Inhibition analysis of aflatoxin by in silico targeting the thioesterase domain of polyketide synthase enzyme in Aspergillus ssp.

The spread of fungal growth causes enormous economic, agricultural, and health problems for humans, such as Aspergillus sp., which produce aflatoxins. Thus, the inhibition of aflatoxin production became a precious target. In this research, the thioesterase (TE) domain from Polyketide synthase enzyme was selected to employ the in silico docking, using AutoDock Vina, against 623 natural compounds from the South African natural compound database (SANCDB), to identify potential inhibitors that can selectively inhibit thioesterase domain. The top ten inhibitors components were pinocembrin, typhaphthalide, p-coumaroylputrescine, dilemmaone A, 9-angelylplatynecine, 2,4,6-octatrienal, 4,8-dichloro-3,7-dimethyl-, (2e,4z,6e)-, lilacinobiose, 1,3,7-octatriene, 5,6-dichloro-2-(dichloromethyl)-6-methyl-, [r*,s*-(e)]-(-)- (9ci), lilacinobiose, 1,3,7-octatriene, 5,6-dichloro-2-(dichloromethyl)-6-methyl-, [r*,s*-(e)]-(-)- (9ci), 1,3,7-octatriene, 1,5,6-trichloro-2-(dichloromethyl)-6-methyl-, [r*,s*-(z,e)] and 9-angelylhastanecine and that depending on the lowest binding energy, the best chemical interactions and the best drug-likeness. The results of those components gave successful inhibition with the thioesterase domain. So, they can be used for inhibition and controlling aflatoxin contamination of agriculture crop yields, specially, pinocembrin which gave promising results.Communicated by Ramaswamy H. Sarma.

In silico Targeting, inhibition and analysis of polyketide synthase enzyme in Aspergillus ssp.

Aflatoxins are toxic and carcinogenic components produced by some Aspergillus species such as Aspergillus flavus. Polyketide synthases enzyme (PKS) plays a central role in aflatoxin s biosynthesis of in Aspergillus flavus, especially the product template (PT) domain, which controls the aldol cyclization of the polyketide forerunner during the biosynthesis of the aflatoxin pathway process. Here, we apply the in silico approaches to validate 623 natural components obtained from the South African Natural Compound Database (SANCDB), to distinguish the PT domain s prospected inhibitors. From the 623 compounds, docking results showed that there are 330 different compounds with energy binding lower than the natural substrate (palmitic acid or PLM) of the Product Templet domain (PT). Three factors were selected to determine the best 10 inhibiting components; 1) energy binding, 2) the strengthen chemical interactions, 3) the drug-likeness. The top ten inhibiting components are kraussianone 6, kraussianone 1, neodiospyrin, clionamine D, bromotopsentin, isodiospyrin, spongotine A, kraussianone 3, 14ß-Hydroxybufa-3,5,20,22-tetraenolide and kraussianone 7. The chemical interactions between 3HRQ domain and the natural substrate in the active site amino acids are highly similar to the 3HRQ with the top ten components, but the main differences are in the binding energy which is the best in the top ten ligands. Those ten components give successful inhibition with PT domain which will lead to the formula to be used for inhibition and control aflatoxin contamination of agriculture crop yields and lessen the degree of harming and sicknesses that are coming about because of acquiring measures of aflatoxin.

Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis.

OBJECTIVES: To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. METHODS: Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmean in the tumour and normal appearing white matter was calculated for both methods. RESULTS: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmean threshold of 1201 × 10-6 mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADCratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). CONCLUSIONS: ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. KEY POINTS: • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study.

Cryptosporidium gastroenteritis in Egyptian children with acute lymphoblastic leukemia: magnitude of the problem.

