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Three Ni(ii)-POCOP pincer complexes [NiCl{C 6 H 2 -4-OH-2,6-(OPPh 2 ) 2 }], 1; [NiCl{C 6 H 2 -4-OH-2,6-(OPtBu 2 ) 2 }], 2 and [NiCl{C 6 H 2 -4-OH-2,6-(OPiPr 2 ) 2 }], 3 were studied as bifunctional molecular sensors for inorganic anions and acetate. In CH 3 CN, fluoride generates a bathochromic shift with a colorimetric change for 1-3 with a simultaneous fluorescence turn on, this optical effect is based on deprotonation of the para-hydroxy group of the POCOP ligand. On the other hand, in a neutral aqueous solution of 80 vol% CH 3 CN, additions of cyanide produce a distinct change of color by forming very stable complexes with the nickel-based receptors 1-3 with log K a in the range of 4.38-5.03 M -1 and pronounced selectivity over other common anions such as iodide, phosphate, and acetate. Additionally, bromide shows a modest spectral change and affinity, but lower than those observed for cyanide. On the basis of 1 H NMR experiments, UV-vis titrations, ESI-MS experiments, and the crystal structure of the neutral bromo complex of 1, it is proposed that the colorimetric change involves an exchange of chloride by CN - on the Ni(ii) atom. The Ni(ii)-based sensor 1 allows the fluorescent selective detection of fluoride with a limit of 5.66 μmol L -1 and colorimetric sensing of cyanide in aqueous medium in the micromolar concentration range.

Kaldar Cave is a key archaeological site that provides evidence of the Middle to Upper Palaeolithic transition in Iran. Excavations at the site in 2014-2015 led to the discovery of cultural remains generally associated with anatomically modern humans (AMHs) and evidence of a probable Neanderthal-made industry in the basal layers. Attempts have been made to establish a chronology for the site. These include four thermoluminescence (TL) dates for Layer 4, ranging from 23,100 ± 3300 to 29,400 ± 2300 BP, and three AMS radiocarbon dates from charcoal samples belonging to the lower part of the same layer, yielding ages of 38,650-36,750 cal BP, 44,200-42,350 cal BP, and 54,400-46,050 cal BP (all at the 95.4% confidence level). Kaldar Cave is the first well-stratified Late Palaeolithic locality to be excavated in the Zagros which is one of the earliest sites with cultural materials attributed to early AMHs in western Asia. It also offers an opportunity to study the technological differences between the Mousterian and the first Upper Palaeolithic lithic technologies as well as the human behaviour in the region. In this study, we present a detailed description of the newly excavated stratigraphy, quantified results from the lithic assemblages, preliminary faunal remains analyses, geochronologic data, taphonomic aspects, and an interpretation of the regional paleoenvironment.

Background and Aims The Arabidopsis thaliana root is a key experimental system in developmental biology. Despite its importance, we are still lacking an objective and broadly applicable approach for identification of number and position of developmental domains or zones along the longitudinal axis of the root apex or boundaries between them, which is essential for understanding the mechanisms underlying cell proliferation, elongation and differentiation dynamics during root development. Methods We used a statistics approach, the multiple structural change algorithm (MSC), for estimating the number and position of developmental transitions in the growing portion of the root apex. Once the positions of the transitions between domains and zones were determined, linear models were used to estimate the critical size of dividing cells (LcritD) and other parameters. Key Results The MSC approach enabled identification of three discrete regions in the growing parts of the root that correspond to the proliferation domain (PD), the transition domain (TD) and the elongation zone (EZ). Simultaneous application of the MSC approach and G2-to-M transition (CycB1;1DB:GFP) and endoreduplication (pCCS52A1:GUS) molecular markers confirmed the presence and position of the TD. We also found that the MADS-box gene XAANTAL1 (XAL1) is required for the wild-type (wt) PD increase in length during the first 2 weeks of growth. Contrary to wt, in the xal1 loss-of-function mutant the increase and acceleration of root growth were not detected. We also found alterations in LcritD in xal1 compared with wt, which was associated with longer cell cycle duration in the mutant. Conclusions The MSC approach is a useful, objective and versatile tool for identification of the PD, TD and EZ and boundaries between them in the root apices and can be used for the phenotyping of different genetic backgrounds, experimental treatments or developmental changes within a genotype. The tool is publicly available at www.ibiologia.com.mx/MSC_analysis., (© The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Anthropogenic disturbances affecting tropical forest reserves have been documented, but their ecological long-term cumulative effects are poorly understood. Habitat fragmentation and defaunation are two major anthropogenic threats to the integrity of tropical reserves. Based on a long-term (four decades) study, we document how these disturbances synergistically disrupt ecological processes and imperil biodiversity conservation and ecosystem functioning at Los Tuxtlas, the northernmost tropical rainforest reserve in the Americas. Deforestation around this reserve has reduced the reserve to a medium-sized fragment (640 ha), leading to an increased frequency of canopy-gap formation. In addition, hunting and habitat loss have caused the decline or local extinction of medium and large herbivores. Combining empirical, experimental, and modeling approaches, we support the hypothesis that such disturbances produced a demographic explosion of the long-lived (≈120 y old, maximum height of 7 m) understory palm Astrocaryum mexicanum, whose population has increased from 1,243-4,058 adult individuals per hectare in only 39 y (annual growth rate of ca 3%). Faster gap formation increased understory light availability, enhancing seed production and the growth of immature palms, whereas release from mammalian herbivory and trampling increased survival of seedlings and juveniles. In turn, the palm's demographic explosion was followed by a reduction of tree species diversity, changing forest composition, altering the relative contribution of trees to forest biomass, and disrupting litterfall dynamics. We highlight how indirect anthropogenic disturbances (e.g., palm proliferation) on otherwise protected areas threaten tropical conservation, a phenomenon that is currently eroding the planet's richest repositories of biodiversity.

