First detection of porcine respirovirus 1 in Germany and the Netherlands

Porcine respirovirus 1, also referred to as porcine parainfluenza virus 1 (PPIV-1), was first detected in deceased pigs from Hong Kong in 2013. It has since then been found in the USA, Chile and most recently in Hungary. Information on the pathogenicity and global spread is sparse. However, it has been speculated to play a role in the porcine respiratory disease complex. To investigate the porcine virome, we screened 53 pig samples from 26 farms within the Dutch-German border region using shotgun metagenomics sequencing (SMg). After detecting PPIV-1 in five farms through SMg, a real-time reverse transcriptase PCR (RT-qPCR) assay was designed, which not only confirmed the presence of the virus in 1 of the 5 farms but found an additional 6 positive farms. Phylogenetic analysis found the closest match to be the first detected PPIV-1 strain in Hong Kong. The Dutch-German region represents a significant area of pig farming within Europe and could provide important information on the characterization and circulation of porcine viruses, such as PPIV-1. With its recent detection in Hungary, these findings suggest widespread circulation of PPIV-1 in Central Europe, highlighting the need for further research on persistence, pathogenicity and transmission in Europe

Assessment of Viral Targeted Sequence Capture Using Nanopore Sequencing Directly from Clinical Samples

Shotgun metagenomic sequencing (SMg) enables the simultaneous detection and characterization of viruses in human, animal and environmental samples. However, lack of sensitivity still poses a challenge and may lead to poor detection and data acquisition for detailed analysis. To improve sensitivity, we assessed a broad scope targeted sequence capture (TSC) panel (ViroCap) in both human and animal samples. Moreover, we adjusted TSC for the Oxford Nanopore MinION and compared the performance to an SMg approach. TSC on the Illumina NextSeq served as the gold standard. Overall, TSC increased the viral read count significantly in challenging human samples, with the highest genome coverage achieved using the TSC on the MinION. TSC also improved the genome coverage and sequencing depth in clinically relevant viruses in the animal samples, such as influenza A virus. However, SMg was shown to be adequate for characterizing a highly diverse animal virome. TSC on the MinION was comparable to the NextSeq and can provide a valuable alternative, offering longer reads, portability and lower initial cost. Developing new viral enrichment approaches to detect and characterize significant human and animal viruses is essential for the One Health Initiative

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Alcohol consumption and mortality in individuals with diabetes mellitus

Studies have suggested that moderate alcohol consumption is associated with a reduced risk of CVD and premature mortality in individuals with diabetes mellitus. However, history of alcohol consumption has hardly been taken into account. We investigated the association between current alcohol consumption and mortality in men and women with diabetes mellitus accounting for past alcohol consumption. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was defined of 4797 participants with a confirmed diagnosis of diabetes mellitus. Men and women were assigned to categories of baseline and past alcohol consumption. Hazard ratios (HR) and 95% CI for total mortality were estimated with multivariable Cox regression models, using light alcohol consumption (>0-6 g/d) as the reference category. Compared with light alcohol consumption, no relationship was observed between consumption of 6 g/d or more and total mortality. HR for >6.12 g/d was 0.89(95% CI 0.61, 1.30) in men and 0.86(95% CI 0.46, 1.60) in women. Adjustment for past alcohol consumption did not change the estimates substantially. In individuals who at baseline reported abstaining from alcohol, mortality rates were increased relative to light consumers: HR was 1.52 (95% CI 0.99, 2.35) in men and 1.81 (95% CI 1.04, 3.17) in women. The present study in diabetic individuals showed no association between current alcohol consumption >6 g/d and mortality risk compared with light consumption. The increased mortality risk among non-consumers appeared to be affected by their past alcohol consumption rather than their current abstinence

