Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.

Breast and cervical cancers comprise 50% of all cancers during pregnancy. In particular, gestational breast cancer is considered one of the most aggressive types of cancers, which is a rare but fatal disease. However, the incidence of this type of cancer is increasing over the years and its prevalence is expected to rise further as more women delay childbearing. Breast cancer occurring after pregnancy is generally triple negative with specific characterizations of a poorer prognosis and outcome. On the other hand, it has been pointed out that this cancer is associated with a specific group of genes which can be used as precise targets to manage this deadly disease. Indeed, combination therapies consisting of gene-based agents with other cancer therapeutics is presently under consideration. We herein review recent progress in understanding the development of breast cancer during pregnancy and their unique subtype of triple negative which is the hallmark of this type of breast cancer.

Book Review: Law in the Roman Provinces, (ed.) K. Czajkowski and B. Eckhardt: Oxford University Press, 2020, xii + 526 str.

BACKGROUND Limited data exist comparing clinical outcomes of two-drug regimens (2DRs) and three-drug regimens (3DRs) in people living with HIV. METHODS Antiretroviral treatment-experienced individuals in RESPOND switching to a new 2DR or 3DR from 1/1/12-1/10/18 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. RESULTS Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median 52.6 years [interquartile range 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%).There were 619 events during 27,159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU [95% CI 20.7-24.5]) on 3DRs, 79 (30.9/1000 PYFU [24.8-38.5]) on 2DRs. The most common events were death (7.5/1000 PYFU [95% CI 6.5-8.6]) and non-AIDS cancer (5.8/1000 PYFU [4.9-6.8]). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio: 0.92 [0.72-1.19]; p=0.53). CONCLUSIONS This is the first large, international cohort assessing clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes; further research on resistance barriers and long-term durability of 2DRs is needed.

U radu su prikazani rezultati istraživanja učinkovitosti skidera Ecotrac 55V. Istraživanje je provedeno u šumskom odjelu 89, gospodarska jedinica »Igman«, uz primjenu studija rada i vremena. Trajanje radnoga vremena ustanovljeno je »povratnom« metodom snimanja. Ovisnost vremena trajanja radnih operacija o utjecajnim čimbenicima utvrđena je uz primjenu višestruke regresijske analize. Primijenjena je sortimentna metoda izrade drva. Snimljeni su ovi utjecajni čimbenici: stanje traktorskoga puta (podloge), udaljenost privlačenja drva skiderom, udaljenost privitlavanja drva, broj komada u tovaru, obujam tovara i uzdužni nagib traktorskoga puta. Udio operativnoga vremena u ukupnom radnom vremenu iznosi 38,75 %, a udio vremena prekida rada 37,56 %. Norme vremena i učinka izražene su u ovisnosti o udaljenosti privlačenja, dok su za ostale utjecajne čimbenike korištene prosječne vrijednosti. Utvrđena je norma vremena u iznosu od 8,34 min/m3 za udaljenost privlačenja od 100 m, odnosno 17,65 min/m3 za 900 m. Učinak se traktora kreće u intervalu od 57,58 m3/radnom danu za udaljenost privlačenja od 100 m do 27,20 m3/radnom danu za 900 m. Analiza je pokazala da postoji mogućnost povećanja učinkovitosti primjenom bolje organizacije rada i smanjenjem udjela prekida rada u ukupnom radnom vremenu, osobito prekida iz organizacijskih i osobnih razloga (prekida zbog jela i prekida zbog odmora i osobnih potreba radnika).

The aim of this article is to present a review of the research surrounding the short-term and long-term psychological and health consequences of child abuse and neglect. Research papers related to the consequences of child abuse and neglect and published in leading academic journals were identified and reviewed. We found that most of the available research suggests that there is a variety of negative outcomes among those exposed to physical, sexual and emotional abuse, neglect, witnessing domestic violence and multi-type childhood abuse. Specifically, there was evidence of significant short-term and long-term consequences encompassing physical and mental health difficulties, subsequent perpetrations, social and cognitive difficulties, and attachment. Conclusion  – The results of this review confirm that there is a wide range of short-term and long-term difficulties that are associated with child abuse and neglect. This variety of difficulties should be taken into account in approaching complex and multidisciplinary assessment and treatment.

