Staphylococcus aureus community-onset pneumonia in patients admitted to children's hospitals during autumn and winter of 2006-2007.

Staphylococcus aureus is a relatively uncommon cause of community-onset pneumonia (COP) that may complicate influenza infection. We reviewed admissions to children's hospitals to describe more systematically this entity. Records of patients hospitalized at three children's hospitals between 1 October 2006 and 30 April 2007 who had a positive S. aureus culture from a sterile site or respiratory specimen were reviewed and data were abstracted for episodes of primary S. aureus COP. Overall, 30 episodes met criteria for primary S. aureus COP; 12 (41%) involved methicillin-resistant S. aureus. Patients in 11 (37%) episodes were seen by a healthcare provider for their symptoms prior to hospital admission; three received an antimicrobial, none of which had activity against the S. aureus isolated. Mechanical ventilation was required in 21 (70%) episodes; five (17%) patients died. When evaluating patients with severe COP, providers should be aware of the potential for S. aureus, including methicillin-resistant strains.

Surveillance for severe community-associated methicillin-resistant Staphylococcus aureus infection.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has rapidly emerged in the USA as a cause of severe infections in previously healthy persons without traditional risk factors. We describe the epidemiology of severe CA-MRSA disease in the state of Georgia, USA and analyse the risk of death associated with three different clinical syndromes of CA-MRSA disease - pneumonia, invasive disease, and skin and soft-tissue infections (SSTIs). A total of 1670 cases of severe CA-MRSA disease were reported during 2005-2007. The case-fatality rate was 3.4%; sex and race of fatal and non-fatal cases did not differ significantly. While CA-MRSA pneumonia and invasive disease were less common than SSTIs, they were about 15 times more likely to result in death [risk ratio 16.69, 95% confidence interval (CI) 10.28-27.07 and 13.98, 95% CI 7.74-25.27, respectively]. When controlling for age and the presence of other clinical syndromes the odds of death in patients manifesting specific severe CA-MRSA syndromes was highest in those with pneumonia (odds ratio 11.34). Possible risk factors for severe CA-MRSA SSTI and pneumonia included the draining of lesions without medical assistance and an antecedent influenza-like illness.

Do glucocorticoids predict fitness? Linking environmental conditions, corticosterone and reproductive success in the blue tit, Cyanistes caeruleus.

Glucocorticoids, including corticosterone (CORT), have been suggested to provide a physiological link between ecological conditions and fitness. Specifically, CORT, which is elevated in response to harsh conditions, is predicted to be correlated with reduced fitness. Yet, empirical studies show that CORT can be non-significantly, positively and negatively linked with fitness. Divergent environmental conditions between years or study systems may influence whether CORT is linked to fitness. To test this, we monitored free-living blue tits (Cyanistes caeruleus) during breeding over 3 years. We quantified foraging conditions during brood rearing, and examined whether they were correlated with parental baseline CORT and reproductive success. We then tested whether CORT predicted fitness. Elevated parental CORT was associated with lower temperatures, greater rainfall and lower territory-scale oak density. Whereas asynchrony with the caterpillar food peak was correlated with reduced nestling mass and fledging success, but not parental CORT. Only low temperatures were associated with both reduced nestling mass and elevated parental CORT. Despite this, parents with elevated CORT had lighter offspring in all years. Contrarily, in 2009 parental CORT was positively correlated with the number fledged. The absence of a direct link between the foraging conditions that reduce nestling quality and elevate parental CORT suggests that parental CORT may provide a holistic measure of conditions where parents are working harder to meet the demands of developing young. As the positive correlation between parental CORT and fledging success differed between years, this suggests that contrasting conditions between years can influence correlations between parental CORT and fitness. Ultimately, as CORT concentrations are intrinsically variable and linked to the prevalent conditions, studies that incorporate environmental harshness will improve our understanding of evolutionary endocrinology.

Estrogen receptor beta activates the human retinoic acid receptor alpha-1 promoter in response to tamoxifen and other estrogen receptor antagonists, but not in response to estrogen.

