The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial.

OBJECTIVE: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. DESIGN: Multicentre randomised controlled trial. SETTING: Hospitals in nine European countries. POPULATION: A cohort of 112 pregnant women with placental tissue. METHODS: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. MAIN OUTCOME MEASURES: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. RESULTS: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05). CONCLUSIONS: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. TWEETABLE ABSTRACT: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

AIMS: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. METHODS: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. RESULTS: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. CONCLUSIONS: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

Tuning Electroluminescence from a Plasmonic Cavity-Coupled Silicon Light Source.

The combination of Moore's law and Dennard's scaling rules have constituted the fundamental guidelines for the silicon-based semiconductor industry for decades. Furthermore, the enormous growth of global data volume has pushed the demand for complex and densely packed devices. In recent years, it has become clear that wired interconnects impose increasingly severe speed and power limitations onto integrated circuits as scaling slows toward a halt. To overcome these limitations, there is a clear need for optical data processing. Despite significant progress in the development of silicon photonics, light sources remain challenging owing to the indirect bandgap of group IV materials. It is therefore highly desirable to develop new concepts for a silicon light source that meets efficiency and footprint requirements similar to their electronic counterparts. Here, we demonstrate an electrically driven and tunable silicon light source by matching the resonant modes of a silver nanocavity with the hot luminescence spectrum of an avalanching p-n junction. The cavity significantly enhances phonon-assisted recombination of hot carriers by tailoring the local density of states at the size-tunable resonance. Such tunable nanoscale emitter may be of great interest for short-reach communications, microdisplays or lab-on-chip applications.

Cylindrospermopsin toxicity in mice following a 90-d oral exposure.

Cylindrospermopsin (CYN) is a toxin associated with numerous species of freshwater cyanobacteria throughout the world. It is postulated to have caused an episode of serious illnesses in Australia through treated drinking water, as well as lethal effects in livestock exposed to water from farm ponds. Toxicity included effects indicative of both hepatic and renal dysfunction. In humans, symptoms progressed from initial hepatomegaly, vomiting, and malaise to acidosis and hypokalemia, bloody diarrhea, and hyperemia in mucous membranes. Laboratory animal studies predominantly involved the intraperitoneal (i.p.) route of administration and confirmed this pattern of toxicity with changes in liver enzyme activities and histopathology consistent with hepatic injury and adverse renal effects. The aim of this study was designed to assess subchronic oral exposure (90 d) of purified CYN from 75 to 300 µg/kg/d in mouse. At the end of the dosing period, examinations of animals noted (1) elevated organ to body weight ratios of liver and kidney at all dose levels, (2) treatment-related increases in serum alanine aminotransferase (ALT) activity, (3) decreased blood urea nitrogen (BUN) and cholesterol concentrations in males, and (4) elevated monocyte counts in both genders. Histopathological alterations included hepatocellular hypertrophy and cord disruption in the liver, as well as renal cellular hypertrophy, tubule dilation, and cortical tubule lesions that were more prominent in males. A series of genes were differentially expressed including Bax (apoptosis), Rpl6 (tissue regeneration), Fabp4 (fatty acid metabolism), and Proc (blood coagulation). Males were more sensitive to many renal end points suggestive of toxicity. At the end of exposure, toxicity was noted at all dose levels, and the 75 µg/kg group exhibited significant effects in liver and kidney/body weight ratios, reduced BUN, increased serum monocytes, and multiple signs of histopathology indicating that a no-observed-adverse-effect level could not be determined for any dose level.

Icebergs in the Nordic Seas Throughout the Late Pliocene.

The Arctic cryosphere is changing and making a significant contribution to sea level rise. The Late Pliocene had similar CO2 levels to the present and a warming comparable to model predictions for the end of this century. However, the state of the Arctic cryosphere during the Pliocene remains poorly constrained. For the first time we combine outputs from a climate model with a thermodynamic iceberg model to simulate likely source regions for ice-rafted debris (IRD) found in the Nordic Seas from Marine Isotope Stage M2 to the mid-Piacenzian Warm Period and what this implies about the nature of the Arctic cryosphere at this time. We compare the fraction of melt given by the model scenarios with IRD data from four Ocean Drilling Program sites in the Nordic Seas. Sites 911A, 909C, and 907A show a persistent occurrence of IRD that model results suggest is consistent with permanent ice on Svalbard. Our results indicate that icebergs sourced from the east coast of Greenland do not reach the Nordic Seas sites during the warm Late Pliocene but instead travel south into the North Atlantic. In conclusion, we suggest a continuous occurrence of marine-terminating glaciers on Svalbard and on East Greenland (due to the elevation of the East Greenland Mountains during the Late Pliocene). The study has highlighted the usefulness of coupled climate model-iceberg trajectory modeling for understanding ice sheet behavior when proximal geological records for Pliocene ice presence or absence are absent or are inconclusive.

