Development of human C-peptide LC-MS isotope-dilution assay : optimization of C-peptide isolation from biological fluids and with ion exchange chromatography

Human C-peptide is an effective marker of insulin secretion in diabetes diagnostics, as it is produced in equimolar amounts with insulin. Little metabolism of C-peptide by the liver also enables its concentrations to be three to five times higher than insulin in the plasma. Although there exists a current demand for higher sensitivity, the method of C-peptide quantitative analysis by Isotope-dilution assays allows for greater specificity as compared to current immunoassay methods

Hot nitrogen deballing of Ball Grid Arrays

Ball Grid Array (BGA) packages are increasingly adopted in high reliability electronics equipment. The main reliability concern is that lead-free (Pb-free) packaged BGAs bring the risks of failures due to tin whiskers growth phenomena associated with tin or tin-rich alloys. Replacing Pb-free solder balls of BGA components with tin-lead solder alloy materials is the most effective risk mitigation strategy. Post-manufacturing processes that can be used to remove (deballing) and then deposit back (reballing) BGA solder balls have been recently developed and increasingly put in practice. This paper reports on the assessment of the thermal responses of BGAs subjected to hot nitrogen (N2) deballing and details the respective conclusions about the risk of thermally induced damage

Synthesis and characterization of biodegradable lignin nanoparticles with tunable surface properties

Lignin nanoparticles can serve as biodegradable carriers of biocidal actives with minimal environmental footprint. Here we describe the colloidal synthesis and interfacial design of nanoparticles with tunable surface properties using two different lignin precursors, Kraft (Indulin AT) lignin and Organosolv (high-purity lignin). The green synthesis process is based on flash precipitation of dissolved lignin polymer, which enabled the formation of nanoparticles in the size range of 45–250 nm. The size evolution of the two types of lignin particles is fitted on the basis of modified diffusive growth kinetics and mass balance dependencies. The surface properties of the nanoparticles are fine-tuned by coating them with a cationic polyelectrolyte, poly(diallyldimethylammonium chloride). We analyze how the colloidal stability and dispersion properties of these two types of nanoparticles vary as a function of pH and salinities. The data show that the properties of the nanoparticles are governed by the type of lignin used and the presence of polyelectrolyte surface coating. The coating allows the control of the nanoparticles’ surface charge and the extension of their stability into strongly basic regimes, facilitating their potential application at extreme pH conditions

Rotation sets of billiards with one obstacle

We investigate the rotation sets of billiards on the $m$-dimensional torus with one small convex obstacle and in the square with one small convex obstacle. In the first case the displacement function, whose averages we consider, measures the change of the position of a point in the universal covering of the torus (that is, in the Euclidean space), in the second case it measures the rotation around the obstacle. A substantial part of the rotation set has usual strong properties of rotation sets

In vivo Two-Photon Imaging of Anesthesia-Specific Alterations in Microglial Surveillance and Photodamage-Directed Motility in Mouse Cortex

Two-photon imaging of fluorescently labeled microglia in vivo provides a direct approach to measure motility of microglial processes as a readout of microglial function that is crucial in the context of neurodegenerative diseases, as well as to understand the neuroinflammatory response to implanted substrates and brain-computer interfaces. In this longitudinal study, we quantified surveilling and photodamage-directed microglial processes motility in both acute and chronic cranial window preparations and compared the motility under isoflurane and ketamine anesthesia to an awake condition in the same animal. The isoflurane anesthesia increased the length of surveilling microglial processes in both acute and chronic preparations, while ketamine increased the number of microglial branches in acute preparation only. In chronic (but not acute) preparation, the extension of microglial processes toward the laser-ablated microglial cell was faster under isoflurane (but not ketamine) anesthesia than in awake mice, indicating distinct effects of anesthetics and of preparation type. These data reveal potentiating effects of isoflurane on microglial response to damage, and provide a framework for comparison and optimal selection of experimental conditions for quantitative analysis of microglial function using two-photon microscopy in vivo.Peer reviewe

Understanding the impact of spinal cord injury on the microbiota of healthy skin and pressure injuries.

Pressure injuries (PI) are a common issue among individuals with spinal cord injury (SCI), especially in the sitting areas of the body. Considering the risk of infections occurring to PI during the wound healing process, the skin microbiome is likely to be a source of bacteria. We investigated the relationship between skin and PI microbiomes, and assessed any correlation with clinically relevant outcomes related to PI. Samples were isolated from SCI patients undergoing reconstructive surgery of PI, severity grades III and IV. DNA samples from skin and PI were analysed using 16S rRNA gene sequencing. Our results showed disparities in microbiome composition between skin and PI. The skin had lower diversity, while PI showed increased bacterial homogeneity as the severity grade progressed. The skin bacterial composition varied based on its location, influenced by Cutibacterium. Compositional differences were identified between PI grades III and IV, with clusters of bacteria colonizing PI, characterized by Pseudomonas, Proteus and Peptoniphilus. The skin and PI microbiomes were not affected by the level of the SCI. Our study highlights the differences in the microbiome of skin and PI in SCI patients. These findings could be used to target specific bacteria for PI treatment in clinical practice

