PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication

DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) lightdamaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol h-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player in replication fork progression in eukaryotic cells

First Experience in Management of Coronavirus Disease 2019 (COVID-19) in Kidney Transplant Patient – Case Report

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has recently emerged in the world. There are limited data describing the clinical progression of COVID-19 in transplanted patients. In the general population, clinical presentation ranges from asymptomatic infection to severe pneumonia and may also develop renal failure. In kidney transplant (KT) patients, management of these patients was mainly based on anecdotal experience. CASE REPORT: We report our first experience of KT patients with COVID-19. A 49-year-old male with KT in 2017 presented on March 20, 2020, with fever, weakness, smell loss, chest pain, and caught. On chest X-ray, he presented ground-glass opacities and bilateral pneumonia. There was a slight progression to acute hypoxic respiratory failure. We reduced immunosuppression therapy and since we suspected seasonal flu, we applied available antiviral oseltamivir till confirmation of RNA sequence of the SARS-CoV-2 virus. Moreover, we applied azithromycin and broad spectrum of antibiotics as well as an anticoagulant therapy. Graft function remained stable during 14 days of hospitalization. The patient clinically improved with decreasing oxygen requirements and manifested clinical recovery. After two negative PCR test, he was discharged and immunosuppression therapy was returned to previous. CONCLUSION: This case highlights the importance of earlier outpatient hospitalization and testing which may improve COVID-19 outcomes among transplanted patients

Seroprevalence of SARS-CoV-2 infection among children in Children’s Hospital Zagreb during the initial and second wave of COVID-19 pandemic in Croatia

The study aimed to investigate the prevalence and titres of anti-SARS-CoV-2 antibodies in children treated at the Children’s Hospital Zagreb in the first and the second wave of the COVID-19 pandemic. Statistical significance of difference at two time points was done to determine how restrictive epidemiological measures and exposure of children to COVID-19 infection affect this prevalence in different age groups. At the first time point (13th to 29th May 2020), 240 samples and in second time point (24th October to 23rd November 2020), 308 serum samples were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECLIA). Confirmation of results and titre determination was done using virus micro-neutralization test. Subjects were divided according to gender, age and epidemiological history. Seroprevalence of anti-SARS-CoV-2 antibodies differs significantly in two time points (P = 0.010). In first time point 2.9% of seropositive children were determined and in second time point 8.4%. Statistically significant difference (P = 0.007) of seroprevalence between two time points was found only in a group of children aged 11-19 years. At the first time point, all seropositive children were asymptomatic with titre < 8. At the second time point, 69.2% seropositive children were asymptomatic with titre ≥ 8. The prevalence of anti-SARS-CoV-2 antibodies was significantly lower at the first time point than at the second time point. Values of virus micro-neutralization test showed that low titre in asymptomatic children was not protective at the first time point but in second time point all seropositive children had protective titre of anti-SARS-CoV-2 antibodies

First detection of Zika virus infection in a Croatian traveler returning from Brazil, 2016

In the last few years, several imported cases of Zika virus (ZIKV) infection were reported in European countries. We report the first imported ZIKV infection case in a Croatian traveler returning from Brazil. The patient presented with a low-grade fever, pruritic rash, general weakness, myalgia, arthralgia and edema of the legs and recovered completely within a week. ZIKV infection was confirmed by detection of IgM/IgG antibodies using enzyme-linked immunosorbent assay (ELISA) and confirmed by plaque-reduction neutralization test (PRNT). ZIKV IgM antibodies cross-reacted with dengue virus (DENV), West Nile virus (WNV) and tick-borne encephalitis virus (TBEV) in ELISA. In indirect immunofluorescence assay (IFA), IgM cross-reactivity was found only with DENV-3. ZIKV IgG antibodies cross-reacted with DENV in both ELISA and IFA. PRNT for DENV was negative. Control serology performed on days 64 and 98 after disease onset showed a decline in cross-reactive heterologous DENV IgG antibodies compared to persistently high titer of homologous ZIKV IgG antibodies

a review of methodological design choices

Publisher Copyright: © 2023 Cambridge University Press. All rights reserved.This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the Disability-Adjusted Life Years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3,053 studies of which 2,948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.publishersversionepub_ahead_of_prin

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results

Applications of Biodegradable Magnesium-Based Materials in Reconstructive Oral and Maxillofacial Surgery: A Review

Reconstruction of defects in the maxillofacial region following traumatic injuries, craniofacial deformities, defects from tumor removal, or infections in the maxillofacial area represents a major challenge for surgeons. Various materials have been studied for the reconstruction of defects in the maxillofacial area. Biodegradable metals have been widely researched due to their excellent biological properties. Magnesium (Mg) and Mg-based materials have been extensively studied for tissue regeneration procedures due to biodegradability, mechanical characteristics, osteogenic capacity, biocompatibility, and antibacterial properties. The aim of this review was to analyze and discuss the applications of Mg and Mg-based materials in reconstructive oral and maxillofacial surgery in the fields of guided bone regeneration, dental implantology, fixation of facial bone fractures and soft tissue regeneration

Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats

This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9\% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.Ministry of Education, Science and Technological Development of the Republic of Serbia {[}III41014]; Military Medical Academy {[}MBMA/3/13-15, MBMA/6/15-17

Preclinical Evaluation of Bioactive Scaffolds for the Treatment of Mandibular Critical-Sized Bone Defects: A Systematic Review

This systematic review evaluated current in vivo research on regenerating critical-sized mandibular defects and discussed methodologies for mandibular bone tissue engineering. Out of the 3650 articles initially retrieved, 88 studies were included, and all studies that used a scaffold reported increased bone formation compared to negative controls. Combining scaffolds with growth factors and mesenchymal stem cells improved bone formation and healing. Bone morphogenic proteins were widely used and promoted significant bone formation compared to controls. However, discrepancies between studies exist due to the various methodologies and outcome measures used. The use of scaffolds with bioactive molecules and/or progenitor cells enhances success in mandibular bone engineering. Scaffold-based mandibular bone tissue engineering could be introduced into clinical practice due to its proven safety, convenience, and cost-effectiveness