Biomechanical and optical characterization of epidermal tissue

Kolorektalni karcinom je jedan od glavnih zdravstvenih problema u razvijenim zemljama. Opto-magnetna imidzing spektroskopija (OMIS) kao nova metoda za karakterizaciju različitih vrsta materijala, uključujući i ljudska tkiva, se u ovoj Disertaciji po prvi put koristi za rano otkrivanje raka debelog creva. OMIS metoda zasniva se na interakciji svetlosti i materije i daje biofizičke parametre za karakterizaciju tkiva zdravo/bolesno. Da bi se izmerila razlika zaostalog magnetizma između zdravog tkiva i tkiva karcinoma debelog creva, primenjen je dvobrzinski spinner magnetometar JR-6A, sa tačnošću 2,4 A/m (3pT). Kako su ove dve metode komplementarne, JR-6A je korišćen da karakteriše ukupnu zapreminu tkiva i potvrdi da optomagnetna imidžing spektroskopija koja meri paramagnetna/dijamagnetna svojstva tkiva u tankim površinskim slojevima daje relevantne podatke za klasifikaciju zdravo/bolesno. OMIS spektri daju tačnost do 92.5% korišćenjem višeslojne neuronske mreže kao klasifikatora, dok podaci magnetometra na bazi parametarskog frakcionog računa daju tačnost 86.1%. Ovim je pokazano da obe metode jasno razlikuju zdravo tkivo od kancerogenog. Dobijeni rezultati pokazuju da bi se ova nova neinvazivna metoda mogla koristiti za karakterizaciju tkiva ex vivo. Međutim, kao takva OMIS metoda otvara mogućnost korišćenja u in vivo uslovima u kombinaciji sa modifikovanom kolonopskopijom što bi lekarima pomoglo u ranijem otkrivanju kancera debelog creva.Colorectal carcinoma is one of the major health problems in industrialized countries. Opto-magnetic imaging spectroscopy (OMIS) as a new imaging method for the characterization of various materials, including human tissues, is used in this Dissertation for the first time for early detection of colon cancer. The OMIS method is based on light-matter interaction and allows biophysical criteria in tissue characterization, healthy/cancer. To measure the difference of the remanent magnetism between healthy and colon cancer tissue, a dual-speed spinner magnetometer JR-6A, with accuracy 2.4 A/m (3pT) was applied. As both of these methods are complementary to each other, JR-6A was used to characterize the total tissue volume and to confirm that opto-magnetic imaging spectroscopy measuring the paramagnetic/diamagnetic properties of tissue in thin surface layers providing relevant data for the healthy/cancer classification. OMIS spectra give an accuracy of up to 92.5% using the Perceptron multilayer neural network as a classifier, while magnetometer data give an accuracy of 86.1%. This shows that both methods clearly distinguish healthy tissue from cancer tissue. The obtained results indicate that this new non-invasive method could be used for ex vivo characterization. However, the OMIS method opens up the possibility of using the same method in in vivo studies in combination with modified colonoscopy to assist physicians in targeting biopsies of colorectal tissue

INTERDEPENDENCE OF CONTROL ACTIVITIES AND MONITORING AS COMPONENTS OF THE INTERNAL CONTROL SYSTEM OF MANUFACTURING COMPANIES IN THE REPUBLIC OF SERBIA

The subject of research in this paper is control activities and monitoring as components of the internal control system in manufacturing companies in the Republic of Serbia. The aim of this paper is to determine not only interdependence of control activities and monitoring, but also the interdependence of these components of the internal control system with indicators of ROA and ROE of a company. An additional goal of this paper is to examine the existence of differences in the assessment of the importance of control activities and monitoring applicable in manufacturing companies of different sizes. The research included a sample of manufacturing companies operating in the Republic of Serbia. The analysis was performed in the SPSS statistical program, where a correlation analysis was performed using the Pearson Coefficient, as well as the Kruskal-Wallis H test and the Mann-Whitney U test. The obtained results showed the existence of a strong positive link between control activities and monitoring, as well as weak links between control activities and monitoring, on one hand, and ROA and ROE indicators of the company, on the other hand. In addition, the results confirmed that there is no difference in the importance of the application of internal control systems, i.e. control activities and monitoring, in manufacturing companies of different sizes

