SEM study of Thermafil obturation technique with 5 endodontic sealers

Aim: To measure layer thickness of 5 endodontic sealers and evaluate sealer distribution and adaptation of thermafil and sealer within root canals. Material and Methods: 20 single-rooted teeth divided into 5 groups were prepared in the crown-down technique. Smear layer was removed and root canals were obturated with Thermafil and 1 of 5 different endodontic sealers: AH Plus, Tubliseal, Acroseal, Apexit and Sealapex. Roots were cross-sectioned in 3 levels resulting in 4 sections for scanning electron microscopy (SEM). Results: Acroseal exhibited the greatest mean layer thickness, followed by AH Plus, while Tubliseal showed the thinnest mean layer. Sealers were unevenly distributed with incomplete layer along root canal perimeter. No sealer formed a continuous layer between the dentinal wall and guttapercha. Gaps of up to 10 μm were observed between core plastic carrier and gutta-percha. Microscopically visible voids were present in different levels of root canals, usually between dentinal wall and sealer/gutta-percha. Conclusions: The layer thickness in decreasing order were: Acroseal > AH Plus > Sealapex > Apexit > Tubliseal. Microgaps between dentinal wall and the obturating material and gutta-percha / carrier could contribute to inadequate adhesion within the root canal and increased microleakage of Thermafil compared to other obturation techniques

Full Newton-Step Interior-Point Method for Linear Complementarity Problems

In this paper we consider an Infeasible Full Newton-step Interior-Point Method (IFNS-IPM) for monotone Linear Complementarity Problems (LCP). The method does not require a strictly feasible starting point. In addition, the method avoids calculation of the step size and instead takes full Newton-steps at each iteration. Iterates are kept close to the central path by suitable choice of parameters. The algorithm is globally convergent and the iteration bound matches the best known iteration bound for these types of methods

Successful treatment of polymedicamentous poisoning with metoprolol, diltiazem and cilazapril

Introduction. Poisoning caused by drugs with cardiodepressive effects is an urgent condition in medicine which is associated with high mortality rate regardless of modern therapeutic methods. Accidental or intentional poisoning whit these drugs produces heart activity depression and cardiovascular collapse as consequences. Current therapy for severe poisoning caused by beta-blockers and calcium channel blockers includes both unspecific and specific antidote therapy whit glucagon, as well as application of adrenergic drugs, calcium, phosphodiesterase inhibitors and hyperinsulinemia/euglycemia therapy. However, even whit the application of these drugs, prompt measures of unspecific detoxication therapy and cardiopulmonary reanimation are crucial for survival of patients with severe poisoning. Case report. A 28-year-old female patient was hospitalized for cardiogenic shock and altered state of conscioussnes (Glasgow coma score = 4), caused by acute poisoning with 2 g of metoprolol (Presolol®), 1.8 g of diltiazem (Cortiazem®) and 50 mg of cilazapril (Zobox®). Prolonged cardiopulmonary resuscitation was applied during the first 16 hours of hospitalization, including administration of crystaline solutions (8 L), 17 mg of adrenaline, 4 mg of atropine, 4 mg of glucagone and 1.6 g of dopamine, with electro-stimulation by temporary pacemaker and mechanical ventilation. In a defined time period, normalized state of consciousness was registered, mechanical ventilation was stopped and normal heart activity and hemodynamic stability were accomplished. During hospitalization the patient was treated for mild pneumonia and after ten days, completely recovered, was released and sent to home treatment. Conclusion. Prompt measures of cardiopulmonary resuscitation and multidisciplinary treatment in intensive care units significantly increase the chances of complete recovery of a patient with severe poisoning caused by drugs with cardiodepressive efects

Pray drying process characterization and modelling in the solid dosage forms development by application of quality by design concept

