Utility of the Guy’s Stone Score in predicting different aspects of percutaneous nephrolithotomy

Objective: To evaluate Guy’s scoring system (GSS) as a grading system for complexity of kidney stone before percutaneous nephrolithotomy (PCNL) as a predictor for different items of outcome.Patients and methods: Between July 2014 till July 2015, 100 patients with renal stone (s) and candidates for prone PCNL were evaluated and graded by GSS preoperatively. All intraoperative and postoperative data and complications using modified Clavien system were recorded, collected and statistically analyzed in relation to different grades of GSS to evaluate its predictive ability to different items of outcome.Results: Mean age of the patients was 47.38 ± 14.6 years. The patients were distributed in different grades of GSS with no statistically significant difference as mean age, sex, and mean BMI of the patients, stone side and previous renal surgery. There was high statistically significant difference in mean operative time, rate of blood transfusion, and mean number of renal punctures between different Guy’s scores, with all of them showed the highest values at GS IV. There was significant correlation between increase in the grade of GS and the need for re-PCNL and auxiliary procedures. The final stone free rate (SFR) was 93% and complication rate was 27% with significant increase in the immediate success rate, SFR, and complication rate with advancement of the grade of GSS.Conclusion: GSS has a positive correlation with SFR, re-treatment rate, need for auxiliary procedure, and rate of complication

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study

Breast cancer is the most common cancer in women, responsible for over half a million deaths in 2020. Almost 75% of FDA-approved drugs are mainly nitrogen- and sulfur-containing heterocyclic compounds, implying the importance of such compounds in drug discovery. Among heterocycles, thiazole-based heterocyclic compounds have demonstrated a broad range of pharmacological activities. In the present study, a novel set of 1,3-thiazole derivatives was designed and synthesized based on the coupling of acetophenone derivatives, and phenacyl bromide was substituted as a key reaction step. The activity of synthesized compounds was screened against the proliferation of two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all compounds exhibited a considerable antiproliferative activity toward the breast cancer cells as compared to staurosporine, with no significant cytotoxicity toward the epithelial cells. Among the synthesized compounds, compound 4 exhibited the most potent antiproliferative activity, with an IC50 of 5.73 and 12.15 µM toward MCF-7 and MDA-MB-231 cells, respectively, compared to staurosporine (IC50 = 6.77 and 7.03 µM, respectively). Exploring the mechanistic insights responsible for the antiproliferative activity of compound 4 revealed that compound 4 possesses a significant inhibitory activity toward the vascular endothelial growth factor receptor-2 (VEGFR-2) with (IC50 = 0.093 µM) compared to Sorafenib (IC50 = 0.059 µM). Further, compound 4 showed the ability to induce programmed cell death by triggering apoptosis and necrosis in MCF-7 cells and to induce cell cycle arrest on MCF-7 cells at the G1 stage while decreasing the cellular population in the G2/M phase. Finally, detailed in silico molecular docking studies affirmed that this class of compounds possesses a considerable binding affinity toward VEGFR2 proteins. Overall, these results indicate that compound 4 could be a promising lead compound for developing potent anti-breast cancer compounds.Faculty of Pharmacy, Suez Canal University, and Faculty of Science, Port Said University, EgyptPrincess Nourah bint Abdulrahman University Researchers SupportingTaif University Researcher

ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo

The proteolytic activity of a disintegrin and metalloproteinase 10 (ADAM10) regulates cell-fate decisions in Drosophila and mouse embryos. However, in utero lethality of ADAM10−/− mice has prevented examination of ADAM10 cleavage events in lymphocytes. To investigate their role in B cell development, we generated B cell–specific ADAM10 knockout mice. Intriguingly, deletion of ADAM10 prevented development of the entire marginal zone B cell (MZB) lineage. Additionally, cleavage of the low affinity IgE receptor, CD23, was profoundly impaired, but subsequent experiments demonstrated that ADAM10 regulates CD23 cleavage and MZB development by independent mechanisms. Development of MZBs is dependent on Notch2 signaling, which requires proteolysis of the Notch2 receptor by a previously unidentified proteinase. Further experiments revealed that Notch2 signaling is severely impaired in ADAM10-null B cells. Thus, ADAM10 critically regulates MZB development by initiating Notch2 signaling. This study identifies ADAM10 as the in vivo CD23 sheddase and an important regulator of B cell development. Moreover, it has important implications for the treatment of numerous CD23- and Notch-mediated pathologies, ranging from allergy to cancer

