Expanding the potential of mutasynthetic approaches for pseudomonic acids

Natural products, particularly polyketides are among the most important sources of antimicrobial compounds. 20% of the top selling drugs are polyketide based. In recent years genetic engineering has played a critical role in modifying biosynthetic pathways of different polyketide compounds as a way to create novel structures with improved clinical properties. Further investigation and understanding of these giant multi-enzyme complexes is necessary to achieve efficient synthetic engineering. In many PKS systems including the mupirocin biosynthesis pathway, the thioesterase (TE) is normally considered as the end of the assembly line. However, expressing the CoA-ligase tmlU from the thiomarinol pathway in the mupirocin producer strain (Pseudomonas fluorescens NCIMB10586) revealed that TmlU could only release truncated pseudomonic acid when a TE domain was present. This finding led to the hypothesis that perhaps the TE domain could act as a tether for TmlU, in order for the latter to be able to capture the growing chain and perhaps load it onto the post TE pathway. This study also presents the first evidence of MmpB being involved in producing the 9-hydroxynonanoic acid in the mupirocin biosynthesis pathway

FORMULATION, EVALUATION, AND IN VIVO ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF MORINGA GRANULES

Objective: Consumption of crude natural products like plants and herbs for mitigation or treatment of illnesses usually accompanied with inconsistent therapeutic effects because of poor solubility and low bioavailability of active phytochemical(s) in addition to product instability. To overcome all of above mentioned drawback ethanol extract of Moringa oleifera leaf was formulated as standardised solid dosage form. Methods: Different types of materials as an adsorbent, surfactant and other necessary excipients were tested to be use in formulation of Moringa granules utilising wet granulation method. The formulated Moringa granules was then evaluated for organoleptic properties and physical characteristics, in vitro dissolution test, compatibility, drug content, heavy metal tests and microbial limit tests. Additionally, the in vivo anti-inflammatory against Carrageenan-induced paw oedema and anti-arthritic activity against CFA-induced arthritis were also assessed. Results: 95% ethanol extract of M. oleifera leaves was successfully formulated as standardised granules for oral administration utilising simple and low-cost techniques. Dissolution rate for the marker compounds was increased by an average of 1.076 fold. Animal groups given the prepared Moringa granules showed an improvement in the anti-inflammatory activity and the anti-arthritic activity compared to animal groups given crude extract at the same dose level. Additionally, all the treatment groups showed a significant difference at P<0.05 and P<0.01 compared to control group. Conclusion: To the best of our knowledge, this work was the first to use gum Arabic in the formulation of a standardised botanical pharmaceutical dosage form of M. oleifera crude extract. Additionally, formulation of Moringa granules apparently improves the drug release profile and bioactivity compare to Crude Moringa extract

