Acute toxicity effects of ibuprofen on behaviour and haematological parameters of African catfish Clarias gariepinus (Burchell, 1822)

Indiscriminate discharge of pharmaceutical waste into the aquatic ecosystem may pose serious health challenges to aquatic biota. The effect of acute exposure to ibuprofen was evaluated using changes in behaviour and haematological parameters under static bio-assay method in Clarias gariepinus. Test specimens were exposed to acute concentrations of ibuprofen (0.28, 0.33, 0.38, 0.43 and 0.48 mg l^?1) for 24, 48, 72 and 96 h durations respectively. Behavioural and phenotypic changes were observed in surviving fish. There were significant (p < 0.05) concentration and duration-dependent increases in erythrocyte (RBC), haemoglobin (Hb), pack cell volume (PCV) and leukocytes (WBC) in treated fish compared to the control. Insignificant decreases (p > 0.05) in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were observed in treated fish compared to the control. Ibuprofen elicited dose and duration- dependent decrease in neutrophil counts with the decreases being significant (p < 0.05) in the higher doses of 0.43 and 0.48 mg l^?1. Ibuprofen did not elicit any significant changes in monocytes, basophils and eosinophils. Changes observed in this study showed that ibuprofen negatively affected the health of the fish and we recommend that discharge of ibuprofen into the aquatic environment should be monitored and controlled.     

QMEANclust: estimation of protein model quality by combining a composite scoring function with structural density information

Background  

The selection of the most accurate protein model from a set of alternatives is a crucial step in protein structure prediction both in template-based and ab initio approaches. Scoring functions have been developed which can either return a quality estimate for a single model or derive a score from the information contained in the ensemble of models for a given sequence. Local structural features occurring more frequently in the ensemble have a greater probability of being correct. Within the context of the CASP experiment, these so called consensus methods have been shown to perform considerably better in selecting good candidate models, but tend to fail if the best models are far from the dominant structural cluster. In this paper we show that model selection can be improved if both approaches are combined by pre-filtering the models used during the calculation of the structural consensus.     

Factors influencing in the response of <i>Schizolobium parahybum</i> (Vell) Blake to <i>Ceratocystis paradoxa</i> and <i>C. moniliformis</i>

In the Ecuadorian coast one of the most destructive diseases of the pachaco is vascular wilt or stem rot caused by Ceratocystis complex, so the aim of this study was to determine the factors that affect the efficiency of the reaction of bark pachaco to this disease. This research was conducted under laboratory conditions, using trees pachaco S38, S41, S98, AE-1, AE-2 and AE-3, and pathogenic species Ceratocystis paradoxa and C. moniliformis. The method utilized was tissue stem bark,with bark sections with 4.5 cm², and a suspension of 3x10⁴ units infection and remained in a humid chamber for 96 hours at 25 ± 5 °C. Were determined grades of resistance/ susceptibility using a scale from 0 to 4, depending on the amount of mycelia and peritecio in each plant sample. Three factors were used: four colonies obtained by several transfers from each fungal specie, four ages of colonies of each fungal specie and four volumes of inoculum applied (units of infection), using for each experiment separately Completely Randomized Design with 4 replications factorial arrangement. For comparison between treatment means was used Tukey test at 5% probability of error. For future trials using this technique, you could use 30-day colonies for C. paradoxa and 40 days for C. moniliformis, and an application volume of 100 μL/cm², it would improve the level of response for the formation of perithecium and mycelia in samples cortex.     

A comparative genomic analysis of the alkalitolerant soil bacterium Bacillus lehensis G1

Bacillus lehensis G1 is a Gram-positive, moderately alkalitolerant bacterium isolated from soil samples. B. lehensis produces cyclodextrin glucanotransferase (CGTase), an enzyme that has enabled the extensive use of cyclodextrin in foodstuffs, chemicals, and pharmaceuticals. The genome sequence of B. lehensis G1 consists of a single circular 3.99 Mb chromosome containing 4017 protein-coding sequences (CDSs), of which 2818 (70.15%) have assigned biological roles, 936 (23.30%) have conserved domains with unknown functions, and 263 (6.55%) have no match with any protein database. Bacillus clausii KSM-K16 was established as the closest relative to B. lehensis G1 based on gene content similarity and 16S rRNA phylogenetic analysis. A total of 2820 proteins from B. lehensis G1 were found to have orthologues in B. clausii, including sodium–proton antiporters, transport proteins, and proteins involved in ATP synthesis. A comparative analysis of these proteins and those in B. clausii and other alkaliphilic Bacillus species was carried out to investigate their contributions towards the alkalitolerance of the microorganism. The similarities and differences in alkalitolerance-related genes among alkalitolerant/alkaliphilic Bacillus species highlight the complex mechanism of pH homeostasis. The B. lehensis G1 genome was also mined for proteins and enzymes with potential viability for industrial and commercial purposes.     