A critical review of the postulated role of the non-essential amino acid, ß-N-methylamino-L-alanine, in neurodegenerative disease in humans.

The compound BMAA (ß-N-methylamino-L-alanine) has been postulated to play a significant role in four serious neurological human diseases: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, Parkinsonism, and dementia that occur globally. ALS/PDC with symptoms of all three diseases first came to the attention of the scientific community during and after World War II. It was initially associated with cycad flour used for food because BMAA is a product of symbiotic cycad root-dwelling cyanobacteria. Human consumption of flying foxes that fed on cycad seeds was later suggested as a source of BMAA on Guam and a cause of ALS/PDC. Subsequently, the hypothesis was expanded to include a causative role for BMAA in other neurodegenerative diseases including Alzheimer's disease (AD) through exposures attributed to proximity to freshwaters and/or consumption of seafood due to its purported production by most species of cyanobacteria. The hypothesis that BMAA is the critical factor in the genesis of these neurodegenerative diseases received considerable attention in the medical, scientific, and public arenas. This review examines the history of ALS/PDC and the BMAA-human disease hypotheses; similarities and differences between ALS/PDC and the other diseases with similar symptomologies; the relationship of ALS/PDC to other similar diseases, studies of BMAA-mediated effects in lab animals, inconsistencies and data gaps in the hypothesis; and other compounds and agents that were suggested as the cause of ALS/PDC on Guam. The review concludes that the hypothesis of a causal BMAA neurodegenerative disease relationship is not supported by existing data.

Characterisation and in vitro antimicrobial potential of liposome encapsulated silver ions against Candida albicans.

Liposomes are biocompatible, biodegradable, controlled delivery systems with the ability to encapsulate both lipophilic and hydrophilic compounds, including metal ions. Liposome encapsulated Ag(+) (lipo-Ag(+)), prepared by reverse-phase evaporation, was used as a controlled delivery system against Candida albicans. Characterisation of the lipo-Ag(+) indicated that the multilamellar vesicles with diameters ranging between ≈ 0.5 and 5.0 µm showed potential as a controlled delivery system to consistently deliver Ag(+) to C. albicans. Results from inductively coupled plasma (ICP) analysis showed higher association of cell bound Ag(+) at 15 mins post exposure when compared to unencapsulated Ag(+). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicate detrimental effects of Ag(+) on C. albicans cell structure. These effects along with the ICP results also correlate with previously reported time kill experiment observations.

Which infants with eczema are at risk of food allergy? Results from a population-based cohort.

BACKGROUND: The relationship between early onset eczema and food allergy among infants has never been examined in a population-based sample using the gold standard for diagnosis, oral food challenge. OBJECTIVE: We characterised the risk of challenge-proven food allergy among infants with eczema in the general population. METHODS: One-year-old infants (n = 4453 meeting criteria for this analysis) were assessed for history of eczema, received a nurse-administered eczema examination and underwent skin prick testing to peanut, egg and sesame. Those with a detectable wheal to one of the test foods underwent an oral food challenge irrespective of wheal size. The risk of food allergy, stratified by eczema severity and age of onset, was estimated using multivariate logistic regression with population sampling weights. RESULTS: One in five infants with eczema were allergic to peanut, egg white or sesame, compared to one in twenty-five infants without eczema (OR 6.2, 95% CI 4.9, 7.9, P < 0.001). The prevalence of peanut allergy was low in the absence of eczema (0.7% 95% CI 0.4, 1.1). Infants with eczema were 11.0 times more likely to develop peanut allergy (95% CI 6.6, 18.6) and 5.8 times more likely to develop egg allergy (95% CI 4.6, 7.4) by 12 months than infants without eczema. 50.8% of infants (95% CI 42.8, 58.9) with early eczema onset (<3 months) who required doctor-prescribed topical corticosteroid treatment developed challenge-proven food allergy. CONCLUSION AND CLINICAL RELEVANCE: Eczema, across the clinical severity spectrum in infancy, is a strong risk factor for IgE-mediated food allergy. Infants with eczema were six times more likely to have egg allergy and 11 times more likely to have peanut allergy by 12 months than infants without eczema. Our data suggest that a heightened awareness of food allergy risk among healthcare practitioners treating infants with eczema, especially if early onset and severe, is warranted.

