A geometric model of defensive peripersonal space

Potentially harmful stimuli occurring within the defensive peripersonal space (DPPS), a protective area surrounding the body, elicit stronger defensive reactions. The spatial features of the DPPS are poorly defined and limited to descriptive estimates of its extent along a single dimension. Here we postulated a family of geometric models of the DPPS, to address two important questions with respect to its spatial features: What is its fine-grained topography? How does the nervous system represent the body area to be defended? As a measure of the DPPS, we used the strength of the defensive blink reflex elicited by electrical stimulation of the hand (hand-blink reflex, HBR), which is reliably modulated by the position of the stimulated hand in egocentric coordinates. We tested the goodness of fit of the postulated models to HBR data from six experiments in which we systematically explored the HBR modulation by hand position in both head-centered and body-centered coordinates. The best-fitting model indicated that 1) the nervous system's representation of the body area defended by the HBR can be approximated by a half-ellipsoid centered on the face and 2) the DPPS extending from this area has the shape of a bubble elongated along the vertical axis. Finally, the empirical observation that the HBR is modulated by hand position in head-centered coordinates indicates that the DPPS is anchored to the face. The modeling approach described in this article can be generalized to describe the spatial modulation of any defensive response

Women's views on screening for Type 2 diabetes after gestational diabetes: a systematic review, qualitative synthesis and recommendations for increasing uptake.

AIM: Many women do not attend recommended glucose testing following a pregnancy affected by gestational diabetes (GDM). We aimed to synthesize the literature regarding the views and experiences of women with a history of GDM on postpartum glucose testing, focusing on barriers and facilitators to attendance. METHODS: We systematically identified qualitative studies that examine women's experiences following GDM relating to glucose testing (diabetes screening) or experience of interventions to promote uptake of testing. We conducted a thematic synthesis to develop descriptive and then analytical themes, then developed recommendations to increase uptake based on the findings. We evaluated the quality of each study and the confidence that we had in the recommendations using published checklists. RESULTS: We included 16 articles after screening 23 160 citations and 129 full texts. We identified four themes of influences relating to the healthcare system and personal factors that affected both ability and motivation to attend: relationship with health care, logistics of appointments and tests, family-related practicalities and concern about diabetes. We developed 10 recommendations addressing diabetes risk information and education, and changes to healthcare systems to promote increased attendance at screening in this population, most with high or moderate confidence. CONCLUSIONS: We have identified a need to improve women's understanding about Type 2 diabetes and GDM, and to adjust healthcare provision during and after pregnancy to decrease barriers and increase motivation for testing. Encouraging higher uptake by incorporating these recommendations into practice will enable earlier management of diabetes and improve long-term outcomes.R.D. is funded by a PhD studentship from the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR; SPCR-S-S102). This paper presents independent research funded by the NIHR SPCR. The views expressed are those of the author(s) and not necessarily those of the NIHR, the NHS or the Department of Health. R.W. is funded by an NIHR Academic Clinical Fellowship. S.G. is supported by the Medical Research Council (MC_UU_12015/4). S.G. is an NIHR Senior Investigator. The University of Cambridge has received salary support in respect of S.G. from the NHS in the East of England through the Clinical Academic Reserve. J.U-S. is funded by a Cancer Research UK Cancer Prevention Fellowship (C55650/A21464)

Temporal variability of Delta C-14, delta C-13, and C/N in sinking particulate organic matter at a deep time series station in the northeast Pacific Ocean

A 6-year time series of Delta(14) C, delta(13) C, and C/N measurements in deep sinking particulate organic matter ( POM) is presented for an abyssal site, Station M in the northeast Pacific Ocean. The Delta(14)C values revealed that sinking POM at 3450 m depth ( 650 m above bottom) contained old carbon despite its presumed short transit time in the water column. The isotopic and chemical properties of the sinking POM varied with time and appear to be controlled by more than one major process. In 1993, 1994, and late 1996, isotopic signatures and C/N molar ratios indicate negligible or vertically homogeneous influence of resuspended particles from the bottom or particles laterally transported from the margin to the study site. However, during early 1995 and 1998, Delta(14)C values were lower than those during other periods and C/N values at three deep depths were not equal, indicating that the study site was influenced by resuspended sediments more severely than during other periods. During mid-1995 to mid-1996, delta(13)C values decreased abruptly while Delta(14)C values increased slightly, and C/N values were extremely high ( up to -80) at 50 and 600 m above bottom; these results suggest input of degraded, modern, terrestrial organic matter. The periods of anomalous isotopic signatures, as well as vertically heterogeneous C/N values [ Smith et al., 2001], were correlated with high discharge periods of California rivers with a time lag of 2 to 4 months. The correlation suggests that regional meteorological events are important in controlling the biogeochemical properties of particles at Station M by varying the intensity of resuspension and transport of organic matter from the continental margin

