Razsejan rak dojk

Več kot tisoč dvesto žensk vsako leto zboli za rakom dojk. Ko se bolnica in njeni zdravniki po postavitvi diagnoze spopademo z boleznijo, skušamo narediti vse, da bolezen pozdravimo. Z operacijo odstranimo tumor ali celo dojko in eno ali več pazdušnih bezgavk, nato pa dojko ali področje odstranjene dojke velikokrat še dodatno obsevamo

Role of selected gene polymorphisms in the development of diabetic kidney disease in patients with type 2 diabetes mellitus

Diabetična nefropatija (DN – izraz, ki ga bolj uporabljamo za biopsijsko dokazano prizadetost ledvic zaradi SB) ali diabetična ledvična bolezen je kronični zaplet pri SB. Proteinurija, povišan krvni tlak in postopen upad ledvične funkcije ob visoki srčno-žilni obolevnosti in umrljivosti so glavne značilnosti razvite diabetične nefropatije pri SB. Okoli 30 do 50% bolnikov razvije klinično očitno DN, vendar ne vemo, kateri bolniki jo bodo razvili in kateri ne. Pravimo, da je DLB večvzročna bolezen in do zdaj so ugotovili, da je v patogenezo okvare ledvice vključenih več genov. Študije o genskem polimorfizmu pri DLB izvajamo z namenom, da bi odkrili gene, ki bi služili kot biomarkerji, in bi na podlagi teh odkritij lahko razvijali terapevtske smernice, s katerimi bi lahko zavrli ali preprečili komplikacije sladkorne bolezni, kot je DLB. Namen naše retrospektivne asociacijske raziskave je bil poiskati povezavo med izbranimi kandidatnimi geni in DLB pri Slovencih s SB2, ki so del kavkaške populacije. V raziskavo smo vključili 651 bolnikov s SB2, ki so imeli bolezen že najmanj 10 let. Za ocenitev ledvične funkcije smo uporabili MDRD enačbo in s-cistatin. Na ta način smo dobili dve skupini bolnikov, in sicer 276 bolnikov z DLB in 375 bolnikov brez DLB, ki so služili kot kontrola. Testirali smo naslednje polimorfizme: polimorfizma rs4340 in rs4341 v genu za angiotenzinsko konvertazo (AK), polimorfizma rs699 in rs4762 v genu za angiotenzinogen (AGT), polimorfizme rs275651, rs931490, rs5182 in rs5186 v genu za receptor tipa 1 za angiotenzin II (AGTR1), polimorfizme rs3087459, rs5370, rs1476046 v genu za endotelin 1 (EDN1), polimorfizem rs3802278 v genu za 5-lipoksigenazo-aktivirajoči proteini (ALOX5AP) in polimorfizem rs12762303 v genu za arahidonat 5-lipoksigenazo (ALOX5). Rezultati niso pokazali statistično pomembne povezave med polimorfizmi rs4340 in rs4341 v genu za angiotenzinsko konvertazo (AK), polimorfizmi rs699 in rs4762 v genu za angiotenzinogen (AGT), polimorfizmi rs275651, rs931490, rs5182 in rs5186 v genu za receptor tipa 1 za angiotenzin II (AGTR1), polimorfizmi rs3087459, rs5370, rs1476046 v genu za endotelin 1 (EDN1) in polimorfizmu rs12762303 v genu za arahidonat 5-lipoksigenazo (ALOX5) in DLB. Nasprotno pa smo ugotovili statistično pomembno povezavo med polimorfizmom rs3802278 v genu za 5-lipoksigenazo-aktivirajoči proteini (ALOX5AP) in DLB. Rezultati logistične regresije so pokazali, da imajo posamezniki z genotipom CC 3,14-krat večjo verjetnost za pojav DLB, v primerjavi s posamezniki z genotipom TT. Torej je genotip CC polimorfizma rs3803278 v genu za ALOX5AP možni dejavnik tveganja za pojav DLB.Diabetic nephropathy (DN) is one of the microvascular complications of T2DM. The main characteristics of established diabetic nephropathy are proteinuria, high blood pressure and a gradual decline in renal function, together with increased morbidity and mortality due to cardiovascular complications. DN is a multifactorial disease with environmental and genetic factors involved in its pathogenesis. Multiple genes are involved in developing DN and its distribution depends, amongst other things, on ethnicity. The main purpose of recognising different genes is to find the ones which can identify groups of patients with T2DM who are more likely to develop DN. This can be used as a marker for screening patients with T2DM and focusing on those groups which would benefit from intensive intervention to prevent or slow down complications, such as DN. The main purpose of our retrospective study was to establish a connection between the selected groups of genes in Slovenian patients with T2DM and DN. We selected 651 Slovenian patients with T2DM of at least 10 years duration. We divided patients into two groups: 276 patients had confirmed DN and 375 patients were without clinical signs of DN, the latter acting as the control group. We tested for the following gene polymorphisms: polymorphisms rs4340 and rs4341 in the gene for angiotensin-converting enzyme (ACE), polymorphisms rs699 and 4762 in the gene for angio-tensinogen, polymorphisms rs275651, rs931490, rs5182 and rs5186 in the gene for angiotensin II receptor type 1 (AGTR1), polymorphisms rs3087459, rs5370, rs1476046 in the gene for endothelin 1, polymorphism rs3802278 in the gene for 5-lipoxygenase-activating protein (ALOX5AP), and polymorphism rs12762303 in the gene for arachidonate 5-lipoxygenase (ALOX5). No connection was found between DN and polymorphisms rs4340 and rs4341 in the gene for angiotensin-converting enzyme (ACE), polymorphisms rs699 and rs4762 in the gene for angio-tensinogen, polymorphisms rs275651, rs931490, rs5182 and rs5186 in the gene for angiotensin II receptor type 1 (AGTR1), polymorphisms rs3087459, rs5370, rs1476046 in the gene for endothelin 1 and polymorphism rs12762303 in the gene for arachidonate 5-lipoxygenase (ALOX5). There was, however, a statistically important difference between polymorphism rs3802278 in the gene for 5-lipoxygenase-activating protein (ALOX5AP) in patients with DN (p = 0.004). We concluded that the CC genotype of the ALOXAP5 gene (rs3803278) was associated with a 3.14-fold increased risk of DN in patients with T2DM (95% CI = 1.18-8.35 p = 0.02)

