Tissue gene expression profiles and communication networks inform candidate blood biomarker identification in psoriasis and atopic dermatitis.

Overlapping clinical and pathomechanistic features can complicate the diagnosis and treatment of inflammatory skin diseases, including psoriasis and atopic dermatitis (AD). Spatial transcriptomics allows the identification of disease- and cell-specific molecular signatures that may advance biomarker development and future treatments. This study identified transcriptional signatures in keratinocytes and sub-basal CD4+ and CD8+ T lymphocytes from patients with psoriasis and AD. In silico prediction of ligand:receptor interactions delivered key signalling pathways (interferon, effector T cells, stroma cell and matrix biology, neuronal development, etc.). Targeted validation of selected transcripts, including CCL22, RELB, and JUND, in peripheral blood T cells suggests the chosen approach as a promising tool also in other inflammatory diseases. Psoriasis and AD are characterized by transcriptional dysregulation in T cells and keratinocytes that may be targeted therapeutically. Spatial transcriptomics is a valuable tool in the search for molecular signatures that can be used as biomarkers and/or therapeutic targets.

Gathering expert consensus to inform a proposed trial in chronic nonbacterial osteomyelitis (CNO).

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and adolescents. CNO is associated with pain, bone swelling, deformity, and fractures. Its pathophysiology is characterized by increased inflammasome assembly and imbalanced expression of cytokines. Treatment is currently based on personal experience, case series and resulting expert recommendations. Randomized controlled trials (RCTs) have not been initiated because of the rarity of CNO, expired patent protection of some medications, and the absence of agreed outcome measures. An international group of fourteen CNO experts and two patient/parent representatives was assembled to generate consensus to inform and conduct future RCTs. The exercise delivered consensus inclusion and exclusion criteria, patent protected (excludes TNF inhibitors) treatments of immediate interest (biological DMARDs targeting IL-1 and IL-17), primary (improvement of pain; physician global assessment) and secondary endpoints (improved MRI; improved PedCNO score which includes physician and patient global scores) for future RCTs in CNO.

Buried graphene heterostructures for electrostatic doping of low-dimensional materials.

The fabrication and characterization of steep slope transistor devices based on low-dimensional materials requires precise electrostatic doping profiles with steep spatial gradients in order to maintain maximum control over the channel. In this proof-of-concept study we present a versatile graphene heterostructure platform with three buried individually addressable gate electrodes. The platform is based on a vertical stack of embedded titanium and graphene separated by an intermediate oxide to provide an almost planar surface. We demonstrate the functionality and advantages of the platform by exploring transfer and output characteristics at different temperatures of carbon nanotube field-effect transistors with different electrostatic doping configurations. Furthermore, we back up the concept with finite element simulations to investigate the surface potential. The presented heterostructure is an ideal platform for analysis of electrostatic doping of low-dimensional materials for novel low-power transistor devices.

Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS: Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS: The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.

Using diffusion MRI data acquired with ultra-high gradient strength to improve tractography in routine-quality data.

The development of scanners with ultra-high gradient strength, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today's state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.

International validation of the Bullous Pemphigoid Disease Area Index severity score and calculation of cut-off values for defining mild, moderate and severe types of bullous pemphigoid.

BACKGROUND: The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES: The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS: Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS: In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P < 0·004), but not with anti-BP230 antibodies (r = 0·17, P = 0·15). CONCLUSIONS: This study suggests cut-off values of 20-57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.

Ex vivo Bone Models and Their Potential in Preclinical Evaluation.

