Time trends for peptic ulcer disease in Denmark, 1981-1993. Analysis of hospitalization register and mortality data.
Since the mid-1980s there has been great improvement in the available diagnostic tools and treatments for peptic ulcers. The aim of this study was to determine whether these improvements have been paralleled by decreasing age- and sex-specific hospitalization and death rates for peptic ulcers in Denmark. The study was based on all discharges from Danish somatic hospitals as registered in the National Hospital Discharge Registry and all the death certificates as registered in the Danish National Board of Health from 1981 through 1993, when a diagnosis of peptic ulcer was recorded. The age- and sex-specific and age-adjusted hospitalization and death rates were estimated. In men the age-adjusted hospitalization rate for all types of peptic ulcers decreased by 0.88, but the mortality increased by 1.19. In women the age-adjusted hospitalization and mortality increased for all types of peptic ulcers. The increasing mortality was mainly due to bleeding and perforated duodenal ulcers. The analysis of the age-specific hospitalization and mortality for peptic ulcer complications showed that the increasing trends mainly occurred among the elderly. The improved medical treatment of peptic ulcers has not been paralleled by decreasing hospitalization or death from complicated peptic ulcers in Denmark. On the contrary, we found an increasing hospitalization and mortality from peptic ulcer complications, particularly in elderly Danish people.


Applications of hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer.
Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) plays a pivotal role in the current treatment of peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Since the first demonstration, benefits for patients and especially an increase in survival have been described. In recent years, feasibility, efficacy and safety of HIPEC have been improved and progress has been made in understanding its oncological mechanism. Areas covered: In this article, leading publications have been reviewed including clinical trials to describe the clinical presentation of PC due to CRC and present recent evidence of the CRS/HIPEC procedure. The surgical approach including evaluation of the extent of PC is described and, in addition, the article reports about different HIPEC techniques as well as several protocols. Furthermore, the development and prognostic benefit of the combination of intraperitoneal and intravenous chemotherapy are outlined. Consideration has been given in particular to patient selection and the use of HIPEC if complete cytoreduction is not feasible. Expert commentary: The CRS/HIPEC procedure represents a curative approach to treat patients with PC from CRC. However, surgical skills and the HIPEC technique still require specialized oncological centers.


Factor XI: purification from porcine plasma by affinity chromatography and some properties of factor XI and activated factor XI.
Porcine factor XI and activated factor XI were purified by the introduction of affinity chromatography on high molecular mass kininogen. On the affinity chromatography, it was observed that high affinity exists between porcine factor XI and high molecular mass kininogen. In the preparation, however, factor XII, plasma prekallikrein and high molecular mass kininogen were not detected. The factor XI forms a dimer, and is a heterogeneous molecule, judging from sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Substrate specificity of activated factor XI and inhibition profile of activated factor XI against proteinase inhibitors were investigated by comparison with those of bovine and human activated factor XI. From these results, the properties of porcine activated factor XI show great similarities with those of bovine and human activated factor XI.


Comparison of trace element concentrations in grey heron and black-crowned night heron chicks.
Cadmium (Cd), lead (Pb), manganese (Mn), zinc (Zn), and iron (Fe) concentrations were measured in the prey and liver of grey heron (Ardea cinerea) and black-crowned night heron (Nycticorax nycticorax) chicks (24-26 days after hatching) at the Pyeongtaek colony, Korea in 2001 (n = 10, respectively) and 2008 (n = 11 and n = 10). Cadmium and Pb concentrations in livers of grey heron (Cd geomean 0.06, Pb 3.90 μg/g dw) and black-crowned night heron (Cd 0.20, Pb 4.24 μg/g dw) chicks were increased with diet concentrations of grey heron (Cd 0.18, Pb 1.76 μg/g dw) and black-crowned night heron (Cd 0.20, Pb 3.96 μg/g dw) chicks. Cadmium and Pb concentrations in prey items of grey heron and black-crowned night heron chicks were a good predictor of chick liver concentrations. Cadmium concentrations in livers of both heron species collected at the Pyeongtaek heronry were relatively low and within the background level (<3 μg/g dw) for birds. Five of 20 (25.0%) grey heron and 4 of 18 (22.2%) black-crowned night heron chicks were higher than the background level for lead (>6 μg/g dw). Prey Cd and Pb concentrations were within the range of other heron and egret studies. Manganese, Zn, and Fe concentrations in grey heron and black-crowned night heron chicks were within the background or normal physiological levels reported earlier in other birds including herons and egrets.


Brillouin neutron scattering in heavy water: evidence for two-mode collective dynamics.
A high resolution (1.5 meV) inelastic neutron scattering experiment was carried out, aiming at an accurate investigation of the high frequency and low momentum dynamic response in heavy water. The experimental data confirm the existence of a dispersionless mode, besides the ordinary longitudinal collective dynamics. A simplified model, based on the interaction of two vibrational branches, is proposed to interpret the observed features of the dynamic spectra. The validity extent of this scheme is proved by applying it to room temperature neutron and x-ray data, to temperature and pressure dependent x-ray data, and to room temperature neutron data of vibrational density of states. The overall successfull results provided by this model, in conjunction with the combined analysis of the x-ray and neutron data on collective dynamics, enable a deeper insight into the complex mechanisms of the water dynamics and provide a simple phenomenological explanation for the transition from ordinary to fast sound.


Theoretical study of superionic phase transition in Li2S.
We have studied temperature-induced superionic phase transition in Li2S, which is one of the most promising Li-S battery cathode material. Concentration of ionic carriers at low and high temperature was evaluated from thermodynamics of defects (using density functional theory) and detailed balance condition (using ab initio molecular dynamics (AIMD)), respectively. Diffusion coefficients were also obtained using AIMD simulations. Calculated ionic conductivity shows that superionic phase transition occurs at T = 900 K, which is in agreement with reported experimental values. The superionic behavior of Li2S is found to be due to thermodynamic reason (i.e. a large concentration of disordered defects).


Circulating Levels of Uric Acid and Risk for Metabolic Syndrome.
Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid, both mechanisms link elevated serum uric acid with metabolic syndrome. The aim of this study is to evaluate the probability for the development of metabolic syndrome in low-income young adults with hyperuricaemia. We evaluated 103 patients less than 40 years of age, from a low-income population, and without history of cardiovascular disease, in all of them the presence of metabolic syndrome was assessed in accordance with the International Diabetes Federation criteria. In all patients, fasting serum uric acid levels were measured; hyperuricaemia was defined as serum uric acid values 6.5 mg/dl in men and 5.1 mg/dl in women. Statistical analysis was performed with odds ratio. 83 of our patients (80.5%) suffered metabolic syndrome, the odds ratio for the presence of metabolic syndrome in patients with hyperuricaemia was 5.1 (p=0.002, I.C 1.8- 14.5). When patients were evaluated by gender a significantly association between hyperuricaemia and metabolic syndrome was found in women (odds ratio 3.6, p=0.048, C.I. 1.0-12.9), and men (odds ratio 10.2, p= 0.015, IC 1.5-13.2). When uric acid was correlated with the components of metabolic syndrome, we only found a positive correlation with waist circumference (r=0.483). Our results showed a significant association between hyperuricemia and metabolic syndrome in low-income young adults in Mexico. DR is associated with estimated risk of CVD in type 2 diabetic patients.


Isoproterenol Increases Left Atrial Fibrosis and Susceptibility to Atrial Fibrillation by Inducing Atrial Ischemic Infarction in Rats.
Left atrial (LA) fibrosis is a major arrhythmogenic substrate for atrial fibrillation (AF). The purpose of this study was to assess whether isoproterenol (ISO) induces LA fibrosis and increases susceptibility to AF, exploring the underlying mechanisms. Male Sprague-Dawley rats were subcutaneously injected ISO once per day for 2 days. Five weeks after injection, the ISO group had higher susceptibility AF and prolonged AF duration compared with the control group. ISO decreased LA conduction velocity (CV) and increased LA conduction heterogeneity. ISO increased fibrosise areas and the protein levels of collagen types I and III in the left atrium. Antifibrosis drug pirfenidone decreased AF occurrence and reduced LA fibrosis in ISO treated rats. ISO injection induced atrial ischemia infarction by increasing heart rate and decreasing diastolic and systolic blood pressures. These findings demonstrated that ISO increases susceptibility to AF by increasing LA fibrosis and LA conduction abnormalities 5 weeks after injection. ISO injection induces atrial ischemic injury is the main cause of fibrosis. Rats with ISO-induced LA fibrosis may be used in further AF research.


Review of the existing maximum residue levels for tetraconazole according to Article 12 of Regulation (EC) No 396/2005.
According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance tetraconazole. To assess the occurrence of tetraconazole residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC, as well as the import tolerances and European authorisations reported by Member States and the UK (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. Although no apparent risk to consumers was identified, some information required by the regulatory framework was missing. Hence, the consumer risk assessment is considered indicative only and, with the exception of the MRL proposal for kaki, all MRL proposals derived by EFSA still require further consideration by risk managers. Regarding triazole derivative metabolites (TDMs), separate indicative exposure assessments were performed and no risk to consumers was identified for what regards these metabolites individually. However, TDMs may be generated by several pesticides belonging to the group of triazole fungicides, and a comprehensive risk assessment has thus to be performed that covers all existing European uses for all pesticides belonging to the class of triazole fungicides. EFSA recommended to elaborate together with risk managers a strategy to ensure that the required data are made available to finalise the overall risk assessment for triazole fungicides.


