Comparative analysis of mechanical conditions in bone union following first metatarsophalangeal joint arthrodesis with varied locking plate positions: A finite element analysis.

BACKGROUND: First metatarsophalangeal joint arthrodesis is a typical medical treatment performed in cases of arthritis or joint deformity. The gold standard for this procedure is arthrodesis stabilisation with the dorsally positioned plate. However, according to the authors' previous studies, medially positioned plate provides greater bending stiffness. It is worth to compare the mechanical conditions for bone formation in the fracture callus for both placements of the locking plate. METHODS: Two finite element models of the first metatarsophalangeal joint with the dorsally and medially positioned plate were defined in the Abaqus software to simulate differentiation of the fracture callus. A simplified load application, i.e. one single step per each day and the diffusion of the mesenchymal stem cells into the fracture region were assumed in an iterative hardening process. The changes of the mesenchymal stem cells into different phenotypes during the callus stiffening were governed by the octahedral shear strain and interstitial fluid velocity according to Prendergast mechanoregulation theory. Basing on the obtained results the progress of the cartilage and bone tissues formation and their distribution within the callus were compared between two models. FINDINGS: The obtained results suggest that after 6 weeks of simulation the healing progress is in general comparable for both plates. However, earlier closing of external callus was observed for the medially positioned plate which had greater vertical bending stiffness. This process enables faster internal callus hardening and promotes symmetrical bridging.

Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury After Massive Burns.

BACKGROUND Acute kidney injury (AKI) is a common and serious complication after massive burn injury. One of the postulated etiologies is destruction of the extracellular matrix of nephrons, caused by a local imbalance between matrix metalloproteinases (MMPs) and specific inhibitors. The aim of this study was to analyze the dynamics of tissue inhibitors of metalloproteinases (TIMPs) during the first 5 days after massive thermal injury and the relationship with the risk of AKI. MATERIAL AND METHODS Thirty-three adults (22 men, 11 women) with severe burns were enrolled in the study. The values of TIMPs 1 to 4 were measured in blood serum and urine using the multiplex Luminex system. The associations between TIMPs and the risk of AKI were analyzed by using the generalized linear mixed models for repeated measurements. RESULTS Significant changes in serum and urine activities of TIMPs were confirmed, especially during the first 2 days after burn injury. Almost half of patients presented renal problems during the study. Significant differences between values of TIMPs in AKI and non-AKI status were also observed. However, a significant relationship between concentration of TIMPs and risk of AKI was confirmed only for urine TIMP-1 and serum TIMP-3. CONCLUSIONS The evaluation of TIMPs in the early stage after burn injury has potential benefits. The important roles of urine TIMP-1 and serum TIMP-3, as novel markers of the risk of AKI development, were confirmed. Other parameters require further analysis.

Antioxidant Activity of Bilirubin in Micellar and Liposomal Systems Is pH-Dependent.

Bilirubin (BR), a product of heme catabolism, plays a critical role in biological systems. Although increased levels of BR result in hyperbilirubinemia or jaundice, there is increasing evidence that lower concentrations substantially decrease the risk of oxidative stress-mediated diseases due to antioxidant functions of BR. We studied the radical-trapping ability of BR in two model systems, micellar and liposomal, at a broad pH range. At pH < 6.0, BR behaves as a retardant; however, at pH ≥ 6.0, BR becomes strong radical trapping antioxidant, with rate constants for reaction with lipidperoxyl radicals (kinh) within the range from 1.2 × 104 M-1 s-1 to 3.5 × 104 M-1 s-1, and in liposomal system, the activity of BR is comparable to α-tocopherol. This transition is likely facilitated by the ionization of carboxyl groups, leading to a conformational shift in BR and improved solubility/localization at the water/lipid interface. This is the first experimental evidence of the role of pH on the antioxidant activity of bilirubin, and the observed pH-dependent radical-trapping ability of BR holds practical significance, particularly in jaundice treatment where light therapy targets the skin's weakly acidic surface. Minor adjustments toward neutral or alkaline pH can enhance radical-trapping action of BR, thereby mitigating oxidative stress induced with blue or violet light exposure.

Integrating artificial intelligence-based epitope prediction in a SARS-CoV-2 antibody discovery pipeline: caution is warranted.

