On the Interplay of Telomeres,Nevi and the Risk of Melanoma

The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or telomere-related SNPs. A total of 796 cases and 770 controls were genotyped for 517 SNPs in 39 telomere-related genes genotyped with a custom-made array. Replication of the top SNPs was conducted in two American populations consisting of 488 subjects from 53 melanoma-prone families and 1,086 cases and 1,024 controls from a case-control study. We estimated odds ratios for associations with SNPs and combined SNP P-values to compute gene region-specific, functional group-specific, and overall P-value using an adaptive rank-truncated product algorithm. In the Mediterranean population, we found suggestive evidence that RECQL4, a gene involved in genome stability, RTEL1, a gene regulating telomere elongation, and TERF2, a gene implicated in the protection of telomeres, were associated with melanoma, the presence of dysplastic nevi and number of nevi, respectively. However, these associations were not found in the American samples, suggesting variable melanoma susceptibility for these genes across populations or chance findings in our discovery sample. Larger studies across different populations are necessary to clarify these associations.     

Effects of Radio-Collars are not Contingent on Socioecological Conditions in Degus

Species-specific research on free-ranging mammals reveals a diversity of effects of radio-collars on behavior, body condition, and fitness. Although these studies indicate rather limited direct effects, radio-collars may cause effects influenced by socio-ecological conditions. Using a 7-year study on a natural population of group-living degus (Octodon degus), we tested the hypothesis that ecological (food availability, burrow density) and social (group size, group male-to-female ratio) conditions modulate effects of radio-collars on body condition (e.g., body mass, ecto- and endoparasite loads, fecal cortisol metabolites) and direct fitness (litter size, adult survival). We determined the effect of radio-collar use on degus by contrasting the presence or absence of radio-collars, quantifying the effects of the number of days carrying a radio-collar, and the relative mass of radio-collars worn by degus in central Chile between 2009 and 2015. Radio-collar use was not associated with direct effects on litter size, adult survival, or with body mass and fecal cortisol metabolites but was linked to low ecto- and endoparasite loads. These seemingly positive effects may reflect decreased mobility, or a research bias for radio-collaring larger, healthier individuals. There was no evidence that ecological and social conditions modulated radio-collar effects on degu body condition and direct fitness. These findings are consistent with evidence from other mammal studies that reported no appreciable detrimental direct or indirect effects of radio-collars. © 2021 The Wildlife Society.     

Physique and Performance of Young Wheelchair Basketball Players in Relation with Classification

The relationships among physical characteristics, performance, and functional ability classification of younger wheelchair basketball players have been barely investigated to date. The purpose of this work was to assess anthropometry, body composition, and performance in sport-specific field tests in a national sample of Italian younger wheelchair basketball players as well as to evaluate the association of these variables with the players’ functional ability classification and game-related statistics. Several anthropometric measurements were obtained for 52 out of 91 eligible players nationwide. Performance was assessed in seven sport-specific field tests (5m sprint, 20m sprint with ball, suicide, maximal pass, pass for accuracy, spot shot and lay-ups) and game-related statistics (free-throw points scored per match, two- and three-point field-goals scored per match, and their sum). Association between variables, and predictivity was assessed by correlation and regression analysis, respectively. Players were grouped into four Classes of increasing functional ability (A-D). One-way ANOVA with Bonferroni’s correction for multiple comparisons was used to assess differences between Classes. Sitting height and functional ability Class especially correlated with performance outcomes, but wheelchair basketball experience and skinfolds did not. Game-related statistics and sport-specific field-test scores all showed significant correlation with each other. Upper arm circumference and/or maximal pass and lay-ups test scores were able to explain 42 to 59% of variance in game-related statistics (P<0.001). A clear difference in performance was only found for functional ability Class A and D. Conclusion: In younger wheelchair basketball players, sitting height positively contributes to performance. The maximal pass and lay-ups test should be carefully considered in younger wheelchair basketball training plans. Functional ability Class reflects to a limited extent the actual differences in performance.     

Alcohol Consumption in Midlife and Cognitive Performance Assessed 13 Years Later in the SU.VI.MAX 2 Cohort

Background

Associations between alcohol consumption and cognitive function are discordant and data focusing on midlife exposure are scarce.

Objective

To estimate the association between midlife alcohol consumption and cognitive performance assessed 13 y later while accounting for comorbidities and diet.

Methods

3,088 French middle-aged adults included in the SU.VI.MAX (1994) study with available neuropsychological evaluation 13 y later. Data on alcohol consumption were obtained from repeated 24h dietary records collected in 1994–1996. Cognitive performance was assessed in 2007–2009 via a battery of 6 neuropsychological tests. A composite score was built as the mean of the standardized individual test scores (mean = 50, SD = 10). ANCOVA were performed to estimate mean differences in cognitive performance and 95% confidence intervals (CI).