Changes in E-Selectin Levels Predict Carotid Stenosis Progression after Carotid Artery Stenting.
We hypothesized that the inflammatory markers (IM) could be the independent predictors of Carotid Stenosis Progression (CSP) after Carotid Artery Stenting (CAS). Between 2010 and 2012, 122 patients undergoing cervicocranial revascularization in our hospital were prospectively recruited. Patients undergoing revascularizations other than CAS were excluded. Carotid duplex ultrasonography was performed before and at 1 week, 6 months (6M), 1 year, and 2 years after CAS. IM levels were recorded before CAS and were followed up immediately and 6M after CAS. The data was analyzed retrospectively. Patients were categorized into the Progression Group (PG) and Nonprogression Group (NPG) based on the presence or absence of CSP, including in-stent restenosis (ISR) and worsening contralateral carotid stenosis. Receiver operating characteristic and multivariate logistic regression analyses were conducted. In Total, 77 patients were enrolled. The frequency of CSP was 24.7% (ISR: 14.3%; worsening contralateral carotid stenosis: 14.3%). Compared with the NPG, the PG had lower E-selectin levels before CAS [PG vs. NPG, 47.90 (42.80, 64.90) vs. 68.25 (52.08, 92.30); p = .01] and a nonreduced E-selectin levels at 6M after CAS [PG vs. NPG, 7.65 (-2.45, 25.75) vs. -16.10 (-33.45, 1.65); p = .002]. The E-selectin changes between 6M after and before CAS had highest predictive accuracy on CSP (area under the curve = 0.74, p = .002). The optimal cut-off level was a 2.95 ng/mL decrease and the adjusted odds ratio for CSP was 10.16 (p = .001). The E-selectin changes between 6M after and before CAS are independent predictors of CSP.


Hypertensive Disorders of Pregnancy and Future Cardiovascular Health.
Hypertensive disorders of pregnancy (HDP) occur in almost 10% of gestations. These women are known to have higher cardiovascular morbidity and mortality later in life in comparison with parous controls who had normotensive pregnancies. Several studies have demonstrated that women with preeclampsia present in a state of segmental impaired myocardial function, biventricular chamber dysfunction, adverse biventricular remodeling, and hypertrophy, a compromised hemodynamic state and indirect echocardiographic signs of localized myocardial ischemia and fibrosis. These cardiac functional and geometric changes are known to have strong predictive value for cardiovascular disease in non-pregnant subjects. A "dose effect" response seems to regulate this relationship with severe HDP, early-onset HDP, coexistence of fetal growth disorders, and recurrence of HDP resulting in poorer cardiovascular measures. The mechanism underlying the relationship between HDP in younger women and cardiovascular disease later in life is unclear but could be explained by sharing of pre-pregnancy cardiovascular risk factors or due to a direct impact of HDP on the maternal cardiovascular system conferring a state of increased susceptibility to future metabolic or hemodynamic insults. If so, the prevention of HDP itself would become all the more urgent. Shortly after delivery, women who experienced HDP express an increased risk of classic cardiovascular risk factors such as essential hypertension, renal disease, abnormal lipid profile, and diabetes with higher frequency than controls. Within one or two decades after delivery, this group of women are more likely to experience premature cardiovascular events, such as symptomatic heart failure, myocardial ischemia, and cerebral vascular disease. Although there is general agreement that women who suffered from HDP should undertake early screening for cardiovascular risk factors in order to allow for appropriate prevention, the exact timing and modality of screening has not been standardized yet. Our findings suggest that prevention should start as early as possible after delivery by making the women aware of their increased cardiovascular risk and encouraging weight control, stop smoking, healthy diet, and daily exercise which are well-established and cost-effective prevention strategies.


Growth promoting influence of siderophore-producing Pseudomonas strains GRP3A and PRS9 in maize (Zea mays L.) under iron limiting conditions.
Maize seeds were bacterized with siderophore-producing pseudomonads with the goal to develop a system suitable for better iron uptake under iron-stressed conditions. Siderophore production was compared in fluorescent Pseudomonas spp. GRP3A, PRS9 and P. chlororaphis ATCC 9446 in standard succinate (SSM) and citrate (SCM) media. Succinate was better suited for siderophore production, however, deferration of media resulted in increased siderophore production in all the strains. Maximum siderophore level (216.23 microg/ml) was observed in strain PRS9 in deferrated SSM after 72 h of incubation. Strains GRP3A and PRS9 were used for plant growth promotion experiments. Strains GRP3A and PRS9 were also antagonistic against the phytopathogens, Colletotrichum dematium, Rhizoctonia solani and Sclerotium rolfsii. Bacterization of maize seeds with strains GRP3A and PRS9 showed significant increase in germination percentage and plant growth. Maximum shoot and root length and dry weight were observed with 10 microM Fe3+ along with bacterial inoculants suggesting application of siderophore producing plant growth promoting rhizobacterial strains in crop productivity in calcareous soil system.


Surface-Enhanced Raman Spectroscopy (SERS) Activity of Gold Nanoparticles Prepared Using an Automated Loop Flow Reactor.
This study used automatic control methods to prepare gold nanoparticles (AuNPs) as the substrate and rhodamine 6G molecule as the probe to investigate the enhancement effect, stability, and consistency of surface-enhanced Raman spectroscopy (SERS). The gold nanosols were prepared via automatic control using loop flow-reactor technology, and the synthesis of nanoparticles with different sizes was precisely controlled by optimizing the ratio of the solution required for the reaction between sodium citrate and chloroauric acid during the preparation process. The morphology, structure, and optical properties of the prepared AuNPs were investigated using field-emission scanning electron microscopy, transmission electron microscopy, and ultraviolet visible spectroscopy. Using the proposed method, AuNPs with average particle sizes of 72, 85, 93, and 103 nm were synthesized in a precisely controlled manner. The 93 nm particles exhibited good SERS activity for rhodamine 6G under 785 nm excitation with a detection limit of 2.5 × 10-10 M. The relative standard deviation of the SERS spectra synthesized multiple times was <3.5%, indicating their good sensitivity and reproducibility. The results showed that the AuNPs prepared by the automatic control of the loop-flow method have high sensitivity, stability, and reproducibility. Moreover, they exhibited notable potential for in situ measurement and quantitative analysis using SERS.


Improved energy model for membrane electroporation in biological cells subjected to electrical pulses.
A self-consistent model analysis of electroporation in biological cells has been carried out based on an improved energy model. The simple energy model used in the literature is somewhat incorrect and unphysical for a variety of reasons. Our model for the pore formation energy E(r) includes a dependence on pore population and density. It also allows for variable surface tension, incorporates the effects of finite conductivity on the electrostatic correction term, and is dynamic in nature. Self-consistent calculations, based on a coupled scheme involving the Smoluchowski equation and the improved energy model, are presented. It is shown that E(r) becomes self-adjusting with variations in its magnitude and profile, in response to pore population, and inhibits uncontrolled pore growth and expansion. This theory can be augmented to include pore-pore interactions to move beyond the independent pore picture.


Unique T cell Ia antigen expressed on a hybrid cell line producing antigen-specific augmenting T cell factor.
Hybrid cell lines were established by fusion between keyhole limpet hemocyanin(KLH) binding T cells of A/J mice and an AKR T cell tumor line, BW5147. Hybrids were selected for the presence of Ia antigen and KLH-specific augmenting activity of their extracts in the secondary antibody response. The detailed phenotypic and functional analysis of 1 of these clones, FL10, is reported here. The hybrid was positive for both Thy1.1 and Thy1.2 antigens and possessed the Lyt-1+,2-,3- phenotype. Both VH and Ia determinants were detected on their cell surface. The IA locus was mapped in the I-A subregion, but the Ia specificities were serologically distinct from those of B cell Ia antigen. This was demonstrated by the fact that anti-Ia antiserum preabsorbed with B cells could react with the hybrid cells, whereas none of the monoclonal anti-Ia specific for private and public determinations of Iak could. The extract from the cell line specifically augmented the in vitro secondary antibody response against dinitrophenylated KLH, and this activity was removed by absorption with antigen and conventional anti-Ia antisera. The results indicate that the cell line, FL10, carries Ia antigen unique to the T cell, which is associated with the antigen-specific augmenting molecule.


In vitro serotonergic activity of black cohosh and identification of N(omega)-methylserotonin as a potential active constituent.
Cimicifuga racemosa (L.) Nutt. (syn. Actaea racemosa L., black cohosh) is used to relieve menopausal hot flashes, although clinical studies have provided conflicting data, and the active constituent(s) and mechanism(s) of action remain unknown. Because serotonergic receptors and transporters are involved with thermoregulation, black cohosh and its phytoconstituents were evaluated for serotonergic activity using 5-HT7 receptor binding, cAMP induction, and serotonin selective re-uptake inhibitor (SSRI) assays. Crude extracts displayed 5-HT7 receptor binding activity and induced cAMP production. Fractionation of the methanol extract led to isolation of phenolic acids and identification of N(omega)-methylserotonin by LC-MS/MS. Cimicifuga triterpenoids and phenolic acids bound weakly to the 5-HT7 receptor with no cAMP or SSRI activity. In contrast, N(omega)-methylserotonin showed 5-HT7 receptor binding (IC50 = 23 pM), induced cAMP (EC50 = 22 nM), and blocked serotonin re-uptake (IC50 = 490 nM). These data suggest N(omega)-methylserotonin may be responsible for the serotonergic activity of black cohosh.


Gender and psychiatric clerkship performance.
This study compared the performance of male and female medical students on a psychiatric clerkship rotation. The women performed at a higher level than the men, although the difference was not significant. In general, the men scored significantly higher on national standardized medical examinations. Correlations between psychiatric clerkship evaluations and national examinations were low, suggesting that the two measures are independent. These findings for psychiatric clerkship are consistent with those for clerkships in medicine, surgery and obstetrics, implying that female clinical clerks are just as capable as male clinical clerks in providing high quality medical care.


Predictive biomarkers and effectiveness of MUC1-targeted dendritic-cell-based vaccine in patients with refractory non-small cell lung cancer.
The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be determined. DCs loaded with MUC1-derived peptide were subcutaneously administered to patients with MUC1-positive non-small cell lung cancer (NSCLC) that was refractory to standard anticancer therapies, every 2 weeks. The effectiveness and tolerability of the vaccine were evaluated, and predictive biomarkers of clinical responses were explored. Between August 2005 and May 2015, 40 patients received the vaccines. The median survival time (MST) after the initial vaccination was 7.4 months, and the 1-year survival rate was 25.0%. The MST for patients who received more than six vaccinations was 9.5 months, and the 1-year survival rate was 39.3%. In this cohort, patients who experienced immune-related adverse events, including skin reactions at the vaccination site and fever, had significantly longer survival times compared with patients without those immune-related adverse events (12.6 versus 6.7 months, p = 0.042). Longer survival times were also observed in patients whose peripheral white blood cells contained >20.0% lymphocytes (12.6 versus 4.5 months; p = 0.014). MUC1-specific cytotoxic immune responses were achieved in all of seven patients analyzed who received six vaccinations. The MUC1-targeted DC-based vaccine induced an antitumor immune response that promoted prolonged survival of patients with refractory NSCLC. The occurrence of immune-related adverse events and having a higher percentage of peripheral lymphocytes were predictive biomarkers of a beneficial clinical response during cancer immunotherapy for NSCLC.