BACKGROUND: SARS-CoV-2-neutralizing antibodies (nABs) showed great promise in the early phases of the COVID-19 pandemic. The emergence of resistant strains, however, quickly rendered the majority of clinically approved nABs ineffective. This underscored the imperative to develop nAB cocktails targeting non-overlapping epitopes. METHODS: Undertaking a nAB discovery program, we employed a classical workflow, while integrating artificial intelligence (AI)-based prediction to select non-competing nABs very early in the pipeline. We identified and in vivo validated (in female Syrian hamsters) two highly potent nABs. FINDINGS: Despite the promising results, in depth cryo-EM structural analysis demonstrated that the AI-based prediction employed with the intention to ensure non-overlapping epitopes was inaccurate. The two nABs in fact bound to the same receptor-binding epitope in a remarkably similar manner. INTERPRETATION: Our findings indicate that, even in the Alphafold era, AI-based predictions of paratope-epitope interactions are rough and experimental validation of epitopes remains an essential cornerstone of a successful nAB lead selection. FUNDING: Full list of funders is provided at the end of the manuscript.

Development and validation of lumbar spine finite element model.

The functional biomechanics of the lumbar spine have been better understood by finite element method (FEM) simulations. However, there are still areas where the behavior of soft tissues can be better modeled or described in a different way. The purpose of this research is to develop and validate a lumbar spine section intended for biomechanical research. A FE model of the 50th percentile adult male (AM) Total Human Model for Safety (THUMS) v6.1 was used to implement the modifications. The main modifications were to apply orthotropic material properties and nonlinear stress-strain behavior for ligaments, hyperelastic material properties for annulus fibrosus and nucleus pulposus, and the specific content of collagenous fibers in the annulus fibrosus ground substance. Additionally, a separation of the nucleus pulposus from surrounding bones and tissues was implemented. The FE model was subjected to different loading modes, in which intervertebral rotations and disc pressures were calculated. Loading modes contained different forces and moments acting on the lumbar section: axial forces (compression and tension), shear forces, pure moments, and combined loading modes of axial forces and pure moments. The obtained ranges of motion from the modified numerical model agreed with experimental data for all loading modes. Moreover, intradiscal pressure validation for the modified model presented a good agreement with the data available from the literature. This study demonstrated the modifications of the THUMS v6.1 model and validated the obtained numerical results with existing literature in the sub-injurious range. By applying the proposed changes, it is possible to better model the behavior of the human lumbar section under various loads and moments.

No Significant Association between 25-OH Vitamin D Status and SARS-CoV-2 Antibody Response after COVID-19 Vaccination in Nursing Home Residents and Staff.

Vitamin D is an essential nutrient for various physiological functions, including immunity. While it has been suggested that higher vitamin D levels/supplementation are associated with a better immune response to COVID-19 vaccination, conflicting data exist. Therefore, we aimed to investigate the association between vitamin D (25-hydroxyvitamin D) deficiency/supplementation, and SARS-CoV-2 antibody responses post-vaccination in nursing home residents (NHRs) and staff (NHS). Blood samples were collected from 115 NHRs and 254 NHS at baseline and 14 days after primary course BNT162b2 vaccination. Baseline samples were assessed for serum 25-hydroxyvitamin D levels, while follow-up samples were analyzed for spike protein S1 receptor-binding domain (S1RBD) IgG antibody concentrations and 50% pseudoneutralization titers. Vitamin D supplementation status was obtained from NHRs medical records. We compared immune responses between (severe) vitamin D-deficient and -sufficient NHRs/NHS and between supplemented and non-supplemented NHRs, stratified for history of SARS-CoV-2 infection and participant type. No significant differences in either binding or neutralizing COVID-19 vaccine antibody response were found between groups. The prevalence of vitamin D deficiency (<20 ng/mL) was 45% (95% CI: 36-54%) among NHRs and 60% (95% CI: 54-66%) among NHS. Although we showed that vitamin D status may not be related to a better COVID-19 vaccine antibody response, addressing the high prevalence of vitamin D deficiency in the nursing home population remains important.

On implementation of fibrous connective tissues' damage in Abaqus software.

