TREATMENT OF RESISTANT AND ULTRA RESISTANT SCHIZOPHRENIA

Schizophrenia is a psychiatric disease which affects one percent of population. It is most common in young adults. It is primarily treated with typical and atypical antipsychotics. Resistant schizophrenia is a condition diagnosed after no response is noticed to two different antipsychotics of which one is atypical. The treatment has to be undertaken with adequate doses and duration of therapy. Clozapine is the golden standard in the treatment of therapy-resistant schizophrenia. It has shown its superiority among other antipsychotics in various studies. Aside from greater effectiveness, advantages include absence of extrapyramidal side effects. During clozapine treatment, regular blood tests should be performed as a screening method for agranulocytosis. Twenty to thirty percent od schizophrenia patients suffer from treatment resistant schizophrenia. Sixty percent of the latter ones show no therapeutic response to clozapine. In conclusion twelve to eighteen percent of all patients suffering from schizophrenia show no response to any form of treatment. Attempts to augment clozapine effectiveness are being made by increasing the dose of monotherapy, using antipsychotic polipharmacy or adding other types of drugs to clozapine. Unfortunately, these augmentation methods have not yet proven themselves to be effective enough to be added to standard therapy algorythms. On the other hand, electroconvulsive therapy is neuromodulatory method that shows promise in increasing therapeutic success. Although many methods of treatment are being researched, therapy-resistant schizophrenia remains a clinical challenge which affects a significant percentage of population and will require additional research

TREATMENT OF RESISTANT AND ULTRA RESISTANT SCHIZOPHRENIA

Schizophrenia is a psychiatric disease which affects one percent of population. It is most common in young adults. It is primarily treated with typical and atypical antipsychotics. Resistant schizophrenia is a condition diagnosed after no response is noticed to two different antipsychotics of which one is atypical. The treatment has to be undertaken with adequate doses and duration of therapy. Clozapine is the golden standard in the treatment of therapy-resistant schizophrenia. It has shown its superiority among other antipsychotics in various studies. Aside from greater effectiveness, advantages include absence of extrapyramidal side effects. During clozapine treatment, regular blood tests should be performed as a screening method for agranulocytosis. Twenty to thirty percent od schizophrenia patients suffer from treatment resistant schizophrenia. Sixty percent of the latter ones show no therapeutic response to clozapine. In conclusion twelve to eighteen percent of all patients suffering from schizophrenia show no response to any form of treatment. Attempts to augment clozapine effectiveness are being made by increasing the dose of monotherapy, using antipsychotic polipharmacy or adding other types of drugs to clozapine. Unfortunately, these augmentation methods have not yet proven themselves to be effective enough to be added to standard therapy algorythms. On the other hand, electroconvulsive therapy is neuromodulatory method that shows promise in increasing therapeutic success. Although many methods of treatment are being researched, therapy-resistant schizophrenia remains a clinical challenge which affects a significant percentage of population and will require additional research

New EU member states’ emigration: Projections for future and lessons for the new EU candidates

Unlike the old member states that compensate the negative net birth rate with immigration, the new EU member states face both migrational and natural demographic decline. In the last decade, poor level of economic development as well as the accession to the EU encouraged net emigration from the new member states. Panel data for the 12 new member states for the 2007 - 2016 period were used to determine how the length of membership and GDP per capita trailing behind the EU average affect the proportion of the net emigration. It has been shown that on average a country has to reach at least 85 percent of the average EU GDP p.c. (measured in PPS) to prevent emigration, but this level increases with each year of membership by 1.37 percentage points

