Falls in elderly patients are not treated according to national recommendations.

INTRODUCTION: The aim of this study was to evaluate health professionals' compliance with recommendations from the Danish Health Authority (DHA) concerning falls, to study the prevalence of acute hospital visits due to falls, and to compare characteristics of fall patients in two geographically and socioeconomically different areas of Denmark. METHODS: The study was conducted in the emergency departments (ED) of Slagelse Hospital (SH) and Nykøbing Falster Hospital (NFH), both located in Denmark. Included were individuals > 50 years visiting the EDs from January 1 to March 31, 2014 who reported a fall. Information concerning demographic data and comorbidity in fall patients was retrieved from the medical records of the patients. RESULTS: A total of 2,664 individuals > 50 years visited the EDs during the study period. In all, 1,100 individuals (41.2%) reported a fall. In the NFH 236 (44%) and in the SH 223 (39%) of the fall patients had a fracture (p = 0.049). Patients in the more socioeconomically deprived area covered by the NFH were younger and had higher fracture and heart failure rates. Only 2% of the medical records contained answers to all four questions recommended by the DHA for risk screening in fall patients. The number of medical records containing answers to any of the four questions ranged from 17.5% to 25.8%. CONCLUSIONS: Only few fall patients were screened according to DHA recommendations. ED staff´s adherence to guidelines concerning fall risk assessment is poor. Fall patients in a socioeconomically deprived area were younger and had higher fracture and heart failure incidences. FUNDING: This study received funding from the public Regional Research Foundation, Region Zealand, Denmark. TRIAL REGISTRATION: not relevant.

Triplex-mediated analysis of cytosine methylation at CpA sites in DNA.

Modified triplex-forming oligonucleotides distinguish 5-methyl cytosine from unmethylated cytosine in DNA duplexes by differences in triplex melting temperatures. The discrimination is sequence-specific; dramatic differences in stabilisation are seen for CpA methylation, whereas CpG methylation is not detected. This direct detection of DNA methylation constitutes a new approach for epigenetic analysis.

Enzymatic polymerisation involving 2'-amino-LNA nucleotides.

The triphosphate of the thymine derivative of 2'-amino-LNA (2'-amino-LNA-TTP) was synthesised and found to be a good substrate for Phusion® HF DNA polymerase, allowing enzymatic synthesis of modified DNA encoded by an unmodified template. To complement this, 2'-amino-LNA-T phosphoramidites were incorporated into DNA oligonucleotides which were used as templates for enzymatic synthesis of unmodified DNA using either KOD, KOD XL or Phusion polymerases. 2'-Amino-LNA-T in the template and 2'-amino-LNA-TTP as a substrate both decreased reaction rate and yield compared to unmodified DNA, especially for sequences with multiple 2'-amino-LNA-T nucleotides.

Amino acids attached to 2'-amino-LNA: synthesis and excellent duplex stability.

The synthesis of 2'-amino-LNA (the 2'-amino derivative of locked nucleic acid) has opened up a number of exciting possibilities with respect to modified nucleic acids. While maintaining the excellent duplex stability inferred by LNA-type oligonucleotides, the nitrogen in the 2'-position of 2'-amino-LNA monomers provides an excellent handle for functionalisation. Herein, the synthesis of amino acid functionalised 2'-amino-LNA derivatives is described. Following ON synthesis, a glycyl unit attached to the N2'-position of 2'-amino-LNA monomers was further acylated with a variety of amino acids. On binding to DNA/RNA complements, the modified ONs induce a marked increase in thermal stability, which is particularly apparent in a buffer system with a low salt concentration. The increase in thermal stability is thought to be caused, at least in part, by decreased electrostatic repulsion between the negatively charged phosphate backbones when positively charged amino acid residues are appended. Upon incorporation of more than one 2'-amino-LNA modification, the effects are found to be nearly additive. For comparison, 2'-amino-LNA derivatives modified with uncharged groups have been synthesised and their effect on duplex thermal stability likewise investigated.

Imidazole pyrimidine amides as potent, orally bioavailable cyclin-dependent kinase inhibitors.

The development of a novel series of imidazole pyrimidine amides as cyclin-dependent kinase (CDK) inhibitors is described. The series was found to have much improved CDK2 inhibition and potent in vitro anti-proliferative effects against cancer cell lines. Control of overall lipophilicity was important to achieve good in vitro potency along with acceptable physiochemical properties and margins against inhibition of both CYP isoforms and the hERG potassium ion channel. A compound with an attractive overall balance of properties was profiled in vivo and possessed suitable physiochemical and pharmacokinetic profiles for oral dosing.