Multiple Indicator Cluster Surveys (MICS), supported by UNICEF, are one of the most important global household survey programs that provide data on health and education of women and children. We analyze the Serbia 2014–2015 MICS dataset using topological data analysis which treats the data cloud as a topological space and extracts information about its intrinsic geometric properties. In particular, our analysis uses the Mapper algorithm, a dimension-reduction and clustering method which produces a graph from the data cloud. The resulting Mapper graph provides insight into various relationships between household wealth—as expressed by the wealth index, an important indicator extracted from the MICS data—and other parameters such as urban/rural setting, ownership of items, and prioritization of possessions. Among other uses, these findings can serve to inform policy by providing a hierarchy of essential amenities. They can also potentially be used to refine the wealth index or deepen our understanding of what it captures.

A strategy toward epitope-selective functionalized nanoparticles is introduced in the following: ultrasmall gold nanoparticles (diameter of the metallic core about 2 nm) were functionalized with molecular tweezers that selectively attach lysine and arginine residues on protein surfaces. Between 11 and 30 tweezer molecules were covalently attached to the surface of each nanoparticle by copper-catalyzed azide alkyne cycloaddition (CuAAC), giving multiavid agents to target proteins. The nanoparticles were characterized by high-resolution transmission electron microscopy, differential centrifugal sedimentation, and 1H NMR spectroscopy (diffusion-ordered spectroscopy, DOSY, and surface composition). The interaction of these nanoparticles with the model proteins hPin1 (WW domain; hPin1-WW) and Survivin was probed by NMR titration and by isothermal titration calorimetry (ITC). The binding to the WW domain of hPin1 occurred with a KD of 41 ± 2 μM, as shown by ITC. The nanoparticle-conjugated tweezers targeted cationic amino acids on the surface of hPin1-WW in the following order: N-terminus (G) ≈ R17 > R14 ≈ R21 > K13 > R36 > K6, as shown by NMR spectroscopy. Nanoparticle recognition of the larger protein Survivin was even more efficient and occurred with a KD of 8 ± 1 μM, as shown by ITC. We conclude that ultrasmall nanoparticles can act as versatile carriers for artificial protein ligands and strengthen their interaction with the complementary patches on the protein surface.

Background Inadequate resection margins in oral cavity squamous cell carcinoma have an adverse effect on patient outcome. Intraoperative assessment provides immediate feedback enabling the surgeon to achieve adequate resection margins. The goal of this study was to evaluate the value of specimen-driven intraoperative assessment by comparing the margin status in the period before and the period after the introduction of specimen-driven assessment as a standard of care (period 2010–2012 vs period 2013–2017). Methods A cohort of patients surgically treated for oral squamous cell carcinoma at the Erasmus MC Cancer Institute, Rotterdam, between 2010–2012 was studied retrospectively and compared to results of a prospectively collected cohort between 2013–2017. The frequency, type and results of intraoperative assessment of resection margins were analyzed. Results One hundred seventy-four patients were included from 2010–2012, 241 patients were included from 2013–2017. An increase in the frequency of specimen-driven assessment was seen between the two periods, from 5% in 2010–2012 to 34% in 2013–2017. When performing specimen-driven assessment, 16% tumor-positive resection margins were found in 2013–2017, compared to 43% tumor-positive resection margins overall in 2010–2012. We found a significant reduction of inadequate resection margins for specimen-driven intraoperative assessment (p < 0.001). Also, tumor recurrence significantly decreased, and disease-specific survival improved when performing specimen-driven intraoperative assessment. Conclusions Specimen-driven intraoperative assessment improves resection margins and consequently, the outcome of oral cancer patients. We advocate this method as standard of care.

The study aims to empirically explore the dependence of savings behavior on demographic changes in the context of the life cycle hypothesis (LCH) in a sample of 18 European transition and post transition countries. The empirical methodology is based on a multifactor modeling approach. The research estimates heterogeneous panel data models by employing three different heterogeneous coefficient estimators: mean group (MG) estimator, common correlated effects mean group (CCEMG) estimator, and augmented mean group (AMG) estimator. The findings demonstrate that the LCH is confirmed in the case of European post-transition countries and rejected as inappropriate in European transition countries due to inconsistency of regression coefficients (age dependency, unemployment rate, urbanization, and health expenditure). The models and their findings presented in this study can be used in policymaking to predict dynamic interactions and variations among selected demographic variables in the determination of savings behavior.

Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate.

Abstract Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3–5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease–related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs.