Perfluoro-tert-butanol for selective on-resin detritylation: a mild alternative to traditionally used methods

Amino Acids - Solid-phase synthesis of cyclic, branched or side-chain-modified peptides typically involves introduction of a residue carrying a temporary side-chain protecting group that undergoes...     

Trends in Prevalence of Overweight and Obesity in Danish Infants,Children and Adolescents – Are We Still on a Plateau?

Background

After the worldwide steep increase in child and adolescent overweight and obesity during the last decades, there is now evidence of a levelling off in the prevalence in many countries in the Western world.

Aim

To examine whether there still is a plateau in the prevalence of overweight and obesity in Danish children and adolescents, or whether the prevalence is decreasing or rising again.

Methods

The trends in the prevalence rates were based on three data sets providing comparable repeated estimates: 1) the Danish Health Visitors Child Health Database (DHVCHD) with measurements on infant and childhood height and weight from 2002 to 2011 (n up to 39,984), 2) the Danish National Birth Cohort (DNBC) with maternal reports of measured infant and childhood height and weight from 1998 to 2010 (n up to 56,826) and 3) the Danish part of the Health Behaviour in School-aged Children survey (HBSC) with self-reported information on adolescent height and weight from the years 2002 to 2010 (n = 16,557). Overweight and obesity were categorized according to WHO growth standards. Trends were assessed by repeated point estimates and linear regression analyses providing regression coefficients for changes in per cent per year with 95% confidence intervals (CI).

Results

The prevalence rates of overweight and obesity for infants, children and adolescents showed a mixed pattern of decline, stability and increase (ranging from -1.10 through 0.29 per cent per year with CI’s from -3.10 through 2.37). Overall, there were no consistent statistically significant trends upwards or downwards, although some significant downward trends in childhood and adolescence were observed.

Conclusion

This study, based on data from 1998 through 2011, showed that the prevalence rates of overweight and obesity among Danish infants, children and adolescents were largely still on a plateau with tendencies for a decline among children and adolescents.     

[18F]FLT and [18F]FDG PET for Non-invasive Treatment Monitoring of the Nicotinamide Phosphoribosyltransferase Inhibitor APO866 in Human Xenografts

Introduction

APO866 is a new anti-tumor compound inhibiting nicotinamide phosphoribosyltransferase (NAMPT). APO866 has an anti-tumor effect in several pre-clinical tumor models and is currently in several clinical phase II studies. 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) is a tracer used to assess cell proliferation in vivo. The aim of this study was non-invasively to study effect of APO866 treatment on [18F]FLT and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake.

Methods

In vivo uptake of [18F]FLT and [18F]FDG in human ovary cancer xenografts in mice (A2780) was studied at various time points after APO866 treatment. Baseline [18F]FLT or [18F]FDG scans were made before treatment and repeated after 24 hours, 48 hours and 7 days. Tumor volume was followed with computed tomography (CT). Tracer uptake was quantified using small animal PET/CT. One hour after iv injection of tracer, static PET scans were performed. Imaging results were compared with Ki67 immunohistochemistry.

Results

Tumors treated with APO866 had volumes that were 114% (24 h), 128% (48 h) and 130% (Day 7) relative to baseline volumes at Day 0. In the control group tumor volumes were 118% (24 h), 145% (48 h) and 339% (Day 7) relative to baseline volumes Day 0. Tumor volume between the treatment and control group was significantly different at Day 7 (P = 0.001). Compared to baseline, [18F]FLT SUVmax was significantly different at 24 h (P<0.001), 48 h (P<0.001) and Day 7 (P<0.001) in the APO866 group. Compared to baseline, [18F]FDG SUVmax was significantly different at Day 7 (P = 0.005) in the APO866 group.

Conclusions

APO866 treatment caused a significant decrease in [18F]FLT uptake 24 and 48 hours after treatment initiation. The early reductions in tumor cell proliferation preceded decrease in tumor volume. The results show the possibility to use [18F]FLT and [18F]FDG to image treatment effect early following treatment with APO866 in future clinical studies.     

Particle-Induced Pulmonary Acute Phase Response Correlates with Neutrophil Influx Linking Inhaled Particles and Cardiovascular Risk

Background

Particulate air pollution is associated with cardiovascular disease. Acute phase response is causally linked to cardiovascular disease. Here, we propose that particle-induced pulmonary acute phase response provides an underlying mechanism for particle-induced cardiovascular risk.

Methods

We analysed the mRNA expression of Serum Amyloid A (Saa3) in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes), diesel exhaust particles and airborne dust collected at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes.

Results

Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points.

Conclusions

Pulmonary acute phase response may constitute a direct link between particle inhalation and risk of cardiovascular disease. We propose that the particle-induced pulmonary acute phase response may predict risk for cardiovascular disease.     

Fertility of gynogenetic Atlantic cod (Gadus morhua L.)

