What is new in the management of high-risk localized prostate cancer?

The current Special Issue, in the Journal of Clinical Medicine, is dedicated to collecting high-quality research that mainly focuses on "Clinical advances in Prostate Cancer Treatments" [...]

Rainfed agriculture: unlocking the potential

Rainfed farming / Soil degradation / Crop production / Climate change / Irrigation methods / Water harvesting / Yield gap / Models / Supplemental irrigation / Water productivity / Watershed management / India

Colorectal Foreign Body: A Case Report

Background:Emergency surgeons seldom encounter cases of foreign body ingestion/insertion. Both children and adults may present with ingestion or insertion of foreign body inside body cavitiesCase presentation: Two foreign nationals were brought by customs officer to emergency department with alleged history of insertion of cocaine packets through anus.Any subjects that caused omission from patients were admitted and rectal examinations were carried out. Rectum was filled with cocaine capsules which were retrieved manually as far as we could reach.Conclusion: It is likely that the use of various objects for anal eroticism is increasing, resulting in an increased incidence of retained rectal foreign bodies.Copyright©2012 Department of Forensic Medicine and Toxicology. Allrights reserved.

Formulation Devlopment Of Mesoporous Silica Nanoparticles As An Injectable Delivery System

Our long term goal is to develop a versatile and robust injectable carrier based on Mesoporous Silica Nanoparticles (MSN) for drug/drug combination therapies. The objective of my dissertation was to optimize surface functionality, particle shape and methods of colloidal stabilization of mesoporous silica by PEG for delivery of drug/drug combinations. This was achieved by pursuing the following three aims: 1. Optimize surface functionality of MSN for high drug loading and controlled release 2. Investigate the effect of particle shape and PEGylation on drug delivery in hypoxic tumor cells 3. Develop MSN capable of delivering drug/drug combinations To investigate the effect of surface functionalization of MSN on crystallization, loading, release and activity of mitoxantrone (MTX), we synthesized thiol (SH), mixed thiol/amine (SH/NH2) and amine (NH2) functionalized MSN by sol-gel process. We observed that NH2 modification of MSN has limited MTX loading. In contrast, modifications of MSN with SH resulted in significant enhancement of MTX loading. MTX loading was controlled by pH of the loading media and surface charge of MSN. The SH-MSN particles maintained a strong negative charge due to silanol and thiol surface groups while amine modified MSN resulted in an overall positive charge. Differences in the loading were due to decrease in the electrostatic interaction between MTX and MSN. Based on the observed pH-dependence of MTX loading, we hypothesized that surface functionalization will provide a simple method of pH controlled MTX release from MSN. Indeed, we observed strong pH-dependence of MTX release in SH-MSN with rapid release in acidic pH and very slow release in neutral pH. In comparison, MTX was released rapidly from NH2-MSN regardless of the pH. Similar to loading, the differences in the release behavior are due to differences in interactions of the drug with the silica matrix. Another important aspect of mesoporous silica is amorphization or crystalline-to-amorphous transformation of drugs in the porous nanoconfinement. We found strong effect of surface functionalization of MSN on crystallization of MTX. In SH-MSN particles, MTX was found to be in the amorphous form while semi-crystalline MTX was present in the NH2-MSN. This is a very interesting feature as surface functionalization serves as a simple tool to allow control over MTX loading, its crystallization and release profile. After optimizing surface functionality, we investigated the effect of surface PEGylation and particle shape on loading and release profile of MTX in hypoxic tumor cells. We synthesized thiol functionalized mesoporous silica nanorods (MSNR) and stabilized them with different amount of covalently attached PEG. The focus on rod-shaped particles was based on studies showing beneficial properties of nanorods for increased blood circulation and tumor accumulation compared with spherical particles. We found that PEGylation decreased zeta potential of MSNR with improved colloidal stability but reduced overall MTX loading as a function of PEG content. PEGylation also increased the rate of MTX release compared to release from non PEGylated MSNR. We found that MTX had better anticancer activity in hypoxic than normoxic conditions, while no clear effect of particle shape was observed. Flow cytometry study confirmed that increased activity of MTX formulations in hypoxic conditions was due to increased cell uptake and retention of the drug in the cells. To achieve our long-term goal of developing a robust and versatile drug delivery carrier, we investigated feasibility of co-loading of hydrophilic-hydrophobic and hydrophobic-hydrophobic drug combinations in MSN. We found that loading of hydrophobic molecules such as PTX and 17-AAG depends on the polarity of solvent, with less polar solvents improving drug loading. We have successfully co-loaded PTX and 17-AAG into the same particles. We observed that PEGylation decreases loading of hydrophobic molecules. We hypothesize that this decrease in the drug loading was due to blocking of access to the pores. This is a new observation and we are currently investigating alternative ways to stabilize co-loaded MSN without compromising drug loading. Inorganic particles like MSN offer an interesting alternative to organic drug delivery systems like polymeric nanoparticles, micelles and liposomes due to high drug loading capacity and biocompatibility. We demonstrated the effect of surface functionalization and PEGylation of MSN on crystallization, drug loading and release, and colloidal stability. We showed effective delivery of MTX using PEGylated MSN in hypoxic conditions that has significant promise in the treatment of clinically important triple negative as well as estrogen positive breast cancers. We also showed MSN are capable of delivering drug-drug combinations for cancer treatment