Tomosyn negatively regulates CAPS-dependent peptide release at Caenorhabditis elegans synapses.
The syntaxin-interacting protein tomosyn is thought to be a key regulator of exocytosis, although its precise mechanism of action has yet to be elucidated. Here we examined the role of tomosyn in peptide secretion in Caenorhabditis elegans tomosyn (tom-1) mutants. Ultrastructural analysis of tom-1 mutants revealed a 50% reduction in presynaptic dense-core vesicles (DCVs) corresponding to enhanced neuropeptide release. Conversely, overexpression of TOM-1 led to an accumulation of DCVs. Together, these data provide the first in vivo evidence that TOM-1 negatively regulates DCV exocytosis. In C. elegans, neuropeptide release is promoted by the calcium-dependent activator protein for secretion (CAPS) homolog UNC-31. To test for a genetic interaction between tomosyn and CAPS, we generated tom-1;unc-31 double mutants. Loss of TOM-1 suppressed the behavioral, electrophysiological, and DCV ultrastructural phenotypes of unc-31 mutants, indicating that TOM-1 antagonizes UNC-31-dependent DCV release. Because unc-31 mutants exhibit synaptic transmission defects, we postulated that loss of DCV release in these mutants and the subsequent suppression by tom-1 mutants could simply reflect alterations in synaptic activity, rather than direct regulation of DCV release. To distinguish between these two possibilities, we analyzed C. elegans Rim mutants (unc-10), which have a comparable reduction in synaptic transmission to unc-31 mutants, specifically attributed to defects in synaptic vesicle (SV) exocytosis. Based on this analysis, we conclude that the changes in DCV release in tom-1 and unc-31 mutants reflect direct effects of TOM-1 and UNC-31 on DCV exocytosis, rather than altered SV release.


[Clinical introduction to aneurysmatic bone cysts].
The aneurysmal bone cyst is according to the description of Jaffe and Lichtenstein (1942) a histomorphological entity. It is a benign centric or eccentrically localized tumor like lesion with preference to the metaphysis. 75% of all aneurysmal bone cysts occur within the first two decades of life. On x-ray the diagnosis is not always clear. In differential diagnosis juvenile bone cyst, giant cell tumor, chondroblastoma, chondromyxoid fibroma, non ossifying fibroma, fibrous dysplasia and telangiectasic osteogenic sarcoma have to be considered. Final diagnosis requires histological evaluation. Curettage or resection with bone grafting is the predominant therapeutic procedure. Radiotherapy might cause malignant degradation and should only be used in elected cases. For propaedeutic evaluations of aneurysmal bone cysts 851 cases in world literature are reported.


Clinicopathologic implication of A20/TNFAIP3 deletion in diffuse large B-cell lymphoma: an analysis according to immunohistochemical subgroups and rituximab treatment.
We analyzed the clinicopathologic implication of A20/tumor necrosis factor α-induced protein 3 deletion in diffuse large B-cell lymphoma (DLBCL) using fluorescence in situ hybridization, according to germinal center B-cell (GCB) versus non-GCB/activated B-cell (ABC) phenotypes and rituximab treatment. Excluding primary central nervous system (CNS) and Epstein-Barr virus (EBV)-positive lymphomas, 134 DLBCLs were analyzed. A20 was deleted in 23.1% (31/134) of DLBCLs including 21.6% (29/ 134) of monoallelic and 1.5% (2/134) of biallelic deletion, with no predilection for GCB versus non-GCB/ABC. In univariate analysis, A20 deletion was marginally associated with favorable prognosis in the rituximab-treated subgroup (n = 109; p = 0.0454), non-gastrointestinal lymphoma (n = 108; p = 0.0320) and nodal lymphoma (n = 46; p = 0.0411). In multivariate analysis in rituximab-treated DLBCL, MUM1 and international prognostic index (IPI) were independent prognostic factors (p = 0.021 [IPI]; p = 009 [MUM1]) with a marginally favorable prognostic effect for A20 deletion (p = 0.047). Taken together, A20 deletion was observed in similar frequencies in GCB and non-GCB/ABC, and was not a poor prognostic factor in DLBCL.


Diurnal intraocular pressure curves in healthy rhesus macaques (Macaca mulatta) and rhesus macaques with normotensive and hypertensive primary open-angle glaucoma.
The authors identify any diurnal intraocular pressure (IOP) variation in healthy Cayo Santiago macaques, as well as Cayo Santiago macaques with normotensive and hypertensive primary open-angle glaucoma (POAG), to further evaluate their potential value as a model for human POAG. Twenty-four monkeys (eight animals each of the healthy control, normotensive glaucoma, and hypertensive glaucoma groups) were sedated with ketamine hydrochloride and the IOP measured hourly from 8:00 AM until 3:00 PM with a Tonopen XL applanation tonometer (Mentor, Norwell, MA, U.S.A.). Mean IOP time profiles, mean IOPs at each observation time, and linear trends in mean IOP over time were compared among groups. Intraocular pressure rate-of-change over time and residual variation about the regression line for each individual eye were analyzed. Cup/disc ratio (C/D) was compared with baseline IOP, IOP profile mean and slope, and IOP residual variation. A significant group and time effect on mean IOP (p = 0.0001 and 0.011, respectively), with highest values at 2:00 PM or 3:00 PM, and a significant increasing linear trend in mean IOP over time in the hypertensive group were observed (p = 0.012). Intermediate readings between control and hypertensive mean IOPs were identified for the normotensive glaucoma group. The biggest range of IOP variation was found in the hypertensive glaucoma monkeys. Higher variations in IOP did not lead to an increase in C/D. This study provides evidence that the Cayo Santiago macaques are a valuable model for human normotensive and hypertensive POAG.


Physical effect of work on healthy individuals: implications for FCE testing.
The objective of this study was to assess the effect of time of day and job type on performance of three functional capacity evaluation measures in healthy (asymptomatic) adults. It was queried whether or not a healthy population of adults would demonstrate a change in physical performance ability, when re-tested at the end of their work day. A convenience sample of 50 healthy adults (19-62 years, 66% male) was used from six work sites in an urban area. Same day pre-test and post-test testing was performed, implementing use of three commonly used functional capacity tests: Jamar dynamometer grip strength test, Turning sub-test of the Complete Minnesota Dexterity Test, and the 50-foot walk test. The study compared morning and afternoon test scores, and using t-tests, assessed the effect of job type (sedentary, light, medium, heavy) on performance using ANOVA. All three measures improved from morning to afternoon; differences were statistically significant for 50-foot walk (mean=0.2 sec, p=0.02) and manual dexterity (mean=5 sec, p< 0.001). Job type had a significant effect on dexterity. Late day performance did not show any significant decline in this sample of healthy adults, and in fact tended to improve or stay relatively stable. Therefore, clinicians who perform functional capacity evaluations should consider alternative explanations for late-day functional declines observed in injured patients. These findings, combined with other test results, may assist clinicians with disability determination.


A review of thanatosis (death feigning) as an anti-predator behaviour.
Thanatosis-also known as death-feigning and, we argue more appropriately, tonic immobility (TI)-is an under-reported but fascinating anti-predator strategy adopted by diverse prey late on in the predation sequence, and frequently following physical contact by the predator. TI is thought to inhibit further attack by predators and reduce the perceived need of the predator to subdue prey further. The behaviour is probably present in more taxa than is currently described, but even within well-studied groups the precise taxonomic distribution is unclear for a number of practical and ethical reasons. Here we synthesise the key studies investigating the form, function, evolutionary and ecological costs and benefits of TI. This review also considers the potential evolutionary influence of certain predator types in the development of the strategy in prey, and the other non-defensive contexts in which TI has been suggested to occur. We believe that there is a need for TI to be better appreciated in the scientific literature and outline potentially profitable avenues for investigation. Future use of technology in the wild should yield useful developments for this field of study. Anti-predatory defences are crucial to many aspects of behavioural ecology. Thanatosis (often called death-feigning) has long been an under-appreciated defence, despite being taxonomically and ecologically widespread. We begin by providing much-needed clarification on both terminology and definition. We demonstrate how apparently disparate observations in the recent literature can be synthesised through placing the behaviour within a cost-benefit framework in comparison to alternative behavioural choices, and how aspects of the ecology differentially affect costs and benefits. Extending this, we provide novel insights into why the evolution of thanatosis can be understood in terms of coevolution between predators and prey. We offer further novel hypotheses, and discuss how these can be tested, focussing on how emerging technologies can be of great use in developing our understanding of thanatosis in free-living animals.


The pinch blepharoplasty revisited.
The prevention of scleral show is truly one of plastic surgery's Holy Grails. This postoperative problem may be considered subtle, but it represents the most common cause of the "operated" look that we all strive to avoid. Of course, the postoperative fear of a true ectropion is all too common. These concerns, borne out in patient results following the traditional skin-muscle technique, are what drove the author to consider the "pinch" blepharoplasty. All patients who were candidates for a lower blepharoplasty, primary or secondary, underwent the pinch blepharoplasty. Patients excluded were only those who underwent a carbon dioxide laser resurfacing of the lower eyelid, as no skin excision was planned. Of the 77 blepharoplasties performed, there were no postoperative findings of lower eyelid malposition: no taping was necessary, no significant scleral show was evident, and no ectropion was produced. There was also noticeably less bruising and swelling postoperatively with this technique. Moreover, it was apparent that the crepe-like skin at the lower eyelid was often fully effaced or improved significantly. The pinch blepharoplasty has proved to be a superior approach to lower eyelid rejuvenation. This series suggests that with this technique significantly more crepe-like skin can be removed with reliably less chance of scleral show.


