Corrigendum: Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection

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Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection

Tick-borne encephalitis virus (TBEV) is a member of the genus Flavivirus. It can cause serious infections in humans that may result in encephalitis/meningoencephalitis. Although several studies have described the involvement of specific genes in the host response to TBEV infection in the central nervous system (CNS), the overall network remains poorly characterized. Therefore, we investigated the response of DAOY cells (human medulloblastoma cells derived from cerebellar neurons) to TBEV (Neudoerfl strain, Western subtype) infection to characterize differentially expressed genes by transcriptome analysis. Our results revealed a wide panel of interferon-stimulated genes (ISGs) and pro-inflammatory cytokines, including type III but not type I (or II) interferons (IFNs), which are activated upon TBEV infection, as well as a number of non-coding RNAs, including long non-coding RNAs. To obtain a broader view of the pathways responsible for eliciting an antiviral state in DAOY cells we examined the effect of type I and III IFNs and found that only type I IFN pre-treatment inhibited TBEV production. The cellular response to TBEV showed only partial overlap with gene expression changes induced by IFN-β treatment – suggesting a virus-specific signature – and we identified a group of ISGs that were highly up-regulated following IFN-β treatment. Moreover, a high rate of down-regulation was observed for a wide panel of pro-inflammatory cytokines upon IFN-β treatment. These data can serve as the basis for further studies of host–TBEV interactions and the identification of ISGs and/or lncRNAs with potent antiviral effects in cases of TBEV infection in human neuronal cells

Lipoblastoma retroperitoneal en un lactante. Caso clínico

ResumenIntroducciónEl lipoblastoma es una neoplasia benigna del tejido adiposo, de presentación infrecuente y casi exclusiva en niños menores de 3 años. Usualmente se presenta en las extremidades como una masa indolora de crecimiento progresivo, estableciéndose su diagnóstico definitivo mediante análisis histológico y citogenético.ObjetivoPresentar un caso clínico de lipoblastoma de ubicación inhabitual en una lactante y revisar la literatura al respecto.Caso clínicoLactante mayor de 16 meses, con aumento de volumen abdominal de 6 meses de evolución, asociado a una ingesta alimentaria disminuida, sin otros síntomas. El estudio de imagen reveló una imagen de aspecto lipoideo que comprometía casi la totalidad de la cavidad abdominal, muy sugerente de lipoblastoma, realizándose la resección de un tumor retroperitoneal de 18cm de diámetro que rechazaba los órganos vecinos. El análisis histológico fue suficiente para confirmar el diagnóstico. En el seguimiento no hubo recidiva.ConclusiónTomando en cuenta la baja frecuencia de esta afección y su inusual presentación, se reporta el caso de esta paciente, para considerarlo dentro del diagnóstico diferencial de masa abdominal en un lactante.AbstractIntroductionLipoblastoma is a benign neoplasia of the adipose tissue. It is a rare conditionand almost exclusively presents in children under 3 years old. It usually occurs in extremities as a painless volume increase of progressive growth, with the definitive diagnosis being established by pathological and cytogenetic analysis. The treatment of choice is complete resection, and follow-up period of up to five years is recommended due to a recurrence of up to 25%.ObjectiveTo present an unusual location of this uncommon condition in an infant, and review the related literature.Case reportA sixteen-month child with an increase in abdominal growth of six-months progression, associated with a decreased food intake, and with no other symptoms. The imaging study revealed a lipoid-like image compromising almost the entire abdominal cavity, very suggestive of lipoblastoma. A resection was performed on an 18cm diameter retroperitoneal tumour that rejected the adjacent organs. Histological analysis was enough to confirm diagnosis without the need for cytogenetic analysis. The follow-up showed no recurrence of the disease.ConclusionGiven the rarity of this disease and its unusual presentation, we communicate this clinical case, in order to be considered in the differential diagnosis of abdominal mass in chilhood