PURPOSE OF REVIEW: Novel therapies for damaged and diseased bone are being developed in a preclinical testing process consisting of in vitro cell experiments followed by in vivo animal studies. The in vitro results are often not representative of the results observed in vivo. This could be caused by the complexity of the natural bone environment that is missing in vitro. Ex vivo bone explant cultures provide a model in which cells are preserved in their native three-dimensional environment. Herein, it is aimed to review the current status of bone explant culture models in relation to their potential in complementing the preclinical evaluation process with specific attention paid to the incorporation of mechanical loading within ex vivo culture systems. RECENT FINDINGS: Bone explant cultures are often performed with physiologically less relevant bone, immature bone, and explants derived from rodents, which complicates translatability into clinical practice. Mature bone explants encounter difficulties with maintaining viability, especially in static culture. The integration of mechanical stimuli was able to extend the lifespan of explants and to induce new bone formation. Bone explant cultures provide unique platforms for bone research and mechanical loading was demonstrated to be an important component in achieving osteogenesis ex vivo. However, more research is needed to establish a representative, reliable, and reproducible bone explant culture system that includes both components of bone remodeling, i.e., formation and resorption, in order to bridge the gap between in vitro and in vivo research in preclinical testing.

Human Papillomavirus-type distribution in anogenital lesions of prepubertal children.

BACKGROUND: In contrast to adults, only limited data are available on the human papillomavirus (HPV)-type spectrum in anogenital warts (AGW) of children. OBJECTIVE: This study aimed to evaluate the HPV-type spectrum in AGW of prepubertal children. MATERIALS & METHODS: In a retrospective German multicentre study, HPV genotyping was performed in AGW biopsies of 55 1- to 12-year-old children using HPV group-specific PCRs followed by hybridization with type-specific probes or sequence analysis. RESULTS: Human papillomavirus-DNA was found in 53 of the 55 AGW. In 58.5% (31/53) of the HPV-positive AGW, mucosal HPV types were detected. HPV6 (27/53, 50.9%) was the predominant type. 43.4% (23/53) of the lesions were induced by cutaneous HPV types (HPV2, HPV27, HPV57). Mucosal HPV types were significantly more common in children under 5 years of age than in children 5 years of age and older (22/25, 88.0% [95% CI: 70.0-95.8] vs. 9/28, 32.1% [95% CI: 17.9-50.7], P < 0.001). In contrast, cutaneous HPV types were significantly more prevalent in the 5- to 12-year age group (4/25, 16.0% [95% CI 6.4-34.7] vs. 19/28, 67.9% [95% CI 49.3-82.1], P < 0.001). CONCLUSION: Anogenital warts in 5- to 12-year-old children are frequently associated with cutaneous HPV types, possibly due to horizontal transmission. HPV typing, in addition to comprehensive clinical and psychosocial evaluation, can potentially help in the assessment of these cases.

A two-stage approach to primary TKA using articulating antibiotic-loaded spacers improve function and eradicate infection in septic arthritic knees.

PURPOSE: The treatment of an infected arthritic knee might be challenging. The failure rate has been reported to be high for open or arthroscopic debridement. A subsequently high rate of infection has been noted in these patients undergoing primary total knee arthroplasty (TKA). In the present study, a two-stage approach using an articulating spacer was used. The hypothesis was that the procedure would eradicate the infection and improve pain and function in these patients. METHODS: A total of 16 consecutive patients were enrolled in this retrospective study. The mean follow-up time was 6.1 years (range 2.0-9.9 years). Patients with advanced osteoarthritis and infection of the knee were included. All patients had previously undergone one or more failed arthroscopic or open procedures for the eradication of infection. All patients received the same homemade metal-on-plastic articulating antibiotic spacer. Double antibiotic therapy was given for 2 weeks intravenously and orally for 4 weeks. TKA implantation was performed 6 weeks after the first stage. RESULTS: The infection was eradicated without recurrence in all patients. The functional results were significantly improved, and pain was significantly reduced after spacer and TKA implantation. The mean amount of knee flexion was 95 ± 30° preoperatively, and it increased to 109 ± 14° (p = 0.012) after spacer implantation and to 119 ± 10° (p = 0.002) after TKA implantation. The mean KSS objective was 58 ± 12 preoperatively, and it increased to 75 ± 14 (p < 0.0001) after spacer implantation and to 96 ± 3 (p < 0.0001) after TKA implantation. The mean KSS function was 17 ± 11 preoperatively, and it increased to 46 ± 10 (p < 0.0001) after spacer implantation and to 86 ± 6 (p < 0.0001) after TKA implantation. The mean VAS score was 65 ± 11 preoperatively, and it decreased to 2 ± 4 (p < 0.0001) after spacer implantation and to 1 ± 2 (p < 0.0001) after TKA implantation. CONCLUSION: The two-stage procedure for the treatment of infected arthritic knees after failed eradication surgery was effective in all patients. Using an antibiotic articulating metal-on-plastic cement spacer showed improved functional results between the stages and at the final follow-up. No intra- or postoperative complications occurred.

