Cedrol, a Major Component of Cedarwood Oil, Ameliorates High-Fat Diet-Induced Obesity in Mice.
Excellent health-promoting effects of cedrol (CED), including anti-inflammatory, anti-arthritic, and antinociceptive effects, have been reported. The present study aims to investigate the preventive effects of CED on high-fat diet (HFD)-induced obesity and the related metabolic syndrome, and to delineate the underlying mechanism. Ten-week-old C57BL/6J mice are fed chow, HFD, or HFD supplemented with CED (0.2% w/w) for 19 weeks. Results demonstrate that CED effectively reduces HFD-induced body weight gain, decreases visceral fat pad weight, and significantly prevents adipocyte hypertrophy in mice. HFD-induced hepatic steatosis, glucose intolerance, insulin resistance, and gluconeogenesis are ameliorated by CED supplementation. 16S rRNA analysis reveals that CED does not change gut microbiota composition at the phylum and genus levels, indicating that CED may have limited effects on gut microbiota in HFD-fed mice. Further transcriptome analysis of epididymal white adipose tissue reveals reprogrammed RNA profiles by CED. These results demonstrate that incorporating CED in the diet can prevent HFD-induced obesity and related metabolic syndrome, and highlight that CED can be a promising dietary component for obesity therapeutic intervention.


Leiden reconstructed human epidermal model as a tool for the evaluation of the skin corrosion and irritation potential according to the ECVAM guidelines.
In the ECVAM validation studies two common skin protocols have been developed, the skin corrosion and skin irritation protocol. Both protocols include next to general and functional conditions that the skin model must meet, also the correct prediction of the activity of certain reference chemicals. For the skin corrosion protocol, the OECD TG 431 defined 12 reference chemicals that should be correctly predicted by the epidermal skin model. For skin irritation 20 test substances should meet the defined criteria. In this study we aimed to subject our Leiden human epidermal (LHE) model to both common protocols according to the ECVAM guidelines. The LHE model generated in this study has been fully characterized and shows very high similarities with the native skin. After minor technical changes in both protocols, corrosion classifications were obtained in concordance with those reported for the validated human skin models EpiSkin and EpiDerm. The results obtained with the common skin irritation protocol were very similar to that of earlier studies with the SkinEthic, EpiSkin and EpiDerm models. This means that the protocols and prediction models developed during the validation studies with a specific skin model can be used with other similar skin models. This study demonstrates that reconstructed human skin equivalents have been proven to be efficient and reliable alternatives to animal testing.


Ecological risk of anthropogenic pollutants to reptiles: Evaluating assumptions of sensitivity and exposure.
A large data gap for reptile ecotoxicology still persists; therefore, ecological risk assessments of reptiles usually incorporate the use of surrogate species. This necessitates that (1) the surrogate is at least as sensitive as the target taxon and/or (2) exposures to the surrogate are greater than that of the target taxon. We evaluated these assumptions for the use of birds as surrogates for reptiles. Based on a survey of the literature, birds were more sensitive than reptiles in less than 1/4 of the chemicals investigated. Dietary and dermal exposure modeling indicated that exposure to reptiles was relatively high, particularly when the dermal route was considered. We conclude that caution is warranted in the use of avian receptors as surrogates for reptiles in ecological risk assessment and emphasize the need to better understand the magnitude and mechanism of contaminant exposure in reptiles to improve exposure and risk estimation.


A transdiagnostic view on MDD and ADHD: shared cognitive characteristics?
Major Depressive disorder (MDD) and Attention Deficit Hyperactivity Disorder (ADHD) are prevalent mental disorders that often co-occur. There is overlap in symptomatology between MDD and ADHD that complicates diagnostics and treatment selection. Hence, to aid diagnostics of single and comorbid disorders, we aimed to examine the discriminative power of common symptom measures and cognitive dysfunction to differentiate between participants diagnosed with MDD, ADHD, ADHD and comorbid MDD and without a mental disorder. Four diagnosed groups were compared: MDD (n = 103), ADHD (n = 78), comorbid MDD + ADHD (n = 29), healthy controls (HC; n = 123). We examined between-group differences and discriminative functions of clinically validated self-report symptom questionnaires, as well as task-based and self-report measures of cognitive dysfunction. Based on the between group comparisons, all patient groups were characterized by clinically relevant levels of ADHD-symptomatology, executive dysfunction, and diminished cognitive performances in the domain of attention; even the MDD-only group. In addition, based on self-reported symptoms of MDD, ADHD, and executive dysfunction, discriminant function analysis classified all HC correctly (100%) and patients diagnosed with ADHD or MDD relatively well (resp. 85% and 82%). Comorbid MDD + ADHD was poorly differentiated from single MDD or ADHD by the commonly used self-report symptom questionnaires for MDD and ADHD (0% correct predictions), which substantially improved by incorporating the questionnaire on executive functioning (42% correct predictions). In both MDD and ADHD, clinical levels of attentional and executive dysfunction were found, while these clinical groups differed in cognitive flexibility, initiating, inhibition and meta-cognition. Comorbid MDD + ADHD was poorly distinguishable from non-comorbid MDD and ADHD based on self-reported symptoms of depression and ADHD. Addition of subjective executive function in the discrimination models resulted in increased discriminative power. Our findings indicate that executive functioning measure can improve the diagnostic process of ADHD and MDD.


Antimicrobial prophylaxis in acute leukaemia: prospective randomized study comparing two methods of selective decontamination.
In a prospective study the efficacy of two regimens for selective decontamination of the digestive tract was studied in patients with acute leukaemia during remission induction therapy. Seventy-eight patients were randomized to receive either a combination of cotrimoxazole, polymyxin B and nystatin (group A) or a combination of nalidixic acid, polymyxin B, neomycin and nystatin. With both regimens the gastrointestinal tract could be decontaminated equally effectively from potential pathogens. In the oropharyngeal region the decontamination from Enterobacteriaceae was significantly better in group A (P less than 0.01). In both groups less than 10% of the acquired infections were caused by gram-negative bacilli and no gram-negative septicaemia occurred in either group. The median time interval until the first acquired infection was 17 days in group A and 36 days in group B, respectively (P less than 0.05). It is concluded that regimen A might be more effective than regimen B though both regimens prevent reliably severe gram-negative infections.


Synthesis and in vitro pharmacological studies of C(4) modified salvinorin A analogues.
Salvinorin A is the most potent naturally occurring opioid agonist with a high selectivity and affinity for kappa-opioid receptor. To explore its structure-activity relationships, modifications at the C(4) position have been studied and a series of salvinorin A derivatives were prepared. These C(4)-modified salvinorin A analogues were screened for binding and functional activities at the human kappa-opioid receptor and several potent new agonists have been identified.


[Ingestion of caustic substances in children: 3 years of experience].
There is no clear consensus on the management of accidental ingestion of caustic substances in paediatrics. The aim of this study was to determine the profile of the paediatric population treated due to caustic ingestion in a Healthcare Centre. A descriptive study was conducted on patients treated for the ingestion of caustic substances in our hospital during the period 2008-2011. A total of 12 patients were treated, with a mean age of 3.8 years (1-13 years), with the majority males (58.8%). An alkaline product was ingested by 58.3%, and an acid by 41.6%. The majority (58.3%) did not refer to symptoms and the remainder referred to vomiting (33.3%), odynophagia (16.6%), haematemesis (8.3%), hyper-salivation (8.3%) and shortness of breath (8.3%). Oral cavity lesions were observed in 75% of cases. All, except one, were accidental. An endoscopy was performed on all of them (100%) between 12 and 24hours post-ingestion, with pathological findings in 41.6%. In the group that ingested an alkali, 2 (16.6%) patients had lesions, one a grade 2B and one a grade 3 oesophagitis. In the acid ingestion group, 4 (33.3%) patients had lesions; one grade 1-2A oesophagitis, two acute non-erosive gastritis, and one acute haemorrhagic gastritis. A follow-up endoscopy was performed depending on the previous endoscopic findings. Only two patients presented with complications. Emphasis is placed on the endoscopic evaluation in the first 24hours of deliberate asymptomatic ingestions, as well as a strict follow-up in those that ingested acids, due to delayed associated lesions.


Pharmacokinetics of intravenous amikacin after rapid and slow infusion with special reference to hemodialysis.
The pharmacokinetics of amikacin, a recently introduced aminoglycoside structurally related to kanamycin, were determined in healthy volunteers after rapid and slow constant-rate intravenous administration of a 7.5 mg/kg dose. The elimination profile of amikacin can be described by two compartment open model kinetics. Peripheral distribution of the drug is extremely rapid, and beta-phase concentrations decay with a half-life averaging about 2 hours, while inter-compartmental equilibrium is achieved in a little over 30 minutes. The volume of distribution averages about 25% of body weight. During hemodialysis, amikacin extraction from the blood reaches 97% +/- 17% (mean +/- 95% confidence interval) that of creatinine and 89% +/- 20% that of blood urea nitrogen. A method of administration adapted to the kinetic properties of the antibiotic is proposed.


Long-term liver stiffness assessment in hepatitis C virus patients undergoing antiviral therapy: Results from a 5-year cohort study.
Observational studies showed significant liver stiffness regression after sustained virological response, but long-term effects of antiviral therapy are still unknown. The aim of this study was to assess the magnitude of change in stiffness up to 5 years after therapy in hepatitis C patients undergoing antiviral treatment. Data of 153 patients were retrieved. Stiffness was assessed by Fibroscan at baseline, end of treatment, 6 months after treatment, and every year hereafter up to 5 years. Seventy patients were treated with interferon-based regimens and 83 with direct antiviral agents. Baseline cirrhosis was diagnosed in 53 (34.6%) patients. Sustained virological response was achieved in 112 patients, whereas 41 were non-responders. In responders, stiffness decreased from 12.3 kPa (9-17.8) to 6.6 kPa (5.3-7.4) at 5 years. A sharper decline was observed immediately after treatment (-2.5 kPa at the end of treatment and -3.7 kPa at 6 months), while from 1 year onwards, the magnitude of stiffness decrease was progressively lower. In non-responders, stiffness showed a slight decrease at the end of treatment (from 19.2 to 18.1 kPa), then returned to baseline levels at 6 months (19.4 kPa), and finally increased over time up to 23.7 kPa (15-32.5) at 5 years. The proportion of cirrhotic patients decreased by 50% at 6 months and finally fell < 5% at 4 years after treatment. Stiffness declines significantly after achieving response, and the magnitude of decline is greater in the first year after treatment, while it tends to plateau from 1 year onwards.