In order to investigate whether meiotic gynogenetic Atlantic cod is fertile and able to produce viable offspring, meiotic gynogenetic females were produced in spring 2010 by activating cod eggs using irradiated sperm. The extrusion of the second polar body was prevented by the application of hydrostatic pressure (56.6 MPa) 36 min after fertilization. In February 2012, their mean round weight was 972 g, and 2580 g in March 2013. In 2012, when the fish were 2 years old, about 52% were mature, 33% were immature, and 13% had undifferentiated gonads. One year later, 77% were mature, 11% were immature, and 11% had undifferentiated gonads. Several of the mature females had malformed gonads, with only one developed ovary lobe or with the two lobes fused. The mean gonadosomic index (GSI) of the 2‐year‐old mature females was 5.2%, with an estimated relative fecundity of 581 000 eggs kg ovary‐free wet weight^?1. Females were stripped for eggs when 2 and 3 years old (2012 and 2013), and fertilized with sperm from normal males. Offspring were obtained from 12 of 17 and 12 of 15 egg batches incubated in 2012 and 2013, respectively, proving that the gynogenetic females are fertile. Furthermore, larvae in all but one of the hatched groups from 2013 had commenced feeding 2 h after being startfed using rotifers 4 days after hatch, indicating viable offspring.     

Life-and-Death Decisions in a Neonatal Intensive Care Unit in Denmark: The Discrete Authority of Origin Stories

In what ways are care and compassion implicated in efforts to establish lives worth living? Drawing on fieldwork in a Danish Neonatal Intensive Care Unit (NICU), in this article we investigate the role of family biographies in conducting life-and-death decisions around premature infants. Guided by a larger literature on citizenship, we view decisions in the NICU as political acts of assigning citizenship. We ask what bodies and biographies can generate and evoke care and compassion among NICU staff and forge entries or exits from the Danish Welfare State. We demonstrate that infants’ origin stories are appointed legitimate forms of suffering in contemporary Danish society and are thus granted an unnoticed form of authority in life-and-death decisions. In this way, we conclude that what comes to constitute a life worth living in the twenty-first-century Danish Welfare State is in fact the worth of the family.     

Associations between dru Types and SCCmec Cassettes

Molecular typing is an important tool in the investigation of methicillin resistant Staphylococcus aureus (MRSA) outbreaks and in following the evolution of MRSA. The staphylococcal cassette chromosome mec (SCCmec) contains a hypervariable region with a variable number of 40 bp repeats named direct repeat units (dru). The dru region has been suggested as a supplementary typing method for MRSA and an international nomenclature exists. The purpose of this study was to investigate the diversity and variability of the dru region in a diverse collection of MRSA. We studied 302 MRSA isolates harbouring SCCmec types I to VI. The isolates represented a broad genetic background based on Staphylococcal protein A (spa) typing and multilocus sequence typing (MLST) and included 68 isolates (68 patients) from an outbreak with t024-ST8-IVa and 26 isolates from the same patient. Sequencing identified 53 dru types (dt) in 283 isolates, while eighteen isolates contained no dru repeats and one isolate resisted sequencing. The most common dru type, dt10a, was present in 53% of the sequenced isolates and was found in all SCCmec types, except type II. Seven (10%) of the 68 epidemiologically related patients had isolates with dru type variants indicating that dru typing is not useful as a first line epidemiological typing tool. However, MRSA isolates cultured from a single patient over a three year period exhibited a single dru type. The finding of dt10a in most SCCmec types suggests that dru and mecA originate from the same Staphylococcus species.     

Modelled population growth based on reproduction differs from life tables based on age determination in Danish raccoon dogs ( Nyctereutes procyonoides )

The population of raccoon dogs (Nyctereutes procyonoides) in Denmark has increased rapidly from 1995 when the first was recorded until today where 3291 raccoon dogs are trapped, shot by hunters or road killed. The aims of this study are to present the first data on reproduction and life tables of raccoon dogs in Denmark and to compare mortality from modelled life tables with game bag records and sampled raccoon dogs in different age groups. In this study, the uteri of 89 adult females (> 10 months) were examined for placental scars (PSC), and 561 individuals (289 males, 272 females) were aged using pulp cavity width and dental lines in canine teeth. The litter size of raccoon dogs in Denmark is to date the largest litter size recorded in the wild (mean ± SE) 10.8 ± 0.4, range 1–16 pubs and fecundity 8.4 ± 0.6 pubs. The percent-reproducing females are 78–83%, based on dark and all PSC, respectively. A significant difference was found between the proportion of individuals composing the different age groups based on age determination of individuals collected (Ntage) and the modelled number of individuals in age groups based on fecundity and different mortality rate (Ntmodel), X2 = 8, p < 0.05. The discrepancy between the relatively high reproduction and lifetables may be due to older and more experienced animals that avoid culling. A low population density in a newly founded Danish population of raccoon dogs, together with a milder climate where raccoon dogs can forage during the winter, may cause an exceptionally high reproduction in Danish raccoon dogs.