Dietary Natural Products as Potential Tumor Chemo-Sensitizers

P-glycoprotein (P-gp) is a membrane ATP-binding transporter that detoxifies cells from different xenobiotics. Multiple drug resistant (MDR) cells can be sensitized toward anticancer agents when treated with P-gp inhibitors/modulators (chemo-sensitizers). Regarding the requirement of high serum concentrations of P-gp inhibitors leading to potential toxicity, dietary phytochemicals are very important and they may interact with co-administered pharmaceuticals as P-gp substrates, leading to altered pharmacokinetics. In silico models for predicting probable binding mode of dietary phytochemicals to P-gp are useful in the early phase of drug discovery projects since they describe structural features in binding to P-gp and hence designing novel anti-MDR scaffolds. Introduction: As a part of our ongoing studies on virtual analysis of bioactive phytochemicals and to explore new substances that do not exhibit significant toxicity at doses required for P-gp inhibition, we aimed to get more insight into the interactions of P-gp and a few dietary natural constituents as tumor chemosensitizing agents. Methods and Results: Radiographic 3D holo structure of P-gp was retrieved from protein data bank (4XWK; www.rcsb.org). Lamarckian genetic algorithm of AutoDock 4.2 was used to simulate the binding of dietary compounds. All ab initio studies were done with functional B3LYP associated with split valence basis set using polarization functions (Def2-SVP) by ORCA quantum chemistry package. Our study proposed the dominant role of R-site in binding to Curcuminoids (Curcumin II;  -8.17 kcal/mol). In the case of black pepper, hydrophobic contacts seemed to be important in Piperine/P-gp complex. It was also proposed that Piperine carbonyl might be a good mimic of Curcumin II enone group due to the formation of H-bonds (Gln986). Among the catechins of green tea, Epicatechin gallate might not be identified as modulator/substrate since relatively similar ΔGbs were recorded within M, H and R sites. Quercetin was not preferentially docked within H-site (-4.77 kcal/mol) in accordance to the previous reports. Within the H-site, Epigallocatechin (green tea) was the weakest binder (-4.31 kcal/mol) and amino acid decomposition analysis dedicated -2.66 and -8.76 kcal/mol attractive forces for interaction with Glu180 and Lys185, respectively. Conclusions: Combined molecular docking/quantum mechanical studies revealed that among assessed phytochemicals, Bergapten (grape fruit) might be identified as P-gp modulator. Other constituents exhibited more affinity toward R-site with Curcumionoids being the top-ranked ones. Results indicated Lys185, Glu871 and Glu986 as important interacted residues with Curcuminoids due to strong hydrogen bondings

Fast Simulation of Electromagnetic Transients in Power Systems:Numerical Solvers and their Coupling with the Electromagnetic Time Reversal Process

The development of modern and future power systems is associated with the definition of new approaches for their simulation, control, and protection. To give an example, the increasing connection of massive renewable energy conversion systems is justifying the integration of DC infrastructures (eventually, multi-terminal HVDC) in the current AC power grids. Furthermore, the existing passive distribution networks are evolving by integration of decentralized and intermittent generation units which results in Active Distribution Networks (ADNs). As a consequence, complex power system topologies are emerging requiring adequate simulation tools capable to reproduce, possibly in real-time, their dynamic behavior. In this context, future operation/protection practices of power networks might rely on the availability of chip-scale real-time simulators (RTS) that will enable the implementation of efficient protection/fault location processes that, in principle, should be capable to comply with the restrictive constraints associated with these complex systems. Within this context, the work presented in the thesis contributes to the integration of new concepts of the fault location in AC/DC systems that can be deployed in chip-scale real-time simulation hardware represented by Field Programmable Gate Arrays (FPGAs). The development of the proposed fault location platform is done in two steps. First, an original fault location method based on the Electromagnetic Time Reversal (EMTR) theory is proposed. The proposed method is validated for the case of various power networks topologies and its performance is assessed. Compared to the existing fault location methods, the proposed approach is suitably applicable to different topologies including MTDCs and ADNs. Next, a new automated FPGA-based solver for RTS is proposed. The developed FPGA-RTS uses a specific automated procedure to couple the simulation platform with an offline simulation environment (EMTR-RV) without the need for Hardware Description Language (HDL). It is able to simulate both power electronics converters and power system grids and thanks to the use of particular parallel computational algorithms, it can accurately simulate, in real-time, Electromagnetic Transient (EMT) phenomena taking place in power converters and travelling wave propagation along multi-conductor transmission lines within very small simulation time steps (in the order of some hundreds of nanoseconds). To overcome the limitations associated with the Fixed Admittance Matrix Nodal Method (FAMNM), a method to assess the optimal value of the parameter of the Associated Discrete Circuit (ADC) switch model used by FAMNM is proposed. Finally, a specific application of the developed FPGA-RTS is explored for the development of a fault location platform by leveraging the EMTR theory. To this end, the proposed EMTR-based fault location method is integrated with the FPGA-RTS to develop an efficient fault location platform. Thanks to the fast EMT simulation capability of the FPGA-RTS, the developed fault location platform is able to estimate the accurate fault location within very short time scales. Moreover, the developed platform is compatible with the constraints characterizing complex topologies such as MTDC networks (e.g., the ultra-fast operation of the protection systems). The developed fault location platform is validated by making reference to an MTDC grid and an ADN, and it is shown to exhibit remarkable fault location accuracy as well as robustness against uncertainties such as fault type, the presence of noise, measurement systems delay, and fault impedance

