A recurrent de novo MAX p.Arg60Gln variant causes a syndromic overgrowth disorder through differential expression of c-Myc target genes.

Cyclin D2 (CCND2) stabilization underpins a range of macrocephaly-associated disorders through mutation of CCND2 or activating mutations in upstream genes encoding PI3K-AKT pathway components. Here, we describe three individuals with overlapping macrocephaly-associated phenotypes who carry the same recurrent de novo c.179G>A (p.

Pharmacokinetic characterisation of a valproate Autism Spectrum Disorder rat model in a context of co-exposure to α-Hexabromocyclododecane.

Assessing the role of α-hexabromocyclododecane α-HBCDD as a factor of susceptibility for Autism Spectrum disorders by using valproic acid-exposed rat model (VPA) required characterizing VPA pharmacokinetic in the context of α-HBCDD-co-exposure in non-pregnant and pregnant rats. The animals were exposed to α-HBCDD by gavage (100 ng/kg/day) for 12 days. This was followed by a single intraperitoneal dose of VPA (500 mg/kg) or a daily oral dose of VPA (500 mg/kg) for 3 days.

Zinc Fingers 10 and 11 of Miz-1 undergo conformational exchange to achieve specific DNA binding.

Miz-1 (ZBTB17) is a poly-zinc finger BTB/POZ transcription factor with 12 consecutive C2H2 zinc fingers (ZFs) that binds transcriptional start sites (TSSs) to regulate the expression of genes involved in cell development and proliferation. As of now, it is not known which of the 12 consecutive ZFs are responsible for the recognition of the 24 base pair consensus sequence found at these TSSs. Evidence suggests ZFs 7-12 plays this role.

Exposure to inorganic particles in paediatric sarcoidosis: the PEDIASARC study.

Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.

Effect of free trade agreements on pharmaceutical market competition: The case of the 2009 US-Peru free trade agreement and its implementation as national drug policy.

Free Trade Agreements (FTA) are controversial for threatening essential aspects of health, especially access to affordable medicines. The US-Peru FTA required changes in the Peruvian pharmaceutical legislation that resulted in the implementation of the National Drug Policy (NDP) of 2009. The NDP included more robust technical requirements for registration, a Peruvian Good Manufacturing Practices certificate, a longer timeline for drug registration, and an increase in registration fees.

Child-Adult Transition in Sarcoidosis: A Series of 52 Patients.

(1) Background: Pediatric sarcoidosis is a rare and mostly severe disease. Very few pediatric series with a prolonged follow-up are reported. We aimed to evaluate the evolution of pediatric sarcoidosis in adulthood.

Monitoring tissue perfusion: a pilot clinical feasibility and safety study of a urethral photoplethysmography-derived perfusion device in high-risk patients.

Continuous monitoring of tissue perfusion in patients with hemodynamic instability remains challenging because of the lack of tools available. Through using urethral photoplethysmography, the urethral perfusion index (uPI) could allow tissue perfusion monitoring through a modified urinary catheter. The first objective of our study was to evaluate the feasibility and safety of the IKORUS UP (Advanced Perfusion Diagnostics, Villeurbanne, France), a new device in the field.

Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy.

Inhibiting MYC has long been considered unfeasible, although its key role in human cancers makes it a desirable target for therapeutic intervention. One reason for its perceived undruggability was the fear of catastrophic side effects in normal tissues. However, we previously designed a dominant-negative form of MYC called Omomyc and used its conditional transgenic expression to inhibit MYC function both in vitro and in vivo.

Trade agreements and drug access: assessment of the impact of the 2009 Peruvian new drug policy on anti-infectives registration and availability.

Background: The United States-Peru Free Trade Agreement required changes in the Peruvian pharmaceutical legislation that resulted in the National Drug Policy (NDP) of 2009. This study evaluated the registration of brand and generic anti-infectives before and after the agreement and implementation of the NDP and assessed the availability of anti-infectives in community pharmacies located in Arequipa-Peru.

Methods: Anti-infectives registration database, provided by DIGEMID (Peruvian Drug Regulatory Authority), was evaluated from January 2005 to August 2014.

Evaluation of surgical margin status in patients with early glottic cancer (Tis-T2) treated with transoral CO laser microsurgery, on local control.

Purpose: To assess the impact of surgical margins status on local control in patients with primary early glottic (Tis-T2) squamous cell carcinoma after treatment with transoral CO laser microsurgery (TLM) and to assess the significance of additional wound bed biopsies.

Methods: Patients with Tis-T2 tumours treated with TLM type I-III resections according to the European Laryngological Society classification between 2009 and 2013 were included in retrospective analysis. Recurrence rate was determined in patients with free versus non-free specimen margins and wound biopsies.

Biophysical characterization of the b-HLH-LZ of ΔMax, an alternatively spliced isoform of Max found in tumor cells: Towards the validation of a tumor suppressor role for the Max homodimers.

It is classically recognized that the physiological and oncogenic functions of Myc proteins depend on specific DNA binding enabled by the dimerization of its C-terminal basic-region-Helix-Loop-Helix-Leucine Zipper (b-HLH-LZ) domain with that of Max. However, a new paradigm is emerging, where the binding of the c-Myc/Max heterodimer to non-specific sequences in enhancers and promoters drives the transcription of genes involved in diverse oncogenic programs. Importantly, Max can form a stable homodimer even in the presence of c-Myc and bind DNA (specific and non-specific) with comparable affinity to the c-Myc/Max heterodimer.

