Family Centered Bioethics: A New Bioethical Framework for Decision-Making in Neonatal and Pediatric Units

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Preventive Newborn Male Circumcision: What Is the Child's Best Interest?

Preventive newborn male circumcision has been at the center of scientific debate for many years. The reason for promoting preventive newborn male circumcision, is the reduction of the incidence of UTIs (in the first six months of life), penile cancer, transmission of STDs/HIV infection/AIDS. However preventive interventions in the newborn involving violations of bodily integrity elicit several ethical questions. In this article, we reviewed the literature regarding circumcision, the prevention of UTIs, penile cancer, transmission of STDs/HIV infection/AIDS and complications of this practice in the neonatal period. The very limited reduction of incidence of UTIs and the uncertain preventive role of newborn male circumcision towards penile cancer, STDs/HIV infection and AIDS, makes it difficult to justify male circumcision in newborns. Moreover, the challenge in obtaining a unanimous opinion on newborn male circumcision derives from the fact that, as a preventive intervention, it requires evaluation criteria that are not comparable to those of therapeutic treatments. Since preventive male circumcision determines permanent alteration of the body, some authors believe that it can be used only in subjects that are capable of giving their valid consent. In the case of a newborn, the ″child's best interest″ should be used as a standard, but preventive newborn male circumcision does not satisfy it

Implementing carrier screening for cystic fibrosis outside the clinic: ethical analysis in the light of the personalist view

Background. Cystic Fibrosis (CF) is an autosomal recessive genetic disease. Two models for screening CF are normally used: newborn screening and population-based CF carrier screening. In turn, there are three main models of population-based CF carrier screening: prenatal carrier screening, preconception carrier screening, and carrier screening outside clinical settings. Aim. To evaluate, in the light of the personalist view, the use of carrier screenings for CF outside the clinic, i.e. in non-clinical settings, such as school and workplaces.Methods. Analysis has been carried out according to the “Perso-nalist approach” (also called “Triangular model”), an ethical method for performing ethical analysis within HTA process. It includes factual, anthropological and ethical data in a ‘‘triangular’’ normative reflection process.Findings. Implementing carrier screening for cystic fibrosis outside the clinical settings allows acquisition of knowledge for informing reproductive choices, that can be considered as valuable; benefit-risk ratio seems to be not much favorable; autonomous and responsible decisions can be taken only under certain conditions; economic ad-vantage is difficult to determine; therefore, from a personalist view, implementing carrier screenings outside the clinic seems not to be ethically justified. Conclusion. In accordance with the personalist perspective, public health programs providing carrier screenings outside the clinic should not be implemented

Sharp boundaries of Dpp signalling trigger local cell death required for Drosophila leg morphogenesis

Article available at http://dx.doi.org/10.1038/ncb1518Morphogens are secreted signalling molecules that govern many developmental processes1. In the Drosophila wing disc, the transforming growth factor (TGF) homologue Decapentaplegic (Dpp) forms a smooth gradient and specifies cell fate by conferring a defined value of morphogen activity. Thus, neighbouring cells have similar amounts of Dpp protein, and if a sharp discontinuity in Dpp activity is generated between these cells, Jun kinase (JNK)-dependent apoptosis is triggered to restore graded positional information2, 3. To date, it has been assumed that this apoptotic process is only activated when normal signalling is distorted. However, we now show that a similar process occurs during normal development: rupture in Dpp activity occurs during normal segmentation of the distal legs of Drosophila. This sharp boundary of Dpp signalling, independently of the absolute level of Dpp activity, induces a JNK—reaper-dependent apoptosis required for the morphogenesis of a particular structure of the leg, the joint. Our results show that Dpp could induce a developmental programme not only in a concentration dependent manner, but also by the creation of a sharp boundary of Dpp activity. Furthermore, the same process could be used either to restore a normal pattern in response to artificial disturbance or to direct a morphogenetic process.This work has been supported by grants from the Dirección General de Investigación Científica y Técnica (BMC 2002-00300), the Comunidad Autónoma de Madrid (08.1/0031/2001.1 and GR/SAL/0147/2004) and an Institutional Grant from the Fundación Ramón Areces. C.M. is a recipient of a Formación del Personal Universitario (F.P.U.) fellowship from the Ministerio de Educación y Ciencia.Peer reviewe

Insulin-Like Peptides and the Target of Rapamycin Pathway Coordinately Regulate Blood Digestion and Egg Maturation in the Mosquito Aedes aegypti

Mosquitoes are insects that vector many serious pathogens to humans and other vertebrates. Most mosquitoes must feed on the blood of a vertebrate host to produce eggs. In turn, multiple cycles of blood feeding promote frequent contacts with hosts and make mosquitoes ideal disease vectors. Both hormonal and nutritional factors are involved in regulating egg development in the mosquito, Aedes aegypti. However, the processes that regulate digestion of the blood meal remain unclear.Here we report that insulin peptide 3 (ILP3) directly stimulated late phase trypsin-like gene expression in blood fed females. In vivo knockdown of the mosquito insulin receptor (MIR) by RNA interference (RNAi) delayed but did not fully inhibit trypsin-like gene expression in the midgut, ecdysteroid (ECD) production by ovaries, and vitellogenin (Vg) expression by the fat body. In contrast, in vivo treatment with double-stranded MIR RNA and rapamycin completely blocked egg production. In vitro experiments showed that amino acids did not simulate late phase trypsin-like gene expression in the midgut or ECD production by the ovaries. However, amino acids did enhance ILP3-mediated stimulation of trypsin-like gene expression and ECD production.Overall, our results indicate that ILPs from the brain synchronize blood meal digestion and amino acid availability with ovarian ECD production to maximize Vg expression by the fat body. The activation of digestion by ILPs may also underlie the growth promoting effects of insulin and TOR signaling in other species