In the title compound, C23H18N3O3 (+)·CF3SO3 (-), the asymmetric unit contains two crystallographically independent organic cations with similar conformations. Each cation shows a moderate distortion between the planes of the amide groups and the quinolinium rings with dihedral angles of 14.90 (2) and 31.66 (2)°. The quinolinium and phenyl rings are slightly twisted with respect to each other at dihedral angles of 6.99 (4) and 8.54 (4)°. The tri-fluoro-methane-sulfonate anions are linked to the organic cations via N-H⋯O hydrogen-bonding inter-actions involving the NH amide groups. In the crystal, the organic cations are linked by weak C-H⋯O(nitro group) inter-actions into supramol-ecular chains propagating along the b-axis direction.

Introduction: Physiological parameters used to measure exercise intensity are oxygen uptake and heart rate. However, perceived exertion (PE) is a scale that has also been frequently applied. The objective of this study is to establish the criterion-related validity of PE scales in children during an incremental exercise test., Methods: Seven electronic databases were used. Studies aimed at assessing criterion-related validity of PE scales in healthy children during an incremental exercise test were included. Correlation coefficients were transformed into z-values and assessed in a meta-analysis by means of a fixed effects model if I2 was below 50% or a random effects model, if it was above 50%., Results: wenty-five articles that studied 1418 children (boys: 49.2%) met the inclusion criteria. Children's average age was 10.5 years old. Exercise modalities included bike, running and stepping exercises. The weighted correlation coefficient was 0.835 (95% confidence interval: 0.762-0.887) and 0.874 (95% confidence interval: 0.794-0.924) for heart rate and oxygen uptake as reference criteria. The production paradigm and scales that had not been adapted to children showed the lowest measurement performance (p < 0.05)., Conclusion: Measuring PE could be valid in healthy children during an incremental exercise test. Child-specific rating scales showed a better performance than those that had not been adapted to this population. Further studies with better methodological quality should be conducted in order to confirm these results., (Sociedad Argentina de Pediatría.)

Objectives: To determine the probability of finding significant coronary lesions, the time to diagnosis, and the safety of a new diagnostic approach based on high-sensitivity cardiac troponin T (hsTnT) testing followed by coronary computed tomography angiography (CCTA) in patients with chest pain of possible coronary origin. The method was compared with our hospital emergency department's standard practice., Material and Methods: Unblinded randomized controlled trial in a tertiary level university hospital between February 2011 and April 2013. We included emergency patients with chest pain and nondiagnostic electrocardiographic findings. Patients were assigned randomly to the new approach (hsTnT assay, followed by CCTA if the assay findings were negative) or the conventional approach (fourth generation TnT assay and, if negative, followed by an exercise stress test). Invasive coronary angiography was ordered in all patients if the results of either troponin assay, the CCTA, or the stress test were positive. We recorded the results of angiography, time until diagnosis, and all-cause mortality, new myocardial infarction, new unstable angina, or need for revascularization within the next 3 months., Results: Of 102 patients randomized, 7 were excluded; 50 of the remaining 95 patients were assigned to the new strategy, and 45 to the conventional approach. Coronary angiography demonstrated significant lesions in 92.9% of the patients treated with the new strategy and 66.7% of those diagnosed conventionally. A higher percentage of patients were diagnosed within 6 hours with the new approach (20.0% vs 4.4% of conventional-approach patients, P = .023). During the 3 months following diagnosis, 1 death occurred in the intervention group and none in the conventional-approach group., Conclusion: The new strategy could accelerate diagnosis and increase the probability of finding significant coronary lesions, but we found no significant differences in adverse events in the 3 months following diagnosis. These findings should be confirmed in studies with larger numbers of patients.

Rating scales of perceived exertion (PE) have been used to measure PE during exercise in the adult population with successful results. However, in children, it is necessary to develop adapted instruments due to their cognitive immaturity. The number of Spanish-language validated instruments for the pediatric population is scarce. Our objective was to develop a new PE rating scale. Research design was divided into three stages: development, content validity, and criterion validity. For development, a panel of five expert members was summoned, who provided indications for the new instrument. A systematic review of the literature to identify other validated instruments was performed. This process resulted in the development of the new EPInfant scale to measure PE, which integrates the expert panel’s indications and the result of the literature systematic review. The evaluation of its content showed a high level of agreement regarding the quality of its design; the content validity index was 1. During the field assessment, a high concurrent criterion validity was observed in healthy adolescents due to the strong correlation shown between PE and heart rate in both boys and girls. The methodology used to develop the EPInfant scale aimed at reducing potential biases that may hinder its psychometric properties. Preliminary results suggest that this may be a validated instrument that could be implemented in healthy adolescents.

