Study of nonstandard auto-antibodies as prognostic markers in auto immune hepatitis in children

<p>Abstract</p> <p>Background</p> <p>Antibodies to chromatin and soluble liver antigen have been associated with severe form of autoimmune hepatitis and/or poor treatment response and may provide guidance in defining subsets of patients with different disease behaviors. The major clinical limitation of these antibodies is their lower individual occurrence in patients with autoimmune hepatitis.</p> <p>Aim</p> <p>To estimate the value of detection of these non-standard antibodies in autoimmune hepatitis as prognostic markers.</p> <p>Methods</p> <p>Both antibodies were tested by enzyme immunoassay in 20 patients with autoimmune hepatitis.</p> <p>Results</p> <p>Antibodies to soluble liver antigen were not detected in any of our patients. On the other hand anti chromatin antibodies were present in 50% (10/20). Antibodies to chromatin occurred more commonly in females than males (8/14 versus 2/6). Of the 14 patients who relapsed 8(57%) had antichromatin antibodies while they were present in only 2 out of 6(33.3%) non relapsers. Antichromatin antibodies were found more in patients with antinuclear (3/4) and anti smooth muscle antibodies (9/13) more than in those with liver kidney microsomal antibodies (1/4) and those seronegative (1/4) i.e. they were +ve in patients with type I (8/12(66.6%)) more than those with type II (1/4(25%)) and those seronegative (1/4(25%)). Antibodies to chromatin are associated with high levels of γ globulin but yet with no statistical difference between seropositive and seronegative counterparts (p = 0.65).</p> <p>Conclusion</p> <p>Antibodies to chromatin may be superior than those to soluble liver antigen in predicting relapse and may be useful as prognostic marker. Further studies with larger number of patients and combined testing of more than one antibody will improve the performance parameters of these antibodies and define optimal testing conditions for them before they can be incorporated into management algorithms that project prognosis.</p

Soil resources and potential for agricultural development in Bahr El Jebel in southern Sudan, Jonglei Canal project area

The author has identified the following significant results. Fourteen LANDSAT scenes were used to produce mosaics of the 167, 474 sq km study area. These were black and white MSS 7 images and false color composite images. Five major soil-landscape units were delineated on the mosaics, and these were subdivided into a total of 40 soil mapping units. Aerial reconnaissance was useful in defining boundaries between mapping units and in estimating the proportion of the various soils which composed each mapping unit. Ground surveying permitted first-hand observation of major soils and sampling for quantitative laboratory analysis. Soil interpretations were made, including properties, potentials, and limitations

Hydroxychloroquine enhances anticancer effect of DOX/folate-phytosterol-carboxymethyl cellulose nanoparticles in A549 lung cancer cells

Purpose: To study the in vitro anticancer effect of doxorubicin-loaded folate-phytosterol-carboxymethyl cellulose nanoparticles (DOX/FPCMC NPs), alone and in combination with the antimalarial drug hydroxychloroquine (HCQ) on human lung cancer cells (A549 cells). Methods: Human lung adenocarcinoma A549 cell line was treated with blank FPCMC NPs, HCQ, free DOX, DOX/FPCMC NPs, free DOX + HCQ or DOX/FPCMC NPs + HCQ. The concentrations of HCQ, DOX and FPCMC NPs varied within the ranges of 20-120 μmol/L, 2-12 mg/L and 50-500 mg/L, respectively. Cell viability and free folate competitive inhibition were determined using MTT assay. Cell proliferation and migration were investigated with wound healing assay, while confocal laser scanning microscopy (CLSM) was used to determine cellular uptake of drugs. Results: In all formulations, the DOX/FPCMC NPs + HCQ produced the highest cytotoxicity in A549 cells due to high cytotoxicity arising from folate-receptor-mediated endocytosis and HCQ-induced inhibition of autophagy. Free folate competitively inhibited the cytotoxicity of DOX/FPCMC NPs on A549 cells. Wound healing assay showed that A549 cells treated with DOX/FPCMC NPs + HCQ had the lowest cell levels of proliferation and migration capacity. The cellular uptake of DOX/FPCMC NPs by A549 cells was higher than that of free DOX. Conclusion: The combination of DOX/FPCMC NPs and HCQ produced the best antitumor effect and had a promising potential for reversal of MDR Keywords: Folate-phytosterol-carboxymethyl cellulose, Doxorubicin, Hydroxychloroquine, Anticancer, Lung cance

Guidelines for data collection on energy performance of higher-education buildings in Egypt: a case study

Reliable energy analysis of buildings relies heavily on high-quality data leading to proper indicators. Previous studies have highlighted the importance of data quality in analyzing energy usage in residential and non-residential buildings in order to transform declarations to actions, optimise energy efficiency policies and monitor progress and failures in countries. Collected data must adhere to national and international standards for energy performance in buildings. This study aims to provide practical guidelines for effectively collecting and preparing data suitable for evaluating energy performance in Egyptian higher-education (HE) buildings. The guidelines are developed based on a comprehensive case study, considering data availability in typical educational facilities. Architectural and civil engineering drawings, construction specifications, and occupancy details are accessible. However, actual monthly electrical and natural gas consumption data for individual buildings are lacking. To address this, the study proposes the creation of detailed datasheets for each building, encompassing all energy sources and their electrical and power specifications, such as equipment, machinery, and HVAC systems. These datasheets were utilized to calculate energy consumption and energy usage indicators (EUI). The findings demonstrate that the datasheets enable adequate assessment of energy usage in various spaces within educational buildings, including staff rooms, lecture halls, and laboratories. This facilitates the identification of areas in need of targeted energy efficiency improvements. Notably, the study reveals that electricity consumption in the Faculty of Engineering building is significantly influenced by PCs, laboratories, lighting, and air conditioning

