Screening Stability, Thermochemistry, and Chemical Kinetics of 3-Hydroxybutanoic Acid as a Bifunctional Biodiesel Additive.

The thermo-kinetic aspects of 3-hydroxybutyric acid (3-HBA) pyrolysis in the gas phase were investigated using density functional theory (DFT), specifically the M06-2X theoretical level in conjunction with the cc-pVTZ basis set. The obtained data were compared with benchmark CBS-QB3 results. The degradation mechanism was divided into 16 pathways, comprising 6 complex fissions and 10 barrierless reactions. Energy profiles were calculated and supplemented with computations of rate coefficients and branching ratios over the temperature range of 600-1700 K at a pressure of 1 bar using transition state theory (TST) and Rice-Ramsperger-Kassel-Marcus (RRKM) methods. Thermodynamics results indicated the presence of six stable conformers within a 4 kcal mol-1 energy range. The estimated chemical kinetics results suggested that TST and RRKM approaches are comparable, providing confidence in our calculations. The branching ratio analysis reveals that the dehydration reaction pathway leading to the formation of H2O and CH3CH═CHCO2H dominates entirely at T ≤ 650 K. At these temperatures, there is a minor contribution from the simple homolytic bond fission reaction, yielding related radicals [CH3•CHOH + •CH2CO2H]. However, at T ≥ 700 K, this reaction becomes the primary decomposition route. At T = 1700 K, there is a minor involvement of a reaction pathway resulting in the formation of CH3CH(OH)•CH2 + •CHO(OH) with an approximate contribution of 16%, and a reaction leading to [•CH3 + •CH2OHCH2CO2H] with around 9%.

Simultaneous Detection of Mycobacterium tuberculosis and Atypical Mycobacteria by DNA-Microarray in Egypt.

BACKGROUND AND OBJECTIVES: Immunocompromised patients are a high-risk group for developing mycobacterial infections with either pulmonary and/or extrapulmonary diseases. Low-cost/density DNA-microarray is considered an easy and efficient method for the detection of typical and atypical mycobacterial species. MATERIALS AND METHODS: Thirty immunocompromised patients were recruited to provide their clinical specimens (sputum, serum, urine, and lymph node aspirates). Real-time polymerase chain reaction (PCR) and DNA-microarray techniques were performed and compared to the conventional methods of Ziehl-Neelsen staining and Lowenstein Jensen culturing. RESULTS: Mycobacterium tuberculosis complex was detected in all 30 clinical specimens (100% sensitivity) by real-time PCR and DNA-microarray. Additionally, coinfection with 4 atypical species belonging to nontuberculous mycobacteria was identified in 7 sputum specimens. These atypical mycobacterial species were identified as M. kansasii 10% (n = 3), M. avium complex 6.6% (n = 2), M. gordanae 3.3% (n = 1), and M. peregrinum 3.3% (n = 1). CONCLUSION: This study documents the presence of certain species of atypical mycobacteria among immunocompromised patients in Egypt.

Antitumor Effects of Scorpion Peptide Smp43 through Mitochondrial Dysfunction and Membrane Disruption on Hepatocellular Carcinoma.

Smp43, a cationic antimicrobial peptide identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, shows cytotoxicity toward hepatoma cell line HepG2 by membrane disruption. However, its underlying detailed mechanisms still remain to be further clarified. In the present study, we evaluated the cellular internalization of Smp43 and explored its effects on cell viability, cell cycle, apoptosis, autophagy, necrosis, and factor expression related to these cellular processes in human HepG2. Smp43 was found to suppress the growth of HepG2, Huh7, and human primary hepatocellular carcinoma cells while showing low toxicity to normal LO2 cells. Furthermore, Smp43 could interact with the cell membrane and be internalized into HepG2 cells via endocytosis and pore formation, which caused a ROS production increase, mitochondrial membrane potential decline, cytoskeleton disorganization, dysregulation of cyclin expression, mitochondrial apoptotic pathway activation, and alteration of MAPK as well as PI3K/Akt/mTOR signaling pathways. Finally, Smp43 showed effective antitumor protection in the HepG2 xenograft mice model. Overall, these findings indicate that Smp43 significantly exerts antitumor effects via induction of apoptosis, autophagy, necrosis, and cell cycle arrest due to its induction of mitochondrial dysfunction and membrane disruption. This discovery will extend the antitumor mechanisms of antimicrobial peptides and contribute to the development of antitumor agents against hepatocellular carcinoma.

