Izrada programske podrške za GSM modemski sklop za bežičnu komunikaciju sa programabilnim logičkim kontrolerom

U radu se opisuje povezivanje TC35 GSM modemskog sklopa s programabilnim logičkim kontrolerom (PLC-om) Simatic S7 200 primjenom RS485 komunikacijskog protokola čime se dobiva mogućnost bežičnog slanja i primanja informacija. Osmišljena je programska podrška za prijem i slanje podataka između korisnika i PLC-a preko TC35 GSM modemskog sklopa. Slanjem SMS poruke definiranog sadržaja moguće je djelovati na stanja ulaza i izlaza PLC-a, tražiti informaciju o stanju nekog ulaza i izlaza ili primiti informaciju o nekoj promjeni stanja varijabli programa. Na osnovi dobivenih informacija moguće je obavijestiti korisnika i/ili djelovati unutar sustava nadzora, i to sve iz bilo koje lokacije koja je pokrivena GSM signalom. Funkcionalnost sklopovlja i programske podrške ispitana je na primjeru nadzora prostorije, gdje je bilo praćeno koliko je ljudi ušlo i izašlo iz prostorije u jednom danu te koliko ih se trenutno nalazi u prostoriji. Nadalje, praćena je temperatura u prostoriji i stanje sustava rasvjete te je također omogućeno da se porukom može promijeniti stanje rasvjete

Determination of Rare Genomic Variants Leading to Hematological Malignancies Using Next-Generation Sequencing

Rare hematological malignancies are a heterogeneous group of the disease. Malignant transformation of a hematopoietic stem cell is a result of gradual accumulation of mutations in a number of genes involved in basic cellular processes. One of the main goals in the study of hematological malignancies is the definition of genomic markers crucial for the development of the disease, as well as for recognition of multiple entities characterized by distinct prognosis and outcome of the disease. Application of new highthroughput technologies has enabled better insight into genomic landscape of hematological malignancies. The most important achievement of genome-based medicine is more precise classification of patients with hematological malignancies, based on newly discovered molecular markers, and molecular–targeted therapy, tailored to genomic profile of a disease. In our studies we applied amplicon based next generation sequencing (NGS) approach, using TruSeq Amplicon Cancer Panel (Illumina, Inc) for analysis of 48 cancer-related genes in primary diffuse large B-cell lymphoma of central nervous system (DLBCL CNS), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Our findings strongly suggested that the TP53 and ATM genes were involved in the molecular pathophysiology of primary DLBCL CNS. Mutations in the PTEN and SMO genes affect survival of the patients. Additionally, we found that AML and ALL contain small number of genetic alterations, contrary to lymphomas. While protein-changing variants were found in tyrosine kinase genes, genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) and in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1) in patients with AML, the mutations detected in ALL patients are related to key signaling pathways, primarily on Ras/RTK cascade. Application of next-generation sequencing technology resulted in the information about genetic profile of each patient. Individual genetic profiling leads to highly specific personalized therapy of hematological malignancies

Individualized therapy: Role of thiopurine S-methyltransferase protein and genetic variants