Human estrogen receptor-alpha (hERalpha) or -beta (hERbeta) transfected into Hep G2 or COS1 cells each responded to estrogen to increase transcription from an estrogen-responsive element (ERE)-driven reporter vector with similar fold induction through a classical mechanism involving direct receptor binding to DNA. ER antagonists inhibited this estrogen induction through both hERalpha and hERbeta, although raloxifene was more potent through ERalpha than ERbeta, and tamoxifen was more potent via ERbeta than ERalpha. We have shown previously that estrogen stimulated the human retinoic acid receptor-alpha-1 (hRARalpha-1) promoter through nonclassical EREs by a mechanism that was ERalpha dependent, but that did not involve direct receptor binding to DNA. We show here that in contrast to hERalpha, hERbeta did not induce reporter activity driven by the hRARalpha-1 promoter in the presence of estrogen. While hERbeta did not confer estrogen responsiveness on this promoter, it did elicit transcriptional activation in the presence of 4-hydroxytamoxifen (4-OH-Tam). Additionally, this 4-OH-Tam agonist activity via ERbeta was completely blocked by estrogen. Like ERalpha, transcriptional activation of this promoter by ERbeta was not mediated by direct receptor binding to DNA. While hERalpha was shown to act through two estrogen-responsive sequences within the promoter, hERbeta acted only at the 3'-region, through two Sp1 sites, in response to 4-OH-Tam. Other ER antagonists including raloxifene, ICI-164,384 and ICI-182,780 also acted as agonists through ERbeta via the hRARalpha-1 promoter. Through the use of mutant and chimeric receptors, it was shown that the 4-OH-Tam activity via ERbeta from the hRARalpha-1 promoter in Hep G2 cells required the amino-terminal region of ERbeta, a region that was not necessary for estrogen-induced ERbeta activity from an ERE in Hep G2 cells. Additionally, the progesterone receptor (PR) antagonist RU486 acted as a weak (IC50 >1 microM) antagonist via hERalpha and as a fairly potent (IC50 approximately 200 nM) antagonist via hERbeta from an ERE-driven reporter in cells that do not express PR. Although RU486 bound only weakly to ERalpha or ERbeta in vitro, it did bind to ERbeta in whole-cell binding assays, and therefore, it is likely metabolized to an ERbeta-interacting compound in the cell. Interestingly, RU486 acted as an agonist through ERbeta to stimulate the hRARalpha-1 promoter in Hep G2 cells. These findings may have ramifications in breast cancer treatment regimens utilizing tamoxifen or other ER antagonists and may explain some of the known estrogenic or antiestrogenic biological actions of RU486.

Oxidative stress, activity behaviour and body mass in captive parrots.

Many parrot species are kept in captivity for conservation, but often show poor reproduction, health and survival. These traits are known to be influenced by oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and ability of antioxidant defences to ameliorate ROS damage. In humans, oxidative stress is linked with obesity, lack of exercise and poor nutrition, all of which are common in captive animals. Here, we tested whether small parrots (budgerigars, Melopsittacus undulatus) maintained in typical pet cages and on ad libitum food varied in oxidative profile, behaviour and body mass. Importantly, as with many birds held in captivity, they did not have enough space to engage in extensive free flight. Four types of oxidative damage, single-stranded DNA breaks (low-pH comet assay), alkali-labile sites in DNA (high-pH comet assay), sensitivity of DNA to ROS (H2O2-treated comet assay) and malondialdehyde (a byproduct of lipid peroxidation), were uncorrelated with each other and with plasma concentrations of dietary antioxidants. Without strenuous exercise over 28 days in a relatively small cage, more naturally 'active' individuals had more single-stranded DNA breaks than sedentary birds. High body mass at the start or end of the experiment, coupled with substantial mass gain, were all associated with raised sensitivity of DNA to ROS. Thus, high body mass in these captive birds was associated with oxidative damage. These birds were not lacking dietary antioxidants, because final body mass was positively related to plasma levels of retinol, zeaxanthin and α-tocopherol. Individuals varied widely in activity levels, feeding behaviour, mass gain and oxidative profile despite standardized living conditions. DNA damage is often associated with poor immunocompetence, low fertility and faster ageing. Thus, we have candidate mechanisms for the limited lifespan and fecundity common to many birds kept for conservation purposes.

Performance of a simple aiming task in hypergravity: I. overall accuracy.

BACKGROUND: Visuo-motor performance is known to be affected by exposure to hyper-gravity (hyper-G), but the underlying mechanisms remain to be determined; the present study investigated the role of target mislocalization. METHOD: Subjects pointed before, during and after exposure to hyper-G at targets without seeing their hand. Target positions were displayed: a) throughout each pointing response; b) before response onset; or c) in normal gravity prior to a set of movements. RESULTS AND CONCLUSIONS: For all display conditions, subjects pointed higher in hyper-G than in normal gravity from the first movement on. We attribute the discrepancy between this finding and previous results (8, 12) to different movement strategies. The effects of hyper-G on pointing performance were small, but sustained when targets were displayed before or throughout each movement, but they were large and transient when targets were memorized in normal-G. We conclude that too-high pointing in hyper-G cannot be simply explained by the "elevator illusion," and propose a tentative interpretation based on known perceptual deficits.

Performance of a simple aiming task in hypergravity: II. detailed response characteristics.