New Highly-Sensitive Ultra-Performance Liquid Chromatography - Mass Spectrometry Method for Quantification of Telmisartan in Human Plasma

Purpose: To develop and validate a simple, rapid, sensitive and specific ultraperformance liquid chromatography mass spectrometry method for the quantification of the angiotensin II receptor antagonist, telmisartan (TEL), in human plasma.Methods: After simple protein precipitation using acetonitrile and methanol, TEL and internal standard (IS) abiraterone were separated on Acquity UPLC BEHTM C18 column (50 x 2.1 mm, i.d. 1.7 μm, Waters, USA) using a mobile phase consisting of acetonitrile: 8 mM ammonium acetate containing 0.15 % formic acid (v/v) (70:30) pumped at a flow rate of 0.3 mL/min and detected by tandem mass spectrometry with positive ion mode. The ion transitions recorded in multiple reaction monitoring mode were m/z 515.27→276.13 for telmisartan and m/z 350.1 > 156.0 for internal standard, abiraterone.Results: The assay exhibited a linear dynamic range of 1 – 200 ng/mL for telmisartan in human plasma with good correlation coefficient (0.995) and limit of quantitation of 1 ng/mL. The relative standard deviation for the intra- and inter-assay precision was between 0.75-11.50Conclusion: The developed UPLC-MS/MS method is simple, rapid and highly sensitive, and should thus be suitable for pharmacokinetic and toxicokinetic studies in both animals and humans.Keywords: Telmisartan, Ultra-Performance liquid chromatography, Tandem mass spectrometry, Pharmacokinetics, Toxicokinetics, High throughput analysi

Ransomware protection in IoT using software defined networking

Internet of things (IoT) is the network of physical objects connected to provide various services. IoT is expanding rapidly, and is positively influencing many areas. The impact of IoT is evident in medical field, manufacturing units and livestock. The IoT is also vulnerable to many cyber threats, owing to its limited resources and battery operation. In contemporary times the security threats like DDoS, botnet malware, man in the middle, flood attacks and ransomware are affecting the smooth functioning of IoT. Ransomware has emerged as one of the biggest threat in cyber world. Ransomware is a type of malware that stops the access to files by encrypting them and decrypts the files only when a ransom is paid. The negligence towards the IoT ransomware can result in disastrous outcomes. In this paper, the growth of ransomware attacks for past few years is shown with special focus on ransomwares threatening IoT. A detection mechanism for IoT ransomware attack is presented that is designed after study of ransomware for IoT. The proposed model monitors the incoming IoT traffic through Software Defined Network (SDN) gateway. It uses policies framed in SDN controller for detection and alleviation of ransomware in IoT

Tradition and Modernity in the Major Novels of Albert Chinualumogu Achebe - An Analytical Study

Albert Chinualumogu Achebe was considered by many as one of the prominent African writer and he is known for original literary artistic writing in English during his times. This research paper critically studied the tradition and modernity in the representative novels of Achebe such as Things Fall Apart and No Longer at Ease. These novels were concerned with the traditional Igbo life as it clashed with colonial powers in the form of missionaries and colonial government. In the final analysis of this paper found that those novels can be seen as a display of the conflict between the desires to retain traditional values and there cognition that change and assimilation are absolutely necessary for survival. Keywords: Tradition, Modernity, Duality, Civilization, Ethinicity