Structural Insights into c-Myc-interacting Zinc Finger Protein-1 (Miz-1) Delineate Domains Required for DNA Scanning and Sequence-specific Binding.

c-Myc-interacting zinc finger protein-1 (Miz-1) is a poly-Cys2His2 zinc finger (ZF) transcriptional regulator of many cell cycle genes. A Miz-1 DNA sequence consensus has recently been identified and has also unveiled Miz-1 functions in other cellular processes, underscoring its importance in the cell. Miz-1 contains 13 ZFs, but it is unknown why Miz-1 has so many ZFs and whether they recognize and bind DNA sequences in a typical fashion.

Miz-1 and Max compete to engage c-Myc: implication for the mechanism of inhibition of c-Myc transcriptional activity by Miz-1.

c-Myc is a basic helix-loop-helix leucine zipper (b-HLH-LZ) transcription factor deregulated in the majority of human cancers. As a heterodimer with Max, another b-HLH-LZ transcription factor, deregulated and persistent c-Myc accumulates at transcriptionally active promoters and enhancers and amplifies transcription. This leads to the so-called transcriptional addiction of tumor cells.

Human genome meeting 2016 : Houston, TX, USA. 28 February - 2 March 2016.

O1 The metabolomics approach to autism: identification of biomarkers for early detection of autism spectrum disorder A. K. Srivastava, Y.

The Exploitation of Drug Users.

Drug users have been exploited in research studies and clinical practice. We explore ways in which exploitation has occurred and strategies to help patients, research subjects and communities to prevent or avoid exploitation.

Seeing is believing, looks are deceiving: what does one see in images of drugs and drug use(rs)?

Images of drugs and drug use(rs) convey meaning, feelings, and beliefs, and what is being seen is often believed. Images can also deceive in content, meaning, and belief. Drug use(r) researchers, who use images as data, must be cautious in interpreting what is being conveyed and why.

Methods for the expression, purification, preparation, and biophysical characterization of constructs of the c-Myc and Max b-HLH-LZs.

Specific heterodimerization and DNA binding by the b-HLH-LZ transcription factors c-Myc and Max is central to the activation and repression activities of c-Myc that lead to cell growth, proliferation, and tumorigenesis (Adhikary and Eilers, Nat Rev Mol Cell Biol 6:635-645, 2005; Eilers and Eisenman, Genes Dev 22:2755-2766, 2008; Grandori et al., Annu Rev Cell Dev Biol 16:653-699, 2000; Whitfield and Soucek, Cell Mol Life Sci 69:931-934, 2011). Although many c-Myc-interacting partner proteins are known to interact through their HLH domain (Adhikary and Eilers, Nat Rev Mol Cell Biol 6:635-645, 2005), current knowledge regarding the structure and the determinants of molecular recognition of these complexes is still very limited.

Pharmaceutical pictograms: a model for development and testing for comprehension and utility.

Background: With concerns about the medication literacy skills of patients comes the need to develop various types of information materials that will enhance understanding and drug use.

Objectives: To review pictogram development projects and to propose a model for pharmaceutical pictogram development and testing for comprehension and use.

Methods: Previous efforts in developing specific types of pictograms in engineering and safety as well as in health care and pharmacy are collected and summarized in terms of level of comprehension and recall.

Drugs on the Internet, Part V: absinthe, return of the emerald mask.

Absinthe, a famous liquor of the 19th century, has become immensely popular with its return to legality and mass marketing and drug culture enhancement of its purported unique effects. The electronic world of the Internet has greatly expedited the extent and depth of societal knowledge about the allure of the green fairy, absinthe. An extensive number of websites exists, representing 22 categories of topics about or using the word absinthe.

Drugs on the internet, part IV: Google's Ngram viewer analytic tool applied to drug literature.

Google Inc.'s digitized book library can be searched based on key words and phrases over a five-century time frame. Application of the Ngram Viewer to drug literature was assessed for its utility as a research tool.

Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies.

Background: The United States (US) Food and Drug Administration (FDA) is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA) and related regulations. These enforcement activities include regulatory letters (i.e.

Failure to consider a radically new scientific idea or theory.

From plate tectonics theory to psychoneuroimmunology, to medical uses of marijuana, and controlled drinking by alcoholics, there has been a consistent failure by scientists and medical researchers to consider radically new ideas and theories. A review and analysis of these cases and other examples identified numerous reasons or barriers for this failure. Learning from these episodes of failure requires attention to and reflection on these barriers, an understanding of how the scientific process progresses and scientific knowledge evolves, and a willingness to test and evaluate these new ideas and theories before passing final judgment on them.

Drugs on the internet, part III: tobacco and smoking on the web.

This study examines the types of tobacco- and smoking-related websites that are available on the Internet. The search terms used were nicotine, tobacco, and cigarette. These terms were searched in the engines Google and Yahoo as well as video-sharing website YouTube and analyzed based on the search engine results pages (SERPs) that were produced.