Mutant of Escherichia coli deficient in osmoregulation of periplasmic oligosaccharide synthesis.
A mutant of Escherichia coli (mdoR) has been isolated which is defective in synthesis of the membrane-derived oligosaccharides (MDO) normally found in the periplasmic space. In media of high osmotic pressure this defect is suppressed and MDO levels approaching those of the wild type are produced. The mdoR mutant also fails to accumulate glycogen; however, genetic analysis showed that mdoR was not cotransducible with the known glg (glycogen) locus. A further relationship between MDO and glycogen metabolism was suggested by two observations that (i) certain glg mutants affect MDO accumulation and (ii) elevated osmotic pressure inhibits glycogen accumulation, in both wild-type and mdoR cells.


Minding the gap: Unlockingthe therapeutic potentialof aptamers and making up for lost time.
Aptamers are RNAs that can bind proteins directly and modulate protein-protein interactions. Given their therapeutic potential, aptamers would be expected to capture the interest of both scientists and investors. However, concerns regarding safety, efficacy, and delivery have delayed aptamer development and dampened investor support. Herein, we discuss the major hurdles stalling the translational application of aptamers over recent years and focus on approaches to overcome current barriers and attract the scientific community and investors to the aptamer field.


Phylogeography of sika deer (Cervus nippon) inferred from mitochondrial cytochrome-b gene and microsatellite DNA.
The genetic diversity and phylogenetic relationships of sika deer of different subspecies are uncertain. In order to explore the phylogenetic relationship of different sika deer subspecies, this study used a wider sample collection to analyze mitochondrial sequences and nuclear microsatellites of sika deer. The full lengths of cytochrome-b gene of 134 sika deer were sequenced, and 16 haplotypes were obtained. Based on phylogenetic and haplotype networks analysis, the sika deer was not clustered according to subspecies but was divided into four lineages. Lineage I includes individuals from C.n.kopschi, C.n.sichuanicus, and C.n.hortulorum subspecies; Lineage II includes individuals from C.n.hortulorum subspecies; Lineage III includes individuals from C.n.centralis, C.n.yakushime, C.n.mageshimae, and C.n.keramae subspecies, namely southern Japanese population; Lineage IV includes individuals from C.n.centralis and C.n.yesoensis subspecies, namely northern Japanese population. The microsatellite analysis showed that the sika deer in China and Japan originated independently. The three subspecies of China have significant genetic differentiation, while the three subspecies of Japan have no significant differentiation. This study provides reference for the research of genetic diversity and phylogenetic relationship of sika deer, and also provides scientific data for the evaluation, protection, and utilization of sika deer resources.


Predicting pharmaceutical inkjet printing outcomes using machine learning.
Inkjet printing has been extensively explored in recent years to produce personalised medicines due to its low cost and versatility. Pharmaceutical applications have ranged from orodispersible films to complex polydrug implants. However, the multi-factorial nature of the inkjet printing process makes formulation (e.g., composition, surface tension, and viscosity) and printing parameter optimization (e.g., nozzle diameter, peak voltage, and drop spacing) an empirical and time-consuming endeavour. Instead, given the wealth of publicly available data on pharmaceutical inkjet printing, there is potential for a predictive model for inkjet printing outcomes to be developed. In this study, machine learning (ML) models (random forest, multilayer perceptron, and support vector machine) to predict printability and drug dose were developed using a dataset of 687 formulations, consolidated from in-house and literature-mined data on inkjet-printed formulations. The optimized ML models predicted the printability of formulations with an accuracy of 97.22%, and predicted the quality of the prints with an accuracy of 97.14%. This study demonstrates that ML models can feasibly provide predictive insights to inkjet printing outcomes prior to formulation preparation, affording resource- and time-savings.


Dextran sulfate sodium leads to chronic colitis and pathological angiogenesis in Endoglin heterozygous mice.
Pathological angiogenesis is an intrinsic component of chronic intestinal inflammation, which results in remodeling and expansion of the gut microvascular bed. Endoglin is essential for endothelial cell function and physiological angiogenesis. In this study we investigated its potential role in the regulation of inflammation by testing the response of Endoglin heterozygous (Eng(+/-)) mice to experimental colitis. C57BL/6 Eng(+/-) and littermate control mice drank water supplemented with 3% dextran sulfate sodium (DSS) for 5 days and were monitored for up to 26 days for clinical signs of colitis. Inflammation, crypt damage, and angiogenic index were scored on histological sections of distal colon. Levels of the vascular endothelial growth factor (VEGF) and angiopoietins were measured by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and/or Western blots. Vascular permeability was assessed using Evans Blue. Eng(+/-) and control mice developed acute colitis, which peaked at day 9. While control mice recovered by days 19-26, Eng(+/-) mice progressed to chronic colitis and showed numerous vascular protrusions penetrating into the serosa of the inflamed distal colon. Prior to DSS induction, VEGF levels and vascular permeability were higher in the distal colon of Eng(+/-) mice, while angiopoietin 1 and 2 levels were unchanged. In the chronic phase of colitis, VEGF levels were increased in both groups of mice and remained significantly higher in the Eng(+/-) mice. Higher VEGF levels and increased vascular permeability in the distal colon may predispose Eng(+/-) mice to progress to chronic and persistent bowel inflammation, associated with pathological angiogenesis.


Protection against aflatoxin-B1-induced liver mutagenesis by Scutellaria baicalensis.
We have measured the inhibition of the mutagenicity of the mycotoxin aflatoxin-B(1) in the liver of the rat by plant material of Scutellaria baicalensis, or Huang-qin. The addition of one percent dried Huang-qin to the feed of the animals reduced the mutant frequency of a subsequent administration of aflatoxin-B1 by approximately 60 and 77%, respectively, for two different batches of the plant material. The addition of Huang-qin also increased the expression of the gene for glutathione S-transferase A5 subunit by 2.5-3.0-fold, and decreased expression of P450 cytochrome 3A2 by 1.8-2.0-fold. The greater increase of the expression of the GST gene may result in the protection shown by Huang-qin. The sensitivity of the hepatic mitochondria to swelling, a measure of the mitochondrial permeability transition, is increased significantly in animals that are on a diet containing Huang-qin. This may lead to increased sensitivity to apoptosis on treatment with toxic compounds. The two batches of Huang-qin material show differences in both chemical composition and preventive potential. This study demonstrates how a combination of generating and analysis of plant varieties together with a mammalian assay for efficacy may improve the search for better plant-based prevention of cancer initiation.


Health Service Quality Scale: Brazilian Portuguese translation, reliability and validity.
The Health Service Quality Scale is a multidimensional hierarchical scale that is based on interdisciplinary approach. This instrument was specifically created for measuring health service quality based on marketing and health care concepts. The aim of this study was to translate and culturally adapt the Health Service Quality Scale into Brazilian Portuguese and to assess the validity and reliability of the Brazilian Portuguese version of the instrument. We conducted a cross-sectional, observational study, with public health system patients in a Brazilian university hospital. Validity was assessed using Pearson's correlation coefficient to measure the strength of the association between the Brazilian Portuguese version of the instrument and the SERVQUAL scale. Internal consistency was evaluated using Cronbach's alpha coefficient; the intraclass (ICC) and Pearson's correlation coefficients were used for test-retest reliability. One hundred and sixteen consecutive postoperative patients completed the questionnaire. Pearson's correlation coefficient for validity was 0.20. Cronbach's alpha for the first and second administrations of the final version of the instrument were 0.982 and 0.986, respectively. For test-retest reliability, Pearson's correlation coefficient was 0.89 and ICC was 0.90. The culturally adapted, Brazilian Portuguese version of the Health Service Quality Scale is a valid and reliable instrument to measure health service quality.


O-glycoproteomics: site-specific O-glycoprotein analysis by CID/ETD electrospray ionization tandem mass spectrometry and top-down glycoprotein sequencing by in-source decay MALDI mass spectrometry.
The sites of mucin-type O-glycosylation are difficult to predict, making structural analysis by mass spectrometry indispensible. This chapter refers to state-of-the-art techniques in the site localization of O-linked glycans and their structural characterization in situ using tandem ESI and MALDI mass spectrometry. Detailed protocols are provided that describe the application of nano-LC-ESI-MS/MS with alternative fragmentation modes (collision-induced dissociation vs. electron-transfer dissociation) for the analysis of O-glycopeptides. Moreover, a top-down sequencing approach by MALDI-MS is presented that is based on the in-source decay of intact glycoproteins or large glycopeptides and allows a ladder sequencing of up to 70 amino acid residues from both termini with unequivocal assignment of modified sites.


Fat crystallization of blends of palm oil and anhydrous milk fat: A comparison between static and dynamic-crystallization.
The application of dynamic-crystallization (a combination of shear with rapid cooling) often plays an important role in the production of industrial fat-based products such as shortenings/margarines but has been rarely reported. In this study, three blends of palm oil (PO) with anhydrous milk fat (AMF) (0, 25 and 50% AMF, w/w) were rapidly crystallized under static (using freezer) and dynamic conditions (using a benchtop scraped surface heat exchanger). Various techniques including differential scanning calorimetry (DSC), X-ray diffraction (XRD), polarized light microscopy (PLM), rheology and texture analysis were applied to investigate physicochemical properties of fat blends as well as their crystal morphology upon the long-term storage (4 weeks) at 5 °C and 15 °C. The results revealed that high cooling rate of dynamic-crystallization not only affected melting behavior of fat blends but also prevented the polymorphic transformation from β' to β crystals. Besides, the application of shear during fat crystallization helped to improve significantly the gel strength of produced shortenings. Although post-crystallization of low melting triacylglycerols (TAGs) occurred for all produced shortenings during storage at 5 °C which was accompanying with a firmness increase, it was more considerable for samples owning higher AMF content. Moreover, this phenomenon promoted the sintering as well as Ostwald ripening between fat crystals of dynamic-crystallized fat blends resulting in the formation of unwanted large aggregates (or granular crystals) with the size ranging from 100 to 500 μm.