Management and functional outcome of Galeazzi fracture dislocation: a single centre retrospective study

Background:Galeazzi fracture dislocation is an unstable fracture dislocation of forearm that includes fracture of distal third or fourth shaft of radius with dislocation of distal radioulnar joint. The aim of the study was to analyse the management and functional outcome of Galeazzi fracture dislocation managed with fixation of radius fracture and distal radioulnar joint stabilisation with two Kirschner wires.Methods:Thirty one patients with Galeazzi fracture dislocation were managed with plate fixation for radius fracture and distal radioulnar joint stabilisation with 2 Kirschner wires. They were clinically and radiographically assessed for functional outcome as well as union, distal radioulnar joint stability and any arthrosis of the wrist joint.Results:Functional outcome was assessed based on disability of shoulder, arm, and hand index. 94% of the patients in our series had good to fair outcome with 6% having poor outcome.Conclusions:All Galeazzi fracture dislocation should be managed with plate fixation for radius fracture and Kirschner wire stabilisation of distal radioulnar joint followed by splinting for 6 weeks for best functional outcome

Identification of Putative Vero Cell Protein(s) that Bind Specifically to Recombinant Envelope Protein of Dengue Virus Type 2

Purpose: To identify protein targets in host (vero) cell since there is currently no therapy or a licensed tetravalent vaccine to combat all the four virus serotypes of dengue virus.Methods: The domain III of the dengue virus encoded envelope protein was expressed in pET28a expression vector and the purified recombinant protein was labeled with biotin without altering its immunogenicity. Vero cell proteins on nitrocellulose membrane reacted with recombinant envelope protein domain III to identify viral target proteins in vero cells.Results: The 45 KDa, 43 KDa and 30 KDa plasma membrane proteins were identified as viral envelope targets. Competitive binding assay showed these proteins competing with dengue virus binding. MTT assay indicate that viability of vero cells increases in cultures pretreated with 45 KDa, 43 KDa and 30 KDa proteins before dengue infection.Conclusion: These results indicate the possible role of these proteins in viral binding to vero cells. The study provides a preliminary insight that would aid in determining the target epitopes against protein E domain III of dengue virus and hence, formulation of a vaccine for preparing neutralizing antibodies.Keywords: Dengue virus envelope, Biotinylation, Ni-NTA purification, Target epitopes, Plaque assay, Competitive blocking assa

Is there a role for stem cell therapy in erectile dysfunction secondary to cavernous nerve injury? Network meta-analysis from animal studies and human trials

Introduction: We carried out systematic review and network meta-analysis to investigate the role of stem cell therapy (SCT) in the management of erectile dysfunction (ED) secondary to cavernous nerve injury in rats and post-radical prostatectomy (RP) in humans. Patients and Methods: The protocol was registered with PROSPERO database. We searched studies analyzing the efficacy of SCT for ED due to bilateral cavernous nerve injury (BCNI) in rats using Healthcare Databases Advanced Search (HDAS) Export software (MEDLINE,EMBASE, Scopus) from inception to September 2020. The outcome measurements, for 29 animal studies, were intracavernosal pressure (ICP), ICP/MAP (mean arterial pressure) ratio, and histological/molecular changes. All three available human trials evaluating SCT in post-RP ED were assessed for International Index for Erectile Function (IIEF) Score and Erection Hardness Score (EHS). Results: For ICP measurement, animal studies were divided into adipose-derived stem cells (ADSCs) subgroup and bone marrow–derived stem cells (BMSCs) subgroup. Pooled analysis of these studies showed a beneficial effect of SCT in improving erectile function in rats with BCNI using network meta-analysis (95% confidence interval, CI; p < 0.001). There was an increase in ICP/MAP ratio in stem cell groups (including co-intervention) compared with control BCNI group. Histological and molecular evaluation of penile tissue revealed an increase in neuronal nitric oxide synthase (nNOS), smooth muscle content, and anti-apoptotic activity. Human trials revealed improved IIEF (70–150% from baseline at 6 months) and EHS (80–200% from baseline). Conclusion: Our results confirm that SCT does improve the erectile function in rats having cavernous nerve injury. Similarly, early human results have shown promising results