Real-time monitoring of specific oxygen uptake rates of embryonic stem cells in a microfluidic cell culture device

Oxygen plays a key role in stem cell biology as a signaling molecule and as an indicator of cell energy metabolism. Quantification of cellular oxygen kinetics, i.e. the determination of specific oxygen uptake rates (sOURs), is routinely used to understand metabolic shifts. However current methods to determine sOUR in adherent cell cultures rely on cell sampling, which impacts on cellular phenotype. We present real-time monitoring of cell growth from phase contrast microscopy images, and of respiration using optical sensors for dissolved oxygen. Time-course data for bulk and peri-cellular oxygen concentrations obtained for Chinese hamster ovary (CHO) and mouse embryonic stem cell (mESCs) cultures successfully demonstrated this non-invasive and label-free approach. Additionally, we confirmed non-invasive detection of cellular responses to rapidly changing culture conditions by exposing the cells to mitochondrial inhibiting and uncoupling agents. For the CHO and mESCs, sOUR values between 8 and 60 amol cell(-1) s(-1) , and 5 and 35 amol cell(-1) s(-1) were obtained, respectively. These values compare favorably with literature data. The capability to monitor oxygen tensions, cell growth, and sOUR, of adherent stem cell cultures, non-invasively and in real time, will be of significant benefit for future studies in stem cell biology and stem cell-based therapies

Bifunctional CD4-DC-SIGN fusion proteins demonstrate enhanced avidity to gp120 and inhibit HIV-1 infection and dissemination.

Early stages of mucosal infection are potential targets for HIV-1 prevention. CD4 is the primary receptor in HIV-1 infection whereas DC-SIGN likely plays an important role in HIV-1 dissemination, particularly during sexual transmission. To test the hypothesis that an inhibitor simultaneously targeting both CD4 and DC-SIGN binding sites on gp120 may provide a potent anti-HIV strategy, we designed constructs by fusing the extracellular CD4 and DC-SIGN domains together with varied arrangements of the lengths of CD4, DC-SIGN and the linker. We expressed, purified and characterized a series of soluble CD4-linker–DC-SIGN (CLD) fusion proteins. Several CLDs, composed of a longer linker and an extra neck domain of DC-SIGN, had enhanced affinity for gp120 as evidenced by molecular-interaction analysis. Furthermore, such CLDs exhibited significantly enhanced neutralization activity against both laboratory-adapted and primary HIV-1 isolates. Moreover, CLDs efficiently inhibited HIV-1 infection in trans via a DC-SIGN-expressing cell line and primary human dendritic cells. This was further strengthened by the results from the human cervical explant model, showing that CLDs potently prevented both localized and disseminated infections. This is the first time that soluble DC-SIGN-based bifunctional proteins have demonstrated anti-HIV potency. Our study provides proof of the concept that targeting both CD4 and DC-SIGN binding sites on gp120 represents a novel antiviral strategy. Given that DC-SIGN binding to gp120 increases exposure of the CD4 binding site and that the soluble forms of CD4 and DC-SIGN occur in vivo, further improvement of CLDs may render them potentially useful in prophylaxis or therapeutics

Transglutaminase 2 limits the extravasation and the resultant myocardial fibrosis associated with factor XIII-A deficiency

