Adaption of pregnancy anxiety questionnaire–revised for all pregnant women regardless of parity: PRAQ-R2

The 10-item Pregnancy-Related Anxiety Questionnaire–Revised (PRAQ-R) is a widely used instrument to assess and identify pregnancy-specific anxiety in nulliparous women. It has good psychometric values and predictive validity for birth and childhood outcomes. Nonetheless, the PRAQ-R is not designed for use in parous women, as particularly one item of the questionnaire is not relevant for women who gave birth before. We tested the factorial and scalar invariance of a modified PRAQ-R2 across nulliparous and parous women with an adapted item to fit both groups of pregnant women. A longitudinal study among 1144 pregnant women (n?=?608 nulliparous and n?=?536 parous) with two repeated measures of the PRAQ-R2 was used to test for measurement invariance of the instrument. Results show metric and scalar invariance, indicating that the PRAQ-R2 measures similar constructs on the same scale for all pregnant women at two different times during pregnancy. We conclude that the PRAQ-R2 can be used, compared, or combined in a sample of nulliparous and parous women.     

GREM1 and POLE variants in hereditary colorectal cancer syndromes

Hereditary factors are thought to play a role in at least one third of patients with colorectal cancer (CRC) but only a limited proportion of these have mutations in known high‐penetrant genes. In a relatively large part of patients with a few or multiple colorectal polyps the underlying genetic cause of the disease is still unknown. Using exome sequencing in combination with linkage analyses together with detection of copy‐number variations (CNV), we have identified a duplication in the regulatory region of the GREM1 gene in a family with an attenuated/atypical polyposis syndrome. In addition, 107 patients with colorectal cancer and/or polyposis were analyzed for mutations in the candidate genes identified. We also performed screening of the exonuclease domain of the POLE gene in a subset of these patients. The duplication of 16 kb in the regulatory region of GREM1 was found to be disease‐causing in the family. Functional analyses revealed a higher expression of the GREM1 gene in colorectal tissue in duplication carriers. Screening of the exonuclease domain of POLE in additional CRC patients identified a probable causative novel variant c.1274A>G, p.Lys425Arg. In conclusion a high penetrant duplication in the regulatory region of GREM1, predisposing to CRC, was identified in a family with attenuated/atypical polyposis. A POLE variant was identified in a patient with early onset CRC and a microsatellite stable (MSS) tumor. Mutations leading to increased expression of genes can constitute disease‐causing mutations in hereditary CRC syndromes. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.     

High Graft-versus-Host Disease-Free,Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged ≥40 years had a higher transplant-related mortality (29.4% versus 7.8%; P = .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (P = .022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged ≥40 years is problematic, and clinical trials addressing this issue are warranted.     

Identification of two abundant Aerococcus urinae cell wall-anchored proteins

Aerococcus urinae is an emerging pathogen that causes urinary tract infections, bacteremia and infective endocarditis. The mechanisms through which A. urinae cause infection are largely unknown. The aims of this study were to describe the surface proteome of A. urinae and to analyse A. urinae genomes in search for genes encoding surface proteins. Two proteins, denoted Aerococcal surface protein (Asp) 1 and 2, were through the use of mass spectrometry based proteomics found to quantitatively dominate the aerococcal surface. The presence of these proteins on the surface was also shown using ELISA with serum from rabbits immunized with the recombinant Asp. These proteins had a signal sequence in the amino-terminal end and a cell wall-sorting region in the carboxy-terminal end, which contained an LPATG-motif, a hydrophobic domain and a positively charged tail. Twenty-three additional A. urinae genomes were sequenced using Illumina HiSeq technology. Six different variants of asp genes were found (denoted asp1-6). All isolates had either one or two of these asp-genes located in a conserved locus, designated Locus encoding Aerococcal Surface Proteins (LASP). The 25 genomes had in median 13 genes encoding LPXTG-proteins (range 6–24). For other Gram-positive bacteria, cell wall-anchored surface proteins with an LPXTG-motif play a key role for virulence. Thus, it will be of great interest to explore the function of the Asp proteins of A. urinae to establish a better understanding of the molecular mechanisms by which A. urinae cause disease.     