Holmium-YAG Laser Ureteroscopic Lithotripsy in a Patient with Ectopic Malrotated Kidney

The incidence of stone disease among patients with congenital renal anomalies including malrotated kidney is more than in normal population due to poor urine drainage and stasis (1). Various minimally invasive options have been used for the management. Ureteroscopy and Holmium:YAG laser lithotripsy have been reported with favorable outcomes (2). We report a 30-year-old male who presented to our hospital having a right side malrotated kidney with a large stone in it. He underwent two session of ureteroscopy and Holmium:YAG laser lithotrips

The Efficacy of IPL in Periorbital Skin Rejuvenation: An Open-Label Study

Introduction: Intense Pulsed Light (IPL) is one of the effective methods used to treat the signs of facial aging. However, its efficacy in improving the appearance of periorbital wrinkles has always been evaluated in the context of whole-face rejuvenation and not studied in its own right. Therefore, in this study we sought to examine the effectiveness and side effects of IPL in periorbital skin rejuvenation.Methods: In this uncontrolled, open-label clinical trial, 38 patients referred to the Behrooz professional skin clinic for signs of periorbital skin aging were recruited. Patients underwent three treatment sessions with IPL, at one-month intervals, and were evaluated for treatment side effects after each session. Six months after the final IPL session, patients were examined to assess the level of symptom improvement. Patients were photographed at each treatment session and at the six-month follow-up visit. Before and after patient images were evaluated by two dermatologists unaffiliated with the study to determine the extent of improvement in the appearance of wrinkles and skin texture.Results: Six months post-treatment, excellent improvement was observed in 3 patients (9.1%), considerable improvement in 7 patients (21.2%), moderate improvement in 9 patients (27.3%), mild improvement in 9 patients (27.3%) and finally little or no improvement was observed in 5 patients (15.1%). Comparison of improvement scores based on Fitzpatrick skin phenotype did not show significant differences (p=0.674). 4 patients (12.1%) were dissatisfied with the treatment whilst 17 patients (51.5%) reported moderate to considerable satisfaction with IPL rejuvenation.Conclusion: During whole face rejuvenation, IPL can be used to improve periorbital skin aging.

Evaluation of the Effects of Low Level Laser Therapy on the Healing Process After Skin Graft Surgery in Burned Patients (A Randomized Clinical Trial)

Background: Skin graft is standard therapeutic technique in patients with deep ulcers but as every surgical procedure has complications. Although several modern dressings are available to enhance comfort of donor site, using techniques that accelerate wound healing may enhance patient’s satisfaction.Low Level Laser Therapy (LLLT) has been used in several medical fields, especially for wound healing but for treating large ulcers, it may last several months to heal completely.Materials and Methods: The protocols and informed consent were reviewed according to Medical Ethics Board of Shahid Beheshti University of Medical Sciences (IR.SBMU.REC.1394.363) and Iranian Registry of Clinical Trials (IRCT2016020226069N2). Nine patients with bilateral similar grade 3 burn ulcer in both hands or both feet, candidate for Split Thickness Skin Graft (STSG) were selected. One side was selected for laser irradiation and the other side as control, randomly. Laser area was irradiated by red, 655 nm laser light, 150 mW, 2 J/Cm2 for the bed of the ulcer and infra red 808 nm laser light, 200 mW for the margins, every day for 7 days.Results: The rate of wound dehiscence after skin graft surgery was significantly lower in laser treated group in comparison to control group which received only classic dressing (P=0.019).Discussion: In the present study for the first time we evaluate the effects of LLLT on the healing process of skin grafted area in burn patients. The results showed LLLT is a safe effective method which improves graft survival and wound healing process and decreases the rate of wound dehiscence in patients with deep burn ulcer

