Dysregulation of Cytokine Response in Canadian First Nations Communities: Is There an Association with Persistent Organic Pollutant Levels?

In vitro and animal studies report that some persistent organic pollutants (POPs) trigger the secretion of proinflammatory cytokines. Whether POP exposure is associated with a dysregulation of cytokine response remains to be investigated in humans. We studied the strength of association between plasma POP levels and circulating cytokines as immune activation markers. Plasma levels of fourteen POPs and thirteen cytokines were measured in 39 Caucasians from a comparator sample in Québec City (Canada) and 72 First Nations individuals from two northern communities of Ontario (Canada). Caucasians showed significantly higher levels of organochlorine insecticides (β-HCH, p,p'-DDE and HCB) compared to First Nations. Conversely, First Nations showed higher levels of Mirex, Aroclor 1260, PCB 153, PCB 170, PCB 180 and PCB 187 compared to Caucasians. While there was no difference in cytokine levels of IL-4, IL-6, IL-10 and IL-22 between groups, First Nations had significantly greater average levels of IFNγ, IL-1β, IL-2, IL-5, IL-8, IL-12p70, IL-17A, TNFα and TNFβ levels compared to Caucasians. Among candidate predictor variables (age, body mass index, insulin resistance and POP levels), high levels of PCBs were the only predictor accounting for a small but significant effect of observed variance (～7%) in cytokine levels. Overall, a weak but significant association is detected between persistent organochlorine pollutant exposure and elevated cytokine levels. This finding augments the already existing information that environmental pollution is related to inflammation, a common feature of several metabolic disorders that are known to be especially prevalent in Canada's remote First Nations communities.     

Access to Awareness for Faces during Continuous Flash Suppression Is Not Modulated by Affective Knowledge

It is a controversially debated topic whether stimuli can be analyzed up to the semantic level when they are suppressed from visual awareness during continuous flash suppression (CFS). Here, we investigated whether affective knowledge, i.e., affective biographical information about faces, influences the time it takes for initially invisible faces with neutral expressions to overcome suppression and break into consciousness. To test this, we used negative, positive, and neutral famous faces as well as initially unfamiliar faces, which were associated with negative, positive or neutral biographical information. Affective knowledge influenced ratings of facial expressions, corroborating recent evidence and indicating the success of our affective learning paradigm. Furthermore, we replicated shorter suppression durations for upright than for inverted faces, demonstrating the suitability of our CFS paradigm. However, affective biographical information did not modulate suppression durations for newly learned faces, and even though suppression durations for famous faces were influenced by affective knowledge, these effects did not differ between upright and inverted faces, indicating that they might have been due to low-level visual differences. Thus, we did not obtain unequivocal evidence for genuine influences of affective biographical information on access to visual awareness for faces during CFS.     

The role of calcium,silicon and salicylic acid treatment in protection of canola plants against boron toxicity stress

Boron (B) toxicity often limits crop yield and the quality of production in agricultural areas. Here, we investigated the effects of calcium (Ca), silicon (Si) and salicylic acid (SA) on development of B toxicity, B allocation in canola (Brassica napus cultivar Sarw 4) and its role in non-enzymatic antioxidants in relation to yield of this cultivar under B toxicity. Canola seedlings were subjected to four B levels induced by boric acid in the absence or presence of Ca, Si and SA. The results showed that Ca, Si and SA addition ameliorated the inhibition in canola growth, water content (WC), and improved siliqua number, siliqua weight and seed index. The B content in shoots and roots and total B accumulation in the whole plant were increased in control plants under B-toxicity-stress, and these parameters were significantly decreased by addition of Ca, Si and SA. The shoot ascorbate pool (ascorbate, AsA, and dehydroascorbate, DHA), α-tocopherol and phenolics (free and bound) were increased under B toxicity, and were significantly decreased in most cases by addition of Ca, Si and SA, except α-tocopherol, which increased at low B levels (0, 25 and 50 mg kg soil^?1). The glutathione content did not obviously change by B stress, while added Ca, Si and SA inhibited its accumulation under B stress. In addition, B toxicity reduced the shoot flavonoids content; however, this reduction was not alleviated by the use of Ca, Si and SA treatments. It could be concluded that growth and yield of canola plants grown under high B concentration improved after external application of Ca, Si or SA.     