PURPOSE: Cryptosporidium species is considered to be an important cause of significant morbidity in immunocompromised individuals. A prospective case-control study of sporadic diarrhea due to Cryptosporidium infection was conducted on children with acute lymphoblastic leukemia (ALL). METHODS: Forty children with ALL on maintenance chemotherapy according to the Berlin-Frankfurt-Munster (BFM-90) protocol and 45 sex- and age-matched controls were studied. The ALL group included 25 patients with acute diarrhea and 15 without diarrhea, and the control group included 30 children with acute diarrhea and 15 without. Collected stool specimens were examined using modified Ziehl-Neelsen (MZN) and modified trichrome stains. Serum Cryptosporidium Parvum immunoglobulin G (IgG) antibodies were detected by enzyme-linked immunosorbent assay. RESULTS: Cryptosporidium oocysts, pathogenic Gram-negative organisms, Giardia lamblia, and Entamoeba histolytica were identified in the stool samples (fecal specimens) of six (24%), eight (32%), four (16%), and two (8%), respectively, of the 25 patients with ALL and actute diarrhea and in one (3%), two (6.5%), six (20%), and five (16.5%), respectively, of the 30 control patients with diarrhea. Serum IgG antibodies were positive in four of the six ALL patients and in one of the control group patients with Cryptosporidium diarrhea who tested positive for oocysts in the stool. Diarrhea duration and severity were greater in ALL patients with stool-positive Cryptosporidium oocysts than in those with non-Cryptosporidium-positive diarrhea (p < 0.000). CONCLUSIONS: Cryptosporidium infection should be considered in children with ALL presenting with prolonged or severe watery diarrhea during chemotherapy, especially those treated with methotrexate and 6-mercaptopurine. Since Cryptosporidium is not routinely tested for in stool examination, a MZN stain is recommended.

Somatosensory evoked potential for detection of subclinical neuropathy in Egyptian children with acute lymphoblastic leukaemia.

To evaluate neurological changes developing during paediatric Acute Lymphoblastic Leukaemia (ALL) therapy clinically and through electrophysiological Study of Somatosensory Evoked Potentials (SSEPs) changes in different phases of therapy. Thirty five-ALL patients with age range from 3-14 years were included compared to 30 healthy controls. History, neurological examination, complete blood counts, cytological examination of bone marrow aspirate and cerebrospinal fluid with Measurement of Serum Methotrexate (MTX) were done. The SSEPs were performed and patients subjected to another SSEP with measurement of serum MTX level before and 10 days after intra-thecal injection (IMTX). Clinical neurological findings in patients after induction were depressed deep tendon reflexes (43.3%), hypotonia (28.6%), lost pain sensation (28.6%), muscle weakness (17.1%) and movement disorders (17.1%). Percentage of delayed SSEPs after induction were at levels of brachial plexus (28.6%), spinal cord (68.6%), cortical conduction (31.4%), ERB-N13 Inter Peak Latency (IPL) (74.3%) and N13-N20 IPL (17.1%) in the studied patients. Significant prolonged latency of N13 (p = 0.005), N20 (p = 0.04) and IPL of ERB-N 13 (p = 0.005), N13-N20 (p = 0.01), Inter-Side Difference (ISD) of N13 (p = 0.01), ERB-N13 (p = 0.02) and N13-N20 (p = 0.03) after induction compared to values at diagnosis. Significant positive correlation were found between serum MTX after IMTX with N13-N20 IPL (p = 0.01), N20 ISD (p = 0.03) with significant prolongation in N20 latency, N13-N20 IPL and ISD of N20 compared to values before injection. ALL patients have prolonged latency of SSEPs at cervical cord and cortical levels which increased after IMTX due to axonal injury throughout the cord. SSEPs could be an early diagnostic tool for subclinical neuropathy.

Esophageal damage during radiofrequency ablation of atrial fibrillation: impact of energy settings, lesion sets, and esophageal visualization.

INTRODUCTION: Atrioesophageal fistula is an uncommon but often lethal complication of atrial fibrillation (AF) ablation. The purpose of our study was to prospectively investigate the incidence of esophageal ulcerations (ESUL) as well as the impact of energy settings, radiofrequency lesion sets, and direct visualization of the esophagus on esophageal wall injury. METHODS AND RESULTS: One hundred seventy-five patients, 57.1% paroxysmal AF, 78.5% male, underwent AF ablation and esophagoscopy 24 hours thereafter. We performed a 2:1:1-randomization as follows: CONTROL GROUP: Ablation without visualization of the esophagus using 25 Watt (W) power limit on the posterior wall, n = 70. Visualization and 15 W maximum: Ablation guided by barium visualization of the esophageal course using a limit of 15 W, n = 35. Visualization and 25 W "short burns": Ablation guided by barium visualization using 25 W and "short burns" (max. 5 sec), n = 35. Patients performed under general anesthesia (n = 35) were separated as a nasogastric tube for visualization of the esophagus was used. In total, we found 2.9% of patients (5/175) presenting ESUL. Parameters discriminating the development of ESUL in a specific patient were type of AF, maximum energy delivered, usage of a nasogastric tube, and additional left atrial lines. Visualization of the esophageal course by barium contrast was not able to prevent ESUL. CONCLUSION: ESUL is a rare finding when using a reasonable energy maximum of 25 W with open-irrigated tip catheters at the posterior wall. Lower energy settings may increase safety without losing efficacy. Additional linear radiofrequency lesions increase the risk of ESUL development.

