Native Morphology Research Articles

Does contemporary total knee designs replicate the anatomy of the native trochlea?

Registry data shows that less surgeons are resurfacing the patella during total knee arthroplasty (TKA). This tendency highlights the importance of matching trochlear and native patellar anatomy. Currently, there is a lack of consensus on implant design that best accommodates native patellae. The objective of this study was to compare the trochlear morphology of a large selection of contemporary TKA designs with the native trochlear anatomy. Three-dimensional models of 13 femoral component designs from seven manufacturers and 37 healthy human femora (average age: 31.2 ± 13.4years) were reconstructed. The trochlear morphology, including trochlear length, sulcus angle, trochlear groove angle, and height and width of the medial and lateral facets, was measured along the trochlea at 15° increments. The prosthetic trochlea was shorter and shallower compared to the native trochlea (p < 0.01). The native trochlea was bilinear and had a medial orientation proximally, whereas all asymmetrical TKA designs had a laterally oriented trochlea, resulting in opposite trochlear groove orientation (TKA, 5.8 ± 3.7°; native -3.1 ± 4.1°, p < 0.001). In addition, a strong correlation (R2 = 0.89) was found in TKA models between the heights of the medial and lateral facets, which was not observed for the native femora (R2 = 0.06). This study highlights that the lateral trochlear orientation in existing TKA models is not anatomical. Given the rising trend in patellar non-resurfacing during TKA, further studies are necessary to improve trochlear design that better accommodates the native patellar morphology.

The Effect of Dipeptide Repeat Proteins on FUS/TDP43-RNA Condensation in C9orf72 ALS/FTD.

Condensation of RNA binding proteins (RBPs) with RNA is essential for cellular function. The most common familial cause of the diseases ALS and FTD is C9orf72 repeat expansion disorders that produce dipeptide repeat proteins (DPRs). We explore the hypothesis that DPRs disrupt the native condensation behavior of RBPs and RNA through molecular interactions resulting in toxicity. FUS and TDP43 are two RBPs known to be affected in ALS/FTD. We use our previously developed 1-bead-per-amino acid and a newly developed 3-bead-per-nucleotide molecular dynamics model to explore ternary phase diagrams of FUS/TDP43-RNA-DPR systems. We show that the most toxic arginine containing DPRs (R-DPRs) can disrupt the RBP condensates through cation-π interactions and can strongly sequester RNA through electrostatic interactions. The native droplet morphologies are already modified at small additions of R-DPRs leading to non-native FUS/TDP43-encapsulated condensates with a marbled RNA/DPR core.

Response surface methology for enzymatic ultrasound assisted sp-ICP-MS assessment of cuonps in seafood: Occurrence and bioaccumulation

A novel approach for a reliable extraction and analytical characterization of copper oxide nanoparticles (CuONPs) at trace levels on seafood samples was tuned up using single particle inductively coupled plasma mass spectrometry (sp-ICP-MS). Variables for enzymatic extraction of CuONPs were optimised via response surface methodology (RSM) analysis, to maximize both the extracted CuONPs mass and number concentrations without altering their native size and morphology. Analytical performance features of the whole (enzymatic ultrasound-assisted/sp-ICP-MS) approach were thoroughly evaluated. Furthermore, the proposed extraction approach demonstrated higher efficiency compared to an alternative alkaline hydrolysis-based methodology. Finally, nine seafood samples from diverse nature were analysed for CuONPs content and particle size by sp-ICP-MS, revealing significant NPs concentrations in most cases. Attained results enabled the assessment of health risks associated with CuONPs bioaccumulation in seafood organisms.

