Current research on the non-invasive prediction of preterm birth is based on an analysis of the contraction intervals found in the electrohysterogram (EHG) signals recorded from the abdomen of pregnant women. We characterised, for the first time, the non-contraction intervals (dummy intervals) of EHG signals accompanied by an external tocogram measuring mechanical uterine activity, in the form of TOCO signals, and thus developed a new method for predicting preterm birth. The peak amplitudes of the power spectra of the EHG and TOCO signals in the frequency band 1.0-2.2 Hz, carrying information on the electro- mechanical influence of the maternal heart on the uterus, are only high during term pregnancies, when the delivery is still far away, while they are low when delivery is close. However, these peak amplitudes are also low during preterm pregnancies, when the delivery is still supposed to be far away, thus suggesting a danger of preterm birth. The newly developed method for preterm and term EHG records recorded early (around the 23rd week of pregnancy, when contractions are likely not present) achieved a 100% classification accuracy when using a publicly available TPEHG DB database. Impact of publication: The paper proposes new original approaches and solutions for the task of prediction of preterm birth. Innovations are following: 1) the proposal a new biophysical marker for the assessment of the danger of preterm birth (the peak amplitudes of the normalized power spectra of the EHG and TOCO signals are high for the records with term delivery which are recorded early during pregnancy, and are low for the records with preterm delivery which are also recorded early); 2) the proposal of a new and simple clinical technique for prediction of preterm birth during which there is no need to seek for contractions (the dummy intervals of uterine records result in equal, or even higher performance of the classification between records with preterm and term delivery, than the contraction intervals); 3) the developed method is suitable for the prediction of preterm birth early during pregnancy, in the 23rd week, while contractions may or may not be present (the achieved classification accuracy is 100% for the early recorded preterm and term records of international publicly available TPEHG DB database).
COBISS.SI-ID: 33916121
A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain. Impact of publication: During Zika epidemic in Brasil in 2016, our reseachers were the first in the world to prove the link between fetal microcephaly in a pregnant woman with a confirmed infection in the 13th week of gestation and microcephaly. The article was published in NEJM and was the most read article for several weeks. NEJM has the highest IF among all journals.
COBISS.SI-ID: 32488409
In collaboration with the Japanese Institute for the Control of Aging (JalCA), Haruoka and School of Human Science and Environment, University of Hyogo, Himeji, Japan, we developed the ELISA procedure for the determination of HEL in various biological samples. The reagent is a commercially available and official product of the Japanese Institute of Reagents (JaICA). Impact of publication: Published evidences indicate that reactive oxygen species (ROS) can induce lipid peroxidation, which plays important role in the pathophysiology of numerous diseases including atherosclerosis, diabetes, cancer and aging process. Monitoring of oxidative modification or oxidative damages of biomolecules may therefore be essential for the understanding of aging, and age-related diseases. N-epsilon-Hexanoyl-lysine (HEL) is a novel lipid peroxidation biomarker which is derived from the oxidation of omega-6 unsaturated fatty acid. In our common research, sample pretreatment with proteases was performed. HEL was successfully detected in oxidized LDL, oxidized serum, and rat serum. HEL ELISA, new biomarker, can be applied to measure urine, serum, and other biological samples independent of the animal species, and is useful for the assessment of omega-6 PUFA oxidation in the living bodies.
COBISS.SI-ID: 1241260
Folate is vital for cell development and growth. It is involved in one-carbon transfer reactions essential for the synthesis of purines and pyrimidines. It also acts in conjunction with cobalamin (vitamin B12) as a fundamental cofactor in the remethylation cycle that converts homocysteine to methionine. A deficiency in folate or vitamin B12 can lead to elevated homocysteine level, which has been identified as an independent risk factor in several health-related conditions. Adequate folate levels are essential in women of childbearing age and in pregnant women, and folate deficiency is associated with several congenital malformations. Low folate levels can be caused by dietary deficiencies, a genetic predisposition or treatment with medicines that affect folate concentration. Women who are pregnant or of child-bearing age commonly use medicines, so it is important to identify the basic biochemical mechanisms by which medicines interfere with the folate-homocysteine-methionine pathway. This review focuses on prescription medicines associated with folate disruption. It also summarizes their undesirable/toxic effects. Recommendations regarding folate supplementation during medical therapy are also reviewed. Impact of publication: The article focused on topical issues in medicines, the use of prescription medicines that has been increasing over the last decades. Medicines such as anti-epileptics, oral contraceptives, antitumor agents and others requiring long-term treatment are controversial not just for pregnant women but also in other vulnerable population groups: women of childbearing age, children, particularly during their first years, and the elderly. In the journal with a high impact factor (IF=5.728), we presented different groups of medicines, that influence the folate cycle with various mechanisms, and also recommendations on folate supplementation. This article is intended for healthcare workers, scientists, and also patients, since it is extremely important that they are aware of folate-drug interactions.