Copy number variation and neuropsychiatric problems in females and males in the general population

Neurodevelopmental problems (NPs) are more common in males, whereas anxiety and depression are more common in females. Rare copy number variants (CNVs) have been implicated in neurodevelopmental disorders. The aim of this study was to characterize the relationship between rare CNVs with NPs, anxiety, and depression in a childhood population sample, as well as to examine sex‐specific effects. We analyzed a sample of N = 12,982 children, of whom 5.3% had narrowly defined NPs (clinically diagnosed), 20.9% had broadly defined NPs (based on validated screening measures, but no diagnosis), and 3.0% had clinically diagnosed anxiety or depression. Rare (<1% frequency) CNVs were categorized by size (100–500 kb or > 500 kb), type, and putative relevance to NPs. We tested for association of CNV categories with outcomes and examined sex‐specific effects. Medium deletions (OR[CI] = 1.18[1.05–1.33], p = .0053) and large duplications (OR[CI] = 1.45[1.19–1.75], p = .00017) were associated with broadly defined NPs. Large deletions (OR[CI] = 1.85[1.14–3.01], p = .013) were associated with narrowly defined NPs. There were no significant sex differences in CNV burden in individuals with NPs. Although CNVs were not associated with anxiety/depression in the whole sample, in individuals diagnosed with these disorders, females were more likely to have large CNVs (OR[CI] = 3.75[1.45–9.68], p = .0064). Rare CNVs are associated with both narrowly and broadly defined NPs in a general population sample of children. Our results also suggest that large, rare CNVs may show sex‐specific phenotypic effects.     

Income change after cruciate ligament injury — A population-based study

ObjectivesTo investigate the association between choice of treatment and patients' income after cruciate ligament (CL) injury and assess the effect of different covariates such as sex, age, comorbidities and type of work.MethodsThis entire-population cohort study in Sweden included working patients with a diagnosed CL injury between 2002 and 2005, identified in The National Swedish Patient Register (n = 13,662). The exposure was the treatment choice (operative or non-operative treatment). The main outcome measure was average yearly income five years after CL diagnosis, adjusted for the following covariates: sex, age, comorbidities, type of work, region, calendar year, education and income.ResultsRelative to non-operative treatment, operative treatment was associated with greater average yearly incomes (nine to 15%) after injury among patients between 20 and 50 years, patients with partial university education, patients living in large cities and patients with one comorbidity, despite no overall significant association in the national cohort. Delayed operative treatment (> 1 year) had no significant association with income change, whereas early operative treatment (< 1 year) was associated with higher average yearly incomes (11 to 16%) among females, patients between 20 and 50 years, patients living in large cities and patients with one comorbidity.ConclusionsIn a broad sense, treatment choice was not associated with changes in income five years after CL injuries among patients in the workforce, however earlier operative treatment was associated with higher average incomes among patients with ages between 20 and 50, females, living in large cities, with one comorbidity and with a high level of education.     

Inventory of molecular markers affecting biological characteristics of avian influenza A viruses

Virus Genes - Avian influenza viruses (AIVs) circulate globally, spilling over into domestic poultry and causing zoonotic infections in humans. Fortunately, AIVs are not yet capable of causing...     

Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses

Natural killer T (NKT) cells recognize glycolipids presented on CD1d. They share features of adaptive T lymphocytes and innate NK cells, and mediate immunoregulatory functions via rapid production of cytokines. Invariant (iNKT) and diverse (dNKT) NKT cell subsets are defined by their TCR. The immunological role of dNKT cells, that do not express the invariant TCRα‐chain used by iNKT cells, is less well explored than that of iNKT cells. Here, we investigated signals driving Toll‐like receptor (TLR) ligand activation of TCR‐transgenic murine dNKT cells. IFN‐γ production by dNKT cells required dendritic cells (DC), cell‐to‐cell contact and presence of TLR ligands. TLR‐stimulated DC activated dNKT cells to secrete IFN‐γ in a CD1d‐, CD80/86‐ and type I IFN‐independent manner. In contrast, a requirement for IL‐12p40, and a TLR ligand‐selective dependence on IL‐18 or IL‐15 was observed. TLR ligand/DC stimulation provoked early secretion of pro‐inflammatory cytokines by both CD62L⁺ and CD62L^? dNKT cells. However, proliferation was limited. In contrast, TCR/co‐receptor‐mediated activation resulted in proliferation and delayed production of a broader cytokine spectrum preferentially in CD62L^? dNKT cells. Thus, innate (TLR ligand/DC) and adaptive (TCR/co‐receptor) stimulation of dNKT cells resulted in distinct cellular responses that may contribute differently to the formation of immune memory.