Long-Range Propagation and Interference of d-Wave Superconducting Pairs in Graphene.

Recent experiments have shown that proximity with high-temperature superconductors induces unconventional superconducting correlations in graphene. Here, we demonstrate that those correlations propagate hundreds of nanometers, allowing for the unique observation of d-wave Andreev-pair interferences in YBa_{2}Cu_{3}O_{7}-graphene devices that behave as a Fabry-Perot cavity. The interferences show as a series of pronounced conductance oscillations analogous to those originally predicted by de Gennes-Saint-James for conventional metal-superconductor junctions. The present demonstration is pivotal to the study of exotic directional effects expected for nodal superconductivity in Dirac materials.

Localized Nanoresonator Mode in Plasmonic Microcavities.

Submicron-thick hexagonal boron nitride crystals embedded in noble metals form planar Fabry-Perot half-microcavities. Depositing Au nanoparticles on top of these microcavities forms previously unidentified angle- and polarization-sensitive nanoresonator modes that are tightly laterally confined by the nanoparticle. Comparing dark-field scattering with reflection spectroscopies shows plasmonic and Fabry-Perot-like enhancements magnify subtle interference contributions, which lead to unexpected redshifts in the dark-field spectra, explained by the presence of these new modes.

Measuring mineralised tissue formation and resorption in a human 3D osteoblast-osteoclast co-culture model.

In vitro tissue engineered bone constructs have been developed, but models which mimic both formation and resorption in parallel are still lacking. To be used as a model for the bone remodeling process, the formation and resorption of mineralised tissue volume over time needs to be visualised, localised and quantified. The goal of this study was to develop a human 3D osteoblast-osteoclast co-culture in which 1) osteoblasts deposit mineralised matrix, 2) monocytes differentiate into resorbing osteoclasts, and 3) the formation and resorption of mineralised matrix could be quantified over time using micro-computed tomography (µCT). Mesenchymal stromal cells were seeded on silk fibroin scaffolds and differentiated towards osteoblasts to create mineralised constructs. Thereafter, monocytes were added and differentiated towards osteoclasts. The presence of osteoblasts and osteoclasts was confirmed using immunohistochemistry. Osteoclastic activity was confirmed by measuring the increased release of osteoclast marker tartrate resistant acid phosphatase (TRAP), suggesting that osteoclasts were actively resorbing mineralised tissue. Resorption pits were visualised using scanning electron microscopy. Mineralised matrix formation and resorption were quantified using µCT and subsequent scans were registered to visualise remodelling. Both formation and resorption occurred in parallel in the co-culture. The resorbed tissue volume exceeded the formed tissue volume after day 12. In conclusion, the current model was able to visualise, localise and quantify mineralised matrix formation and resorption. Such a model could be used to facilitate fundamental research on bone remodeling, facilitate drug testing and may have clinical implications in personalised medicine by allowing the use of patient cells.

Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV).

BACKGROUND: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the United States. OBJECTIVES: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. RESULTS: The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations.

[Epidermolysis bullosa acquisita]. / Epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is a rare acquired subepidermal bullous autoimmune dermatosis, associated with autoantibodies against collagen type VII, the most important component of dermal anchoring fibrils. Blister induction occurs after binding of autoantibodies to collagen type VII, leading to complement activation, recruitment of neutrophils and secretion of proteases. Clinically, the disease is mostly characterized by tense blisters on trauma-exposed body areas which heal with scarring (mechanobullous form of EBA). The second most frequent subtype of EBA is inflammatory EBA, a bullous pemphigoid-like disease associated with pruritus. Involvement of mucous membranes and/or lesions in the head and neck area additionally point to the diagnosis of EBA. The mechanobullous type of EBA and EBA with intensive mucous membrane lesions display a chronic course and are often extremely resistant to therapy. Topical and systemic glucocorticoids, dapsone, colchicine, classical immunosuppressants, anti-CD20 antibodies, immunoadsorption or intravenous immunoglobulins have been reported as treatments.