The Trends of Urolithiasis Therapeutic Interventions over the Last 20 Years: A Bibliographic Study

Introduction: The clinical and economic burden of kidney stones is a challenge for the healthcare system. There is a limited bibliometric project exploring the literature trends on ‘urolithiasis’ and its related management.Methods: A review was conducted to discover the related abstracts regarding each specific issue, investigated year by year from May 2000 to May 2020. To make an effective comparison, the statistics resulting from every single study were allocated to two 10-year periods: period 1 (2000 to 2010) and period 2 (2010 to 2020). We included all English language articles, all non-English articles with English abstracts, and studies in which interventions were used for stone removal, including laser technology.Results: These articles are about ureteroscopy (URS) (n=10360, 33.45%), percutaneous nephrolithotomy (PCN) (n =10790, 34.84%) and extracorporeal shockwave lithotripsy (ESWL) (n=9846, 31.76%). When evaluating the two time periods, there were 9912 studies available in period one, which increased by ×2.12 times (112.71% rise) to 21 084 studies in period two (P=0.001). The increase was 133%, 103.51%, and 70.4% for URS, PCN, and SWL respectively. A total of 855 studies on Laser application via URS were published on PubMed over a 20-year period. There was an increasing trend toward using laser applications via URS over the study period. Also, there were 230 articles published in period one, which increased by nearly 2.71 times to 625 papers in period two (P< 0.001). There was an increasing trend toward using laser application via PCN; 126 papers were published in period one, which increased by nearly 3.05 times (rise of 205.5%) to 385 papers in period two (P = 0.002).Conclusion: The minimal invasive interventions for stone removal, including URS and PCN, increased dramatically in the last decade, and the use of lasers in stone treatment increased significantly in the last decade. DOI:10.34172/jlms.2021.1

Laser Application in Iran Urology: A Narrative Review

The usage of laser in medicine is not recent, and its history in urology goes back to 40 years ago. For the last 2 decades, common uses of laser have been treatments of subjects with urolithiasis, bladder tumors, benign prostatic enlargement, lesions of the genitalia and urinary tract strictures. To evaluate laser application in urology in Iran, we reviewed all of the Iranian literature on the topic. This study was designed to retrieve all studies on laser application in urology in Iran, regardless of publication status or language, covering years 1990–2017. Twenty-six articles were identified: 12 about urolithiasis, 8 about benign prostatic hyperplasia (BPH), 2 case reports, 1 paper about prostate cancer, 1 on female urethral stricture, 1 review and 1 basic sciences study. We conclude that the use of this technology has not yet found its position in Iran, especially in the field of urology. The main causes for it are the difficult accessibility and disturb of laser devices and its accessories, as well as the lack of adequate knowledge of the medical community about this modality

Trans-Ureteral Ureterolithotripsy of Ureteral Calculi:Which is the Best; Pneumatic or Holmium Laser Technique?

INTRODUCTION: Our aim was compare of two types of lithotripter include holmium: YAG laser and pneumatic one in transurethral ureterolithotripsy (TUL) for the management of ureteral calculi ≥1 cm.METHODS: 112 patients with ureteral calculi more than 1 cm were selected in randomized order for pneumatic or holmium: YAG laser transurethral ureterolithotripsy (56 patients in each group). Ultrasonography and intravenous urography were performed for all patients before surgery. Complete clearance and success was defined as the absence of any fragments on post operation KUB and ultrasonography images.RESULTS: Success rate was 85.7% in pneumatic group and 100% in holmium: YAG laser group (p =0.003). Stone migration up in the pelvicalyceal system was observed only in 8 cases of pneumatic group. No statically differences were observed in terms of patient’s age, hospital stay, and complications between two groups.CONCLUSION: According to our experience, for ureteral stone larger than 1 Cm treatment with ureteroscopy and laser lithotripsy is a preferring approach with favorable operation time and hospital admission, and no more significant complication