Context value updating and multidimensional neuronal encoding in the retrosplenial cortex

The retrosplenial cortex (RSC) has diverse functional inputs and is engaged by various sensory, spatial, and associative learning tasks. We examine how multiple functional aspects are integrated on the single-cell level in the RSC and how the encoding of task-related parameters changes across learning. Using a visuospatial context discrimination paradigm and two-photon calcium imaging in behaving mice, a large proportion of dysgranular RSC neurons was found to encode multiple task-related dimensions while forming context-value associations across learning. During reversal learning requiring increased cognitive flexibility, we revealed an increased proportion of multidimensional encoding neurons that showed higher decoding accuracy for behaviorally relevant context-value associations. Chemogenetic inactivation of RSC led to decreased behavioral context discrimination during learning phases in which context-value associations were formed, while recall of previously formed associations remained intact. RSC inactivation resulted in a persistent positive behavioral bias in valuing contexts, indicating a role for the RSC in context-value updating.China Scholarship Council (CSC) https://doi.org/10.13039/501100004543Deutsche Forschungsgemeinschaft (German Research Foundation) https://doi.org/10.13039/501100001659EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj) https://doi.org/10.13039/501100008530Peer Reviewe

The quality and accuracy of mobile apps to prevent driving after drinking alcohol

Background: Driving after the consumption of alcohol represents a significant problem globally. Individual prevention countermeasures such as personalized mobile apps aimed at preventing such behavior are widespread, but there is little research on their accuracy and evidence base. There has been no known assessment investigating the quality of such apps.\ud \ud Objective: This study aimed to determine the quality and accuracy of apps for drink driving prevention by conducting a review and evaluation of relevant mobile apps.\ud \ud Methods: A systematic app search was conducted following PRISMA guidelines. App quality was assessed using the Mobile App Rating Scale (MARS). Apps providing blood alcohol calculators (hereafter “calculators”) were reviewed against current alcohol advice for accuracy.\ud \ud Results: A total of 58 apps (30 iOS and 28 Android) met inclusion criteria and were included in the final analysis. Drink driving prevention apps had significantly lower engagement and overall quality scores than alcohol management apps. Most calculators provided conservative blood alcohol content (BAC) time until sober calculations. None of the apps had been evaluated to determine their efficacy in changing either drinking or driving behaviors.\ud \ud Conclusions: This novel study demonstrates that most drink driving prevention apps are not engaging and lack accuracy. They could be improved by increasing engagement features, such as gamification. Further research should examine the context and motivations for using apps to prevent driving after drinking in at-risk populations. Development of drink driving prevention apps should incorporate evidence-based information and guidance, lacking in current apps

Collaborative challenges of multi-cohort project in pharmacogenetics - why time is essential for meaningful collaborations.

UNSTRUCTURED Multi-cohort projects in medicine provide an opportunity to investigate scientific questions beyond the boundaries of a single institution, and to increase sample size for more reliable results. However, the complications of these kinds of collaborations arise during management, with many administrative hurdles. Hands-on approaches and lessons learned from previous collaborations provide solutions for optimized collaboration models. Here, we use our experience in running the Swiss multi-cohort project PGX-link to show the strategy we used to tackle different challenges from project set up to getting the relevant permits, including ethics approval. We set PGX-link into an international context, since our struggles were similar to those encountered during the SYNCHROS project. We provide ad-hoc solutions for cohorts, general project management strategies, and suggestions for unified protocols between cohorts that would ease current management hurdles. Project managers are not necessarily familiar with medical projects, and even if they are, they are not aware of the intricacies behind decision making, and consequently of the time needed to set up multi-cohort collaborations. This paper is meant to be a brief overview of what we went through with our multi-cohort project and provides the necessary practices for future managers

Collaborative Challenges of Multi-Cohort Projects in Pharmacogenetics-Why Time Is Essential for Meaningful Collaborations

Multi-cohort projects in medicine provide an opportunity to investigate scientific questions beyond the boundaries of a single institution and endeavor to increase the sample size for obtaining more reliable results. However, the complications of these kinds of collaborations arise during management, with many administrative hurdles. Hands-on approaches and lessons learned from previous collaborations provide solutions for optimized collaboration models. Here, we use our experience in running PGX-link, a Swiss multi-cohort project, to show the strategy we used to tackle different challenges from project setup to obtaining the relevant permits, including ethics approval. We set PGX-link in an international context because our struggles were similar to those encountered during the SYNCHROS (SYNergies for Cohorts in Health: integrating the ROle of all Stakeholders) project. We provide ad hoc solutions for cohorts, general project management strategies, and suggestions for unified protocols between cohorts that would ease current management hurdles. Project managers are not necessarily familiar with medical projects, and even if they are, they are not aware of the intricacies behind decision-making and consequently, of the time needed to set up multi-cohort collaborations. This paper is meant to be a brief overview of what we experienced with our multi-cohort project and provides the necessary practices for future managers