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Placental insufficiency is a common cause of intrauterine growth restriction (IUGR). It affects ~10% of pregnancies and increases fetal and neonatal morbidity and mortality. Although Wnt and Hh pathways are crucial for embryonic development and placentation, their role in the pathology of IUGR is still not sufficiently explored. The present study analyzed the expression of positive regulators of the Wnt pathway, WNT5A and β‑catenin, and the expression of the Hh pathway negative regulator suppressor of fused (SUFU). Immunohistochemical and reverse transcription‑quantitative PCR (RT‑qPCR) assays were performed on 34 IUGR and 18 placental tissue samples from physiologic singleton‑term pregnancies. Epigenetic mechanisms of SUFU gene regulation were also investigated by methylation‑specific PCR analysis of its promoter and RT‑qPCR analysis of miR‑214‑3p and miR‑378a‑5p expression. WNT5A protein expression was higher in endothelial cells of placental villi from IUGR compared with control tissues. That was also the case for β‑catenin protein expression in trophoblasts and endothelial cells and SUFU protein expression in trophoblasts from IUGR placentas. The SUFU gene promoter remained unmethylated in all tissue samples, while miR‑214‑3p and miR‑378a‑5p were downregulated in IUGR. The present results suggested altered Wnt and Hh signaling in IUGR. DNA methylation did not appear to be a mechanism of SUFU regulation in the pathogenesis of IUGR, but its expression could be regulated by miRNA targeting.

BackgroundThis study aimed to identify the association of preoperative depressive symptoms and C-reactive protein (CRP) levels with postoperative recovery time of patients undergoing coronary artery bypass grafting (CABG). MethodsThe study included 212 elective CABG patients subdivided into two groups based on the presence or absence of preoperative depressive symptoms measured by the Beck Depression Inventory (BDI-II) and the PRIME-MD/PHQ-9 test score. The CRP was measured before surgery, and sequentially (1-6 days postoperatively) during the patient's in-hospital stay. Three summary scores of postoperative CRP response were generated: I) “early” (1-3) II) “persistent” (3-6) and III) “overall” (1-6 postoperative day). ResultsCABG patients with longer postoperative hospital length of stay (LOS > 7 days) have significantly higher total BDI-II (P = 0.014), and CRP measured on days 3 (P = 0.009), 4 (P = 0.001), 5 (P = 0.001), and 6 (P = 0.001) postoperatively, as well as higher “persistent” (P < 0.001) and “overall” (P = 0.004) CRP response. Association of “persistent” and “overall” CRP response to longer postoperative hospital LOS was also confirmed by binary logistic regression analysis. Patients with longer hospital LOS also had lower (P = 0.001) preoperative hemoglobin, a higher EuroSCORE II (P < 0.001), longer ventilation time (P = 0.016), and prolonged intensive care unit length of stay (P = 0.022) when compared to the group with shorter postoperative LOS (< 7 days). Significantly lower preoperative hemoglobin levels (P = 0.044), higher EuroSCORE II (P < 0.001), and longer ventilation time (P = 0.029) was also recorded among patients with elevated depressive symptoms (BDI-II >13). ConclusionsDepressive symptoms are associated with higher operative risk expressed by calculating EuroSCORE II value, longer postoperative hospital LOS, higher preoperative and on the first postoperative day CRP values. There is also a positive correlation with the former and smoking, a slightly lower ejection fraction and significant anemia. A higher CRP on and after the third postoperative day is a positive predictor of an increase in length of postoperative hospital stay. Clinically compromised elderly CABG patients with pronounced comorbidities and female CABG patients were more prone to preoperative depression.

