Draft Genome Sequences of Two Avian Pathogenic<i> Escherichia coli </i>Strains of Clinical Importance, E44 and E51

Avian pathogenic Escherichia coli strains have remarkable impacts on animal welfare and the production economy in the poultry industry worldwide. Here, we present the draft genomes of two isolates from chickens (E44 and E51) obtained from field outbreaks and subsequently investigated for their potential for use in autogenous vaccines for broiler breeders

Does size really matter? A multisite study assessing the latent structure of the proposed ICD-11 and DSM-5 diagnostic criteria for PTSD

Background: Researchers and clinicians within the field of trauma have to choose between different diagnostic descriptions of posttraumatic stress disorder (PTSD) in the DSM-5 and the proposed ICD-11. Several studies support different competing models of the PTSD structure according to both diagnostic systems; however, findings show that the choice of diagnostic systems can affect the estimated prevalence rates. Objectives: The present study aimed to investigate the potential impact of using a large (i.e. the DSM-5) compared to a small (i.e. the ICD-11) diagnostic description of PTSD. In other words, does the size of PTSD really matter? Methods: The aim was investigated by examining differences in diagnostic rates between the two diagnostic systems and independently examining the model fit of the competing DSM-5 and ICD-11 models of PTSD across three trauma samples: university students (N = 4213), chronic pain patients (N = 573), and military personnel (N = 118). Results: Diagnostic rates of PTSD were significantly lower according to the proposed ICD-11 criteria in the university sample, but no significant differences were found for chronic pain patients and military personnel. The proposed ICD-11 three-factor model provided the best fit of the tested ICD-11 models across all samples, whereas the DSM-5 seven-factor Hybrid model provided the best fit in the university and pain samples, and the DSM-5 six-factor Anhedonia model provided the best fit in the military sample of the tested DSM-5 models. Conclusions: The advantages and disadvantages of using a broad or narrow set of symptoms for PTSD can be debated, however, this study demonstrated that choice of diagnostic system may influence the estimated PTSD rates both qualitatively and quantitatively. In the current described diagnostic criteria only the ICD-11 model can reflect the configuration of symptoms satisfactorily. Thus, size does matter when assessing PTSD

Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors

With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high HLA-A2-binding affinity of this peptide was verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific manner, demonstrating presentation of the peptide on the surface of cancer cells. Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-γ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently detected in both cancer patients and healthy donors. In conclusion, a high-affinity cyclin B1-derived HLA-A2-restricted CTL epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses in cancer patients and healthy donors

Investigation of itch in Parkinson disease

Introduction: Sensory abnormalities (eg, pain) are common in Parkinson disease (PD) with a negative impact on quality of life. As itch is less studied in PD, and pain and itch partially share sensory pathways, we designed this study to identify the occurrence and pattern of spontaneous itch, and responsiveness to a surrogate itch model in PD. Methods: The study protocol was approved (N-20180079) and PD patients and their best matched controls were recruited. A questionnaire was used to collect general information on itch. Sensory alterations were determined by subjective ratings and mechanical sensitivity threshold before and after a standard histamine-dependent itch model on forearms. Itch and pain intensities were rated on visual and numerical rating scales, respectively. Dispersion of itch was drawn on arm charts. Presence and area of alloknesis and hyperknesis were determined. Group comparisons were performed in SPSS with a significant level of 0.05. Descriptive statistic was used for questionnaire’s analysis. Results:Patients(n=20;68.10±7.91y,F/Mratio:8/12)andcontrols(n=20;67.35±7.65y,F/Mratio:8/12)wereexamined.PD patients rated less physical and emotional descriptors, except for the stinging (P = 0.028). No difference was found between the groups in histamine-provoked itch intensity (P = 0.799) or the itchy area. A significantly larger area of hyperknesis was found in PD (P = 0.011), but not for the area of alloknesis (P = 0.221). Sex-related responses yielded only a tendency toward higher responses in female patients. Discussion:PDdoesnotseemtoinfluenceperceptionofitch,neitherspontaneousnorevokeditch,exceptforhyperknesisarea,which was found significantly larger in PD patients following the application of histamine. This finding proposes a potential alteration in central processing of itch that needs further investigation and whether and how it is affected by, for example, PD pathogenesis

