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ly coordinated) and mid-swing (more variable). This may reflect a cautious gait strategy on challenging walkways to maintain stability and help prevent falls.

A growing body of quantitative evidence has been provided regarding age-related differences in plantar foot loading, multi-segment foot kinematics and muscle activity. Fundamental insight into the joint mechanics and energetics of the maturing foot has yet to be provided.

It was hypothesized that so-called 'biomechancial maturation' joint kinetics would be observed in children underneath the age of eight and that older age-groups would not differ from each other in these parameters.

Fourty-three typically developing boys were recruited and allocated to three different age groups 1) an early childhood group, 2) a middle childhood group, and 3) an early and late adolescence group. Multi-segment joint kinematics and kinetics of the Ankle-, Chopart-, Lisfranc- and Hallux joint were collected during barefoot walking. One-way Analysis of Covariance was conducted to examine differences among the outcome measures with group as a fixed factor and walking cadence as covariate.

The youngest group differed significantly from the other two age groups with respect to their ankle and chopart joint peak plantarflexion moment (p < 0.05). Ankle and chopart joint peak power generation as well as the lisfranc peak plantarflexion moment was found to be significantly lower in the youngest age group compared to the oldest group (p < 0.05). At the lisfranc joint, the youngest age group demonstrated a significantly higher peak plantarflexion velocity compared to the two older age groups (p < 0.05).

This study provides novel insight into the biomechanical maturation of the developing foot which may guide clinical interventions in paediatric cohorts.

This study provides novel insight into the biomechanical maturation of the developing foot which may guide clinical interventions in paediatric cohorts.Since the detection of nitrosamines (NA) in valsartan pharmaceuticals, over two years have passed. At present, the occurrence of NAs can be limited to a few drug substances and drug products, but it is already becoming apparent that the issue appears to be much bigger than initially thought. The impact on the global pharmaceutical market has been tremendous and the problem can be attributed mainly to uncritically adopted approval changes and the lack of suitable, modern analytical methods to detect those impurities in time. We hereby demonstrate how lifecycle management (LCM) can be used to develop and improve suitable and universal analytical methods within short time. The resulting SFC-MS/MS method is intended for a universal nitrosamine investigation in drug substances and drug products. Successful NA analysis was demonstrated for seven sartans, metformin, pioglitazone and ranitidine. Additionally, combination drug products, containing also amlodipine, hydrochlorothiazide, vildagliptin and sitagliptin, wers, in order to understand root causes of NA formation, maintain the drug supply and prevent drug shortage.Therapeutic monoclonal and bispecific antibodies are susceptible to modification after protein biosynthesis. These post-translational modifications (PTMs) not only contribute to mass and charge heterogeneity, but they can also negatively impact the molecule's activity, half-life, and immunogenicity. Therefore, identification and quantification of PTMs are critical to ensure the safety and efficacy of an antibody therapeutic as well as demonstrate product consistency and process control. Unprocessed C-terminal lysine on the heavy chain (HC) is a prevalent modification that contributes to this charge heterogeneity in antibodies. Peptide mapping through liquid chromatography tandem mass spectrometry (LC-MS2) enjoys higher selectivity and sensitivity for measuring this PTM relative to global PTM methods, but differences in the ionization efficiencies of the unprocessed C-terminal K peptide and the truncated C-terminal K peptide result in its overestimation. Consequently, large discrepancies in this PTM's measured abundance may exist between different characterization assays used in regulatory filings, which can be further compounded by large variability when multiple mass spectrometers are used to quantify C-terminal K during a therapeutic's lifespan. In this study, we propose a simple new method to quantify unprocessed C-terminal K in antibodies in a single LC-MS2 run that incorporates heavy isotopic standards for both the unprocessed and truncated C-terminal K peptide to build a response curve and correct for the disparity in ionization efficiency between these two different peptide sequences. The approach was evaluated across two different Orbitrap-based mass spectrometers using multiple monoclonal and bispecific therapeutic antibodies, resulting in accurate ( less then 10% error, as determined with peptide standards) and precise C-terminal K quantification during peptide mapping analysis.Epilepsy is one of the most prevalent neurological disorders, affecting approximately 1% of the world population. Despite the availability of dozens of antiepileptic drugs (AEDs) in clinical practice, the number of patients who do not respond to treatment and/or exhibit high pharmacokinetic variability remains significant, highlighting the importance of therapeutic drug monitoring (TDM). Plasma and serum are the main biological matrices applied for the TDM of AEDs, but the necessity of a specialized professional has been an obstacle to sample collection in ambulatory. Thus, drug quantification in saliva arises as a promising alternative. click here Herein, a novel highperformance liquid chromatographic (HPLC) technique with diode-array detection (DAD) was developed and fully validated, in order to simultaneously quantify carbamazepine, carbamazepine-10,11-epoxide, S-licarbazepine, lacosamide and levetiracetam in human saliva. The technique was linear in the following concentration ranges 0.2-6 mg L-1 for carbamazepine a103; r = 0.8428). Our data support that this method can be used in TDM of AEDs using human saliva samples, constituting a new approach to establish individual therapeutic ranges and assess patient's adherence to treatment.