Evolutionary implications of C2 photosynthesis: how complex biochemical trade-offs may limit C4 evolution.

The C2 carbon-concentrating mechanism increases net CO2 assimilation by shuttling photorespiratory CO2 in the form of glycine from mesophyll to bundle sheath cells, where CO2 concentrates and can be re-assimilated. This glycine shuttle also releases NH3 and serine into the bundle sheath, and modelling studies suggest that this influx of NH3 may cause a nitrogen imbalance between the two cell types that selects for the C4 carbon-concentrating mechanism. Here we provide an alternative hypothesis outlining mechanisms by which bundle sheath NH3 and serine play vital roles to not only influence the status of C2 plants along the C3 to C4 evolutionary trajectory, but to also convey stress tolerance to these unique plants. Our hypothesis explains how an optimized bundle sheath nitrogen hub interacts with sulfur and carbon metabolism to mitigate the effects of high photorespiratory conditions. While C2 photosynthesis is typically cited for its intermediary role in C4 photosynthesis evolution, our alternative hypothesis provides a mechanism to explain why some C2 lineages have not made this transition. We propose that stress resilience, coupled with open flux tricarboxylic acid and photorespiration pathways, conveys an advantage to C2 plants in fluctuating environments.

A systematic review and meta-analysis of the stability of peripheral immune markers in healthy adults.

Peripheral immune markers are widely used to predict risk for inflammatory disease. However, whether single assessments of inflammatory biomarkers represent stable individual differences remains unclear. We reviewed 50 studies (N = 48,674; 57 % male; mean age 54 (range 13-79) years) that assessed markers of inflammation on >1 occasion, with time between measures ranging from 24 h to 7+ years. Separate random effects meta-analyses were conducted for each inflammatory marker and time interval. Markers that had broad coverage across most time intervals included C-reactive protein (CRP; k = 37), interleukin (IL)-6 (k = 22), TNF-α (k = 10), and fibrinogen (Fg; k = 9). For CRP, IL-6, and TNF-α, stability estimates generally decreased with time, with strong to moderate stability over intervals <6 months (r's = 0.80-0.61), modest to moderate stability over 6 months - 3 years (r's = 0.60-0.51), and low stability for >3 years (r's = 0.39-0.30). Estimates were less reliable for Fg for time intervals ≤ 3 years although they generally followed the same pattern; more reliable findings suggested greater stability for Fg than other markers for intervals >3 years (r = 0.53). These findings suggest that single measures of inflammatory biomarkers may be an adequate index of stable individual differences in the short term (<6 months), with repeated measures of inflammatory biomarkers recommended over intervals ≥ 6 months to 3 years, and absolutely necessary over intervals >3 years to reliably identify stable individual differences in health risk. These findings are consistent with stability estimates and clinical recommendations for repeated measurement of other cardiovascular measures of risk (e.g., blood lipids, blood pressure).

Disentangling physics and chemistry in AGB outflows: revealing degeneracies when adding complexity.

Observations of the outflows of asymptotic giant branch (AGB) stars continue to reveal their chemical and dynamical complexity. Spherical asymmetries, such as spirals and disks, are prevalent and thought to be caused by binary interaction with a (sub)stellar companion. Furthermore, high density outflows show evidence of dust-gas interactions. The classical chemical model of these outflows - a gas-phase only, spherically symmetric chemical kinetics model - is hence not appropriate for the majority of observed outflows. We have included several physical and chemical advancements step-by-step: a porous density distribution, dust-gas chemistry, and internal UV photons originating from a close-by stellar companion. Now, we combine these layers of complexity into the most chemically and physically advanced chemical kinetics model of AGB outflows to date. By varying over all model parameters, we obtain a holistic view of the outflow's composition and how it (inter)depends on the different complexities. A stellar companion has the largest influence, especially when combined with a porous outflow. We compile sets of gas-phase molecules that trace the importance of dust-gas chemistry and allow us to infer the presence of a companion and porosity of the outflow. This shows that our new chemical model can be used to infer physical and chemical properties of specific outflows, as long as a suitable range of molecules is observed.

