Neonatal mortality in puppies due to bacteremia by Streptococcus dysgalactiae subsp dysgalactiae

We report a case of bacteremia in puppies caused by Streptococcus dysgalactiae subsp. dysgalactiae. Identification was achieved by phenotypic and molecular genetic methods. This is the first report of the recovery of S. dysgalactiae subsp. dysgalactiae from dogs.

Brief and precarious lives: Infant mortality in contrasting sites from medieval and post-medieval England (AD 850-1859)

This study compares the infant mortality profiles of 128 infants from two urban and two rural cemetery sites in medieval England. The aim of this paper is to assess the impact of urbanization and industrialization in terms of endogenous or exogenous causes of death. In order to undertake this analysis, two different methods of estimating gestational age from long bone lengths were used: a traditional regression method and a Bayesian method. The regression method tended to produce more marked peaks at 38 weeks, while the Bayesian method produced a broader range of ages and were more comparable with the expected "natural" mortality profiles. At all the sites, neonatal mortality (28-40 weeks) outweighed post-neonatal mortality (41-48 weeks) with rural Raunds Furnells in Northamptonshire, showing the highest number of neonatal deaths and post-medieval Spitalfields, London, showing a greater proportion of deaths due to exogenous or environmental factors. Of the four sites under study, Wharram Percy in Yorkshire showed the most convincing "natural" infant mortality profile, suggesting the inclusion of all births (i.e., stillbirths and unbaptised infants).

Influence of porcine genotype on the abundance of thyroid hormones and leptin in sow milk and its impact on growth, metabolism and expression of key adipose tissue genes in offspring

Neonatal mortality is greater in commercial porcine genotypes, compared with the ancient Meishan breed that rapidly lay down adipose tissue; this may be related to hormones, such as triiodothyronine (T3) or leptin. Leptin is present in maternal milk; however, the extent to which this supply provides the neonate with leptin is unknown, but may play a role in growth and development. We investigated whether thyroid hormones and leptin concentrations in maternal milk differed between genotypes; and whether this influenced piglet concentrations or expression of genes involved in adipose tissue regulation. Eight Meishan and six commercial sows were entered into the study and milk samples from the day of parturition to day 4 postpartum was taken daily. The median birth weight piglet in each litter had a daily venous blood sample taken and was euthanised on day 4. Gene expressions of IGF-I, IGF-binding protein 3 (IGFBP-3), peroxisome proliferators activated receptor (PPAR) and glucocorticoid receptor (GR) were measured in adipose tissue using real-time PCR. T3 was increased in Meishan milk, but not in piglet plasma. Milk thyroxine was similar between breeds but commercial piglet levels were significantly higher. Leptin was higher in commercial sow milk throughout the study. Milk leptin was strongly correlated to plasma leptin during the first postnatal days and also to organ and body weight in Meishan piglets that also had significantly higher expression of GR, but not IGF-I, IGFBP-3 or PPAR. In conclusion, we have found a significant disparity in the provision of thyroid hormones in Meishan and commercial sow’s milk. These changes are not always translated to plasma concentrations of hormone in the piglet. Leptin appears to have a stronger role in growth and development in the Meishan genotype compared with commercial; along with the increased GR expression, this may also represent a potential mechanism behind the rapid accumulation of adipose tissue in Meishan piglets.

The biomechanics of amnion rupture: an X-ray diffraction study

Pre-term birth is the leading cause of perinatal and neonatal mortality, 40% of which are attributed to the pre-term premature rupture of amnion. Rupture of amnion is thought to be associated with a corresponding decrease in the extracellular collagen content and/or increase in collagenase activity. However, there is very little information concerning the detailed organisation of fibrillar collagen in amnion and how this might influence rupture. Here we identify a loss of lattice like arrangement in collagen organisation from areas near to the rupture site, and present a 9% increase in fibril spacing and a 50% decrease in fibrillar organisation using quantitative measurements gained by transmission electron microscopy and the novel application of synchrotron X-ray diffraction. These data provide an accurate insight into the biomechanical process of amnion rupture and highlight X-ray diffraction as a new and powerful tool in our understanding of this process.

Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction

BACKGROUND: Fibroblast growth factor 9 (FGF9) is secreted from bone marrow cells, which have been shown to improve systolic function after myocardial infarction (MI) in a clinical trial. FGF9 promotes cardiac vascularization during embryonic development but is only weakly expressed in the adult heart. METHODS AND RESULTS: We used a tetracycline-responsive binary transgene system based on the α-myosin heavy chain promoter to test whether conditional expression of FGF9 in the adult myocardium supports adaptation after MI. In sham-operated mice, transgenic FGF9 stimulated left ventricular hypertrophy with microvessel expansion and preserved systolic and diastolic function. After coronary artery ligation, transgenic FGF9 enhanced hypertrophy of the noninfarcted left ventricular myocardium with increased microvessel density, reduced interstitial fibrosis, attenuated fetal gene expression, and improved systolic function. Heart failure mortality after MI was markedly reduced by transgenic FGF9, whereas rupture rates were not affected. Adenoviral FGF9 gene transfer after MI similarly promoted left ventricular hypertrophy with improved systolic function and reduced heart failure mortality. Mechanistically, FGF9 stimulated proliferation and network formation of endothelial cells but induced no direct hypertrophic effects in neonatal or adult rat cardiomyocytes in vitro. FGF9-stimulated endothelial cell supernatants, however, induced cardiomyocyte hypertrophy via paracrine release of bone morphogenetic protein 6. In accord with this observation, expression of bone morphogenetic protein 6 and phosphorylation of its downstream targets SMAD1/5 were increased in the myocardium of FGF9 transgenic mice. CONCLUSIONS: Conditional expression of FGF9 promotes myocardial vascularization and hypertrophy with enhanced systolic function and reduced heart failure mortality after MI. These observations suggest a previously unrecognized therapeutic potential for FGF9 after MI.

Climate change and heat-related mortality in six cities Part 2: climate model evaluation and projected impacts from changes in the mean and variability of temperature with climate change

Previous assessments of the impacts of climate change on heat-related mortality use the "delta method" to create temperature projection time series that are applied to temperature-mortality models to estimate future mortality impacts. The delta method means that climate model bias in the modelled present does not influence the temperature projection time series and impacts. However, the delta method assumes that climate change will result only in a change in the mean temperature but there is evidence that there will also be changes in the variability of temperature with climate change. The aim of this paper is to demonstrate the importance of considering changes in temperature variability with climate change in impacts assessments of future heat-related mortality. We investigate future heatrelated mortality impacts in six cities (Boston, Budapest, Dallas, Lisbon, London and Sydney) by applying temperature projections from the UK Meteorological Office HadCM3 climate model to the temperature-mortality models constructed and validated in Part 1. We investigate the impacts for four cases based on various combinations of mean and variability changes in temperature with climate change. The results demonstrate that higher mortality is attributed to increases in the mean and variability of temperature with climate change rather than with the change in mean temperature alone. This has implications for interpreting existing impacts estimates that have used the delta method. We present a novel method for the creation of temperature projection time series that includes changes in the mean and variability of temperature with climate change and is not influenced by climate model bias in the modelled present. The method should be useful for future impacts assessments. Few studies consider the implications that the limitations of the climate model may have on the heatrelated mortality impacts. Here, we demonstrate the importance of considering this by conducting an evaluation of the daily and extreme temperatures from HadCM3, which demonstrates that the estimates of future heat-related mortality for Dallas and Lisbon may be overestimated due to positive climate model bias. Likewise, estimates for Boston and London may be underestimated due to negative climate model bias. Finally, we briefly consider uncertainties in the impacts associated with greenhouse gas emissions and acclimatisation. The uncertainties in the mortality impacts due to different emissions scenarios of greenhouse gases in the future varied considerably by location. Allowing for acclimatisation to an extra 2°C in mean temperatures reduced future heat-related mortality by approximately half that of no acclimatisation in each city.