Abstract We006: Metabolic Reprogramming to Increase Mitochodnrial Mass, Fusion and Energetics Represents an Important Rate Limiting Step in Direct Cardiac Reprogramming

Direct reprogramming of cardiac fibroblasts (CFs) into induced cardiomyocytes (iCMs) shows promise for treating myocardial infarction (MI). However, low conversion efficiency and relative immaturity of iCMs have so far precluded its clinical translation. Native CM maturation and cell cycle exit is associated with a switch from glycolytic metabolism to mitochondrial fatty acid oxidation (FAO), accompanied by a shift in the dynamic balance of mitochondrial fission (dividing) and fusion (joining) toward fusion. Because CFs lack the energy requirements of CMs, we hypothesized that transdifferentiation of CFs to iCMs requires a similar switch. Combining confocal microscopy with metabolic flux assays, we directly compared native CF and CM mitochondrial morphology and energetics. CMs showed significantly higher mitochondrial mass, fusion and energetics, all metrics relevant for increased reliance on mitochondrial FAO. Applying these techniques to study reprogramming, we found that at later reprogramming time points key metrics move significantly toward the phenotypes of native CMs. We then hypothesized that facilitating metabolic reprogramming by inhibiting fission and/or promoting fusion could improve iCM conversion. A loss of function screen identified certain fission genes, particularly the little studied mitochondrial fission regulator 1-like protein (Mtfr1l), as potent barriers to iCM conversion and maturation. In contrast, the core fusion genes were necessary for successful generation of iCMs, particularly the key fusion effector optical atrophy 1 (Opa1). Mtfr1l has been shown to promote cleavage of Opa1, and indeed concurrent knockdown of Opa1 ablated improvements to reprogramming efficiency. In conclusion, we showed both that iCMs are associated with increased mitochondrial mass, fusion and energetics approaching those of native CMs and that inducing CM-like mitochondria by knocking down Mtfr1l dramatically improved reprogramming, potentially through increased fusion activity of Opa1. By incorporating metabolic reprogramming into traditional direct cardiac reprogramming strategies, we may be able to move the field closer to clinical application to improve outcomes after MI.

The Influence of Functional Composite Coatings on the Properties of Polyester Films before and after Accelerated UV Aging.

The aim of this study was to cover biopolymeric packaging films based on PLA/PHBV blend with a functional composite coating (to retain their ecological character) and to investigate their antimicrobial properties before and after UV irradiation. As an active coating, the carrier hydroxypropyl methyl cellulose (HPMC), as well as its modified form with Achillea millefolium L., Hippophae rhamnoides L., and Hypericum L. extract (E) and a combined system based on the extracts and nano-ZnO (EZ), was used to obtain active formulations. Additionally, film surface morphology (SEM, FTIR-ATR) and color (CIELab scale) analysis of the pre- and post-UV-treatment samples were performed. The results confirmed that the E and EZ-modified films exhibited antibacterial properties, but they were not effective against phage phi6. Q-SUN irradiation led to a decrease in the activity of E coating against Staphylococcus aureus, Pseudomonas syringae, and Candida albicans. In this case, the effectiveness of EZ against C. albicans at 24 h and 72 h UV irradiation decreased. However, the irradiation boosted the antiviral effectiveness of the EZ layer. SEM micrographs of the film surface showed that UV treatment did not significantly influence the native film morphology, but it had an impact on the coated film. FTIR analysis results showed that the coatings based on HPMC altered the IR absorption of the nonpolar groups of the biopolyester material. The applied coatings only marginally affected film color changes and increased their yellowness after UV irradiation, whereas a composite layer of nano-ZnO limited these changes.

Morphology of the native ascending aorta after the Norwood procedure for aortic atresia: impact on survival and right ventricular dysfunction.

