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This study aimed to evaluate the mechanical stability of seven different intraocular lens (IOL) haptic designs by using digital image correlation to measure their mechanical biomarkers (axial displacement, tilt, and rotation) under quasi-static compression. The IOLs were compressed between two clamps from 11.00 up to 9.50 mm whilst a 3D deformation dataset was acquired every 0.04 mm. Results revealed that flexible and mixed IOL designs exhibited better mechanical response for smaller compression diameters compared to stiff designs. Conversely, stiff designs performed better for larger compression diameters. These findings may aid in the selection and development of more mechanically stable IOL designs.

The kinetics of heat-induced color changes in beef meat was determined and implemented in a numerical model for double-sided pan cooking of steak. The CIELab color space was used to obtain the lightness (coordinate L∗) and the reddish tone (coordinate a∗) of the cooked meat. L∗ was the CIELab coordinate that contributed the most to the change in the absolute color. Two response surfaces were found to describe the evolution with time and temperature of both color coordinates, L∗ and a∗. The model results were successfully verified with experimental data of the two coordinates along the thickness of the meat for three degrees of cooking. The Root-Mean-Squared Errors (RMSE) for coordinate L∗ were 5.17 (very rare), 2.02 (medium rare) and 3.83 (done), and for coordinate a∗ 1.44 (very rare), 1.26 (medium rare) and 0.89 (done). The applicability of the model for practical cooking purposes was illustrated by determining the optimum turn over time to achieve a similar color profile on both sides of the meat. The turn over time depended on the desired degrees of cooking, and were comprised between one-half and two-thirds of the final cooking time, increasing from very rare cooking degree to done cooking degree.

The mechanical response of the cornea subjected to a non-contact air-jet tonometry diagnostic test represents an interplay between its geometry, the corneal material behavior and the loading. The objective is to study this interplay to better understand and interpret the results obtained with a non-contact tonometry test. A patient-specific finite element model of a healthy eye, accounting for the load free configuration, was used. The corneal tissue was modeled as an anisotropic hyperelastic material with two preferential directions. Three different sets of parameters within the human experimental range obtained from inflation tests were considered. The influence of the IOP was studied by considering four pressure levels (10-28 mmHg) whereas the influence of corneal thickness was studied by inducing a uniform variation (300-600 microns). A Computer Fluid Dynamics (CFD) air-jet simulation determined pressure loading exerted on the anterior corneal surface. The maximum apex displacement showed a linear variation with IOP for all materials examined. On the contrary, the maximum apex displacement followed a cubic relation with corneal thickness. In addition, a significant sensitivity of the apical displacement to the corneal stiffness was also obtained. Explanation to this behavior was found in the fact that the cornea experiences bending when subjected to an air-puff loading, causing the anterior surface to work in compression whereas the posterior surface works in tension. Hence, collagen fibers located at the anterior surface do not contribute to load bearing. Non-contact tonometry devices give useful information that could be misleading since the corneal deformation is the result of the interaction between the mechanical properties, IOP, and geometry. Therefore, a non-contact tonometry test is not sufficient to evaluate their individual contribution and a complete in-vivo characterization would require more than one test to independently determine the membrane and bending corneal behavior.

The finite element method has been widely used to investigate the mechanical behavior of biological tissues. When analyzing these particular materials subjected to dynamic requests, time integration algorithms should be considered to incorporate the inertial effects. These algorithms can be classified as implicit or explicit. Although both algorithms have been used in different scenarios, a comparative study of the outcomes of both methods is important to determine the performance of a model used to simulate the active contraction of the skeletal muscle tissue. In this work, dynamic implicit and dynamic explicit solutions are presented for the movement of the eye ball induced by the extraocular muscles. Aspects such as stability, computational time and the influence of mass-scaling for the explicit formulation were assessed using ABAQUS software. Both strategies produced similar results regarding range of movement of the eye ball, total deformation and kinetic energy. Using the implicit dynamic formulation, an important amount of computational time reduction is achieved. Although mass-scaling can reduce the simulation time, the dynamic contraction of the muscle is drastically altered.