A simple stochastic model describing the evolution of genomic GC content in asexually reproducing organisms.
A genome's nucleotide composition can usually be summarized with (G)uanine + (C)ytosine (GC) or (A)denine + (T)hymine (AT) frequencies as GC% = 100% - AT%. Genomic AT/GC content has been linked to environment and selective processes in asexually reproducing organisms. A model is presented relating the evolution of genomic GC content over time to AT [Formula: see text] GC and GC [Formula: see text] AT mutation rates. By employing Itô calculus it is shown that if mutation rates are subject to random perturbations, that can vary over time, several implications follow. In particular, an extra Brownian motion term appears influencing genomic nucleotide variability; the greater the random perturbations the more genomic nucleotide variability. This can have several interpretations depending on the context. For instance, reducing the influence of the random perturbations on the AT/GC mutation rates and thus genomic nucleotide variability, to limit fitness decreasing and deleterious mutations, will likely suggest channeling of resources. On the other hand, increased genomic nucleotide diversity may be beneficial in variable environments. In asexually reproducing organisms, the Brownian motion term can be considered to be inversely reflective of the selective pressures an organism is subjected to at the molecular level. The presented model is a generalization of a previous model, limited to microbial symbionts, to all asexually reproducing, non-recombining organisms. Last, a connection between the presented model and the classical Luria-Delbrück mutation model is presented in an Itô calculus setting.


Incorporating life expectancy in glaucoma care.
To calculate for which combinations of age and perimetric disease stage glaucoma patients are unlikely to become visually impaired during their lifetime. We used residual life expectancy data (life expectancy adjusted for the age already reached) as provided by Statistics Netherlands and rates of progression as derived from published studies. We calculated the baseline mean deviation (MD) for which an individual would reach a MD of -20 dB at the end of life as a function of age and rate of progression. For situations in which the individual rate of progression is unknown, we used the 90th percentiles of rate of progression and residual life expectancy. For situations in which the individual rate of progression is known, we used the 95th percentile of the residual life expectancy. An easily applicable graphical tool was developed that enables an accurate estimate of the probability of becoming visually impaired during lifetime, given age, current glaucomatous damage, and--if available--the individual rate of progression. This novel tool enables the clinician to incorporate life expectancy in glaucoma care in a well-founded manner and may serve as a starting point for personalized decision making.


Platelet-activating factor. Role in fetal lung development and relationship to normal and premature labor.
In this overview on the role of PAF in reproductive biology, we have emphasized its relationship to fetal lung maturation and the initiation and maintenance of parturition. In addition, we have discussed the role of this autacoid in certain complications of premature delivery. It should be pointed out, however, that it is our view that other mediators and cytokines also play a role in these processes. In the past, many investigators have suggested a central role for one of these mediators that serves as the "trigger" of these biologic events. It is our view that these systems are regulated by a number of effectors, among which PAF may play an important role.


[History of corticotherapy].
Corticosteroids emerged in the late 1940s, at a time when steroid chemistry began to offer new therapeutic approaches. Extractive chemistry (T. Reichstein), chemical synthesis (E.C. Kendall) and clinical investigations (P. Hench) were combined to result in the discovery of cortisone in 1948, leading to a long series of related derivatives. Besides their first applications to treat Addison's disease and rheumatic or inflammatory diseases, corticosteroids could easily correct many metabolic and functional symptoms. Fluoridation of the steroid skeleton allowed the development of more active and better tolerated molecules. Corticosteroids have revolutionized the treatment of allergic diseases or immunity troubles, graft rejection, many dermatological, respiratory, digestive, eye diseases, etc. It is used today in all areas of therapeutic.


GABA negatively regulates adventitious root development in poplar.
γ-Aminobutyric acid (GABA) influences plant growth, but little is known about how this metabolite regulates adventitious root (AR) development. Here, we investigate the effects of GABA on ARs using poplar lines overexpressing glutamate decarboxilase 2 (GAD2) and by treating poplar stem cuttings with exogenous GABA or vigabatrin (VGB; a specific GABA transaminase inhibitor). Endogenous GABA accumulation not only inhibited AR growth, but it also suppressed or delayed AR formation. Anatomical observations revealed that the GABA and VGB treatments resulted in a 1 d delay in the formation of AR primordia and the appearance of ARs. This delay coincided with changes in primary metabolism, including transient increases in hexose and amino acid levels. GABA-dependent changes in the expression of genes related to hormone synthesis and signalling, as well as analysis of hormone levels revealed that ethylene-dependent pathways were decreased at the earliest stage of AR formation. In contrast, auxin and abscisic acid were increased at 1-5 d as well as GA4 over a 5 d period of AR formation. These results demonstrate that GABA plays a crucial role in AR development. Evidence is presented demonstrating that GABA can interact with hormone-related pathways as well as carbon/nitrogen metabolism. These findings also elucidate the functions of GABA in plant development.


[Dose curves for radiation-induced cytogenetic damage in human lymphocytes].
Insufficient fitness of experimental data with convenient linear and linear-quadratic models of "dose-effect" dependence for the number of chromosome aberrations of different types were revealed. Proposed method of approximation of the experimental "dose-effect" dependence with piece-linear splines allows to obtain more accurate results in the most cases and therefore is more preferable than the linear and linear-quadratic models.


Macrocyclic diterpenes from Euphorbia nivulia.
The latex of Euphorbia nivulia afforded two ingol diterpenes 3,12-diacetyl-8-benzoylingol (4) and 3,12-diacetyl-7-benzoyl-8-nicotinylingol (5) along with three known ingol diterpenes 1, 2,and 3, and two known triterpenes cycloart-25-en-3beta-ol and cyclonivulinol. Their structures have been assigned on the basis of their structural data as well as their acetylated products. The diterpenes 1-5 were tested for the LPS induced PGE(2) inhibition activity.


Study of adsorption of anionic dyes over biofabricated crystalline α-MnO2 nanoparticles.
The leaf extract of Ficus retusa plant was used for fabrication of α-MnO2 nanoparticles (NPs). The extract was utilized as a reducing agent for green synthesis of nanomaterial. The synthesis of nanocrystals was confirmed using different analytical techniques such as field emission scanning electron microscopy (FESEM), energy-dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD) spectroscopy and thermogravimetric analysis (TGA). The synthesis of NPs was studied over a wide range of temperatures from 80 to 800 °C. It was found that perfectly crystalline α-MnO2 NPs were successfully synthesized at 800 °C. The synthesized NPs were applied as an adsorbent for adsorption of azo dyes such as methyl red (MR) and methyl orange (MO) which are released as wastes from industries into water bodies and pollute the water. The removal efficiency was analysed and optimized depending on various parameters like pH, concentration of NPs, and contact time. The experimental data was explained by three isotherm models, viz. Langmuir, Freundlich and Temkin isotherms. Kinetic and thermodynamic studies of adsorption were also carried out, which depicted that the adsorption process of both dyes was exothermic in nature and followed pseudo-second-order kinetics. The results confirmed that NPs are easily fabricated through a green route and prove to be an excellent adsorbent for the removal of MO and MR dyes from their aqueous solutions. The maximum adsorption capacity of NPs synthesized was found to be 116.1 mg g-1 and 74.02 mg g-1 for MO and MR dyes, respectively. Graphical abstract.


Neuraxial drug delivery in pain management: An overview of past, present, and future.
Activation of neuraxial nociceptive linkages leads to a high level of encoding of the message that is transmitted to the brain and that can initiate a pain state with its attendant emotive covariates. As we review here, the encoding of this message is subject to a profound regulation by pharmacological targeting of dorsal root ganglion and dorsal horn systems. Though first shown with the robust and selective modulation by spinal opiates, subsequent work has revealed the pharmacological and biological complexity of these neuraxial systems and points to several regulatory targets. Novel therapeutic delivery platforms, such as viral transfection, antisense and targeted neurotoxins, point to disease-modifying approaches that can selectively address the acute and chronic pain phenotype. Further developments are called for in delivery devices to enhance local distribution and to minimize concentration gradients, as frequently occurs with the poorly mixed intrathecal space. The field has advanced remarkably since the mid-1970s, but these advances must always address the issues of safety and tolerability of neuraxial therapy.


Human haemoglobin - Northfield.
PolyHeme is a chemically modified haemoglobin solution derived from human blood. It has been developed by Northfield Laboratories as an alternative to transfused blood for the treatment of acute blood loss (such as in trauma or surgery). Single molecules of haemoglobin are toxic to the kidneys and cause vasoconstriction. The haemoglobin molecules in PolyHeme are polymerised to create small chains of linked tetramers. In August 2001, Northfield Laboratories stated that it had submitted a Biologics Licence Application (BLA) to the US FDA for approval of PolyHeme as a blood substitute for use in the treatment of urgent, life-threatening blood loss. There were some undisclosed problems with the BLA, and the US FDA asked for more information before it would accept the application or allow the company to conduct a trial for this indication. In March 2003, Northfield Laboratories announced that it had received clearance from the US FDA to proceed with a pivotal phase III trial evaluating the safety and efficacy of PolyHeme in improving patient survival when used to treat severely injured and bleeding trauma patients at the scene of injury and during ambulance transport to the hospital. Because of the severity of patients' injuries, this trial will be conducted under federal regulations that allow clinical research in emergency settings without obtaining informed consent. This trial will be conducted in urban settings where transit times to hospital may be short and not long enough to demonstrate superiority to the control group, therefore dual primary endpoints of superiority and non-inferiority will be evaluated. Northfield Laboratories has initiated a public disclosure and community consultation process; because informed consent will not be possible, this is one of the US FDA requirements that must be met prior to initiating the trial. In June 2003, Northfield Laboratories reached an agreement with the US FDA on Special Protocol Assessment (SPA) for the trial. The SPA is an acknowledgment and agreement between the trial sponsor and the US FDA for successful completion of the proposed trial to form the primary basis for an efficacy claim. In October 2002, Northfield Laboratories announced that it was collaborating with the US Army in developing a treatment Investigational New Drug Application (IND) for the battlefield use of PolyHeme. The IND is being developed to gain authorisation for the use of PolyHeme in patients in shock in remote battlefield settings, where red blood cells are not available. Phase III trials in the UK, Germany and Sweden are underway with Pharmacia Corporation (now Pfizer), who has licenced PolyHeme in these countries. On 16 April 2003, Pharmacia Corporation was acquired by, and merged into, Pfizer. Northfield Laboratories' US phase III trials have focused on elective surgery indications while the European trials are focusing on surgery with acute trauma patients where large amounts of blood are lost. Up to 20 units of PolyHeme have been infused in US trials in trauma patients. This volume represents 200% of an average person's blood volume. Northfield Laboratories has estimated that of the approximately 14 million units of blood which were used for transfusions in the US in 2001, about 8.5 million units were for acute blood loss, for which patient charges amounted to an estimated $US2.5 billion. The US transfusion market consists of two principal segments: the acute blood loss segment, which accounts for about 60% of the total market according to Northfield Laboratories, and the chronic blood loss segment, accounting for the remaining 40%. The former includes transfusions in connection with trauma, surgery and unexpected blood loss, while the latter includes transfusions used in general medical applications and chronic anaemias. Northfield Laboratories believes that PolyHeme's largest potential is in the elective surgery market, at the time estimated to use approximately 6.5 million units of blood in the US annually.Earlier, on 7 March 2003, the newswires quoted er, on 7 March 2003, the newswires quoted the CEO of Northfield Laboratories, stating that it is to administer 10 000 units of PolyHeme to 20 US trauma centres, following US FDA approval of a third phase III trial. Pending market approval of PolyHeme, the company will initially produce 75 000 units of the product, but expects this to increase to 400 000 units annually. Wall Street analysts have estimated the market potential for a substitute blood product to be in the "multibillion-dollar" range, according to the CEO. However, launch of PolyHeme was at the time said to be "a couple of years away".