Vitamin D Status and Seasonal Variation among Danish Children and Adults: A Descriptive Study

The aim of the present study was to describe vitamin D status and seasonal variation in the general Danish population. In this study, 3092 persons aged 2 to 69 years (2565 adults, 527 children) had blood drawn twice (spring and autumn) between 2012 and 2014. A sub-sample of participants had blood samples taken monthly over a year. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by liquid chromatography mass spectrometry, and information on supplement use was assessed from questionnaires. Seasonal variations in 25(OH)D concentrations were evaluated graphically and descriptively, and status according to age, sex, and supplement use was described. It was found that 86% of both adults and children were vitamin D-sufficient in either spring and or/autumn; however, many had a spring concentration below 50 nmol/L. A wide range of 25(OH)D concentrations were found in spring and autumn, with very low and very high values in both seasons. Among adults, women in general had higher median 25(OH)D concentrations than men. Furthermore, vitamin D supplement use was substantial and affected the median concentrations markedly, more so during spring than autumn. Seasonal variation was thus found to be substantial, and bi-seasonal measurements are vital in order to capture the sizable fluctuations in vitamin D status in this Nordic population

Qualitative description – the poor cousin of health research?

<p>Abstract</p> <p>Background</p> <p>The knowledge and use of qualitative description as a qualitative research approach in health services research is limited.</p> <p>The aim of this article is to discuss the potential benefits of a qualitative descriptive approach, to identify its strengths and weaknesses and to provide examples of use.</p> <p>Discussion</p> <p>Qualitative description is a useful qualitative method in much medical research if you keep the limitations of the approach in mind. It is especially relevant in mixed method research, in questionnaire development and in research projects aiming to gain firsthand knowledge of patients', relatives' or professionals' experiences with a particular topic. Another great advantage of the method is that it is suitable if time or resources are limited.</p> <p>Summary</p> <p>As a consequence of the growth in qualitative research in the health sciences, researchers sometimes feel obliged to designate their work as phenomenology, grounded theory, ethnography or a narrative study when in fact it is not. Qualitative description might be a useful alternative approach to consider.</p

Regulation of Sodium Channel Function by Bilayer Elasticity: The Importance of Hydrophobic Coupling. Effects of Micelle-forming Amphiphiles and Cholesterol

Membrane proteins are regulated by the lipid bilayer composition. Specific lipid–protein interactions rarely are involved, which suggests that the regulation is due to changes in some general bilayer property (or properties). The hydrophobic coupling between a membrane-spanning protein and the surrounding bilayer means that protein conformational changes may be associated with a reversible, local bilayer deformation. Lipid bilayers are elastic bodies, and the energetic cost of the bilayer deformation contributes to the total energetic cost of the protein conformational change. The energetics and kinetics of the protein conformational changes therefore will be regulated by the bilayer elasticity, which is determined by the lipid composition. This hydrophobic coupling mechanism has been studied extensively in gramicidin channels, where the channel–bilayer hydrophobic interactions link a “conformational” change (the monomer↔dimer transition) to an elastic bilayer deformation. Gramicidin channels thus are regulated by the lipid bilayer elastic properties (thickness, monolayer equilibrium curvature, and compression and bending moduli). To investigate whether this hydrophobic coupling mechanism could be a general mechanism regulating membrane protein function, we examined whether voltage-dependent skeletal-muscle sodium channels, expressed in HEK293 cells, are regulated by bilayer elasticity, as monitored using gramicidin A (gA) channels. Nonphysiological amphiphiles (β-octyl-glucoside, Genapol X-100, Triton X-100, and reduced Triton X-100) that make lipid bilayers less “stiff”, as measured using gA channels, shift the voltage dependence of sodium channel inactivation toward more hyperpolarized potentials. At low amphiphile concentration, the magnitude of the shift is linearly correlated to the change in gA channel lifetime. Cholesterol-depletion, which also reduces bilayer stiffness, causes a similar shift in sodium channel inactivation. These results provide strong support for the notion that bilayer–protein hydrophobic coupling allows the bilayer elastic properties to regulate membrane protein function

BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM