Clinical genetics and breast cancer

Geneti čki čimbenici već su dugo poznati kao važni rizični čimbenici kod raka dojke. Procjenjuje se da je oko 5 do 10 % slučajeva raka dojke posljedica monogenske geneti čke predispozicije. U medicinskoj obradi raka dojke važno je prepoznati one žene i obitelji kod kojih postoji velika mogućnost monogenske geneti čke predispozicije, kako bi im se omogućila primjerena genetička i klinička obrada. Naime, osobama s visokim rizikom može se ponuditi mogućnost otkrivanja genetičkim testom (dijagnosti čko ili presimptomatsko testiranje) i drugačiju razinu medicinske obrade u smislu rane prevencije i liječenja u usporedbi s općom populacijom.It is known that geneti c factors play an important role as risk factors in breast cancer. 5 to 10% of breast cancer is of monogenetic predispositi on. In the process of clinical evaluati on of pati ents with breast cancer it is very importnat to identify those pati ents with high probability of having cancer predisposing mutati ons and to provide them relevant and professional genetic and clinical management. This can lead to the identification of genetic etiology of breast cancer and allow earlier and more efficient prevention, screening and treatment of breast cancer

C.35delG/ GJB2 and del(GJB6-D13S1830) mutations in Croatians with prelingual non-syndromic hearing impairment

BACKGROUND: C.35delG/GJB2 mutation is the most frequent genetic cause of deafness in Caucasians. Another frequent mutation in some Caucasian populations is del(GJB6-D13S1830). Both GJB2 and GJB6 genes belong to the same DFNB1 locus and when the two mutations are found in combination in a hearing-impaired person, a digenic pattern of inheritance is suggested. METHODS: We examined 63 Croatian subjects (25 familial and 38 sporadic cases) with prelingual non-syndromic hearing impairment by polymerase chain reaction for the presence of the c.35delG/GJB2 and the del(GJB6-D13S1830) mutations. RESULTS: Of the 63 unrelated hearing-impaired subjects, the mutation c.35delG/GJB2 was found in 21 subjects (33.3%). In 5 of them the mutation was found in the heterozygous state, all of them being compound heterozygotes, as sequencing revealed a second mutation within the coding region of the gene in 3 subjects, and a splice site mutation in 2 subjects. The del(GJB6-D13S1830) mutation was not found in the investigated hearing-impaired Croatian subjects. CONCLUSION: Our results contribute to the knowledge of geographic distribution and population genetics of the GJB2 and GJB6 mutations in the Europeans

DNA testing in medicine

Brz razvoj genetike kao znanosti pridonio je boljem poznavanju molekularnih osnova bolesti, što je omogućilo razvoj pouzdane dijagnostičke metode – DNA testiranja. Cilj je DNA testiranja otkriti genetičku promjenu – mutaciju, koja je po molekularnoj logici bolesti metoda izbora u dijagnostici genetički uvjetovanih bolesti. Nužno je poznavati kompleksnosti upotrebe genetičkog testiranja, jer je osim racionalne indikacije važan i izbor odgovarajućeg testa, pravilna interpretacija rezultata, poznavanje njegovih ograničenja, specifičnosti te poznavanje etičkih, legalnih i socijalnih implikacija. Genetičko savjetovanje stoga treba biti integralni dio svakog procesa genetičkog testiranja.The rapid development of genetics as a science has brought with it an increasing knowledge of the molecular bases of diseases, which in turn has allowed the development of better and more accurate diagnostic test – DNA analysis. The goal of DNA analysis in medicine is to detect genetic changes (mutations) which, by molecular logic, is the most accurate way to confirm the presence of genetic disease. It is important to understand the complexity of the use of genetic testing as there are (besides the importance of indicating the appropriate analysis, correct interpretation of any results, an understanding of the limits of testing and its specifity) many legal and ethical implications connected with genetic testing. It therefore follows that genetic counseling should be an integral part of the process of genetic testing

Genomic Testing for Prenatal Clinical Evaluation of Congenital Anomalies

Congenital anomalies occur in about 2–3% of liveborn and 20% of stillborn infants. They constitute a serious public health and epidemiological problem. The etiology of congenital anomalies is complex; they can result from genetic factors, environmental factors, or a combination of both. It is estimated that genetic factors represent an important cause of congenital anomalies and may be due to different genetic mechanisms: aneuploidies, deletions and duplications of DNA segments, and single gene disorders. Due to the genetic complexity, the targeted prenatal genetic diagnostics of congenital anomalies is usually problematic and challenging. In recent years new diagnostic algorithms for prenatal genetic testing are being developed with the advent of new genomic technologies, like molecular karyotyping and next-generation sequencing. These technologies offer testing options that exceed conventional karyotyping and targeted molecular genetic testing with better diagnostic yield. In this chapter, an overview of the conventional genetic diagnostic approach and the use of new genomic technologies in the diagnostic algorithm of prenatally detected congenital anomalies are discussed

