Changing epidemiology of serious bacterial infections in febrile infants without localizing signs.

OBJECTIVE: Historically, management of infants with fever without localizing signs (FWLS) has generated much controversy, with attempts to risk stratify based on several criteria. Advances in medical practice may have altered the epidemiology of serious bacterial infections (SBIs) in this population. We conducted this study to test the hypothesis that the rate of SBIs in this patient population has changed over time. PATIENTS AND METHODS: We performed a retrospective review of all infants meeting FWLS criteria at our institution from 1997-2006. We examined all clinical and outcome data and performed statistical analysis of SBI rates and ampicillin resistance rates. RESULTS: 668 infants met criteria for FWLS. The overall rate of SBIs was 10.8%, with a significant increase from 2002-2006 (52/361, 14.4%) compared to 1997-2001 (20/307, 6.5%) (p = 0.001). This increase was driven by an increase in E. coli urinary tract infections (UTI), particularly in older infants (31-90 days). CONCLUSIONS: We observed a significant increase in E. coli UTI among FWLS infants with high rates of ampicillin resistance. The reasons are likely to be multifactorial, but the results themselves emphasize the need to examine urine in all febrile infants <90 days and consider local resistance patterns when choosing empiric antibiotics.

Experimental evaluation of evolution and coevolution as agents of ecosystem change in Trinidadian streams.

Evolution has been shown to be a critical determinant of ecological processes in some systems, but its importance relative to traditional ecological effects is not well known. In addition, almost nothing is known about the role of coevolution in shaping ecosystem function. Here, we experimentally evaluated the relative effects of species invasion (a traditional ecological effect), evolution and coevolution on ecosystem processes in Trinidadian streams. We manipulated the presence and population-of-origin of two common fish species, the guppy (Poecilia reticulata) and the killifish (Rivulus hartii). We measured epilithic algal biomass and accrual, aquatic invertebrate biomass, and detrital decomposition. Our results show that, for some ecosystem responses, the effects of evolution and coevolution were larger than the effects of species invasion. Guppy evolution in response to alternative predation regimes significantly influenced algal biomass and accrual rates. Guppies from a high-predation site caused an increase in algae relative to guppies from a low-predation site; algae effects were probably shaped by observed divergence in rates of nutrient excretion and algae consumption. Rivulus-guppy coevolution significantly influenced the biomass of aquatic invertebrates. Locally coevolved populations reduced invertebrate biomass relative to non-coevolved populations. These results challenge the general assumption that intraspecific diversity is a less critical determinant of ecosystem function than is interspecific diversity. Given existing evidence for contemporary evolution in these fish species, our findings suggest considerable potential for eco-evolutionary feedbacks to operate as populations adapt to natural or anthropogenic perturbations.

Eco-evolutionary feedbacks in community and ecosystem ecology: interactions between the ecological theatre and the evolutionary play.

Interactions between natural selection and environmental change are well recognized and sit at the core of ecology and evolutionary biology. Reciprocal interactions between ecology and evolution, eco-evolutionary feedbacks, are less well studied, even though they may be critical for understanding the evolution of biological diversity, the structure of communities and the function of ecosystems. Eco-evolutionary feedbacks require that populations alter their environment (niche construction) and that those changes in the environment feed back to influence the subsequent evolution of the population. There is strong evidence that organisms influence their environment through predation, nutrient excretion and habitat modification, and that populations evolve in response to changes in their environment at time-scales congruent with ecological change (contemporary evolution). Here, we outline how the niche construction and contemporary evolution interact to alter the direction of evolution and the structure and function of communities and ecosystems. We then present five empirical systems that highlight important characteristics of eco-evolutionary feedbacks: rotifer-algae chemostats; alewife-zooplankton interactions in lakes; guppy life-history evolution and nutrient cycling in streams; avian seed predators and plants; and tree leaf chemistry and soil processes. The alewife-zooplankton system provides the most complete evidence for eco-evolutionary feedbacks, but other systems highlight the potential for eco-evolutionary feedbacks in a wide variety of natural systems.

Male mice song syntax depends on social contexts and influences female preferences.

In 2005, Holy and Guo advanced the idea that male mice produce ultrasonic vocalizations (USV) with some features similar to courtship songs of songbirds. Since then, studies showed that male mice emit USV songs in different contexts (sexual and other) and possess a multisyllabic repertoire. Debate still exists for and against plasticity in their vocalizations. But the use of a multisyllabic repertoire can increase potential flexibility and information, in how elements are organized and recombined, namely syntax. In many bird species, modulating song syntax has ethological relevance for sexual behavior and mate preferences. In this study we exposed adult male mice to different social contexts and developed a new approach of analyzing their USVs based on songbird syntax analysis. We found that male mice modify their syntax, including specific sequences, length of sequence, repertoire composition, and spectral features, according to stimulus and social context. Males emit longer and simpler syllables and sequences when singing to females, but more complex syllables and sequences in response to fresh female urine. Playback experiments show that the females prefer the complex songs over the simpler ones. We propose the complex songs are to lure females in, whereas the directed simpler sequences are used for direct courtship. These results suggest that although mice have a much more limited ability of song modification, they could still be used as animal models for understanding some vocal communication features that songbirds are used for.