Gold-Catalyzed Cadiot-Chodkiewicz-type Cross-Coupling of Terminal Alkynes with Alkynyl Hypervalent Iodine Reagents: Highly Selective Synthesis of Unsymmetrical 1,3-Diynes.
A new and efficient method for the synthesis of unsymmetrical 1,3-butadiynes by gold-catalyzed C(sp)-C(sp) cross-coupling of terminal alkynes with alkynyl hypervalent iodine(III) reagents has been developed. The reaction features high selectivity and efficiency, mild reaction conditions, wide substrate scope, and functional-group compatibility, and is a highly attractive complement to existing methods. Mechanistic studies reveal that formation of a phenanthrolinyl-ligated gold(I) complex is crucial for the efficiency and selectivity of the target transformation.


Effects of transjugular intrahepatic portosystemic shunt (TIPS) on blood volume distribution in patients with cirrhosis.
Cirrhosis is accompanied by portal hypertension with splanchnic and systemic arterial vasodilation, and central hypovolaemia. A transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension, but also causes major haemodynamic changes. To investigate effects of TIPS on regional blood volume distribution, and systemic haemodynamics. Thirteen cirrhotic patients had their regional blood volume distribution determined with gamma-camera technique before and after TIPS. Additionally, we measured systemic haemodynamics during liver vein and right heart catheterization. Central and arterial blood volume (CBV) and cardiac output (CO) were determined with indicator dilution technique. After TIPS, the thoracic blood volume increased (+10.4% of total blood volume (TBV), p<0.01), whereas the splanchnic blood volume decreased (-11.9% of TBV, p<0.001). CO increased (+22%, p<0.0001), and systemic vascular resistance decreased (-26%, p<0.001), whereas CBV did not change. Finally, right atrial pressure and mean pulmonary artery pressure increased after TIPS (+50%, p<0.005; +40%, p<0.05, respectively). TIPS restores central hypovolaemia by an increase in thoracic blood volume and alleviates splanchnic vascular congestion. In contrast, CBV seems unaltered. The improvement in central hypovolaemia is therefore based on an increase in thoracic blood volume that includes both the central venous and arterial blood volume. This is supported by an increase in preload, combined with a decrease in afterload.


[Ciliopaties - diseases caused by abnormal cilia functioning].
Ciliopathies are a group of genetic diseases caused by defects in the function of cilia, that are cellular processes composed of a microtubule-based core. Ciliopathies present with pathological changes in one or many organs at the same time. Symptoms of ciliopathies depend on the type of damaged tissues and organs. The most common are polycystic kidney and liver, blindness, dysfunction of neural tube, brain anomalies, mental retardation, abnormalities in skeletal system from polydactyly to abnormal short ribs and limbs, abnormalities in ectoderms, obesity, situs inversus, infertility and infections of the upper airways. Both basic and clinical studies provide data regarding novel ciliary proteins the lack or mutation of which are associated with cilia dysfunction and which, in consequence, may give rise to ciliopathies. The number of ciliopathies (35 known at present) is still increasing due to identification of additional genes (187 identified up to now) directly connected with these diseases. In this work, the most important mechanisms responsible for abnormal cilia formation and functioning, that constitute the primary cause of ciliopathies, are presented.


Regulation of Na+, K(+)-ATPase in the rat outer medullary collecting duct during potassium depletion.
Because in outer medullary collecting ducts (OMCD) of K(+)-depleted rats, K+ secretion is abolished, whereas Na+, K(+)-ATPase, which energizes this secretion, is markedly stimulated, it has been proposed that Na+, K(+)-ATPase was mislocated to the apical cell membrane and energized K+ reabsorption. This hypothesis has been supported by paradoxical effects of ouabain in K(+)-depleted compared with normal rats. However, we have recently shown that ouabain inhibits not only Na+, K(+)-ATPase but also apical H+, K(+)-ATPase in the OMCD of K(+)-depleted rats. Therefore, this study was designed to evaluate whether previous observations were accounted for by Na+, K(+)-ATPase or by ouabain-sensitive H+, K(+)-ATPase. Na+, K(+)-ATPase was distinguished from H+, K(+)-ATPase by its insensitivity to Sch-28080. Results indicate that the hydrolytic and transport activities of Na+, K(+)-ATPase, the number of its functional units, and the expression of mRNA of its alpha 1 and beta 1 subunits were increased threefold or more in the OMCD of rats fed a K(+)-depleted diet for 2 wk. By immunofluorescence, Na+, K(+)-ATPase staining was strongly increased in K(+)-depleted rats but remained localized to the basolateral pole of OMCD principal cells. In conclusion, K+ depletion is associated with marked induction of functional Na+, K+ pumps at the basolateral pole of rat OMCD. Therefore, reduced K+ secretion might result from inhibition of apical K+ conductances and stimulation of basolateral K+ recycling. It is proposed that increased Na+, K(+)-ATPase participates in the increased Na+ reabsorption prevailing in collecting ducts of K(+)-depleted rats.


The malfunctioning silastic catheter--radiologic assessment and treatment.
Occlusion of silastic catheters is attributed to several documented causes. One factor not yet adequately documented is fibrin sleeve formation. In this instance, the catheter functions for infusion purposes, but blood withdrawal is no longer feasible. This is a troublesome occurrence when encountered in the clinical setting. This report reviews the assessment of fibrin sleeve formation, the use of catheter phlebography and treatment with low-dose streptokinase. Seventeen instances of the inability to aspirate blood from silastic catheters are evaluated with restoration of full catheter function in all cases after streptokinase administration.


Ion Current Rectification Behavior of Bioinspired Nanopores Having a pH-Tunable Zwitterionic Surface.
The ion current rectification behavior of bioinspired nanopores is modeled by adopting a bullet-shaped nanopore having a pH-tunable zwitterionic surface, focusing on discussing the underlying mechanisms. We show that with its specific geometry, such nanopore is capable of exhibiting several interesting behaviors, including ion concentration polarization and ion current rectification. The influences of the nanopore shape, solution pH, and bulk salt concentration on the associated ion current rectification behavior are examined. We found that if pH exceeds the isoelectric point, the rectification factor has a local maximum as the curvature of the nanopore surface varies, and if it is lower than the isoelectric point, that factor increases (rectification effect decreases) monotonically with increasing surface curvature. In addition to capable of interpreting relevant electrokinetic phenomena, the results gathered also provide necessary information for a sophisticated design of relevant devices.


Incidence of childhood cancer in France: National Children Cancer Registries, 2000-2004.
The French National Registry of Childhood Haematopoietic Malignancies and the French National Registry of Childhood Solid Tumours jointly ensure the surveillance of cancer in children aged less than 15 years in mainland France. During the period 2000-2004, the registries recorded a total of 8473 cases: 3446 cases of haematological malignancies and 5027 cases of solid tumours. The average number of sources per case was 2.7 and diagnosis was documented by cytology/histology in 94% of cases, ensuring high quality data. The age-standardized incidence rate for all cancers combined was 156.6 cases per million children per year, with a sex ratio of 1.2. The most frequent cancers were leukaemia (29%), central nervous system tumour (23%), lymphoma (12%) and neuroblastoma (8%). In France, an estimated one out of every 440 children presents with cancer before the age of 15 years. The incidence rates are close to those of other industrialized countries, but somewhat higher than those estimated by the French local registries for the period 1990-1999, probably because of improved methodology or perhaps a real increase in some rates. The French National Registries of Childhood Cancer have shown that they are able to fulfil public health surveillance missions satisfactorily and support the national programme for research on childhood cancer.


High and persistent excretion of hepatitis A virus in immunocompetent patients.
The duration and level of virus excretion in blood and faeces of patients with hepatitis A virus (HAV) infection were studied in relation to levels of alanine aminotransferase (ALT), disease severity and HAV genotype. Clinical data, blood and faeces were collected from 27 patients with acute hepatitis A (median age: 33 years) for a maximum of 26 weeks. Single blood donations from 55 other patients with acute HAV (median age: 32 years) were also used. Virus loads were quantified by competitive nested RT-PCR. HAV was excreted in faeces for a median period of 81 days after disease onset, with 50% of patients still excreting high levels at Day 36 (2 x 10(6) - 2 x 10(8) copies/ml faeces suspension). Viraemia was detected, but not quantifiable, for a median period of 42 days. In the first 10 days of illness, higher ALT levels were correlated with higher viraemia levels. Comparison of patients infected with genotype 1a with those infected with type 1b did not differ significantly in terms of the duration of HAV excretion or jaundice. In conclusion, faecal excretion of HAV is at a high titre in the first month, perhaps making patients infectious for a longer period than assumed currently. Blood banks should be aware that viraemia may be present for more than 1 month, and genotype did not affect the duration of virus excretion or jaundice.


A "hyperextensive" review of Ehlers-Danlos syndrome.
Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders characterized by hyperextensibility, delayed wound healing, joint hypermobility, thin skin, easy bruising, tissue fragility, "cigarette-paper" scarring over bony prominences, mitral valve prolapse, and other findings. There are 6 main types of EDS. Regardless of presentation as a chief concern or an incidental finding, physicians should be aware that the prominent skin findings of EDS are cutaneous signs of an important systemic disorder.


Fabrication of Novel Printable Electrically Conductive Adhesives (ECAs) with Excellent Conductivity and Stability Enhanced by the Addition of Polyaniline Nanoparticles.
Electrically conductive adhesives (ECAs) are one of the low temperature bonding materials. It can be used to replace toxic Sn-Pb solder. The key issue for the application of ECAs is how to improve their electrical properties. In the present study, we develop an effective method to promote the electrical properties of ECAs by addition of polyaniline (PANI) nanoparticles. PANIs were synthesized via a facile one-step chemical oxidative polymerization method. After adding 0.5 wt% PANI nanoparticles, the conductivity of ECAs increased dramatically by an order of magnitude. The bulk resistivity of 8.8 × 10-5 Ω·cm is achieved for 65 wt% silver fillers with 0.5 wt% PANIs loaded ECAs. Besides, this improvement has no negative effect on the shear strength and the aging life of ECAs. Moreover, the use of PANIs not only lowers the percolation threshold of ECAs, but also reduces the cost and improves the bonding reliability. Finally, PANIs enhanced ECAs patterns were successfully printed by a stencil printing method, which proved their potential applications in replacing conventional solder pastes and printing functional circuits.