Experimental, theoretical, and astrochemical modelling investigation of the gas-phase reaction between the amidogen radical (NH2) and acetaldehyde (CH3CHO) at low temperatures.

The first experimental study of the low-temperature kinetics of the gas-phase reaction of NH2 with acetaldehyde (CH3CHO) has been performed. Experiments were carried out using laser-flash photolysis and laser-induced fluorescence spectroscopy to create and monitor the temporal decay of NH2 in the presence of CH3CHO. Low temperatures relevant to the interstellar medium were achieved using a pulsed Laval nozzle expansion. Rate coefficients were measured over the temperature and pressure range of 29-107 K and 1.4-28.2 × 1016 molecules per cm3, with the reaction exhibiting a negative temperature dependence and a positive pressure dependence. The yield of CH3CO from the reaction has also been determined at 67.1 and 35.0 K, by observing OH produced from the reaction of CH3CO with added O2. Ab initio calculations of the potential energy surface (PES) were combined with Rice-Rampsberger-Kessel-Marcus (RRKM) calculations to predict rate coefficients and branching ratios over a broad range of temperatures and pressures. The calculated rate coefficients were shown to be sensitive to the calculated density of states of the stationary points, which in turn are sensitive to the inclusion of hindered rotor potentials for several of the vibrational frequencies. The experimentally determined rate coefficients and yields have been used to fit the calculated PES, from which low-pressure limiting rate coefficients relevant to the ISM were determined. These have been included in a single-point dark cloud astrochemical model, in which the reaction is shown to be a potential source of gas-phase CH3CO radicals under dark cloud conditions.

Experimental and Theoretical Investigation of the Reaction of NH2 with NO at Very Low Temperatures.

The first experimental study of the low-temperature kinetics of the gas-phase reaction between NH2 and NO has been performed. A pulsed laser photolysis-laser-induced fluorescence technique was used to create and monitor the temporal decay of NH2 in the presence of NO. Measurements were carried out over the temperature range of 24-106 K, with the low temperatures achieved using a pulsed Laval nozzle expansion. The negative temperature dependence of the reaction rate coefficient observed at higher temperatures in the literature continues at these lower temperatures, with the rate coefficient reaching 3.5 × 10-10 cm3 molecule-1 s-1 at T = 26 K. Ab initio calculations of the potential energy surface were combined with rate theory calculations using the MESMER software package in order to calculate and predict rate coefficients and branching ratios over a wide range of temperatures, which are largely consistent with experimentally determined literature values. These theoretical calculations indicate that at the low temperatures investigated for this reaction, only one product channel producing N2 + H2O is important. The rate coefficients determined in this study were used in a gas-phase astrochemical model. Models were run over a range of physical conditions appropriate for cold to warm molecular clouds (10 to 30 K; 104 to 106 cm-3), resulting in only minor changes (<1%) to the abundances of NH2 and NO at steady state. Hence, despite the observed increase in the rate at low temperatures, this mechanism is not a dominant loss mechanism for either NH2 or NO under dark cloud conditions.

Stress-Related Inflammation and Social Withdrawal in Mothers of a Child With Cancer: A 1-Year Follow-Up Study.

OBJECTIVE: Acute inflammation-induced sickness behavior involves changes in social behavior that are believed to promote recovery. Whether chronic inflammation can influence social behaviors in ways that promote recovery is unknown. In a sample of mothers of a child with cancer, this report explores the relationship between inflammation that accompanies the stress of diagnosis and changes in social network, cancer-related stress, and inflammation across 1 year. Three hypotheses tested whether a) initial levels of stress associate with initial levels of inflammation, b) initial levels of inflammation predict social network changes over time, and c) social network changes over time buffer changes in stress and inflammation over time. METHODS: Cancer-related stress (Impact of Events Scale), social network (social roles and contacts from the Social Network Inventory), and systemic inflammation (circulating interleukin [IL]-6) were assessed in 120 mothers three times after their child's cancer diagnosis: after diagnosis (T1), 6-month follow-up (T2), and 12-month follow-up (T3). RESULTS: Consistent with predictions, greater cancer-related stress after diagnosis (T1) was associated with higher IL-6 after diagnosis (T1; b = 0.014, standard error [SE] = 0.01, p = .008). In turn, higher IL-6 after diagnosis (T1) was associated with a decrease in social roles over time (T1 ➔ T3; B = -0.030, SE = 0.01, p = .041). Finally, dropping social roles over time (T1 ➔ T3) was associated with decreases in cancer-related stress (B = 25.44, SE = 12.31, p = .039) and slower increases in IL-6 (B = 1.06, SE = 0.52, p = .040) over time. CONCLUSIONS: This study provides a first indication that chronic stress-related systemic inflammation may predict changes in social behavior that associate with stress recovery and slower increases in inflammation in the year after a major life stressor.