The effect of a urinary incontinence self-management program for older women in South Korea: A pilot study

© 2015 Chinese Nursing Association.Background Although self-management approaches have shown strong evidence of positive outcomes for urinary incontinence prevention and management, few programs have been developed for Korean rural communities. Objectives This pilot study aimed to develop, implement, and evaluate a urinary incontinence self-management program for community-dwelling women aged 55 and older with urinary incontinence in rural South Korea. Methods This study used a one-group pre- post-test design to measure the effects of the intervention using standardized urinary incontinence symptom, knowledge, and attitude measures. Seventeen community-dwelling older women completed weekly 90-min group sessions for 5 weeks. Descriptive statistics and paired t-tests and were used to analyze data. Results The mean of the overall interference on daily life from urine leakage (pre-test: M = 5.76 ± 2.68, post-test: M = 2.29 ± 1.93, t = -4.609, p < 0.001) and the sum of International Consultation on Incontinence Questionnaire scores (pre-test: M = 11.59 ± 3.00, post-test: M = 5.29 ± 3.02, t = -5.881, p < 0.001) indicated significant improvement after the intervention. Improvement was also noted on the mean knowledge (pre-test: M = 19.07 ± 3.34, post-test: M = 23.15 ± 2.60, t = 7.550, p < 0.001) and attitude scores (pre-test: M = 2.64 ± 0.19, post-test: M = 3.08 ± 0.41, t = 5.150, p < 0.001). Weekly assignments were completed 82.4% of the time. Participants showed a high satisfaction level (M = 26.82 ± 1.74, range 22-28) with the group program. Conclusions Implementation of a urinary incontinence self-management program was accompanied by improved outcomes for Korean older women living in rural communities who have scarce resources for urinary incontinence management and treatment. Urinary incontinence self-management education approaches have potential for widespread implementation in nursing practice.

Impact of Kidney Function on Effects of the Dietary Approaches to Stop Hypertension (Dash) Diet.

OBJECTIVES: Although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure in adults with hypertension, how kidney function impacts this effect is not known. We evaluated whether Estimated Glomerular Filtration Rate (eGFR) modifies the effect of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function. METHODS: Secondary analysis of the DASH-Sodium trial, a multicenter, randomized, controlled human feeding study that evaluated the blood pressure lowering effect of the DASH diet at three levels of sodium intake. Data from 92 participants with pre-hypertension or stage 1 hypertension during the 3450 mg /day sodium diet assignment contributed to this analysis. Stored frozen plasma and urine specimens were used to measure kidney related laboratory outcomes. RESULTS: Effects of the DASH diet on blood pressure, phosphorus, intact parathyroid hormone, creatinine, and albuminuria were not modified by baseline eGFR (mean 84.5 ± 18.0 ml/min/1.73 m(2), range 44.1 to 138.6 ml/min/1.73 m(2)) or the presence of chronic kidney disease (N=13%). CONCLUSIONS: The impact of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function does not appear to be modified by eGFR in this small subset of DASH-Sodium trial participants with relatively preserved kidney function. Whether greater reduction in eGFR modifies the effects of DASH on kidney related measures is yet to be determined. A larger study in individuals with more advanced kidney disease is needed to establish the efficacy and safety of the DASH diet in this patient population.

Assessment of toxicity and biodistribution of recombinant AAV8 vector-mediated immunomodulatory gene therapy in mice with Pompe disease.

A preclinical safety study was conducted to evaluate the short- and long-term toxicity of a recombinant adeno-associated virus serotype 8 (AAV2/8) vector that has been developed as an immune-modulatory adjunctive therapy to recombinant human acid α-glucosidase (rhGAA, Myozyme) enzyme replacement treatment (ERT) for patients with Pompe disease (AAV2/8-LSPhGAApA). The AAV2/8-LSPhGAApA vector at 1.6 × 10(13) vector particles/kg, after intravenous injection, did not cause significant short- or long-term toxicity. Recruitment of CD4(+) (but not CD8(+)) lymphocytes to the liver was elevated in the vector-dosed male animals at study day (SD) 15, and in group 8 animals at SD 113, in comparison to their respective control animals. Administration of the vector, either prior to or after the one ERT injection, uniformly prevented the hypersensitivity induced by subsequent ERT in males, but not always in female animals. The vector genome was sustained in all tissues through 16-week postdosing, except for in blood with a similar tissue tropism between males and females. Administration of the vector alone, or combined with the ERT, was effective in producing significantly increased GAA activity and consequently decreased glycogen accumulation in multiple tissues, and the urine biomarker, Glc4, was significantly reduced. The efficacy of the vector (or with ERT) was better in males than in females, as demonstrated both by the number of tissues showing significantly effective responses and the extent of response in a given tissue. Given the lack of toxicity for AAV2/8LSPhGAApA, further consideration of clinical translation is warranted in Pompe disease.