New reference values for vitamin D.
In the recent past, many studies have been published on the association between vitamin D and bone health or the risk of various chronic diseases. Thus, the D-A-CH reference values [D-A-CH arises from the initial letters of the common country identification for the countries Germany (D), Austria (A) and Switzerland (CH)] for the intake of vitamin D have been revised based on a critical review by the German Nutrition Society. Both dietary intake and endogenous synthesis contribute to the body's vitamin D status. Since different factors modulate the extent of endogenous vitamin D formation, quantification is hardly possible. Therefore, the new reference values for vitamin D intake are specified for a situation in which endogenous synthesis is completely missing. Based on the findings of the critical review, serum 25-hydroxyvitamin D concentrations of 50 nmol/l or higher are considered an indicator of an optimal vitamin D status. When endogenous synthesis is missing, adequate vitamin D intake is estimated as 20 µg per day for children, adolescents and adults. Dietary vitamin D intake from habitual diet is not sufficient to achieve this value. This gap has to be covered by endogenous vitamin D synthesis and/or additional intake of vitamin D. It is clearly stated that the desired vitamin D supply can be achieved without using vitamin D supplements by frequent sun exposure.


UBQLN Family Members Regulate MYC in Lung Adenocarcinoma Cells.
The ubiquilin family (UBQLN) of proteins consists of five closely related members (UBQLN1, UBQLN2, UBQLN3, UBQLN4, and UBQLNL) that have a high degree of similarity at the level of both amino acid and domain structure. The role of UBQLN1 and UBQLN2 in regulating processes involved in cancer progression and tumorigenesis is still not completely understood. MYC is an oncogene and is well known to play important roles in cancer progression and metastasis. Herein, we show that the loss of UBQLN1 and UBQLN2 causes increased cell viability, cell proliferation, cell migration, clonogenic potential, and cell cycle progression, which is associated with increased MYC expression. UBQLN1 and UBQLN2 interact with phosphorylated MYC and facilitate its degradation. The overexpression of UBQLN1 reverses the increased expression of MYC following the loss of UBQLN2. Further, we present evidence that decreasing MYC levels back to baseline can reverse phenotypes driven by the loss of UBQLN1 or UBQLN2. Finally, we show that loss of UBQLN1 drives tumorigenesis and lung metastasis in mice which are associated with an increase in the expression of MYC, proteins involved in cell cycle progression, and EMT. Taken together, our results suggest for the first time a novel role of UBQLN1 and UBQLN2 in regulating MYC in lung adenocarcinoma cells.


Critical Review Upon the Role and Potential of Fluorescence and Near-Infrared Imaging and Absorption Spectroscopy in Cancer Related Cells, Serum, Saliva, Urine and Tissue Analysis.
During the last years, non-invasive or minimally invasive diagnostic tools in cancer diagnostics have become more important. Many fluorescence spectroscopic methodologies have been established for nearly all different kinds of cancer. The reason therefore is its high sensitivity, low amount of sample required, short testing time, and the suitability for in situ testing. The potential influence factors for cancer diagnostics and the subsequent suitability of the method to different applications are well described. Near-Infrared spectroscopy (NIRS) is based on differences of endogenous chromophores between cancer and normal tissues using either oxyhaemoglobin or deoxy-haemoglobin, lipid or water bands, or a combination of two or more of these diagnostic markers. These marker bands are known to provide the fundamental for the diagnosis of several cancers and the spectroscopic setup can be applied for the analysis of cells, urine and tissue. For the preparation of this review the literature published during the last fifteen years has been taken into consideration. It will provide an overview on the importance of the fluorescence and NIRS tools in cancer analysis giving hints about how these techniques can play a crucial role in cancer diagnosis, treatment decisions and therapy. The two techniques, fluorescence and near-infrared spectroscopy (NIRS) are faced to each other and individual advantages and/or drawbacks are discussed. Finally, it will be taken into consideration; how the synergistic combination of different approaches can give additional information related to development and progression stages of cancer.


Comparison of Life Tables of Cheilomenes sexmaculata (Coleoptera: Coccinellidae) Under Laboratory and Greenhouse Conditions.
The ladybird Cheilomenes sexmaculata (F.) is an important aphidophagous predator in Asia. In order to mass rear predators for biological control, it is valuable to identify the features of populations that are affected by variations in field conditions. Life tables can provide comprehensive descriptions of the development, survival, and fecundity of a population. However, there are few life table studies of C. sexmaculata. Studies of life history have been carried out in many arthropods using the traditional female age-specific life table, which takes only female individuals into consideration, while the variations in developmental rates amongst individuals are ignored. In this paper, we constructed life tables for C. sexmaculata fed on Myzus persicae (Sulzer) both at constant temperature in the laboratory and fluctuating temperature in the greenhouse, and analyzed the data using the age-stage, two-sex life table. The bootstrap technique was used to estimate the standard errors of the population parameters. The results showed that preadult C. sexmaculata developed more slowly and had lower survival and reproductive rates under greenhouse conditions, as indicated by the curves of age-stage survival rate (s(xj)), age-stage-specific fecundity (f(x j)) of the female stage, age-specific fecundity (m(x)), and age-specific maternity (l(x)m(x)). Our results also showed that the intrinsic rate of increase (r), net reproductive rate (R(0)), and finite rate of increase (λ) under laboratory and greenhouse conditions were 0.1668 d(-1) and 0.1027 d(-1), 192.1 and 53.0, and 1.1815 d(-1) and 1.1082 d(-1), respectively. Our results revealed significantly different life table parameters for C. sexmaculata under laboratory and greenhouse conditions. This information will be useful for developing a successful mass-rearing program for C. sexmaculata for use in biological control.


Relative insensitivity to time-out punishments induced by win-paired cues in a rat gambling task.
Pairing rewarding outcomes with audiovisual cues in simulated gambling games increases risky choice in both humans and rats. However, the cognitive mechanism through which this sensory enhancement biases decision-making is unknown. To assess the computational mechanisms that promote risky choice during gambling, we applied a series of reinforcement learning models to a large dataset of choices acquired from rats as they each performed one of two variants of a rat gambling task (rGT), in which rewards on "win" trials were delivered either with or without salient audiovisual cues. We used a sampling technique based on Markov chain Monte Carlo to obtain posterior estimates of model parameters for a series of RL models of increasing complexity, in order to assess the relative contribution of learning about positive and negative outcomes to the latent valuation of each choice option on the cued and uncued rGT. Rats which develop a preference for the risky options on the rGT substantially down-weight the equivalent cost of the time-out punishments during these tasks. For each model tested, the reduction in learning from the negative time-outs correlated with the degree of risk preference in individual rats. We found no apparent relationship between risk preference and the parameters that govern learning from the positive rewards. The emergence of risk-preferring choice on the rGT derives from a relative insensitivity to the cost of the time-out punishments, as opposed to a relative hypersensitivity to rewards. This hyposensitivity to punishment is more likely to be induced in individual rats by the addition of salient audiovisual cues to rewards delivered on win trials.


Acute care/blood gas laboratories: profile of current operations.
A survey of acute care/blood gas laboratories was conducted through the memberships of the Society of Critical Care Medicine ( SCCM ) and the National Association of Medical Directors of Respiratory Care ( NAMDRC ). Data were obtained from 227 laboratories and analyzed for operational characteristics, personnel, analyses performed, and quality assurance procedures. Analyses included blood gases/pH, saturation, P50, oxygen content, hematocrit/hemoglobin concentration, as well as sodium, potassium, calcium, osmometry, and glucose. Application of appropriate quality control was uneven in terms of types and frequencies of procedures. Education of laboratory personnel ranged from high school to graduate degrees, with the greatest numbers having associate-level and baccalaureate-level educations . Certification of laboratory personnel primarily was through the National Board for Respiratory Therapy, although 36% of the personnel had no certification or registration. Aspects of the acute care laboratory identified as needing improvement are educational and certification requirements for laboratory personnel and application of quality control procedures. The database developed from this survey will serve for ongoing assimilation of information related to the operation of acute care laboratories.


Enantioselective palladium-catalyzed C-H functionalization of indoles using an axially chiral 2,2'-bipyridine ligand.
A palladium-catalyzed enantioselective CH functionalization of indoles was achieved with an axially chiral 2,2'-bipyridine ligand, thus providing the desired indol-3-acetate derivatives with up to 98 % ee. Moreover, the reaction protocol was also effective for asymmetric OH insertion reaction of phenols using α-aryl-α-diazoacetates. This represents the first successful application of bipyridine ligands with axial chirality in palladium-catalyzed carbene migratory insertion reactions.


Moving past neonicotinoids and honeybees: A systematic review of existing research on other insecticides and bees.
Synthetic pesticides (e.g. herbicides, fungicides and insecticides) are used widely in agriculture to protect crops from pests, weeds and disease. However, their use also comes with a range of environmental concerns. One key concern is the effect of insecticides on non-target organisms such as bees, who provide pollination services for crops and wild plants. This systematic literature review quantifies the existing research on bees and insecticides broadly, and then focuses more specifically on non-neonicotinoid insecticides and non-honeybees. We find that articles on honeybees (Apis sp.) and insecticides account for 80% of all research, with all other bees combined making up 20%. Neonicotinoids were studied in 34% of articles across all bees and were the most widely studied insecticide class for non-honeybees overall, with almost three times as many studies than the second most studied class. Of non-neonicotinoid insecticide classes and non-honeybees, the most studied were pyrethroids and organophosphates followed by carbamates, and the most widely represented bee taxa were bumblebees (Bombus), followed by leaf-cutter bees (Megachile) and mason bees (Osmia). Research has taken place across several countries, with the highest numbers of articles from Brazil and the US, and with notable gaps from countries in Asia, Africa and Oceania. Mortality was the most studied effect type, while sub-lethal effects such as on behaviour were less studied. Few studies tested how the effect of insecticides were influenced by multiple pressures, such as climate change and co-occurring pesticides (cocktail effects). As anthropogenic pressures do not occur in isolation, we suggest that future research also addresses these knowledge gaps. Given the changing global patterns in insecticide use, and the increasing inclusion of both non-honeybees and sub-lethal effects in pesticide risk assessment, there is a need for expanding research beyond its current state to ensure a strong scientific evidence base for the development of risk assessment and associated policy.


