Plasma Gelsolin Depletion and Circulating Actin in Sepsis—A Pilot Study

Background: Depletion of the circulating actin-binding protein, plasma gelsolin (pGSN) has been described in septic patients and animals. We hypothesized that the extent of pGSN reduction correlates with outcomes of septic patients and that circulating actin is a manifestation of sepsis. Methodology/Principal Findings: We assayed pGSN in plasma samples from non-surgical septic patients identified from a pre-existing database which prospectively enrolled patients admitted to adult intensive care units at an academic hospital. We identified 21 non-surgical septic patients for the study. Actinemia was detected in 17 of the 21 patients, suggesting actin released into circulation from injured tissues is a manifestation of sepsis. Furthermore, we documented the depletion of pGSN in human clinical sepsis, and that the survivors had significantly higher pGSN levels than the non-survivors (163647 mg/L vs. 89648 mg/L, p = 0.01). pGSN levels were more strongly predictive of 28-day mortality than APACHE III scores. For every quartile reduction in pGSN, the odds of death increased 3.4-fold. Conclusion: We conclude that circulating actin and pGSN deficiency are associated with early sepsis. The degree of pGS

Initiating and continuing participation in citizen science for natural history

Background: Natural history has a long tradition in the UK, dating back to before Charles Darwin. Developing from a principally amateur pursuit, natural history continues to attract both amateur and professional involvement. Within the context of citizen science and public engagement, we examine the motivations behind citizen participation in the national survey activities of the Open Air Laboratories (OPAL) programme, looking at: people’s experiences of the surveys as ‘project-baed leisure’; their motivations for taking part and barriers to continued participation; where they feature on our continuum of engagement; and whether participation in an OPAL survey facilitated their movement between categories along this continuum. The paper focuses on a less-expected but very significant outcome regarding the participation of already-engaged amateur naturalists in citizen science. Methods: The paper draws upon research conducted by the authors (a sociologist of science and a cultural geographer) over a five-year period, who followed the development and implementation of the OPAL surveys. The authors engaged with members of the public and natural history enthusiasts to understand how and why people engaged with the OPAL surveys, seeking to explore the motivations and barriers they faced to any further engagement with natural history. This involved carrying out interviews and focus groups with willing participants. Results: Our main findings relate to: first, how committed amateur naturalists (already-engaged) have also enjoyed contributing to OPAL and the need to respect and work with their interest to encourage broader and deeper involvement; and second, how new (previously-unengaged) and relatively new participants (casually-engaged) have gained confidence, renewed their interests, refocussed their activities and/or gained validation from participation in OPAL. Overall, we argue that engagement with and enthusiasm for the scientific process is a motivation shared by citizens who, prior to participating in the OPAL surveys, were previously-unengaged, casually-engaged or already-engaged in natural history activities. Conclusions: Citizen science has largely been written about by professional scientists for professional scientists interested in developing a project of their own. This study offers a qualitative example of how citizen science can be meaningful to participants beyond what might appear to be a public engagement data collection exercise

Advantages of the Ilizarov external fixation in the management of intra-articular fractures of the distal tibia

<p>Abstract</p> <p>Background</p> <p>Treatment of distal tibial intra-articular fractures is challenging due to the difficulties in achieving anatomical reduction of the articular surface and the instability which may occur due to ligamentous and soft tissue injury. The purpose of this study is to present an algorithm in the application of external fixation in the management of intra-articular fractures of the distal tibia either from axial compression or from torsional forces.</p> <p>Materials and methods</p> <p>Thirty two patients with intra-articular fractures of the distal tibia have been studied. Based on the mechanism of injury they were divided into two groups. Group I includes 17 fractures due to axial compression and group II 15 fractures due to torsional force. An Ilizarov external fixation was used in 15 patients (11 of group I and 4 of group II). In 17 cases (6 of group I and 11 of group II) a unilateral hinged external fixator was used. In 7 out of 17 fractures of group I an additional fixation of the fibula was performed.</p> <p>Results</p> <p>All fractures were healed. The mean time of removal of the external fixator was 11 weeks for group I and 10 weeks for group II. In group I, 5 patients had radiological osteoarthritic lesions (grade III and IV) but only 2 were symptomatic. Delayed union occurred in 3 patients of group I with fixed fibula. Other complications included one patient of group II with subluxation of the ankle joint after removal of the hinged external fixator, in 2 patients reduction found to be insufficient during the postoperative follow up and were revised and 6 patients had a residual pain. The range of ankle joint motion was larger in group II.</p> <p>Conclusion</p> <p>Intra-articular fractures of the distal tibia due to axial compression are usually complicated with cartilaginous problems and are requiring anatomical reduction of the articular surface. Fractures due to torsional forces are complicated with ankle instability and reduction should be augmented with ligament repair, in order to restore normal movement of talus against the mortise. Both Ilizarov and hinged external fixators are unable to restore ligamentous stability. External fixation is recommended only for fractures of the ankle joint caused by axial compression because it is biomechanically superior and has a lower complication rate.</p

