promise for addressing regression and classification problems in various research fields, including the pharmaceutical industry. In this chapter, we briefly review the applications of deep neural networks in QSAR modeling and describe commonly used techniques to improve model performance.


Evaluation of the TMRW vapor phase cryostorage platform using reproductive specimens and in vitro extended human embryo culture.
To assess the impact of shipment and storage of sperm, oocytes, and blastocysts in vapor phase nitrogen compared with static storage in liquid phase nitrogen. Prospective cohort-matched study. Multiple in vitro fertilization laboratories in an in vitro fertilization network. Fifty-eight human embryos, 32 human oocytes, 15 units of bovine semen. Vapor vs. liquid nitrogen. The postwarming survival of oocytes, sperm, and blastocysts, and the developmental potential of blastocysts during in vitro extended culture. Custom-designed labware, for use with the TMRW platform, enables continuous temperature monitoring during shipment and/or storage in the vapor phase robotic storage system. The highest temperature recorded for specimens shipped to a domestic laboratory was -180.2 °C with a mean ± SD of -190.4 ± 0.5 °C during shipment and -181.1 ± 0.6 °C during storage. Likewise, specimens shipped internationally had a high of -180.2 °C with a mean ± SD of -193.5 ± 0.6 °C during shipment and -181.2 ± 0.7 °C during storage. Results from the extended culture assays have revealed no deleterious effect of shipment and storage in nitrogen vapor. The viability of mammalian gametes and embryos was equivalent between the vapor phase and liquid phase storage. The evaluated system did not have any deleterious effects on the postwarming survival of sperm, oocytes, and blastocysts. The postwarming developmental potential of human blastocysts during in vitro extended culture was unaffected by storage and handling in the vapor phase nitrogen TMRW platform when compared with static liquid phase nitrogen storage. Our results suggest that the vapor phase cryostorage platform is a safe system to handle and store reproductive specimens for human assisted reproductive technology.


Steroid receptor forms and their interaction with cytoplasmic modulators.
The cytoplasmic modulator affecting steroid receptor functions was studied. The diminution in the concentration of the low molecular weight substances in the cytosol caused the increased interaction of hormone-receptor complexes with nuclei (a step termed activation). Furthermore, dialysis of rat uterine cytosol in the absence of estrogens subsequently followed by incubation with isolated nuclei resulted in the demonstration of an appearance of unoccupied nuclear receptor which was found to be 4S form. The addition of the dialyzable compound into rat uterine estrogen receptor system caused the suppression of temperature-dependent activation while the already-activated estrogen receptor was not affected by the small molecules in relation to its nuclear binding ability. These results may indicate that this small molecule, so-called the low molecular weight inhibitor, is capable of interacting with nonactivated receptor. In one of the estrogen-independent Leydig cell tumor lines, unique low-affinity estrogen binder with a mol. wt approximately 36,000 was identified. This binder did not show appreciable nuclear binding ability even after conventional heat activation. However, removal of the small molecules from this cytosol resulted in a marked increase in affinity for estrogens with a concomittant alteration of the mol. wt to approximately 70,000. These changes also paralleled a dramatic enhancement of nuclear binding ability. This small molecule might be different from the low molecular weight inhibitor suppressing receptor activation, since this tumor cytosol containing unique estrogen binder had much less inhibitory activity against receptor activation when compared with those in the other cytosol containing usual estrogen receptor systems. In adult rat urine cytosol, a new modulator was identified to recognize only activated estrogen receptor but not glucocorticoid receptor and to induce receptor aggregation with a concomittant loss of its nuclear binding ability. These reactions were accelerated by the presence of physiological or higher KCl concentration and exposure to a relatively high temperature (20-30 degrees C). Interestingly, this factor was not identified in the immature rat uteri or liver.


