Establishment of a children's Drugs and Therapeutics Committee to ensure evidence-based and cost-effective medical treatment for children.

The prevalence of undocumented medical treatments among children is a significant issue, as well as many EU countries lack access to newly developed children-friendly medicines. Consequently, there is a pressing need for supplementary resources that can facilitate informed decision-making regarding children's medication. We therefore aim to describe the process of establishing a children's Drug and Therapeutics Committee (cDTC), as well as the preparing and implementation of recommendations for children in the capital region of Denmark.

RNA origami scaffolds facilitate cryo-EM characterization of a Broccoli-Pepper aptamer FRET pair.

Cryogenic electron microscopy (cryo-EM) is a promising method for characterizing the structure of larger RNA structures and complexes. However, the structure of individual aptamers is difficult to solve by cryo-EM due to their low molecular weight and a high signal-to-noise ratio. By placing RNA aptamers on larger RNA scaffolds, the contrast for cryo-EM can be increased to allow the determination of the tertiary structure of the aptamer.

The covalent reactivity of functionalized 5-hydroxy-butyrolactams is the basis for targeting of fatty acid binding protein 5 (FABP5) by the neurotrophic agent MT-21.

Covalently acting compounds experience a strong interest within chemical biology both as molecular probes in studies of fundamental biological mechanisms and/or as novel drug candidates. In this context, the identification of new classes of reactive groups is particularly important as these can expose novel reactivity modes and, consequently, expand the ligandable proteome. Here, we investigated the electrophilic reactivity of the 3-acyl-5-hydroxy-1,5-dihydro-2-pyrrole-2-one (AHPO) scaffold, a heterocyclic motif that is present in various bioactive natural products.

Aptamer-Targeted Drug Delivery for Biofilm.

Treatment of biofilm infections using conventional antibiotic therapy is challenging as only doses that are sublethal to the biofilm can be administered safely to patients. A potential solution to this challenge is targeted drug delivery. In this study, we tailored an aptamer-targeted liposomal drug delivery system for accumulation and delivery of antibiotics locally in biofilm.

A Cyclopropene Electrophile that Targets Glutathione S-Transferase Omega-1 in Cells.

Cyclopropenes are an important new addition to the portfolio of functional groups that can be used for bioorthogonal couplings. The inert nature of these highly strained compounds in complex biological systems is almost counterintuitive given their established electrophilic properties in organic synthesis. Here we provide the first demonstration of a cyclopropene that is capable of direct conjugation to protein targets in cells and show that this compound preferentially alkylates the active site cysteine of glutathione S-transferase omega-1 (GSTO1).

STEFs: Activated Vinylogous Protein-Reactive Electrophiles.

Reported here is the synthesis of a class of semi-oxamide vinylogous thioesters, designated STEFs, and the use of these agents as new electrophilic warheads. This work includes preparation of simple probes that contain this reactive motif as well as its installation on a more complex kinase inhibitor scaffold. A key aspect of STEFs is their reactivity towards both thiol and amine groups.

Putative new childhood leukemia cancer predisposition syndrome caused by germline bi-allelic missense mutations in DDX41.

DDX41 has recently been identified as a new autosomal dominantly inherited cancer predisposition syndrome causing increased risk of adult onset acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We report for the first time compound heterozygote germline missense DDX41 mutations located in the DEAD-box domain, identified in two siblings by exome sequencing. Both siblings have slight dysmorphic findings, psychomotor delays and intellectual disability, and one developed blastic plasmacytoid dendritic cell neoplasm (BPDCN) at age five.

Catalytic Asymmetric [4+2]-Cycloadditions Using Tropolones: Developments, Scope, Transformations, and Bioactivity.

An organocatalyzed asymmetric [4+2]-cycloaddition between tropolones and electron-deficient dienophiles is presented. Complex and biologically interesting dihydrohomobarrelenone scaffolds are formed through a Diels-Alder reaction utilizing bifunctional Brønsted-base catalysis, affording the corresponding bridged bicyclic cycloadducts in up to quantitative yields with good enantio- (up to 92 % ee) and diastereoselectivity (up to >20:1 d.r.

Stendomycin and Pantomycin Are Identical Natural Products: Preparation of a Functionalized Bioactive Analogue.

The natural products pantomycin and stendomycin were both reported as antimicrobial agents. We demonstrate by gene cluster analysis, LC-MS analysis, and isolation that these polypeptides are identical, and we identify previously unknown congeners. We show that stendomycin can be chemically modified at its electrophilic dehydrobutyrine moiety yielding the first bioactive analogue of this natural product which can undergo additional functionalization.

Hypomyelinating Leukodystrophy due to HSPD1 Mutations: A New Patient.