Examining the Impact of a Nursing Course Redesign on Student Outcomes, Faculty Workload, and Costs.

ABSTRACT: This study examined the impact of a nursing course redesign from traditional face-to-face to a hybrid format on student outcomes, workload allocation, and associated costs. In this quasi-experimental study, baccalaureate students received either traditional (n = 47) or hybrid delivery (n = 46); each group had equal degree-type representation. Average exam scores were analyzed using an independent t-test, with no significant differences found between groups. Faculty workload decreased by one third, and there was a 16.6 percent reduction in overall costs to implement the course. Course redesign can be effective for reducing faculty workload and costs while achieving course outcomes.

Mindfulness-Based Stress Reduction Buffers Glucocorticoid Resistance Among Older Adults: A Randomized Controlled Trial.

OBJECTIVE: Mindfulness interventions have been effective for improving a range of health outcomes; however, pathways underlying these effects remain unclear. Inflammatory processes may play a role, possibly through increased resistance of immune cells to the anti-inflammatory effects of glucocorticoids (i.e., glucocorticoid resistance, or GCR). Here, we conducted an initial examination of whether mindfulness training mitigates GCR among lonely older adults. METHODS: Lonely older adults (65-85 years; n = 190) were randomly assigned to an 8-week Mindfulness-Based Stress Reduction (MBSR) or a matched Health Enhancement Program (HEP). Whole blood drawn before and after the intervention and at 3-month follow-up was incubated with endotoxin and varying concentrations of dexamethasone, and interleukin-6 production was assessed using enzyme-linked immunosorbent assay. GCR was assessed as the concentration of dexamethasone required to decrease the stimulated interleukin-6 response by 50% (half maximal inhibitory concentration), with higher concentrations indicating greater GCR. Mixed-effects linear models tested time (pre, post, follow-up) by condition (MBSR versus HEP) effects. RESULTS: There was no overall time by condition effect on GCR across all time points. However, a significant time by condition effect was observed from preintervention to postintervention (d = 0.29), such that MBSR buffered increases in GCR observed in the HEP group. Although MBSR showed small, nonsignificant reductions in GCR from preintervention to 3-month follow-up, group differences were not maintained at the 3-month follow-up (d = 0.10). CONCLUSIONS: Results suggest that MBSR may protect against declines in the sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids among at-risk lonely older adults and show value in studying this biological mechanism in future trials.Trial Registration: Clinical Trials identifier NCT02888600.

Multifaceted Integration: Memory for Faces Is Subserved by Widespread Connections between Visual, Memory, Auditory, and Social Networks.

