The antiproliferative effect of mulberry (Morus alba L.) plant on hepatocarcinoma cell line HepG2

This study aimed to investigate the antiproliferative effect of aqueous and organic extracts of mulberry leaves (Morus Alba L.) on human hepatocellular carcinoma HepG2 cell line. Mulberry leaf extracts were prepared using the solvents: water, 50% aqueous MeOH, and 100% MeOH for different time intervals, while the cells treated with dimethyl sulfoxide (DMSO) served as control. The effects of aqueous and organic extracts of M. alba L. leaves on HepG2 cell viability, nuclear factor kappa B (NF-κB) gene expression, alfa-fetoprotein (AFP), albumin (ALB), gammaglutamyl transpeptidase (γ-GT) and alkaline phosphatase (ALP) were measured. The results of the cell viability assays showed that water, 50% aqueous MeOH, and 100% MeOH extracts exhibited a highly significant inhibitory effect on HepG2 cell proliferation which was evidenced by a reduction in viable cell count. The results were confirmed by microscopical examination of cell morphology. Furthermore, the mulberry leaf extracts suppressed the activity of NF-κB gene expression of HepG2 cells compared to the control. Also a highly significant depression occurred at the levels of AFP, γ-GT and ALP in HepG2 cells compared with that of controls in a time dependent manner. By contrast, the mulberry leaf extracts increased the secretion of ALB. Therefore, the conclusion was that the organic and aqueous extracts of mulberry leaves inhibit the growth of HepG2 cells through suppressing the activity of NF-κB gene expression and modulate the biochemical markers.Keywords: HepG2 cell line; Morus alba L.; NF-κB; Antiproliferative effect; Alfa-fetoprotei

Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome overwhelmingly progresses to ESRD. More than 30 monogenic genes have been identified to cause steroid-resistant nephrotic syndrome. We previously detected causative mutations using targeted panel sequencing in 30% of patients with steroid-resistant nephrotic syndrome. Panel sequencing has a number of limitations when compared with whole exome sequencing. We employed whole exome sequencing to detect monogenic causes of steroid-resistant nephrotic syndrome in an international cohort of 300 families. DESIGN, SETTING, PARTIIPANTS AND MEASUREMENTS: Three hundred thirty-five individuals with steroid-resistant nephrotic syndrome from 300 families were recruited from April of 1998 to June of 2016. Age of onset was restricted to <25 years of age. Exome data were evaluated for 33 known monogenic steroid-resistant nephrotic syndrome genes. RESULTS: In 74 of 300 families (25%), we identified a causative mutation in one of 20 genes known to cause steroid-resistant nephrotic syndrome. In 11 families (3.7%), we detected a mutation in a gene that causes a phenocopy of steroid-resistant nephrotic syndrome. This is consistent with our previously published identification of mutations using a panel approach. We detected a causative mutation in a known steroid-resistant nephrotic syndrome gene in 38% of consanguineous families and in 13% of nonconsanguineous families, and 48% of children with congenital nephrotic syndrome. A total of 68 different mutations were detected in 20 of 33 steroid-resistant nephrotic syndrome genes. Fifteen of these mutations were novel. NPHS1, PLCE1, NPHS2, and SMARCAL1 were the most common genes in which we detected a mutation. In another 28% of families, we detected mutations in one or more candidate genes for steroid-resistant nephrotic syndrome. CONCLUSIONS: Whole exome sequencing is a sensitive approach toward diagnosis of monogenic causes of steroid-resistant nephrotic syndrome. A molecular genetic diagnosis of steroid-resistant nephrotic syndrome may have important consequences for the management of treatment and kidney transplantation in steroid-resistant nephrotic syndrome

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Potential immunotherapeutic role of interleukin-2 and interleukin-12 combination in patients with hepatocellular carcinoma