Connective fibrous tissues, such as tendons and ligaments, in humans and animals exhibit hyperelastic behaviour. The constitution of the material of these tissues is anisotropic due to the presence of the collagen fibres, where one family of fibres is the typical case. Traumatic events and/or aging may sometimes lead to the damage of the tissue. The study of motion of affected joints or limbs is usually not permitted in vivo. This is where finite element method (FEM) becomes useful as a premise for general analysis, surgical planning or designing of implants and medical treatment. One of the most often used FEM commercial programs is the field of the biomechanics is Abaqus. The present study discusses the potential of user subroutine UANISOHYPER_INV in this code to analyse response of transversely isotropic tissue with damage in quasi-static range. This subroutine requires providing the material energy function and its derivatives only. The stress tensor and constitutive matrix are computed by the software automatically. To the best of the Authors' knowledge this procedure provides the easiest way to simulate the anisotropic hyperelastic material behaviour in Abaqus. In this study its usage is extended onto the damage response simulation. The verification of the approach and its validation against experimental data indicates its efficiency.

Diagnostic performance of the SARS-CoV-2 S1RBD IgG ELISA (ImmunoDiagnostics) for the quantitative detection of SARS-CoV-2 antibodies on dried blood spots.

Dried Blood Spots (DBS) are broadly used in SARS-CoV-2 surveillance studies, reporting either the presence or absence of SARS-CoV-2 antibodies. However, quantitative follow-up has become increasingly important to monitor humoral vaccine responses. Therefore, we aimed to evaluate the performance of DBS for the detection of anti-spike SARS-CoV-2 antibody concentrations using a commercially available assay, reporting in a standardised unitage (International Units/mL; IU/mL). To assess the sensitivity and specificity of the ImmunoDiagnostics ELISA on serum and DBS for SARS-CoV-2 antibody detection, we analysed 72 paired DBS and serum samples. The SARS-CoV-2 S1 IgG ELISA kit (EUROIMMUN) on serum was used as the reference method. We performed a statistical assessment to optimise the cut-off value for DBS and serum and assessed the correlation between DBS and serum antibody concentrations. We found that anti-spike SARS-CoV-2 antibody concentrations detected in DBS are highly correlated to those detected in paired serum (Pearson correlation 0.98; p-value < 0.0001), allowing to assess serum antibody concentration using DBS. The optimal cut-off for antibody detection on DBS was found to be 26 IU/mL, with 98.1% sensitivity and 100% specificity. For serum, the optimal cut-off was 14 IU/mL, with 100% sensitivity and 100% specificity. Therefore, we conclude that the ImmunoDiagnostics ELISA kit has optimal performance in the detection of SARS-CoV-2 antibodies on both DBS and serum. This makes DBS ideal for large-scale follow-up of humoral SARS-CoV-2 immune responses, as it is an easy but valuable sampling method for quantification of SARS-CoV-2 antibodies, compared to serum.

Humoral and Cellular Responses to COVID-19 Vaccination Indicate the Need for Post-Vaccination Testing in Frail Population.

Despite the high efficacy of the BNT162b2 vaccine in the general population, data on its immunogenicity among frail elderly individuals are limited. Recently, levels of anti-SARS-CoV-2 spike IgG antibodies and serum neutralization titers were confirmed as good immune markers of protection against the virus, with evidence showing a reverse correlation between these two parameters and susceptibility to infection. Here we analyzed sera from 138 nursing home residents (median age of 88.9 years) and 312 nursing home staff (median age of 50.7 years) to determine the humoral response to two doses of the BNT162b2 vaccine, and found markedly decreased serum anti-spike antibody levels and neutralization titers in the nursing home resident (NHR) group, with over 11% non-responders compared to only 1.3% among the controls. Moreover, three months post-vaccination, a significant decrease in antibody titers was observed in COVID-19-naive nursing home residents. Subsequent flow cytometry and interferon gamma secretion analyses indicated that antibody non-responders among NHRs also failed to mount cellular responses. The presented data emphasize that additional measures are needed in the population of frail elderly individuals. Given the high proportion of non-responders among NHRs, continued monitoring should be considered in this group.

Medially positioned plate in first metatarsophalangeal joint arthrodesis.