[Pseudotumor pancreatic tuberculosis].
A 59 year-old male with a toxic syndrome an a pancreatic pseudotumoral mass. Two pancreatic fine needle aspiration cytologies were negative. Liver and pancreatic surgical biopsies showed a chronic granulomatous tuberculous inflammation. Mycobacterium tuberculosis was isolated in the gastric juice; the urine and sputum cultures was negative. Tuberculostatic treatment with Rifampicin, Isoniazid and Ethambutol was effective. We emphasize the importance of the histological diagnosis in all of pancreatic mass.


Solvothermal-Based Lignin Fractionation From Corn Stover: Process Optimization and Product Characteristics.
Fractionation of lignocellulosic is a fundamental step in the production of value-added biobased products. This work proposes an initiative to efficiently extract lignin from the corn stover using a single-step solvothermal fractionation in the presence of an acid promoter (H2SO4). The organic solvent mixture used consists of ethyl acetate, ethanol, and water at a ratio of 30: 25:45 (v/v), respectively. H2SO4 was utilized as a promoter to improve the performance and selectivity of lignin removal from the solid phase and to increase the amount of recovered lignin in the organic phase. The optimal conditions for this extraction, based on response surface methodology (RSM), are a temperature of 180°C maintained for 49.1 min at an H2SO4 concentration of 0.08 M. The optimal conditions show an efficient reaction with 98.0% cellulose yield and 75.0% lignin removal corresponding to 72.9% lignin recovery. In addition, the extracted lignin fractions, chemical composition, and structural features were investigated using Fourier transform infrared spectroscopy, thermogravimetric analysis, elemental analysis, and two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance spectroscopy (2D-HSQC NMR). The results indicate that the recovered lignin primarily contains a β-O-4 linking motif based on 2D-HSQC spectra. In addition, new C-C inter-unit linkages (i.e., β-β, and β-5) are not formed in the recovered lignin during H2SO4-catalyzed solvothermal pretreatment. This work facilitates effective valorization of lignin into value-added chemicals and fuels.


Metal-Organic Framework-Derived Co3ZnC/Co Embedded in Nitrogen-Doped Carbon Nanotube-Grafted Carbon Polyhedra as a High-Performance Electrocatalyst for Water Splitting.
The development of efficient, low-cost, and stable electrocatalysts for overall water splitting is of great significance for energy conversion. Transition-metal carbides (TMCs) with high catalytic activity and low cost have attracted great interests. Nevertheless, utilizing an efficient catalyst for overall water splitting is still a challenging issue for TMCs. Herein, we report the synthesis of a high-performance electrocatalyst comprising Co3ZnC and Co nanoparticles embedded in a nitrogen-doped carbon nanotube-grafted carbon polyhedral (Co3ZnC/Co-NCCP) by the pyrolysis of bimetallic zeolitic imidazolate frameworks in a reductive atmosphere of Ar/H2. The Co3ZnC/Co-NCCP exhibits remarkable electrochemical activity in catalyzing both the oxygen evolution reaction and hydrogen evolution reaction, in terms of low overpotential and excellent stability. Furthermore, the Co3ZnC/Co-NCCP catalyst leads to a highly performed overall water splitting in the 1 M KOH electrolyte, delivering a current density of 10 mA cm-2 at a low applied external potential of 1.65 V and shows good stability without obvious deactivation after 10 h operation. The present strategy opens a new avenue to the design of efficient electrocatalysts in electrochemical applications.


Pitch perception and production in congenital amusia: Evidence from Cantonese speakers.
This study investigated pitch perception and production in speech and music in individuals with congenital amusia (a disorder of musical pitch processing) who are native speakers of Cantonese, a tone language with a highly complex tonal system. Sixteen Cantonese-speaking congenital amusics and 16 controls performed a set of lexical tone perception, production, singing, and psychophysical pitch threshold tasks. Their tone production accuracy and singing proficiency were subsequently judged by independent listeners, and subjected to acoustic analyses. Relative to controls, amusics showed impaired discrimination of lexical tones in both speech and non-speech conditions. They also received lower ratings for singing proficiency, producing larger pitch interval deviations and making more pitch interval errors compared to controls. Demonstrating higher pitch direction identification thresholds than controls for both speech syllables and piano tones, amusics nevertheless produced native lexical tones with comparable pitch trajectories and intelligibility as controls. Significant correlations were found between pitch threshold and lexical tone perception, music perception and production, but not between lexical tone perception and production for amusics. These findings provide further evidence that congenital amusia is a domain-general language-independent pitch-processing deficit that is associated with severely impaired music perception and production, mildly impaired speech perception, and largely intact speech production.


Effects of spelling errors on the perception of writers.
The authors investigated the perceived relationship between spelling errors and cognitive abilities in a series of 3 experiments. Specifically, they examined whether college students' ratings of an author's intellectual ability, logical ability, and writing ability were affected by the presence of spelling errors. In the 1st experiment, the presence of 4 spelling errors in a short essay did not significantly affect the ratings. The spelling ability of college students, as measured by a standard oral dictation spelling test, was moderately conelated with a brief test of intelligence. In a 2nd experiment, college students rated the author of a short essay as having lower ability when there was a large number of spelling errors. The effect was more pronounced on the ratings of writing ability than it was on the ratings of logical ability or intellectual ability. This finding was replicated in a 3rd experiment, in which the essay contained misspellings actually made by writers. The results suggest that spelling errors can affect how people perceive writers, particularly when there are many spelling errors. College students appear to attribute spelling errors more to writing ability than they do to general cognitive abilities such as intelligence and logical ability.


Dissimulation strategies on standard neuropsychological tests: A qualitative investigation.
Most previous studies in the area of malingering neuropsychological deficits have focused on the development and validation of measures to detect falsification of symptoms or suboptimal performance. The present study employs qualitative methods to investigate strategies employed by individuals attempting to feign cognitive impairment. This study aims to achieve a richer and more detailed understanding of the phenomenon of feigning. Detailed semi-structured interviews were administered to 15 non-neurological individuals instructed to feign cognitive impairment on a standard neuropsychological test battery. The interviews, which considered the strategies used and the thinking underlying participants' choices, were subjected to Thematic Analysis. Thematic Analysis revealed three main organising themes. Participants described Using Strategies, on specific tests and generally across the battery, Having a Rationale for their decisions and spontaneously commented on their Experience of the Task. The findings of the present study reveal numerous potentially useful identifiers of feigning strategies, including many not previously reported. The resulting themes point to the development of more effective methods for detecting feigned cognitive impairments and could have a significant impact on the way that neuropsychological testing sessions are conducted.


Reducing the use of screen electronic devices in the evening is associated with improved sleep and daytime vigilance in adolescents.
The use of screen electronic devices in the evening negatively affects sleep. Yet, sleep is known to be essential for brain maturation and a key factor for good academic performance, and thus is particularly critical during childhood and adolescence. Although previous studies reported associations between screen time and sleep impairment, their causal relationship in adolescents remains unclear. Using actigraphy and daily questionnaires in a large sample of students (12 to 19 years old), we assessed screen time in the evening and sleep habits over 1 month. This included a 2 week baseline phase, followed by a 40 min sleep education workshop and a 2 week interventional phase, in which participants were asked to stop using screen devices after 9 pm during school nights. During the interventional phase, we found that the reduction of screen time after 9 pm correlated with earlier sleep onset time and increased total sleep duration. The latter led to improved daytime vigilance. These findings provide evidence that restricting screen use in the evening represents a valid and promising approach for improving sleep duration in adolescents, with potential implications for daytime functioning and health.


Addition of bupivacaine to sufentanil in patient-controlled epidural analgesia after lower limb surgery in young adults: effect on analgesia and micturition.
The usefulness of adding bupivacaine to an opioid administered by the epidural route is controversial. This study examines both the quality of pain relief and side effects, in particular urinary retention, during patient-controlled epidural analgesia (PCEA) with sufentanil alone or in combination with two different concentrations of bupivacaine. In a double-blind randomized study, 60 healthy young adults undergoing open knee or ankle surgery with combined spinal-epidural anesthesia received postoperative analgesia via PCEA with sufentanil alone or with 0.06% or 0.12% bupivacaine. In addition to pain scores at rest and during mobilization, bladder function was evaluated. Strict criteria were respected in scoring the occurrence of problems suggestive of urinary retention. The 24-hour analgesic consumption and the incidence of other side effects were also recorded. Patients receiving bupivacaine had better pain relief than those receiving only the opioid, but this difference was more pronounced when measuring dynamic pain scores. The consumption of sufentanil was significantly higher in the group receiving the opioid alone than in the group receiving 0.06% bupivacaine. The bupivacaine dose requirements were twice as high with the 0.12% concentration. Bladder problems occurred significantly more frequently in patients treated with the highest bupivacaine concentration. Motor impairment was not a major problem. A 0.06% bupivacaine-sufentanil combination offered the best results in terms of analgesic quality and lower side effects, mainly micturition problems, which may be explained by the higher consumption of local anesthetic at the higher bupivacaine concentration. Analgesic quality could not be improved by increasing the bupivacaine concentration.


Prostate-associated gene 4 (PAGE4), an intrinsically disordered cancer/testis antigen, is a novel therapeutic target for prostate cancer.
Prostate-associated gene 4 (PAGE4) is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein (IDP) that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun. c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer (PCa). Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.


In Situ Probing the Short-Lived Intermediates in Visible-Light Heterogeneous Photocatalysis by Mass Spectrometry.
Visible-light-mediated heterogeneous photocatalysis has recently emerged as an environmentally friendly and energy-sustainable alternative for organic transformations. Despite the advancements in developing wide varieties of photocatalysts during the past decades, the accurate probing and identification of the photogenerated species, especially the short-lived radical intermediates, are still challenging. In this work, we reported a hybrid ion emitter that integrated with a pico-liter heterogeneous photocatalytic reactor, which was fabricated by depositing the photocatalyst (e.g., TiO2) into the front tip of a quartz micropipette. Benefited from the dual-function feature of the hybrid micropipette (i.e., a clog-free tip-confined pico-liter reactor for heterogeneous photocatalysis and an ion emitter for nanoelectrospray ionization), sensitized photoredox reactions at the catalyst-solution interface can be triggered upon visible-light irradiation using a cheap LED laser (453 nm), and the newly produced transient radical intermediates can be rapidly transformed into gaseous ions for mass spectrometric identification. Using this novel low-delay coupling device, photogenerated intermediates, including the cationic radicals produced during the photooxidation of anilines and the anionic radicals produced during the photoreduction of quinones, were successfully captured by mass spectrometry. We believe that our hybrid photochemical microreactor/ion emitter has provided a new and powerful tool for exploring the complicated heterogeneous photochemical processes, especially their ultrafast initial transformations.


