Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

CIS-based registration of quality of life in a single source approach

Background: Documenting quality of life (QoL) in routine medical care and using it both for treatment and for clinical research is not common, although such information is absolutely valuable for physicians and patients alike. We therefore aimed at developing an efficient method to integrate quality of life information into the clinical information system (CIS) and thus make it available for clinical care and secondary use. Methods: We piloted our method in three different medical departments, using five different QoL questionnaires. In this setting we used structured interviews and onsite observations to perform workflow and form analyses. The forms and pertinent data reports were implemented using the integrated tools of the local CIS. A web-based application for mobile devices was developed based on XML schemata to facilitate data import into the CIS. Data exports of the CIS were analysed with statistical software to perform an analysis of data quality. Results: The quality of life questionnaires are now regularly documented by patients and physicians. The resulting data is available in the Electronic Health Record (EHR) and can be used for treatment purposes and communication as well as research functionalities. The completion of questionnaires by the patients themselves using a mobile device (iPad) and the import of the respective data into the CIS forms were successfully tested in a pilot installation. The quality of data is rendered high by the use of automatic score calculations as well as the automatic creation of forms for follow-up documentation. The QoL data was exported to research databases for use in scientific analysis. Conclusion: The CIS-based QoL is technically feasible, clinically accepted and provides an excellent quality of data for medical treatment and clinical research. Our approach with a commercial CIS and the web-based application is transferable to other sites

What is going on around here? Intolerance of uncertainty predicts threat generalization

Attending to stimuli that share perceptual similarity to learned threats is an adaptive strategy. However, prolonged threat generalization to cues signalling safety is considered a core feature of pathological anxiety. One potential factor that may sustain over-generalization is sensitivity to future threat uncertainty. To assess the extent to which Intolerance of Uncertainty (IU) predicts threat generalization, we recorded skin conductance in 54 healthy participants during an associative learning paradigm, where threat and safety cues varied in perceptual similarity. Lower IU was associated with stronger discrimination between threat and safety cues during acquisition and extinction. Higher IU, however, was associated with generalized responding to threat and safety cues during acquisition, and delayed discrimination between threat and safety cues during extinction. These results were specific to IU, over and above other measures of anxious disposition. These findings highlight: (1) a critical role of uncertainty-based mechanisms in threat generalization, and (2) IU as a potential risk factor for anxiety disorder development

Ablation of Dicer from murine Schwann cells increases their proliferation while blocking myelination

The myelin sheaths that surround the thick axons of the peripheral nervous system are produced by the highly specialized Schwann cells. Differentiation of Schwann cells and myelination occur in discrete steps. Each of these requires coordinated expression of specific proteins in a precise sequence, yet the regulatory mechanisms controlling protein expression during these events are incompletely understood. Here we report that Schwann cell-specific ablation of the enzyme Dicer1, which is required for the production of small non-coding regulatory microRNAs, fully arrests Schwann cell differentiation, resulting in early postnatal lethality. Dicer(-/-) Schwann cells had lost their ability to myelinate, yet were still capable of sorting axons. Both cell death and, paradoxically, proliferation of immature Schwann cells was markedly enhanced, suggesting that their terminal differentiation is triggered by growth-arresting regulatory microRNAs. Using microRNA microarrays, we identified 16 microRNAs that are upregulated upon myelination and whose expression is controlled by Dicer in Schwann cells. This set of microRNAs appears to drive Schwann cell differentiation and myelination of peripheral nerves, thereby fulfilling a crucial function for survival of the organism

Piloting the use of accelerometry devices to capture energy expenditure in agricultural and rural livelihoods: Protocols and findings from northern Ghana

In this study we report on the protocols adopted and the findings from a pilot study in northern Ghana involving 40 respondents wearing accelerometry devices for a week. We show how integrating energy expenditure data from wearable accelerometry devices with data on activity and time-use can provide a window into agricultural and rural livelihoods in developing country contexts that has not been previously available for empirical research. Our findings confirm some of the stylised facts of agricultural and rural livelihoods, but the study also provides several new insights that come from the triangulation of energy expenditure, time use, and activity data. We report findings and explore the potential applications of using accelerometry devices for a better understanding of agriculture-nutrition linkages in developing countries

How do informal information sources influence women’s decision-making for birth? A meta-synthesis of qualitative studies