Background and aims Transglutaminase (TG) 2 and Factor (F) XIII-A have both been implicated in cardiovascular protection and repair. This study was designed to differentiate between two competing hypotheses: that TG2 and FXIII-A mediate these functions in mice by fulfilling separate roles, or that they act redundantly in this respect. Methods Atherosclerosis was assessed in brachiocephalic artery plaques of fat-fed mixed strain apolipoprotein (Apo)e deficient mice that lacked either or both transglutaminases. Cardiac fibrosis was assessed both in the mixed strain mice and also in C57BL/6J Apoe expressing mice lacking either or both transglutaminases. Results No difference was found in the density of buried fibrous caps within brachiocephalic plaques from mice expressing or lacking these transglutaminases. Cardiac fibrosis developed in both Apoe/F13a1 double knockout and F13a1 single knockout mice, but not in Tgm2 knockout mice. However, concomitant Tgm2 knockout markedly increased fibrosis, as apparent in both Apoe/Tgm2/F13a1 knockout and Tgm2/F13a1 knockout mice. Amongst F13a1 knockout and Tgm2/F13a1 knockout mice, the extent of fibrosis correlated with hemosiderin deposition, suggesting that TG2 limits the extravasation of blood in the myocardium, which in turn reduces the pro-fibrotic stimulus. The resulting fibrosis was interstitial in nature and caused only minor changes in cardiac function. Conclusions These studies confirm that FXIII-A and TG2 fulfil different roles in the mouse myocardium. FXIII-A protects against vascular leakage while TG2 contributes to the stability or repair of the vasculature. The protective function of TG2 must be considered when designing clinical anti-fibrotic therapies based upon FXIII-A or TG2 inhibition

Pit and fissure sealants in dental public health – application criteria and general policy in Finland

<p>Abstract</p> <p>Background</p> <p>Pit and fissure sealants (sealants) are widely used as a non-operative preventive method in public dental health in Finland. Most children under 19 years of age attend the community-organized dental health services free of charge. The aims of this study were to find out to what extent sealants were applied, what the attitudes of dental professionals towards sealant application were, and whether any existing sealant policies could be detected among the health centres or among the respondents in general. The study evaluated changes that had taken place in the policies used during a ten year period (1991–2001).</p> <p>Methods</p> <p>A questionnaire was mailed to each chief dental officer (CDO) of the 265 public dental health centres in Finland, and to a group of general dentists (GDP) applying sealants in these health centres, giving a total of 434 questionnaires with 22 questions. The response rate was 80% (N = 342).</p> <p>Results</p> <p>A majority of the respondents reported to application of sealants on a systematic basis for children with increased caries risk. The criteria for applying sealants and the actual strategies seemed to vary locally between the dentists within the health centres and between the health centres nationwide. The majority of respondents believed sealants had short- and long-term effects. The overall use of sealants decreased towards the end of the ten year period. The health centres (N = 28) choosing criteria to seal over detected or suspected enamel caries lesion had a DMFT value of 1.0 (SD ± 0.49) at age 12 (year 2000) compared to a value of 1.2 (SD ± 0.47) for those health centres (N = 177) applying sealants by alternative criteria (t-test, p < 0.05).</p> <p>Conclusion</p> <p>There seems to be a need for defined guidelines for sealant application criteria and policy both locally and nationwide. Occlusal caries management may be improved by shifting the sealant policy from the traditional approach of prevention to interception, i.e. applying the sealants over detected or suspected enamel caries lesions instead of sealing sound teeth.</p

Automated and online characterization of adherent cell culture growth in a microfabricated bioreactor.

Adherent cell lines are widely used across all fields of biology, including drug discovery, toxicity studies, and regenerative medicine. However, adherent cell processes are often limited by a lack of advances in cell culture systems. While suspension culture processes benefit from decades of development of instrumented bioreactors, adherent cultures are typically performed in static, noninstrumented flasks and well-plates. We previously described a microfabricated bioreactor that enables a high degree of control on the microenvironment of the cells while remaining compatible with standard cell culture protocols. In this report, we describe its integration with automated image-processing capabilities, allowing the continuous monitoring of key cell culture characteristics. A machine learning-based algorithm enabled the specific detection of one cell type within a co-culture setting, such as human embryonic stem cells against the background of fibroblast cells. In addition, the algorithm did not confuse image artifacts resulting from microfabrication, such as scratches on surfaces, or dust particles, with cellular features. We demonstrate how the automation of flow control, environmental control, and image acquisition can be employed to image the whole culture area and obtain time-course data of mouse embryonic stem cell cultures, for example, for confluency

Patient information leaflets (PILs) for UK randomised controlled trials : a feasibility study exploring whether they contain information to support decision making about trial participation

Peer reviewedPublisher PD