Purpose A survival gap between weaning from venoarterial-extracorporeal membrane oxygenation (VA-ECMO) and the hospital discharge has been consistently reported. The aim of this study is to investigate the clinical features of patients who underwent successful VA-ECMO decannulation at our institution and to identify the major contributors responsible for adverse outcomes. Methods We retrospectively reviewed all patients supported with VA-ECMO in our institution between January 2013 and June 2020. Only patients that survived VA-ECMO and underwent successful decannulation were included and dichotomized based on survival to hospital discharge: non-survivors versus survivors. The primary study outcome was the cause of death after successful VA-ECMO decannulation. Results Of the 262 adult patients who underwent VA-ECMO decannulation, 72 (27.5%) patients did not survive to hospital discharge. Non-survivors were older (62 vs. 54 years, p Conclusion In our study, one-third of patients decannulated off VA-ECMO did not survive to hospital discharge due to end-stage heart failure, infections or neurological injury. The first 8 post-decannulation days were recognized as a critical period where thorough strategies to prevent acquired infections and cautious support of end-organ function should be warranted. Future large-scale trials are needed to confirm our results.

To determine differential gene expression patterns between osteoblasts and osteocytes that characterize their true in vivo setting.

The anticancer agent 5-azacytidine (5azaC, Vidaza) is a cytosine-based analogue which causes DNA hypomethylation. Here we present data of the impact of 5-azacytidine on mammalian testis in development.

Aim was to present twelve-year (1993-2005) experience in identification of human remains found in mass graves in Croatia and Bosnia and Herzegovina (BH), as well as remains that presumably belonged to Croatian citizens given by Serbia and Montenegro. The unique experience of identification of more than a thousand of skeletal samples is valuable for better organization of post-mortem identifications. Standard forensic methods and methods based on DNA analysis were used for identification of human remains from mass graves. DNA was isolated using standard phenol/chloroform/isoamyl alcohol extraction. In some cases, decalcification and repurification were used prior to the extraction to overcome inhibition of amplification process. Different DNA systems were used for DNA quantitation and amplification (AluQuant, short tandem repeats (STR) commercial systems, Y chromosome STRs, and mitochondrial DNA [mtDNA]). Typing of PCR products was performed on AmpliType (R) PM and AmpliType (R) DQA1 DNA probe strips, ABI PRISM (R) 310 Genetic Analyzer and immobilized sequence-specific oligonucleotide (SSO) probes. Up-to-date analysis of 1, 155 skeletal samples resulted in 703 positively identified bodies: 577 using standard forensic methods, 109 by DNA typing, and 17 by combination of these two methods. The majority of identifications from 1993 to 1999 was, as usual, achieved by standard forensic methods. Later on, these methods were not sufficient and DNA analysis was requested. It was performed in 42% of all cases in 12 years. The crucial step in DNA analysis is extraction of genomic DNA. Standard phenol/chloroform/isoamyl alcohol extraction, complemented with other methods and modifications, proved as the most successful method for this step. In certain cases, the quality and/or quantity of nDNA was not satisfying and the analysis of the mtDNA was performed. Our experience demonstrated that the advent of forensic DNA analysis methods greatly increased our ability to positively identify previously unknown skeletal remains by a comparative genetic analysis with presumptive relatives.

Aim was to determine the correlation of phosphorylated human epidermal growth factor receptor-2 (pHER2) with clinicopathological characteristics of breast cancer (BC) and patients' response to trastuzumab-based therapy. pHER2 was determinated immuno-histochemically in 88 cases of HER2-positive and 50 cases of HER2-negative BC. All patients with HER2-positive BC received trastuzumab-based therapy and 16 of them (18.2%) had disease progression during therapy treatment (i.e. trastuzumab-resistant). pHER2 was predominantly expressed in HER2-positive BC, with 55 cases (62.5%) of tumours expressing pHER2. Six cases of HER2-negative cancer (12.5%) displayed positive expression of pHER2. Expression of pHER2 correlated with younger age of patients and negative oestrogen receptor status. Acquisition of resistance to trastuzumab correlated with negativity for pHER2 (p=0.028). Positive expression of pHER2 may yield additional information regarding the poor prognosis of BC and could be used for pre-selection of patients with HER2-overexpressing BC displaying resistance to trastuzumab treatment.