Stromal-cell-derived factor (SDF) 1-alpha in combination with BMP-2 and TGF-β1 induces site-directed cell homing and osteogenic and chondrogenic differentiation for tissue engineering without the requirement for cell seeding

The clinical translation of tissue engineering approaches is limited by the requirement of a cell source. Cell guidance is a new concept that provides an alternative approach, obviating a requirement for an external cell source. This relies on site-specific homing and differentiation of the patient??s own cells to an implanted scaffold through controlled delivery of cytokines. In this study, we used stromal-cell-derived factor 1-alpha (SDF-1??) in combination with bone morphogenic protein (BMP)-2 or transforming growth factor (TGF)-??1 to induce cell migration and osteogenic or chondrogenic differentiation, respectively, in implanted scaffolds in a rat model. A customized cytokine microdelivery apparatus was used to ensure the constant rate and concentration of cytokine delivery around the scaffold. The formation of osteoid or early cartilage was observed after 4?weeks in specimens treated with SDF-1?? and either BMP-2 or TGF-??1. The density of cellular infiltrate and formation of differentiated tissue were lower in scaffolds treated only with BMP-2 or TGF-??1. Thus, controlled SDF-1?? delivery induces cell migration into scaffolds and can result in enhanced osteogenesis and chondrogenesis when used in combination with differentiation cytokines for purposes of tissue engineering.     

Antimalarial drugs impact chemical messenger secretion by blood platelets

BackgroundAdvances in antimalarial drug development are important for combating malaria. Among the currently identified antimalarial drugs, it is suggested that some interact directly with the malarial parasites while others interact indirectly with the parasites. While this approach leads to parasite elimination, little is known about how these antimalarial drugs impact immune cells that are also critical in malarial response.MethodsHerein, the effects of two common antimalarial drugs, chloroquine and quinine, on platelets were explored at both the bulk level, using high performance liquid chromatography, and the single cell level, using carbon-fiber microelectrode amperometry, to characterize any changes in chemical messenger secretion.ResultsThe data reveal that both drugs cause platelet activation and reduce the number of platelet exocytosis events as well as delay fusion pore opening and closing.ConclusionsThis work demonstrates how chloroquine and quinine quantitatively and qualitatively impact in vitro platelet function.General significanceOverall, the goal of this work is to promote understanding about how antimalarial drugs impact platelets as this may affect antimalarial drug development as well as therapeutic approaches to treat malarial infection.     

Relationships between Methylobacteria and Glyphosate with Native and Invasive Plant Species: Implications for Restoration

After removing invasive plants, whether by herbicides or other means, typical restoration design focuses on rebuilding native plant communities while disregarding soil microbial communities. However, microbial–plant interactions are known to influence the relative success of native versus invasive plants. Therefore, the abundance and composition of soil microorganisms may affect restoration efforts. We assessed the effect of herbicide treatment on phytosymbiotic pink‐pigmented facultative methylotrophic (PPFM) bacteria and the potential consequences of native and invasive species establishment post‐herbicide treatment in the lab and in a coastal sage scrub (CSS)/grassland restoration site. Lab tests showed that 4% glyphosate reduced PPFM abundance. PPFM addition to seeds increased seedling length of a native plant (Artemisia californica) but not an invasive plant (Hirschfeldia incana). At the restoration site, methanol addition (a PPFM substrate) improved native bunchgrass (Nassella pulchra) germination and size by 35% over controls. In a separate multispecies field experiment, PPFM addition stimulated the germination of N. pulchra, but not that of three invasive species. Neither PPFM nor methanol addition strongly affected the growth of any plant species. Overall, these results are consistent with the hypothesis that PPFMs have a greater benefit to native than invasive species. Together, these experiments suggest that methanol or PPFM addition could be useful in improving CSS/grassland restorations. Future work should test PPFM effects on additional species and determine how these results vary under different environmental conditions.     

Internet-Delivered Cognitive Behavioural Therapy for Adults with Mild to Moderate Depression and High Cardiovascular Disease Risks: A Randomised Attention-Controlled Trial

Background and Aim

Mild to moderate depression is common in those with cardiovascular disease and undertreated. We aimed to evaluate the effectiveness of internet-delivered Cognitive Behaviour Therapy (iCBT) on depressive symptom severity and adherence to medical advice and lifestyle interventions in adults with mild to moderate depression and high cardiovascular disease (CVD) risks.

Methods

Randomised double-blind, 12 week attention-controlled trial comparing an iCBT programme (E-couch) with an internet-delivered attention control health information package (HealthWatch, n = 282). The primary outcome was depression symptom level on the nine-item Patient Health Questionnaire (PHQ-9) (trial registration: ACTRN12610000085077).

Results

487/562 (88%) participants completed the endpoint assessment. 383/562 (70%) were currently treated for cardiovascular disease and 314/562 (56%) had at least one other comorbid condition. In ITT analysis of 562 participants iCBT produced a greater decline in the mean PHQ-9 score compared to the attention control of 1.06 (95% CI: 0.23–1.89) points, with differences between the two arms increasing over the intervention period (time by treatment effect interaction p = .012). There were also larger improvements in adherence (2.16 points; 95% CI: 0.33–3.99), reductions in anxiety (0.96 points; 95% CI: 0.19–1.73), and a greater proportion engaging in beneficial physical activity (Odds Ratio 1.91, 95%CI: 1.01–3.61) in the iCBT participants but no effect upon disability, or walking time/day. There were no withdrawals due to study related adverse events.