The prevalence and socio-demographic risk factors of clinical eczema in infancy: a population-based observational study.

BACKGROUND: Socio-demographic predictors for the development of clinically observed, infantile eczema have not been formally examined in a large population-based study. Few studies of eczema risk factors have included current, objective eczema outcomes as well as parent-reported history. OBJECTIVES: We aimed to measure the population prevalence of infantile eczema using novel sampling methodology, and identify socio-demographic risk factors for eczema in the first year of life. METHODS: A population-based cross-sectional study of infantile allergy (the HealthNuts study, n = 4972, response rate 74.1%) was conducted from 2008-2011 in Melbourne, Australia. Infants were examined for current eczema at age 12 months (mean 12.7, SD 0.7). Parents provided information about the infants' history of eczema and demographic factors. Factors associated with eczema were modelled using multinomial logistic regression. RESULTS: The population prevalence of observed eczema at 12 months was 20.3% (95% CI 19.0, 21.5), while cumulative prevalence for parent-reported eczema was 28.0% (95% CI 26.7, 29.4). The strongest predictors of eczema were maternal eczema and asthma (multinomial (M)-OR 1.7, P < 0.001, and M-OR 1.4, P = 0.007), male sex (M-OR 1.4, P < 0.001), and East Asian ethnicity (M-OR 1.6, P < 0.001) with over 80% of infants with all risk factors exhibiting eczema. East Asian parents, particularly recent migrants, reported fewer allergies than other parents. CONCLUSIONS AND CLINICAL RELEVANCE: Approximately, one in three infants developed eczema by 12 months of age. East Asian infants are at increased risk of eczema despite their parents having lower rates of allergy than non-Asian parents. Gene-environment interactions may explain the differential effect seen in this minority group.

Antimicrobial efficacy of liposome-encapsulated silver ions and tea tree oil against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans.

UNLABELLED: The activity of alternative antimicrobial agents such as tea tree oil (TTO) and silver ions (Ag(+) ) with multiple target sites impedes the development of antibacterial resistance and might be useful in improving the current treatment strategies for various chronic wound infections. In this study, liposome-encapsulated TTO, Ag(+) and TTO plus Ag(+) were added to suspension cultures of Pseudomonas aeruginosa (Ps. aeruginosa), Staphylococcus aureus (Staph. aureus) and Candida albicans (C. albicans). Treatment of these cultures using the agents in combination at subminimal lethal concentrations resulted in an enhanced loss of viability compared to treatment with individual agents. The effective concentration, elimination time (to the limit of detection, LOD) and fractional lethal concentration index (FLCI) of liposomal agents in combination were as follows: Candida albicans: 0·05% v/v TTO:PVA30-70 kDa : 8·9 × 10(-5) % w/v Ag(+) :PVA30-70 kDa : 2·0 h, FLCI = 0·73 (indifferent), Staphylococcus aureus: 0·05% v/v TTO:PVA30-70 kDa : 6·0 × 10(-4) % w/v Ag(+) :PVA30-70 kDa : 1·5 h, FLCI = 0·38 (synergistic), Pseudomonas aeruginosa: 0·25% v/v TTO:PVA30-70 kDa : 3·2 × 10(-4) % w/v Ag(+) :PVA30-70 kDa : 30 min, FLCI = 0·33 (synergistic). These results show the potential for improving antimicrobial efficacy by delivering lower effective concentrations of alternative agents, via controlled release systems. NB All values denoted as %w/vAg(+) refer to the concentration of silver ions. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we have shown that encapsulating silver (as the ion Ag(+) ) and tea tree oil (singly and in combination) in a controlled release liposomal carrier system can improve their antimicrobial efficacy as well as reduce the effective concentration required. These findings may impact on the problems of agent toxicity caused by the need for high effective doses or microbial resistance where long term application is required.

Persistent pollen exposure during infancy is associated with increased risk of subsequent childhood asthma and hayfever.