Biomarkers of PTA

© Springer Science+Business Media New York 2015.Prognostic biomarkers may indicate the likelihood of disease development and speed of progression or may serve as predictive indicators of responsiveness to treatment. Joint injuries, particularly severe injuries, may result in post-traumatic osteoarthritis (PTOA), and pre- and post-injury prognostic biomarkers are needed to enhance primary and secondary prevention approaches for PTOA. Several macromolecules from joint structures found in serum, urine, and synovial fluid are promising biochemical markers for monitoring joint metabolism and health before and after joint injury. The use of metabolic profiling (analysis of small molecules) as a predictive tool for osteoarthritis (OA) has increased in the past decade. Although there is some question as to whether PTOA and idiopathic OA are comparable conditions, there is some evidence to suggest that components of their pathogenesis are similar. Potentially, biomarkers important to the high-risk PTOA profile translate to idiopathic OA. Further work is needed to confirm the utility of macromolecules and metabolites as biomarkers for PTOA, particularly focusing on those strongly correlated to clinical efficacy measures important to the patient (e.g., symptoms, physical function, and quality of life) and the causal pathway of PTOA.

Colchicine effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): study protocol for a randomized controlled trial.

BACKGROUND: Despite the high prevalence and global impact of knee osteoarthritis (KOA), current treatments are palliative. No disease modifying anti-osteoarthritic drug (DMOAD) has been approved. We recently demonstrated significant involvement of uric acid and activation of the innate immune response in osteoarthritis (OA) pathology and progression, suggesting that traditional gout therapy may be beneficial for OA. We therefore assess colchicine, an existing commercially available agent for gout, for a new therapeutic application in KOA. METHODS/DESIGN: COLKOA is a double-blind, placebo-controlled, randomized trial comparing a 16-week treatment with standard daily dose oral colchicine to placebo for KOA. A total of 120 participants with symptomatic KOA will be recruited from a single center in Singapore. The primary end point is 30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16. Secondary end points include improvement in pain, physical function, and quality of life and change in serum, urine and synovial fluid biomarkers of cartilage metabolism and inflammation. A magnetic resonance imaging (MRI) substudy will be conducted in 20 participants to evaluate change in synovitis. Logistic regression will be used to compare changes between groups in an intention-to-treat analysis. DISCUSSION: The COLKOA trial is designed to evaluate whether commercially available colchicine is effective for improving signs and symptoms of KOA, and reducing synovial fluid, serum and urine inflammatory and biochemical joint degradation biomarkers. These biomarkers should provide insights into the underlying mechanism of therapeutic response. This trial will potentially provide data to support a new treatment option for KOA. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov as NCT02176460 . Date of registration: 26 June 2014.

Drug-drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor.

BACKGROUND: Edoxaban, an oral direct factor Xa inhibitor, is in development for thromboprophylaxis, including prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). P-glycoprotein (P-gp), an efflux transporter, modulates absorption and excretion of xenobiotics. Edoxaban is a P-gp substrate, and several cardiovascular (CV) drugs have the potential to inhibit P-gp and increase drug exposure. OBJECTIVE: To assess the potential pharmacokinetic interactions of edoxaban and 6 cardiovascular drugs used in the management of AF and known P-gp substrates/inhibitors. METHODS: Drug-drug interaction studies with edoxaban and CV drugs with known P-gp substrate/inhibitor potential were conducted in healthy subjects. In 4 crossover, 2-period, 2-treatment studies, subjects received edoxaban 60 mg alone and coadministered with quinidine 300 mg (n = 42), verapamil 240 mg (n = 34), atorvastatin 80 mg (n = 32), or dronedarone 400 mg (n = 34). Additionally, edoxaban 60 mg alone and coadministered with amiodarone 400 mg (n = 30) or digoxin 0.25 mg (n = 48) was evaluated in a single-sequence study and 2-cohort study, respectively. RESULTS: Edoxaban exposure measured as area under the curve increased for concomitant administration of edoxaban with quinidine (76.7 %), verapamil (52.7 %), amiodarone (39.8 %), and dronedarone (84.5 %), and exposure measured as 24-h concentrations for quinidine (11.8 %), verapamil (29.1 %), and dronedarone (157.6 %) also increased. Administration of edoxaban with amiodarone decreased the 24-h concentration for edoxaban by 25.7 %. Concomitant administration with digoxin or atorvastatin had minimal effects on edoxaban exposure. CONCLUSION: Coadministration of the P-gp inhibitors quinidine, verapamil, and dronedarone increased edoxaban exposure. Modest/minimal effects were observed for amiodarone, atorvastatin, and digoxin.