Developing Liquid Rhizobium Inoculants with Enhanced Long-Term Survival, Storage Stability, and Plant Growth Promotion Using Ectoine Additive.

Liquid microbial inoculants have recently received great attention due to their vital roles for sustainable agricultural practices. However, long-term conservation under ambient temperature conditions and deleterious environmental factors might negatively impact microbial cell survival and limit their efficacy in the field. Thus, developing efficient liquid formulation providing prolonged survival of rhizobia in the final product and after an application is crucial. Therefore, this study investigates the effect of various additives on the long-term survival of rhizobia stored in liquid cultures at room temperature (25 °C) for 12 months. Various yeast sucrose media amended with polyvinylpyrrolidone (PVP) or gum arabic as colloidal agents in combination with ectoine (as a compatible solute) and/or glycerol were evaluated. A dramatic decline in viable cell count was obtained in formulas amended only with PVP from Log 8.5 to Log 5 in the first six months and then to Log 1.5 after 12 months. In contrast, rhizobia stored at PVP-based formulas amended with 10 mg L‒1 ectoine exhibited almost constant survival level till the end of the storage period. The same trend was obtained using formulas based on gum arabic as a colloidal dispersing agent; however, less decline in cell count using a formula containing gum arabic alone as compared to using PVP. On the other hand, PVP based formulas exhibited higher viscosity compared with another formula. Increased viscosity till the 8th month of storage was achieved in the presence of ectoine indicating the increase of exopolymeric substances production. Electrophoretic protein pattern of rhizobial cells (stored for 12 months) exhibited several low molecular weight protein bands in cells stored in PVP based formula with ectoine as compared to the other treatments. Thus, the amendment of the liquid formulation of rhizobia bioinoculant with PVP plus ectoine not only improved cell survival but also enhanced the culture viscosity and consequently ameliorate the colonization and performance of rhizobial inoculants.

Molecular Networking Leveraging the Secondary Metabolomes Space of Halophila stipulaceae (Forsk.) Aschers. and Thalassia hemprichii (Ehrenb. ex Solms) Asch. in Tandem with Their Chemosystematics and Antidiabetic Potentials.

The Red Sea is one of the most biodiverse aquatic ecosystems. Notably, seagrasses possess a crucial ecological significance. Among them are the two taxa Halophila stipulacea (Forsk.) Aschers., and Thalassia hemprichii (Ehrenb. ex Solms) Asch., which were formally ranked together with the genus Enhalus in three separate families. Nevertheless, they have been recently classified as three subfamilies within Hydrocharitaceae. The interest of this study is to explore their metabolic profiles through ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS/MS) analysis in synergism with molecular networking and to assess their chemosystematics relationship. A total of 144 metabolites were annotated, encompassing phenolic acids, flavonoids, terpenoids, and lipids. Furthermore, three new phenolic acids; methoxy benzoic acid-O-sulphate (16), O-caffeoyl-O-hydroxyl dimethoxy benzoyl tartaric acid (26), dimethoxy benzoic acid-O-sulphate (30), a new flavanone glycoside; hexahydroxy-monomethoxy flavanone-O-glucoside (28), and a new steviol glycoside; rebaudioside-O-acetate (96) were tentatively described. Additionally, the evaluation of the antidiabetic potential of both taxa displayed an inherited higher activity of H. stipulaceae in alleviating the oxidative stress and dyslipidemia associated with diabetes. Hence, the current research significantly suggested Halophila, Thalassia, and Enhalus categorization in three different taxonomic ranks based on their intergeneric and interspecific relationship among them and supported the consideration of seagrasses in natural antidiabetic studies.

Whole Exome Sequencing Identifies Candidate Genes Associated with Hereditary Predisposition to Uveal Melanoma.