Koncept dizajniranja kvaliteta predstavlja sistematski pristup farmaceutskom razvoju proizvoda koji podrazumeva procenu, unapređenje razumevanja i optimizaciju formulacije i proizvodnog procesa kombinovanom primenom prethodnog znanja, analize rizika i izvođenja eksperimenata. Tehnologija sušenja raspršivanjem našla je primenu u farmaceutskoj industriji zahvaljujući jednostavnosti i fleksibilnosti procesa, kao jednostepeni proces kojim se tečnost pretvara u prašak čije se brojne osobine mogu kontrolisati manipulacijom procesnih promenljivih. Razumevanje kako promene procesnih parametara mogu uticati na fizičkohemijske osobine dobijenog proizvoda posebno je važno u proizvodnji čvrstih doziranih oblika koja ima za cilj obezbeđenje predviđanja i kontrole performansi. Cilj ovog istraživanja je unapređenje razumevanja sušenja raspršivanjem kroz karakterizaciju i modelovanje procesa, primenom koncepta dizajniranja kvaliteta. Istraživanje se sastoji iz dva dela sa ciljevima: razvoja procesa sušenja raspršivanjem kao tehnologije pogodne za obezbeđivanje homogenosti praškova i, posledično, ujednačenosti doziranja nisko doziranih lekovitih supstanci (model supstanca naratriptan hidrohlorid); i razvoja procesa sušenja raspršivanjem u postupku proizvodnje praška sa teško rastvorljivim model supstancama, u cilju poboljšanja rastvorljivosti formiranjem kompleksa sa ciklodekstrinima (model supstance vorikonazol i aripiprazol). Istraživanje takođe obuhvata ispitivanje mogućnosti primene dva derivata beta-ciklodekstrina: 2-hidroksipropilbeta- ciklodekstrina (HPBCD) i 2-O-metil-beta-ciklodekstrina (2-O-MBCD) u razvoju formulacije rastvora za raspršivanje sa ciljem poboljšanja rastvorljivosti i brzine rastvaranja odabranih model supstanci. Tokom razvoja, u skladu sa ciljanim profilom praška kao međuproizvoda definisanom u smislu kvaliteta, identifikovani su kritični atributi kvaliteta međuproizvoda, zatim definisani kritični atributi kvaliteta ulaznih parametara (osobine materijala, procesni parametri) i određivane su njihove funkcionalne veze sa kritičnim atributima kvaliteta proizvoda. U prvom delu istraživanja ispitivani su efekti procesnih parametara sušenja raspršivanjem (temperatura ulaznog vazduha, brzina pumpe, brzina aspiratora, koncentracija rastvora) na karakteristike procesa i kompozitnog praška naratriptan/laktoza/maltodekstrin (proizvodni prinos, sadržaj vlage i srednja veličina čestica). U drugom delu istraživanja sprovedene su studije rastvorljivosti teško rastvorljivih model supstanci sa ciklodekstrinima, simulacije molekularnog vezivanja, izvršena je karakterizacija praškova dobijenih sušenjem raspršivanjem rastvora lek:ciklodekstrin. Na odabranoj formulaciji sa aripiprazolom i HPBCD, izvršena je karakterizacija i modelovanje sušenja raspršivanjem. Ispitivani su efekti procesnih parametara sušenja raspršivanjem (temperatura ulaznog vazduha, brzina pumpe, koncentracija rastvora) na karakteristike procesa i kompozitnog praška lek:ciklodekstrin (proizvodni prinos, sadržaj vlage). U karakterizaciji i modelovanju procesa primenjeni su eksperimentalni dizajn, metodologija površine odgovora (RSM) i veštačka neuronska mreža tipa višeslojnog perceptrona (MLP). Primena frakcionog faktorijalnog dizajna (24-1) kao skrining metode omogućila je procenu značajnosti ispitivanih parametara, na osnovu koje je iz daljeg istraživanja isključena brzina aspiratora. Primena centralnog kompozitnog dizajna (CCD), RSM i MLP omogućila je modelovanje i karakterizaciju procesa sušenja raspršivanjem ispitivanih formulacija sa sve tri model supstance, tako što su razvijeni značajni modeli (p-vrednost<0.05)...Quality by design concept represents systematic approach to pharmaceutical product development which consists of assessment, improvement of formulation and process understanding and optimization by combined use of previous knowledge, risk analysis and experimental work. Spray drying technology has found its use in pharmaceutical industry thanks to process simplicity and flexibility, as a single-step process in which liquid is transferred into powder with properties easily controlable by process variables manipulation. Understanding how changes in process parameters can influence the physicochemical properties of resulting product, is especially important in production of solid dosage forms where assurance of predictions and control of performance are the main goals. Main goal of this research is spray drying understanding improvement through process characterization and modelling performed by quality by design concept. The research consists of two sections with following goals: spray drying process development as technology suitable for providing homogeneous powders and subsequently, dose uniformity of low-dose drug substances (model substance naratriptan hydrochloride); and spray drying process development in production of powders with poorly soluble drug substances (model substances voriconazole and aripiprazole). The research is also dealing with examination of potential use of two beta-cyclodextrin derivatives: 2- hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD) for the purpose of solubility and dissolution improvement of selected model substances. Within the development process, according to quality target product profile for powder as a intermediate product, critical product quality attributes were identified, and then critical quality attributes for input parameters (material properties, process parameters) were defined and their functional relationships with critical product quality attributes were determined. In first section of research, effects of spray drying process parameters (inlet air temperature, pump speed, aspirator, feed concentration) on process and powder characteristics (production yield, moisture content and mean particle size) were examined. In the second section of research solubility studies with poorly soluble substances and cyclodextrins were conducted, as well as molecular docking simulations, and characterisation of spray dried drug:CD powders was performed. For selected formulation with aripiprazole and HPBCD, spray drying process characterisation and modelling was performed. Effects of spray drying process parameters (inlet air temperature, pump speed, feed concentration) on process and powder characteristics (production yield and moisture content) were examined. Design of experiments, response surface methodology (RSM) and artificial neural networks multilayer perceptron (MLP) were used in process characterisation and modelling. Fractional factorial design (24-1) applied as a screening method enabled examined parameters significance assessment, based on which parameter aspirator was excluded from further study. Use of central composite design (CCD), RSM and MLP helped in spray drying process characterisation and modelling for formulations with all threee model drug substances, and significant models were developed (p-value<0.05). RSM results analysis resulted in definition of functional relationships between input parameters and monitored responses. In case of naratriptan hydrochloride and aripiprazole formulation, observations were similar. Parameter that had the greates influence on each investigated response was pump speed..