Interpretation of multispectral and infrared thermal surveys of the Suez Canal Zone, Egypt

Remote sensing airborne surveys were conducted, as part of the plan of rehabilitation, of the Suez Canal Zone using I2S multispectral camera and Bendix LN-3 infrared passive scanner. The multispectral camera gives four separate photographs for the same scene in the blue, green, red, and near infrared bands. The scanner was operated in the microwave bands of 8 to 14 microns and the thermal surveying was carried out both at night and in the day time. The surveys, coupled with intensive ground investigations, were utilized in the construction of new geological, structural lineation and drainage maps for the Suez Canal Zone on a scale of approximately 1:20,000, which are superior to the maps made by normal aerial photography. A considerable number of anomalies belonging to various types were revealed through the interpretation of the executed multispectral and infrared thermal surveys

Probing the Water Stability Limits and Degradation Pathways of Metal-Organic Frameworks (MOFs)

A comprehensive model to describe the water stability of prototypical metal–organic frameworks (MOFs) is derived by combining different types of theoretical and experimental approaches. The results provide an insight into the early stages of water-triggered destabilization of MOFs and allow detailed pathways to be proposed for the degradation of different MOFs under aqueous conditions. The essential elements of the approach are computing the pKa values of coordinated water molecules and geometry relaxations. Variable-temperature and pH infrared spectroscopy techniques are used to corroborate the main findings. The model developed herein helps to explain stability limits observed for several prototypical MOFs, including MOF-5, HKUST-1, UiO-66, and MIL-101-Cr, in aqueous solutions, and thus, provides an insight into the possible degradation pathways in acidic and basic environments. The formation of a metal hydroxide through the autoprotolysis of metal-coordinated water molecules and the strength of carboxylate–metal interactions are suggested to be two key players that govern stability in basic and acidic media, respectively. The methodology presented herein can effectively guide future efforts, which are especially significant for in silico screening, for developing novel MOFs with enhanced aqueous stability

The BET inhibitor/degrader ARV-825 prolongs the growth arrest response to Fulvestrant + Palbociclib and suppresses proliferative recovery in ER-positive breast cancer

Anti-estrogens or aromatase inhibitors in combination with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are the current standard of care for estrogen receptor-positive (ER+) Her-2 negative metastatic breast cancer. Although these combination therapies prolong progression-free survival compared to endocrine therapy alone, the growth-arrested state of residual tumor cells is clearly transient. Tumor cells that escape what might be considered a dormant or quiescent state and regain proliferative capacity often acquire resistance to further therapies. Our studies are based upon the observation that breast tumor cells arrested by Fulvestrant + Palbociclib enter into states of both autophagy and senescence from which a subpopulation ultimately escapes, potentially contributing to recurrent disease. Autophagy inhibition utilizing pharmacologic or genetic approaches only moderately enhanced the response to Fulvestrant + Palbociclib in ER+ MCF-7 breast tumor cells, slightly delaying proliferative recovery. In contrast, the BET inhibitor/degrader, ARV-825, prolonged the growth arrested state in both p53 wild type MCF-7 cells and p53 mutant T-47D cells and significantly delayed proliferative recovery. In addition, ARV-825 added after the Fulvestrant + Palbociclib combination promoted apoptosis and demonstrated efficacy in resistant RB deficient cell lines. These studies indicate that administration of BET inhibitors/degraders, which are currently being investigated in multiple clinical trials, may potentially improve standard of care therapy in metastatic ER+ breast cancer patients and may further prolong progression-free survival

In silico and in vivo evaluation of the anti-cryptosporidial activity of eugenol

BackgroundCryptosporidiosis is an opportunistic parasitic disease widely distributed worldwide. Although Cryptosporidium sp. causes asymptomatic infection in healthy people, it may lead to severe illness in immunocompromised individuals. Limited effective therapeutic alternatives are available against cryptosporidiosis in this category of patients. So, there is an urgent need for therapeutic alternatives for cryptosporidiosis. Recently, the potential uses of Eugenol (EUG) have been considered a promising novel treatment for bacterial and parasitic infections. Consequently, it is suggested to investigate the effect of EUG as an option for the treatment of cryptosporidiosis.Materials and methodsThe in silico bioinformatics analysis was used to predict and determine the binding affinities and intermolecular interactions of EUG and Nitazoxanide (NTZ) toward several Cryptosporidium parvum (C. parvum) lowa II target proteins. For animal study, five groups of immunosuppressed Swiss albino mice (10 mice each) were used. Group I was left uninfected (control), and four groups were infected with 1,000 oocysts of Cryptosporidium sp. The first infected group was left untreated. The remaining three infected groups received NTZ, EUG, and EUG + NTZ, respectively, on the 6th day post-infection (dpi). All mice were sacrificed 30 dpi. The efficacy of the used formulas was assessed by counting the number of C. parvum oocysts excreted in stool of infected mice, histopathological examination of the ileum and liver tissues and determination of the expression of iNOS in the ileum of mice in different animal groups.Resultstreatment with EUG resulted in a significant reduction in the number of oocysts secreted in stool when compared to infected untreated mice. In addition, oocyst excretion was significantly reduced in mice received a combination therapy of EUG and NTZ when compared with those received NTZ alone. EUG succeeded in reverting the histopathological alterations induced by Cryptosporidium infection either alone or in combination with NTZ. Moreover, mice received EUG showed marked reduction of the expression of iNOS in ileal tissues.ConclusionBased on the results, the present study signified a basis for utilizing EUG as an affordable, safe, and alternative therapy combined with NTZ in the management of cryptosporidiosis