Notranja oksidacija Cu-C in Ag-C kompozitov

The internal oxidation in copper-carbon and silver-carbon composites occurs when they are exposed to air or oxygen at high temperature. Solubility of carbon in copper or in silver is very low. The kinetics of oxidation at high temperature and activation energy were determined and the mechanism of internal oxidation was analysed. The kinetics of internal oxidation was determined for both cases and it is depended from the diffusion of oxygen following parabolic time dependence according to Wagner\u27s theory. The activation energy for Cu-C composite is 70.5 kJ/mol, and for Ag-C composite is 50.1 kJ/mol, what is in both cases close to the activation energy for the volume diffusion of oxygen in copper or in silver. In both cases gas products are formed during the internal oxidation of composites. In the internal oxidation zone pores, bubbles occur. The carbon oxidates directly with the oxygen from solid solution as long there is a contact, which breaks down with the presence of gas products. Then the oxidation occurs over the gas mixture of CO and CO2.Pri visokih temperaturah kompoziti bakra in srebra z ogljikom na zraku ali v kisiku reagirajo po mehanizmu notranje oksidacije. Topnost ogljika v trdnem bakru in trdnem srebru je zelo majhna. Analizirali smo kinetiko oksidacije kompozitov, določili aktivacijsko energijo in mehanizem notranje oksidacije. Kinetika oksidacije je pri obeh skupinah materialov odvisna od difuzije kisika in sledi parabolični odvisnosti od časa v skladu z Wagnerjevo teorijo. Aktivacijska energija procesa je za kompozit Cu-C enaka 70,5 kJ/mol, za kompozit Ag-C pa 50,1 kJ/mol, kar je blizu aktivacijski energiji za volumsko difuzijo kisika v trdnem bakru oziroma srebru. Pri oksidaciji kompozita nastajajo plinski produkti. Oksidacija ogljika poteka neposredno s kisikom iz trdne raztopine, ko pa se zaradi nastanka plinske faze stik prekine, pa preko plinske zmesi CO in CO2

Self-reported perinatal depressive symptoms and postnatal symptom severity after treatment with antidepressants in pregnancy: a cross-sectional study in 12 European countries using the Edinburgh Postnatal Depression Scale

Purpose: To explore the prevalence of self-reported antenatal and postnatal depressive symptoms by severity across multiple countries and the association between antidepressant treatment in pregnancy and postnatal symptom severity. Patients and methods: Multinational web-based study in 12 European countries (n=8069). Uniform data collection was ensured via an electronic questionnaire. Pregnant women at any gestational week and mothers of children with less than one year of age, could participate. We used the Edinburgh Postnatal Depression Scale (EPDS) to measure prevalence of antenatal and postnatal depressive symptoms according to severity, which were corrected by survey-weight adjustment (descriptive analysis). Within mothers with a psychiatric disorder (n=173), we estimated the association between antidepressant treatment in pregnancy and postnatal depressive symptom severity, as standardized EPDS mean scores, via inverse probability of treatment weight (association analysis). Results: In the descriptive analysis (n=8069), the period prevalence of moderate to very severe depressive symptoms was higher in the Western and Eastern regions relative to the Northern, both in the ante- (6.8-7.5% vs 4.3%) and postnatal period (7.6% vs 4.7%). One in two mothers with psychiatric disorders used antidepressant in pregnancy (86 out of 173). In the association analysis, women medicated at any time during pregnancy (adjusted β: -0.34, 95% CI: -0.66, -0.02) had a significant postnatal symptom severity reduction compared with the nonmedicated counterpart. This effect was larger (β: -0.74, 95% CI: -1.24, -0.24) when the analysis was restricted to mothers within six months after childbirth. Conclusions: The prevalence of self-reported antenatal and postnatal depressive symptoms differs across European countries. Among women with psychiatric disorders, those who had been on treatment with antidepressants during pregnancy were less likely to report postnatal depressive symptoms, particularly within the six-month period after childbirth, compared to the nonmedicated counterpart