PharmVar GeneFocus: CYP4F2

\ua9 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.The Pharmacogene Variation Consortium (PharmVar) serves as a global repository providing star (*) allele nomenclature for the polymorphic human CYP4F2 gene. CYP4F2 genetic variation impacts the metabolism of vitamin K, which is associated with warfarin dose requirements, and the metabolism of drugs, such as imatinib or fingolimod, and certain endogenous compounds including vitamin E and eicosanoids. This GeneFocus provides a comprehensive overview and summary of CYP4F2 genetic variation including the characterization of 14 novel star alleles, CYP4F2*4 through *17. A description of how haplotype information cataloged by PharmVar is utilized by the Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) is also provided

Conservative treatment of idiopathic scoliosis according to FITS concept: presentation of the method and preliminary, short term radiological and clinical results based on SOSORT and SRS criteria

<p>Abstract</p> <p>Background</p> <p>Conservative scoliosis therapy according to the FITS Concept is applied as a unique treatment or in combination with corrective bracing. The aim of the study was to present author's method of diagnosis and therapy for idiopathic scoliosis FITS-Functional Individual Therapy of Scoliosis and to analyze the early results of FITS therapy in a series of consecutive patients.</p> <p>Methods</p> <p>The analysis comprised separately: (1) single structural thoracic, thoracolumbar or lumbar curves and (2) double structural scoliosis-thoracic and thoracolumbar or lumbar curves. The Cobb angle and Risser sign were analyzed at the initial stage and at the 2.8-year follow-up. The percentage of patients improved (defined as decrease of Cobb angle of more than 5 degrees), stable (+/- 5 degrees), and progressed (increase of Cobb angle of more than 5 degrees) was calculated. The clinical assessment comprised: the Angle of Trunk Rotation (ATR) initial and follow-up value, the plumb line imbalance, the scapulae level and the distance from the apical spinous process of the primary curve to the plumb line.</p> <p>Results</p> <p>In the Group A: (1) in single structural scoliosis 50,0% of patients improved, 46,2% were stable and 3,8% progressed, while (2) in double scoliosis 50,0% of patients improved, 30,8% were stable and 19,2% progressed. In the Group B: (1) in single scoliosis 20,0% of patients improved, 80,0% were stable, no patient progressed, while (2) in double scoliosis 28,1% of patients improved, 46,9% were stable and 25,0% progressed.</p> <p>Conclusion</p> <p>Best results were obtained in 10-25 degrees scoliosis which is a good indication to start therapy before more structural changes within the spine establish.</p

Physical therapy intervention studies on idiopathic scoliosis-review with the focus on inclusion criteria1

<p>Abstract</p> <p>Background</p> <p>Studies investigating the outcome of conservative scoliosis treatment differ widely with respect to the inclusion criteria used. This study has been performed to investigate the possibility to find useful inclusion criteria for future prospective studies on physiotherapy (PT).</p> <p>Materials and methods</p> <p>A PubMed search for outcome papers on PT was performed in order to detect study designs and inclusion criteria used.</p> <p>Results</p> <p>Real outcome papers (start of treatment in immature samples/end results after the end of growth; controlled studies in adults with scoliosis with a follow-up of more than 5 years) have not been found. Some papers investigated mid-term effects of exercises, most were retrospective, few prospective and many included patient samples with questionable treatment indications.</p> <p>Conclusion</p> <p>There is no outcome paper on PT in scoliosis with a patient sample at risk for being progressive in adults or in adolescents followed from premenarchial status until skeletal maturity. However, papers on bracing are more frequently found and bracing can be regarded as evidence-based in the conservative management and rehabilitation of idiopathic scoliosis in adolescents.</p

Solubility Measurements and Correlation of Modafinil in Neat Solvents and Binary Solvent Mixtures

The solubility of modafinil (MOD) form I, an antinarcoleptic drug, was measured at temperatures ranging from 278.15 to 333.15 K in ten neat solvents (acetone, acetonitrile, dimethylformamide, ethanol, ethyl acetate, methanol, methylethylketone, 1-propanol, 2-propanol, and water) and two binary solvent mixtures (acetone + water and methanol + water). The results employing the polythermal method demonstrate that the solubility increases with increasing temperature in the neat solvents and at constant composition in the binary solvent mixtures. Moreover, the MOD solubility decreases with an increasing mass fraction of water (antisolvent) in the binary solvent mixture methanol + water. In the binary solvent mixture acetone + water, the solubility exceeds its solubility in neat acetone and water, reaching a maximum at a water mass fraction of ∼20 wt %. Based on the calculated average relative deviation (ARD %), the experimental solubility data agree with the correlated data using the modified Apelblat and λh equations. Additionally, powder X-ray diffraction confirms that the recrystallized solid in the neat and binary solvent mixtures was the commercial MOD form I, except for 2-propanol. Thus, the presented solubility data provide a pathway to engineer crystallization processes for MOD toward integrated manufacturing from flow synthesis to crystallization

Synthetic genetic polymers capable of heredity and evolution

Genetic information storage and processing rely on just two polymers, DNA and RNA, yet whether their role reflects evolutionary history or fundamental functional constraints is currently unknown. With the use of polymerase evolution and design, we show that genetic information can be stored in and recovered from six alternative genetic polymers based on simple nucleic acid architectures not found in nature [xeno-nucleic acids (XNAs)]. We also select XNA aptamers, which bind their targets with high affinity and specificity, demonstrating that beyond heredity, specific XNAs have the capacity for Darwinian evolution and folding into defined structures. Thus, heredity and evolution, two hallmarks of life, are not limited to DNA and RNA but are likely to be emergent properties of polymers capable of information storage