Hypocone reduction and Carabelli's traits in contemporary Jordanians and the association between Carabelli's trait and the dimensions of the maxillary first permanent molar

The objective of this study is to determine the prevalence of expression and bilateralism of two dental morphological traits in contemporary Jordanians: The hypocone reduction trait on the maxillary second permanent molar and Carabelli's trait on maxillary permanent first and second molars. Furthermore, inter-trait correlation and the relationship of Carabelli's traits with upper first molar dimensions were investigated. Three hundred subjects of school children at their 10th grade and of an average age of 15.5 +/- 0.4 years were involved. Alginate impressions for the maxillary arch were taken, dental casts were reproduced. The selected accurate casts were of 132 male- and 155 female-students. The frequencies of hypocone reduction trait on the maxillary second molar and Carabelli's trait on the maxillary molars were examined. Buccolingual and mesiodistal diameters of the maxillary first molar were measured and recorded. Paired Sample t test and Nonparametric Correlation analysis were used for data analysis. Hypocone reduction trait on the maxillary second molar was found in 29.8% of the examined students. Positive forms of Carabelli's trait on first and second molars were observed in 65.0% and 3.8%, respectively. Nonparametric correlation analysis revealed positive association between Carabelli's trait on first molar and hypocone reduction trait on the maxillary second molar. The presence of Carabelli's trait on first molar was strongly associated with the increase of buccolingual, but not the mesiodistal, diameter. Bilateralism was found highly significant in the tested traits and both genders (p < 0.001). This finding might be a sign of relatively low environmental stresses in the living Jordanian population and/or great ability of its individuals to buffer the adverse effects of such stresses.     

Insights into plastome of Fagonia indica Burm.f. (Zygophyllaceae): organization,annotation and phylogeny

The enhanced understanding of chloroplast genomics would facilitate various biotechnology applications; however, the chloroplast (cp) genome / plastome characteristics of plants like Fagonia indica Burm.f. (family Zygophyllaceae), which have the capability to grow in extremely hot sand desert, have been rarely understood. The de novo genome sequence of F. indica using the Illumina high-throughput sequencing technology determined 128,379 bp long cp genome, encode 115 unique coding genes. The present study added the evidence of the loss of a copy of the IR in the cp genome of the taxa capable to grow in the hot sand desert. The maximum likelihood analysis revealed two distinct sub-clades i.e. Krameriaceae and Zygophyllaceae of the order Zygophyllales, nested within fabids.     

CB-RAF600E-1 exerts efficacy in vemurafenib-resistant and non-resistant-melanoma cells via dual inhibition of RAS/RAF/MEK/ERK and PI3K/Akt signaling pathways

Background and AimPredicting novel dual inhibitors to combat adverse effects such as the development of resistance to vemurafenib in melanoma treatment due to the reactivation of MAPK and PI3K/AKT signaling pathways is studied to help in reversal of cancer symptoms.Reversal of cancer symptoms in melanoma associated with vemurafenib resistance is driven by reactivation of MAPK and PI3K/Akt signaling pathways. Novel dual inhibitors targeting these proteins would be beneficial to combat resistance.MethodsHigh-throughput virtual screening of the ChemBridge library against B-RAFV600E and Akt was performed using an automated protocol with the AutoDock VINA program. Luminescence and time-resolved fluorescence kits were used to measure enzyme activities. The MTT assay was used to determine proliferation in normal and vemurafenib-resistant A375 cells. Flow cytometry was used to examine apoptosis, cell cycle, and phosphorylation of ERK/Akt signaling pathway.ResultsHigh-throughput screening from the ChemBridge library identified 15 compounds with high binding energy towards B-RAFV600E; among these, CB-RAF600E-1 had the highest ΔG_binding score −11.9 kcal/mol. The compound also had a high affinity towards Akt, with a ΔG_binding score of −11.5 kcal/mol. CB-RAF600E-1 dose-dependently inhibited both B-RAFV600E and Akt with IC₅₀ values of 635 nM and 154.3 nM, respectively. The compound effectively controlled the proliferations of normal and vemurafenib-resistant A375 cells, with GI₅₀ values of 222.3 nM and 230.5 nM, respectively. A dose-dependent increase in the sub G₀/G₁ phase of the cell cycle and total apoptosis was observed following compound treatment in both normal and vemurafenib-resistant melanoma cells. Treatment with CB-RAF600E-1 decreased the pERK/pAkt dual-positive populations in normal and vemurafenib-resistant A375 cells.ConclusionCB-RAF600E-1, identified as a novel dual inhibitor effective against normal and vemurafenib-resistant melanoma cells, requires further attention for development as an effective chemotherapeutic agent for melanoma management.     

Ultrasonographic contrast-agent imaging of sub-millimeter vessel structures with spatial compounding: in vitro analyses.

In clinical diagnostics, ultrasonographic contrast-agent imaging gives access to medical parameters such as perfusion and vascularization. In addition to the artifacts that are typical for ultrasonic imaging, e.g., speckle noise and depth-dependent sensitivity and resolution, contrast-agent imaging shows more pronounced depth dependence and may suffer from shadowing artifacts that arise from high attenuation of the ultrasound waves by the contrast agent at high concentrations. By imaging an object from different viewing angles in one 2D image plane and summing the images obtained (spatial compounding), image quality can be increased and artifacts can be suppressed. In the present study, we combined both techniques to overcome the limitations of contrast-agent imaging. We used a commercially available ultrasound scanner and a custom-made high-precision mechanical system to rotate the ultrasound transducer fully around the object under investigation. Using this set-up, ultrasound data were acquired in reflection mode to generate a 360 degrees compound scan of a flow-mimicking phantom supplied with contrast agent.     