BACKGROUND: Literature proposes three hypotheses for impaired movement execution in hyper-G. The present study attempted to discriminate between these hypotheses by comparing kinematic characteristics and final accuracy of pointing movements in different gravity levels. METHOD: Subjects pointed without seeing their hand at targets presented before, during and after exposure to hyper-G. RESULTS: After factoring out movement amplitude, peak vertical velocity and the skewness of velocity profiles tended to increase, while movement duration tended to decrease with increasing G-level. Further, final response position was slightly less modulated by target position in hyper-G than in normal-G. CONCLUSION: Although not all findings reached statistical significance, the observed pattern of results corroborates the hypothesis (2) that the motor system re-interprets hyper-G as increased arm weight.

Accuracy of aimed arm movements in changed gravity.

We studied the accuracy of aimed arm movements in normal gravity, and during the hypergravity (hyper-G) and microgravity (micro-G) episodes of KC-135 parabolic flights. Subjects pointed at mirror-viewed targets without sight of their arm, and final pointing position was measured by a digitizing pad. Compared with the normal gravity (normal-G) baseline, subjects pointed consistently higher in hyper-G, and still higher in micro-G. Results were not different if subjects viewed targets only during normal-G and pointed at their memorized position under changed gravity (changed-G); this suggests that the "elevator illusion" played a minor role in our study. The observed impairments were attributed to degraded proprioceptive feedback and/or inappropriate motor programs in changed-G. Pointing accuracy improved movement-to-movement but not parabola-to-parabola, indicating that prolonged exposure is needed for sustained adaptation.

Portal vein thrombosis in a child with homozygous sickle-cell disease.

A 13-year-old boy with homozygous sickle-cell (SS) disease died suddenly at home following a short history of abdominal pain. Autopsy revealed venous thrombosis of the hepatic, portal, superior mesenteric and splenic veins. Venous thrombosis is rare in SS disease and thrombosis of mesenteric vessels is most frequently seen in chronic myeloproliferative disorders. Its occurrence in SS disease raises the possibility of a common pathogenesis and adds another pathology to the causes of the abdominal painful crisis.

Validation of swabs as a non-destructive and relatively non-invasive DNA sampling method in fish.

Non-destructive methods of collecting DNA from small fish species can be problematic, as fin clips can potentially affect behaviour or survivorship in the wild. Swabbing body mucus may provide a less invasive method of DNA collection. However, risk of contamination from other individuals in high density groups could give erroneous genotyping results. We compared multilocus microsatellite genotypes from the same individuals when collected at low and high density and compared this with fin clips. We found no differences between these categories, with a genotyping error rate of 0.42%, validating the use of body mucus swabbing for DNA collection in fish.

Impacts of dietary antioxidants and flight training on post-exercise oxidative damage in adult parrots.

After intense physical activity animals generally experience a rise in metabolic rate, which is associated with a proliferation of pro-oxidants. If unchecked, these pro-oxidants can cause damage to DNA and peroxidation of lipids in cell walls. Two factors are thought to ameliorate post-exercise oxidative damage, at least in mammals: dietary antioxidants and exercise training. So far it is unknown whether birds benefit similarly from exercise training, although a positive effect of dietary antioxidants on take-off flight has been indicated. In this experiment, we maintained captive wildtype budgerigars Melopsittacus undulatus on enhanced (EQ) or reduced quality (RQ) diets differing in levels of the dietary antioxidants retinol, vitamin C and alpha-tocopherol for 12 months. Birds were then regularly trained to perform take-off escape flights, a strenuous and biologically relevant form of exercise. For these adult budgerigars, regular exercise training improved escape flight performance, particularly in males on the EQ diet. In terms of oxidative damage, post-exercise levels of malondialdehyde (MDA), a by-product of lipid peroxidation, were significantly decreased after 9 weeks of flight training than after a single exercise session. Thus, individuals achieved faster escape flights with lower oxidative damage, after training. Also, birds that were fatter for their skeletal size initially had higher post-exercise MDA levels than thinner birds, but this relationship was broken by 9 weeks of flight training. Interestingly, there was no impact of diet quality on levels of MDA, suggesting that improved protection against oxidative damage for all birds was due to an up-regulation of endogenous antioxidant systems. Given their diversity, bird species provide rich research opportunities for investigating the interactions between exercise training, pro-oxidants production and antioxidant defences.

The effects of short-term antioxidant supplementation on oxidative stress and flight performance in adult budgerigars Melopsittacus undulatus.