OBJECTIVE: The purpose of this study was to biomechanically compare the stability of first metatarsophalangeal (MTP1) joint arthrodesis with dorsally and medially positioned plates. METHODS: A physical model of the MTP1 joint consists of printed synthetic bones, a titanium locking plate and screws. In the experiments, samples with dorsally and medially positioned plates were subjected to loading of ground load character in a universal testing machine. Force-displacement relations and relative displacements of bones were recorded. The obtained results were used to validate the corresponding finite element models of the MTP1 joint. Nonlinear finite element simulations of the toe-off phase of gait were performed to determine the deformation and stress state in the MTP1 joint for two positions of the plate. RESULTS: In numerical simulations, the maximum displacement in the dorsal direction was noticed at the tip of the distal phalanx and was equal to 19.6 mm for the dorsal plate and 9.63 mm for the medial plate for a resultant force of 150 N. Lower relative bone displacements and smaller plastic deformation in the plate were observed in the model with the medial plate. Stress values were also smaller in the medially positioned plate and locking screws compared to fixation with the dorsal plate. CONCLUSIONS: A medially positioned locking plate provides better stability of the MTP1 joint than a dorsally positioned plate due to greater vertical bending stiffness of the medial plate. Smaller relative bone displacements observed in fixation with the medial plate may be beneficial for the bone healing process. Moreover, lower stress values may decrease the risk of complications associated with hardware failure.

In-depth single-cell analysis of translation-competent HIV-1 reservoirs identifies cellular sources of plasma viremia.

Clonal expansion of HIV-infected cells contributes to the long-term persistence of the HIV reservoir in ART-suppressed individuals. However, the contribution from cell clones that harbor inducible proviruses to plasma viremia is poorly understood. Here, we describe a single-cell approach to simultaneously sequence the TCR, integration sites and proviral genomes from translation-competent reservoir cells, called STIP-Seq. By applying this approach to blood samples from eight participants, we show that the translation-competent reservoir mainly consists of proviruses with short deletions at the 5'-end of the genome, often involving the major splice donor site. TCR and integration site sequencing reveal that cell clones with predicted pathogen-specificity can harbor inducible proviruses integrated into cancer-related genes. Furthermore, we find several matches between proviruses retrieved with STIP-Seq and plasma viruses obtained during ART and upon treatment interruption, suggesting that STIP-Seq can capture clones that are responsible for low-level viremia or viral rebound.

Influence of the femoral offset on the muscles passive resistance in total hip arthroplasty.

BACKGROUND: Soft tissue tension is treated as a crucial factor influencing the post-THA dislocation. The femoral offset is regarded as one of the major parameters responsible for the stabilization of the prosthesis. It is unclear which soft tissue is mostly affected by the offset changes. METHODS: A finite element model of the hip was created. The model comprised muscles, bones, a stem, the acetabular component and a liner. The muscles were modelled as a Hill-type musculo-tendon nonlinear springs. Nonlinear analyses of the hip flexion and internal rotation were performed for the two values of the femoral stem offset. RESULTS: We observed that the quadratus femoris and gluteus medius produce the largest resisting moment opposing the external load excreted by the surgeon during the intraoperative hip dislocation test. CONCLUSIONS: An increased femoral offset increases the stretching of the quadratus femoris muscle significantly and provides the growth of its initial passive force. This muscle serves as a stiff band, providing stabilisation of the hip prosthesis, measured during the simulated intraoperative test.

A New Triage Method for Burn Disasters: Fast Triage in Burns (FTB).

BACKGROUND There are few triage methods based on patient age and extent of burn. However, in case of mass casualties, age might be hard to define. Burn segregation in mass-casualty accidents requires an easy, fast, and effective method. Triage in burns should also segregate casualties requiring treatment in burn centers. The aim of this study was to create a proprietary segregation algorithm dedicated to mass-casualty incidents. MATERIAL AND METHODS A retrospective analysis of 939 burned patients admitted to the Clinical Department of Burns, Plastic and Reconstructive Surgery, Military Institute of Medicine (MIM) in Warsaw and to the Center for the Treatment of Burns (CTB) in Siemianowice Slaskie in 2012 and 2013 was performed. The aim was to reveal which early factors could be used during segregation of burn victims in mass-casualty incidents on the battlefield and in civilian circumstances. Only easy and quick-to-evaluate factors that can be examined without medical equipment and laboratory tests were used in creating the proprietary triage algorithm. RESULTS As a result of our study, we created an algorithm for fast triage in mass-casualty situations. The algorithm is based on parameters that can be easily evaluated without additional equipment. To create the algorithm, we used factors that had the strongest impact on mortality prediction in severely burned patients, in multifactor analysis: advanced age (p<0.001. OR=1.04), extent of the deep burn (p<0.001. OR=1.1), and low systolic arterial pressure (p<0.001. OR=0.96). CONCLUSIONS The FTB (Fast Triage in Burns) algorithm is a new triage method dedicated for massive burn events in civilian circumstances. The FTB algorithm is a simple, quick, and credible means of segregating burn victims. The algorithm is dedicated to use in pre-hospital care, during mass-casualty events both in civilian and battlefield circumstances. The aim is to be able to evaluate burn victims immediately, without access to medical equipment or additional tests and to evaluate indications for burn center care. It is a unique method designed to be used during segregation in isolated burn mass-casualty incidents.