Tiopurin S-metiltransferaza (TPMT: EC 2.1.1.67) jeste enzim koji metaboliše imunosupresivne tiopurinske lekove, koji se koriste za lečenje autoimunih bolesti, malignih oboljenja i u transplantacionoj medicini. Aktivnost enzima TPMT kod pojedinih ljudi je izrazito smanjena ili povećana u odnosu na normalni nivo aktivnosti. Istraživanja strukture i biohemijskih karakteristika proteina TPMT su ukazala na postojanje određenih proteinskih varijanti koje imaju izmenjenu aktivnost. Otkriveni su polimorfizmi u genu za TPMT koji daju različite TPMT alozime. Smanjenoj aktivnosti enzima može doprineti i manja količina sintetisanog proteina, što zavisi i od transkripcione aktivnosti promotora gena za TPMT. Polimorfizmi u samom promotoru, kao što je promenjiv broj tandemskih ponovaka (VNTR), mogu da modulišu transkripciju. Primena tiopurinskih lekova kod pacijenata sa određenim genetskim varijantama TPMT izaziva tešku hematološku toksičnost. Da bi se toksičnost izbegla, terapija se modifikuje u skladu sa genotipom TPMT (farmakogenetika). Mi smo izučavali polimorfizme u egzonima i regulatornim elementima (promotor) gena za TPMT koji dovode do promene aktivnosti enzima TPMT u srpskoj populaciji. Koristili smo metodologiju baziranu na PCR i DNK sekvenciranje za detekciju genetskih varijanti TPMT. Pokazali smo da su u našoj populaciji prisutne genetske varijante u egzonima koje ukupno daju 7,5% varijantnih alozima TPMT koji imaju smanjenu enzimsku aktivnost. Terapija za pacijente koji imaju ove farmakogenetičke markere je modifikovana, što je doprinelo uspešnijem lečenju. Funkcionalnim esejima in vitro smo pokazali da aktivnost promotora gena za TPMT, a samim tim i količina sintetisanog enzima TPMT, zavisi od arhitekture (broja i tipa) VNTR u promotoru. Promotor gena za TPMT specifično odgovara na tretman ćelija K562 tiopurinom zavisno od tipa VNTR. Izučavanje interakcija DNK i proteina je otkrilo da transkripcioni faktori Sp1 i Sp3 interaguju sa VNTR. Naša istraživanja ukazuju na to da bi region VNTR u promotoru gena za TPMT mogao postati novi farmakogenetički marker od kliničkog značaja za individualizaciju tiopurinske terapije.Thiopurine S-methyltransferase (TPMT: EC 2.1.1.67) is an enzyme that metabolizes immunosuppressive thiopurine medications, used in the treatment of autoimmune diseases, cancer and in transplantation medicine. In some individuals, TPMT enzyme activity is significantly increased or decreased compared to the normal TPMT activity level. Structural and biochemical analyses of the TPMT protein revealed the existence of certain protein variants with altered activity. It has been shown that certain TPMT gene polymorphisms exist, that define different TPMT allozymes. Decreased TPMT enzyme activity can also be a consequence of lower protein synthesis, which depends on the promoter transcription activity. Promoter polymorphisms, such as variable number of tandem repeats (VNTR), can modulate the transcription. Administering thiopurine drugs in patients with certain genetic TPMT variants leads to severe hematologic toxicity. To avoid toxicity, therapy is being modified according to the TPMT genotype (pharmacogenetics). We investigated the polymorphisms in exons and regulatory elements (promoter) of the TPMT gene which affect TPMT enzyme activity in the Serbian population. We used PCR-based methodology and sequencing in the detection of genetic variants on TPMT gene. We showed that genetic variants in exons account for 7.5% of all TPMT variants with decreased enzyme activity. The therapy for patients with these pharmacogenetic markers was modified, which contributed to the efficiency of treatment. Functional assays in vitro showed that the TPMT promoter activity and, therefore, the quantity of TPMT protein synthesized, depended on the architecture of VNTRs (i.e. number and type) in the promoter. Promoter of the TPMT gene specifically responds to mercaptopurine treatment of K562 cells in a VNTR-dependent manner. Study of DNA-protein interactions revealed that Sp1 and Sp3 transcription factors interact with VNTRs. Our research pointed out that the VNTR promoter region of the TPMT gene could become a new pharmacogenetic marker, clinically significant for the individualization of thiopurine therapy

Enamel extensions on deciduous teeth- an example on late medieval archaeological sample in Bosnia and Herzegovina

Description of morphological dental traits is an important concept within dental anthropology. The aim of this paper is to describe the case of occurrence of the enamel extensions in deciduous teeth in archaeological sample. The case of occurrence of enamel extensions on deciduous teeth from late medieval child’s skeletal remains is reported, along with other relevant data. Conclusion is that this might be the first such case described in medieval Bosnian archaeological population