Introduction: Nuclear accumulation of a mutant form of the nuclear protein Lamin-A, called Progerin (PG) or Lamin AΔ50, occurs in Hutchinson-Gilford Progeria Syndrome (HGPS) or Progeria, an accelerated aging disease. One of the main symptoms of this genetic disorder is a loss of sub-cutaneous fat due to a dramatic lipodystrophy., Methods: We stably induced the expression of human PG and GFP -Green Fluorescent Protein- as control in 3T3L1 cells using a lentiviral system to study the effect of PG expression in the differentiation capacity of this cell line, one of the most used adipogenic models. Quantitative proteomics (iTRAQ) was done to study the effect of the PG accumulation. Several of the modulated proteins were validated by immunoblotting and real-time PCR. Mitochondrial function was analyzed by measurement of a) the mitochondrial basal activity, b) the superoxide anion production and c) the individual efficiency of the different complex of the respiratory chain., Results: We found that over-expression PG by lentiviral gene delivery leads to a decrease in the proliferation rate and to defects in adipogenic capacity when compared to the control. Quantitative proteomics analysis showed 181 proteins significantly (p<0.05) modulated in PG-expressing preadipocytes. Mitochondrial function is impaired in PG-expressing cells. Specifically, we have detected an increase in the activity of the complex I and an overproduction of Superoxide anion. Incubation with Reactive Oxygen Species (ROS) scavenger agents drives to a decrease in autophagic proteolysis as revealed by LC3-II/LC3-I ratio., Conclusion: PG expression in 3T3L1 cells promotes changes in several Biological Processes, including structure of cytoskeleton, lipid metabolism, calcium regulation, translation, protein folding and energy generation by the mitochondria. Our data strengthen the contribution of ROS accumulation to the premature aging phenotype and establish a link between mitochondrial dysfunction and loss of proteostasis in HGPS.

Malaria is one of the most devastating parasitic diseases worldwide. Plasmodium drug resistance remains a major challenge to malaria control and has led to the re-emergence of the disease. Chloroquine (CQ) and artemisinin (ART) are thought to exert their anti-malarial activity inducing cytotoxicity in the parasite by blocking heme degradation (for CQ) and increasing oxidative stress. Besides the contribution of the CQ resistance transporter (PfCRT) and the multidrug resistant gene (pfmdr), CQ resistance has also been associated with increased parasite glutathione (GSH) levels. ART resistance was recently shown to be associated with mutations in the K13-propeller protein. To analyze the role of GSH levels in CQ and ART resistance, we generated transgenic Plasmodium berghei parasites either deficient in or overexpressing the gamma-glutamylcysteine synthetase gene (pbggcs) encoding the rate-limiting enzyme in GSH biosynthesis. These lines produce either lower (pbggcs-ko) or higher (pbggcs-oe) levels of GSH than wild type parasites. In addition, GSH levels were determined in P. berghei parasites resistant to CQ and mefloquine (MQ). Increased GSH levels were detected in both, CQ and MQ resistant parasites, when compared to the parental sensitive clone. Sensitivity to CQ and ART remained unaltered in both pgggcs-ko and pbggcs-oe parasites when tested in a 4 days drug suppressive assay. However, recrudescence assays after the parasites have been exposed to a sub-lethal dose of ART showed that parasites with low levels of GSH are more sensitive to ART treatment. These results suggest that GSH levels influence Plasmodium berghei response to ART treatment.

Background: Type 2 diabetes mellitus is a chronic disease whose health outcomes are related to patients and healthcare professionals' decision-making. The Diabetes Intervention study in the Canary Islands (INDICA study) aims to evaluate the effectiveness and cost-effectiveness of educational interventions supported by new technology decision tools for type 2 diabetes patients and primary care professionals in the Canary Islands., Methods/design: The INDICA study is an open, community-based, multicenter, clinical controlled trial with random allocation by clusters to one of three interventions or to usual care. The setting is primary care where physicians and nurses are invited to participate. Patients with diabetes diagnosis, 18-65 years of age, and regular users of mobile phone were randomly selected. Patients with severe comorbidities were excluded. The clusters are primary healthcare practices with enough professionals and available places to provide the intervention. The calculated sample size was 2,300 patients. Patients in group 1 are receiving an educational group program of eight sessions every 3 months led by trained nurses and monitored by means of logs and a web-based platform and tailored semi-automated SMS for continuous support. Primary care professionals in group 2 are receiving a short educational program to update their diabetes knowledge, which includes a decision support tool embedded into the electronic clinical record and a monthly feedback report of patients' results. Group 3 is receiving a combination of the interventions for patients and professionals. The primary endpoint is the change in HbA1c in 2 years. Secondary endpoints are cardiovascular risk factors, macrovascular and microvascular diabetes complications, quality of life, psychological outcomes, diabetes knowledge, and healthcare utilization. Data is being collected from interviews, questionnaires, clinical examinations, and records. Generalized linear mixed models with repeated time measurements will be used to analyze changes in outcomes. The cost-effectiveness analysis, from the healthcare services perspective, involves direct medical costs per quality-adjusted life year gained and two periods, a 'within-trial' period and a lifetime Markov model. Deterministic and probabilistic sensitivity analyses are planned., Discussion: This ongoing trial aims to set up the implementation of evidence-based programs in the clinical setting for chronic patients., Trial Registration: Clinical Trial.gov NCT01657227.

