BackgroundCarcinogenesis affects not only humans but almost all metazoan species. Understanding the rules driving the occurrence of cancers in the wild is currently expected to provide crucial insights into identifying how some species may have evolved efficient cancer resistance mechanisms. Recently the absence of correlation across species between cancer prevalence and body size (coined as Peto’s paradox) has attracted a lot of attention. Indeed, the disparity between this null hypothesis, where every cell is assumed to have an identical probability to undergo malignant transformation, and empirical observations is particularly important to understand, due to the fact that it could facilitate the identification of animal species that are more resistant to carcinogenesis than expected. Moreover it would open up ways to identify the selective pressures that may be involved in cancer resistance. However, Peto’s paradox relies on several questionable assumptions, complicating the interpretation of the divergence between expected and observed cancer incidences.DiscussionsHere we review and challenge the different hypotheses on which this paradox relies on with the aim of identifying how this null hypothesis could be better estimated in order to provide a standard protocol to study the deviation between theoretical/theoretically predicted and observed cancer incidence. We show that due to the disproportion and restricted nature of available data on animal cancers, applying Peto’s hypotheses at species level could result in erroneous conclusions, and actually assume the existence of a paradox. Instead of using species level comparisons, we propose an organ level approach to be a more accurate test of Peto’s assumptions.SummaryThe accuracy of Peto’s paradox assumptions are rarely valid and/or quantifiable, suggesting the need to reconsider the use of Peto’s paradox as a null hypothesis in identifying the influence of natural selection on cancer resistance mechanisms.

BackgroundConceptualisation and classification of functional disorders appear highly inconsistent in the health-care system, particularly in primary care. Numerous terms and overlapping diagnostic criteria are prevalent of which many are considered stigmatising by general practitioners and patients. The lack of a clear concept challenges the general practitioner’s decision-making when a diagnosis or a treatment approach must be selected for a patient with a functional disorder. This calls for improvements of the diagnostic categories. Intense debate has risen in connection with the release of the fifth version of the ‘Diagnostic and Statistical Manual of Mental Disorders’ and the current revision of the ‘International Statistical Classification of Diseases and Related Health Problems’. We aim to discuss a new evidence based diagnostic proposal, bodily distress syndrome, which holds the potential to change our current approach to functional disorders in primary care. A special focus will be directed towards the validity and utility criteria recommended for diagnostic categorisation.DiscussionA growing body of evidence suggests that the numerous diagnoses for functional disorders listed in the current classifications belong to one family of closely related disorders. We name the underlying phenomenon ‘bodily distress’; it manifests as patterns of multiple and disturbing bodily sensations. Bodily distress syndrome is a diagnostic category with specific criteria covering this illness phenomenon. The category has been explored through empirical studies, which in combination provide a sound basis for determining a symptom profile, the diagnostic stability and the boundaries of the condition. However, as bodily distress syndrome embraces only the most common symptom patterns, patients with few but impairing symptoms are not captured. Furthermore, the current lack of treatment options may also influence the acceptance of the proposed diagnosis.SummaryBodily distress syndrome is a diagnostic category with notable validity according to empirical studies. Nevertheless, knowledge is sparse on the utility in primary care. Future intervention studies should investigate the translation of bodily distress syndrome into clinical practice. A particular focus should be directed towards the acceptability among general practitioners and patients. Most importantly, it should be investigated whether the new category may provide the basis for better treatment and improved clinical outcome.

BackgroundEmbryo selection has been an integral feature of in vitro fertilization (IVF) almost since its inception. Since the advent of extended blastocyst stage embryo culture, and especially with increasing popularity of elective single embryo transfer (eSET), the concept of embryo selection has increasingly become a mainstay of routine IVF.DiscussionWe here, however, argue that embryo selection via blastocyst stage embryo transfer (BSET), as currently practiced, at best improves IVF outcomes only for a small minority of patients undergoing IVF cycles. For a large majority BSET is either ineffective or, indeed, may actually be harmful by decreasing IVF pregnancy chances. Overall, only a small minority of patients, thus, benefit from prolonged embryo culture, while BSET, as a tool to enhance IVF outcomes, is increasingly utilized as routine care in IVF for all patients.SummarySince newer methods of embryo selection, like preimplantation genetic screening (PGS) and closed system embryo incubation with time-lapse photography are practically dependent on BSET, these concepts of embryo selection, currently increasingly adopted in mainstream IVF, require reconsideration. They, automatically, transfer the downsides of BSET, including decreases in IVF pregnancy chances in some patients, to these new procedures, and in addition raise serious questions about cost-effectiveness.