PURPOSE: To identify susceptibility genes associated with hereditary predisposition to uveal melanoma (UM) in patients with no detectable germline BAP1 alterations. DESIGN: Retrospective case series from academic referral centers. PARTICIPANTS: Cohort of 154 UM patients with high risk of hereditary cancer defined as patients with 1 or more of the following: (1) familial UM, (2) young age (<35 years) at diagnosis, (3) personal history of other primary cancers, and (4) family history of 2 or more primary cancers with no detectable mutation or deletion in BAP1 gene. METHODS: Whole exome sequencing, a cancer gene panel, or both were carried out. Probands included 27 patients with familial UM, 1 patient with bilateral UM, 1 patient with congenital UM, and 125 UM patients with strong personal or family histories, or both, of cancer. Functional validation of variants was carried out by immunohistochemistry, reverse-transcriptase polymerase chain reaction, and genotyping. MAIN OUTCOME MEASURES: Clinical characterization of UM patients with germline alterations in known cancer genes. RESULTS: We identified actionable pathogenic variants in 8 known hereditary cancer predisposition genes (PALB2, MLH1, MSH6, CHEK2, SMARCE1, ATM, BRCA1, and CTNNA1) in 9 patients, including 3 of 27 patients (11%) with familial UM and 6 of 127 patients (4.7%) with a high risk for cancer. Two patients showed pathogenic variants in CHEK2 and PALB2, whereas variants in the other genes each occurred in 1 patient. Biallelic inactivation of PALB2 and MLH1 was observed in tumors from the respective patients. The frequencies of pathogenic variants in PALB2, MLH1, and SMARCE1 in UM patients were significantly higher than the observed frequencies in noncancer controls (PALB2: P = 0.02; odds ratio, 8.9; 95% confidence interval, 1.5-30.6; MLH1: P = 0.04; odds ratio, 25.4; 95% confidence interval, 1.2-143; SMARCE1: P = 0.001; odds ratio, 2047; 95% confidence interval, 52-4.5e15, respectively). CONCLUSIONS: The study provided moderate evidence of gene and disease association of germline mutations in PALB2 and MLH1 with hereditary predisposition to UM. It also identified several other candidate susceptibility genes. The results suggest locus heterogeneity in predisposition to UM. Genetic testing for hereditary predisposition to cancer is warranted in UM patients with strong personal or family history of cancers, or both.

Pomegranate peel and moringa-based diets enhanced biochemical and immune parameters of Nile tilapia against bacterial infection by Aeromonas hydrophila.

We previously reported that Aeromonas hydrophila exhibited the highest prevalence rate amongst 182 bacterial strains isolated from naturally diseased Nile tilapia (Oreochromis niloticus) collected from El-Abassa Fish Farm, Egypt (Hassan et al., Egypt. J. Aquac., 10, 23-43, 2020). The overuse of antibiotics for controlling diseases has led to acquired antibiotics resistance of aquatic bacteria, besides the developments of human, aquatic animal and environmental risks arising from residual antibiotics. Therefore, the evaluation of safe alternative phytotherapies is of great importance. This study was conducted to evaluate and compare growth performance and immune potentiating activities of moringa (Moringa oleifera) leaves extract (Moringa LE) and pomegranate (Punica granatum) peel extract (Pomegranate PE) on Nile tilapia against infection with a pathogenic bacterium, Aeromonas hydrophila. A total of 150 Oreochromis niloticus were randomly divided into 5 groups to be fed at 3% of body weight with isonitrogenous/isoenergetic diets supplemented with Moringa LE at 0.15 and 0.25% kg-1 or Pomegranate PE at of 0.3 and 0.5% kg-1, separately. Growth performance was significantly affected by Moringa LE as compared with the control group without supplementation of plant extract, while Pomegranate PE levels did not affect growth performance. Maximum average daily gains, specific growth rate, albumin, globulin, total protein, A/G ratio, alanine amino transaminase (ALT), aspartate amino transaminase (AST), cholesterol, triglyceride, creatinine, urea, and lysozyme were analyzed. Antioxidant enzymes of catalase and superoxide dismutase were also evaluated in liver tissues. After feeding experiment, the results indicated that the addition of Moringa LE and Pomegranate PE improved lipid profile, liver and kidney functions, immune response towards the emerging bacterial diseases. Besides this, feeding the fishes on diets supplemented with Moringa LE at concentration 0.25% kg-1 showed the best growth performance, and improved immunity. Moreover, it exhibited the highest protection against bacterial infection with Aeromonas hydrophila achieving the lowest mortality rate of 10% as compared to 80% of mortality rate at the control group.