Antioxidants are known to play an important role in quenching reactive oxygen species (ROS), thus ameliorating oxidative stress. Since increased metabolism associated with exercise can increase oxidative stress, dietary antioxidants may be a limiting factor in determining aspects of physical performance. Here we tested whether oxidative stress associated with flight exercise of captive adult budgerigars, Melopsittacus undulatus differed after they received a diet containing either enhanced (EQ) or reduced levels (RQ) of a nutritional supplement (Nutrivit) rich in antioxidants for 4 weeks. We also assessed differences in take-off escape time, a potential fitness-determining physiological capability. Oxidative stress was measured in two ways: comet assay to measure DNA damage; and analysis of malondialdehyde (MDA), a by-product of lipid peroxidation. Flight exercise appeared to increase oxidative stress. Moreover, birds had a higher percentage of intact DNA (fewer alkali labile sites) in one comet measure and lower levels of MDA after an EQ diet than after an RQ diet. We found no difference in flight performance between the two diets. Our results suggested that birds exerted maximum effort in escape flights, regardless of diet. However, this was at a cost of increased oxidative stress post-flight when on a reduced quality diet, but not when on an enhanced, antioxidant-rich diet. We suggest that dietary antioxidants may prove important in reducing exercise-related costs through multiple physiological pathways. Further work is necessary to fully understand the effects of antioxidants and oxidative stress on exercise performance in the longer term.

Yolk androgens and embryo sex: maternal effects or confounding factors?

Maternal effects occur when offspring phenotype is affected by environmental factors experienced by the mother and, in egg-laying species, are often mediated via egg resources. There is currently great interest among behavioural ecologists in maternally allocated yolk androgens, especially their relationship with offspring sex and development. Such studies need embryonic tissue for sexing, however, requiring eggs to be incubated (usually for 3 days). Therefore, there are concerns about whether the androgen concentrations assayed reflect those allocated by the mother. In addition, studies showing sex biases in maternal allocation of androgens could be confounded if male and female embryos uptake or metabolise androgens at different rates. We ran a series of experiments using zebra finch (Taeniopygia guttata) eggs to address these potential confounding factors. First we showed, using eggs naturally incubated for up to 5 days, that eggs containing embryos had lower yolk androgen concentrations than eggs that had failed to form embryos. We then tested various hypotheses for this difference using controlled incubation treatments. Our results suggested that (a) embryo development causes the yolk to become progressively more diluted with albumin; and (b) between 3 and 5 days of incubation embryos start uptaking or metabolising androgens. Crucially, we found no decline in yolk androgen concentration at 3 days incubation, and no evidence for sex-specific rates of uptake or metabolism of androgens. This strongly suggests that yolk androgen levels up to 3 days incubation do reflect those allocated by the mother, and that studies of sex biased maternal allocation of yolk androgens are not confounded by sex differences in embryo development.

Vancomycin-resistant Aureobacterium species cellulitis and bacteremia in a patient with acute myelogenous leukemia.

A 39-year-old male with acute myelogenous leukemia and concomitant porphyria cutanea tarda was admitted to the hospital for consolidation chemotherapy of his leukemia. During his hospitalization, he developed cellulitis of the left hand and persistent bacteremia with a yellow-pigmented, nonfermenting coryneform bacterium that was identified as Aureobacterium sp. The portal of entry for the Aureobacterium infection was probably through the skin lesions due to porphyria cutanea tarda. The infection developed while the patient was receiving vancomycin prophylaxis, and the vancomycin MIC for the isolate was 32 micrograms/ml.

Risk factors for carriage of drug-resistant Streptococcus pneumoniae among children in Memphis, Tennessee.

OBJECTIVES: To determine risk factors for carriage of drug-resistant Streptococcus pneumoniae to understand better the factors promoting spread of these isolates. STUDY DESIGN: We obtained medical and demographic information and nasopharyngeal swab specimens from 216 children less than 6 years old with upper respiratory tract infections, seeking medical care at five Memphis, Tenn, study sites. We evaluated risk factors for carriage of penicillin-nonsusceptible S. pneumoniae (NSSP) among 100 children with S. pneumoniae isolates. Patterns of antimicrobial prescription were recorded for enrolled children. RESULTS: Independent risk factors for carriage of NSSP included an increased number of antimicrobial treatment courses during the previous 3 months and white race. Day care attendance approached statistical significance (p = 0.07). Most children with upper respiratory tract infection received a prescription for antimicrobial drugs. These prescriptions were more common for white children than for black children. CONCLUSIONS: Increased use of antimicrobial drugs enhances the risk of carriage of NSSP. This may contribute to the higher risk among white children of NSSP infection; however, after control for antimicrobial use, white children were still at an increased risk of infection with NSSP, possibly through greater exposure to resistant strains.

Portal vein thrombosis in a child with homozygous sickle-cell disease

A 13-year old boy with homozygous sickle-cell (SS) disease died suddenly at home folllowing a short history of abdominal pain. Autopsy revealed venous thrombosis of the hepatic, portal, superior mesenteric and splenic veins. Venous thrombosis is rare in SS disease and thrombosis of mesenteric vessels is most frequently seen in chronic myeloproliferative disorders. Its occurrence in SS disease raises the possibility of a common pathogenesis and adds another pathology to the causes of abdominal painful crisis.