CFD as a tool for modelling membrane systems

Computational fluid dynamics (CFD) is a computer-based numerical method used to analyse systems that involve fluid flow and/or heat and mass transfer (Versteeg & Malalasekera, 2007). CFD bridges the two different approaches for solving engineering problems before the computer era, theoretical and experimental; it relies on mathematical models while being easy to adapt to almost any realistic condition (Anderson & Wendt, 1995). Another feature of CFD is its versatility, as it allows the analysis of systems for a variety of applications such as chemical reactions (Salehi et al., 2016), aerodynamics (Snel, 2003), dispersion of pollutants (Chu et al., 2005), blood flows (Byun & Rhee, 2004), among many others

Micro-CT imaging reveals<i> Mekk3 </i>heterozygosity prevents cerebral cavernous malformations in <i>Ccm2</i>-deficient mice

Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases

A concept for integrated care pathways for atopic dermatitis-A GA2 LEN ADCARE initiative

INTRODUCTION: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. METHODS: The GA2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2 EN ADCARE centres. RESULTS: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. CONCLUSION: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD

A concept for integrated care pathways for atopic dermatitis—A GA2LEN ADCARE initiative

Introduction: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. Methods: The GA2LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2EN ADCARE centres. Results: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. Conclusion: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD

Functional interdependence of BRD4 and DOT1L in MLL leukemia.

Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation, we found that native BRD4 and DOT1L exist in separate protein complexes. Genetic disruption or small-molecule inhibition of BRD4 and DOT1L showed marked synergistic activity against MLL leukemia cell lines, primary human leukemia cells and mouse leukemia models. Mechanistically, we found a previously unrecognized functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in proximity to superenhancers. DOT1L, via dimethylated histone H3 K79, facilitates histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide new insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this disease with poor prognosis

Deletion of Wntless in myeloid cells exacerbates liver fibrosis and the ductular reaction in chronic liver injury

Background: Macrophages play critical roles in liver regeneration, fibrosis development and resolution. They are among the first responders to liver injury and are implicated in orchestrating the fibrogenic response via multiple mechanisms. Macrophages are also intimately associated with the activated hepatic progenitor cell (HPC) niche or ductular reaction that develops in parallel with fibrosis. Among the many macrophage-derived mediators implicated in liver disease progression, a key role for macrophage-derived Wnt proteins in driving pro-regenerative HPC activation towards a hepatocellular fate has been suggested. Wnt proteins, in general, however, have been associated with both pro-and anti-fibrogenic activities in the liver and other organs. We investigated the role of macrophage-derived Wnt proteins in fibrogenesis and HPC activation in murine models of chronic liver disease by conditionally deleting Wntless expression, which encodes a chaperone essential for Wnt protein secretion, in LysM-Cre-expressing myeloid cells (LysM-Wls mice)

Mask-related facial dermatoses in an asian pediatric population in the era of COVID-19 pandemic: A cross-sectional study

Introduction: Mask-related dermatoses have been widely reported in adults since the global COVID-19 pandemic. Compulsory mask wearing has been mandated in many countries. As pediatric dermatologists, we aim to characterize different types of mask-related dermatoses in the pediatric population, evaluate the prevalence, and potential exacerbating and mitigating factors to improve compliance in children in this era of regular mask wearing. Methods: We conducted a cross-sectional study from November 1, 2020, to January 31, 2021, at a tertiary hospital in the form of an anonymous online questionnaire. This included all children aged (2–20 years old) in our pediatric dermatology clinics, tertiary education students (16–20 years old), and children of hospital/health-care cluster staff (2–20 years old). Results: Of the 577 participants who reported regular mask wearing, 140 (24.3%) reported symptoms. The most common symptoms were itching (74.5%), dryness (49.6%), dyspnea (32.1%), and oily skin (29.9%). The most common rashes were acne (48.9%), eczema (27%), dryness/peeling (23.4%), urticaria (18.2%), and cheilitis (16.8%). The most statistically significant risk factors for developing mask-related symptoms and/or rashes were (a) prolonged duration of mask wearing/day and (b) preexisting dermatoses and/or atopic history (especially atopic dermatitis). Conclusions: As the pediatric population remains vulnerable to emerging COVID-19 variants and other respiratory viruses, masks remain an important form of protection in daily life. Like in adults, regular mask wearing can lead to various facial symptoms/dermatoses in pediatric wearers, adding to dermatological burden during a pandemic. Those with preexisting risk factors should be made aware of this. We recommend all pediatric mask wearers should not exceed continuous mask wearing for 4 h and to take scheduled “mask breaks” in safe, well-ventilated areas

Growth, saturation, and collapse of laser-driven plasma density gratings

The plasma density grating induced by intersecting intense laser pulses can be utilized as optical compressors, polarizers, waveplates, and photonic crystals for the manipulation of ultra-high-power laser pulses. However, the formation and evolution of plasma density grating are still not fully understood as linear models are adopted to describe them usually. In this paper, two theoretical models are presented to study the formation process of plasma density grating in the nonlinear stages. In the first model, an implicit analytical solution based on the fluid equations is presented, while in the second model, a particle-mesh method is adopted. It is found that both models can describe the plasma density grating formation at different stages, well beyond the linear growth stage. More importantly, the second model can reproduce the phenomenon of ion "wave-breaking"of plasma density grating, which eventually induces the saturation and collapse of plasma density grating. Using the second model, the saturation time and maximum achievable peak density of plasma density grating are obtained as functions of laser intensity and plasma density, which can be applied to estimate the lifetime and capability of plasma density grating in experiments. The results from these two newly developed models are verified using particle-in-cell simulations

Transition from backward to sideward stimulated Raman scattering with broadband lasers in plasmas

Broadband lasers have been proposed as future drivers of inertial confined fusion (ICF) to enhance the laser–target coupling efficiency via the mitigation of various parametric instabilities. The physical mechanisms involved have been explored recently, but are not yet fully understood. Here, stimulated Raman scattering (SRS) as one of the key parametric instabilities is investigated theoretically and numerically for a broadband laser propagating in homogeneous plasma in multidimensional geometry. The linear SRS growth rate is derived as a function of scattering angles for two monochromatic laser beams with a fixed frequency difference δω. If δω/ω0 ∼ 1%, with ω0 the laser frequency, these two laser beams may be decoupled in stimulating backward SRS while remaining coupled for sideward SRS at the laser intensities typical for ICF. Consequently, side-scattering may dominate over backward SRS for two-color laser light. This finding of SRS transition from backward to sideward SRS is then generalized for a broadband laser with a few-percent bandwidth. Particle-in-cell simulations demonstrate that with increasing laser bandwidth, the sideward SRS gradually becomes dominant over the backward SRS. Since sideward SRS is very efficient in producing harmful hot electrons, attention needs to be paid on this effect if ultra-broadband lasers are considered as next-generation ICF drivers