COBISS.SI-ID: 4642929
Objective: To evaluate lung and cardiac ultrasound for the assessment of fluid tolerance and fluid responsiveness patients with severe preeclampsia (PE). Methods: Lung ultrasound echo comet score (ECS) was used as a marker of pulmonary congestion. Echocardiographic E/e' ratio, measured by pulsed-wave and tissue Doppler, was used as a marker of diastolic left ventricular function. Measurements obtained 1 day before delivery and 1 and 4 days after delivery were compared in the two groups (PE vs controls). Results: We included 21 women with severe PE and 12 healthy controls. ECS and E/e' ratio were higher in women with PE than in controls, both before delivery (P = 0.002 and P = 0.02) and 1 day postdelivery (P = 0.02 and P = 0.03); however there was no difference at 4 days postdelivery (P = 0.63 and P = 0.90). Conclusions: Excess lung water can be identified by lung ultrasound in PE before appearance of clinical signs. Increase in extravascular lung water in PE could, in part, be caused by disturbed diastolic left ventricular function. Impact of publication: The study introduces a new, simple and nin-invasive diagnostic method to assess hemodynamic status in critically ill pregnant and postpartum patients with preeclampsia. Our results show that lung ultrasound and echocardiography identify severe preeclamptic patients in whom positive fluid balance should be avoided as it may lead to pulmonary edema and at the same time help clinicians to identify patients with severe preeclampsia who are still fluid responsive and in whom further fluid administration could be beneficial.
COBISS.SI-ID: 3162796
The conventional method of human oocyte maturation in vitro in the presence of gonadotrophins continues to be a relatively low-success procedure in the assisted conception programme owing to suboptimal maturation conditions in the absence of an ovarian 'niche' and poor understanding of this procedure at the molecular level in oocytes. In this study, the gene expression profiles of human oocytes were analysed according to their manner of maturation: in vivo (in the ovaries) or in vitro (matured either by the conventional method or by a new approach - co-cultured with cumulus cells of mature oocytes from the same patient). Our results show that the in-vitro maturation procedure strongly affects the gene expression profile of human oocytes, including several genes involved in transcriptional regulation, embryogenesis, epigenetics, development, and the cell cycle. The in-vitro maturation of oocytes co-cultured with cumulus cells from mature oocytes provides an ovarian 'niche' to some degree, which improves oocytematuration rates and their gene expression profile to the extent that they are more comparable to oocytes that naturally mature in the ovarian follicle. Impact of publication: An innovative approach to the maturation of immature human oocytes in vitro was developed, in the coculture of cumulus cells from mature oocytes in the same patient. This method significantly improves the success of the oocyte maturation with the expression of genes that are more comparable to oocytes matured in the natural ovarian environment than in the conventional, suboptimal in vitro maturation process without coculture. The method is successfully translated into the clinical practice.
COBISS.SI-ID: 5000876
To understand proteome composition and diversity during maturation of human oocytes, here we have addressed crucial aspects of oocyte collection and proteome analysis, resulting in the first proteome and secretome maps of human oocytes. Starting from 100 oocytes collected via a novel serum-free hanging drop culture system, we identified 2,154 proteins, whose function indicate that oocytes are largely resting cells with a proteome that is tailored for homeostasis, cellular attachment, and interaction with its environment via secretory factors. In addition, we have identified 158 oocyte-enriched proteins not observed in proteomic studies of other human cell lines or tissues. Exploiting SP3, a novel technology for proteomic sample preparation using magnetic beads, we scaled down proteome analysis to single cells. Despite the low protein content (~100 ng/cell), we consistently identified ~450 proteins from individual oocytes. When comparing individual oocytes at the germinal vesicle (GV) and metaphase II (MII) stage, we found that the protein TDRKH is preferentially expressed in immature oocytes, while Wee2, PCNA, and DNMT1 were enriched in mature cells, indicating that maintenance of genome integrity is crucial during oocyte maturation. An innovative proteomics workflow facilitates analysis of single human oocytes to investigate human oocyte biology. Impact of publication: With the innovative method of cultivation of human oocytes, isolation and proteomic analysis of proteins from them, we determined the first proteome and secretome of human oocytes. For the first time, a proteomic analysis of a single cell in general was performed successfully. A number of other research groups follow this.