Non-carbon loss long-term continuous lactic acid production from mixed sugars using thermophilic Enterococcus faecium QU 50.

In this study, a non-sterile (open) continuous fermentation (OCF) process with no-carbon loss was developed to improve lactic acid (LA) productivity and operational stability from the co-utilization of lignocellulose-derived sugars by thermophilic Enterococcus faecium QU 50. The effects of different sugar mixtures on LA production were firstly investigated in conventional OCF at 50°C, pH 6.5 and a dilution rate of 0.20 hr-1 . The xylose consumption ratio was greatly lower than that of glucose in fermentations with glucose/xylose mixtures, indicating apparent carbon catabolite repression (CCR). However, CCR could be efficiently eliminated by feeding solutions containing the cellobiose/xylose mixture. In OCF at a dilution rate ca. 0.10 hr-1 , strain QU 50 produced 42.6 g L-1 of l-LA with a yield of 0.912 g g-1 -consumed sugars, LA yield of 0.655 g g-1 based on mixed sugar-loaded, and a productivity of 4.31 g L-1 hr-1 from simulated energy cane hydrolyzate. In OCF with high cell density by cell recycling, simultaneous and complete co-utilization of sugars was achieved with stable LA production at 60.1 ± 3.25 g L-1 with LA yield of 0.944 g g-1 -consumed sugar and LA productivity of 6.49 ± 0.357 g L-1 hr-1 . Besides this, a dramatic increase in LA yield of 0.927 g g-1 based on mixed sugar-loaded with prolonged operational stability for at least 500 hr (>20 days) was established. This robust system demonstrates an initial green step with a no-carbon loss under energy-saving toward the feasibility of sustainable LA production from lignocellulosic sugars.

Germline large deletion of BAP1 and decreased expression in non-tumor choroid in uveal melanoma patients with high risk for inherited cancer.

Uveal melanoma (UM) is the most common phenotype in patients with germline BAP1 mutation. This study aimed to identify selection criteria for BAP1 germline testing and assessed the role of large deletion/duplication and epigenetic inactivation. One hundred seventy-two UM patients with high risk of hereditary cancer were included. Germline variants in BAP1 were assessed by direct sequencing and large deletion/duplication by multiplex ligation-dependent probe amplification. BAP1 expression in unaffected choroid tissue from a patient with UM was assessed by quantitative RT-PCR and methylation by pyrosequencing. Twenty-eight patients had one or more germline sequence variants in BAP1; seven of these were pathogenic. One hundred forty patients were assessed for large deletion/duplication and in one BAP1 whole gene deletion was detected. In total, eight patients (4.7%) had pathogenic alterations in BAP1 with the highest frequencies of in patients with a personal/family history of ≥2 BAP1-related cancers 6/16 (38%), age of onset <35 years 4/21 (19%) and familial UM 6/34 (18%). One of 19 non-tumor choroid tissues tested showed uncharacteristically low expression as compared to the controls decrease in BAP1 RNA expression but no evidence of constitutional promotor hypermethylation was detected. UM patients with a strong personal or family history of cancers associated with BAP1, early age of onset and familial UM should be assessed for germline variants in BAP1, including large deletions.

Enhancing the value of women's reproductive rights through community based interventions in upper Egypt governorates: a randomized interventional study.