Our ability to recognize others by their facial features is at the core of human social interaction, yet this ability varies widely within the general population, ranging from developmental prosopagnosia to "super-recognizers". Previous work has focused mainly on the contribution of neural activity within the well described face network to this variance. However, given the nature of face memory in everyday life, and the social context in which it takes place, we were interested in exploring how the collaboration between different networks outside the face network in humans (measured through resting state connectivity) affects face memory performance. Fifty participants (men and women) were scanned with fMRI. Our data revealed that although the nodes of the face-processing network were tightly coupled at rest, the strength of these connections did not predict face memory performance. Instead, face recognition memory was dependent on multiple connections between these face patches and regions of the medial temporal lobe memory system (including the hippocampus), and the social processing system. Moreover, this network was selective for memory for faces, and did not predict memory for other visual objects (cars). These findings suggest that in the general population, variability in face memory is dependent on how well the face processing system interacts with other processing networks, with interaction among the face patches themselves accounting for little of the variance in memory ability.SIGNIFICANCE STATEMENT Our ability to recognize and remember faces is one of the pillars of human social interaction. Face recognition however is a very complex skill, requiring specialized neural resources in visual cortex, as well as memory, identity, and social processing, all of which are inherent in our real-world experience of faces. Yet in the general population, people vary greatly in their face memory abilities. Here we show that in the neural domain this variability is underpinned by the integration of visual, memory and social circuits, with the strength of the connections between these circuits directly linked to face recognition ability.

Efficacy of a Stress Management Intervention for Mothers of Children with Cancer.

OBJECTIVE: Mothers of children with cancer confront life stress that can impact their psychological and physical health and, in turn, the health of the family. Recommendations advocate preemptive stress-management interventions; however, few studies have investigated their efficacy. Here, we report results of a parallel randomized pilot trial examining health benefits of a stress management intervention designed to teach coping skills. METHODS: One hundred twenty mothers (age 36 ± 8 years) of children newly diagnosed with cancer were randomized to a 12-session stress management intervention (n = 60) or usual care (n = 60). Sessions took place in the inpatient or outpatient setting of a children's hospital. Primary outcome variables included psychological function and physical health assessed preintervention and postintervention and at 6-month follow-up (∼12 months postdiagnosis). RESULTS: Enrollment, retention, and satisfaction data supported feasibility and acceptability. Latent change score models showed the intervention reduced perceived stress (d = -0.37, p = 0.03), anxiety symptoms (ds = -0.38 and -0.56, ps < .03) and, a nonsignificant effect for depressive symptoms (d = -0.29, p = .11) across the 6 months following diagnosis. Intervention participants also endorsed fewer depressive symptoms than controls ∼12 months after diagnosis. The intervention improved stress management skills, which associated with the psychological benefits of participation. There were no intervention-related changes in perceived health or markers of inflammation. CONCLUSION: Intervention-related improvements in stress management skills may result in better psychological health in the face of caring for a child with cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02022449.

Circulating Interleukin-6 concentration covaries inversely with self-reported sleep duration as a function of polymorphic variation in the glucocorticoid receptor.

Growing evidence links extremes of self-reported sleep duration with higher circulating markers of inflammatory disease risk, although not all findings are consistent. Extremes of sleep duration also associate with activation of the hypothalamic-pituitary-adrenocortical (HPA) system and the peripheral release of cortisol, a glucocorticoid (GC) important in downregulating transcription of pro-inflammatory molecules. Polymorphic variation in the gene encoding the GC receptor (GR; NR3C1) modulates cellular sensitivity to GC-mediated anti-inflammatory signaling, thereby affecting levels of pro-inflammatory molecules. Thus, we hypothesized that extremes of self-reported sleep duration may covary with circulating levels of inflammatory markers as a function of allelic variation in NR3C1. Specifically, we examine the possibility that a single nucleotide polymorphism of the GR gene-(rs6198), the minor (G) allele of which confers reduced GR sensitivity-moderates an association of sleep duration with interleukin (IL)-6 and C-reactive protein (CRP) among a large sample (IL-6: N = 857; CRP: N = 929) of midlife community volunteers of European ancestry. Findings showed that sleep duration varied inversely with IL-6 (ß = -0.087, p = .012), and this association was stronger among individuals homozygous for the rs6198 G-allele compared to alternate genotypes (ß = -0.071, p = .039). We also found that sleep duration showed a U-shaped association with CRP (polynomial term: ß = 0.093, p = .006), which was not moderated by rs6198 genotype. In conclusion, we show that a common genetic variant in the GR moderates an inverse association of self-reported sleep duration with circulating IL-6, possibly contributing to the increased disease risk observed among some short sleepers.

Negative Ions in Space.

