Use of hormones in doping and cancer risk

Hormones with anabolic properties such as growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are commonly abused among professional and recreational athletes to enhance physical ability. Despite their adverse effects are well-documented, the use of GH and IGF-1 has recently grown. This article highlights the anabolic activity related to mechanisms of cancer development and progression. GH/IGF-1 axis is able to activate cellular mechanisms that modulate every key stage of cancer formation and progression, such as inhibition of apoptosis, resistance to treatments, and induction of angiogenesis, metastatic process and cell proliferation. Results from pre-clinical studies and epidemiological observations in patients with an excess of GH and IGF-1 production or treated with these hormones showed a positive association with the risk to develop several types of cancer. In conclusion, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer, especially if associated with other licit or illicit drugs and/or high-protein diet

Syndromic craniosynostosis can define new candidate genes for suture development or result from the non-specifc effects of pleiotropic genes: Rasopathies and chromatinopathies as examples

Craniosynostosis is a heterogeneous condition caused by the premature fusion of cranial sutures, occurring mostly as an isolated anomaly. Pathogenesis of non-syndromic forms of craniosynostosis is largely unknown. In about 15-30% of cases craniosynostosis occurs in association with other physical anomalies and it is referred to as syndromic craniosynostosis. Syndromic forms of craniosynostosis arise from mutations in genes belonging to the Fibroblast Growth Factor Receptor (FGFR) family and the interconnected molecular pathways in most cases. However it can occur in association with other gene variants and with a variety of chromosome abnormalities as well, usually in association with intellectual disability (ID) and additional physical anomalies. Evaluating the molecular properties of the genes undergoing intragenic mutations or copy number variations (CNVs) along with prevalence of craniosynostosis in different conditions and animal models if available, we made an attempt to define two distinct groups of unusual syndromic craniosynostosis, which can reflect direct effects of emerging new candidate genes with roles in suture homeostasis or a non-specific phenotypic manifestation of pleiotropic genes, respectively. RASopathies and 9p23p22.3 deletions are reviewed as examples of conditions in the first group. In particular, we found that craniosynostosis is a relatively common component manifestation of cardio-facio-cutaneous (CFC) syndrome. Chromatinopathies and neurocristopathies are presented as examples of conditions in the second group. We observed that craniosynostosis is uncommon on average in these conditions. It was randomly associated with Kabuki, Koolen-de Vries/KANSL1 haploinsufficiency and Mowat-Wilson syndromes and in KAT6B-related disorders. As an exception, trigonocephaly in Bohring-Opitz syndrome reflects specific molecular properties of the chromatin modifier ASXL1 gene. Surveillance for craniosynostosis in syndromic forms of intellectual disability, as well as ascertainment of genomic CNVs by array-CGH in apparently non-syndromic craniosynostosis is recommended, to allow for improvement of both the clinical outcome of patients and the accurate individual diagnosis

Complex Muco-cutaneous Manifestations of CARMIL2-associated Combined Immunodeficiency: A Novel Presentation of Dysfunctional Epithelial Barriers.

Abstract is missing (Short communication

Imagining London : the role of the geographical imagination in migrant subjectivity and decision-making

Funding: St Andrews’ Janet T Anderson ScholarshipThis article employs a qualitative, biographical approach, to explore the motivations and subjectivities behind migration of middle‐class Brazilians to London. It uses the concept of the geographical imagination to understand how migrants imagine not only their destinations and places of origin but also how their own identity is shaped by their imagined relationship to these places. The paper argues that for many middle‐class Brazilians, their motivation to migrate is couched in terms of “societal alienation”: a feeling of distance from the place of origin resulting from a lack of identification and trust in its institutions and the very culture of the place itself. This is in contrast to the more popularly understood concept of migrating due to “material alienation”: migrating to access a higher level of material consumption or to acquire financial capital to use “back home.” For those who migrate due to “societal alienation” what is “fetishised” is the cultural and less material aspects of the ‘quality of life’ of the migration destination, which become a kind of commodity in their own right. It argues that social class which often intersects with regional and racial divisions within Brazilian society, is a key marker of difference in these two types of imaginary.PostprintPeer reviewe

[World Health Organization document "Water safety in buildings": Italian translation].

A working group of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI) has translated into Italian the World Health Organization (WHO) guidance document "Water safety in buildings" published in 2011. The document is intended to provide guidance on implementing the WHO Guidelines for drinking-water quality. In the present article, the authors describe the framework of the WHO document and summarize the main points discusse

Clinical genetics can solve the pitfalls of genome-wide investigations: Lesson from mismapping a loss-of-function variant in KANSL1

Massive parallel sequencing of 70 genes in a girl with a suspicion of chromatinopathy detected the (NM_015443.4:)c.985_986delTT variant in exon 2 of KANSL1, which led to a diagnostic consideration of Koolen De Vries syndrome. The same variant was present in the healthy mother, consistent with either incomplete penetrance or variant mismapping. A network of second opinion was implemented among clinical geneticists first, and a diagnosis of Koolen De Vries syndrome was considered unlikely. By MLPA, a duplication spanning exons 1-3 of KANSL1 was detected in both the mother and the daughter. On cDNA sequencing, biallelic wild type mRNA was observed. We concluded that the variant affects the noncoding duplicated gene region in our family, and we finally classified it as benign. Parallel wide genomic sequencing is increasingly the first genetic investigation in individuals with intellectual disability. The c.985_986delTT variant in KANSL1 was described both in individuals with typical KdVS and in a limited number of healthy subjects. This report highlights the role of clinical genetics to correctly classify variants and to define proper clinical and diagnostic correlations