Alkaline gel electrophoresis, pulsed field gel electrophoresis, and quantitative PCR analyses (QPCR) of the nuclear (nDNA) and mitochondrial (mtDNA) genomes were used to assess DNA integrity in the spermatozoa of three species exposed to oxidative stress. In human and murine spermatozoa, the mtDNA was significantly more susceptible to H2O2-mediated damage than nDNA. In both eutherian species, exposure to 250 microM H2O2 induced around 0.6 lesions/10 kb of mtDNA. The mtDNA of human spermatozoa was particularly vulnerable to oxidative stress; 0.25, 1, and 5 mM H2O2 inducing DNA damage equivalent to 0.62, 1.34, and 1.42 lesions/10 kb, respectively. Such results emphasize the diagnostic significance of mtDNA as a biomarker of oxidative stress in the male germ line. In contrast, no damage could be detected by QPCR in the nDNA of either eutherian species, on exposure to H2O2 at doses as high as 5 mM. However, electrophoretic analysis indicated that severe oxidative stress could induce detectable nDNA fragmentation in human, but not murine spermatozoa. The mtDNA of tammar wallaby spermatozoa was relatively resistant to oxidative stress, only exhibiting damage (0.6 lesions/10 kb DNA) on exposure to 5 mM H2O2. By contrast, the nDNA of wallaby spermatozoa was significantly more susceptible to this oxidant than the other species. Such vulnerability is consistent with the lack of disulfide cross-linking in marsupial sperm chromatin and suggests that chromatin condensation during epididymal maturation may be important in establishing the resistance of these cells to the genotoxic effects of reactive oxygen species.

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BackgroundThe objective of the study was to reveal through pragmatic MCDA (EVIDEM) the contribution of a broad range of criteria to the value of the orphan drug lenvatinib for radioiodine refractory differentiated thyroid cancer (RR-DTC) in country-specific contexts.MethodsThe study was designed to enable comprehensive appraisal (12 quantitative, 7 qualitative criteria) in the current disease context (watchful waiting, sorafenib) of France, Italy and Spain. Data on the value of lenvatinib was collected from diverse stakeholders during country-specific panels and included: criteria weights (individual and social values); performance scores (judgments on evidence—collected through MCDA systematic review); qualitative impacts of contextual criteria; and verbal and written insights structured by criteria. The value contribution of each criterion was calculated and uncertainty explored.Results Comparative effectiveness, Quality of evidence (Spain and Italy) and Disease severity (France) received the greatest weights. Four criteria contributed most to the value of lenvatinib, reflecting its superior Comparative effectiveness (16–22% of value), the severity of RR-DTC (16–22%), significant unmet needs (14–21%) and robust evidence (14–20%). Contributions varied by comparator, country and individuals, highlighting the importance of context and consultation. Results were reproducible at the group level. Impacts of contextual criteria varied across countries reflecting different health systems and cultural backgrounds. The MCDA process promoted sharing stakeholders’ knowledge on lenvatinib and insights on context.ConclusionsThe value of lenvatinib was consistently positive across diverse therapeutic contexts. MCDA identified the aspects contributing most to value, revealed rich contextual insights, and helped participants express and explicitly tackle ethical trade-offs inherent to balanced appraisal and decisionmaking.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3258-9) contains supplementary material, which is available to authorized users.

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BackgroundCountry-level HPV genotyping data may be sought by decision-makers to gauge the genotype-specific burden of HPV-related diseases in their jurisdiction and assess the potential impact of HPV vaccines. We investigated, by country, the availability of published literature on HPV genotypes in cervical, vaginal and vulvar cancers and intraepithelial neoplasms (CINs, VaINs and VINs) and on prevalence and incidence of genital HPV infections among women without clinically manifest disease.FindingsPrimary sources of publications were the PubMed/Medline and EMBASE databases. Original studies or meta-analyses published from 2000, covering genotypes 16 and 18 and at least one of genotypes 31/33/45/52/58, were included. Key exclusion criteria were language not English, cervical lesions not histologically confirmed (cytology only), special populations (e.g., immunocompromised) and, for cervical studies, small population (<50). A total of 727 studies reporting HPV genotype-specific data were identified: 366 for cervical cancers and CINs, 43 for vulvar or vaginal cancers and VINs/VaINs, and 395 and 21 for infection prevalence and incidence, respectively, in general female population samples. A large proportion of studies originated from a small set of countries. Cervical cancer/CIN typing data was scarce for several regions with the highest cervical cancer burden, including Eastern, Middle and Western Africa, Central America, South-East Asia, South Asia, and Eastern Europe. Data for vulvar/vaginal disease was limited outside of Europe and North America.ConclusionsAlthough a large body of published HPV genotype-specific data is currently available, data gaps exist for genotype-specific infection incidence and several world regions with the highest cervical cancer burden.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-015-0008-y) contains supplementary material, which is available to authorized users.