Conclusions

In people with mild to moderate depression and high levels of CVD risk factors, a freely accessible iCBT programme (http://www.ecouch.anu.edu.au) produced a small, but robust, improvement in depressive symptoms, adherence and some health behaviours.

Trial Registration

Australian and New Zealand Clinical Trials Registry ACTRN12610000085077     

The Impact of Nationwide Education Program on Clinical Practice in Sepsis Care and Mortality of Severe Sepsis: A Population-Based Study in Taiwan

Objectives

We investigated the effect of a nationwide educational program following surviving sepsis campaign (SSC) guidelines. Physicians’ clinical practice in sepsis care and patient mortality rate for severe sepsis were analyzed using a nationally representative cohort.

Methods

Hospitalizations for severe sepsis with organ failure from 1997 to 2008 were extracted from Taiwan’s National Health Insurance Research Database (NHIRD), and trends in sepsis incidence and mortality rates were analyzed. A before-and-after study design was used to evaluate changes in the utilization rates of SSC items and changes in severe sepsis mortality rates occurred after a national education program conducted by the Joint Taiwan Critical Care Medicine Committee since 2004. A total of 39,706 hospitalizations were analyzed, which consisted of a pre-intervention cohort of 14,848 individuals (2000-2003) and a post-intervention cohort of 24,858 individuals (2005-2008).

Results

The incidence rate of severe sepsis increased from 1.88 per 1,000 individuals in 1997 to 5.07 per 1,000 individuals in 2008. The cumulative mortality rate decreased slightly from 48.2% for the pre-intervention cohort to 45.9% for the post-intervention cohort. The utilization rates of almost all SSC items changed significantly between the pre-intervention and post-intervention cohorts. These changes of utilization rates were found to be associated with mild reduction in mortality rate.

Conclusion

The nationwide education program through a national professional society has a significant impact on physicians’ clinical practice and resulted in a slight but significant reduction of severe sepsis mortality rate.     

Co-administration of Selenium with Inorganic Mercury Alters the Disposition of Mercuric Ions in Rats

Biological Trace Element Research - Mercury (Hg) is a common environmental toxicant to which humans are exposed regularly through occupational and dietary means. Although selenium supplementation...     

Predictable shorebird departure patterns from a staging site can inform collision risks and mitigation of wind energy developments

High-quality staging sites are critical for long-distance migratory shorebirds to rest and refuel but are under threat from human development, including expansion of wind energy projects. However, predicting migration timing and movements in relation to weather conditions at staging sites can increase our understanding and mitigate effects of wind turbine collisions. Here we assessed northward migration timing and orientation in relation to environmental conditions at an inland staging area in Saskatchewan, Canada, with active and proposed wind energy developments. The area is known to host ~25% of North America's Sanderling Calidris alba population and 16 other Arctic-breeding migrant shorebird species. We quantified arrival and departure time of day in relation to weather using data from 140 of 237 Sanderlings radiotagged locally and at a southern staging site in the Gulf of Mexico with the Motus Wildlife Tracking System (April–June, 2015–2017). Although Sanderling arrival times were not related to time of day or weather, departures were more likely at sunset in winds blowing towards the northwest at intermediate speeds (<22 km/h). Departure flights were also primarily oriented north-northwest in the direction of a proposed wind energy development site at a mean ground speed of 21.4 m/s. Based on published climb rates and flight speed data, we estimated that shorebirds needed between 2 and 14 km setback distance to clear maximum turbine heights of 165 m. Given that departure events were predictable in time and space, adaptive mitigation may be useful for planning wind energy developments while reducing risk for staging Arctic-breeding shorebirds.     

Skin and Soft Tissue Infections and Associated Complications among Commercially Insured Patients Aged 0–64 Years with and without Diabetes in the U.S.

Introduction

Skin and soft tissue infections (SSTIs) are common infections occurring in ambulatory and inpatient settings. The extent of complications associated with these infections by diabetes status is not well established.

Methods

Using a very large repository database, we examined medical and pharmacy claims of individuals aged 0–64 between 2005 and 2010 enrolled in U.S. health plans. Diabetes, SSTIs, and SSTI-associated complications were identified by ICD-9 codes. SSTIs were stratified by clinical category and setting of initial diagnosis.

Results

We identified 2,227,401 SSTI episodes, 10% of which occurred in diabetic individuals. Most SSTIs were initially diagnosed in ambulatory settings independent from diabetes status. Abscess/cellulitis was the more common SSTI group in diabetic and non-diabetic individuals (66% and 59%, respectively). There were differences in the frequencies of SSTI categories between diabetic and non-diabetic individuals (p<0.01). Among SSTIs diagnosed in ambulatory settings, the SSTI-associated complication rate was over five times higher in people with diabetes than in people without diabetes (4.9% vs. 0.8%, p<0.01) and SSTI-associated hospitalizations were 4.9% and 1.1% in patients with and without diabetes, respectively. Among SSTIs diagnosed in the inpatient setting, bacteremia/endocarditis/septicemia/sepsis was the most common associated complication occurring in 25% and 16% of SSTIs in patients with and without diabetes, respectively (p<0.01).

Conclusions

Among persons with SSTIs, we found SSTI-associated complications were five times higher and SSTI-associated hospitalizations were four times higher, in patients with diabetes compared to those without diabetes. SSTI prevention efforts in individuals with diabetes may have significant impact on morbidity and healthcare resource utilization.