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria

Kinesiophobia in patients with non-traumatic arm, neck and shoulder complaints: a prospective cohort study in general practice

BACKGROUND: Complaints of arm, neck and shoulder are common in Western societies. Of those consulting a general practitioner (GP) with non-traumatic arm, neck or shoulder complaints, about 50% do not recover within 6 months.Kinesiophobia (also known as fear of movement/(re)injury) may also play a role in these complaints, as it may lead to avoidance behaviour resulting in hypervigilance to bodily sensations, followed by disability, disuse and depression. However, in relation to arm, neck and shoulder complaints little is known about kinesiophobia and its associated variables.Therefore this study aimed to: describe the degree of kinesiophobia in patients with non-traumatic complaints of arm, neck and shoulder in general practice; to determine whether mean scores of kinesiophobia change over time in non-recovered patients; and to evaluate variables associated with kinesiophobia at baseline. METHODS: In this prospective cohort study set in general practice, consulters with a first or new episode of non-traumatic arm, neck or shoulder complaints (aged 18-64 years) entered the cohort. Baseline data were collected on kinesiophobia using the Tampa Scale for Kinesiophobia, the 13-item adjusted version: TSK-AV, and on patient-, complaint-, and psychosocial variables using self-administered questionnaires. The mean TSK-AV score was calculated. In non-recovered patients the follow-up TSK-AV scores at 6 and 12 months were analyzed with the general linear mixed model. Variables associated with kinesiophobia at baseline were evaluated using multivariate linear regression analyses. RESULTS: The mean TSK-AV score at baseline was 24.8 [SD: 6.2]. Among non-recovered patients the mean TSK-AV score at baseline was 26.1 [SD: 6.6], which remained unchanged over 12- months follow-up period. The strongest associations with kinesiophobia were catastrophizing, disability, and comorbidity of musculoskeletal complaints. Additionally, having a shoulder complaint, low social support, high somatization and high distress contributed to the kinesiophobia score. CONCLUSION: The mean TSK-AV score in our population seems comparable to those in other populations in primary care.In patients who did not recover during the 12- month follow-up, the degree of kinesiophobia remained unchanged during this time period.The variables associated with kinesiophobia at baseline appear to be in line with the fear-avoidance model