COBISS.SI-ID: 3089836
Introduction: Neurotoxicity due to acute prenatal exposure to high-dose of mercury (Hg) is well documented. However, the effect of prenatal exposure to low Hg levels on child neurodevelopment and the question about "safety" of fish-eating during pregnancy remain controversial. International comparisons of Hg concentrations in mother-child biological samples and neurodevelopmental scores embedded in birth cohort studies may provide useful evidence to explore this issue. Materials and methods: The Mediterranean (Italy, Slovenia, Croatia, and Greece) cohort study included 1308 mother-child pairs enrolled in the Public Health Impact of long-term, low-level, Mixed Element exposure in a susceptible population EU Sixth Framework Programme (PHIME). Maternal hair and venous blood, cord blood and breast milk samples were collected, and total Hg (THg) levels were measured. Demographic and socioeconomic information, lifestyles and nutritional habits were collected through questionnaires at different phases of follow-up. Children at 18 months of age underwent neurodevelopmental testing using the Bayley Scales (BSID-III). Multivariate linear and logistic regressions were performed to assess the association between THg and BSID-III scores, Results: The meta-analysis of multivariate linear models found an overall positive association between language composite score and receptive communication scaled score and increasing THg in maternal hair. The meta-analysis of logistic regression models showed that the overall adjusted OR between THg in cord blood and suboptimal gross motor score was borderline significant. Language composite score and THg concentrations in maternal venous blood were positively related. In Slovenia THg level in breast milk was associated with suboptimal fine motor performance. Conclusions: This study showed an inverse relation between THg levels and developmental motor scores at 18 months. No evidence of detrimental effects of THg was found for cognitive and language outcomes at these concentrations and age. Impact of publication: Neurotoxicity due to acute prenatal exposure to high-dose of mercury (Hg) is well documented. However the effect of prenatal exposure to low Hg levels on child neurodevelopment and the question about "safety" of fish-eating during pregnancy remain controversial. We have explored this issue by collecting mother-child biological samples of Hg concentrations at delivery and scored neurodevelopment of these children at their age of 18 months. The cohort study included 1308 mother-child pairs from 4 Mediterranean countries enrolled in the PHIME project. Maternal hair and venous blood, cord blood and breast milk samples were collected, and total Hg (THg) levels were measured and nutritional habits were recorded at different levels of the study. Children at 18 months of age underwent neurodevelopmental testing using the Bayley Scales (BSID-III). Multivariate linear and logistic regressions were performed, for each country, to assess the association between THg and BSID-III scores. The results showed an inverse relation between THg levels and developmental motor scores at 18 months. No evidence of detrimental effects of THg was found for cognitive and language outcomes at these concentrations and age.
COBISS.SI-ID: 4559217
Objective: this article argues that rhetorical skills are an important quality factor of midwifery care. In particular, it aims to identify and discuss the relevance of three classical means of persuasion: ethos, pathos and logos. Design: secondary analysis, rhetorical analysis of semi-structured interviews. Findings: analysis identified the presence of all three means of persuasion in the interaction between midwives and women. Focusing on midwives, the quality of their awareness and command of rhetorical skills remains questionable. In particular, women experienced lack of a rational account of the situation and decisions made by health-care professionals involved in maternity care. Key Conclusions: acknowledging professional ethics, awareness and good command of all three means of persuasion [but above all, argumentative persuasion (logos)] is an integral component of midwifery care. It can contribute to collaborative relations between midwives and women, and thus promote women-centred midwiferycare. Implications For Practice: knowledge of the three classical rhetorical means of persuasion should be integrated into professional midwifery curricula. Impact of publication: The contribution is the result of an interdisciplinary work of authors from various fields (sociology, epistemology, women's studies). It is an innovative approach to analyzing the work of health professionals, which goes beyond the narrow field of midwifery and addresses the key ethical aspects of care. The article of Slovenian scientists in a renowned professional journal of midwifery and citations is a contribution on the international level to modern knowledge of health care based on the ethics of care, which is a base of its paradigmatic shift in the 21st century.
COBISS.SI-ID: 4142699
In two families affected by premature ovarian insufficiency accompanied by hearing loss (together, these symptoms compose Perrault syndrome), exome sequencing revealed mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase: homozygous c.1565C)A (p.Thr522Asn) in a consanguineous Palestinian family and compound heterozygous c.1077delT and c.1886C)T (p.Thr629Met) in a nonconsanguineous Slovenian family. A recently developed method of detecting remote homologies revealed threonine at this site in consensus sequences derived from multiple-species alignments seeded by human and E. coli residues at this region. Yeast complementation indicated that LARS2 c.1077delT is nonfunctional and that LARS2 p.Thr522Asn is partially functional. LARS2 p.Thr629Met was functional in this assay but might be insufficient as a heterozygote with the fully nonfunctional LARS2 c.1077delT allele. A known C. elegans strain with the protein-truncating alteration LARS-2 p.Trp247Ter was confirmed to be sterile. After HARS2, LARS2 is the second gene encoding mitochondrial tRNA synthetase to be found to harbor mutations leading to Perrault syndrome, further supporting a critical role for mitochondria in the maintenance of ovarian function and hearing. Impact of publication: The genetic causes of premature ovarian insufficiency (POi) are highly heterogeneous, and causative mutations have been identified in more than ten genes so far. Encoding mitochondrial leucyl-tRNA synthetase were found and functionally evaluated in our study mutations in LARS2,. After HARS2, LARS2 is the second gene encoding mitochondrial tRNA synthetase to be found to harbor mutations leading to Perrault syndrome, further supporting a critical role for mitochondria in the maintenance of ovarian function and hearing.
COBISS.SI-ID: 777388