A null mutation for Fmr1 in female mice: effects on regional cerebral metabolic rate for glucose and relationship to behavior.
As a measure of functional activity we determined regional cerebral metabolic rate for glucose (rCMR(glc)) in adult, female wild type and fragile X (Fmr1 null) mice homozygous and heterozygous for the null mutation. To ascertain if the sexes differ with respect to the severity of the effects of the mutation we compared our results with results of our previous study on male Fmr1 null mice [Qin M, Kang J, Smith CB (2002) Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 99:15758-15763.]. In contrast to the male Fmr1 null mouse, rCMR(glc) was unchanged in the homozygous female except in the dorsal raphe where rCMR(glc) was increased by 36%. There were no differences in rCMR(glc) between heterozygous and wild type female mice. We compared male and female mice for effects of the null mutation on behavior. We found that the female Fmr1 null mouse is similar to the male with deficits in performance on a passive avoidance task, general hyperactivity, and increased susceptibility to audiogenic seizures. Both homozygous and heterozygous female mice exhibited hyperactivity and increased susceptibility to seizures, whereas only the homozygous mice had a deficit on the passive avoidance test. Male Fmr1 null mice had a tendency for lower anxiety-like behavior in an open field, whereas this was not evident in females. Compared with male wild type, male Fmr1 null mice also had a diminished acoustic startle response at higher stimulus intensities, whereas all three female genotypes had responses similar to those of male Fmr1 null mice. Whether estrogen affords female Fmr1 null mice some protection from the effects of the mutation remains to be determined.


Suppression of inducible nitric oxide synthase and cyclooxygenase-2 expression by tussilagone from Farfarae flos in BV-2 microglial cells.
Activated microglia produce diverse neurotoxic factors such as nitric oxide (NO) and prostaglandin E(2) (PGE(2)) that may cause neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. From the EtOAc soluble fraction of Farfarae flos (Tussilago farfara), we purified tussilagone as a bioactive compound by monitoring the inhibitory potential of NO production in activated microglia through the purification procedures. Tussilagone showed dose-dependent inhibition of NO and PGE(2) production in LPS-activated microglia with IC(50) values of 8.67 microM and 14.1 microM, respectively. It suppressed the expression of protein and mRNA of inducible nitric oxide synthase and cyclooxygenase-2 through the inhibition of 1-kappaBalpha degradation and nuclear translocation of p65 subunit of NF-kappaB. Therefore tussilagone from Farfarae flos may have therapeutic potential in the treatment of neuro-inflammatory diseases through the inhibition of overproduction of NO and PGE(2).


Introducing a methodology for estimating duration of surgery in health services research.
The duration of surgery is an indicator for the quality, risks, and efficiency of surgical procedures. We introduce a new methodology for assessing the duration of surgery based on anesthesiology billing records, along with reviewing its fundamental logic and limitations. The validity of the methodology was assessed through a population-based cohort of patients (n=480,986) undergoing elective operations in 246 Ontario hospitals with 1,084 anesthesiologists between April 1, 1992 and March 31, 2002 (10 years). The weaknesses of the methodology relate to missing data, self-serving exaggerations by providers, imprecisions from clinical diversity, upper limits due to accounting regulations, fluctuations from updates over the years, national differences in reimbursement schedules, and the general failings of claims base analyses. The strengths of the methodology are in providing data that match clinical experiences, correspond to chart review, are consistent over time, can detect differences where differences would be anticipated, and might have implications for examining patient outcomes after long surgical times. We suggest that an understanding and application of large studies of surgical duration may help scientists explore selected questions concerning postoperative complications.


Promoter-dependent disruption of genes: simple, rapid, and specific PCR-based method with application to three different yeast.
PCR product-based gene disruption has greatly accelerated molecular analysis of Saccharomyces cerevisiae. This approach involves amplification of a marker gene (e.g., URA3) including its flanking regulatory (promoter and polyadenylation) regions using primers that include at their 5' ends about 50 bases of homology to the targeted gene. Unfortunately, this approach has proved less useful in organisms with higher rates of non-homologous recombination; e.g., in the yeast Candida glabrata, desired recombinants represent < or =2% of transformants. We modified the PCR-based approach by eliminating marker-flanking regions and precisely targeting recombination such that marker expression depends on the regulatory sequences of the disrupted gene. Application of this promoter-dependent disruption of genes (PRODIGE) method to three C. glabrata genes (SLT2, LEM3, and PDR1) yielded desired recombinants at frequencies of 20, 31, and 11%, the latter representing a weakly expressed gene. For Candida albicans LEM3 and RHO1, specificity was 79-95% for one or both alleles, >sixfold higher than the published results with conventional PCR-based gene disruption. All 5 C. glabrata and C. albicans mutants had predicted phenotypes of calcofluor hypersensitivity (slt2Delta and RHO1/rho1Delta), cycloheximide hypersensitivity (pdr1Delta), or miltefosine resistance (lem3Delta and lem3Delta/lem3Delta). PRODIGE application to the S. cerevisiae PDR5 gene in strains with and without the Pdr1-Pdr3 transcriptional activators of this gene confirmed that transformant yield and growth rate depend on promoter strength. Using this PDR5 promoter-URA3 recombinant, we further demonstrate a simple extension of the method that yields regulatory mutants via 5-fluoroorotic acid selection. PRODIGE warrants testing in other yeast, molds, and beyond.


Healthcare Provider Communication Patterns during Consultations about Treating Localized Prostate Cancer.
Disparities in mortality in prostate cancer may reflect differences in healthcare providers' communication. This study examined physicians' communication with African American and Caucasian men when making decisions about treatment for localized prostate cancer to determine whether information-giving and partnership-building behaviors varied by the age, education level, and race of the patient. The study was a secondary analysis of data from a larger study examining decisionmaking among men with prostate cancer. Verbatim transcripts of physician communication with 13 African American and 32 Caucasian patients were coded using a well-established scheme. Physicians tended to use information-giving and partnership-building behaviors more often with patients who were Caucasian, but this practice was tempered by the patient's age or education level. Information-giving and partnership-building behaviors should be studied relative to patient outcomes, such as treatment adherence and satisfaction. Communication is a two-way interaction, and patients' perceptions should be included in future studies. Biases, assumptions, and differential behavior toward patients who are older, minorities, or less educated must be addressed during all healthcare providers' socialization and education. All will benefit from their education in communication and partnership-building with patients.


Particulate pollution in different housing types in a UK suburban location.
To investigate the levels of particulate pollution in residential built environments measurements of PM(10), PM(2.5), and PM(1) and concentrations were made between 2004 and 2008 in various residencies in a UK suburban location. Measurements were carried out in three different residential settings (Types I, II and III). In type I non-smoking living rooms, the highest 24-hour mean concentrations were found in summer. When smoking took place in type I residences, the concentrations of PM(10), PM(2.5) and PM(1), during the winter were almost double those in summer. In type II houses the concentrations were higher in the houses with open plan kitchens than in those with separate kitchens. In type III houses, mean concentrations were significantly higher in wood heated living rooms than those using central heating. In kitchens, cooking resulted in substantially higher concentrations of particulate matter with levels above those in smoking living rooms in winter. The hourly maximum values of number concentration were considerably higher in smoking rooms than non-smoking ones. Cooking resulted in increased number concentrations, with the average hourly maximum concentration of 179,110 #/cm(3). Particle mass and number emission rates were determined for a number of activities. In kitchens grilling had the highest average number emission rate, followed by boiling and frying. The results clearly highlight the impact of different forms of dwelling and their use and management by occupants on the levels of particulate matter in naturally ventilated residential built environments.


Structural transition in micelles: novel insight into microenvironmental changes in polarity and dynamics.
Structural transitions involving shape changes play an important role in cellular physiology. Such transition can be conveniently induced in charged micelles by increasing ionic strength of the medium. Shape changes have recently been shown to result in altered packing and lowering of micellar polarity. As a consequence of reduced polarity, the ionization states of micelle-bound molecules vary in micelles of different shape. The changes in micellar organization and dynamics due to structural transition can be effectively monitored utilizing the red edge excitation shift (REES). These changes are influenced by the position (location) of the probe in the micelle, i.e., the region of the micelle being monitored. Changes in organization and dynamics of probes and peptides upon structural transition are discussed with representative examples. We envisage that the reduction in micellar polarity and tighter packing upon structural transition represent important factors in the incorporation of drugs in micelles (nano-carriers), since micellar polarity plays a crucial role in the incorporation of drugs.


NADPH-diaphorase activity increases during estrous phase in the bed nucleus of the accessory olfactory tract in the female rat.
We investigated the presence of nitric oxide in the bed nucleus of the accessory olfactory tract (BAOT) in males, diestrous females and estrous females using NADPH-diaphorase. Our results demonstrate a significant increase in the density of the medium-stained cells in the estrous female rats suggesting that during estrous a specific subpopulation of nitrinergic cells are activated in the BAOT. This might be related to the physiological and behavioral changes that occurs in estrous.