Abdulwahab Ali Gabeen,1 Fatma Farag Abdel-Hamid,1 Motawa Eisa El-Houseini,2 Shadia Abdel-Hamid Fathy1 1Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt; 2Cancer Biology Department, National Cancer Institute (NCI), Cairo University, Cairo, Egypt Background: Many recent therapeutic interventions are necessary to improve the treatment of hepatocellular carcinoma (HCC), including immunotherapy, which seems to offer one of the new realistic therapeutic modalities. This study aims to investigate the optimization of immunotherapy for HCC patients by appraisal of both interferon (IFN)-&gamma; levels and phenotyping of lymphocytes obtained from peripheral blood and fine-needle aspirates. Methods: The isolated lymphocytes were cultured in the presence of interleukins (IL)-2, IL-4, and IL-12. Enzyme-linked immunosorbent assay and flow cytometric techniques were used for the assessment of human IFN-&gamma; production and the studied T-cell subpopulations, respectively. Results: Mixed cell populations of peripheral blood lymphocytes and tumor infiltrating lymphocytes treated with IL-2 plus IL-12 showed a marked and significant elevation in IFN-&gamma; levels in their culture media, a significant decrease in the percentage of cluster of differentiation (CD)4+CD25+ regulatory T-cells, and a nonsignificant increase in the percentage of CD8+ cytotoxic T-cells. Meanwhile, IL-2 plus IL-4 treatment demonstrated nonsignificant effects. Conclusion: Our data suggested that IL-12 together with IL-2 caused a suppression of CD4+CD25+ regulatory T-cells and an elevation of IFN-&gamma; levels, which play a crucial immunotherapeutic role in the management of HCC patients. Keywords: HCC, immunotherapy, fine-needle aspirates, tumor infiltrating lymphocytes, interferon-gamma, interleukin

A Novel Indexing Method for Scalable IoT Source Lookup

When dealing with a large number of devices, the existing indexing solutions for the discovery of Internet of Things (IoT) sources often fall short to provide an adequate scalability. This is due to the high computational complexity and communication overhead that is required to create and maintain the indices of the IoT sources particularly when their attributes are dynamic. This paper presents a novel approach for indexing distributed IoT sources and paves the way to design a data discovery service to search and gain access to their data. The proposed method creates concise references to IoT sources by using Gaussian mixture models. Furthermore, a summary update mechanism is introduced to tackle the change of sources availability and mitigate the overhead of updating the indices frequently. The proposed approach is benchmarked against a standard centralized indexing and discovery solution. The results show that the proposed solution reduces the communication overhead required for indexing by three orders of magnitude while depending on IoT network architecture it may slightly increase the discovery time

Thyroid dysfunction among type 2 diabetic female Egyptian subjects

Ibrahim N Elebrashy,1 Amr El Meligi,1 Laila Rashed,2 Randa F Salam,1 Elham Youssef,1 Shaimaa A Fathy1 1Department of Internal Medicine, Diabetes, and Endocrinology, 2Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Giza, Egypt Purpose: High prevalence of thyroid disorders is more common in type 1 diabetes compared to type 2 diabetes, due to associated autoimmunity. Hypothyroidism is the most common disorder. The objective was to assess the prevalence of thyroid dysfunction among type 2 diabetic Egyptian females and to find the correlation between metabolic syndrome components and autoimmune thyroid dysfunction. Materials and methods: The study included 62 type 2 diabetic Egyptian females and 27&nbsp;sex- and age-matched controls. All patients in the study were subjected to anthropometric measures, including HbA1c, lipid profile, serum uric acid, thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, anti-thyroid peroxidase (TPO), antithyroglobulin (anti-Tg), and thyroid ultrasound. Results: Hypothyroidism was found in 45.2% of patients (5.49&plusmn;3.37 &micro;IU/mL) versus 11.1% of controls (1.79&plusmn;1.21 &micro;IU/mL) (P&lt;0.001). Anti-TPO was found in 75.8% (347.15&plusmn;244.87&nbsp;IU/mL) of patients versus 7.4% (32.89&plusmn;33.26 IU/mL) of controls (P&lt;0.001). Anti-Tg was found in 61.3% (508.03&plusmn;369.16 IU/mL) of patients versus 0 (51.26&plusmn;35.53 IU/mL) controls (P&lt;0.001). A significant positive correlation was found between TSH and antithyroid antibodies (anti-Tg, anti-TPO; P=0.002 and P=0.043, respectively) and between TSH and thyroid-gland volume (P=0.002) in diabetic patients. No correlation was found between any components of metabolic syndrome and thyroid antibodies in diabetic patients. Conclusion: Autoimmune thyroid disease is more common in Egyptian women with type 2 diabetes than nondiabetic women, and thus points to a role of autoimmunity in the pathogenesis of type 2 diabetes. Keywords: autoimmune thyroid dysfunction, TSH, anti-TPO, anti-Tg, T2 diabetes, metabolic syndrom