Our goal was to evaluate the impact of variable morphology of the native ascending aorta after the Norwood I procedure in patients with hypoplastic left heart syndrome/aortic atresia on long-term survival and systemic right ventricular dysfunction. Of 151 survivors of the Norwood procedure for hypoplastic left heart syndrome/aortic atresia at our institution between January 2001 and December 2020, we included patients with available and measurable aortograms prior to stage II palliation. The diameter of the native ascending aorta, the length of the native ascending aorta and the angle between the native ascending aorta and the proximal pulmonary artery were measured. We investigated the impact of these morphologic parameters on mortality and on right ventricular dysfunction (defined as at least moderate). Angiograms were available for 78 patients. The median diameter of the native ascending aorta was 3.2 mm (2.6-3.7), the median length of the native ascending aorta was 15.4 mm (13.3-17.9) and the median angle between the native ascending aorta and the proximal pulmonary artery was 44° (35°-51°). During the median follow-up of 6.5 years, 8 (10%) patients died and systemic right ventricular dysfunction occurred in 19 patients (24%). No significant association between aortic morphology and mortality could be detected. Right ventricular function was negatively affected by a larger angle between the native ascending aorta and the proximal pulmonary artery [odds ratio 1.07 (1.01-1.14), P = 0.02]. In survivors of the Norwood procedure for hypoplastic left heart syndrome/aortic atresia with available angiograms, no significant association between native aortic morphology and mortality could be demonstrated after stage II palliation, within the scope of this limited study. A larger anastomosis angle between the native ascending aorta and the proximal pulmonary artery emerged as a risk factor for right ventricular dysfunction.

Ultrastructural insights into cellular organization, energy storage and ribosomal dynamics of an ammonia-oxidizing archaeon from oligotrophic oceans.

Nitrososphaeria, formerly known as Thaumarchaeota, constitute a diverse and widespread group of ammonia-oxidizing archaea (AOA) inhabiting ubiquitously in marine and terrestrial environments, playing a pivotal role in global nitrogen cycling. Despite their importance in Earth's ecosystems, the cellular organization of AOA remains largely unexplored, leading to a significant unanswered question of how the machinery of these organisms underpins metabolic functions. In this study, we combined spherical-chromatic-aberration-corrected cryo-electron tomography (cryo-ET), scanning transmission electron microscopy (STEM), and energy dispersive X-ray spectroscopy (EDS) to unveil the cellular organization and elemental composition of Nitrosopumilus maritimus SCM1, a representative member of marine Nitrososphaeria. Our tomograms show the native ultrastructural morphology of SCM1 and one to several dense storage granules in the cytoplasm. STEM-EDS analysis identifies two types of storage granules: one type is possibly composed of polyphosphate and the other polyhydroxyalkanoate. With precise measurements using cryo-ET, we observed low quantity and density of ribosomes in SCM1 cells, which are in alignment with the documented slow growth of AOA in laboratory cultures. Collectively, these findings provide visual evidence supporting the resilience of AOA in the vast oligotrophic marine environment.

Three-Dimensional Microfibrous Scaffold with Aligned Topography Produced via a Combination of Melt-Extrusion Additive Manufacturing and Porogen Leaching for In Vitro Skeletal Muscle Modeling.

Skeletal muscle tissue (SMT) has a highly hierarchical and anisotropic morphology, featuring aligned and parallel structures at multiple levels. Various factors, including trauma and disease conditions, can compromise the functionality of skeletal muscle. The in vitro modeling of SMT represents a useful tool for testing novel drugs and therapies. The successful replication of SMT native morphology demands scaffolds with an aligned anisotropic 3D architecture. In this work, a 3D PCL fibrous scaffold with aligned morphology was developed through the synergistic combination of Melt-Extrusion Additive Manufacturing (MEAM) and porogen leaching, utilizing PCL as the bulk material and PEG as the porogen. PCL/PEG blends with different polymer ratios (60/40, 50/50, 40/60) were produced and characterized through a DSC analysis. The MEAM process parameters and porogen leaching in bi-distilled water allowed for the development of a micrometric anisotropic fibrous structure with fiber diameters ranging from 10 to 100 µm, depending on PCL/PEG blend ratios. The fibrous scaffolds were coated with Gelatin type A to achieve a biomimetic coating for an in vitro cell culture and mechanically characterized via AFM. The 40/60 PCL/PEG scaffolds yielded the most homogeneous and smallest fibers and the greatest physiological stiffness. In vitro cell culture studies were performed by seeding C2C12 cells onto a selected scaffold, enabling their attachment, alignment, and myotube formation along the PCL fibers during a 14-day culture period. The resultant anisotropic scaffold morphology promoted SMT-like cell conformation, establishing a versatile platform for developing in vitro models of tissues with anisotropic morphology.

