Oleaginous fungi: a promising source of biofuels and nutraceuticals with enhanced lipid production strategies.

Oleaginous fungi have attracted a great deal of interest for their potency to accumulate high amounts of lipids (more than 20% of biomass dry weight) and polyunsaturated fatty acids (PUFAs), which have a variety of industrial and biological applications. Lipids of plant and animal origin are related to some restrictions and thus lead to attention towards oleaginous microorganisms as reliable substitute resources. Lipids are traditionally biosynthesized intra-cellularly and involved in the building structure of a variety of cellular compartments. In oleaginous fungi, under certain conditions of elevated carbon ratio and decreased nitrogen in the growth medium, a change in metabolic pathway occurred by switching the whole central carbon metabolism to fatty acid anabolism, which subsequently resulted in high lipid accumulation. The present review illustrates the bio-lipid structure, fatty acid classes and biosynthesis within oleaginous fungi with certain key enzymes, and the advantages of oleaginous fungi over other lipid bio-sources. Qualitative and quantitative techniques for detecting the lipid accumulation capability of oleaginous microbes including visual, and analytical (convenient and non-convenient) were debated. Factors affecting lipid production, and different approaches followed to enhance the lipid content in oleaginous yeasts and fungi, including optimization, utilization of cost-effective wastes, co-culturing, as well as metabolic and genetic engineering, were discussed. A better understanding of the oleaginous fungi regarding screening, detection, and maximization of lipid content using different strategies could help to discover new potent oleaginous isolates, exploit and recycle low-cost wastes, and improve the efficiency of bio-lipids cumulation with biotechnological significance.

In Vitro and In Silico Antioxidant Efficiency of Bio-Potent Secondary Metabolites From Different Taxa of Black Seed-Producing Plants and Their Derived Mycoendophytes.

Oxidative stress is involved in the pathophysiology of multiple health complications, and it has become a major focus in targeted research fields. As known, black seeds are rich sources of bio-active compounds and widely used to promote human health due to their excellent medicinal and pharmaceutical properties. The present study investigated the antioxidant potency of various black seeds from plants and their derived mycoendophytes, and determined the total phenolic and flavonoid contents in different extracts, followed by characterization of major constituents by HPLC analysis. Finally, in silico docking determined their binding affinities to target myeloperoxidase enzymes. Ten dominant mycoendophytes were isolated from different black seed plants. Three isolates were then selected based on high antiradical potency and further identified by ITS ribosomal gene sequencing. Those isolated were Aspergillus niger TU 62, Chaetomium madrasense AUMC14830, and Rhizopus oryzae AUMC14823. Nigella sativa seeds and their corresponding endophyte A. niger had the highest content of phenolics in their n-butanol extracts (28.50 and 24.43 mg/g), flavonoids (15.02 and 11.45 mg/g), and antioxidant activities (90.48 and 81.48%), respectively, followed by Dodonaea viscosa and Portulaca oleracea along with their mycoendophytic R. oryzae and C. madrasense. Significant positive correlations were found between total phenolics, flavonoids, and the antioxidant activities of different tested extracts. The n-butanol extracts of both black seeds and their derived mycoendophytes showed reasonable IC50 values (0.81-1.44 mg/ml) compared to the control with significant correlations among their phytochemical contents. Overall, seventeen standard phenolics and flavonoids were used, and the compounds were detected in different degrees of existence and concentration in the examined extracts through HPLC analysis. Moreover, the investigation of the molecular simulation results of detected compounds against the myeloperoxidase enzyme revealed that, as a targeted antioxidant, rutin possessed a high affinity (-15.3184 kcal/mol) as an inhibitor. Taken together, the black seeds and their derived mycoendophytes are promising bio-prospects for the broad industrial sector of antioxidants with several valuable potential pharmaceutical and nutritional applications.

Testing the reproducibility and robustness of the cancer biology literature by robot.