The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes.
The let-7 microRNA (miRNA) plays important roles in human liver development and diseases such as hepatocellular carcinoma, liver fibrosis and hepatitis wherein oxidative stress accelerates the progression of these diseases. To date, the role of the let-7 miRNA family in modulation of heme oxygenase 1 (HMOX1), a key cytoprotective enzyme, remains unknown. Our aims were to determine whether let-7 miRNA directly regulates Bach1, a transcriptional repressor of the HMOX1 gene, and whether indirect up-regulation of HMOX1 by let-7 miRNA attenuates oxidant injury in human hepatocytes. The effects of let-7 miRNA on Bach1 and HMOX1 gene expression in Huh-7 and HepG2 cells were determined by real-time qRT-PCR, Western blot, and luciferase reporter assays. Dual luciferase reporter assays revealed that let-7b, let-7c, or miR-98 significantly decreased Bach1 3'-untranslated region (3'-UTR)-dependent luciferase activity but not mutant Bach1 3'-UTR-dependent luciferase activity, whereas mutant let-7 miRNA containing base complementarity with mutant Bach1 3'-UTR restored its effect on mutant reporter activity. let-7b, let-7c, or miR-98 down-regulated Bach1 protein levels by 50-70%, and subsequently up-regulated HMOX1 gene expression by 3-4 fold, compared with non-specific controls. Furthermore, Huh-7 cells transfected with let-7b, let-7c or miR-98 mimic showed increased resistance against oxidant injury induced by tert-butyl-hydroperoxide (tBuOOH), whereas the protection was abrogated by over-expression of Bach1. In conclusion, let-7 miRNA directly acts on the 3'-UTR of Bach1 and negatively regulates expression of this protein, and thereby up-regulates HMOX1 gene expression. Over-expression of the let-7 miRNA family members may represent a novel approach to protecting human hepatocytes from oxidant injury.


Atrial function in heart transplant recipients operated with the bicaval technique.
In heart transplantation (HTx) with the bicaval technique the whole right atrium (RA) is donor tissue while the left atrium (LA) consists of both donor and recipient tissue. The aims of the study were to describe atrial function in comparison with healthy controls and to identify determinants of dysfunction. Forty-three patients and 30 controls were retrospectively included. Echocardiography was performed within 24 h of right heart catheterization (RHC) (HTx recipients). The peak longitudinal atrial systolic strain (ɛ) described the atrial reservoir function. The LA and RA reservoir function were reduced versus controls (LA-ɛ 18 ± 8 versus 44 ± 10%; RA-ɛ 22 ± 10 versus 69 ± 17%, p < 0.001). There were moderate relationships between atrial-ɛ and ventricular filling pressure (r = -0.64 for LA-ɛ; r = -0.57 for RA-ɛ). In a multiple regression analysis the LA-ɛ was determined by pulmonary capillary wedge pressure (PCWP) and LA minimum volume index (r = -0.71) while RA-ɛ was dependent on the right ventricular ɛ (r = -0.77). Atrial reservoir function is markedly reduced in HTx recipients related to elevated PCWP and LA-enlargement in the LA and in the RA impaired longitudinal right ventricular function.


Personality and insomnia: A systematic review and narrative synthesis.
The inherent nature of personality serves as a predisposing, and possible maintaining, factor of insomnia. However, methodological differences limit the ability to draw causal conclusions regarding the specific traits involved in the aetiology of the disorder. This systematic review of the relationship between insomnia and personality provides a narrative synthesis of the literature to date. Here, we identified N = 76 studies meeting the inclusion/exclusion criteria. The outcomes reliably evidenced the experience of insomnia to be associated with personality traits that are typically considered to be negative or maladaptive in nature. More specifically, insomnia was related to neuroticism, introversion, perfectionistic doubts and concerns, elevated personal standards, negative affect, social inhibition and avoidance, hysteria, hypochondriasis, psychasthenia, impulsive behaviour, anger, hostility, and psychopathic tendencies, schizotypal and borderline traits, reduced conscientiousness and self-directedness, and negatively perceived perception of the self. Several studies examined the role that personality plays in predicting the treatment efficacy and adherence of CBTi. Moving forward, longitudinal research, methodological consistency, the mediating role of treatment outcomes and adherence, and clinical and population representative samples should be prioritised. Methodological strengths and limitations of the literature are discussed alongside the next steps that should be taken to advance our understanding of the literature.


Management of intestinal failure in middle-income countries, for children and adults.
Intestinal failure is a life-threatening medical condition that remains as a rare or orphan disease in most countries. The prevalence of intestinal failure and the therapeutic options available in middle-income countries (MIC) remain unclear. We aim to provide an overview on the current differences in management of intestinal failure patients in MIC from Latin America and Asia. In order to fulfil the challenge, and after facing the difficulties of going over a topic with scarce available data, from countries with an extreme variety of social and economic problems, which are closely related to the treatment of intestinal failure patients, we have used both the existing publications and personal surveys to draft this document. Our results have shown that there is still significant disparity among MIC over the last years, concepts such as the need for establishing multidisciplinary dedicated teams as well as the need to evolve first home parenteral nutrition (HPN), then rehabilitation, and finally transplantation, have become important signals of an adequate understanding of this evolving field. The manuscript presents, for the first time, an overview of the different developments and needs to manage intestinal failure patients in MIC from Latin America and Asia. Future discussions will emerge from this manuscript, aiming to pursue the development of registries, guidelines and health policies to continue improving the long-term care of intestinal failure patients in all MIC.


Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis.
The pathway of sterol biosynthesis is highly conserved in all eucaryotic cells. We demonstrated structural and functional conservation of the rate-limiting enzyme of the mammalian pathway, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase), between the yeast Saccharomyces cerevisiae and humans. The amino acid sequence of the two yeast HMG-CoA reductase isozymes was deduced from DNA sequence analysis of the HMG1 and HMG2 genes. Extensive sequence similarity existed between the region of the mammalian enzyme encoding the active site and the corresponding region of the two yeast isozymes. Moreover, each of the yeast isozymes, like the mammalian enzyme, contained seven potential membrane-spanning domains in the NH2-terminal region of the protein. Expression of cDNA clones encoding either hamster or human HMG-CoA reductase rescued the viability of hmg1 hmg2 yeast cells lacking this enzyme. Thus, mammalian HMG-CoA reductase can provide sufficient catalytic function to replace both yeast isozymes in vivo. The availability of yeast cells whose growth depends on human HMG-CoA reductase may provide a microbial screen to identify new drugs that can modulate cholesterol biosynthesis.


Circulating proteasomes are functional and have a subtype pattern distinct from 20S proteasomes in major blood cells.
20S proteasomes, the proteolytic core particles of the major intracellular protein degradative pathway, are potential disease markers because they are detectable in human plasma as circulating proteasomes and their concentrations are increased in patients suffering from various diseases. To investigate the origin of circulating proteasomes, we compared some of their features with those of proteasomes isolated from major blood cells. We isolated circulating proteasomes from the plasma of 2 patients with rheumatoid arthritis and 2 with systemic lupus erythematosus and from human plasma from healthy donors. We purified the proteasomes to apparent homogeneity and then used electron microscopy for imaging and chromatography for subtype spectrum analysis. We compared subtype results with those from 20S proteasomes purified from 4 major blood cell populations. We also tested proteasomes for enzymatic activity and immunosubunit content. Circulating proteasomes from plasma of healthy donors and from patients with autoimmune disease were found to have the same size and shape as erythrocyte proteasomes, be proteolytically active, and contain standard- and immunosubunits. Chromatography revealed 6 circulating proteasome subtype peaks in healthy donor plasma and 7 in patient donor plasma. Proteasomes from erythrocytes had 3 subtype peaks and those of monocytes, T-lymphocytes, and thrombocytes each had 5 different subtype peaks. Circulating proteasomes were intact and enzymatically active in plasma from healthy donors and from patients with autoimmune disease. Because the subtype patterns of circulating proteasomes clearly differ from those of proteasomes from blood cells, these cells cannot be regarded as a major source of circulating proteasomes.


Clinical results of sfericase (AI-794) in chronic parasinusitis.
Forty patients with chronic sinusitis were treated orally with sfericase tablets (each tablet = 10,000 units), a proteolytic enzyme preparation, at a daily dosage of six tablets for adults and three tablets for children in three divided doses after each main meal for 4 weeks. As regards subjective symptoms, very favorable results were obtained after 4-week treatment with sfericase as evidenced by an efficacy rate of 81.6% for postnasal rhinorrhea, 66.7% for rhinorrhea, and 43.6% for nasal obstruction. However, with respect to objective symptoms, the efficacy rate was 28.9% for redness and 30.8% for swelling of the nasal mucosa, with a somewhat lower rate than that obtained for subjective symptoms. According to the patient's and physician's global assessments, sfericase was effective in 65 and 57.5% of the cases. None of the cases showed undesirable reactions to sfericase.