BACKGROUND: In 2012, the WHO described the quality of health care as the route to equity and dignity for women and children. AIM OF THE WORK: To provide community based support and empowerment to women in childbearing period to seek optimal prenatal, natal and postnatal healthcare. Achieving this is anticipated to decrease maternal morbidity and mortality in Egypt. SUBJECTS AND METHODS: An interventional study was conducted among women in childbearing period in the poorest two governorates of Upper Egypt. The study passed through three stages over three and a half years; pre-interventional assessment of awareness (n = 1000), educational interventions targeting the health providers and all women in childbearing period in their communities (n = 20,494), and post-intervention evaluation of change in awareness of their rights for prenatal, natal and postnatal care (no = 1150). RESULTS: The studied indicators relating to receiving care in pregnancy, labor, and puerperium have changed dramatically as a result of the study interventions. Results of the study showed that before interventions, the surveyed women had inaccurate knowledge regarding most of the items related to their rights. The percentages of women aware of their right to have pregnancy card increased and those who possessed a pregnancy card were doubled with a significant percent change of more than 25%. Some indicators showed more than 75% improvement, including; percent of surveyed women who knew that it's their right to follow up their pregnancy and to deliver with a specialized doctor, a trained nurse or at an equipped health facility, and those who knew their right to have at least two home preparations necessary for safe delivery at home. CONCLUSION AND RECOMMENDATIONS: More work is needed in order to achieve the targeted reduction of maternal mortality. This could be achieved by ensuring accessible and high quality care provided by the governmental health facilities together with increasing the awareness of women regarding their rights in receiving such care.

Contribution of CYP27B1 and CYP24A1 genetic variations to the incidence of acute coronary syndrome and to vitamin D serum level.

Cardiovascular diseases remain a major public health burden worldwide. It was reported that vitamin D protects the cardiovascular system through several mechanisms mainly by hindering atherosclerosis development. Genetic variations in vitamin D metabolic pathway were found to affect vitamin D levels. This study aimed at investigating the association between single nucleotide polymorphisms in genes involved in vitamin D metabolism, CYP27B and CYP24A1; 25-hydroxyvitamin D (25(OH)D) levels; and susceptibility to acute coronary syndrome (ACS). One hundred and eighty-five patients and 138 healthy controls were recruited. CYP24A1 rs2762939 was genotyped using fast real-time PCR, while CYP24A1 rs4809960 and CYP27B1 rs703842 were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). 25(OH)D3 and 25(OH)D2 levels were measured using ultra-performance liquid chromatography tandem mass spectrum. Vitamin D level was significantly lower in patients than controls (p < 0.05). The GG genotype of rs2762939 was significantly associated with the risk of ACS development, but not correlated to the vitamin D level. rs4809960 and rs703842 genetic variations were not associated with ACS nor with 25(OH)D level. The genetic variant rs2762939 of CYP24A1 is remarkably associated with ACS. Meanwhile, the variants rs4809960 and rs703842 are not associated with ACS incidence.

Temperature-Dependent Resistive Properties of Vanadium Pentoxide/Vanadium Multi-Layer Thin Films for Microbolometer & Antenna-Coupled Microbolometer Applications.

In this study, vanadium oxide (VxOy) semiconducting resistive thermometer thin films were developed, and their temperature-dependent resistive behavior was examined. Multilayers of 5-nm-thick vanadium pentoxide (V2O5) and 5-nm-thick vanadium (V) films were alternately sputter-deposited, at room temperature, to form 105-nm-thick VxOy films, which were post-deposition annealed at 300 °C in O2 and N2 atmospheres for 30 and 40 min. The synthesized VxOy thin films were then patterned into resistive thermometer structures, and their resistance versus temperature (R-T) characteristics were measured. Samples annealed in O2 achieved temperature coefficients of resistance (TCRs) of -3.0036 and -2.4964%/K at resistivity values of 0.01477 and 0.00819 Ω·cm, respectively. Samples annealed in N2 achieved TCRs of -3.18 and -1.1181%/K at resistivity values of 0.04718 and 0.002527 Ω·cm, respectively. The developed thermometer thin films had TCR/resistivity properties suitable for microbolometer and antenna-coupled microbolometer applications. The employed multilayer synthesis technique was shown to be effective in tuning the TCR/resistivity properties of the thin films by varying the annealing conditions.