In Vitro Cytotoxicity Study of Pt Nanoparticles Decorated TiO2 Nanotube Array

تم تحضير الانابيب النانوية لثاني اوكسيد التيتانيوم بأنودة صفائح التيتانيوم في محلول الاثيلين كلايكول و تمت تغطيتة سطحها بجسيمات البلاتين النانوية بطريقة الترسيب الكهربائي بأستخدام خمس مشتقات من معقدات البلاتين لقواعد مانخ التي استخدمت كمصدر او بأدء للبلاتين .تم تقييم متوسط الحجم والشكل وتركيب العناصر لانابيب التيتانيوم داي اوكسيد النانوية وجسيمات البلاتين المترسبة عليها بتقنيات مختلفة مثل المجهر الالكتروني الماسح (FE-SEM) ، المجهر الإلكتروني النافذ (TEM) ، نمط حيود الأشعة السينية ( XRD) و الأشعة السينية المشتتة للطاقة (EDX). من كل هذه الفحوصات ، تم تشخيص TiO2NTs وجسيمات البلاتين النانوية المودعة عليها وقد اثبتت الدراسة ان جميع جسيمات البلاتين النانوية  ذات حجم  أقل من 50 نانومتر. تم معاملة خطوط الخلايا السرطانية MCF-7 وخطوط الخلايا الطبيعية WRL68 بتركيز 800 ، 400 ، 200 ، 50 ، 25 ، 12.5 ميكروجرام / مل من TiO2NTs و(2)،( Pt \ TiO2NTs (1  لمدة 48 ساعة باستخدام اختبار MTT . بالاضافة الى ذلك تم حساب IC50 ومعدل التثبيط لهم. تظهر النتيجة أن Pt \ TiO2NTs لها تأثير تثبيط أكبر على خطوط الخلايا السرطانية من صفيف TiO2NTs.Titanium dioxide nanotubes were synthesized by anodizing Ti sheets in the ethylene glycol solution and were covered in Pt nanoparticles onto the surface of TiO2NTs using electrodeposition method from using five derivatives of Mannich base Pt complexes which have been used as precursor of platinum. The mean size, shape, elemental composition of the titanium dioxide nanotubes and platinum deposited on the template were evaluated by different techniques such as field emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction pattern (XRD), and energy dispersive X-ray (EDX) technique. From all these analyses, the TiO2NTs prepared and Ptnanoparticles deposited on it were identified. The diagnoses proved that all the Pt nanoparticles have a size less than 50 nm. The MCF-7 cancer cell lines and WRL68 normal cell lines were treated with concentration 800, 400,200,100, 50, 25, 12.5µg\ml of TiO2NTs and Pt\TiO2NTs(1) and (2) for 48hours using MTT assay.IC50 and inhibition rate were calculated. The result shows that the Pt\TiO2NTs have more inhibition effect on cancer cell lines than TiO2NTs array

Association of Oral Contraceptives use with Breast Cancer and Hormone Receptor Status in Iraqi Women

BACKGROUND: Worldwide, there is a significant concern regarding the association of breast cancer risk and oral contraceptives use. Differences in demographical and pathological breast cancer characteristics in Iraqi patients have been reported compared to other western countries; however, studies addressing the risk of breast cancer among oral contraceptive users in Iraq and subsequent correlation with hormonal receptor status are lacking. AIM: The aim of the study was to evaluate association of breast cancer risk and oral contraceptives use in patients visiting tertiary oncology center and to correlate hormone receptor status with history of oral contraception use in breast cancer patients. PATIENTS AND METHODS: Two hundred women with breast cancer were compared regarding patterns of oral contraceptives use with 300 age-matched healthy female controls by personal interview and questionnaire. Patient’s records were reviewed for hormone receptor status. RESULTS: A significantly higher proportion (49%) of women with breast cancer reported a positive history of combined oral contraceptives use as compared with (35.7%) healthy controls. Ever oral contraceptives users had a significantly increased risk of breast cancer (odds ratio [OR] = 1.73; 95%, confidence interval = 1.2–2.5, p = 0.003), with the highest risk was seen in early use before the age of 20 (OR = 6.62, p = 0.02); whereas increased duration of use did not significantly increase the risk of breast cancer. There was no significant association between estrogen and progesterone receptors expression profile in breast cancer patients and combined oral contraceptive use. CONCLUSION: In Iraqi women, the risk of breast cancer increases with oral contraceptives intake particularly when starts early before the age of 20 years. The hormonal receptor status of breast cancer patients is not significantly affected by combined oral contraceptives use

Etterlevelse av legemiddelbehandling, samt viktige årsaker til manglende etterlevelse hos ulike pasientgrupper, målt ved hjelp av et eget utarbeidet spørreskjema - En kvantitativ studie