АЛЛОГЕННЫЕ КОСТНОПЛАСТИЧЕСКИЕ МАТЕРИАЛЫ: СОВРЕМЕННОЕ СОСТОЯНИЕ ПРОБЛЕМЫ

Worldwide population aging and associated with it epidemics of osteoporosis, widespread of bone and joint reconstructive surgery and first of all joint replacement lead to explosive growth of interest in bone grafting.Although autografts are still the golden standard in bone regeneration, allogeneic bone substitutes have reached a state that allows for their application with satisfying clinical results. However, it has repeatedly been supposed that the different allogeneic materials underwent different purification processes, which modifies bone regeneration properties of these materials and also for different safety conditions. In the present publication, the treatment of the precursor tissue, the safety conditions, and the regenerative possibilities of C+TBA bone blocks based in preclinical and clinical data are described. Thus, it is described how the risks of infections and also immunological reactions becomes completely eliminated, while the special purification process allows for preservation of the native structure of the bone block. Both the in vitro studies and the clinical trials including histological follow-ups showed the optimal regeneration properties of these bone blocks. It has been shown that the allogeneic bone grafts have been integrated without causing inflammatory anomalies at the implantation site. Altogether, the allogeneic bone substitute material serves as an excellent basis for the formation of new bone. Finally, the combination of the allogeneic C+TBA bone blocks with different antibiotics is described. Interestingly, it is possible to combine the allogeneic bone substitute ether with antibiotics in the sense of prophylaxis and/or with bone marrow aspirate in order to accelerate bone remodeling.Старение населения планеты и ассоциированная с ним эпидемия остеопороза, а также широкое распространение реконструктивных операций на костях и суставах, в первую очередь эндопротезирования, привели к взрывному росту интереса к костной пластике.Несмотря на то, что аутотрансплантаты по-прежнему остаются «золотым стандартом» при замещении костных дефектов, аллогенные костнозамещающие материалы достигли такого уровня качества, который позволяет с успехом применять их в клинической практике. Неоднократно высказывались предположения, что разные способы обработки различных типов аллогенных материалов по-разному меняют их регенеративные свойства и характеристики безопасности. В статье описана технология обработки исходного материала, перечислены требования к безопасности аллокости, регенеративные возможности костных блоков C+TBA. Приводятся подтверждающие данные доклинических и клинических исследований. Технология C+TBA позволяет практически полностью исключить риск развития иммунологических реакций и передачи инфекции, а специальные этапы обработки позволяют сохранить естественную структуру костного блока. Клинические и in vitro исследования с гистологическим контролем на разных этапах показали оптимальные регенеративные характеристики таких костных блоков. Аллогенная кость интегрировалась, не вызывая локальных воспалительных реакций в месте трансплантации. В целом аллогенные костнозамещающие материалы являются отличной основой для формирования новой кости. В статье описаны комбинации аллогенных костных блоков C+TBA с различными антибиотиками с целью профилактики инфекции и/или с пунктатом костного мозга для стимуляции перестройки кости

Agreement and accuracy using the FIGO, ACOG and NICE cardiotocography interpretation guidelines.

INTRODUCTION: One of the limitations reported with cardiotocography (CTG) is the modest interobserver agreement observed in tracing interpretation. This study compared agreement, reliability and accuracy of CTG interpretation using the FIGO, ACOG and NICE guidelines. MATERIAL AND METHODS: A total of 151 tracings was evaluated by 27 clinicians from three centers where FIGO, ACOG and NICE guidelines were routinely used. Interobserver agreement was evaluated using the proportions of agreement (PA) and reliability with the kappa (k) statistic. The accuracy of tracings classified as "pathological/category III" was assessed for prediction of newborn acidemia. For all measures, 95% confidence intervals (95%CI) were calculated RESULTS: CTG classifications were more distributed with FIGO (9%, 52%, 39%) and NICE (30%, 33%, 37%) than with ACOG (13%, 81%, 6%). The category with the highest agreement was ACOG category II (PA=0.73 95%CI 0.70-76), and the ones with the lowest agreement were ACOG categories I and III. Reliability was significantly higher with FIGO (k=0.37, 95%CI 0.31-0.43), and NICE (k=0.33, 95%CI 0.28-0.39) than with ACOG (k= 0.15, 95%CI 0.10-0.21), however all represent only slight/fair reliability. FIGO and NICE showed a trend towards higher sensitivities in prediction of newborn acidemia (89% and 97% respectively) than ACOG (32%,), but the latter achieved a significantly higher specificity (95%) CONCLUSIONS: With ACOG guidelines there is high agreement in category II, low reliability, low sensitivity and high specificity in prediction of acidemia. With FIGO and NICE guidelines there is higher reliability, a trend towards higher sensitivity, and lower specificity in prediction of acidemia. This article is protected by copyright. All rights reserved

Effects of dendritic core-shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors

The biological impact of novel nano-scaled drug delivery vehicles in highly topical therapies of bone diseases have to be investigated in vitro before starting in vivo trials. Highly desired features for these materials are a good cellular uptake, large transport capacity for drugs and a good bio-compatibility. Essentially the latter has to be addressed as first point on the agenda. We present a study on the biological interaction of maltose-modified poly(ethyleneimine) (PEI-Mal) on primary human mesenchymal stem cell, harvested from reaming debris (rdMSC) and osteoblasts obtained from four different male donors. PEI-Mal-nanoparticles with two different molecular weights of the PEI core (5000 g/mol for PEI-5k-Mal-B and 25,000 g/mol for PEI-25k-Mal-B) have been administered to both cell lines. As well dose as incubation-time dependent effects and interactions have been researched for concentrations between 1 μg/ml to 1 mg/ml and periods of 24 h up to 28 days. Studies conducted by different methods of microscopy as light microscopy, fluorescence microscopy, transmission-electron-microscopy and quantitative assays (LDH and DC-protein) indicate as well a good cellular uptake of the nanoparticles as a particle- and concentration-dependent impact on the cellular macro- and micro-structure of the rdMSC samples. In all experiments PEI-5k-Mal-B exhibits a superior biocompatibility compared to PEI-25k-Mal-B. At higher concentrations PEI-25k-Mal-B is toxic and induces a directly observable mitochondrial damage. The alkaline phosphatase assay (ALP), has been conducted to check on the possible influence of nanoparticles on the differentiation capabilities of rdMSC to osteoblasts. In addition the production of mineralized matrix has been shown by von-Kossa stained samples. No influence of the nanoparticles on the ALP per cell has been detected. Additionally, for all experiments, results are strongly influenced by a large donor-to-donor variability of the four different rdMSC samples. To summarize, while featuring a good cellular uptake, PEI-5k-Mal-B induces only minimal adverse effects and features clearly superior biocompatibility compared to the larger PEI-25k-Mal-B

Effects of dendritic core-shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors

The biological impact of novel nano-scaled drug delivery vehicles in highly topical therapies of bone diseases have to be investigated in vitro before starting in vivo trials. Highly desired features for these materials are a good cellular uptake, large transport capacity for drugs and a good bio-compatibility. Essentially the latter has to be addressed as first point on the agenda. We present a study on the biological interaction of maltose-modified poly(ethyleneimine) (PEI-Mal) on primary human mesenchymal stem cell, harvested from reaming debris (rdMSC) and osteoblasts obtained from four different male donors. PEI-Mal-nanoparticles with two different molecular weights of the PEI core (5000 g/mol for PEI-5k-Mal-B and 25,000 g/mol for PEI-25k-Mal-B) have been administered to both cell lines. As well dose as incubation-time dependent effects and interactions have been researched for concentrations between 1 μg/ml to 1 mg/ml and periods of 24 h up to 28 days. Studies conducted by different methods of microscopy as light microscopy, fluorescence microscopy, transmission-electron-microscopy and quantitative assays (LDH and DC-protein) indicate as well a good cellular uptake of the nanoparticles as a particle- and concentration-dependent impact on the cellular macro- and micro-structure of the rdMSC samples. In all experiments PEI-5k-Mal-B exhibits a superior biocompatibility compared to PEI-25k-Mal-B. At higher concentrations PEI-25k-Mal-B is toxic and induces a directly observable mitochondrial damage. The alkaline phosphatase assay (ALP), has been conducted to check on the possible influence of nanoparticles on the differentiation capabilities of rdMSC to osteoblasts. In addition the production of mineralized matrix has been shown by von-Kossa stained samples. No influence of the nanoparticles on the ALP per cell has been detected. Additionally, for all experiments, results are strongly influenced by a large donor-to-donor variability of the four different rdMSC samples. To summarize, while featuring a good cellular uptake, PEI-5k-Mal-B induces only minimal adverse effects and features clearly superior biocompatibility compared to the larger PEI-25k-Mal-B

Effect of coronavirus disease 2019 (COVID‐19) on maternal, perinatal and neonatal outcome: systematic review.