Discovery of potent polyphosphate kinase 1 (PPK1) inhibitors using structure‐based exploration of PPK1Pharmacophoric space coupled with docking analyses

Inorganic polyphosphate (polyP) is present in all living forms of life. Studied mainly in prokaryotes, polyP and its associated enzymes are vital in diverse metabolic activities, in some structural functions, and most importantly in stress responses. Bacterial species, including many pathogens, encode a homolog of a major polyP synthesis enzyme, Poly Phosphate Kinase (PPK) with 2 different genes coding for PPK1 and PPK2. Genetic deletion of the ppk1 gene leads to reduced polyP levels and the consequent loss of virulence and stress adaptation responses. This far, no PPK1 homolog has been identified in higher‐order eukaryotes, and, therefore, PPK1 represents a novel target for chemotherapy. The aim of the current study is to investigate PPK1 from Escherichia coli with comprehensive understanding of the enzyme's structure and binding sites, which were used to design pharmacophores and screen a library of compounds for potential discovery of selective PPK1 inhibitors. Verification of the resultant inhibitors activities was conducted using a combination of mutagenic and chemical biological approaches. The metabolic phenotypic maps of the wild type E. coli (WT) and ppk1 knockout mutant were generated and compared with the metabolic map of the chemically inhibited WT. In addition, biofilm formation ability was measured in WT, ppk1 knockout mutant, and the chemically inhibited WT. The results demonstrated that chemical inhibition of PPK1, with the designed inhibitors, was equivalent to gene deletion in altering specific metabolic pathways, changing the metabolic fingerprint, and suppressing the ability of E. coli to form a biofilm.     

In Vitro Selection and Identification of Potential Probiotics Isolated from the Gastrointestinal Tract of Nile Tilapia, <Emphasis Type="Italic">Oreochromis niloticus</Emphasis>

Fish gut bacteria can be used as probiotics for aquaculture. The aim of this study is to screen and identify beneficial probiotic bacteria from the gut of Nile tilapia, Oreochromis niloticus. Nine out of one hundred thirty-five isolates were non-pathogenic through intraperitoneal injection and had antibacterial activities with at least a strain from the five isolated fish pathogens, Aeromonas sobria, Aeromonas hydrophila, Pseudomonas aeruginosa, Pseudomonas putida, and Staphylococcus aureus. Further tests showed that such isolates can survive in the presence of high bile concentration (10%) and at different acidic pH values. A strains (14HT) was sensitive to all selected antibiotics, two strains were (9HT and 11HT) resistant to streptomycin and three strains (9HT, 11HT and 38HT) had resistance to two antibiotics. Four isolates (11HT, 33HT, 38HT and 41HT) had an amylase and a protease activities and one strain (47HT) showed only amylase activity. Based on 16S rRNA gene analysis, the isolated strains were identified as follows: Lactococcus lactis (8HT, 9HT, 11HT and 33HT); Enterococcus faecalis (14HT), Lysinibacillus sp. (38HT) and Citrobacter freundii (39HT, 41HT and 47HT).     

<Emphasis Type="Italic">Braf</Emphasis>, <Emphasis Type="Italic">Kras</Emphasis> and <Emphasis Type="Italic">Helicobacter pylori</Emphasis> epigenetic changes-associated chronic gastritis in Egyptian patients with and without gastric cancer

We aimed to study MLH1 and MGMT methylation status in Helicobacter pylori-associated chronic gastritis in Egyptian patients with and without gastric cancer. 39 patients were included in our study. They were divided into 2 groups; patients without (group I) and with gastric adenocarcinoma (group II). Patients were subjected to clinical examination, abdominal ultrasound and upper endoscopy for gastric biopsy. Biopsies were subjected to urease test, histological examination, and DNA purification. H. pylori, Braf, Kras, MLH1 and MGMT methylation were assessed by quantitative PCR. DNA sequencing was performed to assess Braf and Kras genes mutation. qPCR of H. pylori was significantly higher in patients with adenocarcinoma (group II) than those without adenocarcinoma (group I); with a p < 0.001 as well as in patients with age above 50 years with a p value = 0.008. By applying logistic regression analysis it was reported that the H. pylori qPCR is a significant predictor to the adenocarcinoma with OR = 1.025 (95 % CI: 1. 002–1.048), with sensitivity of 90 % and specificity of 100 %. Adenocarcinoma patients had a significantly higher mean age and levels of H. Pylori, Braf, K-ras, methylated MGMT and methylated MLH1 than those of gastritis patients. DNA sequence analysis of Braf (codon 12) and Kras (codon 600) had genes mutation in gastric adenocarcinoma versus chronic gastritis. Conclusion: H. pylori may cause epigenetic changes predisposing the patients to cancer stomach. Estimation of H. pylori by qPCR can be a good predictor to adenocarcinoma. Braf and Kras genes mutation were reveled in gastritis and adenocarcinoma patients.     