Buprenorphine versus morphine. A comparison of intra-operative and postoperative analgesia.
A randomised double-blind trial comparing morphine and buprenorphine and postoperative analgesia combined with droperidol was conducted in 60 patients. Compared with morphine, taken as the standard analgesic, buprenorphine was shown to be a satisfactory analgesic for major surgery, with no difference in the incidence of unwanted effects.


[Comparative estimation of open and mini-invasive interventions in the treatment of hepatic abscesses and accumulations of liquid of postoperative genesis].
A comparative aspect of the treatment results for pyogenic hepatic abscesses and extraorgan accumulations of postoperative liquid, using transcutaneous ultrasonografically controlled and open-access interventions, was studied up in 328 patients. The efficacy and concurrent ability of miniinvasive technologies in such patients was proved.


U-shaped relationship between uric acid and residual renal function decline in continuous ambulatory peritoneal dialysis patients.
There is little information on the relationship between uric acid (UA) and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD). The aim of this research is to study the influence of UA on RRF decline in CAPD patients. A retrospective observational cohort study of 304 patients who started CAPD without anuria between 2001 and 2010 was conducted at a single medical center. The outcomes measured in the study included the rate of RRF decline and anuria. A multiple ordinal logistic regression model with backward elimination was conducted to determine the independent factors of the slope of RRF decline. A Cox proportional hazard model was conducted to determine the independent variables of time to anuria. The average rate of RRF decline was -0.12 ± 0.22 mL/min per month. Multivariate analysis showed that lower UA group (<0.372 mmol/L), higher UA group (≧0.421 mmol/L), male gender, diabetes mellitus (DM), the use of calcium channel blocker (CCB), and RRF at baseline were linked positively with the rate of RRF decline; on the other hand, independence in dialysate exchanges and BUN were negatively associated with the risk of RRF decline. In addition, male gender, DM, diuretics, and CCB were associated with a higher risk of progression to anuria, whereas 24-h urine amount at baseline conferred a protective role in the development of anuria. A U-shaped relationship was found between UA levels and the rate of RRF decline in patients on CAPD, with a faster decline rate in those of higher and lower UA groups.


Melorheostosis--a very rare entity in neurosurgery.
Melorheostosis is of minor importance in neurosurgery. A case of this disease is reported, which required neurosurgical activity and the literature is reviewed.


Which vaginal douching agent is the best choice before oocyte retrieval? A systematic review and network meta-analysis.
The aim of this study was to evaluate six vaginal douching agents (Iodine, Saline, Iodine followed by saline, chlorhexidine acetate followed by saline, Ozone, Potassium permanganate) on oocytes pick-up related pelvic infection (OPU-PI) and IVF outcome in patients underwent assisted reproduction technology (ART). Through searching PubMed, Embase, Cochrane Library, Web of Science, Ovid, CINAHL CNKI, only human clinical trials were collected to study the effects of the six vaginal douching agents on OPU-PI and IVF outcomes. The included studies were evaluated for methodological quality by the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. The clinical trials were collected between the earliest available date and June 2022. Eight studies were included, the total sample size used in the study was 12,567. The results of the network meta-analysis showed that Ozone can significantly decrease OPU-PI; Iodine followed by saline can be a antiseptic protocol ranked first without affecting the quality of oocytes and Chlorhexidine acetate followed by saline can improve patients' clinical pregnancy rate. Based on Ranking Plot of the Network, this review reports the best evidence available regarding different vaginal douching agents used before OPU.


Melatonin prevents free radical formation due to the interaction between beta-amyloid peptides and metal ions [Al(III), Zn(II), Cu(II), Mn(II), Fe(II)].
Alzheimer's disease, among other pathological features, is characterized by an over-accumulation of amyloid-beta peptide, metal ions, and oxidative stress proteins in the brain. Amyloid-beta aggregated peptides with bound metal ions may initiate free radical generation with consequent protein and lipid oxidation, reactive oxygen species formation and eventually neuronal death. Melatonin is able to dramatically reduce the free radical formation which follows the interaction between transition metal ions and amyloid-beta. This paper reports the scavenging effect of melatonin of reactants generated by amyloid peptides in combination with some metal ions.


Tolerability and effectiveness of povidone-iodine or mupirocin versus saline sinus irrigations for chronic rhinosinusitis.
The role of topical anti-infectives in acute exacerbations of chronic rhinosinusitis is controversial. Povidone-iodine is an anti-bacterial and anti-viral that is affordable and available over-the-counter and may demonstrate advantages over mupirocin as a sinus irrigation therapy. The objective was to compare povidone-iodine or mupirocin versus saline sinus irrigations for sinusitis exacerbations in post-surgery subjects as well as to assess tolerability of povidone-iodine sinus irrigations. This was a prospective single-blinded (clinician only) randomized controlled trial. Subjects were post-surgery with acute exacerbations of chronic rhinosinusitis and gram-positive bacteria on culture. They received povidone-iodine, mupirocin, or saline sinus irrigations, twice daily for 30 days. Outcomes were post-treatment culture negativity (primary) and Sinonasal Outcome Test-20 and Lund-Kennedy endoscopic score change (secondary). Of the 62 subjects analyzed, post-treatment culture negativity rate was higher in the MUP (14/20, 70%) group compared to the PI (9/21, 43%) and SAL (9/19, 47%) groups, although this was not significant (p = 0.29). Povidone-iodine sinus irrigations at the 1% concentration were very well-tolerated, similar to saline irrigations. There were no significant differences in Sinonasal Outcome Test-20 score (povidone-iodine -0.3 [-0.6, 0.05] vs. mupirocin -0.3 [-0.7, 0.05] vs. saline -0.4 [-0.8, 0.05]; p = 0.86) or Lund-Kennedy endoscopic score (povidone-iodine -3.5 [-7, -0.5] vs. mupirocin -2 [-4, 2] vs. saline -3 [-5, 0]; p = 0.45) change. No serious adverse effects were reported. In patients who have had prior sinus surgery with acute exacerbations of CRS and gram-positive bacteria on culture, mupirocin sinus irrigations achieved a better post-treatment culture "control" rate compared to saline and povidone-iodine. In addition, 1% povidone-iodine solution was well-tolerated as a sinus irrigation and may represent a feasible method for temporarily disinfecting the sinonasal cavity of bacteria and viruses such as COVID-19.


Cultures for mental health care of young people: an Australian blueprint for reform.
Mental ill health is now the most important health issue facing young people worldwide. It is the leading cause of disability in people aged 10-24 years, contributing 45% of the overall burden of disease in this age group. Despite their manifest need, young people have the lowest rates of access to mental health care, largely as a result of poor awareness and help-seeking, structural and cultural flaws within the existing care systems, and the failure of society to recognise the importance of this issue and invest in youth mental health. We outline the case for a specific youth mental health stream and describe the innovative service reforms in youth mental health in Australia, using them as an example of the processes that can guide the development and implementation of such a service stream. Early intervention with focus on the developmental period of greatest need and capacity to benefit, emerging adulthood, has the potential to greatly improve the mental health, wellbeing, productivity, and fulfilment of young people, and our wider society.


Nanotechnology and tuberculosis: An old disease with new treatment strategies.
Tuberculosis is an intracellular infectious disease caused by Mycobacterium tuberculosis, which mainly affects the lungs. Especially in patients infected by the Human Immunodeficiency Virus (HIV) or other immunosuppressed patients, tuberculosis is considered one of the infectious diseases with higher morbidity and mortality rates. Despite considerable improvements in diagnosis and treatment during the last decades, the drugs currently used in tuberculosis treatment still have limitations, such as low plasma levels after oral administration, low solubility in water, fast metabolization by the liver with a short 1/2 life and low patient adherence to treatment. Another limiting point is drug-resistant strains. Thus, to overcome such limitations, nanotechnology emerges as a promising alternative due to the drug release systems and its recent advances that show potential improvements, such as improved bioavailability and reduction of the therapeutic dose. In this context, this manuscript aimed to highlight the nanotechnology-based drug delivery systems studies pointing to those most effective for tuberculosis treatment. Studies based on polymeric nanoparticles are promising in diagnosing, treating, and even preventing tuberculosis because they have the high stability and transport capacity of these drugs. Solid lipid nanoparticles are another type of promising nanocarriers for treating tuberculosis, mainly for delivering drugs to the remote lymphatic system. Other promising nanosystems are the liposomes, since they have also shown efficacy in significantly reducing bacterial load compared to conventional drug administration. Given the results presented, the administration of drugs through nanotechnology-based drug delivery systems has benefits in treating tuberculosis since in vitro and in vivo studies have revealed that nanotechnology through nano- and micro-scale systems is an effective and promising approach for the treatment of tuberculosis. Furthermore, the increase in the number of patents for nanosystems aimed at treating TB has demonstrated researchers' commitment in the quest to improve the therapeutic arsenal against tuberculosis.


Fusarium toxins in cereals of integrated and organic cultivation from the Federal State of Brandenburg (Germany) harvested in the years 2000-2007.
Over a period of 8 years (2000-2007), wheat (n = 407) and rye (n = 510) samples of integrated and organic cultivation in the Federal State of Brandenburg were analyzed by HPLC for the Fusarium toxins deoxynivalenol (DON) and zearalenone (ZEA). In the years 2002 and 2007, the overall contamination level was higher than in the other years. The percentage of DON-positives (>50 µg/kg) varied from 5 to 86%, the median and maximum levels varied from 50 to 380 µg/kg and from 50 to 10,400 µg/kg, respectively. The percentage of ZEA-positives (>3 µg/kg) varied from 2 to 41%, the median and maximum levels varied from 8 to 84 µg/kg and from 10 to 451 µg/kg. In the 8 years of testing, frequency and levels of DON and ZEA were significantly lower in cereals of organic cultivation compared with cereals of integrated cultivation.


