Amino-functionalized mesoporous silica nanoparticles (NH2-MSiNPs) impair the embryonic development of the sea urchin Paracentrotus lividus

Nanoparticles have found use in a wide range of applications, mainly as carriers of active biomolecules. It is thus necessary to assess their toxicity for human health, as well as for the environment, on which there is still a gap of knowledge. In this work, sea urchin Paracentrotus lividus, a widely used model for embryotoxicity and spermiotoxicity, has been used to assess potential detrimental effects of amino-functionalized mesoporous silica nanoparticles (NH₂-MSiNPs) on embryonic development. Specifically, gametes quality, embryogenesis morphological and timing alterations, and cellular stress markers, such as mitochondrial functionality, were assessed in presence of different concentrations of NH₂-MSiNPs in filtered seawater (FSW). Furthermore, dorsal-ventral axis development and skeletogenesis were characterized by microscopy imaging and gene expression analysis. NH₂-MSiNPs determined a strong reduction in the egg fertilization rate. Consequently, the presence of NH₂-MSiNPs resulted detrimental in P. lividus embryonic development, with severe morphological alterations correlated with an increased embryos mortality. Finally, NH₂-MSiNPs treatment was responsible for other toxic effects, such as reduced mitochondrial function and skeletogenesis alterations, according to the reduced mineralization sites in the endoskeleton formation and the related genes altered expression. Taken together, these results suggest the potential toxic effects of NH₂-MSiNPs on the marine ecosystem, with consequences for the development and reproduction of its organisms. Despite their promising potential as carriers of biomolecules, it is pivotal to consider that their uncontrolled use may result harmful to the environment and, consequently, to living organisms.     

Cross‐country evidence on the social determinants of the post‐socialist mortality crisis in Europe: a review and performance‐based hierarchy of variables

An unprecedented mortality crisis befell the former socialist countries between 1989 and 1995, representing one of the greatest demographic shocks of the period after the Second World War. While it is likely that country‐level variation in the post‐socialist mortality crisis in Eastern Europe can be explained by a constellation of political and socio‐economic factors, no comprehensive review of the existing scholarly attempts at explaining these factors exists. We review 39 cross‐national multi‐variable peer reviewed studies of social determinants of mortality in post‐socialist Europe in order to assess the social factors behind the post‐socialist mortality crisis, determine the gaps in the existing literature and to make suggestions for future research. We propose a novel methodology to determine the relative importance of variables based on the ratio of significant to insignificant findings for each variable. The literature identifies inequality, welfare payments, religious composition, democracy, economic performance and unemployment as the leading factors that have a significant influence on mortality outcomes. Existing cross‐country studies fail to establish a definitive connection between mortality and diets, drinking patterns, liberalisation, trust, health expenditure and war. We also point out that the level of analysis is not a neutral methodological choice but might influence the results themselves.     

A discussion of the unresolved 2016/17 plans for regulating the Polish dietary supplements market

The Polish dietary supplement market is growing steadily. However, even though these products may have an impact on health they are not as strongly regulated as pharmaceuticals. In 2016/17 the introduction of new regulations covering the marketing of dietary supplements in Poland was proposed. This article briefly describes the Polish market for dietary supplements and assesses the benefits and risks associated with its development. A range of potential legislative changes, such as a total ban on dietary supplements, a ban on using the images and recommendations of authoritative entities, increased fines for breaking the law, and other measures are under consideration. We describe the advantages (e.g., better customer protection, and the limitation of inappropriate, misleading advertising) and disadvantages (e.g., a decrease in product innovation, deterioration in product offerings, and rises in product prices) of the proposed changes. As a European Union member, Poland adopts EU law, but EU directives have only harmonized some issues relating to dietary supplement marketing, other key aspects remaining within the competence of member states, but it is noted that some proposed changes in Polish law (e.g., an advertising ban) are so strict that they are unlikely to be acceptable to the EU.     