Konstrukcija robotske ruke s pneumatskim mišićima kao aktuatorima

Rad se bavi analiziranjem pneumatskih mišića kao aktuatora u pneumatici. Pneumatski mišić vrlo je specifičan aktuator čija je primjena još uvijek rijetka zbog nemogućnosti precizne regulacije. Kako pneumatski mišići posjeduju niz prednosti kao što su mala masa, povoljan omjer mase i sile koju mogu proizvesti, lakoća održavanja i dr., omogućena im je primjena u robotskim sustavima antropoidne strukture odnosno humanoidnim robotima. Sve više se primjenjuju i u industrijskoj automatici, međutim, za rašireniju primjenu nužno je savladavanje njihovih negativnih svojstava kao što je npr. nelinearno dinamičko ponašanje. \Na početku se razmatra princip rada mišića koji je važan za daljnju analizu, posebno kod modeliranja i regulacije. Kada se u mišić dovodi zrak, njegova membrana se širi u radijalnom smjeru, a u isto vrijeme se skuplja u aksijalnom smjeru izazivajući vlačnu silu. Spominje se i McKibbenov mišić koji se može smatrati pretečom današnjih umjetnih pneumatskih mišića. Treće poglavlje bavi se konstrukcijom, a na kraju i izradom jednostavnog pneumatskog manipulatora koji koristi dva pneumatska mišića kao aktuatore, čijim se gibanjem preko prijenosnika gibanja prenosi sila, odnosno moment pomoću kojeg se zakreće rukam anipulatora s ugrađenom prihvatnicom. četvrto poglavlje uključuje stvaranje modela pneumatskog mišića koji je korišten u simulaciji. Da bi model bio donekle zadovoljavajući u obzir su uzeti određeni parametri dobiveni eksperimentalnim putem. Treba naglasiti da model koji bi točno opisivao cijeli ovaj sustav može zahtijevati složen postupak analize i sinteze. U petom poglavlju razmatra se regulacija kuta zakreta poluge manipulatora primjenom P,PID, odnosno PI regulatora. Regulacija je moguća, međutim, zbog oscilatornog ponašanja mišića u radu kao i nedovoljno točnog dinamičkog modela sustava, ona je otežana.Za izvedbu regulacijskih algoritama korišteni su programski paketi Matlab i Simulink, te program Matlab – Real Time Workshop koji omogućuje dobivanje izvršne verzije upravljačkog algoritma direktno iz modela načinjenog u Simulinku a koji se može koristiti na samom realnom procesu. Pri tome se upravljački algoritam izvodi u realnom vremenu. Na taj način se jako skraćuje vrijeme kreiranja i naknadnog editiranja algoritma regulacije

Asymmetric cell division and “differential inheritance of aging“

Asimetričnom staničnom diobom nastaju stanice kćeri koje su međusobno različite. Pri takvoj diobi dolazi do diferencijalnog nasljeđivanja centrosoma, molekula DNA, molekula RNA, proteina i proteinskih agregata. Kod viših eukariota asimetrična je dioba osnovni mehanizam diferencijacije stanica. S evolucijskog gledišta asimetričnu staničnu diobu možemo povezati s procesom starenja. U ovom radu uspoređeni su mehanizmi nasljeđivanja navedenih staničnih komponenti pri asimetričnoj diobi stanica različitih vrsta. Zbog njihove jednostavnosti, povezanost asimetrične diobe i starenja najbolje se može istražiti kod bakterija i kvasca. Centrosomi, kompartimentalizacija i citoplazmatski mikrotubuli su stanične strukture zadužene za nejednaku raspodjelu determinanti u stanice kćeri nastale asimetričnom diobom. U cilju boljeg razumijevanja povezanosti asimetrične stanične diobe i procesa starenja potrebno je unaprijediti postupke vizualizacije mikrotubula te lokalizacije proteina i molekula RNA.Asymmetric cell division is a proces in which different daughter cells arise. During that division there is a differential inheritance of centrosomes, DNA molecules, RNA molecules, proteins and protein aggregates. In higher eukaryotes, asymmetric cell division is a fundamental mechanism of cell differentiation. From the evolutionary point of view, asymmetric cell division can be related with aging process. In this work, mechanisms of cell components inheritance during asymmetric cell division in different organisms were compared. Because of their simplicity, bacteria and yeast are the best organisms to study the relation between asymmetric cell division and aging process. Centrosomes, compartimentalization and cytoplasmic microtubules are structures responsible for differential distribution of determinants in two daughter cells during asymmetric cell division. In the purpose of better understanding the relation between asymmetric cell division and aging process it is needed to improve the quality of methods required for microtubules visualization and protein and RNA localization

Hepatitis B virus genotyping and detection of reverse transcriptase drug resistance mutations