Minerals and insulin dependent diabetes in children: A review article

Background: The human body contains trace levels of minerals and other micronutrients. Particularly advantageous for physiologic processes, a wide range of biochemical processes, stabilizing proteins and enzymes, and serving as cofactors for different enzymes. These essential micronutrients have a major physiological effect and are significantly associated with diabetes. Cobalt, boron, chromium, copper, Sulphur, iodine, fluoride, selenium, manganese, zinc, and molybdenum are examples of trace elements. Sodium, potassium, calcium, phosphorus, magnesium, and iron related to macro elements. The main focus of this review is the effect of particular minerals and trace elements on childhood insulin-dependent diabetes. Objective: Our understanding of how minerals and trace elements affect insulin-dependent diabetes in children will be improved as a result of this review, which is its main goal. Conclusion: The interaction, development, and outcomes of insulin-dependent diabetes in children are significantly influenced by minerals and trace elements

Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice

ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared to Th1 prone controls. To further understand this regulation, ADAM17 and TNF were studied in C57Bl/6 and Balb/c mice deficient in ADAM10. C57-ADAM10B-/- were more adept at increasing ADAM17 levels and thus TNF cleavage resulting in excess follicular TNF levels and abnormal secondary lymphoid tissue architecture not noted in Balb-ADAM10B-/-. Moreover, the level of B cell ADAM10 as well as Th context is critical for determining IgE production potential. Using a murine house dust mite airway hypersensitivity model, we describe that high B cell ADAM10 level in a Th2 context (Balb/c WT) is optimal for disease induction including bronchoconstriction, goblet cell metaplasia, mucus, inflammatory cellular infiltration, and IgE production. Balb/c mice deficient in B cell ADAM10 have attenuated lung and airway symptoms compared to Balb WT and are actually most similar to C57 WT (Th1 prone). C57-ADAM10B-/- have even further reduced symptomology. Taken together, it is critical to consider both innate B cell levels of ADAM10 and ADAM17 as well as Th context when determining host susceptibility to allergic disease. High B cell ADAM10 and low ADAM17 levels would help diagnostically in predicting Th2 disease susceptibility; and, we provide support for the use ADAM10 inhibitors in treating Th2 disease

Synthesis and pharmacological activities of some condensed 4-chloro-2,2-dialkyl chromene-3-carbaldehyde derivatives

Novi hidrazono- 5a,b, tiosemikarbazono- 6a-c i oksimo kromeni 7a-c sintetizirani su iz odgovarajućeg β-klorkarbaldehida 3 i hidrazina, aromatskog hidrazina, tiosemikarbazida ili hidroksilamin hidroklorida, dok su eterski derivati 8a-h pripremljeni iz pripadajućih aldoksima 7a-c. Novi spojevi ispitani su na protuupalno i ulcerogeno djelovanje, a njihovo djelovanje uspoređeno je s djelovanjem indometacina.Some new hydrazono- 5a,b, thiosemicarbazono- 6a-c, and oximo chromenes 7a-c were prepared via the reaction of the corresponding β-chlorocarbaldehyde 3 with hydrazine, aromatic hydrazine, thiosemicarbazide and hydroxylamine hydrochloride, respectively. In addition, ether derivatives 8a-h were prepared from the corresponding aldoximes 7a-c. The new products were tested for anti-inflammatory and ulcerogenic score activities compared to indomethacin

Low grade energy engines

It is clear that there is no long-term solution to energy supply problems other than planned and continuous conservation. The use of low-grade energy as an unlimited resource will play an important part in maintaining the balance between the future of the world for both developed and developing countries alike. energy supply and demand A literature survey reviewing the most , the construction of low-grade energy engines has been conducted. The V promising approaches to' validity of each feasible system has been examinéd and the of operation described principles cycle utilizing common suitable refrigerants (e.g. halo-carbons) as A feasibility study concerning the adoption_of the organic Rankine ` working fluids has been conducted. In particular, the use of a multiple vane expander as the prime mover has been A suite of computer programs has been developed to fully investigated; describe working fluid properties optimise the geometrical and dynamical parameters of the Rankine cycle to achieve the most efficient operation in both steady and`transient states ' ' optimise the mechanical design of the expander depending upon the mode of operation and-the source and sink characteristics ' fully flexible experimental test facility was constructed so ., as to be capable of testing a wide variety of prime movers. This has _ been operated for a real time test period in excess of 300 hours. ` The test results are encouraging. Efficiencies were measured V in_accordance with the mathematical predictions and a portfolio of - and_reliable expander capable of utilising low has been produced. , Fruitful links with relevant have been forged. ,"Demonstrations of the system are planned the UK and overseas. L A ' ~ within British industries grade thermal energy suggested modifications towards a high efficiency, low-cost, robus