Analysis of the exome aggregation consortium (ExAC) database suggests that the BAP1-tumor predisposition syndrome is underreported in cancer patients.

The BAP1-tumor predisposition syndrome (BAP1-TPDS) has been recently identified to predispose patients to a variety of cancers and preneoplastic lesions. About 130 unrelated probands have been identified worldwide; however, the impact of the syndrome is suspected to be much larger given the diversity of the cancer phenotype. To evaluate the frequency of germline BAP1 mutations in the general and cancer populations, we analyzed the Exome Aggregation Consortium (ExAC), a database that contains 53105 exomes of unrelated individuals unaffected by cancer (general population) and exomes of 7601 unrelated individuals affected by cancer provided by the Cancer Genome Atlas (TCGA, cancer subjects). BAP1 null variants were seen at much higher frequency in the cancer subjects (0.0526%) compared to the general population (0.00188%) with a relative risk of 27.93 and (P = 0.0011, [95% CI: 3.122-249.883], Fisher's exact test). We also studied a reported BAP1 null variant, c.1203T > G, p.T401* (rs200156887), observed commonly in the general population. Sequencing and restriction fragment polymorphism of the RT-4 cell line that contains this variant revealed that it is in fact a 3bp deletion/insertion, c.1201_1203delinsGAG, a likely benign missense alteration p.Y401E explaining the relative high frequency of this variant in the general population. In conclusion, germline null mutations in BAP1 have a significantly higher frequency in cancer patients than the general population. Given the low frequency of reported families with BAP1-TPDS, our results suggest that the syndrome is underreported especially in patients with cancer.

Influences of Chlorella vulgaris dietary supplementation on growth performance, hematology, immune response and disease resistance in Oreochromis niloticus exposed to sub-lethal concentrations of penoxsulam herbicide.

Little is known regarding the impact of penoxsulam, a fluorinated benzenesulfonamid rice herbicide, on Oreochromis niloticus (O. niloticus). Therefore, the current study was undertaken to highlight the effects of penoxsulam exposure on O. niloticus and to evaluate the advantages of Chlorella vulgaris (CV) dietary supplementation against the induced effects. The 96-h lethal concentration 50 (LC50) penoxsulam value for O. niloticus was estimated at 8.948 mg/L by probit analysis in a static bioassay experiment. Next, 360 healthy fish were randomly allocated into 6 treatment groups. The T1 group served as the negative control and was fed a basal diet. The T2 group served as the positive control and was fed a basal diet supplemented with 10% CV. The fish in the T3 and T4 groups were exposed to 1/10 the 96-h LC50 of penoxsulam (0.8948 mg/L) and were fed the basal diet alone or the basal diet supplemented with 10% CV, respectively. The fish in the T5 and T6 groups were exposed to 1/5 the 96-h LC50 of penoxsulam (1.7896 mg/L) and fed the basal diet alone or the basal diet supplemented with 10% CV, respectively. Sub-acute penoxsulam exposure significantly altered hematological indices, as well as compromised the fish's immune defense mechanisms, including the phagocytic percentage, phagocytic index, nitric oxide production, immunoglobulin M levels and lysozyme, anti-trypsin and bactericidal activities subsequently decreasing O. niloticus's resistance to the Aeromonus sobria challenge and increasing disease symptoms and the mortality rate. Furthermore, sub-chronic penoxsulam exposure markedly altered growth performance, oxidant/antioxidant status and liver status and down-regulated the expression of interleukin-1ß (IL-1ß) and tumor necrosis-α (TNF-α). Interestingly, incorporating 10% CV into the diet protects fish against sub-acute penoxsulam-induced immunotoxicity via improvement of immune responses that increases the resistance against bacterial infection. Further, it improved the growth performance, oxidant/antioxidant status, liver status and markedly up-regulated immune-related gene expression, IL-1ß and TNF-α, in the spleens of fish sub-chronically exposed to penoxsulam. These outcomes showed that dietary CV supplementation can protect the commercially valuable freshwater fish O. niloticus against penoxsulam toxicity and may be a potential feed supplement for Nile tilapia in aquaculture.

