Melanocytic naevi and melanoma in survivors of childhood cancer.

There is evidence from previous studies of small numbers of children who received cytotoxic therapy for cancer, that they may develop increased numbers of melanocytic naevi (moles), the strongest known risk factors for melanoma. Our aim was to investigate a large number of survivors of childhood cancer in order to test the hypothesis that they have more melanocytic naevi than matched controls. Total-body naevus counts were obtained from 263 oncology patients ascertained in paediatric oncology departments in Queensland, Australia, and from 263 hospital controls matched for age and sex. Additional information was gathered from children's parents about concurrent factors influencing naevus development such as type of complexion and history of sun exposure. Matched analyses, both crude and adjusted for possible confounding factors, revealed no significant difference in overall density of naevi among oncology patients and control subjects, according to diagnosis or to duration or type of chemotherapy. However significantly more oncology patients had atypical naevi (P < 0.05) and acral naevi (P < 0.0001) than controls. One patient developed a malignant melanoma 13 years after chemotherapy and radiotherapy for rhabdomyosarcoma. These findings support an association between treatment for childhood cancer and acral naevi and suggest that atypical naevi may also be associated with chemotherapy in childhood

The prevalence of naturally acquired multiple infections of Wuchereria bancrofti and human malarias in anophelines

Malaria and filaria infection rates were determined for anopheline mosquitoes collected whilst biting and resting in village houses in Papua New Guinea. The number of anophelines infected with both parasites was greater than expected from the infection rates of each parasite and this difference was significant in resting collections. The excess of multiply infected mosquitoes is probably a result of a vector population composed of individuals with differing numbers of opportunities to become infected. Malaria-positive, Anopheles punctulatus from resting catches had a significantly greater number of Stage 3 Wuchereria bancroftilarvae than malaria-negative mosquitoes. However, multiply infected mosquitoes appear to suffer greater mortality than non-infected or singly infected mosquitoes when the filarial worm reaches the third stage. Any potential increase in transmission resulting from multiple infections is thereby offset by a greater mortality rate in these mosquitoe

Exercise for health: a randomized, controlled trial evaluating the impact of a pragmatic, translational exercise intervention on the quality of life, function and treatment-related side effects following breast cancer

Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Outcomes included quality of life (QoL), function (fitness and upper body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5 weeks PS], mid-intervention [6 months PS], post-intervention [12 months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n = 67), Tel (n = 67) and UC (n = 60) groups. There were significant (p < 0.05) interaction effects on QoL, fitness and fatigue with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side effects between groups. This translational intervention trial, delivered either FtF or Tel, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment

Synthetic Biology of Proteins: Tuning GFPs Folding and Stability with Fluoroproline

Proline residues affect protein folding and stability via cis/trans isomerization of peptide bonds and by the C(gamma)-exo or -endo puckering of their pyrrolidine rings. Peptide bond conformation as well as puckering propensity can be manipulated by proper choice of ring substituents, e.g. C(gamma)-fluorination. Synthetic chemistry has routinely exploited ring-substituted proline analogs in order to change, modulate or control folding and stability of peptides.In order to transmit this synthetic strategy to complex proteins, the ten proline residues of enhanced green fluorescent protein (EGFP) were globally replaced by (4R)- and (4S)-fluoroprolines (FPro). By this approach, we expected to affect the cis/trans peptidyl-proline bond isomerization and pyrrolidine ring puckering, which are responsible for the slow folding of this protein. Expression of both protein variants occurred at levels comparable to the parent protein, but the (4R)-FPro-EGFP resulted in irreversibly unfolded inclusion bodies, whereas the (4S)-FPro-EGFP led to a soluble fluorescent protein. Upon thermal denaturation, refolding of this variant occurs at significantly higher rates than the parent EGFP. Comparative inspection of the X-ray structures of EGFP and (4S)-FPro-EGFP allowed to correlate the significantly improved refolding with the C(gamma)-endo puckering of the pyrrolidine rings, which is favored by 4S-fluorination, and to lesser extents with the cis/trans isomerization of the prolines.We discovered that the folding rates and stability of GFP are affected to a lesser extent by cis/trans isomerization of the proline bonds than by the puckering of pyrrolidine rings. In the C(gamma)-endo conformation the fluorine atoms are positioned in the structural context of the GFP such that a network of favorable local interactions is established. From these results the combined use of synthetic amino acids along with detailed structural knowledge and existing protein engineering methods can be envisioned as a promising strategy for the design of complex tailor-made proteins and even cellular structures of superior properties compared to the native forms