Results

In women, abstainers displayed lower cognitive scores than did low-to-moderate alcohol drinkers (1 to 2 drinks/day) (mean difference = −1.77; 95% CI: −3.29, −0.25). In men, heavy drinkers (>3 drinks/day) had higher cognitive scores than did low-to-moderate (1 to 3 drinks/day) (mean difference = 1.05; 95% CI: 0.10, 1.99). However, a lower composite cognitive score was detected in male drinkers consuming ≥90 g/d (≈8 drinks/d). A higher proportion of alcohol intake from beer was also associated with lower cognitive scores. These associations remained significant after adjustment for diet, comorbidities and sociodemographic factors.

Conclusion

In men, heavy but not extreme drinking was associated with higher global cognitive scores. Given the known harmful effects of alcohol even in low doses regarding risk of cancer, the study does not provide a basis for modifying current public health messages.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00272428","term_id":"NCT00272428"}}NCT00272428     

Phylogeographic patterns, genetic affinities and morphological differentiation between Epipactis helleborine and related lineages in a Mediterranean glacial refugium

Background and Aims

In the Mediterranean basin, the Italian peninsula has been suggested to be one of the most important glacial refugia for temperate tree species. The orchid genus Epipactis is widely represented in the Italian peninsula by widespread species and several endemic, localized taxa, including selfing and outcrossing taxa. Here the phylogenetic and phylogeographic relationships in a group of closely related taxa in Epipactis are investigated with the aim of understanding the role of this refugial area for cladogenesis and speciation in herbaceous species, such as terrestrial orchids.

Methods

Ribosomal DNA (rDNA) was employed to assess phylogenetic relationships, and plastid sequence variation in the rbcL–accD spacer was used to reveal phylogeographic patterns among plastid haplotypes using a parsimony network.

Key Results

Low genetic variation and shared ribotypes were detected in rDNA, whereas high levels of sequence variation and a strong phylogeographic structure were found in the examined plastid region. The parsimony plastid haplotype network identified two main haplotype groups, one including E. atrorubens/microphylla/muelleri/leptochila and the other including all accessions of E. helleborine and several localized and endemic taxa, with a combination of widespread and rare haplotypes detected across the Italian peninsula. A greater genetic divergence separated the Italian and other European accessions of E. helleborine.

Conclusions

Phylogenetic and phylogeographic patterns support a working hypothesis in which the Italian peninsula has only recently been colonized by Epipactis, probably during the most recent phase of the Quaternary age and, nevertheless, it acted as a remarkable centre of diversification for this orchid lineage. Changes in pollination strategy and recurrent shifts in mating system (from allogamy to autogamy) could have represented the mechanism promoting this rapid diversification and the observed high taxonomic complexity detected in the E. helleborine species complex.     

Influence of MDR1 C1236T polymorphism on lopinavir plasma concentration and virological response in HIV-1-infected children

Background

Variability in MDR1 and PXR has been associated with differences in drug plasma levels and response to antiretroviral therapy. We investigated whether polymorphisms in MDR1 (T-129C, C1236T and C3435T) and PXR (C63396T) affect lopinavir plasma concentration and the virological or immunological response to HAART in HIV-1-infected children.

Methods

Genotypes were identified in 100 blood donors and 38 HIV-1-infected children. All children received HAART with lopinavir boosted with ritonavir (LPV/r) at the time of LPV plasma level quantification, before (C_trough) and between 1 and 2 h after (C_post-dose) the administration of the next dose of drug. CD4⁺ T-cell counts and plasma viral load were analyzed before and after the initiation of LPV/r.

Results

MDR1 1236T, MDR1 3435T and PXR 63396T alleles showed a frequency of ~ 50% while the MDR1 -129C allele only reached 5%. Children heterozygotes 1236CT showed a significantly lower LPV C_post-dose than homozygotes 1236TT (median C_post-dose = 3.04 μg/ml and 6.50 μg/ml, respectively; p = 0.016). Children heterozygotes 1236CT also had a lower decrease of viral load after 36 weeks of LPV/r exposure compared with homozygotes 1236CC (median viral load changes = − 0.50 log₁₀ copies/ml and − 2.08 log₁₀ copies/ml, respectively; p = 0.047). No effect on the immunological response was observed for polymorphisms of MDR1 or PXR.

Conclusions

Our results suggest that the MDR1 C1236T SNP significantly reduces LPV plasma concentration affecting the virological response to HAART. Heterozygotes 1236CT might have an altered level of P-gp expression/activity in enterocytes and CD4⁺ T lymphocytes that limits the absorption of LPV leading to an impaired virological suppression.