Objectives: The aim of the present study was to perform a comparative cost-effectiveness analysis of the different strategies used to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis., Methods: We performed a cost-effectiveness decision analysis of 4 prophylactic strategies (nonsteroidal anti-inflammatory drugs or NSAIDs, pancreatic stent, stent plus rectal indomethacin, and no prophylaxis) in a simulated cohort of 300 patients during 1 year. Treatment effectiveness was defined as the number of patients who did not develop post-ERCP pancreatitis., Results: The baseline costs of each strategy were as follows: rectal NSAID $359,098, pancreatic stent $426,504, stent plus rectal indomethacin $479,153, and no prophylaxis $491,275. The mean number of cases developing post-ERCP pancreatitis was 16, 21, 23, and 37 for the strategies rectal NSAID, pancreatic stent, stent plus rectal indomethacin, and no prophylaxis, respectively. Taking rectal NSAID prophylaxis as the reference strategy, the odds ratio of an episode of post-ERCP acute pancreatitis after pancreatic stent placement was 1.33 (95% confidence interval [CI], 0.68-2.61); after stent plus indomethacin, it was 1.40 (95% CI, 0.72-2.73), and after no prophylaxis, it was 2.49 (95% CI, 1.35-4.59)., Conclusions: Rectal NSAID administration proved to be the most cost-effective prophylactic strategy used to prevent post-ERCP pancreatitis. The strategy of no prophylaxis for this complication should be avoided.

Chronic renal allograft injury is reflected by interstitial fibrosis and tubular atrophy (IF/TA) and by the accumulation of extracellular matrix (ECM). Metalloproteinases (MMPs) are renal physiologic regulators of ECM degradation. Changes in MMPs expression or activity may disturb ECM turnover leading to glomerular scarring and worsening renal function. Our goal was to investigate intragraft MMP2 and MMP9 activities and their correlation with renal dysfunction. Plasma MMP2 and MMP9 activities were analyzed as noninvasive markers of renal allograft deterioration. Transplanted patients were biopsied and histopathologically characterized as IF/TA+ or IF/TA-. Renal function was evaluated by serum creatinine, glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease equation and urinary protein/creatinine ratio. Kidney and plasma MMP2 and MMP9 activities were analyzed by zymography. A significant renal dysfunction was observed in IF/TA+ patients. Intragraft proMMP9 showed a significant higher activity in IF/TA+ than in IF/TA- samples and was inversely correlated with the GFR. Intragraft proMMP2 activity tended to increase in IF/TA+ samples, although no statistic significance was reached. Circulating proMMP2 and proMMP9 activities did not show significant differences between groups. Our data provide evidence that correlates intragraft proMMP9 activity with the fibrotic changes and renal dysfunction observed in IF/TA., (© 2014 Steunstichting ESOT.)

Physiological vascular function regulation is essential for cardiovascular health and depends on adequate control of molecular mechanisms triggered by endothelial cells in response to mechanical and chemical stimuli induced by blood flow. Endothelial dysfunction is one of the main risk factors of cardiovascular pathology, where the imbalance between the synthesis of vasodilator and vasoconstrictor molecules is common in the development of vascular disorders in systemic and placental circulation. In the placenta, an organ without autonomic innervations, the local control of vascular tone is critical for maintenance of fetal growth and mechanisms that underlie shear stress response induced by blood flow are essential during pregnancy. In this field, shear stress induced by moderate exercise is one of the most important mechanisms to improve vascular function through nitric oxide synthesis and stimulation of mechanical response of endothelial cells triggered by ion channels, caveolae, endothelial NO synthase, and vascular endothelial growth factor, among others. The demand for oxygen and nutrients by tissues and organs, especially in placentation and pregnancy, determines blood flow parameters, and physiological adaptations of vascular beds for covering metabolic requirements. In this regard, moderate exercise versus sedentarism shows potential benefits for improving vascular function associated with the enhancement of molecular mechanisms induced by shear stress. In this review, we collect evidence about molecular bases of physiological response to shear stress in order to highlight the relevance of moderate exercise-training for vascular health in adult and fetal life.

Objectives: Low triiodothyronine levels, as part of the nonthyroidal illness syndrome, are common in dialysis patients and have repeatedly been shown to be associated with increased (cardiovascular) mortality rates. We hypothesized that increased vascular calcification may mediate this relationship., Methods: A total of 84 patients from the Stockholm region receiving maintenance peritoneal dialysis were included in the study. Serum concentrations of free triiodothyronine (fT3), thyroxine and thyroid-stimulating hormone were measured. Coronary artery calcium (CAC) scores were assessed by cardiac computed tomography scans. Surrogates of arterial stiffness included aortic diastolic and systolic blood pressures, pulse pressure, augmentation pressure and Buckberg's subendocardial viability ratio measured by pulse waveform analyses. Patients were subsequently followed, and events of death and censoring were recorded. Thyroid hormone concentrations were associated with CAC scores, measures of arterial stiffness and all-cause mortality. The associations between CAC scores and arterial stiffness surrogates and mortality were also determined to evaluate a possible causal pathway., Results: Both CAC scores and arterial stiffness surrogates were substantially higher in individuals with low fT3 levels. These associations persisted in multivariate logistic and linear regression analyses. During a median (interquartile range) follow-up of 32 (22-42) months, 24 patients died. Both fT3 levels below the median value [HR crude 4.1, 95% confidence interval (CI) 1.4-12.6] and CAC scores above the median value (HR crude 5.8, 95% CI 1.7-20.1) were strongly associated with mortality., Conclusions: In patients undergoing peritoneal dialysis, fT3 levels were strongly associated with arterial stiffness, coronary artery calcification and mortality. We speculate that the association between nonthyroidal illness and mortality may be partly mediated by acceleration of vascular calcification., (© 2013 The Association for the Publication of the Journal of Internal Medicine.)