AGXT2 and DDAH-1 genetic variants are highly correlated with serum ADMA and SDMA levels and with incidence of coronary artery disease in Egyptians.

Dimethylarginine aminodehydrolase (DDAH1) and alanine glyoxylate aminotransferase2 (AGXT2) are two enzymes that contribute in asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) metabolism. Hence they affect production and bioavailability of eNOS-derived nitric oxide (NO) and consequently healthy blood vessels. The major aims of the current study were to investigate the association of genetic variants of AGXT2 rs37369, AGXT2 rs16899974 and DDAH1 rs997251 SNPs with incidence of coronary artery disease (CAD) in Egyptians and to correlate these variants with the serum levels of ADMA and SDMA. The study included 150 subjects; 100 CAD patients and 50 healthy controls. Genotyping was performed by qPCR while the ADMA and SDMA concentrations were assayed by ELISA. Both serum ADMA and SDMA concentrations were significantly higher in CAD patients compared to controls (both p < 0.0001). Genotype distributions for all studied SNPs were significantly different between CAD patients and controls. Carriers of AGXT2 rs37369-T allele (CT + TT genotypes) and AGXT2 rs16899974-A allele (CA + AA genotypes) had 2.4- and 2.08-fold higher risk of having CAD than CC genotype in both SNPs (p = 0.0050 and 0.0192, respectively). DDAH1 rs997251 TC + CC genotypes were associated with 2.3-fold higher risk of CAD than TT genotype (p = 0.0063). Moreover, the AGXT2 rs37369 TT and AGXT2 rs16899974 AA genotypes were associated with the highest serum ADMA and SDMA while DDAH1 rs997251 CC genotype was associated with the highest ADMA. AGXT2 rs37369-T, AGXT2 rs16899974-A, and DDAH1 rs997251-C alleles represent independent risk factors for CAD in the Egyptians.

The prevalence of metabolic syndrome in patients receiving antipsychotics in Qatar: a cross sectional comparative study.

BACKGROUND: Metabolic abnormalities are common in patients maintained on antipsychotics. These abnormalities increase the risk of cardiovascular diseases and mortality in this population. The aim of this study is to assess the prevalence of metabolic syndrome (MetS) in subjects maintained on antipsychotics relative to controls in Qatar, and to assess the factors contributing to the development of MetS. METHODS: A cross sectional design was used to collect data and fasting blood samples from subjects maintained on antipsychotics for at least six months (n = 112) and from a control group (n = 114). The groups were compared in regard to prevalence of MetS, and multiple regression analysis was used to determine the risk factors in each group. RESULTS: The two groups (antipsychotics vs. control) were similar in regard to age (35.73 ± 10.28 vs. 35.73 ± 8.16 years) and gender ratio. The MetS was higher among the subjects on antipsychotics, but this difference did not reach statistical significance. Blood pressure (BP) was significantly higher in the antipsychotics group and BMI was the major risk factor to develop MetS in this group. CONCLUSIONS: The prevalence of MetS in both groups is high and mostly attributed to obesity and high BP. Public health interventions are needed to address this major health problem overall. Larger studies are needed to further assess the impact of antipsychotics and mental illness on the development of MetS.

Novel coumarin-6-sulfonamides as apoptotic anti-proliferative agents: synthesis, in vitro biological evaluation, and QSAR studies.

Herein, we report the synthesis of different novel sets of coumarin-6-sulfonamide derivatives bearing different functionalities (4a, b, 8a-d, 11a-d, 13a, b, and 15a-c), and in vitro evaluation of their growth inhibitory activity towards the proliferation of three cancer cell lines; HepG2 (hepatocellular carcinoma), MCF-7 (breast cancer), and Caco-2 (colon cancer). HepG2 cells were the most sensitive cells to the influence of the target coumarins. Compounds 13a and 15a emerged as the most active members against HepG2 cells (IC50 = 3.48 ± 0.28 and 5.03 ± 0.39 µM, respectively). Compounds 13a and 15a were able to induce apoptosis in HepG2 cells, as assured by the upregulation of the Bax and downregulation of the Bcl-2, besides boosting caspase-3 levels. Besides, compound 13a induced a significant increase in the percentage of cells at Pre-G1 by 6.4-folds, with concurrent significant arrest in the G2-M phase by 5.4-folds compared to control. Also, 13a displayed significant increase in the percentage of annexin V-FITC positive apoptotic cells from 1.75-13.76%. Moreover, QSAR models were established to explore the structural requirements controlling the anti-proliferative activities.

