Display omitted
Orodispersible films (ODF) are innovative drug formulations that introduce a promising approach to pharmacotherapy. They represent single- or multi-layer polymer films that show ...sufficient stability but disintegrate easily. Often no water is needed for ingestion. Therefore, ODF are suitable for patients with swallowing difficulties such as elderly people, children, or patients with restricted transport in the gastrointestinal tract. Also, to avoid the first-pass effect when the drug is already absorbed via the mucosa. Initially developed as niche products ODFs are currently the subject of industrial and university research as dosage forms for improved application and compliance for medical treatment of a multitude of different diseases. An interesting aspect is that ODF can also be produced in an individualized way. This can support the trend toward personalized medicine. Here, we provide at first an overview of the historical background, characterization, and composition of ODFs. Subsequently, technical aspects of the manufacturing process, including three-dimensional printing technology and inkjet printing will be reviewed. As ODFs are promising drug delivery systems for customized small-scale pharmacy preparations, we place particular emphasis on product examples giving the possibility for individualization for their consumers. Finally, we summarize formulations, applications in development, limitations, and the current patent situation.
Pharmacometric methods have hugely benefited from progress in analytical and computer sciences during the past decades, and play nowadays a central role in the clinical development of new medicinal ...drugs. It is time that these methods translate into patient care through therapeutic drug monitoring (TDM), due to become a mainstay of precision medicine no less than genomic approaches to control variability in drug response and improve the efficacy and safety of treatments. In this review, we make the case for structuring TDM development along five generic questions: 1) Is the concerned drug a candidate to TDM? 2) What is the normal range for the drug's concentration? 3) What is the therapeutic target for the drug's concentration? 4) How to adjust the dosage of the drug to drive concentrations close to target? 5) Does evidence support the usefulness of TDM for this drug? We exemplify this approach through an overview of our development of the TDM of imatinib, the very first targeted anticancer agent. We express our position that a similar story shall apply to other drugs in this class, as well as to a wide range of treatments critical for the control of various life-threatening conditions. Despite hurdles that still jeopardize progress in TDM, there is no doubt that upcoming technological advances will shape and foster many innovative therapeutic monitoring methods.
The interactions that take place in physical education (PE) between teachers and students have received large attention from the scientific community. However, despite the existence of different ...studies aiming to promote motivation among students through school interventions, there seem to be no interventions based on motivational strategies in which interventions are personalized to better fit teachers’ own characteristics on the basis of theoretical contents grounded in self-determination theory. This study aims to present a protocol intervention in the PE context based on SDT to improve teaching behaviours through an individualized and lifelong training program. This protocol is a convenience study in which PE teachers will design and implement motivational strategies to increase students’ motivation in class. The training program will take place along the intervention to allow teachers to personalize their implementation of motivational strategies according to their specific context. Data collection will be conducted before, during and after the intervention using recorded sessions (observational methodology), interviews (qualitative approach), and questionnaires (quantitative approach). The measures will assess teachers’ and students’ perceived teaching styles. This intervention program is expected to change and improve the quality of teaching behaviours, which could foster students’ psychosocial health.
Spermiogenesis is the longest phase of spermatogenesis, with dramatic morphological changes and a final step of spermiation, which involves protein degradation and the removal of excess cytoplasm; ...therefore, we hypothesized that macroautophagy/autophagy might be involved in the process. To test this hypothesis, we examined the function of ATG5, a core autophagy protein in male germ cell development. Floxed Atg5 and Stra8− iCre mice were crossed to conditionally inactivate Atg5 in male germ cells. In Atg5
flox/flox
; Stra8− iCre mutant mice, testicular expression of the autophagosome marker LC3A/B-II was significantly reduced, and expression of autophagy receptor SQSTM1/p62 was significantly increased, indicating a decrease in testicular autophagy activity. The fertility of mutant mice was dramatically reduced with about 70% being infertile. Sperm counts and motility were also significantly reduced compared to controls. Histological examination of the mutant testes revealed numerous, large residual bodies in the lumen of stages after their normal resorption within the seminiferous epithelium. The cauda epididymal lumen was filled with sloughed germ cells, large cytoplasmic bodies, and spermatozoa with disorganized heads and tails. Examination of cauda epididymal sperm by electron microscopy revealed misshapen sperm heads, a discontinuous accessory structure in the mid-piece and abnormal acrosome formation and loss of sperm individualization. Immunofluorescence staining of epididymal sperm showed abnormal mitochondria and acrosome distribution in the mutant mice. ATG5 was shown to induce autophagy by mediating multiple signals to maintain normal developmental processes. Our study demonstrated ATG5 is essential for male fertility and is involved in various aspects of spermiogenesis.
Abbreviations: AKAP4: a-kinase anchoring protein 4; ATG5: autophagy-related 5; ATG7: autophagy-related 7; ATG10: autophagy-related 10; ATG12: autophagy-related 12; cKO: conditional knockout; DDX4: DEAD-box helicase 4; MAP1LC3/LC3/tg8: microtubule-associated protein 1 light chain 3; PBS: phosphate-buffered saline; PIWIL2/MILI: piwi like RNA-mediated gene silencing 2; RT-PCR: reverse transcription-polymerase chain reaction; SQSTM1/p62: sequestosome 1; TBC: tubulobulbar complexes; WT: wild type.