Scientific results should not just be 'repeatable' (replicable in the same laboratory under identical conditions), but also 'reproducible' (replicable in other laboratories under similar conditions). Results should also, if possible, be 'robust' (replicable under a wide range of conditions). The reproducibility and robustness of only a small fraction of published biomedical results has been tested; furthermore, when reproducibility is tested, it is often not found. This situation is termed 'the reproducibility crisis', and it is one the most important issues facing biomedicine. This crisis would be solved if it were possible to automate reproducibility testing. Here, we describe the semi-automated testing for reproducibility and robustness of simple statements (propositions) about cancer cell biology automatically extracted from the literature. From 12 260 papers, we automatically extracted statements predicted to describe experimental results regarding a change of gene expression in response to drug treatment in breast cancer, from these we selected 74 statements of high biomedical interest. To test the reproducibility of these statements, two different teams used the laboratory automation system Eve and two breast cancer cell lines (MCF7 and MDA-MB-231). Statistically significant evidence for repeatability was found for 43 statements, and significant evidence for reproducibility/robustness in 22 statements. In two cases, the automation made serendipitous discoveries. The reproduced/robust knowledge provides significant insight into cancer. We conclude that semi-automated reproducibility testing is currently achievable, that it could be scaled up to generate a substantive source of reliable knowledge and that automation has the potential to mitigate the reproducibility crisis.

Adaptive method for multicriteria optimization of intensity-modulated proton therapy.

PURPOSE: Provide an adaptive multicriteria optimization (MCO) method for intensity-modulated proton therapy (IMPT) utilizing GPU technology. Previously described limitations of MCO such as Pareto approximation and limitation on the number of objectives were addressed. METHODS: The treatment planning process for IMPT must account for multiple objectives, which requires extensive treatment planning resources. Often a large number of objectives (>10) are required. Hence the need for an MCO algorithm that can handle large number of objectives. The novelty of the MCO method presented here lies on the introduction of the adaptive weighting scheme that can generate a well-distributed and dense representation of the Pareto surface for a large number of objectives in an efficient manner. In our approach the generated Pareto surface is constructed for a set of DVH objectives. The MCO algorithm is based on the augmented weighted Chebychev metric (AWCM) method with an adaptive weighting scheme. This scheme uses the differential evolution (DE) method to generate a set of well-distributed Pareto points. The quality of the Pareto points' distribution in the objective space was assessed quantitatively using the Pareto sampling metric. The MCO algorithm was developed to perform multiple parallel searches to achieve a rapid mapping of the Pareto surface, produce clinically deliverable plans, and was implemented on a GPU cluster. The MCO algorithm was tested on two clinical cases with 10 and 18 objectives. For each case one of the MCO-generated plans was selected for comparison with the clinically generated plan. The MCO plan was randomly selected out of the set of MCO plans that had target coverage similar to the clinically generated plan and the same or better sparing of the organs at risk (OAR). Additionally, a validation study of the AWCM method vs the weighted sum method was performed. RESULTS: The adaptive MCO algorithm generated Pareto points on the Pareto hypersurface in a fast (2-3 hr) and efficient manner for 2 cases with 10 and 18 objectives. The MCO algorithm generated a dense and well-distributed set of Pareto points on the objective space, and was able to achieve minimization of the Pareto sampling metric. The selected MCO plan showed an improvement of the DVH objectives in comparison to the clinically optimized plan in both cases. For case one, the MCO plan showed a 48% reduction of the 50% dose to OARs and a 16% reduction of the 1% dose to OARs. For case 2, the MCO plan showed a 72% reduction of the 50% dose to OARs and a 42% reduction of the 1% dose to OARs. The comparison of AWCM to WS showed that the AWCM method has a dosimetric advantage over WS for both patient cases. CONCLUSION: We introduced an adaptive MCO algorithm for IMPT accelerated using GPUs. The algorithm is based on an adaptive method for generating Pareto plans in the objective space. We have shown that the algorithm can provide rapid and efficient mapping of the multicriteria Pareto surface with clinically deliverable plans.

Impact of allergy on children with attention deficit hyperactivity disorder.