Little information exists about the association of anti-SSA/Ro60 and anti-Ro52/TRIM21 with systemic lupus erytematosus (SLE) features. In this work, we analysed the associations of both anti-Ro reactivities with clinical and immunological manifestations in 141 SLE patients. Photosensitivity and xerophtalmia/xerostomia were found to be positively associated with both anti-SSA/Ro60 (P = 0.024 and P = 0.019, resp.) and anti-Ro52/TRIM21 (P = 0.026 and P = 0.022, resp.). In contrast, a negative association was detected regarding anti-phospholipid antibodies, anti-SSA/Ro60 having a stronger effect (P = 0.014) than anti-Ro52/TRIM21. Anti-SSA/Ro60 showed a specific positive association with hypocomplementemia (P = 0.041), mainly with low C4 levels (P = 0.008), whereas anti-Ro52/TRIM21 was found to be positively associated with Raynaud's phenomenon (P = 0.026) and cytopenia (P = 0.048) and negatively associated with anti-dsDNA (P = 0.013). Lymphocytes are involved in the relationship between anti-Ro52/TRIM21 and cytopenia since positive patients showed lower cell levels than negative patients (P = 0.036). In conclusion, anti-SSA/Ro60 and anti-Ro52/TRIM21 showed both common and specific associations in SLE. These data thus increase evidence of the different associations of the two anti-Ro specificities even in a particular disease.

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is intimately related to insulin resistance and ranges from a benign course to liver fibrosis and cirrhosis. NAFLD management mainly involves dietary modification and weight loss. Although no fully successful pharmacological intervention is available, alternative therapies to treat NAFLD have shown promising results. Experimental studies have shown that D-002, a mixture of beeswax alcohols with antioxidant effects, is hepatoprotective. The aim of this study was to investigate the efficacy and safety of D-002 in patients with NALFD., Methods: Fifty patients with NAFLD were randomized to receive a placebo or D-002 (100 mg/day) for 24 weeks. The primary endpoint was a significant ultrasonography-detected reduction of liver fat infiltration versus a placebo. Secondary endpoints were decreases in the homeostatic model assessment (HOMA) index, insulin levels, serum liver enzymes, increases in plasma total antioxidant status (TAS) and improved clinical symptoms versus the placebo recipients., Results: At randomization, all indicators were comparable in both groups. At study completion, seven (28.0%) D-002-patients, but none of the placebo recipients, exhibited a normal liver echo pattern on ultrasonography (p < 0.01). Also, D-002 significantly reduced (p < 0.01 vs. baseline and placebo) the HOMA index and insulin levels and increased the TAS, but did not affect other parameters. The proportion of D-002-patients (12/25, 48.0%) showing symptom improvement was higher (p < 0.001) than that of the placebo group (1/25, 4.0%). The treatment was safe and well tolerated. Three patients in each group withdrew from the study., Conclusions: D-002 (100 mg/day) improved ultrasonographic findings, indicators of insulin resistance, plasma TAS and clinical evolution on NAFLD patients. Further studies, however, are needed to confirm these results.

We devise a way to calculate the dimensions of symmetry sectors appearing in the particle entanglement spectrum (PES) and real space entanglement spectrum (RSES) of multiparticle systems from their real space wave functions. We first note that these ranks in the entanglement spectra equal the dimensions of spaces of wave functions with a number of particles fixed. This also yields equality of the multiplicities in the PES and the RSES. Our technique allows numerical calculations for much larger systems than were previously feasible. For somewhat smaller systems, we can find approximate entanglement energies as well as multiplicities. We illustrate the method with results on the RSES and PES multiplicities for integer quantum Hall states, Laughlin and Jain composite fermion states, and for the Moore-Read state at filling ν = 5/2 for system sizes up to 70 particles.

Umbilical cord stroma mesenchymal stem cells were differentiated toward chondrocyte-like cells using a new in vitro model that consists of the random formation of spheroids in a medium supplemented with fetal bovine serum on a nonadherent surface. The medium was changed after 2 days to one specific for the induction of chondrocyte differentiation. We assessed this model using reverse transcriptase-polymerase chain reaction, flow cytometry, immunohistochemistry, and secretome analyses. The purpose of this study was to determine which proteins were differentially expressed during chondrogenesis. Differential gel electrophoresis analysis was performed, followed by matrix-assisted laser desorption/ionization mass spectrometry protein identification. A total of 97 spots were modulated during the chondrogenesis process, 54 of these spots were identified as 39 different proteins and 15 were isoforms. Of the 39 different proteins identified 15 were down-regulated, 21 were up-regulated, and 3 were up- and down-regulated during the chondrogenesis process. Using Pathway Studio 7.0 software, our results showed that the major cell functions modulated during chondrogenesis were cellular differentiation, proliferation, and migration. Five proteins involved in cartilage extracellular matrix metabolism found during the differential gel electrophoresis study were confirmed using Western blot. The results indicate that our in vitro chondrogenesis model is an efficient and rapid technique for obtaining cells similar to chondrocytes that express proteins characteristic of the cartilage extracellular matrix. These chondrocyte-like cells could prove useful for future cell therapy treatment of cartilage pathologies.