Optimizing Decellularization of Bovine Ovarian Tissue: Toward a Transplantable Artificial Ovary Scaffold with Minimized Residual Toxicity and Preserved Extracellular Matrix Morphology

Introduction: The decellularized extracellular matrix (dECM) from ovarian tissue could be the best scaffold for the development of a transplantable artificial ovary. Typically, dECM from ovarian tissue has been obtained using sodium dodecyl sulfate (SDS), at a concentration of 1% for 24 h. However, SDS can leave residues in the tissue, which may be toxic to the seeded cells. This study aimed to obtain dECM from bovine ovarian tissue using SDS and NaOH at a minimum concentration in the shortest incubation time. Methods: The respective SDS and NaOH concentrations investigated were 1% and 0.2 m; 0.5% and 0.1 m; 0.1% and 0.02 m; and 0.05% and 0.01 m, with 24-, 12-, and 6-h incubation periods. After the incubation time, the tissue was washed in 50 mL of distilled water for 6 h. Results: Histological analysis confirmed decellularization and showed the conservation of collagen fibers in all samples following treatment. Furthermore, the lowest SDS and NaOH concentrations that showed no DNA remaining during electrophoresis analysis were 0.1% and 0.02 m when incubated for 24 and 12 h. DNA quantification resulted in <0.2 ng DNA/mg ovarian tissue using these protocols. Additionally, the coculture of dECM (obtained by 0.1% SDS and 0.02 m NaOH for 12 h) with ovarian cells showed that there was no toxic effect for the cells for up to 72 h. Conclusion: The protocol involving 0.1% SDS and 0.02 m NaOH for 12-h incubation decellularizes bovine ovarian tissue, generating a dECM that preserves the native ECM morphology and is nontoxic to ovarian cells.

Impact of acetabular roof's angle on precision of cup center of rotation reproduction and placement in total hip arthroplasty.

Total hip arthroplasty (THA) is nowadays considered as the most effective treatment option for end-stage hip osteoarthritis (OA) and one of the most successful orthopedic procedures. Precise reproduction of the center of rotation (COR) is among the most important aspects of recreating native hip biomechanics after THA as it is strictly related to muscle tension and force distribution within the hip joint. Both vertical and horizontal shift in cup positioning and COR restoration are commonly observed radiological signs corresponding with lesser functional outcome. The aim of this study was to assess whether the superior border of the native acetabulum morphology has an impact on cup positioning and COR restoration in patients undergoing THA as treatment of primary OA of the hip. A cohort of 150 consecutive patients with diagnosis of end-stage primary hip OA who underwent THA via an anterolateral approach with the same implant in 2021 was analyzed retrospectively. Standard standing pelvic X-rays were performed pre- and postoperatively and appropriate measurements were taken. Several radiological parameters on obtained X-rays were assessed. Statistical analysis of all the measurements was performed. There was a statistically significant positive weak correlation between cup offset and acetabular roof angle (rs = 0.25, p = 0.002). There were statistically insignificant positive correlations between acetabular roof angle and COR restoration (rs = 0.14, p = 0.097), acetabular roof angle and total offset (rs = 0.087, p = 0.29) and a negative correlation between acetabular roof angle and femoral offset (rs = 0.071, p = 0.39). The present study revealed that preoperative acetabular roof angle influences the positioning of the prosthetic cup in the transverse axis. There also seems to be a correlation between the acetabular roof angle and COR restoration, but its significance needs further evaluation. Surgeons could use this knowledge to preoperatively assess the risk of cup malposition and adjust their technique during the THA procedure with probable improvement of hip function.

Scanning ion conductance microscopy revealed cisplatin-induced morphological changes related to apoptosis in single adenocarcinoma cells.