Karakterizacija dupleks tvrdih prevlaka sa dodatnom ionskom primjenom

In this paper, we present the results of a study of TiN thin films which are deposited by a Physical Vapour Deposition (PVD) and Ion Beam Assisted Deposition (IBAD). In the present investigation the subsequent ion implantation was provided with N+2 ions. The ion implantation was applied to enhance the mechanical properties of surface. The thin film deposition process exerts a number of effects such as crystallographic orientation, morphology, topography, densification of the films. The evolution of the microstructure from porous and columnar grains to densel packed grains is accompanied by changes in mechanical and physical properties. A variety of analytic techniques were used for characterization, such as scratch test, calo test, Scanning electron microscopy (SEM), Atomic Force Microscope (AFM), X-ray diffraction (XRD) and Energy Dispersive X-ray analysis (EDAX).U ovom radu pretstavljaju se rezultati istraživanja TiN tankih fi lmova, nanešenih fi zičkim odlaganjem iz parne faze i te podržani ionskim snopom. U ovom istraživanju je izvršena i naknadna ionska primjena sa N+2 ionima. Ionska primjena je sprovedena radi poboljšanja mehaničkih svojstava površina. Proces nanošenja tankih fi lmova karakterizira veliki broj učinaka, kao što su: kristalografska orijentacija, morfologija, topografi ja, gustoća fi lma. Razvoj mikrostrukture od porozne i stubaste u zrnastu gusto pakovanu, se dešava uz istovremenu promjenu mehaničkih i fi zičkih svojstava. Za karakterizaciju su rabljene različite analitičke tehnike, kao što su test zaparavanja, kalo test, skenirajući elektronski mikroskop (SEM), mikroskop atomskih sila (AFM), rentgenska difrakcija X zraka (XRD) i energijska disperzivna analiza X zraka (EDAX)