Evidence procedure, comparative legal regulation of criminal procedure in the united states of america and republic of slovenia

Dokazni postopek kot ena izmed faz kazenskega postopka je njegov pomemben del, saj so predstavljeni dokazi oziroma dokazna sredstva podlaga za kasnejšo odločitev v konkretni kazenski zadevi. Gre za psihološki proces, ki se giblje med določenimi stopnjami verjetnosti ter katerega namen je dognanje resnice. Resnico o obstoju pomembnega dejstva pa lahko pridobimo iz dokaznih sredstev. Namen dokaznega postopka je ugotovitev pravno pomembnih dejstev za zakonito sodbo. V kontinentalnih pravnih redih velja sodnik kot aktivni in pasivni subjekt postopka, kjer priskrbuje dokaze po uradni dolžnosti, medtem ko v anglo-ameriških sistemih te pristojnosti zbiranja dokazov ne poznajo. Preko zagovora in zaslišanja obdolženca, prič, izvedencev in listin pridemo do ugotovitve obstoja dejstev, ki kasneje služijo kot podlaga za odločitev sodišča. Vendar vsak dokaz tudi ni zakonito pridobljen, moramo se zavedati dejstva, da če sodišče želi priti do zakonite odločbe, jo mora pridobiti na podlagi zakonito pridobljenih dokazov. Torej nezakoniti dokazi ne smejo biti podlaga za odločanje o kazenski odgovornosti obdolženca. Ti nezakoniti dokazi so predmet ekskluzije ali izločitve dokaza iz kazenskega postopka, saj sodišče ne sme uporabiti zoper obdolženca neustavno ali nezakonito pridobljenih dokazov. Vendar vsako pravilo pozna določene izjeme, ki jih je razvila predvsem ameriška sodna praksa in jih kontinentalni pravni sistemi ne poznajo. Kadar pa do ekskluzije dokazov ne pride pravočasno, obstaja določena nevarnost psihološke okužbe sodišča z nezakonitimi dokazi in nevarnost odločanja o zadevi na podlagi teh nedovoljenih dokazov. Zato bo v nalogi predstavljen slovenski sistem, kot predstavnik kontinentalne skupine sistemov, in ameriški sistem, na podlagi teh dveh bodo podane razlike med enim in drugim. Čeprav v obeh sistemih prihaja do sodbe, še ne pomeni, da je sam potek postopka, kako je prišlo do te odločitve, enak v obeh sistemih.Evidence procedure is one of the stages of criminal procedure and is an important part of it since there are evidence presented for a subsequent decision taken in a specific criminal case. It is a psychological process that moves among certain degrees of probability, and whose purpose is knowledge of the truth. The truth about the existence of an important fact may be obtained from the evidence. The purpose of evidence procedure is finding legally significant facts for legal judgment. In continental legal orders a judge is an active and passive subject of proceedings in which evidences are provided ex officio, while in the Anglo-American system, such competence of gathering evidences is not familiar with. Since the hearing of the accused one, and with witnesses, experts and documents, we can conclude the existence of facts, which later serves as the basis for the Court\u27s decision. But, we need to be aware of the fact, that if the Court wants to get a lawful decision or judgment, it must obtain a legally gained evidence. Therefore, illegal evidence are not a basis for making decision on the criminal liability of the accused. Those illegal evidence are subject to exclusion of evidence in the criminal procedure, since the Court cannot use unconstitutional or illegal evidence against the accused. But every rule is familiar with a number of exceptions, mainly developed by American case law and of which the continental legal systems are not familiar with. When, however, the exclusion of evidence does not occur in time, there is a risk of psychological infection of the Court with illegal evidence and there is a risk of deciding in case on the basis of these illegal evidence. Therefore, in the thesis will be presented a Slovenian system, as a representative of the continental system and the American system, on the basis of which, these two systems will be compared. Even though that in both systems we have judgment, that does not necessarily mean that the procedure how we came to this decision is the same in both systems