The hypomyelinating leukodystrophies (HMLs) encompass the X-linked Pelizaeus-Merzbacher disease (PMD) caused by PLP1 mutations and known as the classical form of HML as well as Pelizaeus-Merzbacher-like disease (PMLD) (Online Mendelian Inheritance in Man [OMIM] 608804 and OMIM 260600) due to GJC2 mutations. In addition, mutations in at least 10 other genes are known to cause HMLs. In 2008, an Israeli family with clinical and neuroimaging findings similar to those found in PMD was reported.

[Hereditary hypokaliaemic periodic paralysis in a 13-year-old boy].

Hypokaliaemic periodic paralysis is a rare hereditary neuro-muscular disease caused by an error in the ion-canals in muscle cells resulting in decreased excitabiliy. It presents itself in the late childhood or teenage years with a periodic paralysis without involving respiratory and heart muscles. Our patient was a 13-year-old boy, who woke up with decreased strength in arms and legs after excessive physical activity and a high carbo-hydrate intake.

Overweight and obesity trends in Copenhagen schoolchildren from 2002 to 2007.

Aim: The purpose of this study is to monitor the prevalence trend in overweight and obesity among Copenhagen schoolchildren from the school years 2002 to 2007.

Methods: Copenhagen community health service doctors conducted routine examinations at school entry (ages 5-8 years) and exit (ages 14-16 years). Body mass index (kg/m²) of 33,245 schoolchildren was calculated.

[Quality management in Danish health care--from development to control?].

This article defines the concept of "quality management" and describes the development in quality management in Danish health care. We claim that a shift in form and focus of such management has occurred. When quality improvement was introduced as a concept in Danish health care approximately 20 years ago, the efforts started out as ad hoc projects driven by professionals.

The role of vascular adhesion molecules PECAM-1 (CD 31), VCAM-1 (CD 106), E-selectin (CD62E) and P-selectin (CD62P) in severe porcine pancreatitis.

Inflammatory cytokines have been shown to mediate organ damage by their action on vascular endothelia and leukocytes, in part by upregulating the expression of adhesion molecules, which in turn convey transmigration of leukocytes into tissue. The upregulation and activation of vascular cell adhesion molecules on the endothelial cells avail firm leukocyte adhesion to the vascular endothelium and enhance their transmigration and consecutive tissue injury. The aim of this study was to evaluate the expression of vascular adhesion molecules CD 31 (PECAM-1), CD 106 (VCAM-1), CD 62E (E-Selectin) and CD 62P (P-Selectin) in the pancreas and distant organs of pigs suffering from acute necrotizing pancreatitis (AP).

[Monitoring the prevalence of obesity].

The Danish Fitness and Nutrition Council has proposed a model to monitor the prevalence of overweight and obesity in Denmark. The model should make it possible to assess whether different initiatives reduce the prevalence of obesity and to gain knowledge on how to prevent obesity. The prevalence of obesity should be estimated in a non-biased randomly selected sample of the population once yearly, using all available data from routine measurements and encouraging new measurements conducted in professional settings where routine data are not available.

Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses.

Recently, single chain peptides have been designed that target the insulin receptor and mimic insulin action. The aim of this study is to explore if activation of the insulin receptor with such an optimized peptide (S597) leads to the same activation of signaling pathways and biological endpoints i.e.

Microsatellite analysis in serum DNA as a diagnostic tool for distinction of patients with unknown pancreatic masses.

The clinical distinction between cancer and chronic pancreatitis is difficult in patients with pancreatic masses. To test whether detection of aberrant serum DNA could assist in this important differential diagnosis, we tested a panel of 12 microsatellitemarkers from chromosomes 17p, 17q, 13q, 9p, 5q, and 2p in the blood of 35 pancreatic cancer patients, 22 patients with chronic pancreatitis, and 20 healthy individuals. An average of 2.

Screening Copenhagen school children at risk of type 2 diabetes mellitus using random capillary blood glucose.

Aim: To screen adolescents at risk of type 2 diabetes mellitus (T2DM) using random capillary blood glucose (RCBG).

Methods: Ninth grade pupils who were overweight and/or had a family history of T2DM were offered to have RCBG measured and were referred for further investigation if the value was > or = 7.8 mmol/L.

[Prevalence of urinary incontinence among young female college students.].

Objective: The aim was to study the prevalence of urinary incontinence in young Icelandic female college students. We also studied how the incontinence effected their daily life, and also if they ever received any education and/or instruction on pelvic floor exercises.

Material And Methods: A total of 311 women in age range 16-19 years old were randomly selected from eight college schools in Iceland.

Oxygen radical formation does not have an impact in the treatment of severe acute experimental pancreatitis using free cellular hemoglobin.

Aim: Microcirculatory dysfunction and free oxygen radicals are important factors in the pathogenesis of severe acute pancreatitis. Additional oxygen delivery might enhance lipid peroxidation but may also improve pancreatic microcirculation. This study assesses the effect of free cellular bovine hemoglobin on the formation of oxygen radicals and microcirculation in a rodent model of severe acute pancreatitis.