Effect of rifampin on the pharmacokinetics of rosiglitazone in healthy subjects.
Rifampin (INN, rifampicin) causes several drug interactions with coadministered antidiabetic drugs. Rosiglitazone is a novel thiazolidinedione antidiabetic drug, but little is known about the drug interaction between rifampin and rosiglitazone. Our objective was to investigate the effect of rifampin on the pharmacokinetics of rosiglitazone in humans. In an open-label, randomized, 2-way crossover study, 10 healthy Korean male subjects were treated once daily for 6 days with 600 mg rifampin or with placebo. On day 7, a single dose of 8 mg rosiglitazone was administered orally. Plasma rosiglitazone concentrations were measured. Rifampin significantly decreased the mean area under the plasma concentration-time curve for rosiglitazone by 65% (2947.9 ng. h/mL versus 991.5 ng. h/mL, P <.001) and the mean elimination half-life from 3.9 to 1.5 hours (P <.001). The peak plasma concentration of rosiglitazone was significantly decreased by rifampin (537.7 ng/mL versus 362.3 ng/mL, P <.01). The apparent oral clearance of rosiglitazone increased about 3-fold after rifampin treatment (2.8 L/h versus 8.5 L/h, P <.001). This study showed that rifampin affected the disposition of rosiglitazone in humans, probably by the induction of cytochrome P450 (CYP) 2C8 and, to a lesser extent, CYP2C9. Therefore caution should be exercised during the coadministration of rifampin and rosiglitazone.


Diagnostic and prognostic criteria of chronic left ventricular failure obtained during exercise-201Tl imaging.
Lung thallium fixation was studied during stress effort and redistribution in 39 patients with proven coronary artery disease (CAD) and in 11 control patients. The quantitative indices (Lung Stress Index (LSI), Lung Redistribution Index (LRI), and their ratio (LSI/LRI] were tested. The last one best correlated with left ventricular end diastolic pressure elevation and positive stress test. Detection of left ventricular failure was possible (sensitivity 80%, specificity 95%) using LSI and LSI/LRI. These indices could detect left ventricular failure in high-risk patients.


EDTA retention and emissions from remediated soil.
EDTA-based remediation is reaching maturity but little information is available on the state of chelant in remediated soil. EDTA soil retention was examined after extracting 20 soil samples from Pb contaminated areas in Slovenia, Austria, Czech Republic and USA with 120 mM kg(-1) Na2H2EDTA, CaNa2EDTA and H4EDTA for 2 and 24 h. On average, 73% of Pb was removed from acidic and 71% from calcareous soils (24 h extractions). On average, 15% and up to 64% of applied EDTA was after remediation retained in acidic soils. Much less; in average 1% and up to the 22% of EDTA was retained in calcareous soils. The secondary emissions of EDTA retained in selected remediated soil increased with the acidity of the media: the TCLP (Toxicity Characteristic Leaching Procedure) solution (average pH end point 3.6) released up to 36% of EDTA applied in the soil (28.1 mmol kg(-1)). Extraction with deionised water (pH > 6.0) did not produce measurable EDTA emissions. Exposing soil to model abiotic (thawing/freezing cycles) and biotic (ingestion by earthworms Lumbricus rubellus) ageing factors did not induce additional secondary emissions of EDTA retained in remediated soil.


The legal framework for language access in healthcare settings: Title VI and beyond.
Over the past few decades, the number and diversity of limited English speakers in the USA has burgeoned. With this increased diversity has come increased pressure--including new legal requirements--on healthcare systems and clinicians to ensure equal treatment of limited English speakers. Healthcare providers are often unclear about their legal obligations to provide language services. In this article, we describe the federal mandates for language rights in health care, provide a broad overview of existing state laws and describe recent legal developments in addressing language barriers. We conclude with an analysis of key policy initiatives that would substantively improve health care for LEP patients.


Artificial intelligence tools in clinical neuroradiology: essential medico-legal aspects.
Commercial software based on artificial intelligence (AI) is entering clinical practice in neuroradiology. Consequently, medico-legal aspects of using Software as a Medical Device (SaMD) become increasingly important. These medico-legal issues warrant an interdisciplinary approach and may affect the way we work in daily practice. In this article, we seek to address three major topics: medical malpractice liability, regulation of AI-based medical devices, and privacy protection in shared medical imaging data, thereby focusing on the legal frameworks of the European Union and the USA. As many of the presented concepts are very complex and, in part, remain yet unsolved, this article is not meant to be comprehensive but rather thought-provoking. The goal is to engage clinical neuroradiologists in the debate and equip them to actively shape these topics in the future.