COMPARATIVE LEGAL REGULATION OF EVIDENTARY PROCEDURE IN UNITED STATES OF AMERICA AND REPUBLIC OF SLOVENIA

V diplomskem delu bomo predstavili kazenski postopek Republike Slovenije in Združenih držav Amerike, ki velja v 21. stoletju za edino svetovno velesilo. Zakaj smo se odločili primerjati slovenski postopek z ameriškim je zato, ker sta sistema v določenih pogledih enaka, vendar imata vseeno temeljne razlike. Primerjava velesile in majhne države, ki je večina sveta ne pozna se zdi dobra tema. Da država poskrbi za kaznovanje storilcev kaznivega dejanja je potreben ne samo zakon o kaznivih dejanjih in določenih sankcijah, ampak tudi zakon, ki določa potek postopka in omogoča pravičen postopek za vsakogar. Torej je kazenski postopek urejen s pravnimi pravili, ki se jih procesni subjekti kazenskega postopka morajo držati. Najpomembnejši se zdi postopek na glavni obravnavi, saj je tamkajšnjo dogajanje največjega pomena za obsodbo ali oprostitev domnevnega storilca kaznivega dejanja. Kot bomo zasledili, imata obe državi glavno obravnavo, kjer poteka dokazni postopek in sprejemanje končne odločitve, vendar se pristojnosti subjektov razlikujejo. V Sloveniji poznamo poklicne sodnike ki sprejemajo odločitve, medtem ko si pristojnost v Ameriki deli sodnik skupaj s poroto. Vendar obe državi strmita k pravičnemu kazenskemu postopku in k odkritju resnice s kaznovanjem storilca kaznivega dejanja. In s tem zagotavljata red v državi.In diploma thesis we will present criminal procedure the Republic of Slovenia and the United States of America, which applies in the 21st century as the only world superpower. Why we decided to compare the Slovenian process with the American is because these two systems are in some ways the same, but still have fundamental differences. Comparing the world superpower with small country like Slovenia, which the most of the world don\u27t even know, seems a good topic for a diploma. Therefore, is the state\u27s concern to punish offenders and it is not only required an Act of crime and penalties, but also an Act that sets the course of the proceedings and enable a fair process for everyone. So the criminal procedure is regulated by legal rules that criminal procedure subject most obey. Most significant appears the procedure at the main hearing, because the events there have the greates importance for convinction or an exemption the alleged offender. As we will notice, both countries have the main hearing in which evidence is taken and the final decision is taken, but there are also some differences in procedure subjects. In Slovenia, there are proffesional judges who make decisions, while the powers in America are divided alonge the judge and the jury. However, both countries are staring at a fair criminal procedure and uncovering the truth by punishing the offender. And with that provides order in the country

Angiotensinogen (AGT) gene missense polymorphisms (rs699 and rs4762) and diabetic nephropathy in Caucasians with type 2 diabetes mellitus

Gene polymorphisms associated with the renin–angiotensin–aldosterone system (RAAS) have been extensively studied in diabetic nephropathy (DN) patients, due to therapeutic potential of targeting the RAAS and slowing down the disease progression. The aim of our study was to examine the association between angiotensinogen (AGT) gene polymorphisms (rs699 and rs4762) and DN in Caucasians with type 2 diabetes mellitus (T2DM). A total of 651 unrelated Slovenian (Caucasian) T2DM patients were tested for AGT rs699 and rs4762 polymorphisms using a novel fluorescence-based kompetitive allele-specific polymerase chain reaction (KASPar) assay. A study group consisted of 276 T2DM patients with DN, while control group included 375 patients without DN but who have had T2DM for >10 years. For rs699 polymorphism, the frequencies of GG, GA and AA genotypes were 20.6%, 52.2% and 27.2%, respectively in T2DM patients and 23.4%, 48.1% and 28.5%, respectively in controls. The distributions of GG, GA and AA genotypes for rs4762 polymorphism were 73.9%, 23.2% and 2.9%, respectively in T2DM patients and 70.4%, 27.5% and 2.1%, respectively in controls. No significant differences in the allele frequencies were found between T2DM patients and controls for both polymorphisms. AGT rs699 and rs4762 missense polymorphisms are not associated with DN in our subset of Slovenian T2DM patients