BACKGROUND: Few studies have focused on pollen exposure and asthma in children. None have examined associations between persistent exposure to pollen in infancy and aeroallergen sensitisation and asthma in childhood. OBJECTIVES: To examine the association between higher ambient levels of pollen in the first 3-6 months of life and risk of eczema, sensitization to food and aeroallergens at 2 years and asthma or hayfever at age 6-7 years combined. METHODS: Using a birth cohort of 620 infants with a family history of allergic disease born between 1990 and 1994, we examined risk of eczema or allergic sensitization (SPT > 3 mm to at least one of cow's milk, egg white, peanut, house dust-mite, rye grass, and cat dander) by age 2 and asthma or hayfever at age 6-7. Daily ambient levels of pollen were measured during this period. RESULTS: Cumulative exposure to pollen concentrations up to 6 months was associated with aeroallergen sensitization with the highest risk occurring at 3 months (aOR = 1.34, 95% CI 1.06-1.72). Cumulative exposure to pollen up to 3 months was also associated with hayfever (aOR = 1.14, 95% CI 1.009-1.29) and between 4 and 6 months exposure with asthma only (aOR=1.35, 95% CI 1.07-1.72). CONCLUSION: Persistent pollen exposure in infancy appears to increase the risk of asthma and hayfever in children. These results support the hypothesis that there is a critical window of opportunity in early development which may be important for modification of allergic outcomes.

Population and age-group trends in weekend sun protection and sunburn over two decades of the SunSmart programme in Melbourne, Australia.

BACKGROUND: In response to the high skin cancer burden in Australia, the multicomponent, community-wide SunSmart programme has worked since 1988 to reduce excessive sun exposure. OBJECTIVE: To examine trends in key sun-protection behaviours and sunburn for the Melbourne population from 1987 to 2007, and examine for the first time patterns of change among age groups. METHODS: Representative cross-sectional weekly telephone surveys of weekend sun protection and sunburn were conducted over 11 of the summers in the period 1987-88 to 2006-07. Trends were analysed for the population and for age groups, adjusting for ambient temperature and ultraviolet radiation, which are environmental determinants of sun-related behaviour and sunburn. RESULTS: The general pattern of trends suggests two distinct periods, one with rapid improvement in behaviours (more sunscreen use, less unprotected body exposure and less sunburn) from 1987-88 to 1994-95, and the second from 1997-98 to 2006-07 with fewer changes in behaviours noted. The age-group analyses showed a similar pattern of change over time across groups, with a few notable exceptions. CONCLUSIONS: The similarity of the pattern of trends among age groups suggests that external influences including the SunSmart programme's activity had a relatively similar impact across the population. Sun-related behaviours continue to be amenable to change. More recent relative stability with some declines in sun protection suggests further intensive campaigns and other strategies may be needed to maintain previous successes and to achieve more universal use of sun protection.

Environmental and demographic risk factors for egg allergy in a population-based study of infants.

BACKGROUND: Although egg allergy is the most common food allergy in infants and young children, risk factors for egg allergy remain largely unknown. This study examined the relationship between environmental and demographic factors and egg allergy in a population-based infant cohort. METHODS: In a study of 5276 infants (HealthNuts), infants underwent skin prick testing (SPT) to egg white at 12 months of age. Questionnaire data on relevant exposures were obtained. 699/873 (80%) infants eligible for oral food challenge (detectable wheal on SPT) attended for formal assessment of egg allergy status; 453 had confirmed egg allergy (positive challenge and SPT ≥ 2 mm). Associations between environmental and demographic factors and egg allergy were investigated using multivariable logistic regression. RESULTS: Children with older siblings and those with a pet dog at home were less likely to develop egg allergy by 1 year of age (adjusted OR [aOR], 0.72; 95% CI, 0.62, 0.83 per sibling; and aOR, 0.72; 95% CI, 0.52, 0.99, respectively). Caesarean section delivery, antibiotic use in infancy, childcare attendance and maternal age were not associated with egg allergy. History of allergic disease in an immediate family member and having parents born in East Asia were strong risk factors for infantile egg allergy (aOR, 1.82; 95% CI, 1.40, 2.36; and aOR, 3.30; 95% CI, 2.45, 4.45, respectively). CONCLUSIONS: Exposure in the first year of life to siblings and dogs may decrease the risk of subsequent egg allergy. Infants with a family history of allergy and those with parents born in East Asia are at increased risk of egg allergy.

Pets at birth do not increase allergic disease in at-risk children.