Bakgrunn: Manglende etterlevelse er vist å være et stort problem både i Norge og på verdensbasis, særlig blant eldre og de med kroniske sykdommer. En rapport fra WHO viser at så mange som 30-50% ikke følger anbefalt legemiddelbehandling. Dårlig etterlevelse kan skyldes mange årsaker. WHO har delt opp ulike årsaker til dårlig etterlevelse av legemiddelbehandling inn i fem kategorier, og ifølge dem avgjøres etterlevelse av samspillet mellom de fem hovedkategoriene. Dårlig etterlevelse kan være et problem for en pasient, og ikke minst for samfunnet. Følgene kan være alt fra ubetydelig til fatale. Man kan vurdere lav etterlevelse, og iverksette tiltak for å forbedre den gjennom ulike måter. En måte å vurdere etterlevelsen på er via et selvrapportert etterlevelsesspørreskjema. Hensikt: Målet med denne studien var å designe et eget generelt selvrapportert etterlevelsesspørreskjema. Skjemaet skulle blant annet basere seg på WHOs fem dimensjoner med ulike årsaker. Deretter skulle dette brukes til å måle etterlevelsen, samt kvantifisere viktige årsaker til eventuell manglende etterlevelse hos pasienter med hjerte- og karsykdommer, og på tvers av andre pasientgrupper. Man skulle også se om det var forskjell i etterlevelse blant ulike pasientgrupper. Metode: En kvantitativ forskningsmetode ble brukt. Et anonymt digitalt spørreskjema i Nettskjema ble benyttet til å samle inn data med. Målpopulasjonen var alle typer voksne pasienter, 18 år eller eldre, som hadde brukt et eller flere legemidler, forskrevet på resept og/eller etter anbefaling fra lege, i løpet av de siste 12 månedene. Distribusjon av spørreskjemaet ble gjort på sosiale medier, først og fremst på Facebook. Respondenter ble rekruttert fra ulike Facebook-grupper over en periode på tre måneder. Resultat: Totalt ble 954 respondenter rekruttert, hvorav 28 ikke var i målgruppen. Majoriteten av de som deltok var kvinner 842 (88,5% mot 10,8%). Flertallet av respondentene brukte legemidler for hjerte- og karsykdommer (29,16%), smerter (41,79%) og allergi (33,37%). De som hadde tatt høyere utdanning på universitet og/eller høgskole i 5 år eller høyere (12,3%) rapporterte en bedre etterlevelsen i forhold til de som hadde lavere utdanning. De med ingen utdanning hadde dårligst etterlevelse. De som brukte kun ett legemiddel rapporterte en lavere etterlevelse i forhold til de som brukte ti eller flere legemidler (p-verdi = 0,02). De med hjerte- og karsykdommer hadde en bedre etterlevelse enn de i smertegruppen (p-verdi = 3,27x10-9) og alle andre pasienter samlet (p-verdi = 2,01x10-7). At man glemte å ta legemidlene var den viktigste årsaken til manglende etterlevelse hos de med hjerte- og karsykdommer, og hos alle respondenter samlet. At man følte seg bedre fra smertene var den viktigste årsaken til at de i smertegruppen hadde manglende etterlevelse. Konklusjon: Studien viste at etterlevelse av legemiddelbehandling hos pasienter har et potensiale til å bli enda bedre enn det den er i dag, ved å se på hvilke viktige årsaker som ligger til grunne for den eventuelle manglende etterlevelsen. Resultatene tydet på at etterlevelsen av legemiddelbehandling ifølge selvrapportering hos ulike pasientgrupper var mer eller mindre forskjellig. Både utdanningsnivå, polyfarmasi og ulike sykdomsdiagnoser kan påvirke etterlevelsen til pasienter i ulik grad. De med hjerte- og karsykdommer hadde en bedre etterlevelse enn alle andre pasienter samlet og de med diagnosen smerter. Pasienter med forskjellige typer sykdomsdiagnoser rapporterte ulike viktige årsaker til manglende etterlevelse. Noen av de viktige årsakene var at de hadde glemt å ta legemidlene og de følte seg friskere. Det utviklede selvrapporterte etterlevelsesspørreskjemaet målte det man ønsket å måle og var egnet til sitt formål i tilstrekkelig stor grad, men skjemaet kan gjøres bedre gjennom for eksempel å validere det. Nøkkelord: etterlevelse, selvrapportering, spørreskjema, årsaker til manglende etterlevelse, kvantitativ forsknin

The evaluation of a bicycle simulator

Bicycle simulators are safer to create many scenarios that would be difficult to be implemented in the real environment. The present study evaluates the reliability of a mobile based bicycle simulator that is built on motion platform to validate the model for future human-machine interaction experiments. The motion cues and the bicycle dynamics parameters were manipulated to form two driving profile. The driving task has also changed during the experiment. Motion sickness symptoms, subjective workload questionnaire, eye movements, and pupil dilation were recorded to compare how the workload change for the different driving profiles and driving tasks of the study. The present study revealed that one driving profile led to more motion sickness than the other profile which shows the importance of choosing the right parameters for the right setup of the bicycle simulator. Driving scenarios were rated approximately as optimally demanding without a difference between them. Two pupil dilation parameters, namely low pass filter and standard deviation, showed a difference in one scenario compared to others which could be interpreted as a change in the cognitive workload