Appropriateness of antibiotic treatment in intravenous drug users, a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Infectious disease is often the reason for intravenous drug users being seen in a clinical setting. The objective of this study was to evaluate the appropriateness of treatment and outcomes for this patient population in a hospital setting.</p> <p>Methods</p> <p>Retrospective study of all intravenous drug users hospitalized for treatment of infectious diseases and seen by infectious diseases specialists 1/2001–12/2006 at a university hospital. Treatment was administered according to guidelines when possible or to alternative treatment program in case of patients for whom adherence to standard protocols was not possible. Outcomes were defined with respect to appropriateness of treatment, hospital readmission, relapse and mortality rates. For statistical analysis adjustment for multiple hospitalizations of individual patients was made by using a generalized estimating equation.</p> <p>Results</p> <p>The total number of hospitalizations for infectious diseases was 344 among 216 intravenous drug users. Skin and soft tissue infections (n = 129, 37.5% of hospitalizations), pneumonia (n = 75, 21.8%) and endocarditis (n = 54, 15.7%) were most prevalent. Multiple infections were present in 25%. Treatment was according to standard guidelines for 78.5%, according to an alternative recommended program for 11.3%, and not according to guidelines or by the infectious diseases specialist advice for 10.2% of hospitalizations. Psychiatric disorders had a significant negative impact on compliance (compliance problems in 19.8% of hospitalizations) in multiple logistic regression analysis (OR = 2.4, CI 1.1–5.1, p = 0.03). The overall readmission rate and relapse rate within 30 days was 13.7% and 3.8%, respectively. Both non-compliant patient behavior (OR = 3.7, CI 1.3–10.8, p = 0.02) and non-adherence to treatment guidelines (OR = 3.3, CI 1.1–9.7, p = 0.03) were associated with a significant increase in the relapse rate in univariate analysis. In 590 person-years of follow-up, 24.6% of the patients died: 6.4% died during hospitalization (1.2% infection-related) and 13.6% of patients died after discharge.</p> <p>Conclusion</p> <p>Appropriate antibiotic therapy according to standard guidelines in hospitalized intravenous drug users is generally practicable and successful. In a minority alternative treatments may be indicated, although associated with a higher risk of relapse.</p

An Analysis of the Myocardial Transcriptome in a Mouse Model of Cardiac Dysfunction with Decreased Cholinergic Neurotransmission

Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KDHOM) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KDHOM mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression in mutant hearts, which might contribute to increased ROS levels observed in these cardiomyocytes. In contrast, in another model of cardiac remodeling and autonomic imbalance, induced through chronic isoproterenol treatment to increase sympathetic drive, these genes did not appear to be altered in a pattern similar to that observed in VAChT KDHOM hearts. These data suggest the importance of maintaining a fine balance between the two branches of the autonomic nervous system and the significance of absolute levels of cholinergic tone in proper cardiac function

Effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease:A randomized controlled trial

Objective: The aim of the study is to determine the effect of lutein combined with vitamin and mineral supplementation on contrast sensitivity in people with age-related macular disease (ARMD). Design: A prospective, 9-month, double-masked randomized controlled trial. Setting: Aston University, Birmingham, UK and a UK optometric clinical practice. Subjects: Age-related maculopathy (ARM) and atrophic age-related macular degeneration (AMD) participants were randomized (using a random number generator) to either placebo (n = 10) or active (n=15) groups. Three of the placebo group and two of the active group dropped out. Interventions: The active group supplemented daily with 6 mg lutein combined with vitamins and minerals. The outcome measure was contrast sensitivity (CS) measured using the Pelli-Robson chart, for which the study had 80% power at the 5% significance level to detect a change of 0.3log units. Results: The CS score increased by 0.07 ± 0.07 and decreased by 0.02 ± 0.18 log units for the placebo and active groups, respectively. The difference between these values is not statistically significant (z = 0.903, P = 0.376). Conclusion: The results suggest that 6 mg of lutein supplementation in combination with other antioxidants is not beneficial for this group. Further work is required to establish optimum dosage levels

New Insights into the Mechanisms of Embryonic Stem Cell Self-Renewal under Hypoxia: A Multifactorial Analysis Approach

Previous reports have shown that culturing mouse embryonic stem (mES) cells at different oxygen tensions originated different cell proliferation patterns and commitment stages depending on which signaling pathways are activated or inhibited to support the pluripotency state. Herein we provide new insights into the mechanisms by which oxygen is influencing mES cell self-renewal and pluripotency. A multifactorial approach was developed to rationally evaluate the singular and interactive control of MEK/ERK pathway, GSK-3 inhibition, and LIF/STAT3 signaling at physiological and non-physiological oxygen tensions. Collectively, our methodology revealed a significant role of GSK-3-mediated signaling towards maintenance of mES cell pluripotency at lower O2 tensions. Given the central role of this signaling pathway, future studies will need to focus on the downstream mechanisms involved in ES cell self-renewal under such conditions, and ultimately how these findings impact human models of pluripotency