Background: Women approach birth using various methods of preparation drawing from conventional healthcare providers alongside informal information sources (IIS) outside the professional healthcare context. An investigation of the forms in which these informal information sources are accessed and negotiated by women, and how these disconnected and often conflicting elements influence women’s decision-making process for birth have yet to be evaluated. The level of antenatal preparedness women feel can have significant and long lasting implications on their birth experience and transition into motherhood and beyond. The aim of this study was to provide a deeper understanding of how informal information sources influence women’s preparation for birth. Methods: Seven electronic databases were searched with predetermined search terms. No limitations were imposed for year of publication. English language studies using qualitative methods exploring women’s experiences of informal information sources and their impact upon women’s birth preparation were included, subject to a quality appraisal framework. Searches were initiated in February 2016 and completed by March 2016. Studies were synthesised using an interpretive meta-ethnographic approach. Results: Fourteen studies were included for the final synthesis from Great Britain, Australia, Canada and the United States. Four main themes were identified: Menu Birth; Information Heaven/Hell; Spheres of Support; and Trust. It is evident that women do not enter pregnancy as empty vessels devoid of a conceptual framework, but rather have a pre-constructed embodied knowledge base upon which other information is superimposed. Allied to this, it is clear that informal information was sought to mitigate against the widespread experience of discordant information provided by maternity professionals. Conclusion: Women’s access to the deluge of informal information sources in mainstream media during pregnancy have significant impact on decision making for birth. These informal sources redefine the power dynamic between women and maternal healthcare providers, simultaneously increasing levels of anxiety and challenging women’s pre- existing ideations and aspirations of personal birth processes. A lack of awareness by some professionals of women’s information seeking behaviours generates barriers to women-centred support, leaving an experience expectation mismatch unchecked

SDF1 in the dorsal corticospinal tract promotes CXCR4+ cell migration after spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Stromal cell-derived factor-1 (SDF1) and its major signaling receptor, CXCR4, were initially described in the immune system; however, they are also expressed in the nervous system, including the spinal cord. After spinal cord injury, the blood brain barrier is compromised, opening the way for chemokine signaling between these two systems. These experiments clarified prior contradictory findings on normal expression of SDF1 and CXCR4 as well as examined the resulting spinal cord responses resulting from this signaling.</p> <p>Methods</p> <p>These experiments examined the expression and function of SDF1 and CXCR4 in the normal and injured adult mouse spinal cord primarily using CXCR4-EGFP and SDF1-EGFP transgenic reporter mice.</p> <p>Results</p> <p>In the uninjured spinal cord, SDF1 was expressed in the dorsal corticospinal tract (dCST) as well as the meninges, whereas CXCR4 was found only in ependymal cells surrounding the central canal. After spinal cord injury (SCI), the pattern of SDF1 expression did not change rostral to the lesion but it disappeared from the degenerating dCST caudally. By contrast, CXCR4 expression changed dramatically after SCI. In addition to the CXCR4+ cells in the ependymal layer, numerous CXCR4+ cells appeared in the peripheral white matter and in the dorsal white matter localized between the dorsal corticospinal tract and the gray matter rostral to the lesion site. The non-ependymal CXCR4+ cells were found to be NG2+ and CD11b+ macrophages that presumably infiltrated through the broken blood-brain barrier. One population of macrophages appeared to be migrating towards the dCST that contains SDF1 rostral to the injury but not towards the caudal dCST in which SDF1 is no longer present. A second population of the CXCR4+ macrophages was present near the SDF1-expressing meningeal cells.</p> <p>Conclusions</p> <p>These observations suggest that attraction of CXCR4+ macrophages is part of a programmed response to injury and that modulation of the SDF1 signaling system may be important for regulating the inflammatory response after SCI.</p

Prevalence of apical periodontitis and endodontic treatment in a Kosovar adult population

<p>Abstract</p> <p>Background</p> <p>Despite numerous studies on the prevalence of apical periodontitis (AP) and endodontic treatment in diverse geographical populations, there are currently no data on the prevalence of these conditions in populations of adults native to Kosovo. Therefore, little is known about how widespread these conditions are, and whether there is any correlation between root canal treatment and AP. The purpose of our research was to address this anomaly by investigating AP and endodontic treatment in an adult Kosovar population based on radiographic examination.</p> <p>Methods</p> <p>The sample used for this study consisted of randomly selected individuals referred to the University Dentistry Clinical Center of Kosovo in the years 2006-2007. Orthopantomographs of 193 patients were evaluated. The periapical status of all teeth (with the exception of third molars) was examined according to Ørstavik's Periapical Index. The quality of the root canal filling was rated as 'adequate' or 'inadequate' based on whether all canals were filled, the depth of fill relative to the radiographic apex and the quality of compaction (absence/presence of voids). Data were analyzed statistically using the Chi-square test and calculation of odds ratios.</p> <p>Results</p> <p>Out of 4131 examined teeth, the prevalence of apical periodontitis (AP) and endodontic treatment was 12.3% and 2.3%, respectively. Of 95 endodontically-treated teeth, 46.3% were associated with AP. The prevalence of AP increased with age. The prevalence in subjects aged over 60 years old (20.2%) was higher than in other age groups. A statistically significant difference was found for the frequency of endodontically-treated teeth associated with AP in the 40-49 year age group (P < 0.001). Of some concern was the discovery that only 30.5% of the endodontically-treated teeth examined met the criteria of an acceptable root canal filling. Inadequately root-filled teeth were associated with an increased AP risk.</p> <p>Conclusions</p> <p>The prevalence of AP and the frequency of endodontically-treated teeth with AP in this Kosovar population are higher than those found in other countries. Inadequate root canal fillings were associated with an increased prevalence of AP.</p