The studies of drug-induced apoptosis play a vital role in the identification of potential drugs that could treat diseases such as cancer. Alterations in the native morphology of cancer cells following treatment with anticancer drugs serve as one of the indicators that reveal drug efficacy. Various techniques such as optical microscopy, electron microscopy (EM), and atomic force microscopy (AFM) have been used to map the three dimensional (3D) morphological changes in cells induced with drugs. However, caution should be exercised when interpreting morphological data from techniques that might alter the native morphology of cells, caused by phototoxicity, electron beam invasiveness, intrusive sample preparation, and cell membrane deformation. Herein, we have used scanning ion conductance microscopy (SICM) to study the 3D morphology and roughness of A549 adenocarcinoma cells under physiological conditions before and after cisplatin induced apoptosis, where we observed an increase in height, overall shrinkage of the cells, and irregular features form on the cell membrane. Tracking the morphology of the same single A549 cells exposed to cisplatin unveiled heterogeneity in response to the drug, formation of membrane blebs, and an increase in membrane roughness. We have also demonstrated the use of SICM for studying the effect of cisplatin on the dynamic changes in the volume of A549 cells over days. SICM is demonstrated as a technique for studying the effect of drug induced apoptosis in the same cells over time, and for multiple different single cells.

Engineering Sensory Ganglion Multicellular System to Model Tissue Nerve Ingrowth.

Discogenic pain is associated with deep nerve ingrowth in annulus fibrosus tissue (AF) of intervertebral disc (IVD). To model AF nerve ingrowth, primary bovine dorsal root ganglion (DRG) micro-scale tissue units are spatially organised around an AF explant by mild hydrodynamic forces within a collagen matrix. This results in a densely packed multicellular system mimicking the native DRG tissue morphology and a controlled AF-neuron distance. Such a multicellular organisation is essential to evolve populational-level cellular functions and in vivo-like morphologies. Pro-inflammatory cytokine-primed AF demonstrates its neurotrophic and neurotropic effects on nociceptor axons. Both effects are dependent on the AF-neuron distance underpinning the role of recapitulating inter-tissue/organ anatomical proximity when investigating their crosstalk. This is the first in vitro model studying AF nerve ingrowth by engineering mature and large animal tissues in a morphologically and physiologically relevant environment. The new approach can be used to biofabricate multi-tissue/organ models for untangling pathophysiological conditions and develop novel therapies.

Five-Year Outcomes After Bicuspid Aortic Valve Replacement With a Novel Tissue Bioprosthesis

BackgroundThis study investigated the safety and effectiveness of surgical aortic valve replacement with RESILIA tissue (Edwards Lifesciences) through 5 years in patients with native bicuspid aortic valves. Outcomes were compared with those for patients with tricuspid aortic valves. MethodsOf 689 patients from the COMMENCE (ProspeCtive, nOn-randoMized, MulticENter) trial who received the study valve, 645 had documented native valve morphology and core laboratory-evaluable echocardiograms from any postoperative visit, which were used to model hemodynamic outcomes over 5 years. Linear mixed-effects models were used to estimate longitudinal changes in mean gradient and effective orifice area. ResultsPatients with native bicuspid aortic valves (n = 214) were more than a decade younger than those with tricuspid aortic valves (n = 458; 59.8 ± 12.4 years vs 70.2 ± 9.5 years; P < .001). The bicuspid aortic valve cohort exhibited no structural valve deterioration over 5 years, and rates of paravalvular leak and transvalvular regurgitation were low (0.7% and 2.9%, respectively [all mild] at 5 years). These outcomes mirrored those in patients with native tricuspid aortic valves. The model-estimated postoperative mean gradient and effective orifice area, as well as the rate of change of these outcomes, adjusted for age, body surface area, and bioprosthesis size, did not differ between the 2 cohorts. ConclusionsAmong patients with bicuspid aortic valves, RESILIA tissue valves demonstrated excellent outcomes to 5 years, including no structural valve deterioration and very low rates of paravalvular and transvalvular regurgitation. These results are encouraging for RESILIA tissue durability in young patients.

Spontaneous Orthogonal Alignment of Smooth Muscle Cells and Endothelial Cells Captures Native Blood Vessel Morphology in Tissue-Engineered Vascular Grafts.