Quick and easy method for extraction and purification of Pfu-Sso7d, a high processivity DNA polymerase.
The polymerase chain reaction is an extensively used technique with numerous applications in the field of biological sciences. In addition to naturally occurring DNA polymerases with varying processivity and fidelity, genetically engineered recombinant DNA polymerases are also used in PCR. The Pfu-Sso7d, a fusion DNA polymerase, is obtained by the fusion of Sso7d, a small DNA binding protein, to the polymerase domain of the Pfu DNA polymerase. Pfu-Sso7d is known for its high processivity, efficiency, and fidelity. Expensive commercial variants of Pfu-Sso7d are sold under various trade names. Here, we report a quick, cost and time-efficient purification protocol and an optimized buffer system for Pfu-Sso7d. We evaluated precipitation efficiencies of varying concentrations of ethanol and acetone and compared the activities of the precipitated enzyme. Although both the solvents efficiently precipitated Pfu-Sso7d, acetone showed better precipitation efficiency. Purified Pfu-Sso7d showed excellent activity in the PCR of templates with varying lengths and GC contents. We also report a buffer system that works with Pfu-Sso7d as efficiently as commercially available buffers. This quick and efficient purification scheme and buffer system will provide researchers cost-efficient access to fusion polymerase.


Orthogonal array designs for the optimization of liquid-liquid-liquid microextraction of nonsteroidal anti-inflammatory drugs combined with high-performance liquid chromatography-ultraviolet detection.
Orthogonal array designs (OADs) were applied for the first time to optimize liquid-liquid-liquid microextraction (LLLME) conditions for the analysis of three nonsteroidal anti-inflammatory drug residues (2-(4-chlorophenoxy)-2-methylpropionic acid, ketoprofen, and naproxen) in wastewater samples. Six relevant factors were investigated: type of organic solvent, composition of donor phase and acceptor phase, stirring speed, extraction time and salt concentration. In the first stage, mixed-level orthogonal array design, an OA16 (4(1) x 2(12)) matrix was employed to study the effect of six factors, by which the effect of each factor was estimated using individual contributions as response functions. Based on the results of the first stage, 1-octanol was chosen as organic solvent for extraction. The other five factors were selected for further optimization using an OA16 (4(5)) matrix and a 4 x 4 table to locate more exact levels for each variable. The relative standard deviations for the reproducibility of optimized LLLME varied from 6.2 to 7.1%. The coefficients of determination for calibration curves were higher than 0.9950. The method detection limits for drugs spiked in ultrapure water were in the range of 0.03-0.3 ng/mL. The final optimized conditions were applied to the analysis of drug residues in three wastewater samples in Singapore.


Microhabitat heterogeneity and population ecology of an herbivorous rodent, Microtus californicus.
Existing models of microtine population regulation and life history evolution rely on data derived from empirical studies which assume spatial homogeneity of the sampling unit, and infer that population dynamics can be described adequately by aggregation of individuals differing in sex, age and social status. These assumptions were not supported in the present study, and their application would have obscured relationships of ecological and evolutionary importance. From 1975 to 1981 a population of Microtus californicus exhibited seasonal fluctuations in numbers along with two extreme peaks in abundance. Floristic richness changed under the impact of heavy grazing by M. californicus, but floristic spatial pattern showed little interannual variation. All parameters of female survival and reproduction were correlated with floristic micropattern. Voles performed better in vegetation dominated by the native perennial grass Elymus triticoides. Female dispersion was more restricted than that of males. There are no reasons to believe the microhabitat preferred by females affords superior nutrition or protection from predation during peaks of abundance. However, it should provide higher probability of survival during summer, the time of greatest stringency in central California. The implications of these results for current theory are discussed, and a hypothesis developed which emphasises the importance of improved conditions in the most unfavourable season for peaks in abundance.