Until a decade ago, the only anion observed to play a prominent role in astrophysics was H-. The bound-free transitions in H- dominate the visible opacity in stars with photospheric temperatures less than 7000 K, including the Sun. The H- anion is also believed to have been critical to the formation of molecular hydrogen in the very early evolution of the Universe. Once H2 formed, about 500 000 years after the Big Bang, the expanding gas was able to lose internal gravitational energy and collapse to form stellar objects and "protogalaxies", allowing the creation of heavier elements such as C, N, and O through nucleosynthesis. Although astronomers had considered some processes through which anions might form in interstellar clouds and circumstellar envelopes, including the important role that polycyclic aromatic hydrocarbons might play in this, it was the detection in 2006 of rotational line emission from C6H- that galvanized a systematic study of the abundance, distribution, and chemistry of anions in the interstellar medium. In 2007, the Cassini mission reported the unexpected detection of anions with mass-to-charge ratios of up to ∼10 000 in the upper atmosphere of Titan; this observation likewise instigated the study of fundamental chemical processes involving negative ions among planetary scientists. In this article, we review the observations of anions in interstellar clouds, circumstellar envelopes, Titan, and cometary comae. We then discuss a number of processes by which anions can be created and destroyed in these environments. The derivation of accurate rate coefficients for these processes is an essential input for the chemical kinetic modeling that is necessary to fully extract physics from the observational data. We discuss such models, along with their successes and failings, and finish with an outlook on the future.

Immune function in Trachemys scripta following exposure to a predominant brevetoxin congener, PbTx-3, as a model for potential health impacts for sea turtles naturally exposed to brevetoxins.

Many species of marine life in southwestern Florida, including sea turtles, are impacted by blooms of the toxic dinoflagellate, Karenia brevis. Sublethal exposure to toxins produced by K. brevis has been shown to impact sea turtle health. Since all sea turtles in the Gulf of Mexico have protected status, a freshwater turtle, Trachemys scripta, was used as a model for immune system effects following experimental exposure to a predominant brevetoxin congener in K. brevis blooms, PbTx-3. Exposure to PbTx-3 was oral or intratracheal and health effects were assessed using a suite of immune function parameters: innate immune function (phagocytosis, plasma lysozyme activity), adaptive immune function (lymphocyte proliferation), and measures of oxidative stress (superoxide dismutase (SOD) and glutathione-S-transferase (GST) activity in plasma). Inflammation was also measured using plasma protein electrophoresis. In addition, differential expression of genes in peripheral blood leukocytes was determined using suppression subtractive hybridization followed by real-time PCR of specific genes. The primary immune effects of sublethal brevetoxin exposure in T. scripta following PbTx-3 administration, appear to be an increase in oxidative stress, a decrease in lysozyme activity, and modulation of immune function through lymphocyte proliferation responses. Plasma protein electrophoresis showed a decreased A:G ratio which may indicate potential inflammation. Genes coding for oxidative stress, such as thioredoxin and GST, were upregulated in exposed animals. That sublethal brevetoxin exposures impact immune function components suggests potential health implications for sea turtles naturally exposed to toxins. Knowledge of physiological stressors induced by brevetoxins may contribute to the ultimate goal of developing directed treatment strategies in exposed animals for reduced mortality resulting from red tide toxin exposure in sea turtles.

Development of glucocorticoid resistance over one year among mothers of children newly diagnosed with cancer.

Chronic distress associates with peripheral release of cortisol and a parallel upregulation of innate inflammation. Typically, cortisol functions to down-regulate inflammatory processes. However, in the context of chronic stress, it is hypothesized that glucocorticoid receptors within immune cells become less sensitive to the anti-inflammatory effects of cortisol, resulting in increased systemic inflammation. Caring for a child newly diagnosed with cancer is a particularly provocative chronic stressor. Here, we examine evidence for the development of cellular resistance to glucocorticoids among 120 mothers (Aged 18-56 years; 86% Caucasian) across the 12 months following their child's new diagnosis with cancer. Measures of psychological distress, interleukin (IL)-6, and glucocorticoid resistance (GCR) were assessed 1, 6, and 12 months after the diagnosis. A latent factor for distress was derived from the covariation among symptoms of anxiety, depression, and post-traumatic stress. Latent change score models revealed a significant positive association between change in distress and change in GCR from 0 to 6 months, and 6 months-1 year. This finding provides initial evidence for a longitudinal association between change in maternal distress and change in GCR from the onset of a chronic stressor through one year. Although levels of IL-6 increased during the first six months after the child's diagnosis, the magnitude of this change was not related to change in distress or change in GCR. Given the possible health consequences of reduced immune sensitivity to glucocorticoids, future work should further explore this stress response and its clinical significance.