The effect of test presentation on children with autism spectrum disorders and neurotypical peers.
The purpose of this experiment was to determine if there is alternate forms reliability for paper- and computer-administered standardized vocabulary tests. Another purpose was to determine whether the behavioral ratings of children with autism spectrum disorders (ASDs) would improve during the computer-administered testing sessions secondary to a decreased need for social interaction. Thirty-six school-age children (half with ASDs, half neurotypical [NT]) took 2 versions (i.e., paper vs. computer) of the Expressive One-Word Picture Vocabulary Test (EOWPVT-2000; Brownell, 2000a) and the Receptive One-Word Picture Vocabulary Test (ROWPVT-2000; Brownell, 2000b). Order of presentation was counterbalanced across participants. Test sessions were videotaped, and randomly selected 1-min intervals were rated for behaviors. Standardized test scores and behavior ratings were compared for equivalence across the test presentation methods. Standard scores for both versions of the tests were not significantly different for both groups of participants. There were no differences in behavioral ratings between the two methods of test presentation. Alternate forms reliability was found, thus expanding the options for testing for school-age populations. The use of computers had no effect on the behaviors of the children with ASDs. The ramifications of this finding for assessment and intervention for children with ASDs are discussed.


Blood pressure during induction and termination of the dorsal immobility response.
Evidence has indicated that afferent baroreceptor input may play a role in the induction of the dorsal and tonic immobility responses, which are behaviorally similar, but involve opposite posture changes upon induction (i.e., upright versus inverted, respectively). Information is lacking on the topography of the blood pressure response during periods of dorsal immobility. The blood pressure response of the adult Wistar rat during induction and termination of dorsal immobility was compared to the blood pressure response during a condition which controlled for posture change. Each animal received two control trials, ten dorsal immobility trials and then two control trials in two successive sessions four and ten days after surgery. A precise second-by-second topographical analysis of the dorsal immobility response revealed a sharp rise in blood pressure at trial onset of 18.4 mmHg, followed by a return below pretrial levels and then subsequent recovery back to pretrial levels by the tenth-trial second. This level was maintained until the last five seconds of immobility when a rapid blood pressure elevation occurred. This terminating elevation correlated highly with the observation of large movement and probably reflected motor activity that eventually culminated in escape from immobility. The vertical posture change of the control condition, on the other hand, resulted in a gradual diminution of blood pressure, which implied that the initial blood pressure elevation during initiation of the dorsal immobility response could not be accounted for simply by posture change.(ABSTRACT TRUNCATED AT 250 WORDS)


Resveratrol as an antitumor agent for glioblastoma multiforme: Targeting resistance and promoting apoptotic cell deaths.
Glioblastoma multiforme (GBM) is one of the most aggressive brain and spinal cord tumors. Despite the significant development in application of antitumor drugs, no significant increases have been observed in the survival rates of patients with GBM, as GBM cells acquire resistance to conventional anticancer therapeutic agents. Multiple studies have revealed that PI3K/Akt, MAPK, Nanog, STAT 3, and Wnt signaling pathways are involved in GBM progression and invasion. Besides, biological processes such as anti-apoptosis, autophagy, angiogenesis, and stemness promote GBM malignancy. Resveratrol (RESV) is a non-flavonoid polyphenol with high antitumor activity, the potential of which, regulating signaling pathways involved in cancer malignancy, have been demonstrated by many studies. Herein, we present the potential of RESV in both single and combination therapy- targeting various signaling pathways- which induce apoptotic cell death, re-sensitize cancer cells to radiotherapy, and induce chemo-sensitizing effects to eventually inhibit GBM progression.


Myofascial Pain Syndrome: A Narrative Review Identifying Inconsistencies in Nomenclature.
There is currently confusion surrounding the phenotype of and diagnostic criteria for myofascial pain syndrome (MPS) in the published literature. This narrative literature review investigated whether there is consensus regarding the descriptive terminology used for MPS and the trend of MPS publications over time. The phrase "myofascial pain syndrome" was used to search PubMed and Web of Science, returning 923 articles. Of these, we included only full-text, primary research articles containing "myofascial pain syndrome" in the title, reducing the total articles reviewed to 167. We identified 116 descriptors and categorized them under one of five clusters that shared similar findings and are commonly associated with MPS: "trigger points," "muscle," "pain," "nervous system," and "fascia." The frequency of the clinical criteria of Travell and Simons was tabulated. Terms pertaining to the clusters "trigger points," "muscle," or "pain" appeared in approximately 90% of the articles; "nervous system" in 46%; and "fascia" in 20%. Only 42% used the criteria of Travell and Simons. Most articles (122) included a combination of three or four clusters to describe MPS. In addition, MPS publications have doubled since 2010 compared to the prior decade. The publication patterns, determined by changes in which specialty journals articles on MPS have been published, have shifted from investigational to intervention studies. This may have been influenced by heterogeneity in the usage of MPS terminology. This underscores the lack of a reliable MPS diagnosis and limits human subjects research. Improved consistency in terminology is needed to establish consensus within the field and to inform future research studying the pathophysiology of MPS.


Arterial territories of the human brain.
We present a brain map of the areas supplied by various arteries in the brainstem, cerebellum and cerebral hemispheres. Arterial territories are depicted in a form that is directly applicable to neuroimaging slices in clinical practice. The arterial territories are outlined based on an extensive overview of anatomical studies of cerebral blood supply. For arterial territories of the hemispheres, we present the variability of the cortical territories of the three main cerebral arteries and define the minimal and maximal cortical supply areas.


Serum hyaluronate in malignant pleural mesothelioma.
The diagnostic value of hyaluronate concentration in effusions of malignant mesothelioma has been extensively reported but no information is available about serum hyaluronate in patients with this cancer. Using a new enzymoimmunologic assay based on hyaluronate-hyaluronectin interaction, serum levels of hyaluronate were measured in 16 patients with malignant pleural mesothelioma, 50 patients with other pleural effusions, and 94 healthy blood donors. The mean serum hyaluronate level in patients with mesothelioma (mean, 750 micrograms/l; range, 29 to 5833 micrograms/l) was significantly higher than in patients with other pleural effusions (mean, 56 micrograms/l; range, 4 to 137 micrograms/l) and than in blood donors (mean, 24 micrograms/l; range, 0 to 94 micrograms/l). Comparison of serum hyaluronate values observed in mesotheliomas with the clinical course of the disease suggests that serum hyaluronate might increase only at an advanced stage of the cancer. Therefore, serum hyaluronate determination has probably no clinical value for early detection of malignant mesothelioma, but might be useful to evaluate the clinical course of this malignancy.


Quantitative proteomics using stable isotope labeling with amino acids in cell culture.
Stable isotope labeling with amino acids in cell culture (SILAC) is a simple in vivo labeling strategy for mass spectrometry-based quantitative proteomics. It relies on the metabolic incorporation of nonradioactive heavy isotopic forms of amino acids into cellular proteins, which can be readily distinguished in a mass spectrometer. As the samples are mixed before processing in the SILAC methodology, the sample handling errors are also minimized. Here we present protocols for using SILAC in the following types of experiments: (i) studying inducible protein complexes, (ii) identification of Tyr kinase substrates, (iii) differential membrane proteomics and (iv) studying temporal dynamics using SILAC 5-plexing. Although the overall time is largely dependent on the rate of cell growth and various sample processing steps employed, a typical SILAC experiment from start to finish, including data analysis, should take anywhere between 20 and 25 d.


Phosphorus as a driver of nitrogen limitation and sustained eutrophic conditions in Bolinao and Anda, Philippines, a mariculture-impacted tropical coastal area.
The dynamics of nitrogen (N) and phosphorus (P) was studied in mariculture areas around Bolinao and Anda, Philippines to examine its possible link to recurring algal blooms, hypoxia and fish kills. They occur despite regulation on number of fish farm structures in Bolinao to improve water quality after 2002, following a massive fish kill in the area. Based on spatiotemporal surveys, coastal waters remained eutrophic a decade after imposing regulation, primarily due to decomposition of uneaten and undigested feeds, and fish excretions. Relative to Redfield ratio (16), these materials are enriched in P, resulting in low N/P ratios (~6.6) of regenerated nutrients. Dissolved inorganic P (DIP) in the water reached 4μM during the dry season, likely exacerbated by increase in fish farm structures in Anda. DIP enrichment created an N-limited condition that is highly susceptible to sporadic algal blooms whenever N is supplied from freshwater during the wet season.


The degradation and biocompatibility of pH-sensitive biodegradable polyurethanes for intracellular multifunctional antitumor drug delivery.
To obtain controllable stepwise biodegradable polymer for multifunctional antitumor drug carriers, pH-sensitive biodegradable polyurethanes were firstly synthesized using poly(ε-caprolactone) (PCL) and pH-sensitive poly(ε-caprolactone)-hydrazone-poly(ethylene glycol)-hydrazone-poly(ε-caprolactone) macrodiol (PCLH) as soft segment; l-lysine ethyl ester diisocyanate (LDI), l-lysine derivative tripeptide and 1,4-butandiol (BDO) as hard segment; and hydrazone-linked methoxyl-poly(ethylene glycol)(m-PEG-Hyd) as end-capper. Then, an extensive degradation process of the prepared pH-sensitive polyurethanes was investigated in vitro with proton nuclear magnetic resonance spectra ((1)H NMR), gel permeation chromatograph (GPC), scanning electron microscopy (SEM), and weight loss. It was found that the degradation of these polyurethanes occurred via the random hydrolytic ester cleavage along the PCL segments close to PEG segments in enzymatic solutions while the hydrazone bond in the polymer chain was more easily cleaved in acidic media, which was accelerated with decreasing pH value. Furthermore, the biocompatibility in vivo was evaluated in an intramuscular implantation model on Sprague-Dawley rats, using SEM and light microscopy. The result showed that the prepared polyurethanes can be easily degraded and the degradation products do not induce any adverse response from surrounding muscle tissues. Our work suggests that the prepared pH-sensitive polyurethanes could be promising materials as controllable biodegradable and non-cyctotoxic multifunctional carriers for active intracellular drug delivery.


A Pair of Chromone Epimers and an Acetophenone Glucoside from the Mangrove Endophytic Fungus Mycosphaerella sp. L3A1.
Three new compounds, including a pair of chromone derivatives (1-2), and an acetophenone glucoside (3), together with three known compounds (4-6), were isolated from the mangrove endophytic fungus Mycosphaerella sp. L3A1. Their structures were elucidated by HR-ESI-MS analysis and extensive spectroscopic data. The absolute configurations of new compounds were determined using single-crystal X-ray diffraction analysis, electronic circular dichroism (ECD) calculations and chemical hydrolysis. In bioassays, compound 4 showed moderate cytotoxic activity against MDA-MB-435, HCT116, and SNB19 with IC50 values in the range of 18.5-26.29 μM.