An in-vitro assessment of the accuracy of fitting and occlusal surfaces of digitally and conventionally fabricated occlusal appliances

Purpose: This study compared the accuracy of the fitting and occlusal surfaces of digitally printed and conventionally fabricated occlusal appliances. Materials and Methods: Ten intraoral scans (TRIOS 3, 3Shape) of zirconia master models (Zr MM) were sent to a commercial dental laboratory to design and fabricate Digital Occlusal Appliances (DOAs) using a 3-D printing technology. Ten alginate impressions of the same zirconia models were utilized by the commercial dental laboratory to fabricate Ten Conventional Occlusal Appliances (COAs). The lab technician was instructed not to carry out any adjustments following manufacturing of the appliances. Benchtop scans were obtained of the DOAs and COAs fitting and occlusal surfaces to determine the accuracy compared to the benchtop scan of the Zr MM. In addition, linear measurements of the scans were compared for both DOAs and COAs. Results: A statistically significant difference in the individual tooth fit was observed; DOAs showed significantly higher conformity of the shapes of the fitting surfaces of selected teeth (#18, #16, #13, #23, #26, and #28). However, COAs showed significantly lower linear distortions in the arch level in most dimensions. DOAs on the other hand, showed significant distortions in linear measurements, especially in mediolateral dimensions. This mediolateral distortion in the DOAs was found to be positively correlated with increased arch length in these appliances. Conclusion: While DOAs can reproduce fitting surfaces of individual teeth at significantly higher accuracy than COAs, substantial linear distortions were observed in DOAs in the arch level, especially mediolaterally.Dentistry, Faculty ofGraduat

Green synthesis approach and applications of engineered nanomaterials in food safety

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Nowadays, food safety has received more awareness because of increasing foodborne illness outbreaks around the world that involved biological and chemical substances. Therefore, there are growing interests in using the emerging novel nanomaterials to solve food safety issues. However, the wide use of nanomaterials in the manufacturing of different products, especially in the food industry, raises more concerns about their toxicity and harmful effects on human health since flammable and hazardous substances are used in the synthesis process of these materials. This dissertation aimed to use nanomaterials (silver or gold nanoparticles, nanorods) as novel surface-enhanced Raman spectroscopy (SERS) substrates to detect chemical contaminants in various matrices of food samples, and use green chemistry methods to establish an environmentally-friendly procedure for the synthesis of green nanoparticles. Specific objectives of this study were to: (i) develop a facile and reproducible procedure to prepare standing gold nanorod arrays. The gold nanorod arrays can be coupled with the SERS technique to detect pesticides in fruit juice and milk samples; (ii) use plant extract to synthesize silver nanoparticles (AgNPs) and investigate their antibacterial activity against foodborne bacteria in broth and chicken meat; and (iii) evaluate the toxicity of green synthesized AgNPs on human colon cancerous epithelial (Caco-2) cells and human intestinal bacteria

The atelier- an environment for children’s development and learning.

Syftet med denna studie var att undersöka hur förskollärare beskriver ateljén som en miljö för barns utveckling och lärande. Vi har i denna kvalitativa studie intervjuat åtta förskollärare från förskolor med olika inriktningar, för att få insikt i förskollärares förhållningssätt, tankar, och erfarenheter kring de aktiviteter som sker i ateljén. Resultatet synliggör tre teman; ateljéns fysiska rum, ateljéns möjligheter och förhållningssätt. Förskollärarna i studien beskriver ateljén som en betydelsefull miljö för barns lärande och utveckling där pedagoger och barn samspelar, inspirerar och utmanar varandra. En inbjudande och tillåtande miljö i ateljén med rikt och stimulerande material beskrivs av förskollärarna som viktiga delar för att främja flera olika aspekter av barns utveckling och lärande.