Nutritional status and health-related quality of life in men with advanced castrate-resistant prostate cancer

Despite professional recommendations malnutrition is not adequately addressed in cancer patients. Here, we explored whether nutritional status (NS) is associated with HRQoL in men with metastatic castrate-resistant prostate cancer (mCRPC). Methods: Men with mCRPC enrolled into this prospective observational study were allocated to one of the four NS categories based on clinical, laboratory, and patient self-reported criteria: well-nourished (WN), nutritional risk without criteria for cachexia/sarcopenia (NR), sarcopenia, and cachexia. The HRQoL was evaluated by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Association between NS and self-reported HRQoL was sought by the linear regression model, which was adjusted for known prognostic variables and body mass index. Results: Over the period of two years, 141 patients were enrolled. Their median age was 74.1 years (IQR 68.6–79.4 years) and majority of them were minimally symptomatic. Fifty-nine patients (41.8%) were WN, followed by 24 (17%), 42 (29.8%), and 16 (11.4%) patients with NR, sarcopenia, and cachexia, respectively. As compared to WN patients, all three other NS categories were significant negative predictors of HRQoL (P<0.04). Conclusions: Abnormal NS is highly prevalent in men with mCRPC and is negatively associated with their HRQoL, which supports the recommendation for management of malnutrition in these patients

Interleukin-4 (IL4) -590C/T (rs2243250) gene polymorphism is not associated with diabetic nephropathy (DN) in Caucasians with type 2 diabetes mellitus (T2DM)

Diabetic nephropathy (DN) is a microvascular complication that affects up to 40% of diabetic patients and can lead to end-stage kidney disease. Inflammatory cytokines such as interleukin 1 (IL-1), IL-6, IL-18 and tumor necrosis factor-α (TNFα) have been linked to the development and progression of DN. The aim of our study was to examine the relationship between interleukin-4 (IL4) -590C/T (rs2243250) gene polymorphism and DN in patients with type 2 diabetes mellitus (T2DM). This study is a continuation of our previous research on the association between angiotensinogen (AGT) gene polymorphisms and DN in patients with T2DM. We included 651 unrelated Slovenian (Caucasian) patients who had had T2DM for at least 10 years. The participants were classified into a group of T2DM patients with DN (276 cases) and a group without DN (375 controls). IL4 rs2243250 polymorphism was analyzed using a TaqMan SNP genotyping assay and StepOne Real-Time PCR System. The frequencies of rs2243250 TT, CT and CC (wild type) genotypes were 3.2%, 29.4% and 67.4%, respectively in patients with DN, and 2.7%, 34.4% and 62.9%, respectively in controls. Our logistic regression analysis adjusted for gender, age, diabetes duration, and glycated hemoglobin showed no association between rs2243250 and the risk for DN (OR 1.06; CI 0.37-3.05; p = 0.9). IL4 rs2243250 is not associated with DN in our subset of Slovenian patients with T2DM

PECAM-1 Leu125Val (rs688) Polymorphism and Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus

Objectives. Platelet endothelial cell adhesion molecule-1 (PECAM-1) plays a key role in the transendothelial migration of circulating leukocytes during inflammation and in the maintenance of vascular endothelial integrity. We hypothesized that genetic variation in PECAM-1 gene could be associated with diabetic nephropathy (DN) and with the level of soluble PECAM-1 in Caucasians with type 2 diabetes mellitus (T2DM). Design and Methods. We analyzed the rs688 single nucleotide polymorphism of PECAM-1 gene C373G (Leu125Val) at exon 3, which encodes the first extracellular Ig-like domain that mediates the homophilic binding of PECAM-1, in 276 T2DM subjects with documented DN (cases) and 375 T2DM subjects without DN (controls), using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy. Level of plasma soluble PECAM-1 (sPECAM-1) was measured by ELISA in a subpopulation of 120 diabetics with DN. Results. We found no association between the Leu125Val polymorphism and DN in subjects with T2DM. Likewise, the Leu125Val polymorphism was not associated with serum sPECAM-1 levels in a subpopulation of 120 diabetics with DN. Conclusion. The Leu125Val polymorphism of PECAM-1 and the level of sPECAM-1 are not associated with DN in T2DM subjects of Slovenian origin