Vaccine hesitancy: parental, professional and public responsibility

The opposition to vaccinations is a well-known phenomenon that dates back to the Victorian age when it was self-limited by the awareness of the importance to be protected against fearsome infectious diseases. In the XX century, the mass use of vaccination has 12 instead 12 consented to eradicate or drastically reduce the burden of diseases such as smallpox and polio. These positive effects of the vaccination campaigns have blurred out, if not erased, the memory of the tragic consequences of the past\u2019s widespread diseases, leading people to underestimate the severity of the harm that vaccinations prevent. In recent years, a complex mixture of contextual factors have promoted an amplification of that paradoxical situation, leading experts to study causes and consequences of the so called \u201cvaccine hesitancy\u201d. Several studies have shown the impact for children and for the community of the refusal or hesitation towards vaccinations from different points of view, including epidemiological, clinical, social and economic evaluation. This article provides an analysis of vaccine hesitancy from an ethical perspective: parental, professional and public responsibilities are analysed and described according to the \u201cresponsibility of the fathers towards the children\u201d, as articulated by Hans Jonas in 1979

A Geometrical Model for DNA Organization in Bacteria

Recent experimental studies have revealed that bacteria, such as C. crescentus, show a remarkable spatial ordering of their chromosome. A strong linear correlation has been found between the position of genes on the chromosomal map and their spatial position in the cellular volume. We show that this correlation can be explained by a purely geometrical model. Namely, self-avoidance of DNA, specific positioning of one or few DNA loci (such as origin or terminus) together with the action of DNA compaction proteins (that organize the chromosome into topological domains) are sufficient to get a linear arrangement of the chromosome along the cell axis. We develop a Monte-Carlo method that allows us to test our model numerically and to analyze the dependence of the spatial ordering on various physiologically relevant parameters. We show that the proposed geometrical ordering mechanism is robust and universal (i.e. does not depend on specific bacterial details). The geometrical mechanism should work in all bacteria that have compacted chromosomes with spatially fixed regions. We use our model to make specific and experimentally testable predictions about the spatial arrangement of the chromosome in mutants of C. crescentus and the growth-stage dependent ordering in E. coli

A Role for Drosophila dFoxO and dFoxO 5′UTR Internal Ribosomal Entry Sites during Fasting

One way animals may cope with nutrient deprivation is to broadly repress translation by inhibiting 5′-cap initiation. However, under these conditions specific proteins remain essential to survival during fasting. Such peptides may be translated through initiation at 5′UTR Internal Ribosome Entry Sites (IRES). Here we show that the Drosophila melanogaster Forkhead box type O (dFoxO) transcription factor is required for adult survival during fasting, and that the 5′UTR of dfoxO has the ability to initiate IRES-mediated translation in cell culture. Previous work has shown that insulin negatively regulates dFoxO through AKT-mediated phosphorylation while dFoxO itself induces transcription of the insulin receptor dInR, which also harbors IRES. Here we report that IRES-mediated translation of both dFoxO and dInR is activated in fasted Drosophila S2 cells at a time when cap-dependent translation is reduced. IRES mediated translation of dFoxO and dInR may be essential to ensure function and sensitivity of the insulin signaling pathway during fasting

Eating episode frequency and fruit and vegetable consumption among Italian university students

Objective. To analyze breakfast consumption, regularity of meals, fruit and vegetable consumption in the Italian university student population on a national level. Design. Descriptive analysis evaluating data taken from the Sportello Salute Giovani (SSG) questionnaire. Participants. 12 000 university students who self-administered a confidential survey. 8292 questionnaires were analyzed. Variables measured. Age; sex; self-reported economic status; BMI; number of breakfast and portions of vegetables and portions of fruit usually consumed per week; number of eating episodes per day; intended weight loss. Analysis. Descriptive and logistic regression analyses were conducted. Gender and age differences were tested by c2 and Mann-Whitney tests. Results. 15.8% of males and 26.3% of females declared to consume at least one portion of fruit every day. Similar results were found for vegetable consumption. Age does not influence fruit or vegetables consumption, frequency of eating episodes or breakfast habit. Both a regular breakfast and a higher number of eating episodes are significantly associated both with a higher frequency of fruit and vegetables intake. Conclusions and implications. This study underlines the need to promote nutritional education campaigns to increase adherence to nutritional guidelines

Transcriptional responses of ecologically diverse drosophila species to larval diets differing in relative sugar and protein ratios

We utilized three ecologically diverse Drosophila species to explore the influence of ecological adaptation on transcriptomic responses to isocaloric diets differing in their relative proportions of protein to sugar. Drosophila melanogaster, a cosmopolitan species that breeds in decaying fruit, exemplifies individuals long exposed to a Western diet higher in sugar, while the natural diet of the cactophilic D. mojavensis, is much lower in carbohydrates. Drosophila arizonae, the sister species of D. mojavensis, is largely cactophilic, but also utilizes rotting fruits that are higher in sugars than cacti. We exposed third instar larvae for 24 hours to diets either (1) high in protein relative to sugar, (2) diets with equal amounts of protein and sugar, and (3) diets low in protein but high in sugar. As we predicted, based upon earlier interspecific studies of development and metabolism, the most extreme differences in gene expression under different dietary conditions were found in D. mojavensis followed by D. arizonae. No differential expression among diets was observed for D. melanogaster, a species that survives well under all three conditions, with little impact on its metabolism. We suggest that these three species together provide a model to examine individual and population differences in vulnerability to lifestyle-associated health problems such as metabolic syndrome and diabetes