Rešavanje problema interfejsne prsline u elasto-plastičnim i ojačanim materijalima

Prslina se najčešće pojavljuje na interfejsu između dva različita materijala, jer je žilavost interfejsa manja od žilavosti materijala koji ga obrazuju. Određivanje žilavosti interfejsne prsline u bimaterijalnim kombinacijama je osnovno za analizu mehanizma loma u primenjenim materijalima. U disertaciji je razmatran problem prsline koja skreće sa interfejsa i nastavlja da se širi u jednom od materijala. Analiziran je uticaj elastičnosti materijala koji obrazuju interfejs na ponašanje prsline koja se širi na interfejsu, kao i prsline koja se približava interfejsu. Rezultati dobijeni u disertaciji navode na zaključak da će prslina težiti da ostane na interfejsu bez obzira na opterećenje ukoliko je elastičniji materijal jači od interfejsa, a materijal veće krtosti jak bar koliko i interfejs. U ovoj disertaciji je prikazano i rešenje za problem prsline na interfejsu između dva elastično-plastična materijala unutar okvira definisanog nelinearnom mehanikom loma u homogenim materijalima. Rešenja su izvedena za materijale opisane J2 -deforma- cionom teorijom. Naponsko polje blizu vrha prsline za spojene elasto-plastične materijale u uslovima tečenja u malom obimu, dobro se slaže sa mešovitim modom HRR polja za homogene materijale. U okviru disertacije data je i analiza ponašanja tankih filmova i prevlaka primenjujući elastičnu mehaniku loma. Data je analiza ivičnog raslojavanja prevlake i uticaja položaja ivice prevlake u odnosu na ivicu osnove kao i uslovi pod kojima nastupa raslojavanje bubrenjem. Analizom se došlo do zaključka da uglovne ivice osnovnog materijala daju suštinsku unutrašnju zaštitu protiv raslojavanja prevlaka interfejsa. Unutrašnje ivice nemaju tu karakteristiku. Na osnovu analize prikazane u ovoj disertaciji može da se izvede zaključak da elastične karakteristike osnove imaju značajan uticaj na raslojavanje prevlake bubrenjem u obliku dugačkog ravnostranog mehura. Data je takođe i analiza raslojavanja tankog filma sa osnove u uslovima kada se u jednom od materijala koji čine interfejs javljaju nelinearne, elasto-plastične deformacije. Koristeći se prednostima programskog paketa Mathematica® uz analitičko-numeričku analizu određene su granice u kojima se javlja tečenje u malom i velikom obimu. Analizom je prikazano da u slučaju pojave elasto-plastičnih deformacija debljina filma igra značajnu ulogu na veličinu pobudne sile samo u jednom malom opsegu. Čim se ta zona pređe u oblasti vrha prsline se javljaju samo tečenja u malom obimu i se mogu primeniti zaključci iz glave tri ovog rada.In this dissertation is considered the problem of an interfacial crack that is deflecting from the interface and continues to propagate in one of the two materials. The influence of elasticity of materials that constitute the interface, on behavior of a crack that propagates along the interface and the crack approaching the interface was analyzed. Results obtained in this research point to the conclusion that the crack would tend to remain at the interface regardless of the applied loading if the more ductile of the two materials is tougher than the interface and the more brittle material is at least as tough as the interface. The solution for the problem of a crack at the interface between the two elastic-plastic materials, within the framework defined by the nonlinear fracture mechanics, is also presented in this dissertation. The solutions were derived for materials defined by the J2-deformation theory. The stress field at the crack tip for the joined elastic-plastic materials, within the small scale yielding conditions, is in good agreement with the mixed mode HRR field for the homogeneous materials. Analysis of the thin films behavior and coatings is also presented with application of the elastic fracture mechanics. An analysis is presented of the coating edge delamination, as well as analysis of influence of the edge position with respect to the edge of the substrate and the conditions in which the delamination by bubbling would occur. That analysis led to conclusion that corner edges of the substrate material act as substantial interior protection against the interface delamination. The interior edges do not possess that characteristic. Based on analysis, presented in this dissertation, one can come up with the conclusion that elastic characteristics of the substrate have significant influence on coating delamination by bubbling in the case of the straight double-sided blister. The analysis of thin film delamination from the substrate is also presented for the case when in one of the materials, which constitute the interface, appear nonlinear, elastic-plastic strains. The limits of appearance of the small scale or large scale yielding were established by exploiting the advantages of the symbolic programming routine Mathematica, accompanied by the analytical-numerical analysis. It was shown, that in the case of appearance of the elastic-plastic strains, the thin film thickness imposes the significant influence on magnitude of the excitation force, only within the small range. As soon as that range is exceeded, in the vicinity of the crack tip appear only the small scales yielding conditions

