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

Effectiveness, cost-effectiveness and cost-benefit of a single annual professional intervention for the prevention of childhood dental caries in a remote rural Indigenous community

Background The aim of the study is to reduce the high prevalence of tooth decay in children in a remote, rural Indigenous community in Australia, by application of a single annual dental preventive intervention. The study seeks to (1) assess the effectiveness of an annual oral health preventive intervention in slowing the incidence of dental caries in children in this community, (2) identify the mediating role of known risk factors for dental caries and (3) assess the cost-effectiveness and cost-benefit of the intervention. Methods/design The intervention is novel in that most dental preventive interventions require regular re-application, which is not possible in resource constrained communities. While tooth decay is preventable, self-care and healthy habits are lacking in these communities, placing more emphasis on health services to deliver an effective dental preventive intervention. Importantly, the study will assess cost-benefit and cost-effectiveness for broader implementation across similar communities in Australia and internationally. Discussion There is an urgent need to reduce the burden of dental decay in these communities, by implementing effective, cost-effective, feasible and sustainable dental prevention programs. Expected outcomes of this study include improved oral and general health of children within the community; an understanding of the costs associated with the intervention provided, and its comparison with the costs of allowing new lesions to develop, with associated treatment costs. Findings should be generalisable to similar communities around the world. The research is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12615000693527; date of registration: 3rd July 2015

Lower trunk motion and speed-dependence during walking

Abstract Background There is a limited understanding about how gait speed influences the control of upper body motion during walking. Therefore, the primary purpose of this study was to examine how gait speed influences healthy individual's lower trunk motion during overground walking. The secondary purpose was to assess if Principal Component Analysis (PCA) can be used to gain further insight into postural responses that occur at different walking speeds. Methods Thirteen healthy subjects (23 ± 3 years) performed 5 straight-line walking trials at self selected slow, preferred, and fast walking speeds. Accelerations of the lower trunk were measured in the anterior-posterior (AP), vertical (VT), and mediolateral (ML) directions using a triaxial accelerometer. Stride-to-stride acceleration amplitude, regularity and repeatability were examined with RMS acceleration, Approximate Entropy and Coefficient of Multiple determination respectively. Coupling between acceleration directions were calculated using Cross Approximate Entropy. PCA was used to reveal the dimensionality of trunk accelerations during walking at slow and preferred speeds, and preferred and fast speeds. Results RMS acceleration amplitude increased with gait speed in all directions. ML and VT trunk accelerations had less signal regularity and repeatability during the slow compared to preferred speed. However, stride-to-stride acceleration regularity and repeatability did not differ between the preferred and fast walking speed conditions, partly due to an increase in coupling between frontal plane accelerations. The percentage of variance accounted for by each trunk acceleration Principal Component (PC) did not differ between grouped slow and preferred, and preferred and fast walking speed acceleration data. Conclusion The main finding of this study was that walking at speeds slower than preferred primarily alters lower trunk accelerations in the frontal plane. Despite greater amplitudes of trunk acceleration at fast speeds, the lack of regularity and repeatability differences between preferred and fast speeds suggest that features of trunk motion are preserved between the same conditions. While PCA indicated that features of trunk motion are preserved between slow and preferred, and preferred and fast speeds, the discriminatory ability of PCA to detect speed-dependent differences in walking patterns is limited compared to measures of signal regularity, repeatability, and coupling.</p

Nurse practitioner interactions in acute and long-term care : an exploration of the role of knotworking in supporting interprofessional collaboration

BACKGROUND: Interprofessional care ensures high quality healthcare. Effective interprofessional collaboration is required to enable interprofessional care, although within the acute care hospital setting interprofessional collaboration is considered suboptimal. The integration of nurse practitioner roles into the acute and long-term care settings is influencing enhanced care. What remains unknown is how the nurse practitioner role enacts interprofessional collaboration or enables interprofessional care to promote high quality care. The study aim was to understand how nurse practitioners employed in acute and long-term care settings enable interprofessional collaboration and care. METHOD: Nurse practitioner interactions with other healthcare professionals were observed throughout the work day. These interactions were explored within the context of "knotworking" to create an understanding of their social practices and processes supporting interprofessional collaboration. Healthcare professionals who worked with nurse practitioners were invited to share their perceptions of valued role attributes and impacts. RESULTS: Twenty-four nurse practitioners employed at six hospitals participated. 384 hours of observation provided 1,284 observed interactions for analysis. Two types of observed interactions are comparable to knotworking. Rapid interactions resemble the traditional knotworking described in earlier studies, while brief interactions are a new form of knotworking with enhanced qualities that more consistently result in interprofessional care. Nurse practitioners were the most common initiators of brief interactions. CONCLUSIONS: Brief interactions reveal new qualities of knotworking with more consistent interprofessional care results. A general process used by nurse practitioners, where they practice a combination of both traditional (rapid) knotworking and brief knotworking to enable interprofessional care within acute and long-term care settings, is revealed

How many mailouts? Could attempts to increase the response rate in the Iraq war cohort study be counterproductive?