Inflammatory modulation of the response of bronchial epithelial cells to lipopolysaccharide with pretreatment by montelukast

Montelukast, a leukotriene receptor antagonist, is the most prescribed nonsteroidal anti-inflammatory drug used as an add-on therapy for asthma. Besides its effect on blocking leukotriene action, montelukast has been proposed to have secondary anti-inflammatory properties. This study aimed to investigate the modulatory effect of montelukast on the expression of major genes involved in airway inflammation (TNF, IL6) and remodeling (MMP9, TGFB1) in response to lipopolysaccharide (LPS) in vitro. The expression of selected genes was measured by quantitative real-time polymerase chain reaction 0h and 24h after LPS stimulation in cells pretreated with montelukast. Montelukast was found to significantly attenuate increased TNF and IL6 gene expression, to have a mild effect on MMP9 and have no effect on TGFB1 expression upon stimulation with LPS. The results of our study indicate that patients on montelukast therapy would have an adequate response to acute microorganism-induced inflammation, so additional anti-inflammatory effects of montelukast should be better exploited

TGFB1 Gene Promoter Polymorphisms in Serbian Asthmatics

Background. Asthma is a chronic respiratory disease caused by a combination of genetic and environmental factors. Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine that plays an important role in airway remodeling in asthma. Objectives. The aim of this study was to analyze common TGFB1 gene promoter polymorphisms C-509T and G-800A in Serbian asthmatics and to investigate their association with exacerbations. Material and Methods. The study involved 102 asthmatics and 58 healthy individuals from Serbia, age and gender matched. An analysis of the TGFB1 promoter was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. For polymorphism C-509T a significant difference in the allele frequency was observed between the patients and the controls (p = 0.011), while the genotype distribution was similar in the analyzed groups, with statistical significance near the borderline (p = 0.061). For the polymorphism G-800A no difference was observed between the groups. The frequency of the -509TT genotype was higher in patients with exacerbations compared to patients without exacerbations (36.4% vs. 17.0%), with statistical significance near the borderline (p = 0.080). Conclusions. The results suggest that polymorphism C-509T may be associated with asthma and disease exacerbations, while G-800A is not significant for the etiology and clinical course of the disease. These findings should be confirmed in a larger study group, and since the TGFB1 promoter is highly complex and very responsive to environmental factors, future studies should also take other genetic and non-genetic factors into consideration

Evaluation of toxicity and antioxidative effects of Tussilago farfara and Verbascum thapsus water extracts in zebrafish and in bronchial epithelial cells

Tussilago farfara (coltsfoot) and Verbascum thapsus (mullein) have been used as folk remedies for treating respiratory disorders. The aim of this study was to test the toxicity of the water extracts of T. farfara and V. thapsus in vivo in zebrafish and in vitro in BEAS 2B epithelial bronchial cells. To the best of our knowledge, this is the first study to investigate the antioxidative properties of T. farfara and V. thapsus extracts in cell culture. Our results show that the T. farfara leaf extract does not produce toxic effects on zebrafish embryos or BEAS 2B cells, and that it has a protective effect in BEAS 2B after induction of oxidative stress. The water extract from V. thapsus displayed pronounced toxic effects on zebrafish embryos and BEAS 2B cells and did not exhibit a significant antioxidative effect on BEAS 2B cells exposed to oxidative stress. Our results suggest that the use of T. farfara water leaf extract is potentially safe and effective in treating respiratory disorders, whereas the use of V. thapsus needs further investigation

Adrb2 gene polymorphisms and salbutamol responsiveness in Serbian children with asthma

Inhaled beta 2 adrenergic receptor (beta 2-AR) agonists are the mainstay of asthma therapy. The beta 2-AR protein is encoded by the ADRB2 gene and variants within this gene can have significant consequences for modulating the response to asthma therapy. This cross-sectional study performed at the University Children's Hospital in Belgrade, included 54 children with asthma. The subjects were genotyped for ADRB2 +46A gt G (Arg16Gly, rs1042713) and +79C gt G (G1n27G1u, rs1042714) polymorphisms and the association with asthma severity and response to inhaled salbutamol was examined. In Serbian asthmatic children, allele +46A was detected with a frequency of 41.7% and allele +79G was detected with a frequency of 23.1%. Allele +460 was found to be associated with a better response to inhaled salbutamol (p lt 0.05) and with mild form of asthma (p lt 0.05). Polymorphism ADRB2 +46A gt G may be a determinant of asthma severity and response to salbutamol in children with asthma. We did not find any association of +79C gt G polymorphisms with the asthma severity and bronchodilator response to inhaled salbutamol. The results of this study can be potentially useful for personalization of asthma treatment

