Prenatal infections and congenital abnormalities: probable relationship

Moguća povezanost prenatalnih infekcija s raznim kongenitalnim malformacijama istraživana je u 194 novorođenčadi, fetusa te mrtvorođenčadi. Različite izolirane kongenitalne malformacije zabilježene su u 92 djece; u 38 višestruke malformacije te autosomne trisomije u 64. Klinički podaci, povijesti bolesti te protokoli cjelokupne anatomije analizirani su u svih bolesnika. Konzultirani su subspecijalisti, učinjene radiološke i ultrazvučne pretrage te obavljena rutinska klinička praksa kod sve novorođenčadi. PCR analiza korištena je za detekciju virusa rubeole, herpes simpleks tipa 1, citomegalovirusa, Toxoplasma gondii i klamidije trahomatis u uzorcima krvi i urina; te u uzorcima tkiva srca, jetre, mozga, kralježnične moždine, bubrega, pluća te tankog crijeva fiksiranih u formalinu ili uklopljenih u parafin. Prisustvo infektivnog uzročnika dokazano je u 76,1% slučajeva izoliranih kongenitalnih malformacija te u 86,1% višestrukih malformacija. Virus rubeole izoliran je u 58,6% djece s autosomnom trisomijom.Possible relation of prenatal infections with various congenital malformations was examined in 194 cases including newborns, fetuses, and stillbirths. 92 children had various isolated congenital malformations; 38 – multiple malformations; and 64 – autosomal trisomy. Clinical data, case history and gross anatomy protocols were analyzed for all patients. Subspecialty consultation, radiological and ultrasound examinations have been applied together with routine clinical studies to all newborns. PCR-analysis was used for diagnostics of rubella virus, herpes simplex virus type 1, cytomegalovirus, Toxoplasma gondii and Chlamydia trachomatis in blood and urine samples; and in autopsy formalin-fixed-paraffin-mbedded tissue samples of heart, liver, brain, spinal cord, kidneys, lungs, small intestine. Presence of infectious agents was found in 76.1 % of cases with isolated congenital malformations and in 86.1 % of multiple malformations. Rubella virus was detected in 58.6 % of children with autosomal trisomy

Effects of diabetes family history and exercise training on the expression of adiponectin and leptin and their receptors

The daughters of patients with diabetes have reduced insulin sensitivity index (ISI) scores compared with women with no family history of diabetes, but their ISI increase more in response to exercise training(1). The present study aimed to determine whether differences between these groups in exercise-induced changes in circulating adiponectin and leptin concentrations and expression of their genes and receptors in subcutaneous adipose tissue (SAT), could explain differences in the exercise-induced changes in ISI between women with and without a family history of diabetes

Rationale and design of the open-label, prospective, randomized study of the efficacy of intravenous versus oral iron deficiency therapy in improving left ventricular systolic function in patients with myocardial infarction (OPERA-MI)

Aim. Iron has a protective effect on cardiomyocytes during hypoxia, while iron deficiency (ID) directly affects its function, disrupting mitochondrial respiration, reducing their contractility and relaxation. Some studies have shown that ID is a predictor of adverse outcomes  in patients with acute coronary syndrome (ACS).  However, the impact of ID and its treatment, quality of life and prognosis of patients with ID and myocardial infarction (MI) has not been fully established. The study aim is to determine the effectiveness of intravenous ferric carboxymaltose  (FCM) compared  with oral iron (ferrous sulfate) in relation to left ventricular (LV) systolic function, assessed by echocardiography.Material and methods. This open-label, prospective, randomized study includes 360 patients  with or without ID who were  hospitalized  with acute  myocardial infarction (MI).  Patients with ID will be randomized (1:1) to intravenous FCM and oral ferrous sulfate therapy. Treatment in groups will be started at the time of hospitalization. Patients without ID will form the control group.  The follow-up period for patients will be 1 year. The primary endpoint was a reduction  in LV wall motion score  index (WMSI) in the FCM group compared  to the ferrous sulfate group. The key secondary endpoint is a composite endpoint of cardiovascular death, non-fatal MI and stroke, and hospitalization for decompensated heart failure.Conclusion. The OPERA-MI study will determine the effect  of ID treatment with intravenous FCM compared  with oral ferrous sulfate on WMSI, which reflects LV systolic function

Development of DNA-Biochip for Identification of Influenza A Virus Subtypes

Developed was the DNA-biochip to identify subtypes of influenza A virus, pathogenic for humans. Microchip was capable of detecting H1, H3, H5-subtypes of hemagglutinin (including H1-subtype of pandemic A/H1N1(2009) influenza virus ) and neuraminidase subtypes N1,N2 of influenza virus. This microchip was successfully tested on the strains of A/H5N1 highly pathogenic avian influenza virus, A/H1N1(2009) pandemic influenza virus, A/H1N1 and A/H3N2 seasonal influenza viruses

Оценка сопоставимости результатов определения фенола в иммунобиологических лекарственных препаратах