Projected impacts on heat-related mortality from changes in the mean and variability of temperature with climate change

The aim of this paper is to demonstrate the importance of changing temperature variability with climate change in assessments of future heat-related mortality. Previous studies have only considered changes in the mean temperature. Here we present estimates of heat-related mortality resulting from climate change for six cities: Boston, Budapest, Dallas, Lisbon, London and Sydney. They are based on climate change scenarios for the 2080s (2070-2099) and the temperature-mortality (t-m) models constructed and validated in Gosling et al. (2007). We propose a novel methodology for assessing the impacts of climate change on heat-related mortality that considers both changes in the mean and variability of the temperature distribution.

Climate change and heat-related mortality in six cities Part 1: model construction and validation

Heat waves are expected to increase in frequency and magnitude with climate change. The first part of a study to produce projections of the effect of future climate change on heat-related mortality is presented. Separate city-specific empirical statistical models that quantify significant relationships between summer daily maximum temperature (T max) and daily heat-related deaths are constructed from historical data for six cities: Boston, Budapest, Dallas, Lisbon, London, and Sydney. ‘Threshold temperatures’ above which heat-related deaths begin to occur are identified. The results demonstrate significantly lower thresholds in ‘cooler’ cities exhibiting lower mean summer temperatures than in ‘warmer’ cities exhibiting higher mean summer temperatures. Analysis of individual ‘heat waves’ illustrates that a greater proportion of mortality is due to mortality displacement in cities with less sensitive temperature–mortality relationships than in those with more sensitive relationships, and that mortality displacement is no longer a feature more than 12 days after the end of the heat wave. Validation techniques through residual and correlation analyses of modelled and observed values and comparisons with other studies indicate that the observed temperature–mortality relationships are represented well by each of the models. The models can therefore be used with confidence to examine future heat-related deaths under various climate change scenarios for the respective cities (presented in Part 2).

Associations between elevated atmospheric temperature and human mortality: a critical review of the literature

The effects of the anomalously warm European summer of 2003 highlighted the importance of understanding the relationship between elevated atmospheric temperature and human mortality. This review is an extension of the brief evidence examining this relationship provided in the IPCC’s Assessment Reports. A comprehensive and critical review of the literature is presented, which highlights avenues for further research, and the respective merits and limitations of the methods used to analyse the relationships. In contrast to previous reviews that concentrate on the epidemiological evidence, this review acknowledges the inter-disciplinary nature of the topic and examines the evidence presented in epidemiological, environmental health, and climatological journals. As such, present temperature–mortality relationships are reviewed, followed by a discussion of how these are likely to change under climate change scenarios. The importance of uncertainty, and methods to include it in future work, are also considered.

Effect of acute administration of recombinant human leptin during the neonatal period on body temperature and endocrine profile of the piglet

Background: Leptin is produced predominantly by white adipocytes; in adults it regulates appetite and energy expenditure but its role in the neonate remains to be fully established. Objectives: To examine the effects of acute administration of recombinant human leptin on the endocrine profile and thermoregulation of neonatal pigs. Methods: 24 pairs of siblings (n = 48) were administered with either a single dose (4 mu g ml(-1) kg(-1) body weight) of leptin (L: n = 24) or a placebo (P: n = 24) on day 6 of neonatal life. Rectal temperature was recorded, and tissue samples were taken at 1 (n = 12), 2 (n = 12), 4 (n = 12) or 6 (n = 12) hours post-administration. Plasma concentrations of hormones and metabolites were determined in conjunction with messenger RNA (mRNA) for leptin and uncoupling protein-2. Results: Plasma leptin increased following leptin administration, and differences in concentrations of insulin, thyroxine and non-esterified fatty acids were observed between the two groups. Initially, rectal temperature decreased in L pigs but returned to start values by 1.5 h. This decline in rectal temperature was delayed in placebo animals, resulting in differences between treatments at 1.5 and 2 h. Conclusions: Acute leptin administration alters the endocrine profile of pigs and influences the thermoregulatory ability of the neonate. Copyright (C) 2007 S. Karger AG, Basel.