BACKGROUND: The literature is contradictory concerning pet exposure and risk of allergic disease in childhood especially among those with a family history of allergy. OBJECTIVE: To investigate the relationship between cat and dog exposure at birth and allergic outcomes over the first 12 years in a birth cohort selected for familial allergy. METHODS: A prospective birth cohort of 620 infants with a family history of allergic diseases was recruited. Data on pet keeping, family demographics and cord blood samples were collected at birth. Information on childhood wheeze, eczema and hay fever was collected 18 times in the first 2 years, at 7 years and at 12 years. Skin prick tests were conducted at 2, 7 and 12 years, and in parents. Regression analyses were used to investigate the relevant associations while adjusting for potential confounders. RESULTS: Exposure to cats or dogs at birth showed a moderate reduction in risk of wheeze (aOR = 0.76; 95% CI 0.53, 1.09) and hay fever (aOR = 0.71; 0.49, 1.02) after 7 years of age. Protective effects were stronger in children of non-sensitized fathers (aOR wheeze 0.55; 0.31, 0.98; aOR hay fever 0.33; 0.15, 0.77 on exposure to cats alone, or cats or dogs at birth). Pet keeping was not related to cord blood IgE or sensitization from 2 to 12 years. CONCLUSIONS AND CLINICAL RELEVANCE: Pets at birth either decreased or had no effect on allergic disease up to age 12. We found no evidence that exposure to cats or dogs at birth increases the risk of allergic disease in high-risk children.

Converging shocks in elastic-plastic solids.

We present an approximate description of the behavior of an elastic-plastic material processed by a cylindrically or spherically symmetric converging shock, following Whitham's shock dynamics theory. Originally applied with success to various gas dynamics problems, this theory is presently derived for solid media, in both elastic and plastic regimes. The exact solutions of the shock dynamics equations obtained reproduce well the results obtained by high-resolution numerical simulations. The examined constitutive laws share a compressible neo-Hookean structure for the internal energy e=e(s)(I(1))+e(h)(ρ,ς), where e(s) accounts for shear through the first invariant of the Cauchy-Green tensor, and e(h) represents the hydrostatic contribution as a function of the density ρ and entropy ς. In the strong-shock limit, reached as the shock approaches the axis or origin r=0, we show that compression effects are dominant over shear deformations. For an isothermal constitutive law, i.e., e(h)=e(h)(ρ), with a power-law dependence e(h) is proportional to ρ(α), shock dynamics predicts that for a converging shock located at r=R(t) at time t, the Mach number increases as M is proportional to [log(1/R)](α), independently of the space index s, where s=2 in cylindrical geometry and 3 in spherical geometry. An alternative isothermal constitutive law with p(ρ) of the arctanh type, which enforces a finite density in the strong-shock limit, leads to M is proportional to R(-(s-1)) for strong shocks. A nonisothermal constitutive law, whose hydrostatic part e(h) is that of an ideal gas, is also tested, recovering the strong-shock limit M is proportional to R(-(s-1)/n(γ)) originally derived by Whitham for perfect gases, where γ is inherently related to the maximum compression ratio that the material can reach, (γ+1)/(γ-1). From these strong-shock limits, we also estimate analytically the density, radial velocity, pressure, and sound speed immediately behind the shock. While the hydrostatic part of the energy essentially commands the strong-shock behavior, the shear modulus and yield stress modify the compression ratio and velocity of the shock far from the axis or origin. A characterization of the elastic-plastic transition in converging shocks, which involves an elastic precursor and a plastic compression region, is finally exposed.

Antimicrobial efficacy of silver ions in combination with tea tree oil against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans.

Tea tree oil (TTO) and silver ions (Ag(+)), either alone or in combination with other antimicrobial compounds, have been used in the treatment of topical infections. However, there appears to be little data on the efficacy of TTO combined with silver in the absence of any other agents. TTO and Ag(+) were added, alone and in combination, to suspension cultures of Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Treatment of these cultures with TTO and Ag(+) at sub-minimal lethal concentrations resulted in an enhanced loss of viability compared with treatment with individual agents. The order of sensitivity to the combined agents was P. aeruginosa>S. aureus>C. albicans. The fractional lethal concentration index (FLCI) showed that these combinations of TTO and Ag(+) exerted a synergistic effect against P. aeruginosa (FLCI=0.263) and an indifferent effect against S. aureus and C. albicans (FLCI=0.663 and 1.197, respectively). The results indicate that combining these antimicrobial agents may be useful in decreasing the concentration of antimicrobial agents required to achieve an effective reduction in opportunistic pathogenic microorganisms that typically infect wounds.