The article presents the practical assessment of the possibility of harmonization and standardization of methods for the determination of phenol in the immunebiological medicines. The evaluation of the statistical significance of differences in the results of determinations of phenol existing methods described in the standard documentation for foreign and domestic preparations: used ANOVA with Fisher’s exact test (F-test). The conclusion of the interchangeability of the studied methods for the determination of phenol in the immune-biological medicines and the opportunity of the development and certification of standard reference and sample validation measurements.В статье представлены материалы практической оценки сопоставимости результатов определения содержания фенола в иммунобиологических лекарственных препаратах полученных различными методами. Проведена оценка статистической значимости различий результатов определения фенола методами, описанными в НД на зарубежные и отечественные препараты: использован однофакторный дисперсионный анализ с применением критерия Фишера (F-критерия). Сделан вывод о взаимозаменяемости исследованных методов определения фенола в ИЛП и актуальности разработки и аттестации стандартного образца сравнения и образца подтверждения правильности измерений

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Microarray Analysis of Human Monocytes Infected with Francisella tularensis Identifies New Targets of Host Response Subversion

Francisella tularensis is a gram-negative facultative bacterium that causes the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. In order to help understand the mechanisms by which this occurs, we performed Affymetrix microarray analysis on transcripts from blood monocytes infected with the virulent Type A Schu S4 strain. Results showed that expression of several host response genes were reduced such as those associated with interferon signaling, Toll-like receptor signaling, autophagy and phagocytosis. When compared to microarrays from monocytes infected with the less virulent F. tularensis subsp. novicida, we found qualitative differences and also a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes in the Schu S4 strain. Notably, the PI3K / Akt1 pathway appeared specifically down-regulated following Schu S4 infection and a concomitantly lower cytokine response was observed. This study identifies several new factors potentially important in host cell subversion by the virulent Type A F. tularensis that may serve as novel targets for drug discovery

Segmental Duplications Arise from Pol32-Dependent Repair of Broken Forks through Two Alternative Replication-Based Mechanisms

The propensity of segmental duplications (SDs) to promote genomic instability is of increasing interest since their involvement in numerous human genomic diseases and cancers was revealed. However, the mechanism(s) responsible for their appearance remain mostly speculative. Here, we show that in budding yeast, replication accidents, which are most likely transformed into broken forks, play a causal role in the formation of SDs. The Pol32 subunit of the major replicative polymerase Polδ is required for all SD formation, demonstrating that SDs result from untimely DNA synthesis rather than from unequal crossing-over. Although Pol32 is known to be required for classical (Rad52-dependant) break-induced replication, only half of the SDs can be attributed to this mechanism. The remaining SDs are generated through a Rad52-independent mechanism of template switching between microsatellites or microhomologous sequences. This new mechanism, named microhomology/microsatellite-induced replication (MMIR), differs from all known DNA double-strand break repair pathways, as MMIR-mediated duplications still occur in the combined absence of homologous recombination, microhomology-mediated, and nonhomologous end joining machineries. The interplay between these two replication-based pathways explains important features of higher eukaryotic genomes, such as the strong, but not strict, association between SDs and transposable elements, as well as the frequent formation of oncogenic fusion genes generating protein innovations at SD junctions

Limitations and opportunities of cancer treatment in the COVID-19 pandemic

The COVID-19 pandemic has affected all medical fields and brought up a lot of serious problems. The features of the COVID-19 infection in patients with cancer are important to understand. According to many articles, patients with cancer are more vulnerable to COVID-19 infection. Patients undergoing anticancer treatment have 1-4% morbidity rate. Patients with hematological diseases and lung cancer are at higher risk of SARS-CoV-2 infection and also have more severe symptoms and complications. In this article we discuss the effect of the tumors on the immune system and comprehend the pathogenesis of the coronavirus disease according to its impact on the immunity. Moreover, in the review we analyze available data about the influence of the different types of cancer therapy (chemotherapy, target therapy, radiotherapy and immunotherapy) on the severity of the COVID-19 infection. Evidence on the effect of chemotherapy on severity and mortality from COVID-19 is contradictory. Whereas there are some authors concluding that chemotherapy treatment is not affecting the severity of COVID-19 disease, there are also some works where the connection between these facts was established. At the same time target therapy, radio- and immunotherapy most likely do not worsen the SARS-CoV-2 infection and are not associated with the development of complications. But it’s important to say that the amount of data available for today is insufficient to make a unambiguous conclusion

Polymerase δ replicates both strands after homologous recombination-dependent fork restart

To maintain genetic stability DNA must be replicated only once and replication completed even when individual replication forks are inactivated. Because fork inactivation is common, the passive convergence of an adjacent fork is insufficient to rescue all inactive forks. Thus, eukaryotic cells have evolved homologous recombination-dependent mechanisms to restart persistent inactive forks. Completing DNA synthesis via Homologous Recombination Restarted Replication (HoRReR) ensures cell survival, but at a cost. One such cost is increased mutagenesis caused by HoRReR being more error prone than canonical replication. This increased error rate implies that the HoRReR mechanism is distinct from that of a canonical fork. Here we exploit the fission yeast Schizosaccharomyces pombe to demonstrate that a DNA sequence duplicated by HoRReR during S phase is replicated semi-conservatively, but that both the leading and lagging strands are synthesised by DNA polymerase delta