Tissue-engineered vascular grafts (TEVGs) have emerged as a potential alternative to autologous grafts for replacing small-diameter blood vessels during bypass surgery. The axial alignment of endothelial cells (ECs) and the circumferential alignment of smooth muscle cells (SMCs) are crucial for functional native blood vessels (NBVs). However, achieving this cellular alignment in TEVGs remains a formidable challenge. In this study, TEVGs were developed using a low-cost technique that aligned ECs axially and SMCs circumferentially within hours. The TEVGs comprised an electrospun polycaprolactone (PCL) layer and a gelatin methacryloyl (GelMA) cast layer. A freezing-induced alignment technique was developed that partially aligns the electrospun fibers axially, thereby promoting rapid axial alignment of ECs. Furthermore, SMCs cultured in a GelMA layer with intermediate stiffness (5-12 kPa) surrounding a PCL tube could promote conformation of the SMCs to the curvature of the PCL tube, resulting in their spontaneous circumferential alignment. Additionally, the TEVGs demonstrated mechanical properties similar to those of NBVs, which could facilitate future translation. This approach represents a significant advance in tissue engineering, enabling the fabrication of TEVGs with appropriate mechanical properties that recapitulate key NBV cell structural features within hours using a scalable and accessible method.

Fracture Patterns of Rocks Observed under Cryogenic Conditions Using Cryo-Scanning Electron Microscopy

Cryogenic fracturing, which uses liquid nitrogen (LN2) as a fracturing fluid, is a waterless fracturing method. However, previous attempts to investigate the fracture morphology of rocks after LN2 quenching have been mainly based on standard scanning electron microscopy (SEM) analysis at room temperature. This can be problematic since thermally-induced fractures created by temperature difference tend to close as a sample warms and thermal stress relaxes. To address this issue, we established a novel approach employing Cryo-scanning electron microscopy (Cryo-SEM) to investigate the fracture patterns induced by liquid nitrogen quenching under cryogenic conditions. This method can achieve in-situ visualization of fractures and pores with a nano-scale resolution at −190 °C. X-ray computed tomography (CT) is also employed to illustrate the fracture distribution inside samples. Cryo-SEM and standard SEM are compared, and statistical assessments are conducted to quantify fracture aperture size and closure scale. The results demonstrate that Cryo-SEM can more accurately preserve native fracture morphology and provide a more accurate means of evaluating fracture scales generated during LN2 quenching, particularly at higher temperature differences between rock and liquid nitrogen. Distinct fracture patterns and fracture width are observed for various rock types (i.e., coal, sandstone, shale, granite) by using these methods. More prominently, the maximum fracture width of coal, sandstone, shale and granite were 89.17 µm, 1.29 µm, 0.028 µm and 2.12 µm when the temperature difference between LN2 and rock samples were 296 °C. LN2 is shown to exhibit superior fracturing efficiency on coal and granite, characterized by complex fracture networks with branched fractures. This research contributes to our understanding of liquid nitrogen fracturing mechanisms and may offer effective approaches for unconventional reservoirs stimulation.

Pivots coniques en arthroplastie totale de hanche chez la hanche dysplasique : une étude longitudinale

IntroductionConical tapered stems may be useful implants to manage the reconstruction of complex dysplastic anatomies. The aims of this paper were to assess: the preoperative CT features of the dysplastic femurs, survival rates, complications and reasons for revision, the clinical outcomes and the radiographic outcomes of single-taper conical stems in dysplasia (defined as center edge angle <20°) at a long-term follow-up. HypothesisMonoblock conical stem provides a 10-year survival rate of at least 95%, with excellent clinical outcomes and bony ingrowth. Materials and methodsIn total 100, THAs in 85 patients (15 bilateral cases) were enrolled. The average age of the patients at surgery was 50.9±11.5 years. Assessment of the native femoral morphology was performed using CT scan, coronal (neck-shaftangle, offset, center of rotation position) and axial parameters (anteversion, mediolateral and anteroposterior femoral diameters). Clinical (HHS score) and radiological (osseointegration, subsidence and offset reconstruction) outcomes were evaluated at the last available follow-up. ResultsThe mean follow-up was 9.34±5.61 years. Severely distorted anatomies from Crowe I to Crowe IV were included, with a mean canal flare of 4.3 and a mean femoral antetorsion of 34°. The survival rates were stable at long-term (98.9% at 10 and 15 years): no aseptic loosening occurred. The mean postoperative HHS was 89.8±6.8 points. Ninety-nine percent of the stems showed bone ingrowth, from 6 months to the last available follow-up. Subsidence occurred in 18% of the cases (mean value: 2.5mm, range: 1–6mm) in the first month, with subsequent stabilization. A mild proximal stress shielding occurred in 28% of the THAs. Radiolucent lines were detected in the 8% of the cases. There was a postoperative loss of offset in 12% of the cases. DiscussionConical stems in dysplastic hips achieved bony ingrowth at long-term outcome, even in complex anatomies. Subsidence, proximal stress shielding and imperfect offset restoration may occur with this implant. Level of evidenceIV; retrospective study.