Relationship between organizational climate and empowerment of nurses in Menoufiya hospitals, Egypt.

One factor influencing the outcome of care may be the nursing staffs experience of organizational work climate. We compared organizational climate and nurse's empowerment in specialty units at 2 hospitals in Egypt. Data were collected from 164 diploma school staff nurses using 2 tools: the situational outlook questionnaire to assess organizational climate and the psychological empowerment in the workplace questionnaire. There was no statistically significant difference in the level of organizational climate between the 2 hospitals, which the majority of nurses classified as moderate. Most nurses reported a moderate level of empowerment in both hospitals and there was a statistically significant positive correlation between organizational climate and nurse's empowerment.

Relationship between organizational climate and empowerment of nurses in Menoufiya hospitals, Egypt

One factor influencing the outcome of care may be the nursing staff's experience of organizational work climate. We compared organizational climate and nurse's empowerment in specialty units at 2 hospitals in Egypt. Data were collected from 164 diploma school staff nurses using 2 tools: the situational outlook questionnaire to assess organizational climate and the psychological empowerment in the workplace questionnaire. There was no statistically significant difference in the level of organizational climate between the 2 hospitals, which the majority of nurses classified as moderate. Most nurses reported a moderate level of empowerment in both hospitals and there was a statistically significant positive correlation between organizational climate and nurse's empowerment

Effect of two single doses of ivermectin in treatment of asymptomatic bancroftian filariasis in two villages in the Nile Delta, Egypt.

To evaluate the efficacy and longitudinal effect of two single (100 micrograms/kg) doses of ivermectin, 3 months apart, 240 asymptomatic male subjects from 2 endemic Egyptian villages were enrolled in a one-year double-blind study. Subjects aged 15-55 years were randomly assigned placebo (40) or ivermectin (200). Microfilaria (MF) density in 1 ml blood was measured by membrane filtration before and every 3 months after treatment. Initial mean MF density was 462 (range 14-2869/ml). Clinical examination performed daily for 3 days after each treatment revealed brief, mild side effects: fever, headache, weakness, nausea, and epigastric pain, with no adverse physical or laboratory findings. Three months after initial dose, 31% of MF counts had completely cleared; in the remainder, mean MF density was 11.0 (2.4% of pretreatment level). At 3, 6 and 9 months after the second dose there was complete MF clearance in 60%, 45% and 47%; in those still infected, MF densities were 1.7, 4.6 and 6.1% of the pretreatment level. Therefore, treatment with two doses of ivermectin reduced microfilaremia, without inducing severe side effects. Prolonged suppression of microfilaremia may indicate an effect of ivermectin on the adult worms and may reduce the potential for MF acquisition by mosquitoes, reducing transmission of lymphatic filariasis. It was concluded that ivermectin is a useful drug for public health measure, including asymptomatic filariasis patients.

Occurrence of keratinolytic fungi and related dermatophytes in soils in Cairo, Egypt.

120 soil samples collected from various sites of Cairo were processed for the isolation of keratinophilic fungi by "ToKaVa" hair baiting technique. 22 species belonging to 6 genera were isolated viz.: Chrysosporium tropicum, C. indicum, C. keratinophilum, C. queenslandicum, C. merdarium, C. anamorph of Arthroderma curreyi, C. pannicola, C. lobatum, C. anamorph of Renispora flavissima, C. pseudomerdarium, Microascus mangini, Malbranchea gypsea, Ml. State of Uncicarpus reesii, Ml. State of Coccidioides immitis, Microsporum gypseum, Mr. distortum Mr. audouinii, Mr. fulvum, Trichophyton mentagrophytes, T. terrestre, T. verrucosum and Epidermophyton floccosum. The frequency of occurrence of the isolated fungi was determined. Microsporum gypseum, Chrysosporium tropicum and Chrysosporium indicum were the most frequent species recovered from soil. Most species of keratinophilic fungi were isolated from university, public garden and zoo garden. The distribution of the isolates are discussed.

On the shortage of registered nurses: an economic analysis of the RN market.

Hassanein gives us an economist's view of the nursing shortage as well as new ways to perceive it. Nursing supply and demand are examined as they interplay with various other factors including physician supply.

A new direct lead technique for histochemical demonstration of alkaline phosphatase activity.

A lead method for demonstrating alkaline phosphatase is described. The method is based on direct precipitation of lead as lead phosphatase at pH 9.5, the pH optimum of the enzyme. Stable incubation medium was achieved by using tartrate, instead of maleate, as chelating for lead. The method was found to be suitable for visualization of alkaline phosphatase in different types of tissues.