Približno 257 milijuna osoba u svijetu boluje od kronične infekcije virusom hepatitisa B, što u slučaju neliječenja dovodi do ciroze jetre ili hepatocelularnog karcinoma. Virus hepatitisa B je DNA virus s reverznom transkriptazom (RT) koja nema egzonukleaznu aktivnost, što rezultira visokom stopom mutacija. Infekcija se najčešće liječi kompeticijskim inhibitorima reverzne transkriptaze koji ometaju replikaciju virusa. Kao posljedica selekcijskog pritiska uzrokovanog terapijom, ali i imunosnim odgovorom, javljaju se mutacije koje mogu dovesti do rezistencije. Cilj ovog istraživanja bio je po prvi puta odrediti genotipove virusa HBV u 30 ispitanika iz Hrvatske te mutacije koje su odgovorne za rezistenciju na inhibitore RT kao i one odgovorne za izbjegavanje imunosnog odgovora. Sangerovim sekvenciranjem interdomene A-B gena za RT te analizom sekvencija u algoritmu Geno2Pheno određeni su genotipovi te tražene mutacije. Od deset HBV genotipova koji su identificirani u svijetu, u Hrvatskoj su prisutni genotip A (A2) u 20% i genotip D (D1, D2, D3) u 80% ispitanika. U dva ispitanika genotipa A detektirane su mutacije koje uzrokuju rezistenciju na inhibitore RT. Mutacije za izbjegavanje imunosnog odgovora detektirane su u 6 ispitanika genotipa A te u 8 ispitanika genotipa D. Distribucija genotipova kao i prevalencija mutacija odgovara onima zabilježenim u ostalim zemljama Europe.Approximately 257 million people in the world have had chronic hepatitis B virus infection, which, in case of non-treatment, causes liver cirrhosis or hepatocellular carcinoma. Hepatitis B virus is a DNA virus with a reverse transcriptase (RT) lacking exonuclease activity resulting in a high rate of viral mutations. Infection is mostly treated with competitive inhibitors of reverse transcriptase that obstruct the virus replication. The consequences of selective pressure caused by treatment as well as the immune response, may be the mutations leading to resistance. The goal of this research was to define the genotypes of HBV for the first time in a group of 30 examinees from Croatia and define the mutations responsible for the resistance to the RT inhibitors as well as the immuno-escape mutations. By sequencing A-B interdomain of the HBV RT gene by Sanger method and analysis of the sequences in the Geno2Pheno algorithm has determined virus genotypes and mutations. Out of the ten genotypes identified in the world, genotype A (A2) is present in 20% and genotype D (D1, D2, D3) in 80% of examinees in Croatia. In two genotype A examinees a mutation was detected, which caused resistance to the RT inhibitors. Immune-escape mutations were detected in 6 genotype A examinees and 8 genotype D examinees. Distribution of genotypes as well as the mutation prevalence are similar to those recorded in the other European countries

CORRELATION BETWEEN PROLACTIN AND SYMPTOM PROFILE IN ACUTE ADMITTED WOMEN WITH RECURRENT SCHIZOPHRENIA

Background: The prevalence of hyperprolactinemia among psychiatric patients receiving antipsychotic medications was estimated to be between 30% and 70%. A review of the literature on prolactin and schizophrenia symptoms suggests that the correlation between them is complex and not limited to the adverse effects of antipsychotics. Relations with specific symptom dimensions have not been found consistently across studies. The association between increased prolactin and recurrent episodes of schizophrenia needs to be replicated in larger samples and in a population of female patients. The aim of this study was to find out whether elevated prolactin is related to specific symptoms or dimensions of schizophrenia, which is a heterogenic entity. Subjects and methods: The sample consisted of 119 consecutively acute admitted women, aged 18 to 45 years with recurrent schizophrenia diagnosed on bases of DSM-5 criteria. Assessment for all the enrolled subjects comprised a psychiatric evaluation and blood draw to determine the prolactin level. Symptoms of schizophrenia were determined using the Positive and Negative Syndrome Scale (PANSS). Data were analyzed by regression analysis and the Independent Samples t Test. Values are given as means ±SD. Results: Hyperprolactinemia was detected in 74.79% patients (n=89), whereas the group without hyperprolactinemia comprised 25.21% of the sample. When plasma prolactin levels and clinical features between groups were compared, there was a statistically significant difference in the negative subscale scores of the PANSS (p=0.0011), positive subscale scores of the PANNS (p=0.0043), general subscale scores of the PANSS (p=0.0226) and total scores of the PANNS (p=0.0003). Conclusion: There were statistically significant differences in the clinical symptoms between two compared groups in total score and in the positive, negative and general subscores