Tryptic cleavage as a probe of conformational differences between active and inactive forms of ornithine aminotransferase.
Treatment of ornithine aminotransferase with trypsin resulted in rapid and complete loss of enzyme activity in a process that coincided with a reduction in subunit Mr of about 3000. However, electrophoresis showed that a substantial proportion of the enzyme had not been digested. The component of the preparation of ornithine aminotransferase that was insusceptible to trypsin contained a naturally occurring but enzymically inactive form of the enzyme, and when this had been removed, the remaining fully active enzyme was completely digested. Irreversible inactivation with a substrate analogue made all of the enzyme insusceptible to trypsin. The hydrolyzed enzyme still underwent a very slow half-reaction with ornithine. Sequence analysis of the truncated protein, prepared by blotting from electrophoretic gels, showed that hydrolysis had occurred at peptide bond Lys26-Tyr27.


Evaluation of the Eiken latex agglutination test for anti-Toxoplasma antibodies and seroprevalence of Toxoplasma infection among factory workers in Addis Ababa, Ethiopia.
Sera from 170 factory workers aged 18-45 years enrolled in a pilot study of human immunodeficiency virus 1 (HIV-1) infection in Addis Ababa, Ethiopia, were screened for anti-Toxoplasma immunoglobulin G antibodies by the Sabin-Feldman test (reference standard) and the Eiken latex agglutination test (under evaluation for use in developing countries). Based on the Sabin-Feldman test, the prevalence of anti-Toxoplasma antibodies was 80.0% (95% confidence interval 73.9-86.1%). The sensitivity and specificity of the Eiken latex agglutination test were 96.3% and 97.1%, respectively, showing its validity for the detection of anti-Toxoplasma antibodies. The prevalence of antibodies did not differ between individuals infected and uninfected with HIV-1 (74.2% versus 83.3%, P > 0.05). However, antibody titres were higher in HIV-infected persons than in those who were uninfected (P < 0.001). Based on these findings, we expect that toxoplasmic encephalitis will be a common opportunistic infection among HIV-infected Ethiopians, and chemoprophylaxis with co-trimoxazole may be beneficial to those with low CD4+ T cell counts. The prognostic significance of high titres of anti-Toxoplasma antibodies remains to be established among Ethiopian HIV-infected individuals.


Effects of Exendin-4 on pancreatic islets function in treating hyperglycemia post severe scald injury in rats.
It has been established that glucagon-like peptide 1 (GLP 1) inhibits pancreatic β-cell apoptosis, increases insulin secretion, and improves glucose tolerance in scald injury. However, the effects of Exendin-4, a long-acting incretin similar to GLP 1, remained unclear in severe scald injury. Hence, this study attempted to investigate whether Exendin-4 had similar effects by protecting the histology of pancreas in severely scalded rats. One hundred sixty-two adult Wistar rats were equally randomized to sham burn group, burn group and burn with Exendin-4 treatment group. Rats were subjected to full skin thickness scald injuries (total body surface area: 50%) and were injected subcutaneously with Exendin-4 (4 μg/kg) twice daily. The histological changes of islets, the apoptosis of β cells, the amount of glucagon and insulin, and the concentration of plasma glucagon and insulin were observed; and the intraperitoneal glucose tolerance test was performed as well. The islets and β cells were injured and the number of secretory granules decreased in the scalded rats, but less histopathological changes were seen in the rats treated with Exendin-4. The apoptosis index of treated rats was significantly lower than that of the scalded rats (p < 0.05). There was significant difference in β-cell density postinjury between the two groups (p < 0.05). More insulin and less glucagon in islets and plasma were found in the treated rats (p < 0.05), suggesting improved intraperitoneal glucose tolerance (p < 0.05) and fasting blood glucose (p < 0.05) in this group. Based on our previous finding that GLP-1 could control hyperglycemia by increasing insulin secretion and inhibiting β-cell apoptosis in severe scald injuries, this study further confirmed that Exendin-4 could increase glycemic control following severe scald by preserving the histology of β cells in pancreatic islets and inhibiting their apoptosis.


A chemiresistive thin-film translating biological recognition into electrical signals: an innovative signaling mode for contactless biosensing.
An innovative signaling mode in which a chemiresistive thin-film electrode monitors the specific gaseous component that results from a biological recognition event to indirectly detect targets in the liquid phase is developed for highly-efficient contactless biosensing. This signaling mode may open a new horizon in designing robust biosensing devices for bioanalysis.


Data mining techniques utilizing latent class models to evaluate emergency department revisits.
The use of machine learning techniques is especially pertinent to the composite and challenging conditions of emergency departments (EDs). Repeat ED visits (i.e. revisits) are an example of potentially inappropriate utilization of resources that can be forecasted by these techniques. To track the ED revisit risk over time using the hidden Markov model (HMM) as a major latent class model. Given the HMM states, we carried out forecasting of future ED revisits with various data mining models. Information integrated from four distributed sources (e.g. electronic health records and health information exchange) was integrated into four HMMs which capture the relationships between an observed and a hidden progression that shift over time through a series of hidden states in an adult patient population. Assimilating a pre-analysis of the various patients by applying latent class models and directing them to well-known classifiers functioned well. The performance was significantly better than without utilizing pre-analysis of HMM for all prediction models (classifiers(. These findings suggest that one prospective approach to advanced risk prediction is to leverage the longitudinal nature of health care data by exploiting patients' between state variation.


False positive PSMA PET for tumor remnants in the irradiated prostate and other interpretation pitfalls in a prospective multi-center trial.
Readers need to be informed about potential pitfalls of [68Ga]Ga-PSMA-11 PET interpretation. Here we report [68Ga]Ga-PSMA-11 PET findings discordant with the histopathology/composite reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer. Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy (n = 11); other false positive findings were noted for prostate bed post prostatectomy (T, n = 2), pelvic nodes (N, n = 2), or extra pelvic lesions (M, n = 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) (n = 5), pelvic nodes (n = 1), and extra pelvic lesions (n = 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake. [68Ga]Ga-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of [68Ga]Ga-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants. ClinicalTrials.gov Identifiers: NCT02940262 and NCT03353740.


Prevalence and characteristics of upper or mid-back pain in Finnish men.
Descriptive epidemiologic study. To examine the 1-year prevalence, severity, and frequency of mid-back pain in a general population sample of men, with comparisons to neck and low back pain. No previous studies reporting the characteristics of mid-back pain in a general population were found. A total of 600 Finnish men 35 to 70 years of age were drawn from a population-based twin sample and interviewed with standardized pain questions. The 1-year prevalence of mid-back pain was 17.0% (95% confidence interval, 14.3-19.7) compared to 64.0% (95% confidence interval, 60.6-67.5) for neck and 66.8% (95% confidence interval, 63.4-70.3) for low back pain. The frequency of pain over the previous year among those with mid- and low back pain was less than for neck pain. The mean severity of the worst pain episode was highest for low back pain followed by mid-back and neck pain, which were similar. Associated disability tended to be less frequent from mid-back pain (23.5% vs. 30.3%-41.1%). Odds ratios for neck and low back pain when mid-back pain was reported were 2.32 and 2.86, respectively. The prevalence of mid-back pain was approximately one fourth that of neck and low back pain and was somewhat less likely to be disabling. In cases of mid-back pain, spinal comorbidity was nearly always reported.


Health beliefs among individuals at increased familial risk for type 2 diabetes: implications for prevention.
To evaluate perceived risk, control, worry, and severity about diabetes, coronary heart disease (CHD) and stroke among individuals at increased familial risk of diabetes. Data analyses were based on the Family Healthware™ Impact Trial. Baseline health beliefs were compared across three groups: (1) no family history of diabetes, CHD or stroke (n=836), (2) family history of diabetes alone (n=267), and (3) family history of diabetes and CHD and/or stroke (n=978). After adjusting for age, gender, race, education and BMI, scores for perceived risk for diabetes (p<0.0001), CHD (p<0.0001) and stroke (p<0.0001) were lowest in Group 1 and highest in Group 3. Similar results were observed about worry for diabetes (p<0.0001), CHD (p<0.0001) and stroke (p<0.0001). Perceptions of control or severity for diabetes, CHD or stroke did not vary across the three groups. Among individuals at increased familial risk for diabetes, having family members affected with CHD and/or stroke significantly influenced perceived risk and worry. Tailored lifestyle interventions for this group that assess health beliefs and emphasize approaches for preventing diabetes, as well as its vascular complications, may be an effective strategy for reducing the global burden of these serious but related chronic disorders.