Isocitrate dehydrogenase 1 R132C mutation occurs exclusively in microsatellite stable colorectal cancers with the CpG island methylator phenotype

The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.     

Principal trabecular structural orientation predicted by quantitative ultrasound is strongly correlated with \upmu FEA determined anisotropic apparent stiffness

The microarchitecture and alignment of trabecular bone adapts to the particular mechanical milieu applied to it. Due to this anisotropic mechanical property, measurement orientation has to be taken into consideration when assessing trabecular bone quality and fracture risk prediction. Quantitative ultrasound (QUS) has demonstrated the ability in predicting the principal structural orientation (PSO) of trabecular bone. Although the QUS prediction for PSO is very close to that of \(\upmu \) CT, certain angle differences still exist. It remains unknown whether this angle difference can induce significant differences in mechanical properties or not. The objective of this study was to evaluate the mechanical properties in different PSOs predicted using different methods, QUS and \(\upmu \) CT, thus to investigate the ability of QUS as a means to predict the PSO of trabecular bone noninvasively. By validating the ability of QUS to predict the PSO of trabecular bone, it is beneficial for future QUS applications because QUS measurements in the PSO can provide information more correlated with the mechanical properties than with other orientations. In this study, seven trabecular bone balls from distal bovine femurs were used to generate finite element models based on the 3-dimensional \(\upmu \) CT images. Uniaxial compressive loading was performed on the bone ball models in the finite element analysis (FEA) in six different orientations (three anatomical orientations, two PSOs predicted by QUS and the longest vector of mean intercept length (MIL) tensor calculated by \(\upmu \) CT). The stiffness was calculated based on the reaction force of the bone balls under loading, and the von Mises stress results showed that both the mechanical properties in the PSOs predicted by QUS are significantly higher than the anatomical orientations and comparatively close to the longest vector of MIL tensor. The stiffness in the PSOs predicted by QUS is also highly correlated with the stiffness in the MIL tensor orientation (ATTmax vs. MIL, \(R^{2}\)  = 0.98, \(p<001\) ; UVmax vs. MIL, \(R^{2}\)  = 0.92, \(p<001\) ). These results were validated by in vitro mechanical testing on the bone ball samples. This study demonstrates that the PSO of trabecular bone predicted by QUS has an equally strong apparent stiffness with the orientation predicted by \(\upmu \) CT.     

Trends in First-Line Antiretroviral Therapy in Asia: Results from the TREAT Asia HIV Observational Database

Background

Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.

Methods

Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed.

Results

Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus <30years), female sex (1.29 [1.11–1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based).

Conclusions

The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.     

Characterisation of Structures in Salivary Secretion Film Formation. An Experimental Study with Atomic Force Microscopy

The purpose of the present study was to characterise the structure dynamics of pure salivary secretions retained on controlled surfaces with different surface energies in the early stage of salivary film formation. Germanium prisms prepared to have either low surface energy or medium surface energy were incubated in fresh secretions of either human parotid saliva (HPS) or human submandibular/sublingual saliva (HSMSLS) for 15, 90, and 180 min. After controlled rinsing with distilled water, the surfaces were air dried and thereafter imaged with atomic force microscopy (AFM). The amount of adsorbed material and the size of the structures detected increased with increased saliva exposure time. The film thicknesses varied from 10 to 150 nm, and both HPS and HSMSLS films contained structures with diameters varying from 40 nm to 2 μm. Some of these were clustered into special formations. The HPS films exhibited a more granular morphology than the HSMSLS films. Furthermore, branched lines were detected on the low surface energy germanium prisms incubated in saliva. The results indicate that exposure time, surface energy, and type of salivary secretion all are factors affecting the adsorption characteristics of salivary films.     

Immunocytochemical localization of testosterone in human hepatocellular carcinoma

Summary A study of 10 hepatoma patients was carried out for the detection and localization of oestrogen, progesterone, testosterone, and their corresponding binding sites in liver tumour cells using immunoperoxidase and immunofluorescent techniques on histopathological sections and cultured monolayers. None of the hepatomas was positive for progesterone and its receptor; one was positive for oestrogen and its receptor; five were positive for testosterone and its receptor. Oestrogen, testosterone and their respective receptors localized predominantly to the cytoplasm of hepatoma cells. The results obtained in this investigation reveal an association between testosterone and human liver cancer which may be useful in the selection and monitoring of liver cancer patients to future hormonal therapy.