Characterization of duplex hard coatings with additional ion implantation

In this paper, we present the results of a study of TiN thin fi lms which are deposited by a Physical Vapour Deposition (PVD) and Ion Beam Assisted Deposition (IBAD). In the present investigation the subsequent ion implantation was provided with N⁺² ions. The ion implantation was applied to enhance the mechanical properties of surface. The thin film deposition process exerts a number of eff ects such as crystallographic orientation, morphology, topography, densifi cation of the fi lms. The evolution of the microstructure from porous and columnar grains to densel packed grains is accompanied by changes in mechanical and physical properties. A variety of analytic techniques were used for characterization, such as scratch test, calo test, Scanning electron microscopy (SEM), Atomic Force Microscope (AFM), X-ray diff raction (XRD) and Energy Dispersive X-ray analysis (EDAX)

Hybrid dysgenesis in two natural populations of Drosophila melanogaster

nul

7T functional MRI finds no evidence for distinct functional subregions in the subthalamic nucleus during a speeded decision-making task

The subthalamic nucleus (STN) is a small, subcortical brain structure. It is a target for deep brain stimulation, an invasive treatment that reduces motor symptoms of Parkinson’s disease. Side effects of DBS are commonly explained using the tripartite model of STN organization, which proposes three functionally distinct subregions in the STN specialized in cognitive, limbic, and motor processing. However, evidence for the tripartite model exclusively comes from anatomical studies and functional studies using clinical patients. Here, we provide the first experimental tests of the tripartite model in healthy volunteers using ultra-high field 7 Tesla (T) functional magnetic resonance imaging (fMRI). Thirty-four participants performed a random-dot motion decision-making task with a difficulty manipulation and a choice payoff manipulation aimed to differentially affect cognitive and limbic networks. Moreover, participants responded with their left and right index finger, differentially affecting motor networks. We analysed BOLD signal in three subregions of the STN along the dorsolateral-ventromedial axis, identified using manually delineated high resolution anatomical images and based on a previously published atlas. Using these paradigms, all segments responded equally to the experimental manipulations, and the tasks did not provide evidence for the tripartite model

Charting human subcortical maturation across the adult lifespan with in vivo 7 T MRI

The human subcortex comprises hundreds of unique structures. Subcortical functioning is crucial for behavior, and disrupted function is observed in common neurodegenerative diseases. Despite their importance, human subcortical structures continue to be difficult to study in vivo. Here we provide a detailed account of 17 prominent subcortical structures and ventricles, describing their approximate iron and myelin contents, morphometry, and their age-related changes across the normal adult lifespan. The results provide compelling insights into the heterogeneity and intricate age-related alterations of these structures. They also show that the locations of many structures shift across the lifespan, which is of direct relevance for the use of standard magnetic resonance imaging atlases. The results further our understanding of subcortical morphometry and neuroimaging properties, and of normal aging processes which ultimately can improve our understanding of neurodegeneration