Summary: Background. Attention deficit hyperactivity disorder (ADHD) is commonly present worldwide, causing serious problems to those affected. ADHD was suggested to be secondary to allergic disorder or its medication. Both ADHD and allergy depend on complex environmental and genetic interaction, and they meet the hypersensitivity criteria. Objective. Detect the percentage of allergy in ADHD children, the common allergic disorders and allergens, and the effect of allergy on symptom and severity of ADHD. Material and methods. 100 children with ADHD were subjected to psychiatric assessment for ADHD type and severity, history of allergy, skin prick test to common environmental allergens, serum total IgE levels and open food challenge. Co-morbid neuropsychiatric disorders, below average intelligence quotient (IQ), and chronic illnesses were excluded. A control of 60 healthy children was chosen to compare the results of skin prick test and serum total IgE levels. Results. 35 ADHD children (35%) were allergic. Most cases had combined allergic rhinitis and bronchial asthma (25%). Common allergens were hay dust (43%) followed by different pollens (37.5%). There were statistical significant differences between coexistence of allergy, type of ADHD, early onset and severity of symptoms. Conclusion. Children with ADHD had an increased prevalence of allergic diseases. Evaluation of allergy in ADHD is mandatory, to decrease the burden of the condition.

Fecal microbiota profile in atopic asthmatic adult patients.

Summary: Background. Studies proposed a link between gut microbiota and airway tract. Objective. Study the diversity and density of gut microbiota in healthy and asthmatic patients. Method. Semi-quantitative stool cultures were performed from fecal samples collected from 80 adult asthmatic patients and 40 healthy individuals. Data on gender, age, dietetic history, clinical examination and investigations as skin prick test and pulmonary function testing were also collected. Results.Lactobacilli were found to be higher among patient group than control group. E. coli density was statistically higher in patient than control group. No significant difference was detected between male and female patients or controls. Lactobacilli were statistically more prevalent in stool culture of male cases than that of male controls. No difference was found between female cases and controls. There was no relationship between type of microbial growth and disease related parameters including age, duration of illness, number of allergens and pulmonary function test in cases. Conclusion. Atopic asthma is significantly associated with gut microbiota Lactobacilli and E. coli. It is important to determine the organism involved, to focus on microbiome-driven disease and therapies.

Direct Evaluation of the Quark Content of Nucleons from Lattice QCD at the Physical Point.

We evaluate the light, strange, and charm scalar content of the nucleon using one lattice QCD ensemble generated with two degenerate light quarks with mass fixed to their physical value. We use improved techniques to evaluate the disconnected quark loops to sufficient accuracy to determine the strange and charm nucleon σ terms in addition to the light quark content σ_{πN}. We find σ_{πN}=37.2(2.6)(4.7/2.9) MeV, σ_{s}=41.1(8.2)(7.8/5.8) MeV, and σ_{c}=79(21)(12/8) MeV, where the first error is statistical and the second is the systematic error due to the determination of the lattice spacing, the assessment of finite volume, and residual excited state effects.

Prevalence of diabetic foot disorders and related risk factors among Egyptian subjects with diabetes.