Differential effects of thyroid hormone manipulation and ß adrenoceptor agonist administration on uncoupling protein mRNA abundance in adipose tissue and thermoregulation in neonatal pigs

We have shown that there is significant disparity in the expression of uncoupling proteins (UCP) 2 and 3 between modern-commercial and ancient-Meishan porcine genotypes, commercial pigs also have higher plasma triiodothyronine (T(3)) in on the first day of life. T(3) and the sympathetic nervous system are both known to regulate UCPs in rodents and humans; their role in regulating these proteins in the pig is unknown. This study examined whether thyroid hormone manipulation or administration of a selective beta3 adrenoceptor agonist (ZD) influenced plasma hormones, colonic temperature and UCP expression in adipose tissue of two breeds of pig. To mimic the differences observed in thyroid hormone status, piglets from Meishan and commercial litters were randomly assigned to control (1 ml/kg water), T(3) (10 mg/kg) (Meishan only), methimazole (a commonly used antithyroid drug) (50 mg/kg) (commercial only) or ZD (10 mg/kg) oral administration for the first 4 days of postnatal life. Adipose tissue UCP2/3 mRNA abundance was measured on day 4 using PCR. T(3) administration raised plasma T(3) concentrations and increased colonic temperature on day 4. UCP3 mRNA abundance was higher in Meishan, than commercial piglets (p = 0.042) and was downregulated following T(3) administration (p = 0.014). Irrespective of genotype, ZD increased UCP2 mRNA abundance (Meishan p = 0.05, commercial p = 0.03). Expression of neither UCP2 nor 3 was related to colonic temperature, regardless of treatment. In conclusion, we have demonstrated a dissociation between thyroid hormones and the sympathetic nervous system in the regulation of UCPs in porcine adipose tissue. We have also suggested that expression of adipose tissue UCP2 and 3 are not related to body temperature in piglets.

The effect of selective decontamination of the digestive tract on mortality in multiple trauma patients: a multicenter randomized controlled trial

Objective: Evaluation of selective decontamination of the digestive tract (SDD) on late mortality in ventilated trauma patients in an intensive care unit (ICU). Methods: A multicenter, randomized controlled trial was undertaken in 401 trauma patients with Hospital Trauma Index-Injury Severity Score of 16 or higher. Patients were randomized to control (n = 200) or SDD (n = 201), using polymyxin E, tobramycin, and amphotericin B in throat and gut throughout ICU treatment combined with cefotaxime for 4 days. Primary endpoint was late mortality excluding early death from hemorrhage or craniocerebral injury. Secondary endpoints were infection and organ dysfunction. Results: Mortality was 20.9% with SDD and 22.0% in controls. Overall late mortality was 15.3% (57/372) as 29 patients died from cerebral injury, 16 SDD and 13 control. The odds ratio (95% confidence intervals) of late mortality for SDD relative to control was 0.75 (0.40-1.37), corresponding to estimates of 13.4% SDD and 17.2% control. The overall infection rate was reduced in the test group (48.8% vs. 61.0%). SDD reduced lower airway infections (30.9% vs. 50.0%) and bloodstream infections due to aerobic Gram-negative bacilli (2.5% vs. 7.5%). No difference in organ dysfunction was found. Concluson: This study demonstrates that SDD significantly reduces infection in multiple trauma, although this RCT in 401 patients was underpowered to detect a mortality benefit.

Mammal reproductive strategies driven by offspring mortality-size relationships

Trade-offs have long been a major theme in life-history theory, but they have been hard to document. We introduce a new method that reveals patterns of divergent trade-offs after adjusting for the pervasive variation in rate of resource allocation to offspring as a function of body size and lifestyle. Results suggest that preweaning vulnerability to predation has been the major factor determining how female placental mammals allocate production between a few large and many small offspring within a litter and between a few large litters and many small ones within a reproductive season. Artiodactyls, perissodactyls, cetaceans, and pinnipeds, which give birth in the open on land or in the sea, produce a few large offspring, at infrequent intervals, because this increases their chances of escaping predation. Insectivores, fissiped carnivores, lagomorphs, and rodents, whose offspring are protected in burrows or nests, produce large litters of small newborns. Primates, bats, sloths, and anteaters, which carry their young from birth until weaning, produce litters of one or a few offspring because of the need to transport and care for them.