<p>Abstract</p> <p>Background</p> <p>Low response and reporting errors are major concerns for survey epidemiologists. However, while nonresponse is commonly investigated, the effects of misclassification are often ignored, possibly because they are hard to quantify. We investigate both sources of bias in a recent study of the effects of deployment to the 2003 Iraq war on the health of UK military personnel, and attempt to determine whether improving response rates by multiple mailouts was associated with increased misclassification error and hence increased bias in the results.</p> <p>Methods</p> <p>Data for 17,162 UK military personnel were used to determine factors related to response and inverse probability weights were used to assess nonresponse bias. The percentages of inconsistent and missing answers to health questions from the 10,234 responders were used as measures of misclassification in a simulation of the 'true' relative risks that would have been observed if misclassification had not been present. Simulated and observed relative risks of multiple physical symptoms and post-traumatic stress disorder (PTSD) were compared across response waves (number of contact attempts).</p> <p>Results</p> <p>Age, rank, gender, ethnic group, enlistment type (regular/reservist) and contact address (military or civilian), but not fitness, were significantly related to response. Weighting for nonresponse had little effect on the relative risks. Of the respondents, 88% had responded by wave 2. Missing answers (total 3%) increased significantly (p < 0.001) between waves 1 and 4 from 2.4% to 7.3%, and the percentage with discrepant answers (total 14%) increased from 12.8% to 16.3% (p = 0.007). However, the adjusted relative risks decreased only slightly from 1.24 to 1.22 for multiple physical symptoms and from 1.12 to 1.09 for PTSD, and showed a similar pattern to those simulated.</p> <p>Conclusion</p> <p>Bias due to nonresponse appears to be small in this study, and increasing the response rates had little effect on the results. Although misclassification is difficult to assess, the results suggest that bias due to reporting errors could be greater than bias caused by nonresponse. Resources might be better spent on improving and validating the data, rather than on increasing the response rate.</p

Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells

<p>Abstract</p> <p>Background</p> <p>Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation.</p> <p>Methods</p> <p>Naïve CBA mice (H2^k) underwent transplantation of a C57BL/6 (B6, H2^b) heart and were exposed to one of three types of music--opera (<it>La Traviata</it>), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed.</p> <p>Results</p> <p>CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4⁺cells, or CD4⁺CD25⁺cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to that from splenocytes of untreated recipients. Flow cytometry studies showed an increased CD4⁺CD25⁺Forkhead box P3 (Foxp3)⁺cell population in splenocytes from those mice.</p> <p>Conclusion</p> <p>Our findings indicate that exposure to opera music, such as La traviata, could affect such aspects of the peripheral immune response as generation of regulatory CD4⁺CD25⁺cells and up-regulation of anti-inflammatory cytokines, resulting in prolonged allograft survival.</p

The effect of the timing of exposure to Campylobacter jejuni on the gut microbiome and inflammatory responses of broiler chickens

Background Campylobacters are an unwelcome member of the poultry gut microbiota in terms of food safety. The objective of this study was to compare the microbiota, inflammatory responses, and zootechnical parameters of broiler chickens not exposed to Campylobacter jejuni with those exposed either early at 6 days old or at the age commercial broiler chicken flocks are frequently observed to become colonized at 20 days old. Results Birds infected with Campylobacter at 20 days became cecal colonized within 2 days of exposure, whereas birds infected at 6 days of age did not show complete colonization of the sample cohort until 9 days post-infection. All birds sampled thereafter were colonized until the end of the study at 35 days (mean 6.1 log10 CFU per g of cecal contents). The cecal microbiota of birds infected with Campylobacter were significantly different to age-matched non-infected controls at 2 days post-infection but generally the composition of the cecal microbiota were more affected by bird age as the time post infection increased. The effects of Campylobacter colonization on the cecal microbiota were associated with reductions in the relative abundance of OTUs within the taxonomic family Lactobacillaceae and the Clostridium cluster XIVa. Specific members of the Lachnospiraceae and Ruminococcaceae families exhibit transient shifts in microbial community populations dependent upon the age at which the birds become colonized by C. jejuni. Analysis of ileal and cecal chemokine/cytokine gene expression revealed increases in IL-6, IL-17A and Il-17F consistent with a Th17 response but the persistence of the response was dependent on the stage/time of C. jejuni colonization that coincide with significant reductions in the abundance of Clostridium cluster XIVa. Conclusions This study combines microbiome data, cytokine/chemokine gene expression with intestinal villus and crypt measurements to compare chickens colonized early or late in the rearing cycle to provide insights into the process and outcomes of Campylobacter colonization. Early colonization results in a transient growth rate reduction and pro-inflammatory response but persistent modification of the cecal microbiota. Late colonization produces pro-inflammatory responses with changes in the cecal microbiota that will endure in market ready chickens

Physician and patient attitudes towards complementary and alternative medicine in obstetrics and gynecology

<p>Abstract</p> <p>Background</p> <p>In the U.S., complementary and alternative medicine (CAM) use is most prevalent among reproductive age, educated women. We sought to determine general attitudes and approaches to CAM among obstetric and gynecology patients and physicians.</p> <p>Methods</p> <p>Obstetrician-gynecologist members of the American Medical Association in the state of Michigan and obstetric-gynecology patients at the University of Michigan were surveyed. Physician and patient attitudes and practices regarding CAM were characterized.</p> <p>Results</p> <p>Surveys were obtained from 401 physicians and 483 patients. Physicians appeared to have a more positive attitude towards CAM as compared to patients, and most reported routinely endorsing, providing or referring patients for at least one CAM modality. The most commonly used CAM interventions by patients were divergent from those rated highest among physicians, and most patients did not consult with a health care provider prior to starting CAM.</p> <p>Conclusion</p> <p>Although obstetrics/gynecology physicians and patients have a positive attitude towards CAM, physician and patients' view of the most effective CAM therapies were incongruent. Obstetrician/gynecologists should routinely ask their patients about their use of CAM with the goal of providing responsible, evidence-based advice to optimize patient care.</p