SMAD4-201 transcript as a putative biomarker in colorectal cancer

Background: Transcripts with alternative 5'-untranslated regions (UTRs) result from the activity of alternative promoters and they can determine gene expression by influencing its stability and translational efficiency, thus executing complex regulation of developmental, physiological and pathological processes. Transcriptional regulation of human SMAD4, a key tumor suppressor deregulated in most gastrointestinal cancers, entails four alternative promoters. These promoters and alternative transcripts they generate remain unexplored as contributors to the SMAD4 deregulation in cancer. The aim of this study was to investigate the relative abundance of the transcript SMAD4-201 in colorectal cell lines and tissues in order to establish if its fluctuations may be associated with colorectal cancer (CRC). Methods: Relative abundance of SMAD4-201 in total SMAD4 mRNA was analyzed using quantitative PCR in a set of permanent human colon cell lines and tumor and corresponding healthy tissue samples from patients with CRC. Results: The relative abundance of SMAD4-201 in analyzed cell lines varied between 16 and 47%. A similar relative abundance of SMAD4-201 transcript was found in the majority of analyzed human tumor tissue samples, and it was averagely 20% lower in non-malignant in comparison to malignant tissue samples (p = 0.001). Transcript SMAD4-202 was not detectable in any of the analyzed samples, so the observed fluctuations in the composition of SMAD4 transcripts can be attributed to transcripts other than SMAD4-201 and SMAD4-202. Conclusion: The expression profile of SMAD4-201 in human tumor and non-tumor tissue samples may indicate the translational potential of this molecule in CRC, but further research is needed to clarify its usability as a potential biomarker for early diagnosis

Different types of colorectal carcinoma characterization using stained and non stained plates by opto-magnetic spectroscopy

Prema podacima Svjetske zdravstvene organizacije, karcinom je vodeći uzrok smrti u svijetu, a na trećem mjestu je najuobičajeniji i najopasniji kolorektalni karcionom sa stopom od 17.3/100,000 pacijenata. Stoga je potrebno iznaći efektivna rješenja za poboljšanje kvaliteta i brzine dijagnostičkih alata koji će moći odgovoriti na izazove strategija prevencije koji su sastavni dio brze dijagnostike kod velikog broja pacijenata. Ciljevi istraživanja sprovedenog u ovom ispitivanju (in vitro) su: (1) ispitivanje mogućnosti primjene optomagnetne spektroskopije za karakterizaciju različitih vrsta karcinoma debelog crijeva, uz pomoć obojenih i neobojenih pločica, (2) validacija metode, (3) određivanje parametara za istraživanje u in vivo uslovima, i (4) primjena u kliničkim istraživanjima kako bi se poboljšala efikasnost i dobile pouzdanije dijagnoze. U ovom radu predstavljamo optomagnetnu spektroskopiju (OMIS) kao novu optičku metodu za diferenciranje različitih vrsta karcinoma debelog crijeva, kao i značajne sličnosti između obojenih i neobojenih pločica na osnovu uzajamnog djelovanja svjetlosti i tkiva. Rezultati su pokazali da se uz pomoć OMIS-a može naći razlika između kolorektalnog i drugih vrsta karcinoma debelog crijeva, kao i dokazati da je moguće izbjeći (bojenje) pločica.According to the World Health Organization cancer is the leading cause of death worldwide and on the third place is the most common and dangerous colorectal cancer with the rate of 17.3/100,000 people. Therefore, it is necessary to find effective solutions to improve the quality and speed of diagnostic tools so that they can respond to the challenges of prevention strategies which are an integral part of the rapid diagnosis of a large number of patients. The objectives of the research conducted in this study (in vitro) are: (1) examining the possibilities of application of opto-magnetic imaging spectroscopy for characterization between different types of colon cancer, stained and non-stained plates, (2) method validation, (3) parameters determination for research in in vivo conditions, and (4) application in clinical trial to increase the efficiency and give more reliable diagnosis. In this paper we present Opto-magnetic imaging spectroscopy (OMIS) as a novel optical method for differentiation of different types of colon cancer, significant similarity between stained and non-stained plates based on light-tissue interaction. Results have showed that OMIS can make a difference between colorectal carcinoma and other types of colon cancer, as well as prove that plates staining can be avoided