Evaluating Benefit-risk Decision-making in Spinal Muscular Atrophy: A First-ever Study to Assess Risk Tolerance in the SMA Patient Community

PurposePatients’ perceptions of benefit–risk are essential to informing the regulatory process and the context in which potential therapies are evaluated. To bring this critical information to regulators, Cure SMA launched a first-ever Benefit-Risk Survey for spinal muscular atrophy (SMA) to characterize decision-making and benefit–risk trade-offs in SMA associated with a potential therapy. We hypothesized that risk tolerance would be correlated with SMA type/severity and disease progression. This article presents the results of a benefit–risk survey to enhance understanding of how patients with SMA and caregivers evaluate specific benefits and risks associated with potential therapies.MethodsAffected adults, representing all SMA types (I–IV) within the Cure SMA database, and caregivers of affected individuals of all ages/types were invited via e-mail to participate. Best–worst scaling (BWS) was used to assess participants’ priorities on benefit–risk trade-offs, as it provides higher discrimination and importance scaling among tested attributes. Twelve potentially clinically meaningful treatment benefits and 11 potential risks (ranging in severity and immediacy) were tested. Multiple factors were correlated with individual responses, including: SMA type/disease severity, stage of disease, respondent type, sex, and quality of life/level of independence (current and expected). Survey respondents were also evaluated for "risk-taking attitudes."FindingsA total of 298 responses were evaluated (28% affected adults and 72% caregivers, mostly parents). Most respondents were diagnosed >5 years ago (67.3%), with 22.1% SMA type I, 45.6% SMA type II, and 27.9% SMA type III. No strong correlation was found between risk tolerance and SMA type, stage of disease progression, respondent type, sex, quality of life assessment, or rated levels of independence. Irrespective of SMA type, respondents consistently rated the following risks, associated with a potential treatment, as "least tolerable": life-threatening allergic reactions; 1 in 1000 risk of life-threatening side effects leading to possible organ failure; or worsening quality of life. Furthermore, all SMA type respondents rated these risks as "most tolerable": invasive mode of treatment administration (including need for general anesthesia); side effect of dizziness; and other common side effects such as nausea, vomiting, loss of appetite, headaches, back pain, or fatigue.ImplicationsWith the approval of the first SMA treatment, these findings offer a unique opportunity to assess and characterize baseline risk-tolerance in SMA against which to evaluate future SMA treatment options. Although differences had been expected in risk tolerance among respondents based on disease baseline and certain patient attributes, this was not observed. Survey results should inform future SMA drug development and benefit–risk assessments.     

The importance of how research participants think they are perceived: results from an electronic monitoring study of antiretroviral therapy in Uganda

Novel monitoring technologies in HIV research, such as electronic adherence monitors (EAMs), have changed the nature of researcher-participant interactions. Yet little is known about how EAMs and the resulting interaction between researchers and participants affect research participation and the data gathered. We interviewed participants and research assistants (RAs) in an observational cohort study involving EAMs for HIV antiretroviral therapy (ART) in Uganda. We qualitatively explored interviewees’ views about ethical issues surrounding EAMs and assessed data with conventional and directed content analysis. Participants valued their relationships with RAs and were preoccupied with RAs’ perceptions of them. Participants were pleased when the EAM revealed regular adherence, and annoyed when it revealed non-adherence that contradicted self-reported pill-taking behavior. For many, the desire to maintain a good impression incentivized adherence. But some sought to creatively conceal non-adherence, or refused to use the EAM to avoid revealing non-adherence to RAs. These findings show that participants’ perceptions of the study staff's perceptions of them affected the experience of being monitored, study participation, and ultimately the data gathered in the study. Investigators in monitoring-based research should be aware that social interactions between participants and study staff could affect both the practical and ethical conduct of that research.     

Expectation affects neural repetition suppression in infancy

Recent work provides evidence that the infant brain is able to make top-down predictions, but this has been explored only in limited contexts and domains. We build upon this evidence of predictive processing in infants using a new paradigm to examine auditory repetition suppression (RS). RS is a well-documented neural phenomenon in which repeated presentations of the same stimulus result in reduced neural activation compared to non-repeating stimuli. Many theories explain RS using bottom-up mechanisms, but recent work has posited that top-down expectation and predictive coding may bias, or even explain, RS. Here, we investigate whether RS in the infant brain is similarly sensitive to top-down mechanisms. We use fNIRS to measure infants’ neural response in two experimental conditions, one in which variability in stimulus presentation is expected (occurs 75% of the time) and a control condition where variability and repetition are equally likely (50% of the time). We show that 6-month-old infants exhibit attenuated frontal lobe response to blocks of variable auditory stimuli during contexts when variability is expected as compared to the control condition. These findings suggest that young infants’ neural responses are modulated by predictions gained from experience and not simply by bottom-up mechanisms.