Sublethal effects of hexaflumuron on development and reproduction of the diamondback moth,Plutella xylostella (Lepidoptera: Yponomeutidae)

Abstract Effects of hexaflumuron at 10% lethal concentration (LC₁₀) and LC₂₅ on development and reproduction parameters of the diamondback moth, Plutella xylostella (Linnaeus, 1753) (Lep.: Yponomeutidae) were investigated. Estimated LC₅₀, LC₁₀ and LC₂₅ values of leaf dip bioassay of hexaflumuron on the third instar larvae of the P. xylostella were 1.48, 0.59 and 0.91 mg/L, respectively. Hexaflumuron decreased pupal weight in the parent generation at sublethal concentrations but in the offspring generation, this effect was not observed. Sublethal concentrations increased egg, first and second larval instar and pupa developmental time and shortened life span of adults, but did not change the third and fourth larval instars and pre‐pupa developmental period. Also fecundity of females reduced significantly but hatchability of treatments and control were similar. Survival rate of pre‐adult stages declined significantly at LC₂₅ concentration. Reproduction parameters such as reproductive rate (R₀) and intrinsic rate of increase in sublethal concentrations were significantly lower compared with control, but gross reproduction rate (GRR) at the LC₁₀ concentration was increased and it could be hormoligosis. Also hexaflumuron significantly increased doubling time (Dt). We conclude that the sublethal effects of hexaflumuron might exhibit significant effects on the population dynamics of P. xylostella.     

Down-regulation of nestin in mesenchymal stem cells derived from peripheral blood through blocking bone morphogenesis pathway

Different signaling pathways are implicated in proliferation and differentiation of stem cells. Bone Morphogenesis Pathway (BMP) signaling was known to display an important function in osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). In the present study, the authors investigated whether blocking BMP signaling was associated with down regulation of Nestin expression as neural stem cell marker in peripheral blood derived mesenchymal stem cells (PB-MSCs). At first, MSCs were isolated from peripheral blood by plastic adherent ability and flow cytometry analysis. After reaching the confluence, the cells were treated with medium containing Noggin as antagonist of BMP signaling upon 8 days. Real time PCR analysis indicated that the expression of Nestin was diminished in PB-MSCs by attenuating BMP signaling. The obtained results suggested that BMP signaling might have a regulatory function on the Nestin expression in mesenchymal stem cells.     

Appraisal of Transdermal Water-in-Oil Nanoemulgel of Selegiline HCl for the Effective Management of Parkinson’s Disease: Pharmacodynamic,Pharmacokinetic, and Biochemical Investigations

In the present study, the potential of transdermal nanoemulsion gel of selegiline hydrochloride for the treatment of Parkinson’s disease was investigated. Water-in-oil nanoemulsions were developed by comparing low- and high-energy methods and were subjected to thermodynamic stability tests, in vitro permeation, and characterization studies. In vitro studies indicated that components of nanoemulsion acted as permeation enhancers with highest flux of 3.531 ± 1.94 μg/cm²/h from nanoemulsion SB6 containing 0.5 mg selegiline hydrochloride, 3% distilled water, 21% S _mix (Span 85, Tween 80, PEG 400), and 76% isopropyl myristate by weight. SB6 with the least droplet size of 183.4 ± 0.35 nm, polydispersity index of 0.42 ± 0.06 with pH of 5.9 ± 0.32 and viscosity of 22.42 ± 0.14 cps was converted to nanoemulsion gel NEGS4 (viscosity = 22,200 ± 400 cps) by addition of Viscup160® for ease of application and evaluated for permeation, safety, and pharmacokinetic profile in Wistar rats. It provided enhancement ratio 3.69 times greater than conventional gel. NEGS4 showed 6.56 and 5.53 times increase in bioavailability in comparison to tablet and conventional gel, respectively, along with sustained effect. Therefore, the developed water-in-oil nanoemulsion gel promises to be an effective vehicle for transdermal delivery of selegiline hydrochloride.     

Lifestyle factors and quality of life among primary health care physicians in Madinah,Saudi Arabia

BackgroundPhysicians are considered to be a high-risk population for a poor quality of life (QoL), but few studies of lifestyle factors include the QoL among them.ObjectivesThis study aimed to investigate the relationship between lifestyle factors and a positive QoL among primary health care (PHC) physicians.MethodsA cross-sectional study was conducted at 20 primary healthcare centers in Madinah, Saudi Arabia. A self-administered questionnaire was used, including sociodemographic characteristics, lifestyle data, and the short version of the World Health Organization Quality of Life questionnaire. Appropriate statistical analyses were used, including multivariate logistic regression models.ResultsThe response rate was 85.7% (72/84) physicians. The mean score of the total QoL and its four studied domains (physical, psychological, social, and environmental) was relatively high, with no statistically significant difference between the consultants and general practitioners. The positive total QoL in this study was significantly lower among physicians with obesity (OR = 0.55, 95%CI = 0.25–0.97), those using butter and animal fat for cooking (OR = 0.10, 95%CI = 0.02–0.81), and those eating meals out > 3 times per week (OR = 0.30, 95%CI = 0.10–0.90). Although non-significant, vegetable consumption and a high level of physical activity were associated with a positive QoL, with adjusted ORs of 2.5 (95%CI = 0.82–7.58) and 1.5 (95%CI = 0.33–6.65), respectively.ConclusionThe findings indicate a relatively good QoL among the participating physicians; however, a lower QoL was associated with unhealthy lifestyle factors. QoL was significantly associated with obesity, cooking practices, and eating meals from restaurants.