Outcome of early rehabilitation of patients with traumatic brain injury during COVID-19 pandemic in The Republic of Srpska, Bosnia and Herzegovina

IntroductionThe COVID-19 pandemic has placed a tremendous burden on the healthcare system. Patients with traumatic brain injury (TBI) have to get fast track treatment which is independent of environmental conditions. The aim of this study was to investigate epidemiological and clinical outcomes of early rehabilitation and compare it with the literature data during the non-COVID-19 period.Materials and methodsA retrospective study included 174 patients with TBI, average 57 ± 19.08 years. They all underwent treatment in the University Clinical Center, Republic of Srpska, Bosnia and Herzegovina during the period January-December 2021. We have analyzed the epidemiological data and clinical course in 174 patients as well as the outcome of early rehabilitation in 107 patients. In clinical evaluation were used: Glasgow Coma Score (GCS), Functional Independence Measure (FIM) and Barthel Index on admission and at discharge, as well as Glasgow Outcome Scale (GOS) at discharge. ANOVA, SPANOVA, Student t-test and Pearson correlation coefficient were used in statistical analysis. The value (p < 0.05) was used for statistical significance.ResultsA total of 174 patients with TBI were included in this study. Most of the patients (n = 94) were older than 60, male (n = 125) and the most frequent cause of TBI was falling over (n = 88). About a half (n = 92) had a mild TBI, almost one third of the sample had moderate (n = 52), while only 30 patients had severe TBI. Total of 139 (80.3%) patients had the improved outcome, the worsening was registered in 2 (1.2%), while the fatal outcome was reported with 33 (18.5%) patients. When comparing the scores on admission and at discharge, the improvement of mean parameter values was reported for GCS (9.9 vs. 14.1), for Barthel Index (57.25 vs. 86.85), and for FIM (67.35 vs. 105.15), (p < 0.001). A complete recovery at discharge was found in 63.79%, a mild deficit in 8.62%, while serious deficit was found with 6.32%, and vegetative state with 2.29% patients.ConclusionThe COVID-19 pandemic had a significant effect on the epidemiological data but not on the clinical outcome of patients with TBI. Early rehabilitation proved to be effective and to contribute to positive treatment outcome

3D analysis of different metamaterial geometry and simulation of metamaterial usage

Ovaj rad istražuje uticaj različitih geometrijskih struktura na nove koncepte formiranja tehničkih sistema. Sposobnost da neke geometrijske strukture budu u stanju da izdrže određeni nivo deformacije, koristilo se za zamenu zglobova u određenim sklopovima tehničkih sistema. Sada sva ta kretanja mogu da se postignu deformacijom geometrijskih struktura. Dobijeni rezultati iz simulacija, definišu nivo deformacije koje strukture mogu izdržati. Projektovanje 3D modela i simulacija sprovedeno je u SoildWorks 2016. U okviru ovog rada ispitano je nekoliko različitih struktura metamaterijala. Izvršene su 64 simulacije promenom unutrašnje strukture, debljine i orijentacije metamaterijala. Za svaki simulaciju kao rezyltat su dobijani naponi i pomeranja. Pored toga, izvršena je simulacija tri modela klješta, u kojima su upotrebljeni meta-materijali ispitivane geometrije, a rezultati su upoređeni sa rezultatima prethodnih simulacija.This paper investigates the influence of different geometrical structures on new concepts for the formation of technical systems. The ability of some geometric structures to withstand a certain level of deformation, was used to replace joints in certain assemblies of technical systems. Now, all movements are accomplished with deformation of geometrical structures. Obtained results from simulations define the level of deformation which structures can withstand. Designing of 3D models and simulations were conducted in SOLIDWORKS 2016. Several different structures of metamaterials will be examined. Sixty-four simulations were conducted by changing the internal structure, thickness and orientation of metamaterials. For each simulation, the results were presented as stresses and displacements. Additionally, three model of pliers have been simulated, and its results were compared with the results from previous simulations