EURO – THE FIRST STOCK-TAKING

Autor kritizira uvođenje eura s pozicije nacionalne i političke ekonomije. Svoju kritiku temelji na četirima pretpostavkama. Prva je da uvođenje eura donosi pravne probleme. Neke zemlje nisu ispunjavale kriterije za uvođenje eura, ali je euro ipak uveden. To znači da se Europski parlament kao i nacionalne vlade i parlamenti više ne drže zakona. Druga je postavka da je stanje dugova u visi 120% nacionalnog proizvoda nemoguće servisirati u demokracijama koje od svojih građana ne mogu zahtijevati akcije štednje koje se protežu na više legislativnih mandata. Treća je kritička primjedba utemeljena na činjenici da se europske zemlje nalaze na različitim stupnjevima razvoja, zbog čega je monetarna unija previše rizična. Četvrta kritika polazi od ideje da zajednička valuta znači i zajedničku politiku, a time i kraj nacionalnih država u Europi. Hrvatska se može priključiti EU, ali će time njena nacionalna suverenost doći u pitanje.The author is critical of the introduction of the euro from the point of view of national and political economy. His criticism is based on four assumptions. The first is that the introduction of the euro gives rise to certain legal concerns. Some countries had not met the criteria for the introduction of the euro, yet it was introduced, which means that the European parliament and the national governments and their parliaments do no longer respect the due process of law. The second is that the foreign debt whose servicing amounts to a 120 percent of GNP is impossible to repay in those democracies that are not in the position to impose austerity measures that would include several legislatures. The third criticism is based on the fact that European countries are at different levels of development which makes the monetary union much too vulnerable. The fourth criticism refers to the fact that common currency means common policy, and consequently the end of nation-states in Europe. Croatia may join the EU, but this would pose a challenge to its national sovereignty

The viral vector vaccine VSV-GP boosts immune response upon repeated applications

Background: Vesicular stomatitis virus (VSV) is a potent candidate vaccine vector for various viral diseases (e.g. HIV, HCV, RSV). The biggest limitation of VSV, however, is its neurotoxicity, which limits application in humans. The second drawback is that VSV induces neutralizing antibodies rapidly and is thus ineffective as a vaccine vector upon repeated applications. Our group has recently shown that VSV pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV), VSV-GP, is not neurotoxic. The aim of this project was to evaluate the potential of VSV-GP as a vaccine vector. Methods: For this purpose, we used Ovalbumin (OVA) as a model antigen and analyzed immunogenicity of GP-pseudotyped and wildtype VSV containing OVA (VSV-GP-OVA and VSV-OVA) in vitro and in vivo in mouse models. Results: We showed that both vectors infected murine bone marrow-derived dendritic cells (bmDCs) in vitro. These bmDCs were able to activate OVA specific CD8+ and CD4+ T cells. Immunization experiments in mice revealed that both VSV-OVA and VSV-GP-OVA induced functional OVA-specific cytotoxic T cells (CTLs) after a single immunization. In addition, with both viruses, mice generated antibodies against OVA. However, boosting with the same virus was only possible for the GP-pseudotyped virus but not for wild type VSV. The efficacy of repeated immunization with VSV-OVA was most likely limited by high levels of neutralizing antibodies, which we detected after the first immunization. In contrast, no neutralizing antibodies against VSV-GP were induced even after boosting. Conclusion: Taken together, we showed that the non-neurotoxic VSV-GP is able to induce specific T cell and B cell responses against the model antigen OVA to the same level as the wild type VSV vector. However, in contrast to wild type VSV, VSV-GP-OVA boosted the immune response upon repeated applications. Thus, VSV-GP is a promising novel vaccine vector

Late Missed Monteggia Lesions—Reconstruction of the Humeroradial Joint

Objective:: Reconstruction of the humeroradial joint resulting in immediate functional stability. Indications:: Missed traumatic dislocation of the radial head. Congenital dislocation of the radial head. Contraindications:: Secondary dislocation of the radial head in instances of dysplasia or aplasia of the capitellum. Relative: deformation of the radial head in adults. Surgical Technique:: Open reduction of the radial head without reconstruction of the annular ligament. Osteotomy of the shaft of the proximal ulna and installation of an external fixator with open clamps. Three-dimensional correction of the ulna under visual control of the humeroradial joint until the radial head is relocated in its anatomic position. Results:: Between 01/1998 and 05/2001, we performed an osteotomy of the proximal ulna, external fixation, and open reduction of the radial head in 14 patients presenting with a late missed Monteggia lesion (Bado type I). The average age of the seven girls and seven boys at the time of reconstruction was 9 (5-15) years, the mean interval between index trauma and reconstruction amounted to 21 months (2 weeks to 7 years). Removal of the external fixator after an average of 12 (7-16) weeks. In twelve patients the reduction was maintained, and in two patients the radial head redislocated postoperatively. In one of these patients a closed reduction was successful, whereas in the other patient an open reduction was done and the external fixation modified. In both patients the joint position was maintained. Preoperatively seven out of 14 patients showed a decreased range of motion; it improved postoperatively in most. A clinical and radiologic follow-up averaging 14 (3-44) months was possible in 13 patients. No complications were recorde