Temporal Trends in Fall Rates with the Implementation of a Multifaceted Fall Prevention Program: Persistence Pays Off.

BACKGROUND: Most fall prevention programs are only modestly effective, and their sustainability is unknown. An academic medical center implemented a series of fall prevention interventions from 2001 to 2014. METHODS: The medical center's series of fall prevention interventions were as follows: reorganized the Falls Committee (2001), started flagging high-risk patients (2001), improved fall reporting (2002), increased scrutiny of falls (2005), instituted hourly nursing rounds (2006), reorganized leadership systems (2007), standardized fall prevention equipment (2008), adapted to a move to a new hospital building (2008), routinely investigated root causes (2009), mitigated fall risk during hourly nursing rounds (2009), educated patients about falls (2011), and taught nurses to think critically about risk (2012). To evaluate temporal trends in falls and injury falls, piecewise negative binomial regression with study unit-level random effects was used to analyze structured validated data sets available since 2003. RESULTS: From July 2003 through December 2014, the crude fall rate declined from 3.07 to 2.22 per 1,000 patient days, and injury falls declined from 0.77 to 0.65 per 1,000 patient days. Nonsignificant increases in falls occurred after nurses started rounding hourly and after the move to the new hospital. On the basis of regression models, significant declines occurred after nurses began to mitigate fall risk during hourly rounds (p = 0.009). CONCLUSION: Instituting incremental changes for more than a decade was associated with a meaningful (about 28%) and sustained decline in falls, although the rate of decline varied over time. Hospitals interested in reducing falls but concerned about competing clinical and financial priorities may find an incremental approach to be effective.

An 11-year-old with mallet finger.

An 11-year-old girl presented with pain and deformity in her right little finger distal interphalangeal joint (DIPJ). She was active in several sports including hurling and had a history of dyspraxia with frequent minor soft tissue injuries which had not required hospital assessment. Her mother was concerned about the possibility of a recent injury.Examination showed flexion deformity of the right fifth finger with complete loss of extension at the DIPJ. There was mild swelling and tenderness of the DIPJ with no bruising, erythema or warmth. An X-ray was performed (figure 1). emermed;35/11/679/F1F1F1Figure 1An teroposterior (AP) and lateral radiographs of the right little finger. QUESTION: What is the diagnosis?Salter-Harris type 1 fracture of distal phalanxDystelephalangyExtensor digiti minimi tendon injuryClinodactyly.

Health Characteristics and Blood Bacterial Assemblages of Healthy Captive Red Drum: Implications for Aquaculture and Fish Health Management.

The newly emerging tissue microbiota hypothesis suggests that bacteria found in blood and tissues play a role in host health, as these bacterial communities have been associated with various noncommunicable diseases such as obesity, liver disease, and cardiovascular disease. Numerous reports have identified bacteria in the blood of healthy finfish, indicating bacteremia may not always indicate disease. Current research priorities in aquaculture include the development of technologies and practices that will allow for an effective reduction in antibiotic use for the prevention and treatment of disease. Overall, a better understanding of fish health is needed, particularly among species selected for commercial-scale production. This study investigated blood characteristics of cultured Red Drum Sciaenops ocellatus with the tissue microbiota hypothesis in mind. Bacterial assemblages within the blood were characterized using next-generation sequencing and compared with other various blood characteristics, including innate immune function enzymes, between two fish cohorts reared in aquaculture. A total of 137 prokaryotic operational taxonomic units (OTUs) were identified from the blood of Red Drum. Microbiota diversity and structure varied greatly among individuals, for which the number of OTUs ranged from 4 to 58; however, predicted metagenomic function was highly similar between individuals and was dominated by the metabolism of carbohydrates and amino acids and membrane transport. Communities were dominated by Proteobacteria, followed by Bacteroidetes, Firmicutes, and Actinobacteria. The most commonly identified genera included Acinetobacter, Bacillus, Corynebacterium, and Pseudomonas. Three genera previously identified as containing marine fish pathogens were detected: Corynebacterium, Pantoea, and Chryseobacterium. A subset of bacterial OTUs were positively correlated with superoxide dismutase activity and negatively correlated with lysozyme activity, indicating a relationship between blood microbiota and the innate immune system. The results of this study provide further evidence for the tissue microbiota hypothesis and demonstrate the potential for these bacterial communities to be linked to immunological characteristics often used as biomarkers for fish health.

