Experimental delayed contact sensitization to diazolidinyl urea (Germall II) in guinea pigs

Diazolidinyl urea (Germall II) is a new preservative recommended for use in certain consumer products. Although 2 reports document the human sensitization rates of this preservative, no publications quantify its sensitization potential in controlled animal experiments. Diazolidinyl urea induced mild sensitization (grade 2) under maximization test conditions. Further, there was evidence of cross-reactions with both imidazolidinyl urea (Germall 115) and formaldehyde in diazolidinyl-urea-sensitized animals. Rechallenge of diazolidinyl-urea-sensitized animals with diazolidinyl urea 4 weeks following the primary challenge only elicited a weak response (0.5) from 1 animal out of 8.     

Contact sensitizers downregulate the expression of the chemokine receptors CCR6 and CXCR4 in a skin dendritic cell line

Chemokines are involved in the control of dendritic cell (DC) trafficking, which is critical for the immune response, namely in allergic contact dermatitis (ACD). In this work, we investigated by flow cytometry the effect of the contact sensitizers 2,4-dinitrofluorobenzene (DNFB), 1,4-phenylenediamine (PPD) and nickel sulfate (NiSO₄), on the surface expression of the chemokine receptors CCR6 and CXCR4 in DC. As an experimental model of a DC we used a fetal skin-derived dendritic cell line (FSDC), which has morphological, phenotypical and functional characteristics of skin DC. Our results show that all the skin sensitizers studied decreased the membrane expression of the chemokine receptors CCR6 and CXCR4. In contrast, 2,4-dichloronitrobenzene (DCNB), the inactive analogue of DNFB without contact sensitizing properties, was without effect on the surface expression of these receptors. Lipopolysaccharide (LPS), which induces the maturation of DC, also reduced surface CCR6 and CXCR4 expression.     

North American male reference population for speed of sound in bone at multiple skeletal sites.

Alternatives to dual-energy X-ray absorptiometry (DXA) have been sought to increase access to low-cost osteoporosis risk assessment. Early quantitative ultrasound (QUS) systems measured speed of sound (SOS) and broadband ultrasound attenuation (BUA) at the calcaneus, and these were demonstrated to be good predictors of hip fracture risk. Recent studies have demonstrated the usefulness of other peripheral sites to assess bone status. The Sunlight Omnisense (Sunlight Medical, Rehovot, Israel) is a portable, inexpensive QUS device capable of multiple-site SOS measurement. To provide a robust male reference database, 588 healthy Caucasian males aged 20-90 yr were recruited from 6 centers across North America. SOS measurements were taken at the distal 1/3 radius, proximal third phalanx, midshaft tibia, and fifth metatarsal. A female reference database has previously been collected at North American sites. The results indicate that SOS in males exhibits an age-related decline beginning in the fifth decade at the radius, phalanx, and metatarsal, whereas the tibial SOS remains nearly constant until the ninth decade. Although females reach a higher-peak SOS than males at most sites, SOS is higher in males at all sites after the sixth decade, as a result of a more gradual decline in SOS. Longitudinal monitoring of healthy men should be performed to confirm these cross-sectional results.     

Transmission of programming effects across generations

Numerous epidemiological studies have shown that exposure to an adverse environment in early life is associated with a substantially increased risk of later disease; a phenomenon termed 'early life programming'. There is increasing evidence that these effects may not be limited to the first, directly exposed generation but may also be transmissible to subsequent generations through non-genomic mechanisms. There are a number of mechanisms which may underpin the intergenerational transmission of the programmed phenotype, including persistence of the abnormal environment across generations, programmed effects on maternal physiology and the transmission of epigenetic information through the germline. In this review we discuss the evidence for these mechanisms in human and animal studies and the potential importance of this field for child health.     

Serum total hCGβ level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract

Background:

Serum total human chorionic gonadotrophin β subunit (hCGβ) level might have prognostic value in urothelial transitional cell carcinoma (TCC) but has not been investigated for independence from other prognostic variables.

Methods:

We utilised a clinical database of patients receiving chemotherapy between 2005 and 2011 for urothelial TCC and an independent cohort of radical cystectomy patients for validation purposes. Prognostic variables were tested by univariate Kaplan–Meier analyses and log-rank tests. Statistically significant variables were then assessed by multivariate Cox regression. Total hCGβ level was dichotomised at < vs ⩾2 IU l⁻¹.

Results:

A total of 235 chemotherapy patients were eligible. For neoadjuvant chemotherapy, established prognostic factors including low ECOG performance status, normal haemoglobin, lower T stage and suitability for cisplatin-based chemotherapy were associated with favourable survival in univariate analyses. In addition, low hCGβ level was favourable when assessed either before (median survival not reached vs 1.86 years, P=0.001) or on completion of chemotherapy (4.27 vs 0.42 years, P=0.000002). This was confirmed in multivariate analyses and in patients receiving first- and second-line palliative chemotherapy, and in a radical cystectomy validation set.

Conclusions:

Serum total hCGβ level is an independent prognostic factor in patients receiving chemotherapy for urothelial TCC in both curative and palliative settings.     

Connectivity analysis of novelty process in habitual short sleepers

Neurophysiological processes underlying auditory memory and attention are impaired in habitually short sleepers. The aim of this study was to use dynamic causal modeling (DCM) to study the mechanisms of these impairments in short sleepers. Eight normal sleepers (total sleep time (TST)=7-8h) and nine habitual short sleepers (TST≤6h) participated. The time in bed was increased from habitual (≤6h) to extended (~8.5h) for one week in the short sleep group. Event related potentials (ERPs) were collected using an auditory novelty task in "IGNORE" and "ATTEND" conditions. Fourteen DCM models were considered using different configurations of connections among the following six areas: left and right primary auditory cortices, superior temporal gyri (STG), and inferior temporal gyri (IFG). After fitting the ERPs to the 14 models (separately for the IGNORE and ATTEND conditions), the best model (across subjects) was chosen using the Bayesian model comparison. For both conditions, the connection from right-STG to right-IFG for normal sleepers was significantly greater than habitual short sleepers. This connection did not differ in habitual short sleepers before and after one week of extended sleep time. This connection for normal sleepers was not significantly greater than the habitual short sleepers after one week of extended sleep. These results show that the deficiency of novelty processing, seen in short sleepers, can be explained by the differences in connectivity of the pathway between frontal and temporal brain areas as compared to the normal sleepers. In addition, one week of extended time in bed was not enough to fully normalize this neuronal pathway between STG and IFG in short sleepers.     

Children's palliative care: a global concern

Children's palliative care (CPC) is a specialty in itself, albeit closely related to adult palliative care (World Health Organization (WHO), 2002). However, although there are many children who require palliative care, in much of the world CPC has a poor profile and is inaccessible to those who need it (Downing et al, 2010; Knapp et al, 2011). The provision of high-quality palliative care for children is a global concern, with 27% of the world population being under the age of 15, rising to as many as 49% in countries such as Uganda (WHO, 2010). It has been estimated that as many as 7 million of these children around the world will need palliative care each year (Rushton et al, 2002), although the true figure is likely to be higher. The public health approach to palliative care is key to the development of CPC services, as is the development of models that integrate services into existing health structures.