The biological removal of hydrogen sulfide at low concentration (<120 ppmv) was studied in a laboratory-scale biofilter packed with sugarcane bagasse and inoculated with a sulfur-oxidizing bacterial consortium isolated from activated sludge from a wastewater treatment plant (WWTP). Inlet loads from 1.31 to 20.2 g Sm(-3) h(-1) were supplied to the biofilter, and empty bed residence times (EBRTs) of 30, 20 and 10 s were tested. In all cases, the removal efficiency was greater than 99%. Two methods for the pH control were tested: increasing the phosphate buffer capacity of the mineral medium (method I), and a new method, which involves the addition of solid CaCO(3) to the bagasse at the upper inlet of the biofilter (method II). For method I, pH increased gradually along the bed (from the bottom to the top), from a constant value of 3.0 to 7.0. For method II, pH was constant (2.4 ± 0.8) along the bed, and then a steep increase of pH was observed at the top to 7.1. We suggest the use of CaCO(3) instead of phosphate buffer because the former is less expensive, it is a simple method and the results obtained with the two methods are similar.

Objective: Penile metastases are late manifestations of a primary tumor, and they are a sign of poor prognosis. We report a case of a rare presentation: penile metastases from prostate cancer., Methods: 77 year-old male presented hematuria and acute urinary retention; on physical examination multiple hard lesions were detected. The patient underwent a Doppler ultrasound, subsequent penile and prostate biopsy, and staging study. Currently he is being treated with complete androgen blockade., Results: A histological study of the penile biopsy showed penile metastasis from prostate adenocarcinoma. The histological study of prostate biopsy confirmed Gleason 8 (4+4) adenocarcinoma., Conclusions: Despite of the different therapeutic alternatives for treatment of symptomatic penile metastases, it would be with palliative target; due to the median survival of these patients is less than a year.

Background: Anticentromere autoantibodies have been reported to be associated with scleroderma and serve as a marker in different rheumatic diseases in humans. Major centromere autoantigens described so far include constitutive kinetochore proteins such as CENPA, CENPB, CENPC and CENPH and facultative proteins such as CENPE, CENPF and INCENP. We examined the inner kinetochore component CENPI as a new putative centromere autoantigen in scleroderma patients., Methods: To test for the presence of CENPI centromere autoantibodies, 72 sera from patients with systemic lupus erythematosus and systemic sclerosis were assayed by immunofluorescence and further tested by immunoblots with an Nt-CENPI recombinant protein., Results: 8 out of 31 (25.8%) patients diagnosed of scleroderma or Undifferentiated Connective Tissue Disease (UCTD) produced anti-CENPI autoantibodies. Epitopes were demonstrated to be located mainly but not exclusively in the N-terminal domain of the human CENPI protein. Five of the 8 (62.5%) CENPI positive sera also had other autoantibodies related to primary biliary cirrhosis. Further, two patients (25%) with anti-CENPI autoantibodies had concurrent diagnosis of primary biliary cirrhosis., Conclusions: This study demonstrates that CENPI, a centromere protein that localizes to the inner kinetochore structure, is a human autoantigen. The significance of anti-CENPI autoantibodies could be relevant in scleroderma patients as a marker for concurrent autoimmune liver disease., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Vascular calcification plays a major role in cardiovascular disease, which is one of the main causes of mortality in chronic kidney disease patients. Vascular calcification is determined by prevalent traditional and uraemia-related (non-traditional) risk factors. It occurs mainly in the arteries, which are classified into three types according to their size and structural characteristics. In addition, vascular calcification has been associated with bone loss and fractures in chronic kidney disease patients and the general population, stressing the fact that both disorders can share pathogenetic pathways. The strategies to control vascular calcification involve several measures, chief among them the control of hyperphosphataemia. Furthermore, it has been recently described that strategies that reduce bone resorption and increase bone mineralization may decrease the risk of vascular calcifications; however, this approach still remains controversial. The mechanisms involved in vascular calcification are complex and not yet fully understood. Phosphorus plays a major role, while other factors related to bone formation have been recently identified., (Copyright © 2011 S. Karger AG, Basel.)