Parallel evaluation of alternative skin barrier models and excised human skin for dermal absorption studies in vitro

Skin permeation is a primary consideration in the safety assessment of cosmetic ingredients, topical drugs, and human users handling veterinary medicinal products. While excised human skin (EHS) remains the ‘gold standard’ for in vitro permeation testing (IVPT) studies, unreliable supply and high cost motivate the search for alternative skin barrier models. In this study, a standardized dermal absorption testing protocol was developed to evaluate the suitability of alternative skin barrier models to predict skin absorption in humans. Under this protocol, side-by-side assessments of a commercially available reconstructed human epidermis (RhE) model (EpiDerm-200-X, MatTek), a synthetic barrier membrane (Strat-M, Sigma-Aldrich), and EHS were performed. The skin barrier models were mounted on Franz diffusion cells and the permeation of caffeine, salicylic acid, and testosterone was quantified. Transepidermal water loss (TEWL) and histology of the biological models were also compared. EpiDerm-200-X exhibited native human epidermis-like morphology, including a characteristic stratum corneum, but had an elevated TEWL as compared to EHS. The mean 6 h cumulative permeation of a finite dose (6 nmol/cm2) of caffeine and testosterone was highest in EpiDerm-200-X, followed by EHS and Strat-M. Salicylic acid permeated most in EHS, followed by EpiDerm-200-X and Strat-M. Overall, evaluating novel alternative skin barrier models in the manner outlined herein has the potential to reduce the time from basic science discovery to regulatory impact.

Association between left ventricular lead position and intrinsic QRS morphology with regard to clinical outcome in cardiac resynchronization therapy for heart failure.

Left ventricular (LV) lead position may be an important factor for delivering effective cardiac resynchronization therapy (CRT). We therefore aimed to evaluate the effects of LV lead position, stratified by native QRS morphology, regarding the clinical outcome. A total of 1295 CRT-implanted patients were retrospectively evaluated. LV lead position was classified as lateral, anterior, inferior, or apical, and was determined using the left and right anterior oblique X-ray views. Kaplan Meier and Cox regression were performed to evaluate the effects on all-cause mortality and heart failure hospitalization, and the potential interaction between LV lead position and native ECG morphologies. A total of 1295 patients were included. Patients were aged 69 ± 7 years, 20% were female, 46% received a CRT-Pacemaker (vs. CRT-Defibrillator), mean LVEF was 25% ± 7%, and median follow-up was 3.3 years [IQR 1.6-5-7 years]. Eight hundred and eighty-two patients (68%) had a lateral LV lead location, 207 (16%) anterior, 155 (12%) apical, and 51 (4%) inferior. Patients with lateral LV lead position had larger QRS reduction (-13 ± 27 ms vs. -3 ± 24 ms, p < .001). Non-lateral lead location was associated with a higher risk for all-cause mortality (HR 1.34 [1.09-1.67], p = .007) and heart failure hospitalization (HR 1.25 [1.03-1.52], p = .03). This association was strongest for patients with native left or right bundle branch block, and not significant for patients with prior paced QRS or nonspecific intraventricular conduction delay. In patients treated with CRT, non-lateral LV lead positions (including apical, anterior, and inferior positions) were associated with worse clinical outcome and less reduction of QRS duration. This association was strongest for patients with native LBBB or RBBB.