INTRODUCTION: Multiple pathologies including diabetic neuropathy, peripheral vascular disease (PVD) and infection contribute to lower extremities amputation in diabetes. AIM: We examined the prevalence of diabetic foot problems and related risk factors in Egypt. SUBJECTS AND METHODS: Between July 2008 and December 2009, 1000 male and 1000 female consecutive adult patients with diabetes (≥ 18-year-old) attending the Alexandria University Diabetic Foot Screening Clinic were surveyed for history/presence of foot ulcers and/or amputations, skin/nail changes, joint mobility, sensory neuropathy (10 g-Semmes-Weinstein Monofilament) and peripheral vascular disease (PVD) using Ankle Brachial Index (ABI). RESULTS: The majority of patients had type 2 diabetes (96.75%) with a mean age of 57.30 ± 10.47 years and a mean disease duration of 11.76 ± 8.26 years. The mean body mass index was 32.84 ± 6.31 kg/m(2) with 29.55% being current or ex-smokers. In these subjects, 4.4% had a past history of non-traumatic amputation (male:female: 6.2% vs. 2.6%, p < 0.001); 6.1% had past history (10.3% vs. 7%, p = 0.009) and 8.7% had active foot ulceration (8.1% vs. 4.1% p < 0.001) with a male preponderance. The prevalence of sensory neuropathy was 29.3% (M:F: 30.7%: 27.9%) and peripheral vascular disease (PVD) was 11% (M:F 11.8%:10.2%). Diabetic foot complications were associated with disease duration (p < 0.001), history of coronary artery disease (p = 0.001), stroke (p = 0.009), PVD (p < 0.001), laser photocoagulation (p < 0.001), sensory neuropathy (p < 0.001) and renal replacement therapy (p < 0.001). On multivariate analysis, diabetes duration, foot fissures, Charcot's foot, limited joint mobility, PVD and sensory neuropathy remained independently associated with diabetic foot disorders. CONCLUSION: In Egypt, a mosaic of risk factors contributes to the high prevalence of diabetic foot disease in type 2 diabetes. These findings call for regular assessment of vascular, neuropathic and skin status to prevent these serious foot complications.

Centralized Pan-Middle East Survey on the Under-Treatment of Hypercholesterolemia: Results from the CEPHEUS Study in Egypt.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality; however, the risks associated with this disease can be reduced by targeting circulating low-density lipoprotein cholesterol (LDL-C) with lipid-lowering drugs, as recommended in many treatment guidelines. Their effectiveness for hypercholesterolemia management depends on appropriate use in at-risk patients. Observational studies have shown varying adherence to national and international guidelines on reaching LDL-C treatment goals. METHODS: The Centralized Pan-Middle East Survey on the under-treatment of hypercholesterolemia (CEPHEUS) study observed the current management of hypercholesterolemia in patients on lipid-lowering drugs in seven Middle Eastern countries, and results from 1,043 patients in Egypt are presented here. RESULTS: Overall, less than 50% of patients achieved their LDL-C treatment goal, with patients at higher risk of a cardiovascular event being less likely to attain their target. Nearly, three-quarters of patients in this study were considered high or very high risk, with only 10% of high-risk patients reaching their treatment goal. CONCLUSIONS: Management of hypercholesterolemia in Egypt is comparatively worse than the average for similar countries in the region, and many patients with high risk of CVD are not being effectively treated. Initiatives to improve physicians' management of these patients and patient compliance to treatment are urgently needed. FUNDING: AstraZeneca, Cairo, Egypt.

Formulation of microemulsion gel systems for transdermal delivery of celecoxib: In vitro permeation, anti-inflammatory activity and skin irritation tests.

The aim of this study was to develop suitable microemulsion gel systems for transdermal delivery that could assist dissolution enhancement of poorly water soluble celecoxib and thus improve its skin permeability. Long term oral administration of celecoxib causes serious gastrointestinal adverse effects, which makes it a good candidate for transdermal formulations, yet its low water solubility (4 mg/L) makes this challenging. Ternary phase diagrams were constructed using isopropyl myristate and oleic acid as oils, Tween 80 as surfactant, and Cremophor RH40 as cosurfactant. Microemulsion areas were identified and two systems each of 36 formulas were prepared and assessed for visual inspection, spreadability, pH measurements, and droplet size analysis. Drug release and in vitro permeation of celecoxib from microemulsion formulas through semi-permeable membranes and excised abdominal rabbit skin, respectively, were carried out and compared to celecoxib cream. In all tested formulas, celecoxib was released and permeation was at a higher rate than that from the corresponding cream. The optimized formula (F12) was found to be superior to all other formulas. This formula increased the permeation rate of celecoxib up to 11 times compared to that of the cream. Its stability was retained after one year of storage under ambient conditions and its anti-inflammatory effect was significantly higher than that of celecoxib cream and the oral commercial formula. Skin irritancy and histopathological investigation of rat skin revealed its safety. The results revealed that the developed microemulsion gel has great potential for transdermal delivery of celecoxib.