Objectives: To study the validity of Matrix Metalloproteinase 9 as a complementary marker to PSA for the diagnosis and prognosis of Prostate Cancer., Methods: Prospective study structured as a hospital-based cohort of 100 consecutive patients undergoing prostate biopsy. Serum determination of MMP-9 was carried out by means of inmunoassay. Statistical analysis was performed using the Stata/SE 8.2 software., Results: 32 patients were diagnosed with prostate cancer and 52% had a Gleason score equal to or greater than 7. The values of serum MMP-9 varied between 225.7 and 1932.3 ng/ml, without significant differences among patients with benign, malignant and uncertain histology (p=0.429). The differences approached statistical significance in the subgroup of patients with PSA at 4-10 ng/ml (p=0.058), and significant differences were observed in the subgroup with free PSA to total PSA coefficient of less than 15% (p=0.037). No relationship between the Gleason score and the level of MMP-9 was shown (p=0.739). The levels of PSA and MMP-9 were shown to be independent (Pearson coefficient of correlation -0.1)., Conclusions: It was not possible to show the efficacy of MMP-9 in predicting the result of the biopsy. In the group of patients with slightly increased levels of PSA (between 4 and 10 ng/ml) all the descriptive variables were higher in the group with malignant histology, though they did not reach statistical significance, they did reach significance when the coefficient of free PSA over total PSA was less than 15%, but this finding is not relevant clinically, as these patients already have a clear indication for biopsy. Neither was the relationship with the prognosis shown as there are no differences of MMP-9 expression at varying Gleason scores.

Unlabelled: Polymorphisms Q279R, P574R and -1562 C/T of matrix metalloproteinase-9 (MMP-9) gene have been linked with the risk of cancer and with tumoral aggressiveness in various types of cancer. So far there are no studies in the literature analysing the link between polymorphisms Q279R, P574R and -1562 C/T of MMP-9 and prostate cancer., Objectives: To establish the presence of the MMP-9's gene polymorphisms (Q279R, P574R and -1562 C/T)in relation to results of prostate biopsy, PSA values and Gleason score., Methods: Hospital cohort of 100 patients with suspected prostate cancer, subjected to prostate biopsy, in whom the MMP-9 polymorphisms (Q279R, P574R and -1562 C/T) were analysed using the PCR-RLFP technique., Results: No statistically significant differences were found in the presence of the Q279R, P574R and -1562 C/T polymorphisms in terms of prostate biopsy results (p = 0.264, p = 0.406, p = 0.860, respectively), or Gleason score (p = 0.373, p = 0.367, p = 0.476). Comparing the genotypes of the Q279R, P574R and -1562 C/T polymorphisms resulting from prostate biopsy, using subgroups according to PSA values, no statistically significant differences were found either (p = 0.332 y p = 0.393, respectively ). However, statistically significant differences were found when comparing the genotypes of the -1562 C/T polymorphism of the MMP-9 in patients showing positive biopsy for malignant tumour in comparison to a negative biopsy for a malignant tumour in the subgroup of patients with PSA 10 ng/ml (p=0.049). The joint analysis of the three MMP-9 polymorphisms, using logistical regression study did not reveal any statistically significant differences as far as the risk of developing prostate cancer is concerned based on the presence of the Q279R, P574R and -1562 C/T polymorphisms., Conclusion: The Q279R, P574R and -1562 C/T polymorphisms are not linked with the aggressiveness in prostate cancer, neither they are linked to the risk of suffering prostate cancer.

Ensenada Harbor is one of the most important ports of Mexico. Anthropogenic activities have affected the area over several decades, leading to the accumulation of contaminants in its sediments, which eventually are re-suspended into the water column. In spite of water treatment of the tributaries that discharge into the Ensenada Harbor, the water circulation patterns of the harbor, which consist of closed eddies in the northern and southeastern sector, favor the accumulation of those contaminants and hinder exchange with adjacent seawater. Samples collected in October of 2005 registered 63 microM total inorganic nitrogen and 280 mg/L of COD, confirming that this is a highly contaminated environment when compared with other water bodies of North America. Such concentrations can be lowered up to 80% by using a wave energy pumping system that demonstrates the possibility to gradually dilute these contaminants and rehabilitate the Ensenada Harbor., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The present study was conducted to investigate the effect of beta-glucan (derived from Saccharomyces cerevisiae) on the immune response and its protection against an infection of the bacterial pathogen Aeromonas hydrophila in zebrafish (Danio rerio). Zebrafish received beta-glucan by intraperitoneal injection at three different concentrations (5, 2 and 0.5 mgml(-1)) at 6, 4 and 2 days prior the challenge. On challenge day the control and beta-glucan pretreated zebrafish were intraperitoneally injected with A. hydrophila and mortality was recorded for 4 days. Intraperitoneal injection of 5 mgml(-1) of beta-glucan significantly reduced the mortality. A single injection of 5 mgml(-1) of beta-glucan 6 days before challenge also enhanced significantly the survival against the infection. The treatment with beta-glucan increased the myelomonocytic cell population in the kidney at 6h postchallenge with A. hydrophila. Moreover it enhanced the ability of kidney cells to kill A. hydrophila. beta-glucan did not affect the expression of TNFalpha or IL-1 beta but seemed to modulate IFNgamma and chemokine expression in kidney.