Molecular genetic markers as a basis for personalized medicine

Genetika i genomika su danas potpuno integrisane u medicinsku praksu. Personalizovana medicina, poznata i kao medicina zasnovana na genomu, koristi znanja o genetičkoj osnovi bolesti da bi se individualizovalo lečenje svakog pacijenta. Veliki broj genetičkih varijanti, molekularno-genetičkih markera, već se koristi u kliničkoj praksi za dijagnozu, prognozu i praćenje bolesti (monogenska nasledna oboljenja, fuzioni geni i rearanžmani u pedijatrijskim i adultnim leukemijama) i presimptomatsku procenu rizika od obolevanja (BRCA1/2 za kancer dojke). Osim toga, primena farmakogenomike u kliničkoj praksi značajno je doprinela individualizaciji terapije u skladu sa genotipom i profilom ekspresije gena pacijenta. Genetičko testiranje za nekoliko farmakogenomičkih markera (TPMT, UGT1A1, CYP2C9, VKORC1) obavezno je ili se preporučuje pre započinjanja terapije. Najvažniji doprinos medicine zasnovane na genomu je ciljana molekularna terapija, prilagođena genetskom profilu bolesti. Testiranje genetičkih varijanti u malignim oboljenjima (BCR-ABL, PML/RARa, RAS, BCL-2, KIT, PDGFR, EGF) doprinosi tačnijoj stratifikaciji različitih kancera i adekvatnom izboru terapije. Krajnji cilj medicinske nauke je da primeni gensku terapiju koja bi eliminisala uzrok bolesti ili prevenirala bolest, ciljajući genetički defekt koji leži u osnovi bolesti. Tehnologija koja prati gensku terapiju veoma se brzo razvija i već se uspešno primenjuje. Iako je medicina oduvek suštinski bila "personalizovana", prilagođena svakom pacijentu, personalizovana medicina danas koristi modernu tehnologiju i znanja iz oblasti molekularne genetike i genomike, omogućujući stepen personalizacije koji vodi ka značajnom napretku medicinske prakse.Nowadays, genetics and genomics are fully integrated into medical practice. Personalized medicine, also called genome-based medicine, uses the knowledge of the genetic basis of disease to individualize treatment for each patient. A number of genetic variants, molecular genetic markers, are already in use in medical practice for the diagnosis, prognosis and follow-up of diseases (monogenic hereditary disorders, fusion genes and rearrangements in pediatric and adult leukemia) and presymptomatic risk assessment (BRCA 1/2 for breast cancer). Additionally, the application of pharmacogenomics in clinical practice has significantly contributed to the individualization of therapy in accordance with the patient's genotype and gene expression profile. Genetic testing for several pharmacogenomic markers (TPMT, UGT1A1, CYP2C9, VKORC1) is mandatory or recommended prior to the initiation of therapy. The most important achievement of genome-based medicine is molecular-targeted therapy, tailored to the genetic profile of a disease. Testing for gene variants in cancer (BCR-ABL, PML/RARa, RAS, BCL-2) is part of the recommended evaluation for different cancers, in order to achieve better management of the disease. The ultimate goal of medical science is to develop gene therapy which will fight or prevent a disease by targeting the disease-causing genetic defect. Gene therapy technology is rapidly developing, and has already been used with success. Although medicine has always been essentially "personal" to each patient, personalized medicine today uses modern technology and knowledge in the field of molecular genetics and genomics, enabling a level of personalization which leads to significant improvement in health care

Pharmacogenomics and pharmacotranscriptomics of acute leukemia in children: a path to personalized medicine

Personalized medicine is focused on research disciplines which contribute to the individualization of therapy, like pharmacogenomics and pharmacotranscriptomics. Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. It is one of the pediatric malignancies with the highest cure rate, but still a lethal outcome due to therapy accounts for 1- 3% of deaths. Further improvement of treatment protocols is needed through implementation of pharmacogenomics and pharmacotranscriptomics. Emerging high-throughput technologies, microarrays and next-generation sequencing, have provided an enormous amount of molecular data with potential to be implemented in childhood ALL treatment protocols. In the current review, we summarized the contribution of these novel technologies to pharmacogenomics and pharmacotranscriptomics of childhood ALL. We have presented data on molecular markers responsible for efficacy, side effects and toxicity of the drugs commonly used for childhood ALL treatment, i.e., glucocorticoid drugs, vincristine, asparaginase, anthracyclines, thiopurines and methotrexate. Big data was generated using high-throughput technologies, but their implementation in clinical practice is poor. Research efforts have to be focused on data analysis and designing prediction model using machine learning algorithms. Bioinformatics tools and implementation of artificial intelligence are expected to open the door wide for personalized medicine in clinical practice of childhood ALL.Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina - ABMBBIH May, 202

Precision medicine and COVID-19: Importance of host genome profiling

Introduction: The clinical picture and the course of the disease in COVID-19 patients, caused by coronavirus SARS-CoV-2, vary from asymptomatic to fatal outcome. As the same agent cause the disease, the individual genomic profile of the patient could contribute to better understanding of this phenomenon. The current knowledge about genetic markers responsible for a wide range of clinical pictures, as well as possible application of individualized treatment, will be presented. Methods: Variantsin genesresponsible for predisposition and response to SARS-CoV-2 infection, pharmacogenetic variantsrelated to drugs used in the treatment of COVID-19, nutrigenetic markersin genes relevant for the metabolism of the micronutrients(vitamin D,selenium and zinc) were investigated using GWAS, PCR and sequencing. Genotype data were extracted from database previously obtained using TruSight One Gene Panel (Illumina). Results: Eleven pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment and 10 variants affecting the structure and/or function of proteinsimportant forsusceptibility and resistance to SARS-CoV-2 infection were identified. Several variants in genes related to micronutrients were associated with severe COVID-19. Moreover, GWAS detected a significant genetic signal associated with COVID-19 related pneumonia. Conclusion: Multidisciplinary approach, modern sequencing technologies, comprehensive studies with well-characterized patients’groups, as well as the design of robust bioinformatics tools, enable identification of novel human genetic markers associated with COVID-19. Newly gained knowledge will empower the development of the targeted therapy, as well as the implementation of nutrigenomics/pharmacogenomics, leading to the application of precision medicine in the treatment of COVID-19 patients