Ligamentous rupture of the ACL associated with dislocated fracture of the proximal tibial physis in a 12-year-old boy

BACKGROUND: Dislocated fracture of the proximal physeal plate of the tibia with or without metaphyseal fragment is rare in children. This unusual fracture classically excludes rupture of the anterior cruciate ligament due to the ligament's stability. A combination of both injuries has not been previously published in the literature. CASE PRESENTATION: The authors report the case of a 12-year-old boy who presented with a dislocated fracture (Salter-Harris II) of the proximal tibia combined with ligamentous rupture of the anterior cruciate ligament after a sporting accident

Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy

Background: Glioblastoma is the most frequent and most malignant primary brain tumor with a poor prognosis. The translation of therapeutic strategies for glioblastoma from the experimental phase into the clinic has been limited by insufficient animal models, which lack important features of human tumors. Lentiviral gene therapy is an attractive therapeutic option for human glioblastoma, which we validated in a clinically relevant animal model. Methodology/Principal Findings: We used a rodent xenograft model that recapitulates the invasive and angiogenic features of human glioblastoma to analyze the transduction pattern and therapeutic efficacy of lentiviral pseudotyped vectors. Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In contrast, pseudotyped gammaretroviral vectors, similar to those evaluated for clinical therapy of glioblastoma, showed inefficient gene transfer in vitro and in vivo. Both pseudotyped lentiviral vectors transduced cancer stem-like cells characterized by their CD133-, nestin- and SOX2-expression, the ability to form spheroids in neural stem cell medium and to express astrocytic and neuronal differentiation markers under serum conditions. In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk) fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001) compared to control groups. In all recurrent tumors, surviving eGFP-positive tumor cells were found, advocating prodrug application for several cycles to even enhance and prolong the therapeutic effect. Conclusions/Significance: In conclusion, lentiviral pseudotyped vectors are promising candidates for gene therapy of glioma in patients. The inefficient gene delivery by gammaretroviral vectors is in line with the results obtained in clinical therapy for GBM and thus confirms the high reproducibility of the invasive glioma animal model for translational research

Marked Increase in Avidity of SARS-CoV-2 Antibodies 7-8 Months After Infection Is Not Diminished in Old Age

The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection obtained from 217 participants of the Ischgl cohort, Austria, was studied 0.5-1.5 months (baseline) and 7-8 months (follow-up) after infection. The IgG avidity assay, using a modified IgG enzyme-linked immunosorbent assay (ELISA) and 5.5 M urea, revealed that old age does not diminish the increase in avidity, detected in all participants positive at both time points, from 18% to 42%. High avidity was associated with a marked residual neutralization capacity in 97.2.% of participants (211/217), which was even higher in the older age group, revealing an important role of avidity assays as easy and cheap surrogate tests for assessing the maturation of the immune system conveying potential protection against further SARS-CoV-2 infections without necessitating expensive and laborious neutralization assays

Ocorrência de Leptospira spp. e fatores associados à infecção em equinos de contingente militar no estado do Rio Grande do Sul, Brasil

The seroprevalence of Leptospira spp. and infection risk factors were investigated in horses from a military contingent in the Rio Grande do Sul State, Brazil. A total of 446 horses were evaluated and categorized into 309 mares, 11 stallions, and 126 horses with an average age of three years. To determine seroprevalence, serum samples from all horses were submitted to the microscopic agglutination test against 12 serovars belonging to nine serogroups, usually circulating in equine populations. To investigate the possible risk factors of infection by Leptospira spp., questionnaires were applied in that military unit. The seroprevalence in the horses with an average age of 3 years, mares, and stallions were 57.94% (73/126), 54.05% (165/309), and 45.45% (5/11), respectively. The main risk factors identified were contact with different water sources, the presence of rodents, and contact with wild and domestic animals. The high seroprevalence of anti‑Leptospira spp. antibodies may be associated with the presence of these risk factors. Therefore, the exposure of horses to possible reservoirs of Leptospira spp. should be minimized. Also, the immunoprophylaxis protocol should be reviewed and a shorter interval between vaccinations adopted to control leptospirosis in this herd. A soroprevalência de Leptospira spp. e os fatores de risco para infecção foram investigados em cavalos de um contingente militar no Rio Grande do Sul, Brasil. Um total de 446 cavalos foram avaliados e categorizados em 309 éguas, 11 garanhões e 126 cavalos com idade média de três anos. Para determinação da soroprevalência, amostras de soro de todos os equinos foram submetidas ao teste de aglutinação microscópica contra 12 sorovares pertencentes a nove sorogrupos, normalmente circulantes em populações equinas. Para investigar os possíveis fatores de risco da infecção por Leptospira spp., foi aplicado um questionário naquela unidade militar. A soroprevalência nos cavalos com idade média de três anos, éguas e garanhões foi de 57,94% (73/126), 54,05% (165/309) e 45,45% (5/11), respectivamente. Os principais fatores de risco identificados foram o contato com diferentes fontes de água, a presença de roedores e o contato com animais silvestres e domésticos. A alta soroprevalência de anticorpos anti-Leptospira spp. pode estar associada à presença desses fatores de risco. Portanto, a exposição destes equinos aos possíveis reservatórios de Leptospira spp. deve ser minimizada. Além disso, o protocolo de imunoprofilaxia deve ser revisto e, possivelmente, um menor intervalo entre as vacinas deve ser adotado para o controle da leptospirose neste plantel