Nano-Antenna Coupled Infrared Detector Design.

Since the 1940s, infrared (IR) detection and imaging at wavelengths in the two atmospheric windows of 3 to 5 and 8 to 14 µm has been extensively researched. Through several generations, these detectors have undergone considerable developments and have found use in various applications in different fields including military, space science, medicine and engineering. For the most recently proposed generation, these detectors are required to achieve high-speed detection with spectral and polarization selectivity while operating at room temperature. Antenna coupled IR detectors appear to be the most promising candidate to achieve these requirements and has received substantial attention from research in recent years. This paper sets out to present a review of the antenna coupled IR detector family, to explore the main concepts behind the detectors as well as outline their critical and challenging design considerations. In this context, the design of both elements, the antenna and the sensor, will be presented individually followed by the challenging techniques in the impedance matching between both elements. Some hands-on fabrication techniques will then be explored. Finally, a discussion on the coupled IR detector is presented with the aim of providing some useful insights into promising future work.

Germline BAP1 alterations in familial uveal melanoma.

Uveal melanoma (UM) is the most commonly diagnosed primary intraocular tumor in adults. Familial UM (FUM), defined as two or more family members diagnosed with UM, is rare and estimated at less than 1% of all UM. Currently, BAP1 is the only gene known to contribute significant risk for UM. In this study we aimed to estimate the frequency of BAP1 mutation in FUM and to characterize the family and personal histories of other cancers in these families. We identified 32 families with FUM, including seven families previously reported by our group. BAP1 mutation testing was carried out by direct sequencing of the coding exons and the adjacent untranslated regions of the gene. Germline deletion and duplication analysis of BAP1 was assessed by multiplex ligation-dependent probe amplification (MLPA). Germline BAP1 mutations were found in 6/32 (19%) families. No deletions or duplications were identified in any of the 24 samples tested by MLPA. Combined with published studies, the frequency of BAP1 mutations was 14/64 (22%) in FUM. FUM families without BAP1 mutations have distinct family histories with high rates of prostate cancer in first- and second-degree relatives. It is likely that additional genes conferring risk for FUM exist. It is important to understand key shared features of FUM to focus future research on identifying these additional tumor predisposition syndromes. Though BAP1 should be tested first in these families, FUM families without BAP1 mutation should be explored for additional predisposition genes. © 2016 Wiley Periodicals, Inc.

Phospholipid dependent mechanism of smp24, an α-helical antimicrobial peptide from scorpion venom.

Determining the mechanism of action of antimicrobial peptides (AMPs) is critical if they are to be developed into the clinical setting. In recent years high resolution techniques such as atomic force microscopy (AFM) have increasingly been utilised to determine AMP mechanism of action on planar lipid bilayers and live bacteria. Here we present the biophysical characterisation of a prototypical AMP from the venom of the North African scorpion Scorpio maurus palmatus termed Smp24. Smp24 is an amphipathic helical peptide containing 24 residues with a charge of +3 and exhibits both antimicrobial and cytotoxic activity and we aim to elucidate the mechanism of action of this peptide on both membrane systems. Using AFM, quartz crystal microbalance-dissipation (QCM-D) and liposomal leakage assays the effect of Smp24 on prototypical synthetic prokaryotic (DOPG:DOPC) and eukaryotic (DOPE:DOPC) membranes has been determined. Our data points to a toroidal pore mechanism against the prokaryotic like membrane whilst the formation of hexagonal phase non-lamellar phase structures is seen in eukaryotic like membrane. Also, phase segregation is observed against the eukaryotic membrane and this study provides direct evidence of the same peptide having multiple mechanisms of action depending on the membrane lipid composition.