Primjena Balanced Scorecard metode u javnom zdravstvu : Studij slučaja Primorsko-goranske županije

Strateški problemi javnog zdravstva Primorsko-goranske županije (PGŽ) očituju se su u slaboj povezanosti te neujednačenoj kvaliteti i dostupnosti zdravstvene zaštite. Pokazatelji zdravlja su značajno bolji od nacionalnog prosjeka ali su u usporedbi s europskim prosjecima i dalje loši. Boljom suradnjom javnih i privatnih zdravstvenih ustanova osigurala bi se veća konkurentnost, niži troškovi, učinkovitija, dostupnija i kvalitetnija zdravstvena zaštita za sve stanovnike i turiste PGŽ. Promocijom Županije kao prepoznate destinacije za razvoj zdravstvenog, sportsko-rekreativnog i drugih oblika turizma olakšao bi se izlazak na inozemna tržišta dok bi se poticanjem razvoja dobrovoljnih zdravstvenih osiguranja rasteretilo javni sustav zdravstva. Kako bi zdravstveni turizam PGŽ postao samoodrživ u današnjem izrazito konkurentskom poslovnom okruženju, ustanove koje se bave zdravstvenim turizmom trebale bi posvetiti dosta vremena i energije zaposlenika za ostvarenje svojih strateških ciljeva. Ti ciljevi su ugrađeni u misiji i viziji poslovanja javnozdravstvenih ustanova. Vodstvo organizacija treba iskoristiti te ciljeve, te edukacijom zaposlenika prikazati gdje žele vidjeti svoje ustanove u budućnosti. Stoga je glavni cilj ovog rada definirati model za mjerenje ostvarenja ciljeva razvoja zdravstvenog turizma PGŽ. Metodom studija slučaja definira se rezultat ovog istraživanja odnosno ključni pokazatelji poslovanja, grupirani u 4 perspektive, koji omogućavaju operacionalizaciju strateških ciljeva razvoja zdravstvenog turizma PGŽ. Sustavi koji mjere, prate i bilježe informacije o učinkovitosti poslovanja javnozdravstvenih ustanova su puni nedostataka. Osnovne mjere praćenja poslovanja su financijske naravi te prikazuju povijesne podatke, čime ne mogu usmjeriti kako će se organizacije ponašati u budućnosti. Balanced Scorecard (BSC) je model koji prevodi strategiju organizacije u ciljeve učinaka, mjera i inicijativa kroz uravnotežene perspektive. BSC ne gleda samo financijsko stanje organizacije već sagledava i poslovanje s aspekata kupaca, internih procesa te zaposlenika u pogledu učenja i rasta poduzeća.Strategic problems of Public Health of the Primorsko-goranska County (PGC) are poorly linked and unequal quality and availability of health care. Health indicators are significantly better than the national average but are still poor compared to European averages. Better co-operation between public and private health institutions would ensure greater competitiveness, lower costs, more efficient, accessible and better quality health care for all residents and tourists of PGC. The promotion of the County as a recognized destination for the development of health, sports and recreational and other forms of tourism would facilitate the emergence of foreign markets, while the promotion of the development of voluntary health insurance would relieve the public health system. In order to make PGC health tourism sustainable in today's highly competitive business environment, healthcare institutions should dedicate enough time and energy to achieving their strategic goals. These goals are embedded in the mission and vision of public health institutions. Leadership organizations should take advantage of these goals and educate employees to show where they want to see their institutions in the future. Therefore, the main goal of this work is to define a model for measuring the achievement of the goals of development of health tourism in PGC. The method of case studies defines the result of this research, i.e. key performance indicators, grouped in 4 perspectives, which enable the operationalization of the strategic goals of the development of health tourism in the PGC region. Systems that measure, monitor and record information on the efficiency of public health care operations are full of disadvantages. Basic business monitoring measures are financial in nature that displays historical data, so they cannot direct how organizations will behave in the future. The Balanced Scorecard (BSC) is a model that translates the organization's strategy into the goals of impacts, measures and initiatives through a balanced perspective. The Balanced Scorecard is not just looking at the financial state of the organization, but it also uses customer information, internal processes, employees, learning and growth