The effects of acute psychological stress on circulating and stimulated inflammatory markers: A systematic review and meta-analysis.

Inflammatory reactivity to acute laboratory stress is thought to reflect individual differences in responsivity to environmental stressors and may confer future health risk. To characterize this response, we conducted a meta-analysis of 34 studies that measured circulating inflammatory markers and 15 studies that measured stimulated production of inflammatory markers before and after exposure to laboratory challenge. Results showed significant stress-related increases in circulating interleukin (IL)-1ß (d=0.66, p<0.001), IL-6 (d=0.35, p<0.001), IL-10 (d=0.69, p<0.001), and tumor necrosis factor(TNF)-α (d=0.28, p<0.001), but not IL-1ra, IL-2, interferon-γ, or C-reactive protein. There were sufficient data to assess the time course of IL-6, IL-1ß, and TNF-α reactivity. IL-6 increased from baseline to measures taken 40-50, 60-75, 90, and 120min following stress, with the largest effect at 90min post-stress (d=0.70, p<0.001). IL-1ß increased from baseline to 20-30, 40-50, and 60-70min following stress, with the largest effect between 40 and 50min post-stress (d=0.73, p=0.02). For TNF-α, there was a significant increase from baseline to 31-50min post stress (d=0.44, p=0.01), but not at later times. There was no difference in magnitude of IL-6 reactivity as a function of type of stress (social-evaluative versus other). For stimulated inflammatory markers, results showed stress-related increases in IL-1ß when measured 20-120min post-stress (d=1.09, p<0.001), and in IL-4 and interferon-γ when measured 0-10min post stressor (d=-0.42, p<0.001 and d=0.47, p<0.001). These results extend findings from a prior meta-analysis (Steptoe et al., 2007) to show reliable increases in circulating IL-6, IL-1ß, IL-10 and TNF-α and stimulated IL-1ß, IL-4 and interferon-γ in response to acute stress. It is possible that these responses contribute to associations between exposure to life challenges and vulnerability to inflammatory disease.

Clinical Effectiveness and Cost of a Hospital-Based Fall Prevention Intervention: The Importance of Time Nurses Spend on the Front Line of Implementation.

OBJECTIVE: The aim of this study is to evaluate the clinical effectiveness and incremental net cost of a fall prevention intervention that involved hourly rounding by RNs at 2 hospitals. BACKGROUND: Minimizing in-hospital falls is a priority, but little is known about the value of fall prevention interventions. METHODS: We used an uncontrolled before-after design to evaluate changes in fall rates and time use by RNs. Using decision-analytical models, we estimated incremental net costs per hospital per year. RESULTS: Falls declined at 1 hospital (incidence rate ratio [IRR], 0.47; 95% confidence interval [CI], 0.26-0.87; P = .016), but not the other (IRR, 0.83; 95% CI, 0.59-1.17; P = .28). Cost analyses projected a 67.9% to 72.2% probability of net savings at both hospitals due to unexpected declines in the time that RNs spent in fall-related activities. CONCLUSIONS: Incorporating fall prevention into hourly rounds might improve value. Time that RNs invest in implementing quality improvement interventions can equate to sizable opportunity costs or savings.