Validity of biomarkers in screening for neonatal sepsis – A single center –hospital based study

Background: The diagnosis of neonatal sepsis still considered to be a challenge for both clinicians and the laboratory due to the non-specific clinical presentations. The present study aimed to compare and assess the diagnostic & prognostic values of C-reactive protein (CRP), high sensitivity CRP (hsCRP), presepsin, interleukin-6 (IL-6) and procalcitonin (PCT) in neonatal sepsis separately and in combination. Methods: This hospital-based cross-sectional study has been conducted on 168 neonates recruited from the neonatal intensive care unit (NICU) of Qena University Hospitals, Upper Egypt. Measurements of CRP using latex agglutination test, hsCRP, presepsin, IL6 and PCT assays using commercially available ELISA assay kits were done to all included neonates. Results: There were significantly higher serum levels of CRP among late onset versus early onset sepsis group with significantly higher serum levels of hsCRP and presepsin among early onset compared with the late onset sepsis group (p 6 mg/dl showed lower sensitivity and specificity than that of hsCRP at cutoff >140 ng/ml in diagnosing neonatal sepsis. The cutoff value of presepsin >200 ng/ml showed equal sensitivity and specificity to IL-6 at cutoff >22 pg/ml. The cutoff value of PCT at > 389 pg/ml showed sensitivity and specificity approximate to that of hsCRP. Conclusions: CRP could be a helpful prognostic marker in late onset neonatal sepsis. hsCRP and PCT have higher diagnostic accuracy in neonatal sepsis in comparison to other studied markers. Both IL-6 and presepsin have equal diagnostic utility in neonatal sepsis, but presepsin could be helpful diagnostic marker in early onset neonatal sepsis. Key Words: high sensitivity CRP, interleukin-6, neonatal sepsis, presepsin, procalcitoni

Outcome of retrograde flexible ureterorenoscopy and laser lithotripsy for treatment of multiple renal stones

Objective: To evaluate the efficacy and safety of retrograde intrarenal surgery (RIRS) using flexible ureterorenoscopy (F-URS) and laser lithotripsy as a treatment option for multiple renal stones greater than 1 cm.Patients and methods: Between June 2015 and February 2017, 42 patients who were treated with RIRS via F-URS and laser lithotripsy were evaluated. Stones were divided into two categories according to stone burden, 11–20 mm and 21–30 mm. Patient’s demographics, stones characteristics, operative outcomes and complications were evaluated prospectively. Stone free rate (SFR) was determined 4 weeks postoperatively using findings on non-contrast computed tomography (NCCT).Results: Mean stones burden was 25.7 mm (range from 1.3 to 30 mm), 8 patients had 11–20 mm stones burden with SFR 100% and 34 had 21–30 mm stone burden with SFR 91.2%. The overall SFR was 92.8%. Multiple stones were two in 31 patients (73.8%), three in 9 (21.4%) and four in 2 (4.8%). Regarding stone number per kidney and SFR, SFR was 100%, 77.7% and 50% for kidneys with two, three and four stones respectively. In terms of stone location in the pelvi-calyceal system and corresponding SFR, there were renal pelvic stones in 6 (14.3%) patients with 100% SFR, upper calyx and or mid calyx and or renal pelvis in 12 (28.6%) with SFR 91.6% and lower calyx with or without other locations in 24 with SFR 91.6% also. Complications were minor and included, UTI in 3 patients (7.1%), hematuria of 4 days duration in 2 (4.8%), severe DJ stent irritative symptoms in one (2.4%) and minor ureteral perforations in one (2.4%).Conclusion: RIRS via F-URS and laser lithotripsy is a safe and effective treatment option with high success rate for patients with multiple renal stones of 11–30 mm stone burden. It is indicated when other stone treatment modalities contraindicated or have failed. However, for complex or challenging stones, staged procedures may be required.Keywords: Renal stones; Retrograde; Flexible ureterorenoscopy; Laser lithotrips