Prevalences of nevi and solar keratoses differ markedly between patients with head and neck melanomas or LMM and patients with melanomas of the trunk. Cutaneous melanomas may arise through two pathways, one associated with melanocyte proliferation and the other with chronic exposure to sunlight.

A B S T R A C T PurposeSunlight is the principal environmental risk factor for cutaneous melanoma. A current hypothesis postulates that the role of sunlight in causing melanoma differs according to anatomic site. We tested this hypothesis in a population-based case-case comparative study of melanoma patients. MethodsPatients were sampled from the Queensland cancer registry in three groups: superficial spreading or nodular melanomas of the trunk (n ϭ 154), of the head and neck (HN; n ϭ 76), and lentigo maligna (LM) and lentigo maligna melanoma (LMM; for both LM and LMM, n ϭ 76). Data were collected on school-age sun exposure and occupational and recreational sun exposure in adulthood. Odds ratios (OR) and 95% CIs were calculated using polytomous logistic regression. ResultsHN melanoma patients were substantially more likely than trunk patients to have higher levels of sun exposure in adulthood (OR, 2.43; 95% CI, 0.98 to 5.99) and specifically, higher levels of occupational exposure (OR, 3.25; 95% CI, 1.32 to 8.00), but lower levels of recreational sun exposure (OR, 0.50; 95% CI, 0.21 to 1.19). LM and LMM patients reported higher occupational exposure and lower recreational sun exposure than trunk melanoma patients, although this was not significant. We found no significant differences between the groups for school-age sun exposures. ConclusionMelanomas developing at different body sites are associated with distinct patterns of sun exposure. Melanomas of the head and neck are associated with chronic patterns of sun exposure whereas trunk melanomas are associated with intermittent patterns of sun exposure, supporting the hypothesis that melanomas may arise through divergent causal pathways. J Clin Oncol 24:3172-3177. © 2006 by American Society of Clinical Oncology INTRODUCTIONSeveral decades of research have confirmed that the relationship between sun exposure and melanoma is complex and is strongly modified by host factors including pigmentation and propensity to develop nevi. 1 The pattern of exposure to sunlight has been hypothesized to be the key determinant in melanoma development, with intermittent exposure considered to be causal and chronic exposure protective.2 While epidemiologic evidence has accumulated in support of the intermittent exposure hypothesis, 3 several features of the occurrence of melanoma indicate that chronic exposure to sunlight has a causal role.We have previously proposed a divergent pathway model for cutaneous melanoma irrespective of histologic classification which seeks to explain the development of melanoma by incorporating the role of sunlight, host susceptibility, and anatomic site. 4,5 In support of this model, we found marked differences in the prevalence of nevi and solar keratoses between patients with head and neck melanomas and those with trunk melanomas. 5 Similar findings have been reported by others, 6,7 and coupled with emerging molecular evidence that somatic genetic aberrations in cutaneous melanoma also vary by site, 8,9 suggest that melanomasarisingatdifferentanatom...

Background Muscle wasting and weakness in Duchenne muscular dystrophy (DMD) causes severe locomotor limitations and early death due in part to respiratory muscle failure. Given that current clinical practice focuses on treating secondary complications in this genetic disease, there is a clear need to identify additional contributions in the aetiology of this myopathy for knowledge‐guided therapy development. Here, we address the unresolved question of whether the complex impairments observed in DMD are linked to elevated mitochondrial H 2 O 2 emission in conjunction with impaired oxidative phosphorylation. This study performed a systematic evaluation of the nature and degree of mitochondrial‐derived H 2 O 2 emission and mitochondrial oxidative dysfunction in a mouse model of DMD by designing in vitro bioenergetic assessments that attempt to mimic in vivo conditions known to be critical for the regulation of mitochondrial bioenergetics. Methods Mitochondrial bioenergetics were compared with functional and histopathological indices of myopathy early in DMD (4 weeks) in D2.B10‐DMD mdx /2J mice (D2. mdx )—a model that demonstrates severe muscle weakness. Adenosine diphosphate's (ADP's) central effect of attenuating H 2 O 2 emission while stimulating respiration was compared under two models of mitochondrial‐cytoplasmic phosphate exchange (creatine independent and dependent) in muscles that stained positive for membrane damage (diaphragm, quadriceps, and white gastrocnemius). Results Pathway‐specific analyses revealed that Complex I‐supported maximal H 2 O 2 emission was elevated concurrent with a reduced ability of ADP to attenuate emission during respiration in all three muscles (mH 2 O 2 : +17 to +197% in D2. mdx vs. wild type). This was associated with an impaired ability of ADP to stimulate respiration at sub‐maximal and maximal kinetics (−17 to −72% in D2. mdx vs. wild type), as well as a loss of creatine‐dependent mitochondrial phosphate shuttling in diaphragm and quadriceps. These changes largely occurred independent of mitochondrial density or abundance of respiratory chain complexes, except for quadriceps. This muscle was also the only one exhibiting decreased calcium retention capacity, which indicates increased sensitivity to calcium‐induced permeability transition pore opening. Increased H 2 O 2 emission was accompanied by a compensatory increase in total glutathione, while oxidative stress markers were unchanged. Mitochondrial b...

We investigated the validity of food intake estimates obtained by a self-administered FFQ relative to weighed food records (WFR) and the extent to which demographic, anthropometric, and social characteristics explain differences between these methods. A community-based sample of 96 Australian adults completed a FFQ and 12 d of WFR over 12 mo. The FFQ was adapted to the Australian setting from the questionnaire used in the US Nurses' Health Study. Spearman rank correlation coefficients ranged from 0.08 for "other vegetables" to 0.88 for tea. Exact agreement by quartiles of intake ranged from 27% (eggs) to 63% (tea). Differences between FFQ and WFR regressed on personal characteristics were significantly associated with at least 1 characteristic for 20 of the 37 foods. Sex was significantly associated with differences for 17 food groups, including 5 specific vegetable groups and 2 "total" fruit and vegetable groups. Use of dietary supplements and the presence of a medical condition were associated with differences for 5 foods; age, school leaving age, and occupation were associated with differences for 1-3 foods. BMI was not associated with differences for any foods. Regression models explained from 3% (whole-meal bread) to 37% (for all cereals and products) of variation in differences between methods. We conclude that the relative validity of intake estimates obtained by FFQ is different for men and women for a large number of foods. These results highlight the need for appropriate adjustment of diet-disease relations for factors affecting the validity of food intake estimates.

Like human fathers, male marmosets help raise their young, yet the ways in which fatherhood influences the brain remain largely unknown. We show that first-time and experienced marmoset fathers have enhanced density of dendritic spines on pyramidal neurons in prefrontal cortex as compared to non-fathers. In parallel, the abundance of vasopressin V1a receptors and the proportion of V1a receptor-labeled dendritic spines increase.