Statistical shape modeling of the large acetabular defect in hip revision surgery.

The assessment of three-dimensional bony defects is important to inform the surgical planning of hip reconstruction. Mirroring of the contralateral side has been previously used to measure the hip center of rotation (CoR). However, the contralateral side may not be useful when diseased or replaced. Statistical Shape Models (SSMs) can aid reconstruction of patient anatomy. Previous studies have been limited to computational models only or small patient cohorts. We used SSM as a tool to help derive landmarks that are often absent in hip joints of patients with large acetabular defects. Our aim was to compare the reconstructed pelvis with patients who have previously undergone hip revision. This retrospective cohort study involved 38 patients with Paprosky type IIIB defects. An SSM was built on 50 healthy pelvises and used to virtually reconstruct the native pelvic morphology for all cases. The outcome measures were the difference in CoR for (1) SSM versus diseased hip, (2) SSM versus plan, and (3) SSM versus contralateral healthy hip. The median differences in CoR were 31.17 mm (interquartile range [IQR]: 43.80-19.87 mm), 8.53 mm (IQR: 12.76-5.74 mm), and 7.84 mm (IQR: 10.13-5.13 mm), respectively. No statistical difference (p > 0.05) was found between the SSM versus plan and the SSM versus contralateral CoRs. Our findings show that the SSM model can be used to reconstruct the absent bony landmarks of patients with significant lysis regardless of the defect severity, hence aiding the surgical planning of hip reconstruction and implant design.

The Changi-Marina Bay Corridor: green strategies for Singapore’s soft power

Singapore’s city-making strategies are seen by many Asia Pacific cities as a model to achieve today’s desired ‘world-class city’ status. They represent a source of innovation to design alternative configurations and rethink established norms of urban and social standards. This article looks at the urban landscape of the city of Singapore through infrastructural systems instead of individual design masterpieces, focusing on the urban corridor defined by the connection of Changi Airport, East Coast Parkway (ECP), and Marina Bay as a single urban entity, unified by a visual and experiential choreography. At a time of intense global competition in the aviation industry, Changi has deployed new strategies to sustain its reputation as an innovative transportation hub. The leg between Changi Airport and Marina Bay is an integral part of Singapore, experienced by the majority of its annual visitors arriving in the city-state. The 19-kilometre route, a major infrastructural project begun in the 1970s and still in progress, is a highly landscaped and scenic artery of the island, through which the airport has injected its hyper-urbanism into the city. While conveying the history of the developments of the Corridor, we consider the soft power strategies used by the city state to develop a form of transnational elite urbanism based on leisure and recreation, where urban planning, design, and green infrastructure play a key role. We reflect on the global and local dimension of Singapore, discussing how the ECP corridor reveals only one side of the city’s double character.On the one hand, this article critically analyses the rhetorical use of landscaping ingrained in the Corridor to attract foreign investment and tourism, where the artificialisation of green interventions has overwritten the presence of the native vegetation and morphology. On the other hand, we reflect on the less evident but nonetheless split that the Corridor has generated between the city’s southern residential areas and foreshore. While cutting through the urban tissue of part of the island seamlessly and without interruption, the Corridor does in fact separate out substantial residential areas, turning Singapore successful green strategies into a form of urban injustice. The twofold nature of the corridor – at the same time, that of the ‘connector’ and ‘divider’ – thus reflects Singapore’s intrinsic ambiguity: its manifestation of global ambitions set against its local realities. This article unpacks the planning mechanisms used to design this development, including the land reclamation powers of the state and the government land sales programme. It also discusses the strategies and choices underpinning the urban sequence of the ECP’s infrastructural nodes, from the Jewel (2019) to the Conservatories (2012). Drawing on official documentation from Singapore’s Urban Redevelopment Authority (URA), field research, and using a multidisciplinary lens, this article interpolates architectural and planning studies with insights gleaned by onsite investigation.