Objective To evaluate the effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome by performing a systematic review of available published literature on pregnancies affected by COVID-19. Methods We performed a systematic review to evaluate the effect of COVID-19 on pregnancy, perinatal and neonatal outcome. We conducted a comprehensive literature search using PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure Database and Wan Fang Data up to and including 20 April 2020 (studies were identified through PubMed alert after that date). For the search strategy, combinations of the following keywords and medical subject heading (MeSH) terms were used: ‘SARS-CoV-2’, ‘COVID-19’, ‘coronavirus disease 2019’, ‘pregnancy’, ‘gestation’, ‘maternal’, ‘mother’, ‘vertical transmission’, ‘maternal–fetal transmission’, ‘intrauterine transmission’, ‘neonate’, ‘infant’ and ‘delivery’. Eligibility criteria included laboratory-confirmed and/or clinically diagnosed COVID-19, patient being pregnant on admission and availability of clinical characteristics, including at least one maternal, perinatal or neonatal outcome. Exclusion criteria were non-peer-reviewed or unpublished reports, unspecified date and location of the study, suspicion of duplicate reporting and unreported maternal or perinatal outcomes. No language restrictions were applied. Results We identified a high number of relevant case reports and case series, but only 24 studies, including a total of 324 pregnant women with COVID-19, met the eligibility criteria and were included in the systematic review. These comprised nine case series (eight consecutive) and 15 case reports. A total of 20 pregnant patients with laboratory-confirmed COVID-19 were included in the case reports. In the combined data from the eight consecutive case series, including 211 (71.5%) cases of laboratory-confirmed and 84 (28.5%) of clinically diagnosed COVID-19, the maternal age ranged from 20 to 44 years and the gestational age on admission ranged from 5 to 41weeks. The most common symptoms at presentation were fever, cough, dyspnea/shortness of breath, fatigue and myalgia. The rate of severe pneumonia reported amongst the case series ranged from 0% to 14%, with the majority of the cases requiring admission to the intensive care unit. Almost all cases from the case series had positive computed tomography chest findings. All six and 22 cases that had nucleic-acid testing in vaginal mucus and breast milk samples, respectively, were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Only four cases of spontaneous miscarriage or termination were reported. In the consecutive case series, 219/295 women had delivered at the time of reporting and 78% of them had Cesarean section. The gestational age at delivery ranged from 28 to 41 weeks. Apgar scores at both 1 and 5 min ranged from 7 to 10. Only eight neonates had birth weight <2500 g and nearly one-third of neonates were transferred to the neonatal intensive care unit. There was one case of neonatal asphyxia and death. In 155 neonates that had nucleic-acid testing in throat swab, all, except three cases, were negative for SARS-CoV-2. There were no cases of maternal death in the eight consecutive case series. Seven maternal deaths, four intrauterine fetal deaths (one with twin pregnancy) and two neonatal deaths (twin pregnancy) were reported in a non-consecutive case series of nine cases with severe COVID-19. In the case reports, two maternal deaths, one neonatal death and two cases of neonatal SARS-CoV-2 infection were reported. Conclusions Despite the increasing number of published studies on COVID-19 in pregnancy, there are insufficient good-quality data to draw unbiased conclusions with regard to the severity of the disease or specific complications of COVID-19 in pregnant women, as well as vertical transmission, perinatal and neonatal complications. In order to answer specific questions in relation to the impact of COVID-19 on pregnant women and their fetuses, through meaningful good-quality research, we urge researchers and investigators to present complete outcome data and reference previously published cases in their publications, and to record such reporting when the data of a case are entered into one or several registries.post-print1026 K

Metaviromics reveals unknown viral diversity in the biting midge Culicoides impunctatus

Biting midges (Culicoides species) are vectors of arboviruses and were responsible for the emergence and spread of Schmallenberg virus (SBV) in Europe in 2011 and are likely to be involved in the emergence of other arboviruses in Europe. Improved surveillance and better understanding of risks require a better understanding of the circulating viral diversity in these biting insects. In this study, we expand the sequence space of RNA viruses by identifying a number of novel RNA viruses from Culicoides impunctatus (biting midge) using a meta-transcriptomic approach. A novel metaviromic pipeline called MetaViC was developed specifically to identify novel virus sequence signatures from high throughput sequencing (HTS) datasets in the absence of a known host genome. MetaViC is a protein centric pipeline that looks for specific protein signatures in the reads and contigs generated as part of the pipeline. Several novel viruses, including an alphanodavirus with both segments, a novel relative of the Hubei sobemo-like virus 49, two rhabdo-like viruses and a chuvirus, were identified in the Scottish midge samples. The newly identified viruses were found to be phylogenetically distinct to those previous known. These findings expand our current knowledge of viral diversity in arthropods and especially in these understudied disease vectors