Objectives: To determine the prevalence and characteristics of premalignant gastric lesions and its relationship with helicobacter pylori infection., Methods: We performed a cross-sectional retrospective study. Between january and june 2008, consecutive subjects of middle and high socioeconomic status were evaluated by upper gastrointestinal endoscopy during a gastric cancer screening in Central FAP Hospital. The demografic, clinic and endoscopic information were analysed., Results: 2616 patients were evaluated. Diagnosis histological of premalignant gastric lesions was made in 187 patients (7.1%) 34 (1.3%) atrophic gastritis (AG), 55 (2.1%), complete intestinal metaplasia (CIM), 92 (3.5%) incomplete intestinal metaplasia (IIM), and 6 (0.2%) dysplasia. The frequency of helicobacter pylori infection was 76.5% (p=0.04), 65.5% (p=NS), 55.4% (p=NS) and 16.7% (p=0.03), in AG, CIM, IIM and dysplasia, respectively. The median age of presentation was similar between the lesions: 53.5 (+/-9.3), 52.6 (+/-11.2), 54.3 (+/-7.8) y 54.2 (+/-12.1) years in AG, CIM, IIM and dysplasia, respectively. The premalignant gastric lesions were more frequent in male subjects and under 60 years (p=NS). There were no significant differences among the differents gastric premalignant lesions and family history of gastric cancer, smoking and alcohol consumption (p=NS). CONCLUSIONS. The prevalence of premalignant gastric lesions in our study was low. The frequency of H. pylori infection was decreased in premalignant lesions more advanced. Association significant was only found among H. pylori infection and AG and dysplasia.

Abnormal eggs of Trichuris trichiura were found in the stools of one of the patients during a study on the prevalence of intestinal parasitoses among an institutionalized population. The abnormalities observed included great variation in shape, size, and color. Similar atypical whipworm eggs have been reported in patients after treatment with mebendazole, thiabendazole, tetracloroethylene, and dithiazanine. Apparently some anthelminthics have an effect on the reproductive system of female T. trichiura, resulting in production of abnormal eggs, which could lead to misdiagnosis of the infection, since they can be mistaken as eggs of other parasites or artifacts.

The rhabdovirus viral haemorrhagic septicemia virus (VHSV) is the etiological agent of one of the most important salmonid viral diseases. In the present work, the ability of VHSV to infect and replicate in zebrafish at low temperature (15 degrees C) was demonstrated. Zebrafish was also used to determine the effectiveness of the recombinant virus rIHNV-Gvhsv GFP as a live attenuated vaccine against the virulent VHSV strain. Fish intraperitoneally injected with 3 x 10(6) to 3 x 10(5)TCID50/ml of the wild type VHSV showed a 100% of cumulative mortality, meanwhile only 57% of mortality was obtained in bath infections. Infected fish showed external clinical signs and histological observations revealed the appearance of small haemorrhages in the muscle, kidney, liver and dermis. Neither mortalities nor clinical signs were recorded in fish infected with a live attenuated recombinant virus. By RT-PCR technique, VHSV was detected in all the organs as early as 24h, but the recombinant virus was not detected in all the sampled days. VHSV was able to replicate "in vitro" in head kidney cells but the replication capacity of the attenuated viral strain was limited. The recombinant virus rIHNV-Gvhsv GFP was able to protect against VHSV with a survival rate ranging from 20% to 60% depending of the vaccine dose. The increase of TLR3, IFNalphabeta, Mx, IFNgamma and TNFalpha expression at 72h post-infection in the kidney of VHSV-infected fish contrasted with the results obtained with the avirulent virus, which did not induce an increment of this expression in infected fish. Zebrafish is a suitable animal model to study VHSV infection and immune (innate and adaptive) responses and, more importantly, we demonstrate for the first time the usefulness of the zebrafish as a vaccination model to viral diseases. In addition, the high protection obtained with the live attenuated virus demonstrates that the zebrafish is able to mount an efficient antiviral immune response at 15 degrees C.

The molecular mechanisms by which the malarial parasite has managed to develop resistance to many antimalarial drugs remain to be completely elucidated. Mutations in the pfmdr1 gene of Plasmodium falciparum, as well as an increase in pfmdr1 copy number, have been associated with resistance to the quinoline-containing antimalarial drugs. We investigated the mechanisms of drug resistance in Plasmodium using a collection of P. yoelii lines with different drug resistance profiles. The mdr1 gene of P. yoelii (pymdr1) was identified and characterized. A 2- to 3-fold increase in the pymdr1 gene copy number was observed in the P. yoelii ART line (artemisinin resistant) when compared with the NS parental line. The pymdr1 gene was mapped to a chromosome of 2.1 Mb in all lines analyzed. Reverse transcriptase-polymerase chain reaction and Western blot experiments confirmed the expression of the gene at the RNA and protein levels.

The rapid emergence of multidrug-resistant Plasmodium falciparum is a worldwide concern. Despite the magnitude of the problem, the mechanisms involved in this phenomenon are not well understood. One current proposal suggests that toxic heme molecules are degraded by glutathione (GSH), and that anti-malarial drugs, such as chloroquine (CQ), inhibit this degradation, thus implicating GSH in drug resistance. Furthermore, in some strains of Plasmodium berghei and P. falciparum, chloroquine resistance is accompanied by an increase in glutathione levels and increased activity in GSH-related enzymes. We are investigating the relationship between the gamma-glutamylcysteine synthetase (ggcs) gene, the rate-limiting enzyme in de novo synthesis of GSH, and drug resistance in P. berghei at the molecular level. In this report, we have demonstrated an increase in pbggcs mRNA levels associated with CQ and mefloquine (MFQ) resistance. In addition, the pbggcs gene locus structure was shown to be similar and localized to chromosome 8 in four parasite lines of P. berghei with different drug resistance profiles. This work suggests a link between increased GSH levels and drug resistance in Plasmodium.