Display omitted
Due to a high inter-individual variability in its pharmacokinetics, tacrolimus dose individualization is mandatory. Even though the expert opinion has defined the area under the curve ...(AUC) as the best marker to use when performing dose adjustment of tacrolimus, most centres only use trough levels. Multiple targets have been proposed for this parameter and physicians rely largely on their personal experience when making a decision about dose adjustment. Several population pharmacokinetics models (POPPK) allowing AUC determination have been developed, but only a few are actually used in routine practice for dose individualization. These POPPK models can also be used to perform Monte Carlo simulations that help to establish different dosing rules or to anticipate the pharmacokinetics of tacrolimus in particular populations, without conducting clinical trials. Various available applications of POPPK models to assist the prescriber in choosing the best tacrolimus dose are discussed in this paper as well as the difficulties in introducing them into routine therapeutic drug monitoring.
Cooperation, acoustically signaled through vocal convergence, is facilitated when group members are more similar. Excessive vocal convergence may, however, weaken individual recognizability. This ...study aimed to explore whether constraints to convergence can arise in circumstances where interlocutors need to enhance their vocal individuality. Therefore, we tested the effects of group size (3 and 5 interactants) on vocal convergence and individualization in a social communication scenario in which individual recognition by voice is at stake.
In an interactive game, players had to recognize each other through their voices while solving a cooperative task online. The vocal similarity was quantified through similarities in speaker i-vectors obtained through probabilistic linear discriminant analysis (PLDA). Speaker recognition performance was measured through the system Equal Error Rate (EER).
Vocal similarity between-speakers increased with a larger group size which indicates a higher cooperative vocal behavior. At the same time, there was an increase in EER for the same speakers between the smaller and the larger group size, meaning a decrease in overall recognition performance.
The decrease in vocal individualization in the larger group size suggests that ingroup cooperation and social cohesion conveyed through acoustic convergence have priority over individualization in larger groups of unacquainted speakers.
Many trends, such as cyber-physical systems, Internet of Things or digital twins are currently predominant in research and development. However, the teaching and training of these topics is often ...neglected. Especially, students or participants of a training course cannot develop and apply new technologies on their own. In order to meet this demand, this paper presents an approach that segments an automated production system into modules. The complexity of the system can be varied depending on the needs of the students or participants. With this, classical automation topics as well as state-of-the-art topics can be touched and trained. Additionally, the concept is designed in such a way that it is not only applicable in university education, but also that individual topics can be taught in half-day or one-day seminars with appropriate previous experience.
: In elite athletes, training individualization is widely recommended to optimize competitive performance. Previous studies have evidenced the impact of hormonal fluctuations on different performance ...parameters among female athletes. While consideration of menstrual cycle (MC) phases as a parameter in training individualization strategies is necessary, systematic evidence identifying such impacts in elite athletes should be evaluated.
: Systematically review publications that have investigated the link between MC phases and performance in elite female athletes. The overarching aim is to identify whether a consensus across studies exists enabling evidence-based recommendations for training individualization depending on menstrual cycle phases.
: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three major scientific publication databases were searched from inception until November 3, 2020. Studies included focused on the influence of physiological or psychological parameters throughout at least one phase of the menstrual cycle of elite athletes.
: A total of 780 search results were yielded and 26 references from a past bibliography were added manually. About 662 papers were reviewed of which 218 studies were assessed for eligibility. Of these, only seven (1%) precisely investigated the influence of a performance or physical parameter during at least one menstrual cycle phase. These seven studies included a total of 314 elite female participants (20.58 ± 1.91 years). Three used interviews, questionnaires or prospective analyses of reports. Four conducted several performance tests or included physical measures although only two performed tests during training or before/during competition. Among the seven studies, five performed hormonal testing through sampling of blood, saliva, or urine. The remaining relied on athletes' menstruation diaries. The current evidence suggests a variable association between menstrual cycle and a few performance-related outcomes, such as endurance or power resistance, ligament stiffness, decision making skills, psychology, or competitiveness.
: Different sports performance-related parameters are affected during the menstrual cycle among elite athletes, but the parameters themselves and the magnitude and the direction of the effects are inconclusive. Additional longitudinal and prospective studies to systematically monitor on-field performance parameters are urgently required in order to enable recommendations and training individualization in female elite athletes.
The authors develop a conceptual model of how the congruence of political ideology and persuasive appeals enhances sustainable behaviors. In study 1, persuasive appeals consistent with ...individualizing and binding moral foundations were developed to enhance liberal and conservative recycling. In study 2, individualizing and binding appeals were tested on actual recycling behavior using a longitudinal field study to demonstrate the effectiveness of messages congruent with the moral foundations of liberals and conservatives. Study 3 demonstrated that enhanced fluency represents the underlying psychological process that mediates the relationship between message congruence and intentions. Moreover, study 3 established that spillover effects resulting from increased intentions to engage in sustainable disposition behavior enhance intentions to engage in sustainable acquisition and consumption behaviors. Finally, study 4 ruled out potential message confounds to demonstrate the robustness of the findings. Practical implications for marketers and public policy officials interested in increasing sustainable behaviors are offered.
Cet article interroge la transition vers l’âge adulte dans le monde occidental contemporain, où la mythique individualiste est prégnante. Nous avons voulu explorer l’impact de ce discours sur le ...processus d’individuation propre à l’adolescence. Pour ce faire, nous avons observé et analysé le fonctionnement trigénérationnel de 4 familles « tout-venant » avec un adolescent de genre masculin, afin de voir quelles étaient la créativité et la restructuration de leur système familial. Cette transformation a été étudiée suivant une approche systémique sous trois angles : celui de l’adolescent, du couple parental et celui des grands-parents. Notre travail a permis de mettre en évidence, à une échelle certes petite, l’importance du travail de transformation au sein de chaque famille. L’implication du groupe familial dans la transition permet de constituer une sorte de « moi-peau familial » suffisamment contenante afin d’organiser ce passage à l’âge adulte pour ces 4 adolescents.