[The Nocturnal Respiratory Rate in COPD Patients of Varying GOLD Severity with/without Nicotine Consumption: Calculation by Means of Breath Sound Analysis]. / Die nächtliche Atemfrequenz bei COPD-Patienten unterschiedlicher GOLD-Schweregrade mit/ohne Nikotinkonsum: Berechnet mittels Atemgeräuschanalyse.

Respiratory rate is an important risk marker and enables early detection of critically ill and vulnerable patients in clinical routine. The aim of this pilot study with 31 patients (COPD severity levels II - IV) was to determine the mean nocturnal respiratory rate based on breath sound recordings and to investigate the dependence of respiratory rate on COPD severity level and smoker status. The mean respiratory rate of the total collective was 19/min. For the COPD-GOLD severity levels, no significant differences in mean respiratory rate could be observed. When nicotine consumption is taken into account, active smokers showed a significantly higher mean respiratory rate of 20.84 ±â€Š4.45/min compared to non-smokers with 17.41 ±â€Š3.14/min (p < 0.05). In addition, active smokers in the study were significantly more frequent among patients with night-time wheezing (60 % vs. 23.8 %). This might suggest that smokers need to perform increased breathing work with increased breathing rate to compensate for oxygen deficiency in bronchial obstruction. The results of the present study show that with the acoustic recording of breath sounds, a reliable representation and calculation of the breath frequency is possible.

[Research agenda oral care for older people in the Netherlands and Flanders (Belgium)]. / Wetenschapsagenda 'Mondzorg voor ouderen' in Nederland en Vlaanderen.

Oral care for older people is an underexposed topic in dentistry as well as in general healthcare, while oral care professionals are increasingly confronted with frail and multimorbid older people with complex care needs. The research agenda 'Oral care for the elderly' was developed to encourage the collaboration of researchers in the Netherlands and Flanders (Belgium) to do more research in this area and in this way, to achieve an expansion and implementation of knowledge. This will make possible the provision of a socially responsible and robust basis for sustainable oral care for frail older people. The focus of the agenda is on 3 themes, namely oral health and oral function for older people; multi/interdisciplinary collaboration within primary care and the costs, benefits and long-term effect(s) of oral care throughout the entire course of life. This article provides an overview of this research agenda and the way in which it has been established.

IL10 promoter haplotypes may contribute to altered cytokine expression and systemic inflammation in celiac disease.

Celiac disease (CD) is an autoimmune/inflammatory condition triggered by dietary gluten intake in genetically predisposed individuals. Though associations with MHC class II HLA-DQ2 or -DQ8 are the primary and necessary genetic predisposition for CD, >97% of genetically predisposed individuals never develop CD. Cytokines were measured in the serum of CD patients and controls. Possible associations with IL10 promoter variants were investigated. Cytokine expression from PBMCs was monitored in response to gluten exposure, or CD3/TCR complex stimulation in the absence or presence of recombinant IL-10. Serum cytokines varied between patients with CD at the time of diagnosis, after dietary elimination of gluten, and healthy controls. Serum IL-17A reflected disease activity. Reduced IL-10 serum levels and altered IL-10 expression by PBMCs coincided with IL10 promoter haplotypes that encode for "low" IL-10 expression (ATA). Increased prevalence of ATA IL10 promoter haplotypes and subsequently reduced IL-10 expression may be an immunological cofactor in individuals genetically predisposed for the development of CD. Resulting cytokine imbalances may be utilized as disease biomarkers in CD.

CD14+ monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3 inflammasome expression.