A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

<p>Abstract</p> <p>Background</p> <p>The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS.</p> <p>Method</p> <p>Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m²iv days 1 and 4, ifosfamide 1500 mg/m²iv days 1 - 4, doxorubicin 50 mg/m²day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA.</p> <p>Result</p> <p>Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far.</p> <p>Conclusion</p> <p>The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published data on neo-/adjuvant chemotherapy in this setting. However, the definitive role of chemotherapy remains unclear in the absence of large, randomized trials. Therefore, the current regimen can only be recommended within a clinical study, and a possibly increased risk of secondary leukemias has to be taken into account.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01382030">NCT01382030</a>, EudraCT 2004-002501-72</p

A case study of a mother's intertwining experiences with incest and postpartum depression

The association between childhood sexual abuse (CSA) and major depression disorder (MDD) gives reason to suspect that many mothers with postpartum depression (PPD) have a history of CSA. However, few studies have investigated how CSA and PPD are related. In this case study we explore how the experience of incest intertwines with the experience of postpartum depression. We focus on participant subject “Nina,” who has experienced both. We interviewed her three times and we analysed the interviews with Giorgi's phenomenological descriptive method to arrive at a contextualised meaning structure. Nina's intruding fantasies of men who abuse her children merge with her recollections of her own incest experiences. She may succeed in forcing these fantasies out of her consciousness, but they still alter her perceptions, thoughts, and emotions. She feels overwhelmed and succumbs to sadness, while she also is drawn towards information about CSA, which in turn feeds her fantasies. The psychodynamic concepts of repetition compulsion, transference, and projection may provide some explanation of Nina's actions, thoughts, and emotions through her past experiences. With our phenomenological stance, we aim to acknowledge Nina's descriptions of her everyday life here and now. With reference to Husserl, Heidegger, Merleau-Ponty, and Minkowski, we show that Nina's past is not a dated memory; rather it determines the structure of her consciousness that constitutes her past as her true present and future. Incest dominates Nina's world, and her possibilities for action are restricted by this perceived world. Any suspension of action implies anguish, and she resolves this by incest-structured action that in turn feeds and colours her expectations. Thus anxiety and depression are intertwined in the structure of this experience

Cirrhotic livers reveal genetic changes in the MDM2-P14ARF system of cell cycle regulators

The genesis of hepatocellular carcinoma is promoted by changes in the regulatory MDM2-P14ARF system. The incidence of such changes has to date not been analysed in non-tumourous livers showing regenerative proliferation. In the present study, 24 cirrhotic livers of alcohol-, autoimmue disorder- or HCV-caused genesis were screened for MDM2-P14ARF alterations at the level of protein, DNA and mRNA. Using confocal laser scanning microscopy, the absence of MDM2 and P14ARF expression was detected in all samples except three HCV-infected livers (four livers) which contained hepatocytes overexpressing MDM2 (P14ARF) protein. In two of the samples lacking P14ARF expression, laser microdissection and PCR demonstrated deletion of the P14ARF gene. The P14ARF gene amplified from other specimens did not carry mutations. MDM2 splicing variants were present in tissues from alcohol- and autoimmune disorder-induced cirrhoses. Sequencing of full-size mRNA revealed a MDM2 mis-sense mutation in an alcohol-induced cirrhosis. One sample contained regenerative nodules with genetic instability occurring at MDM2 locus D12S83 according to the data of automatic PCR fragment analysis. In summary, this study gives first evidence for different types of MDM2 and P14ARF alterations in cirrhotic livers. We suggest that the changes impair the regulatory MDM2-P14ARF system, thus possibly favouring regenerative proliferation and transformation

Scandinavian Flagship Universities: an Appraisal of Leading National Universities in the European Context

In the immediate post-Sputnik era, Clark Kerr saw America’s breed of universities as “multiversities,” characterized by growing enrollment, an increasingly diversified academic community, and as the emerging driver of knowledge production and innovation (Kerr 2001: xi). This is now a widely shared vision throughout the world. Governments have provided additional funding, fueling further growth in academic programs and attracting talent. One result: the number of perceived stakeholders has increased, along with their expectations