Thyroid volumes and urinary iodine in Swiss school children, 17 years after improved prophylaxis of iodine deficiency

Salt iodine content in Switzerland was raised from 7.5 to 15 mg per kg in 1980, and since then dietary iodine intake has been considered to be sufficient, even though a slight decrease due to imported food has recently been reported. The aim of this study was to establish normal values for thyroid volumes of school children who can be assumed to have had a sufficient iodine intake all their lifetime. Moreover, the present investigation was undertaken to verify that iodine sufficiency had been achieved equally in two regions each served by one of the two Swiss salt producers. Mean iodine concentration in urine spot samples from school children was 16.1 μg/dl, and it was identical in both the city of Lausanne (n=215) and the city of Solothurn (n=208). Thus it can be stated that in both cities (served by two different salt producers) iodine intake is equal and sufficient. Accordingly, thyroid volumes measured by ultrasound in school children aged 6 to 16 years were the same in both Lausanne (n=202) and Solothurn (n=207). Moreover, the age-adjusted median volumes at the 97th percentiles closely agree with and validate provisional international reference values recently proposed by the World Health Organisation and by the International Council for Control of Iodine Deficiency Disease.

Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

Background: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data. Methods. Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications. Results: Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood). Conclusion: Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

Responses Of Mytilus-Edulis On Exposure To The Water-Accommodated Fraction Of North-Sea-Oil

Individuals of Mytilus edulis L., collected from the Erme estuary (S.W. England) in 1978, were exposed to low concentrations (7 to 68 μg l-1) of the water-accommodated fraction (WAF) of North Sea crude oil. The pattern of accumulation of petroleum hydrocarbons in the body tissues was affected by the presence of algal food cells, the period of exposure, the hydrocarbon concentration in seawater, the type of body tissue and the nature of the hydrocarbon. Many physiological responses (e.g. rates of oxygen consumption, feeding, excretion, and scope for growth), cellular responses (e.g. lysosomal latency and digestive cell size) and biochemical responses (e.g. specific activities of several enzymes) were significantly altered by short-term (4 wk) and/or long-term (5 mo) exposure to WAF. Stress indices such as scope for growth and lysosomal latency were negatively correlated with tissue aromatic hydrocarbons.

Primary Production In A Turbid Estuary

The primary production in the Bristol Channel, U.K., was studied from 1973 to 1977: in this estuary, the euphotic zone extends from less than 0.5 m to greater than 10m and there is a large riverine input of inorganic nutrients. The standing stock of phytoplankton chlorophyll a was measured in 1973 and 1974 and was similar throughout the Bristol Channel but the rate of primary production was much greater where the water was less turbid. The estimated primary production was 6.8g C m−2 for the most turbid region and 164.9g C m−2 for the Outer Bristol Channel. A larger proportion of the annual primary production occurred in the spring in the Outer Channel than in the most turbid regions. Phaeocystis developed into blooms in some, but not all, years and exhibited a different light saturation curve to other phytoplankton populations. Serial incubations of short duration gave higher fixation rates than day-long incubations and it is argued that photoinhibition is probably insignificant in a mixed water column. Excretion rates of dissolved organic carbon by phytoplankton were always low.

Combined Effects Of Body Size Food Concentration And Season On Physiology Of Mytilus-Edulis

Multivariate experiments are used to study the effects of body size, food concentration, and season on the oxygen consumption, ammonia excretion, food assimilation efficiency and filtration rate of Mytilus edulis adults. Food concentrations and season affect both the intercept and the slope of the allometric equation describing oxygen uptake as a function of body size. Multiple regression and response surface techniques are used to describe and illustrate the complex relationship between metabolic rate, ration, season and the body size of M. edulis. Filtration rate has a relatively low weight exponent Q> = 038) and the intercept for the allometric equation is not significantly affected by food concentration, season or acclimation temperatures between 5 and 20 °C. Food assimilation efficiency declines exponentially with increasing food concentration and is dependent on body size at high food levels. The rate of ammonia excretion shows a similar seasonal cycle to that of oxygen consumption. They are both minimal in the autumn/winter and reach a maximum in the spring /summer.