BackgroundProstate cancer (PCa) is the most commonly diagnosed cancer and kills about 28,000 American men annually. Although progress has been made in understanding the molecular features of different forms of the disease, PCa is considered incurable when it becomes resistant to standard therapies. Prostate specific antigen (PSA) test has been a gold standard of diagnosis for PCa, however, it can result in lead to the unnecessary biopsies and treatment of indolent cancers due to the low specificity. Thus, the limitations of PSA screening for PCa have prompted much focus on strategies how to enhance the accuracy of PSA for distinction between aggressive and indolent cancers.DiscussionStudies of miRNAs in PCa patients have suggested differentially expressed miRNAs between healthy controls and those with PCa, providing potential biomarker candidates using body fluids including urine and blood. Virus infection has been considered to associate with PCa incidence. Virus infected PCa cells may shed extracellular vesicles and communicate with neighboring cells, which were not infected yet, however, no mechanistic approaches were performed to understand the biology. The miRNAs composition in the shedding extracellular vesicles, and its role in PCa are completely undefined. In the near future, new insights to connect between the viral derived miRNAs and PCa progression might provide an opportunity to diagnose, risk prediction and therapeutic strategies.SummaryThe goal of this debate article is to provide a short review on miRNAs, virus infection and viral encoded miRNAs in PCa, with a primary focus on circulating miRNAs as potential non-invasive biomarkers for PCa patients.

BackgroundCarcinogenesis affects not only humans but almost all metazoan species. Understanding the rules driving the occurrence of cancers in the wild is currently expected to provide crucial insights into identifying how some species may have evolved efficient cancer resistance mechanisms. Recently the absence of correlation across species between cancer prevalence and body size (coined as Peto’s paradox) has attracted a lot of attention. Indeed, the disparity between this null hypothesis, where every cell is assumed to have an identical probability to undergo malignant transformation, and empirical observations is particularly important to understand, due to the fact that it could facilitate the identification of animal species that are more resistant to carcinogenesis than expected. Moreover it would open up ways to identify the selective pressures that may be involved in cancer resistance. However, Peto’s paradox relies on several questionable assumptions, complicating the interpretation of the divergence between expected and observed cancer incidences.DiscussionsHere we review and challenge the different hypotheses on which this paradox relies on with the aim of identifying how this null hypothesis could be better estimated in order to provide a standard protocol to study the deviation between theoretical/theoretically predicted and observed cancer incidence. We show that due to the disproportion and restricted nature of available data on animal cancers, applying Peto’s hypotheses at species level could result in erroneous conclusions, and actually assume the existence of a paradox. Instead of using species level comparisons, we propose an organ level approach to be a more accurate test of Peto’s assumptions.SummaryThe accuracy of Peto’s paradox assumptions are rarely valid and/or quantifiable, suggesting the need to reconsider the use of Peto’s paradox as a null hypothesis in identifying the influence of natural selection on cancer resistance mechanisms.

BackgroundPneumococcal diseases remain a leading cause of vaccine-preventable death worldwide in children <5 years of age. The seven-valent pneumococcal conjugate vaccine (PCV7) was approved in 2001 in Europe and was introduced into the national immunization programmes of many European countries from 2006–2008. In 2009, higher-valent PCVs (PCV10 and PCV13) became available, replacing PCV7 from 2009–2011. This article describes the evolution of vaccine and non-vaccine serotypes causing invasive pneumococcal disease (IPD) following the introduction of PCVs in Western Europe, based on data from publicly-available medical publications and national surveillance systems from January 2010 to May 2015.DiscussionIn countries with high vaccine uptake, 5–7 years after PCV7 introduction IPD caused by vaccine serotypes has almost disappeared in children. Non-PCV7 serotypes have emerged, particularly serotypes 19A, 7 F, 3 and 1. A rapid and significant reduction of the additional serotypes included in higher-valent vaccines has been observed consistently following the introduction of these vaccines. A significant and rapid decline of serotypes 19A, 7 F, 1 and 6A in both vaccine-eligible and older age groups has been observed in countries using PCV13 while serotype 19A and 3 has increased in countries using PCV10. Serotype 3 has become one of the most prevalent serotypes in adults, with some reduction only in the UK and France. Serotype diversity increased and varied by age group, the type of vaccine in use, and the time since the introduction of higher-valent PCVs. Serotypes that are currently more frequent include 24 F, 22 F, 8 and 15A in countries that use PCV13, and serotypes 19A and 3 in countries that use PCV10. Compared with the time before the introduction of higher valent PCVs, to date, there is no single ‘19A-like’ serotype emerging across countries and most of the newly emerging non-PCV13 vaccine types are less invasive with a low case-carrier ratio.ConclusionsIt is important to closely monitor not only evolving serotypes but also the magnitude of the effect in order to evaluate the overall impact of pneumococcal vaccination programmes and to initiate the appropriate vaccination strategy. Emerging serotypes may also need to be considered for the future development of new vaccines.