N-chlorotaurine is highly active against respiratory viruses including SARS-CoV-2 (COVID-19) in vitro

N-chlorotaurine (NCT) a long-lived oxidant generated by leukocytes, can be synthesized chemically and applied topically as an anti-infective to different body sites, including the lung via inhalation. Here, we demonstrate the activity of NCT against viruses causing acute respiratory tract infections, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, and respiratory syncytial virus (RSV). Virucidal activity of NCT was tested in plaque assays, confirmed by RT-qPCR assays. Attack on virus proteins was investigated by mass spectrometry. NCT revealed broad virucidal activity against all viruses tested at 37°C and pH 7. A significant reduction in infectious particles of SARS-CoV-2 isolates from early 2020 by 1 log10 was detected after 15 min of incubation in 1% NCT. Proteinaceous material simulating body fluids enhanced this activity by transchlorination mechanisms (1 -2 log10 reduction within 1–10 minutes). Tested SARS-CoV-2 variants B.1.1.7 (Alpha) und B.1.351 (Beta) showed a similar susceptibility. Influenza virus infectious particles were reduced by 3 log10 (H3N2) to 5 log10 (H1N1pdm), RSV by 4 log10. Mass spectrometry of NCT-treated SARS-CoV-2 spike protein and 3C-like protease, influenza virus hemagglutinin and neuraminidase, and RSV fusion glycoprotein disclosed multiple sites of chlorination and oxidation as the molecular mechanism of action. Application of 1.0% NCT as a prophylactic and therapeutic strategy against acute viral respiratory tract infections deserves comprehensive clinical investigation.Peer Reviewe

Prevalence of RT-qPCR-detected SARS-CoV-2 infection at schools: First results from the Austrian School-SARS-CoV-2 prospective cohort study.

BACKGROUND: The role of schools in the SARS-CoV-2 pandemic is much debated. We aimed to quantify reliably the prevalence of SARS-CoV-2 infections at schools detected with reverse-transcription quantitative polymerase-chain-reaction (RT-qPCR). METHODS: This nationwide prospective cohort study monitors a representative sample of pupils (grade 1-8) and teachers at Austrian schools throughout the school year 2020/2021. We repeatedly test participants for SARS-CoV-2 infection using a gargling solution and RT-qPCR. We herein report on the first two rounds of examinations. We used mixed-effects logistic regression to estimate odds ratios and robust 95% confidence intervals (95% CI). FINDINGS: We analysed data on 10,734 participants from 245 schools (9465 pupils, 1269 teachers). Prevalence of SARS-CoV-2 infection increased from 0·39% at round 1 (95% CI 028-0·55%, 28 September-22 October 2020) to 1·39% at round 2 (95% CI 1·04-1·85%, 10-16 November). Odds ratios for SARS-CoV-2 infection were 2·26 (95% CI 1·25-4·12, P = 0·007) in regions with >500 vs. ≤500 inhabitants/km2, 1·67 (95% CI 1·42-1·97, P<0·001) per two-fold higher regional 7-day community incidence, and 2·78 (95% CI 1·73-4·48, P<0·001) in pupils at schools with high/very high vs. low/moderate social deprivation. Associations of regional community incidence and social deprivation persisted in a multivariable adjusted model. Prevalence did not differ by average number of pupils per class nor between age groups, sexes, pupils vs. teachers, or primary (grade 1-4) vs. secondary schools (grade 5-8). INTERPRETATION: This monitoring study in Austrian schools revealed SARS-CoV-2 infection in 0·39%-1·39% of participants and identified associations of regional community incidence and social deprivation with higher prevalence. FUNDING: BMBWF Austria