Linearized Richtmyer-Meshkov flow analysis for impulsively accelerated incompressible solids.

We present an analytical study of the linearized impulsive Richtmyer-Meshkov flow for incompressible elastic solids. Seminumerical prior investigations of a related shock-driven compressible elastic problem suggest that the interface amplitude remains bounded in time, in contrast to the unstable behavior found for gases. Our approach considers a base unperturbed flow and a linearization of the conservation equations around the base solution. The resulting initial and boundary value problem is solved using Laplace transform techniques. Analysis of the singularities of the resultant function in the Laplace domain allows us to perform a parametric study of the behavior of the interface in time. We identify two differentiated long-term patterns for the interface, which depends on the material properties: standing wave and oscillating decay. Finally, we present results for the vorticity distribution, which show that the shear stiffness of the solids is responsible both for the stabilization of the interface, and also for the period of the interface oscillations. Comparisons with previous results are discussed.

Lineage tracing and resulting phenotype of haemopoietic-derived cells in the pancreas during beta cell regeneration.

AIMS: Transplantation of bone marrow-derived haemopoietic stem cells following streptozotocin (STZ) treatment to induce pancreatic beta cell loss in mice causes the partial regeneration of beta cell mass, with many haemopoietic cells demonstrating endothelial cell markers. This study used genetically tagged haemopoietic lineage-derived cells to determine how endogenous cells are mobilised following beta cell loss and subsequent replacement. METHODS: A double transgenic mouse model, Vav-iCre; R26R-enhanced yellow fluorescent protein (YFP), was used where only haemopoietic lineage cells expressed the Vav1 gene promoter allowing expression of the YFP reporter gene. Between postnatal days 2 and 4 mice were injected with STZ or vehicle (control) and body weight and glycaemia were monitored. Mice were killed between days 10 and 130, and the pancreases were examined by immunofluorescence microscopy. RESULTS: YFP-expressing cells infiltrated the pancreas at all ages, being present around newly forming islets at the pancreatic ducts, and within larger islets. Small numbers of YFP-positive cells (<5%) co-stained for the macrophage markers F4/80 or Mac1, for cytokeratin 19, or for the transcription factor pancreatic and duodenal homeobox 1 (PDX-1), but no co-localisation was seen with insulin or other endocrine hormones. Within islets approximately 30% of YFP-positive cells co-stained for the endothelial cell marker CD31, and following STZ the number of haemopoietic-derived cells, and the proportion that were CD31-positive, both significantly increased after 21 and 40 days, coincident with a partial replacement of beta cells. CONCLUSIONS: Our results suggest that following beta cell loss endogenous haemopoietic-lineage cells contribute to intra-islet angiogenesis, which supports a partial recovery of beta cell mass.

Effects of atorvastatin on the regeneration of pancreatic {beta}-cells after streptozotocin treatment in the neonatal rodent.

To investigate the role of statins in beta-cell regeneration a model of streptozotocin (STZ)-induced beta-cell injury was used in the neonatal rat. We hypothesized that beta-cell growth and regeneration would increase following treatment with atorvastatin and that this would be associated with intraislet vasculogenesis. Pregnant Wistar rats were gavaged with 20 or 40 mg/kg atorvastatin for 21 days commencing on gestation day 15. Atorvastatin was detected in the circulation of the offspring. On postnatal day 4, the pups were given either a control or STZ (70 mg/kg ip) injection. beta-Cell mass had partially recovered by postnatal day 44 following STZ treatment, and atorvastatin (20 mg/kg) significantly increased beta-cell mass in both STZ-treated and control animals. An increase in the numbers of small islets at postnatal day 44 was seen in STZ-treated animals following atorvastatin, suggestive of neogenesis, and glucose tolerance was improved. Treatment with atorvastatin caused an increase in the numbers of intraislet endothelial cells at postnatal day 14 and the percentage of endothelial cells undergoing DNA synthesis, suggesting that angiogenesis had preceded the increase in beta-cell mass. The results indicate that functional beta-cell mass was expanded with atorvastatin in both control and STZ-treated neonatal rats and suggests a novel effect of a statin in promoting islet plasticity.