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" [...]

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

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

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

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

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

Comparison of outcomes of active surveillance in intermediate-risk versus low-risk localised prostate cancer patients: A systematic review and meta-analysis

Currently, there is no clear consensus regarding the role of active surveillance (AS) in the management of intermediate-risk prostate cancer (IRPC) patients. We aim to analyse data from the available literature on the outcomes of AS in the management of IRPC patients and compare them with low-risk prostate cancer (LRPC) patients. A comprehensive literature search was performed, and relevant data were extracted. Our primary outcome was treatment-free survival, and secondary outcomes were metastasis-free survival, cancer-specific survival, and overall survival. The DerSimonian–Laird random-effects method was used for the meta-analysis. Out of 712 studies identified following an initial search, 25 studies were included in the systematic review. We found that both IRPC and LRPC patients had nearly similar 5, 10, and 15 year treatment-free survival rate, 5 and 10 year metastasis-free survival rate, and 5 year overall survival rate. However, cancer-specific survival rates at 5, 10, and 15 years were significantly lower in IRPC compared to LRPC group. Furthermore, IRPC patients had significantly inferior long-term overall survival rate (10 and 15 year) and metastasis-free survival rate (15 year) compared to LRPC patients. Both the clinicians and the patients can consider this information during the informed decision-making process before choosing AS

Evaluation of the role of posterior malleolus fixation in trimalleolar ankle fractures: a prospective study

Background: Trimalleolar ankle fractures are relatively rare and complex ankle injuries, the prognosis of which is worse than bimalleolar fracture. The three malleoli are bony restraints of the ankle and all three are fractured in trimalleolar fractures. Hence, there is disruption of the weight bearing portion of the tibial plafond along with talus dislocation/subluxation. Management of such fractures is challenging and confounded by the dilemma of posterior malleolus fixation. Aim: The aim of the present study was to evaluate the radiological and clinical outcome of fixation of large (>25%) posterior malleolus fragment in trimalleolar fractures.Methods: 25 patients underwent fixation of the three malleoli and evaluated prospectively. Different methods for fixation from plating to lag screws were used for posterior malleolus.Results: 92% of patients in our series had excellent to good clinical outcome. Radiologically, there was anatomical reduction of the ankle joint and none of the patient had postoperative talus subluxation or arthrosis.Conclusions: Our study shows that there is consistent and reproducible clinical advantage of fixing the posterior malleolus in trimalleolar ankle fractures.