Environmentally benign first derivative synchronous spectrofluorimetry for the analysis of two binary mixtures containing duloxetine with avanafil or tadalafil in spiked plasma samples

Antidepressants can cause sexual dysfunction side effects, necessitating the co-administration of phosphodiesterase type 5 inhibitors. The simultaneous determination of these drugs in biological fluids is critical for therapeutic drug monitoring. For the first time, two binary mixtures containing duloxetine with either avanafil or tadalafil were estimated utilizing simple green spectrofluorimetric methods without the need for a previous separation step. The study was based on first derivative synchronous spectrofluorimetry in ethanol using a change in wavelength difference (∆λ) of 20 and 25 nm for the first and second combinations, respectively. Duloxetine and avanafil were estimated at 297.7 and 331 nm in their binary mixture, while duloxetine and tadalafil were determined at 290.3 and 297.7 nm, respectively. The linearity was achieved over the ranges of 0.1–1.5 μg mL⁻¹ for both duloxetine and avanafil and 0.01–0.40 μg mL⁻¹ for tadalafil, with limits of detection of 0.013, 0.022, and 0.004 μg mL⁻¹ for duloxetine, avanafil, and tadalafil, respectively. Successful application of the developed approaches was accomplished for the estimation of the two mixtures in dosage forms as well as human plasma with excellent percentage recoveries (96–103.75% in plasma), which supports their suitability for use in quality control laboratories and pharmacokinetic studies. Moreover, the adopted approaches' greenness was evidenced by applying three tools.     

Diagnostic dilemma of cardiac syncope in pediatric patients

Aims

Syncope is defined as temporary loss of consciousness and postural tone resulting from an abrupt transient decrease in cerebral blood flow. The present work aimed at determining how diagnostic tests are used in the evaluation of pediatric syncope at a tertiary pediatric referral center and to report on the utility and the yield of these tests.

Settings and Design

Retrospective study conducted at a tertiary referral arrhythmolology service

Methods and Material

The clinical charts of 234 pediatric patients presenting with a primary complaint of syncope with an average age of 7.48 ± 3.82(3.5-16) years were reviewed by the investigators.

Statistical analysis used

Statistical Package of social science (SPSS) version 9,0 was used for analysis of data.

Results

The commonest trigger for syncope in the study population was early following exercise (n=65) and the commonest prodrome was palpitation, noted in 25 patients. A murmur was present in 19 of our patients (8.3%) while 10.7% (n=25) had abnormal ECGs. Of the 106 echocardiograms done, 14 (13.2%) were abnormal. Only two of them were missed by ECG. All patients were offered ambulatory 24 hour ECG. One patient with sick sinus syndrome was diagnosed only with Holter.

Conclusions

Clues to the presence of cardiac syncope may include acute onset of syncope, frequent episodes, low difference between blood pressure readings in supine and erect positions (after standing for 2 minutes) and most importantly an abnormal 12 lead ECG. Transthoracic echo and Holter monitoring have low yield in pediatric syncope.     

Insecticidal and synergistic effects of Majorana hortensis essential oil and some of its major constituents

The essential oil from leaves of Majorana hortensis Moench (Lamiaceae) was isolated by hydrodistillation with a yield of 1.6% (wt/wt). The insecticidal activity of the oil was evaluated against fourth instars of Spodoptera littoralis Boisduval (Lepidoptera: Noctuidae) and adults of Aphis fabae L. (Hemiptera: Aphididae). The oil showed a remarkable toxic effect against S. littoralis in a topical application assay (LD₅₀ = 2.48 μg per larva) and in a residual film assay (LC₅₀ = 3.14 g/l). The oil of M. hortensis also exhibited a pronounced toxic effect against A. fabae adults with LC₅₀ values of 1.86 and 2.27 g/l in rapid dipping and residual film assays, respectively. Gas chromatography-mass spectrometry analyses of M. hortensis essential oils revealed the presence of 31 compounds and the main components were terpinen-4-ol (30.0%), γ-terpinene (11.3%), and trans -sabinene hydrate (10.8%). Repeated column chromatography of M. hortensis oil on silica gel led to the isolation of two major constituents, which were characterized based on ¹H-nuclear magnetic resonance and mass spectrometric data, as terpinen-4-ol and γ-terpinene. These two components were examined for their insecticidal and synergistic activities towards S. littoralis and A. fabae . Terpinen-4-ol and γ-terpinene exhibited a significant insecticidal activity against both insects, but γ-terpinene was more toxic than terpinen-4-ol. When tested in a binary mixture with the synthetic insecticides profenofos and methomyl, it was found that both compounds enhanced the insecticidal activity of these insecticides by two- to threefold. These results show that terpinen-4-ol and γ-terpinene have a synergistic effect on the insecticidal activities of synthetic insecticides profenofos and methomyl.