In recent years, a huge number of germline mutational variants had been identified in breast cancer by next-generation sequencing technologies. Even though a considerable portion of them are variants with low variant allele fraction (< 30%), which could give rise to suspicion among us regarding whether they might be false or true, recent pioneering studies have begun to corroborate that a certain amount of them are true variants associated with mutational mosaicism. In this study, we present pathogenic mosaic germline mutational landscape in 490 breast cancer patients by carrying out targeted next-generational sequencing of 62 cancer-associated genes. We discovered 112 pathogenic, 37 likely pathogenic and 252 VUS mosaic germline mutations with variant allele fraction less than 30%. PRSS1 (97%), ATM (22%), PMS2 (11%), BARD1 (11%), PTEN (8%), BRCA2 (8%), BRCA1 (7%), APC (5%), MSH2 (5%) and NF1 (5%) mosaic mutations occurred in the top 10 biggest portions among the 490 patients, respectively. Gene pairs showing statistically significant mutual exclusivity in mutation carriers are PRSS1 and FANCC (p < 0.01), PRSS1 and PTEN (P < 0.01), and PRSS1 and ATM (p < 0.01). Genes showing the biggest fractions of mosaic mutational clusters PRSS1 (FDR < 10^-6), BARD1 (FDR < 10^-5), PTEN (FDR < 10^-4), ATM (FDR < 10^-4), VHL (FDR < 10^-4), PMS2 (FDR < 10^-4), NBN (FDR < 10^-3), PTCH (FDR < 10^-3), MSH6 (FDR < 10^-3), and BRCA2 (FDR < 10^-2). Protein pfam domain hit most by those mosaic mutations is Tryp_SPc (trypsin-like serine protease). The most affected pathways by mosaic mutations are TP53, cell cycle, RTK-RAS and PI3K pathways. By using 34 drug-gene mutation interaction database sources for clinically actionable pathogenic mutations, we identified drug candidates for most of mosaic pathogenic mutations in this study. Furthermore, by using pharmacogenomics approach through integrating drug sensitivity, genomic mutation and expression profiling data for 1200 human cancer cell lines, we validated the drug sensitivity and effectiveness of NVP-BEZ235 and temsirolimus for RB1, Camptothecin for TP53, and AZD8055 for NF1 and MSH2 mutated cancer cell lines. Taken together, this study elucidates pathogenic mosaic germline mutational landscape in breast cancer patients and also provides pharmacologists, clinicians, clinical oncologists and surgeons with fresh guidance for choosing candidate pharmaceutical drugs for carriers with pathogenic mosaic germline mutations and for diagnosing and treating them.

Given increasing constraints on health care resources and cost, there is a need to assess the relative value of high efficacy therapies for different disease including cancers. In addition, decision makers in middle-income countries also need to manage certain therapeutic categories, especially for chronic disease such as MS, in an attempt to control costs and give access to new, often more expensive, therapies within limited health care budgets. For countries with limited resources, economic evaluations based on decision analytic modeling may be a suitable alternative to extensive trial-based economic evaluations. In this presentation, we are going to review the principals of the methods which are common to investigate the value of new therapies including cost-effectiveness studies, Health Technology Assessment (HTA), and Multiple-criteria decision analysis (MCDA). First of all, the concept of cost in pharmacoeconomics would be reviewed in terms of different perspectives such as payer, health system, and etc. Then, different consequences will be reviewed focusing on the concept of utility and Quality Adjusted Life Years (QALYs). Subsequently, cost-effectiveness plane would be reviewed interpreting the willingness-to-pay threshold for choosing the cost-effective strategies. Then, two common modeling approaches (decision tree and Markov models) would be reviewed. Afterwards, the limitation of cost-effectiveness studies will be discussed together with the concept of deterministic and probabilistic sensitivity analysis. Finally, the HTA and MCDA methods would be reviewed as alternative or complementary methods to cost-effectiveness studies. In view of a tight healthcare budget, these decision analysis methods may provide healthcare decision makers with the requisite insights to make informed choices.

The aim of improving the quality of pharmaceutical end products and optimizing production efficiency drives the need for progress in real-time quality control with process analytical technology (PAT) tools for monitoring critical quality and performance attributes. Multiparticulate dosage forms – using coated or uncoated pellets or granules – are increasingly used in the production of solid dosage forms as they enable favourable release profiles of active ingredients. With these, the Critical Quality Attributes (CQAs) that affect the physicochemical properties of drug substances and final dosage forms are particle size, particle shape and, with coating applications, also coating thickness and coating uniformity. The machine vision technology brings advantages over other PAT techniques as it provides means of contactless, non-invasive, non-destructive, fast and accurate automatic measurements of particles together with easy implementation and calibration. The benefits of the presented PAT technology offer new possibilities for optimizing and a better understanding of production processes and, subsequently, of the end product quality assurance.

