Ortholog of the polymerase theta helicase domain modulates DNA replication in Trypanosoma cruzi

DNA polymerase theta (Polθ), a member of the DNA polymerase family A, exhibits a polymerase C-terminal domain, a central domain, and an N-terminal helicase domain. Polθ plays important roles in DNA repair via its polymerase domain, regulating genome integrity. In addition, in mammals, Polθ modulates origin firing timing and MCM helicase recruitment to chromatin. In contrast, as a model eukaryote, Trypanosoma cruzi exhibits two individual putative orthologs of Polθ in different genomic loci; one ortholog is homologous to the Polθ C-terminal polymerase domain, and the other is homologous to the Polθ helicase domain, called Polθ-polymerase and Polθ-helicase, respectively. A pull-down assay using the T. cruzi component of the prereplication complex Orc1/Cdc6 as bait captured Polθ-helicase from the nuclear extract. Orc1/Cdc6 and Polθ-helicase directly interacted, and Polθ-helicase presented DNA unwinding and ATPase activities. A T. cruzi strain overexpressing the Polθ-helicase domain exhibited a significantly decreased amount of DNA-bound MCM7 and impaired replication origin firing. Taken together, these data suggest that Polθ-helicase modulates DNA replication by directly interacting with Orc1/Cdc6, which reduces the binding of MCM7 to DNA and thereby impairs the firing of replication origins

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Transfusion: Case Report

The principal indications for exchange transfusion are hemolytic diseases of the newborn with hyperbilirubinemia. However, there are some potential complications of exchange transfusion such as infection, coagulopathies (i.e., thrombocytopenia), electrolyte abnormalities (i.e., hypocalcemia), metabolic acidosis, hypoglycemia, and necrotizing enterocolitis. Stored blood develops some platelet-white cell microaggregates. These microaggregates or blood debris have been found to produce changes in pulmonary hemodynamics in animals and have been implicated in post-traumatic pulmonary insufficiency in man. Authors suggested that pulmonary gas exchange alterations following blood transfusion were primarily due to increased dead-space ventilation secondary to vasoconstriction and occlusion of the pulmonary microvasculature because of microaggregates. In this article, a newborn with transient pulmonary perfusion abnormality who had massive exchange transfusion for Rh isoimmunization and hyperbilirubinemia was reported

and Hepatitis C Virus Co-infections

Background: Because of their similar modes of transmission, the simultaneous infection of viral hepatitis and human immunodeficiency virus are increasingly seen as a big problem related to human health.Aims: To determine the drug mutations in hepatitis B virus and/or hepatitis C virus co-infected human immunodeficiency virus-1 patients in Turkey.Study Design: Retrospective cross-sectional study.Methods: The present study was conducted between 2010 and 2017. HBsAg, anti-hepatitis C virus, and anti-human immunodeficiency vim were tested with ELISA. All anti-human immunodeficiency virus positive results by ELISA were verified for anti-human immunodeficiency virus positivity by a Western blot test, and Antihuman immunodeficiency virus positive patients with HBsAg andior anti-hepatitis C virus positivity were included in the study. Subtyping and genotypic resistance analyses were performed by population sequencing of the viral protease and reverse transcriptase regions of the human immunodeficiency virus-1 pol gene.Results: We detected 3896 human immunodeficiency virus-1 positive patients whose sera were sent from numerous hospitals across the country to our polymerase chain reaction unit for detection of drug resistance mutations and whose molecular laboratory tests were completed. Viral hepatitis co-infections were detected in 4.3% (n=170) of patients. Hepatitis B virus and hepatitis C virus co-infection were observed in 3.2% and 0.5% of all human immunodeficiency virus-I infected patients, respectively. The major human immunodeficiency virus-1 subtype detected was group M, subtype B (62.9%). However, 13.5% of drug resistance mutation motifs were found in human immunodeficiency virus-1 genomes of patients included in the study.Conclusion: Due to similar transmission routes, HIV1 patients are at risk of hepatitis B and C virus co-infection. However, antiretroviral drug resistance mutation model is similar to patients with hepatitis negative.C1 [Sayan, Murat] Kocaeli Univ, PCR Unit, Clin Lab, Sch Med, Kocaeli, Turkey.[Sayan, Murat] Hlth Sci Near East Univ, Res Ctr Expt, North Nicosia, Northern Cyprus, Turkey.[Ozguler, Muge] Univ Hlth Sci, Elazig Fethi Sekin City Hosp, Clin Infect Dis & Clin Microbiol, Elazig, Turkey.[Yildirim, Figen Sarigul] Univ Hlth Sci, Antalya Training & Res Hosp, Clin Infect Dis & Clin Microbiol, Antalya, Turkey.[Yildirmak, Taner] Univ Hlth Sci, Okmeydan Training & Res Hosp, Clin Infect Dis & Clin Microbiol, Istanbul, Turkey.[Gunduz, Alper] Univ Hlth Sci, Sisli Etfal Training & Res Hosp, Clin Infect Dis & Clin Microbiol, Istanbul, Turkey.[Dokuzoguz, Basak] Univ Hlth Sci, Ankara Training & Res Hosp, Clin Infect Dis & Clin Microbiol, Ankara, Turkey.[Celen, Mustafa Kemal] Dicle Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Diyarbakir, Turkey.[Inan, Dilara] Akdeniz Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Antalya, Turkey.[Heper, Yasemin] Uludag Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Bursa, Turkey.[Ersoz, Gulden] Mersin Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Mersin, Turkey.[Karaoglan, Ilkay] Gaziantep Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Gaziantep, Turkey.[Ceran, Nurgul] Univ Hlth Sci, Haydarpasa Numune Training & Res Hosp, Clin Infect Dis & Clin Microbiol, Istanbul, Turkey.[Deveci, Aydin] Ondokuz Mayis Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Samsun, Turkey.[Ozturk, Servet] Univ Hlth Sci, Fatih Sultan Mehmet Training & Res Hosp, Clin Infect Dis & Clin Microbiol, Istanbul, Turkey.[Kutlu, Selda Sayin] Pamukkale Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Denizli, Turkey.[Ozdemir, Hulya Ozkan] Univ Hlth Sci, Bozyaka Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Izmir, Turkey.[Akbulut, Ayhan] Firat Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Elazig, Turkey.[Yazici, Saadet] Medeniyet Univ, Goztepe Training & Res Hosp, Clin Infect Dis & Clin Microbiol, Istanbul, Turkey.[Sener, Alper] Onsekiz Mart Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Canakkale, Turkey.[Cagatay, Atahan] Istanbul Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Istanbul, Turkey.[Unal, Serhat] Hacettepe Univ, Dept Infect Dis & Clin Microbiol, Sch Med, Ankara, Turkey