The pathophysiology of chronic nonbacterial osteomyelitis (CNO) remains incompletely understood. Increased NLRP3 inflammasome activation and IL-1ß release in monocytes from CNO patients was suggested to contribute to bone inflammation. Here, we dissect immune cell infiltrates and demonstrate the involvement of monocytes across disease stages. Differences in cell density and immune cell composition may help to discriminate between BOM and CNO. However, differences are subtle and infiltrates vary in CNO. In contrast to other cells involved, monocytes are a stable element during all stages of CNO, which makes them a promising candidate in the search for "drivers" of inflammation. Furthermore, we link increased expression of inflammasome components NLRP3 and ASC in monocytes with site-specific DNA hypomethylation around the corresponding genes NLRP3 and PYCARD. Our observations deliver further evidence for the involvement of pro-inflammatory monocytes in the pathophysiology of CNO. Cellular and molecular alterations may serve as disease biomarkers and/or therapeutic targets.

A history of obesity leaves an inflammatory fingerprint in liver and adipose tissue.

BACKGROUND/OBJECTIVES: Dieting is a popular yet often ineffective way to lower body weight, as the majority of people regain most of their pre-dieting weights in a relatively short time. The underlying molecular mechanisms driving weight regain and the increased risk for metabolic disease are still incompletely understood. Here we investigate the molecular alterations inherited from a history of obesity. METHODS: In our model, male high-fat diet (HFD)-fed obese C57BL/6J mice were switched to a low caloric chow diet, resulting in a decline of body weight to that of lean mice. We measured body composition, as well as metrics of glucose, insulin and lipid homeostasis. This was accompanied by histological and gene expression analysis of adipose tissue and liver to assess adipose tissue inflammation and hepatosteatosis. Moreover, acute hypothalamic response to (re-) exposure to HFD was assessed by qPCR. RESULTS & CONCLUSIONS: Within 7 weeks after diet switch, most obesity-associated phenotypes, such as body mass, glucose intolerance and blood metabolite levels were reversed. However, hepatic inflammation, hepatic steatosis as well as hypertrophy and inflammation of perigonadal, but not subcutaneous, adipocytes persisted in formerly obese mice. Transcriptional profiling of liver and perigonadal fat revealed an upregulation of pathways associated with immune function and cellularity. Thus, we show that weight reduction leaves signs of inflammation in liver and perigonadal fat, indicating that persisting proinflammatory signals in liver and adipose tissue could contribute to an increased risk of formerly obese subjects to develop the metabolic syndrome upon recurring weight gain.

Localisation of mineralised tissue in a complex spinner flask environment correlates with predicted wall shear stress level localisation.

Spinner flask bioreactors have often been employed for bone tissue engineering. However, the reasons for their success in facilitating bone growth remain inconclusive. It was hypothesised that engineered bone tissue formation can be attributed to mechanical stimuli, which can be predicted in the tissue engineered construct. To test the hypothesis and draw conclusions as to how mechanical stimulation affects cell behaviour, a multi- disciplinary approach using cell culture experiments and computational fluid dynamics (CFD) to simulate the complex flow within the spinner flask and scaffold was employed. Micro-computed tomography and histology showed that statically cultured human bone marrow derived stromal cells on silk fibroin scaffolds did not form extracellular matrix (ECM) or deposit minerals. However, constructs cultured at 60 rpm resulted in ECM formation and mineralisation, mainly at the bottom of the scaffold (bottom: 78 ± 7 %, middle: 17 ± 5 %, top: 5 ± 2 % of total mineralised volume). Culturing at 300 rpm led to a more homogeneously distributed ECM (bottom: 40 ± 14 %, middle: 33 ± 1 %, top: 27 ± 14 % of total mineralised volume). These observations were in agreement (Pearson correlation coefficient: 97 %) with the computational simulations that predicted maximal scaffold mineralisation, based on wall shear stress stimulation, in the bottom at 60 rpm and in the main body at 300 rpm. Such combinations of CFD modelling and experimentation could advance our knowledge of the mechanical stimuli that cells experience in vitro and link them to biological responses.