Primjena Balanced Scorecard metode u javnom zdravstvu : Studij slučaja Primorsko-goranske županije

Strateški problemi javnog zdravstva Primorsko-goranske županije (PGŽ) očituju se su u slaboj povezanosti te neujednačenoj kvaliteti i dostupnosti zdravstvene zaštite. Pokazatelji zdravlja su značajno bolji od nacionalnog prosjeka ali su u usporedbi s europskim prosjecima i dalje loši. Boljom suradnjom javnih i privatnih zdravstvenih ustanova osigurala bi se veća konkurentnost, niži troškovi, učinkovitija, dostupnija i kvalitetnija zdravstvena zaštita za sve stanovnike i turiste PGŽ. Promocijom Županije kao prepoznate destinacije za razvoj zdravstvenog, sportsko-rekreativnog i drugih oblika turizma olakšao bi se izlazak na inozemna tržišta dok bi se poticanjem razvoja dobrovoljnih zdravstvenih osiguranja rasteretilo javni sustav zdravstva. Kako bi zdravstveni turizam PGŽ postao samoodrživ u današnjem izrazito konkurentskom poslovnom okruženju, ustanove koje se bave zdravstvenim turizmom trebale bi posvetiti dosta vremena i energije zaposlenika za ostvarenje svojih strateških ciljeva. Ti ciljevi su ugrađeni u misiji i viziji poslovanja javnozdravstvenih ustanova. Vodstvo organizacija treba iskoristiti te ciljeve, te edukacijom zaposlenika prikazati gdje žele vidjeti svoje ustanove u budućnosti. Stoga je glavni cilj ovog rada definirati model za mjerenje ostvarenja ciljeva razvoja zdravstvenog turizma PGŽ. Metodom studija slučaja definira se rezultat ovog istraživanja odnosno ključni pokazatelji poslovanja, grupirani u 4 perspektive, koji omogućavaju operacionalizaciju strateških ciljeva razvoja zdravstvenog turizma PGŽ. Sustavi koji mjere, prate i bilježe informacije o učinkovitosti poslovanja javnozdravstvenih ustanova su puni nedostataka. Osnovne mjere praćenja poslovanja su financijske naravi te prikazuju povijesne podatke, čime ne mogu usmjeriti kako će se organizacije ponašati u budućnosti. Balanced Scorecard (BSC) je model koji prevodi strategiju organizacije u ciljeve učinaka, mjera i inicijativa kroz uravnotežene perspektive. BSC ne gleda samo financijsko stanje organizacije već sagledava i poslovanje s aspekata kupaca, internih procesa te zaposlenika u pogledu učenja i rasta poduzeća.Strategic problems of Public Health of the Primorsko-goranska County (PGC) are poorly linked and unequal quality and availability of health care. Health indicators are significantly better than the national average but are still poor compared to European averages. Better co-operation between public and private health institutions would ensure greater competitiveness, lower costs, more efficient, accessible and better quality health care for all residents and tourists of PGC. The promotion of the County as a recognized destination for the development of health, sports and recreational and other forms of tourism would facilitate the emergence of foreign markets, while the promotion of the development of voluntary health insurance would relieve the public health system. In order to make PGC health tourism sustainable in today's highly competitive business environment, healthcare institutions should dedicate enough time and energy to achieving their strategic goals. These goals are embedded in the mission and vision of public health institutions. Leadership organizations should take advantage of these goals and educate employees to show where they want to see their institutions in the future. Therefore, the main goal of this work is to define a model for measuring the achievement of the goals of development of health tourism in PGC. The method of case studies defines the result of this research, i.e. key performance indicators, grouped in 4 perspectives, which enable the operationalization of the strategic goals of the development of health tourism in the PGC region. Systems that measure, monitor and record information on the efficiency of public health care operations are full of disadvantages. Basic business monitoring measures are financial in nature that displays historical data, so they cannot direct how organizations will behave in the future. The Balanced Scorecard (BSC) is a model that translates the organization's strategy into the goals of impacts, measures and initiatives through a balanced perspective. The Balanced Scorecard is not just looking at the financial state of the organization, but it also uses customer information, internal processes, employees, learning and growth