[...]when the same protein is manufactured under different condi- tions, as in the case of biosimilars, there might be changes in the pattern of post-translational modifications and the immunogenic potential of the protein. Unwanted immunogenicity can occur at a level, which will not be detected by such studies when conducted at a pre-approval stage, due to the small number of patients participating in the study. [...]it is often necessary to continue assessment of unwanted immunogenicity and its clinical significance post-approval, usually as part of pharmacovigilance surveillance.

ObjectivesTo explore the opinions and perceptions of key stakeholders on the integration between community pharmacy and primary care, within the Valencian Autonomous Community. Specific objectives include identifying strategic interventions to facilitate this integration. Additionally, the manuscript discusses the formulation of a novel model for the integration of community pharmacy and primary care.DesignQualitative, with data from five virtual focus groups (FG) and 12 semistructured interviews analysed thematically using NVivo and interventions prioritised through a virtual nominal group technique.SettingValencian Autonomous Community (Spain).ParticipantsFG involved community pharmacists (CP) and primary care stakeholders including general practitioners, primary care nurses, general practitioner pharmacists, social services managers and administrators. Interviewees were government representatives and professionals from organisations. Selection was through snowball sampling and invitations by Official Colleges of Pharmacists.ResultsFive themes emerged, revealing the multifaceted nature of integrating community pharmacies and primary care. ‘Integration’ was identified as an ambitious target, anchored in collaboration and communication efforts. The role of CP was particularly noted for their direct patient interaction and trust, vital in fostering medication adherence. Barriers like role ambiguity and regulatory environment were highlighted. Seven interventions were identified to enable integration, with three of them prioritised: ‘bidirectional communication’, ‘protocol standardisation’ and ‘multidisciplinary team strengthening’. These interventions, linked with prior components of health system integration, led to a pioneer integration model.ConclusionsRecognising stakeholder insights is essential in shaping workable, practical and adaptable models for integration. Tailoring these temporal models to stakeholders' immediate needs and strategic priorities may serve as effective starting points for integration. Support from professional bodies and proactive stakeholders’ engagement will optimise the integration success and its acceptance across healthcare levels.

Introduction: Glaucoma, a leading cause of blindness worldwide, is primarily caused by elevated intraocular pressure (IOP). Accurate and reliable IOP measurements are the key to diagnose the pathology in time and to provide for effective treatment strategies. The currently available methods for measuring IOP include contact and non contact tonometers (NCT), which estimate IOP based on the corneal deformation caused by an external load, that in the case of NCT is an air pulse. The deformation of the cornea during the tonometry is the result of the coupling between the IOP, the mechanical properties of the corneal tissue, the corneal thickness, and the external force applied. Therefore, there is the need to decouple the four contributions to estimate the IOP more reliably. Methods: This paper aims to propose a new methodology to estimate the IOP based on the analysis of the mechanical work performed by the air jet and by the IOP during the NCT test. A numerical eye model is presented, initially deformed by the action of a falling mass to study the energy balance. Subsequently, Fluid-Structure Interaction (FSI) simulations are conducted to simulate the action of Corvis ST. Results and discussion: The new IOP estimation procedure is proposed based on the results of the simulations. The methodology is centred on the analysis of the time of maximum apex velocity rather than the point of first applanation leading to a new IOP estimation not influenced by the geometrical and mechanical corneal factors.

Monogenic diabetes can be misdiagnosed as type 1 or type 2 diabetes in children. The right diagnosis is crucial for both therapeutic choice and prognosis and influences genetic counseling. The main objective of this study was to search for monogenic diabetes in Spanish pediatric patients suspected of type 1 diabetes with lack of autoimmunity at the onset of the disease. We also evaluated the extra value of ZnT8A in addition to the classical IAA, GADA and IA2A autoantibodies to improve the accuracy of type 1 diabetes diagnosis. Four hundred Spanish pediatric patients with recent-onset diabetes (mean age 8.9 ± 3.9 years) were analyzed for IAA, GADA, IA2A and ZnT8A pancreatic-autoantibodies and HLA-DRB1 alleles. Patients without autoimmunity and those with only ZnT8A positive were screened for 12 monogenic diabetes genes by next generation sequencing. ZnT8A testing increased the number of autoantibody-positive patients from 373 (93.3%) to 377 (94.3%). An isolated positivity for ZnT8A allowed diagnosing autoimmune diabetes in 14.8% (4/27) of pediatric patients negative for the rest of the antibodies tested. At least 2 of the 23 patients with no detectable autoimmunity (8%) carried heterozygous pathogenic variants: one previously reported missense variant in the INS gene (p.Gly32Ser) and one novel frameshift variant (p.Val264fs) in the HNF1A gene. One variant of uncertain significance was also found. Carriers of pathogenic variants had HLA-DRB1 risk alleles for autoimmune diabetes and clinical characteristics compatible with type 1 diabetes except for the absence of autoimmunity. ZnT8A determination improves the diagnosis of autoimmune diabetes in pediatrics. At least 8% of pediatric patients suspected of type 1 diabetes and with undetectable autoimmunity have monogenic diabetes and can benefit from the correct diagnosis of the disease by genetic study.

Understanding the corneal mechanical properties has great importance in the study of corneal pathologies and the prediction of refractive surgery outcomes. Non-Contact Tonometry (NCT) is a non-invasive diagnostic tool intended to characterize the corneal tissue response in vivo by applying a defined air-pulse. The biomarkers inferred from this test can only be considered as indicators of the global biomechanical behaviour rather than the intrinsic biomechanical properties of the corneal tissue. A possibility to isolate the mechanical response of the corneal tissue is the use of an inverse finite element method, which is based on accurate and reliable modelling. Since a detailed methodology is still missing in the literature, this paper aims to construct a high-fidelity finite-element model of an idealized 3D eye for in silico NCT. A fluid-structure interaction (FSI) simulation is developed to virtually apply a defined air-pulse to a 3D idealized eye model comprising cornea, limbus, sclera, lens and humors. Then, a sensitivity analysis is performed to examine the influence of the intraocular pressure (IOP) and the structural material parameters on three biomarkers associated with corneal deformation. The analysis reveals the requirements for the in silico study linked to the correct reproduction of three main aspects: the air pressure over the cornea, the biomechanical properties of the tissues, and the IOP. The adoption of an FSI simulation is crucial to capture the correct air pressure profile over the cornea as a consequence of the air-jet. Regarding the parts of the eye, an anisotropic material should be used for the cornea. An important component is the sclera: the stiffer the sclera, the lower the corneal deformation due to the air-puff. Finally, the fluid-like behavior of the humors should be considered in order to account for the correct variation of the IOP during the test which will, otherwise, remain constant. The development of a strong FSI tool amenable to model coupled structures and fluids provides the basis to find the biomechanical properties of the corneal tissue in vivo .

PurposeAtraumatic mesh fixation for abdominal hernia repair has been developed to avoid the disadvantages of classical fixation with sutures, which is considered a cause of chronic pain and discomfort. This study was designed to analyze, in the short and medium term, the biological and mechanical behavior of two self-fixing meshes compared to that of a polypropylene (PP) mesh fixed with a cyanoacrylate (CA) tissue adhesive.MethodsPartial abdominal wall defects (6 × 4 cm) were created in New Zealand rabbits (n = 36) and repaired using a self-adhesive hydrogel mesh (Adhesix™), a self-gripping mesh (ProGrip™) or a PP mesh fixed with CA (Surgipro™ CA). After 14 and 90 days, the host tissue incorporation, macrophage response and biomechanical strength were examined.ResultsAt 14 and 90 days, the ProGrip and Surgipro CA meshes showed good host tissue incorporation; however, the Adhesix implants presented poor integration, seroma formation and a higher degree of shrinkage. The Adhesix hydrogel was completely reabsorbed at 14 days, whereas ProGrip microhooks were observed at all study times. The macrophage response was higher in the ProGrip and Surgipro CA groups at 14 and 90 days, respectively, and decreased over time. At 90 days, the ProGrip implants showed the highest tensile strength values and the Adhesix implants showed the highest failure stretch.ConclusionMeshes with mechanical microgrip self-fixation (ProGrip) show better biological and mechanical behavior than those with adhesive hydrogel (Adhesix) in a preclinical model of abdominal hernia repair in rabbits.