Changes in biologically active ultraviolet radiation reaching the Earth's surface.
Stratospheric ozone levels are near their lowest point since measurements began, so current ultraviolet-B (UV-B) radiation levels are thought to be close to their maximum. Total stratospheric content of ozone-depleting substances is expected to reach a maximum before the year 2000. All other things being equal, the current ozone losses and related UV-B increases should be close to their maximum. Increases in surface erythemal (sunburning) UV radiation relative to the values in the 1970s are estimated to be: about 7% at Northern Hemisphere mid-latitudes in winter/spring; about 4% at Northern Hemisphere mid-latitudes in summer/fall; about 6% at Southern Hemisphere mid-latitudes on a year-round basis; about 130% in the Antarctic in spring; and about 22% in the Arctic in spring. Reductions in atmospheric ozone are expected to result in higher amounts of UV-B radiation reaching the Earth's surface. The expected correlation between increases in surface UV-B radiation and decreases in overhead ozone has been further demonstrated and quantified by ground-based instruments under a wide range of conditions. Improved measurements of UV-B radiation are now providing better geographical and temporal coverage. Surface UV-B radiation levels are highly variable because of cloud cover, and also because of local effects including pollutants and surface reflections. These factors usually decrease atmospheric transmission and therefore the surface irradiances at UV-B as well as other wavelengths. Occasional cloud-induced increases have also been reported. With a few exceptions, the direct detection of UV-B trends at low- and mid-latitudes remains problematic due to this high natural variability, the relatively small ozone changes, and the practical difficulties of maintaining long-term stability in networks of UV-measuring instruments. Few reliable UV-B radiation measurements are available from pre-ozone-depletion days. Satellite-based observations of atmospheric ozone and clouds are being used, together with models of atmospheric transmission, to provide global coverage and long-term estimates of surface UV-B radiation. Estimates of long-term (1979-1992) trends in zonally averaged UV irradiances that include cloud effects are nearly identical to those for clear-sky estimates, providing evidence that clouds have not influenced the UV-B trends. However, the limitations of satellite-derived UV estimates should be recognized. To assess uncertainties inherent in this approach, additional validations involving comparisons with ground-based observations are required. Direct comparisons of ground-based UV-B radiation measurements between a few mid-latitude sites in the Northern and Southern Hemispheres have shown larger differences than those estimated using satellite data. Ground-based measurements show that summertime erythemal UV irradiances in the Southern Hemisphere exceed those at comparable latitudes of the Northern Hemisphere by up to 40%, whereas corresponding satellite-based estimates yield only 10-15% differences. Atmospheric pollution may be a factor in this discrepancy between ground-based measurements and satellite-derived estimates. UV-B measurements at more sites are required to determine whether the larger observed differences are globally representative. High levels of UV-B radiation continue to be observed in Antarctica during the recurrent spring-time ozone hole. For example, during ozone-hole episodes, measured biologically damaging radiation at Palmer Station, Antarctica (64 degrees S) has been found to approach and occasionally even exceed maximum summer values at San Diego, CA, USA (32 degrees N). Long-term predictions of future UV-B levels are difficult and uncertain. Nevertheless, current best estimates suggest that a slow recovery to pre-ozone depletion levels may be expected during the next half-century. (ABSTRACT TRUNCATED)


Computer-driven optimization of complex gradients in comprehensive two-dimensional liquid chromatography.
Method development in comprehensive two-dimensional liquid chromatography (LC × LC) is a complicated endeavor. The dependency between the two dimensions and the possibility of incorporating complex gradient profiles, such as multi-segmented gradients or shifting gradients, renders method development by "trial-and-error" time-consuming and highly dependent on user experience. In this work, an open-source algorithm for the automated and interpretive method development of complex gradients in LC × LC-mass spectrometry (MS) was developed. A workflow was designed to operate within a closed-loop that allowed direct interaction between the LC × LC-MS system and a data-processing computer which ran in an unsupervised and automated fashion. Obtaining accurate retention models in LC × LC is difficult due to the challenges associated with the exact determination of retention times, curve fitting because of the use of gradient elution, and gradient deformation. Thus, retention models were compared in terms of repeatability of determination. Additionally, the design of shifting gradients in the second dimension and the prediction of peak widths were investigated. The algorithm was tested on separations of a tryptic digest of a monoclonal antibody using an objective function that included the sum of resolutions and analysis time as quality descriptors. The algorithm was able to improve the separation relative to a generic starting method using these complex gradient profiles after only four method-development iterations (i.e., sets of chromatographic conditions). Further iterations improved retention time and peak width predictions and thus the accuracy in the separations predicted by the algorithm.


Prolongation of heart rate-corrected QT interval is a predictor of cardiac autonomic dysfunction in patients with systemic lupus erythematosus.
Heart rate-corrected QT interval duration (QTc) has been shown to be related to cardiac autonomic dysfunction in patients with diabetes mellitus, although this association has not been previously described in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed the medical records of 91 SLE patients and 144 non-SLE connective tissue disease patients visiting our clinic from November 2010 to April 2011. We compared ambulatory heart rate identified by pulse measured by automated machine in an outpatient waiting area versus resting heart rate identified on prior screening electrocardiogram. Heart rate differences were analyzed in relation to QTc interval and other characteristics. Ambulatory and resting heart rate differences were larger among SLE patients with QTc prolongation (QTc > 430 ms) than those without QTc prolongation (mean difference, 15.9 vs. 9.6, p = 0.001). In multivariate analysis, differences in heart rate were associated with QTc prolongation (OR 1.10, 95 % CI 1.01-1.21; p = 0.038), independent of age, duration of disease, immunosuppressant use, hydroxychloroquine use, diabetes mellitus, cardiac abnormality, anti-Ro/SS-A antibody positivity, or resting heart rate. Cardiac autonomic dysfunction is a common manifestation of SLE and may be related to QTc prolongation.


Morphometric evaluation of histological sections of the thyroid gland in benign and malignant follicular lesions.
A morphometric analysis was made on histological sections of thyroid tissue in various aspects of follicular cell pathologies (goiter, adenoma, and carcinoma) and in normal follicular cells. Three cases of each aspect and 150 cells of each case were measured. The results obtained demonstrate the importance of the nuclear area in the differential diagnosis of normal thyroid, goiter, adenoma, and carcinoma. The other parameters considered, i.e., perimeter, maximum diameter, and nuclear form factor, proved to be able to exclusively distinguish between benign lesions (normal thyroid, goiter and, adenoma) and malignant ones (carcinoma).


[The effectiveness of Mycobacteria tuberculosis isolation by polymerase chain reaction: results of a randomized trial].
The results of testing sputum for Mycobacterium tuberculosis by different methods: polymerase chain reaction (PCR), luminescence microscopy, and culture tests were compared. Clinical sputum samples were studied in 62 patients with pulmonary tuberculosis and 72 patients with non-specific diseases of the lung. The specificity of PCR was 98.7%. The sensitivity of PCR was 59.6%; that of cultural tests was 43.8%.


The dual role of Zn-acid medium for one-step rapid synthesis of M@rGO (M = Au, Pt, Pd and Ag) hybrid nanostructures at room temperature.
We report a new protocol for the synthesis of M@rGO (M = Au, Pt, Pd, Ag and rGO = reduced graphene oxide) hybrid nanostructures at room temperature in Zn-acid medium. The roles of Zn-acid are to reduce the GO by generated hydrogen and the deposition of metal nanoparticles on rGO by galvanic replacement reaction between Zn and M(n+).


Molecular epidemiologic analysis of Staphylococcus aureus isolated from four burn centers.
Staphylococcus aureus has been a major cause of hospital-acquired infections. Methicillin-resistant Staphylococcus aureus (MRSA) has emerged since 1980s as an epidemiologic problem in hospitals. This old pathogen brings a new challenge to all physicians and bacteriologists. Hence, effective measures of MRSA control are in critical need. S. aureus or MRSA is one of the leading causes of infection among burn centers, resulting in a number of poor outcomes and even death. The present study performed a molecular epidemiologic analysis of S. aureus isolated from four burn centers in the southeast of China. A total of 85 isolates were collected, and molecular characters were determined for further investigation. In this study, the prevalent clone of MRSA among four burn centers was found to be SCCmec III (spa-type t030, agr I), which is resistant to 4 kinds of antimicrobials including erythromycin, clindamycin, kanamycin and mupirocin. Discrepancy between mecA detection and conventional tests used for MRSA identification was observed unintentionally. Our data demonstrated that the overall prevalence rate of MRSA was 55.3%, and drugs such as sulfamethoxazole/trimethoprim, linezolid and fusidic acid are efficient antibiotic options for treating S. aureus or MRSA infections among four burn centers studied in present investigation.


Berberine induces apoptosis through a mitochondria/caspases pathway in human hepatoma cells.
Berberine, a main component of Coptidis Rhizoma, is a plant alkaloid with a long history of medicinal use in Chinese medicine. Berberine has indicated significant antimicrobial activity against a variety of organisms including bacteria, viruses, fungi. The mechanism by which berberine initiates apoptosis remains poorly understood. In the present study, we demonstrated that berberine exhibited significant cytotoxicity in hepatoma HepG2 cells but is ineffective in Chang liver cells. Herein we investigated cytotoxicity mechanism of berberine in HepG2 cells. The results showed that HepG2 cells underwent internucleosomal DNA fragmentation after 24-h treatment with berberine (50 microM). Moreover, berberine induced the activation of caspase-8 and -3, and caused the cleavage of poly ADP-ribose polymerase (PARP) and the cytochrome c release, whereas the expression of Bid and anti-apoptosis factor Bcl-XL were decreased markedly. The loss of mitochondrial membrane potential (Delta psim) at 24 h and activation of Fas at 12 h were also seen in the berberine-treated HepG2 cells. These findings supported the fact that the inhibitors of caspases, DEVD-FMK, IETD-FMK and VAD-FMK, prevented apoptosis and restored the expression of Bcl-XL, Bcl-2 and Bid. These results indicated that the potential of anti-hepatoma activity of berberine may be mediated through a caspases-mitochondria-dependent pathway.


Procedural factors associated with percutaneous coronary intervention-related ischemic stroke.
This study sought to determine whether procedural factors during percutaneous coronary intervention (PCI) are associated with the occurrence of ischemic stroke or transient ischemic attack (PCI-stroke). Stroke is a devastating complication of PCI. Demographic predictors are nonmodifiable. Whether PCI-stroke is associated with procedural factors, which may be modifiable, is unknown. We performed a single-center retrospective study of 21,497 PCI hospitalizations between 1994 and 2008. We compared procedural factors from patients who suffered an ischemic stroke or transient ischemic attack related to PCI (n=79) and a control group (n=158), and matched them 2:1 based on a predicted probability of stroke developed from a logistic regression model. PCI-stroke procedures involved the use of more catheters (median: 3 [quarter (Q) 1, Q3: 3, 4] vs. 3 [Q1, Q3: 2, 3], p<0.001), greater contrast volumes (250 ml vs. 218 ml, p=0.006), and larger guide caliber (median: 7-F [Q1, Q3: 6, 8] vs. 6-F [Q1, Q3: 6, 8], p<0.001). The number of lesions attempted (1.7±0.8 vs. 1.5±0.8, p=0.14) and stents placed (1.4±1.2 vs. 1.2±1.1, p=0.35) were similar between groups, but PCI-stroke patients were more likely to have undergone rotational atherectomy (10% vs. 3%, p=0.029). Overall procedural success was lower in the PCI-stroke group compared with controls (71% vs. 85%, p=0.017). Evaluation of the entire PCI population revealed no difference in the rate of PCI-stroke between radial and femoral approaches (0.4% vs. 0.4%, p=0.78). Ischemic stroke related to PCI is associated with potentially modifiable technical parameters. Careful procedural planning is warranted, particularly in patients at increased risk.