Hypersensitivity reactions to heparins.
This article provides an update on hypersensitivity reactions to heparins and novel oral anticoagulants, with special emphasis on diagnostic methods and management of patients. Although heparins are drugs widely used, hypersensitivity reactions are uncommon. Cutaneous delayed hypersensitivity reactions after subcutaneous administration affects up to 7.5% of patients. Heparin-induced thrombocytopenia is another unusual but severe condition in which early recognition is crucial. Immediate hypersensitivity reactions to heparins have been also reported, but with the novel oral anticoagulants are much more uncommon, although reports of exanthemas have been notified.Skin tests and subcutaneous provocation test are useful tools in the diagnosis of hypersensitivity reactions, except in heparin-induced thrombocytopenia in which biopsy of lesional skin and in-vitro tests are the modalities of choice to confirm the diagnosis.Management of hypersensitivity reactions includes finding an alternative depending on the type of reaction. Fondaparinux and novel oral anticoagulants may be safe alternatives. Delayed skin lesions after subcutaneous heparin are the most common type of hypersensitivity reactions, followed by life-threatening heparin-induced thrombocytopenia. Immediate reactions are uncommon. Allergologic studies may be useful to find an alternative option in patients with skin lesions in which heparin-induced thrombocytopenia has been previously excluded, as well as in heparin immediate reactions.


Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain metastases from malignant melanoma: a phase II DeCOG/ADO study.
Temozolomide has shown some efficacy in metastatic melanoma and recently received extended approval to treat brain tumours. The purpose of this study was to test a dose-intensified regimen of temozolomide in melanoma patients with brain metastases in a prospective, open-label, multicentre phase II trial. Forty-five patients with asymptomatic brain metastases from melanoma were stratified into arm A (no prior chemotherapy; n = 21) and arm B (previous chemotherapy; n = 24). Patients received oral temozolomide either 150 mg/m(2)/day (arm A) or 125 mg/m(2)/day (arm B), days 1-7 and 15-21, every 28 days. The primary study end point was objective response, and secondary end points were overall survival and safety. Two patients (4.4%) achieved a partial response (PR) in brain metastases (one in each arm), one of them (2.2%) also showing a PR in extracerebral disease. An additional five patients (11.1%; two in arm A, three in arm B) showed disease stabilisation (SD) in brain and other sites. However, 82% revealed progressive disease (PD) already evident 8 weeks after therapy initiation. Median survival time from therapy onset was 3.5 months (range 0.7-8.3; arm B) and 4.3 months (range 1.6-11.8; arm A), P = 0.43. Dose modifications and prolongations of therapy cycles due to toxicity were required in 20% of patients. Grade 3/4 toxicity was observed in one patient only (2.2%). Oral administration of temozolomide given bi-weekly is well-tolerated in melanoma patients with cerebral involvement. However, the efficacy is limited, with lower than 5% objective responses observed in brain and extracerebral metastases.


Identification of recalcitrant hydrocarbons present in a drilling waste-polluted soil.
During spills of hydrocarbons in soil, it has been observed that aliphatic and the slightly aromatic hydrocarbons are first to be removed, however, branched aliphatic and aromatic compounds, polycyclic aromatic hydrocarbons (PAHs) and their similar heteroatoms with sulfur (PAS) remain strongly absorbed to soil particles. It is important to point out that studies of biodegradation of alkyl-substituted PAHs and PAS are scarce and most of them have been carried out using only available standard compounds. The aim of this investigation was to identify and to quantify the aliphatic, alkyl polycyclic aromatic, and sulfured recalcitrant fractions present in a contaminated soil with drilling wastes. A modified method of shaking-centrifugation extraction was implemented for the extraction of compounds from contaminated soil. The organic extract obtained was purified and fractionated using aluminum oxide. Gas Chromatograph with flame ionization detector (GC-FID) and Gas Chromatograph with mass spectrometer detector (GC-MS) identified the aliphatic, PAHs and PAS fractions. Hydrocarbon composition in the soil contaminated with 140,000 mg TPHs/Kg soil, consisted in 80% of branched aliphatic compounds of C10 to C22, 15% of alkyl PAHs, and 5% of PAS compounds. Lineal, lineal branched, and cyclic branched aliphatic hydrocarbons, as well as their alkyl naphthalene, anthracene and phenantrene, methyldibenzothiophene, dimethyldibenzothiophene, and dimethylnaphto[2,3-b]thiophene compounds were identified by CG-MS. The identification of compounds in soil P31, allowed us to speculate on the origin of the contamination and the natural attenuation that had occurred at this site.


Treating gout in kidney transplant recipients.
To review the etiology, treatment, and preventive strategies of hyperuricemia and gout in kidney transplant recipients. Primary literature was obtained via Medline (1966-June 2003). Studies evaluating treatment and prevention of hyperuricemia and gout in kidney transplantation were considered for evaluation. English-language studies were selected for inclusion. Approximately 14,000 kidney transplantations were performed in the United States in 2003, and of those transplant recipients, nearly 13% will experience a new onset of gout. The prevalence of hyperuricemia is even greater. There are several mechanisms by which hyperuricemia and gout develop in kidney transplant recipients. Medication-induced hyperuricemia and renal dysfunction are 2 of the more common mechanisms. Prophylactic and treatment options include allopurinol, colchicine, corticosteroids, and, if absolutely necessary, nonsteroidal antiinflammatory drugs. It is generally recommended to decide whether the risks of prophylactic therapy and treatment outweigh the benefits. Often, the risk of adverse events associated with agents to treat these ailments tends to outweigh the benefits; therefore, treatment is usually reserved for symptomatic episodes of acute gout. Practitioners must also decide if changes in immunosuppressive regimens may be of benefit on a patient-by-patient basis.


Influence of silica particles on mucociliary structure and MUC5B expression in airways of C57BL/6 mice.
Purpose: Impaired mucociliary clearance is an initial characteristic of recurrent cough, respiratory infection and chronic respiratory diseases. It has been demonstrated that prolonged inhalation of respirable silica particles results in a variety of pulmonary diseases, but whether the mucociliary system is involved in this process is unclear. This study aims to evaluate the effects of silica particles on mucociliary structure and MUC5B production in respiratory tract.Materials and Methods: C57BL/6 mice were administered with 2.5 mg silica particles through a single intratracheal instillation. The changes of mucociliary structure and MUC5B expression in trachea was evaluated by HE and AB-PAS staining, transmission electron microscopy and immunohistochemistry on days 1, 7, 28 and 84 post-exposure.Results: The mucociliary structure of airway epithelium was obviously impaired by silica particles, showing disordered, shortened or partially lost cilia on the surface, increased mucus in mucous layer and submucosal glands from day 7 to day 84. A variety of ultrastructural abnormalities were discovered in silica-exposed airway cilia, including absence of central pair microtubules, disorganized microtubules and clusters of axoneme on day 1 and 7. The numbers of ciliary axonemes and basal bodies in ciliated epithelial cells were significantly decreased, whereas the proportion of abnormal axonemes was gradually increased with exposure to silica particles (P < 0.05). In addition, silica particles significantly decreased MUC5B expression on the surface of airway epithelium on day 28 and 84, but obviously increased its production in submucosal glands from day 1 to day 84 (P < 0.01).Conclusions: Silica particles could lead to ultrastructural defects in airway cilia, mucus hypersecretion and altered MUC5B expression in trachea, indicating that impaired mucociliary structure and altered MUC5B production might participate in the development of silica-related respiratory diseases.


Validation of variants in SLC28A3 and UGT1A6 as genetic markers predictive of anthracycline-induced cardiotoxicity in children.
The use of anthracyclines as effective antineoplastic drugs is limited by the occurrence of cardiotoxicity. Multiple genetic variants predictive of anthracycline-induced cardiotoxicity (ACT) in children were recently identified. The current study was aimed to assess replication of these findings in an independent cohort of children. . Twenty-three variants were tested for association with ACT in an independent cohort of 218 patients. Predictive models including genetic and clinical risk factors were constructed in the original cohort and assessed in the current replication cohort. . We confirmed the association of rs17863783 in UGT1A6 and ACT in the replication cohort (P = 0.0062, odds ratio (OR) 7.98). Additional evidence for association of rs7853758 (P = 0.058, OR 0.46) and rs885004 (P = 0.058, OR 0.42) in SLC28A3 was found (combined P = 1.6 × 10(-5) and P = 3.0 × 10(-5), respectively). A previously constructed prediction model did not significantly improve risk prediction in the replication cohort over clinical factors alone. However, an improved prediction model constructed using replicated genetic variants as well as clinical factors discriminated significantly better between cases and controls than clinical factors alone in both original (AUC 0.77 vs. 0.68, P = 0.0031) and replication cohort (AUC 0.77 vs. 0.69, P = 0.060). . We validated genetic variants in two genes predictive of ACT in an independent cohort. A prediction model combining replicated genetic variants as well as clinical risk factors might be able to identify high- and low-risk patients who could benefit from alternative treatment options.


Role of oxygen vacancies in colossal polarization in SmFeO3-δ thin films.
The orthorhombic rare-earth manganates and ferrites multiferroics are promising candidates for the next generation multistate spintronic devices. However, their ferroelectric polarization is small, and transition temperature is far below room temperature (RT). The improvement of ferroelectricity remains challenging. Here, through the subtle strain and defect engineering, an RT colossal polarization of 4.14 μC/cm2 is achieved in SmFeO3-δ films, which is two orders of magnitude larger than its bulk and is also the largest one among the orthorhombic rare-earth manganite and ferrite family. Meanwhile, its RT magnetism is uniformly distributed in the film. Combining the integrated differential phase-contrast imaging and density functional theory calculations, we reveal the origin of this superior ferroelectricity in which the purposely introduced oxygen vacancies in the Fe-O layer distorts the FeO6 octahedral cage and drives the Fe ion away from its high-symmetry position. The present approach can be applied to improve ferroelectric properties for multiferroics.


An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP.
Activity-regulated gene expression is believed to play a key role in the development and refinement of neuronal circuitry. Nevertheless, the transcriptional networks that regulate synapse growth and plasticity remain largely uncharacterized. Here, we show that microRNA 132 (miR132) is an activity-dependent rapid response gene regulated by the cAMP response element-binding (CREB) protein pathway. Introduction of miR132 into hippocampal neurons enhanced dendrite morphogenesis whereas inhibition of miR132 by 2'O-methyl RNA antagonists blocked these effects. Furthermore, neuronal activity inhibited translation of p250GAP, a miR132 target, and siRNA-mediated knockdown of p250GAP mimicked miR132-induced dendrite growth. Experiments using dominant-interfering mutants suggested that Rac signaling is downstream of miR132 and p250GAP. We propose that the miR132-p250GAP pathway plays a key role in activity-dependent structural and functional plasticity.