The present study investigated the level of alcohol in cases referred to the centre as a post mortem cases and to the assault clinic from 2014 -2018 detection of alcohol is of extreme importance to the investigation and the cause of death. To evaluate the problem on alcohol intake and its relation to nationality, age, and gender and cause of death. Samples used for testing alcohol level: vitros fluid, blood, urine. Alcohol intake in Saudi Arabia is banned, this includes consuming, importing, brewing and selling so all cases suspected for drinking alcohol are referred to the toxicology centre and the forensic centre.

Chronic pancreatitis (CP) is characterized by pancreatic inflammation and fibrosis, which leads to impairment of pancreas function. The present study was designed to investigate the possible mechanisms of chronic pancreatitis and the anti-inflammatory, antioxidant and anti-fibrotic effect of nimbolide (NB), active constituent of neem tree Azadirachta indica in cerulein-induced CP. 

Objective: Curcumin is a natural polyphenolic substance with anti-oxidative, anti-inflammatory and anti-cancer properties. Its therapeutic potential is substantially hindered by the rather low water solubility, rapid metabolism and low bioavailability, hence the need for suitable carriers. In the present study we aimed to evaluate effects of polymeric micelles of curcumin on experimental colon cancer model in Rat.

Method: Pathogen-free male Sprague–Dawley rats divided into 4 groups. animals from group A, B, C started to receive DMH intraperitoneal injection once a week at a dose of 20 mg/kg body weight in 0.9% normal saline. Group A served as DMH control. B, C were treated with nano-micelle curcumin and 5-FU respectively starting 4 weeks before first carcinogen challenge and continued till week 30 of experimentation. At the end of the 4 weeks all animals were killed by cervical dislocation.and their colon removed and investigated for morphological and immunohistochemistry studies of apoptosis which expression of Bcl2, BAX and Caspase9 have been investigated.

Results: Morphological changes in Nano-curcumin groups was significant compared with DMH group but in protein expression of apoptotic factors, although decrease in Bcl2 expression and increase in BAX and caspase9 occurred in Nano-micelle group but these changes were not significant compared with DMH group(P>0.05)

Conclusion: According to results of this study, Nano-micelle of curcumin has some preventive effect in experimental model of colon cancer in vivo but has not induced apoptotic effect completely and more complementary studies are needed.

The goal of endodontic treatment is to remove all the vital and necrotic tissues, microorganisms and microbial byproducts from root canal system. This goal can be achieved through chemical and mechanical debridement of root canals. This article narrates the specifics and requirements of the irrigation solutions. Sodium hypochlorite is proposed as the primary irrigant by virtue of its organic tissue dissolution capacity and broad antimicrobial properties. On the other hand, chelation solutions are recommended as auxiliary solutions to remove the smear layer or to hinder its formation on dentin surface. Thus, it's hoped that sealers and root canal fillers can penetrate to dentin tubules and obturate the canals hermetically. There are new studies on traditional irrigants especially on some irrigants that can replace sodium hypoclorite. This article reviews the new irrigants which can be used in future endodontic practice, and their advantages and limitations. Moreover, actions and interactions of recently used irrigants are adverted.

The presentation will give an overview in the impacted teeth problems and how can we solve them. An impacted tooth is a tooth that is not erupted fully or at all in the oral cavity. Its related to the space provided for the teeth in the mandible and maxilla and to the time of eruption of each tooth. Therefore the most common impacted teeth are the third molars, then the canines and much less premolars and lateral incisors. The impacted teeth may have or not symptoms such as pain, swollen, infection in the adjacent gums, crowded teeth, open space (mainly in canines and lateral insicors), difficulty in mouth opening and sometimes even headaches. This lecture will provide the tools we have in our hands for the diagnosis of the type of impaction, (OPG, CBCT) and therefore the treatment plan which must be chosen for the better result. We will discuss the surgical techniques best fits in each type of tooth impaction for the best treatment outcome, as well as the preoperative and post-operative approach in order to help the patient receive the best treatment. We will see the possible obstacles we might face in the treatment of such cases. We will discuss also the collaboration with the Orthodontist in cases where the teeth needs to be erupted in the oral cavity. We will discuss also the possible complications during or after the surgical procedure and how we can manage them.

The present lecture will reveal a new approach to improve the behaviour and response of the frightened and uncooperative patient who visits a dental clinic for the everyday general dental treatment as well as excessive or more advanced treatment plans. Dental anxiety, fear, and phobia are all related terms that need to be clearly clarified. According to numerous Dental Fear Surveys (DFS), between 10% and 20% of adults in the United States avoid seeking regular dental treatment due to extreme dental fear. Through the use of the Hypnotherapy treatment we are able to flip the patients’ discomfort fear and phobia towards the dentist and the dental procedures in to acceptance and tolerance. The psychological trauma the dental treatment has created in the past or in the present situation can effectively be cured by this approach. Through this lecture we will discover the ways (Theory of the mind, flip, etc), the trends (cognitive therapy, self- awareness etc) and the opportunities the Hypnotherapy can create, as well as the paths that the Therapist is using in order to flip the whole unpleasant and uncomfortable experience of a dental treatment to a positive one. It is a great new “tool” in the dentist’s quiver to approach more effectively and with better long term results his/her patients’ fears and discomforts. And as every dentist knows a happy patient makes to more satisfied and happy dentist.