The influence of a change in the meniscus cross-sectional shape on the medio-lateral translation of the knee joint and meniscal extrusion.

OBJECTIVE: The purpose of this study was to evaluate the influence of a change in the meniscus cross sectional shape on its position and on the biomechanics of a knee joint. METHODS: One main finite element model of a left knee joint was created on the basis of MRI images. The model consisted of bones, articular cartilages, menisci and ligaments. Eight variants of this model with an increased or decreased meniscus height were then prepared. Nonlinear static analyses with a fixed flexion/extension movement for a compressive load of 1000 N were performed. The additional analyses for those models with a constrained medio-lateral relative bone translation allowed for an evaluation of the influence of this translation on a meniscus external shift. RESULTS: It was observed that a decrease in the meniscus height caused a decrease in the contact area, together with a decrease in the contact force between the flattened meniscus and the cartilage. For the models with an increased meniscus height, a maximal value of force acting on the meniscus in a medio-lateral direction was obtained. The results have shown that the meniscus external shift was approximately proportional to the meniscus slope angle, but that relationship was modified by a medio-lateral relative bone translation. It was found that the translation of the femur relative to the tibia may be dependent on the geometry of the menisci. CONCLUSIONS: The results have suggested that a change in the meniscus geometry in the cross sectional plane can considerably affect not only the meniscal external shift, but also the medio-lateral translation of the knee joint as well as the congruency of the knee joint.

The Influence of Articular Cartilage Thickness Reduction on Meniscus Biomechanics.

OBJECTIVE: Evaluation of the biomechanical interaction between meniscus and cartilage in medial compartment knee osteoarthritis. METHODS: The finite element method was used to simulate knee joint contact mechanics. Three knee models were created on the basis of knee geometry from the Open Knee project. We reduced the thickness of medial cartilages in the intact knee model by approximately 50% to obtain a medial knee osteoarthritis (OA) model. Two variants of medial knee OA model with congruent and incongruent contact surfaces were analysed to investigate the influence of congruency. A nonlinear static analysis for one compressive load case was performed. The focus of the study was the influence of cartilage degeneration on meniscal extrusion and the values of the contact forces and contact areas. RESULTS: In the model with incongruent contact surfaces, we observed maximal compressive stress on the tibial plateau. In this model, the value of medial meniscus external shift was 95.3% greater, while the contact area between the tibial cartilage and medial meniscus was 50% lower than in the congruent contact surfaces model. After the non-uniform reduction of cartilage thickness, the medial meniscus carried only 48.4% of load in the medial compartment in comparison to 71.2% in the healthy knee model. CONCLUSIONS: We have shown that the change in articular cartilage geometry may significantly reduce the role of meniscus in load transmission and the contact area between the meniscus and cartilage. Additionally, medial knee OA may increase the risk of meniscal extrusion in the medial compartment of the knee joint.

Early and Late Acute Kidney Injury in Severely Burned Patients.

BACKGROUND This study evaluated factors influencing early and late occurrence of AKI in severely burned patients and assessed the relationship between time of occurrence of AKI and mortality of AKI patients. MATERIAL AND METHODS Renal function was evaluated at 3 time points: at admission, at the critical point or middle point of hospitalization, and at the endpoint for which death or a discharge from the center was considered. AKI criteria were: decrease in GFR of less than 60 ml/min at admission, decrease in GFR of more than 75% compared to baseline, and decrease in the daily diuresis of less than 500 ml/24 h. RESULTS At admission, 15.1% of the patients had eGFR <60 ml/min. AKI occurred in 38.5% of cases. The occurrence of AKI was associated with: elderly age (p<0.001), female sex (p=0.017), overweight and obesity (p=0.055); extent and depth of burns, respiratory failure, low protein concentration (for all p<0.001), low blood pressure (p=0.014), and high WBC (p=0.010). Early AKI was detected in 28% of patients. Mortality was 100% with the initial GFR ≥60, 100% with the initial GFR <60 and early deterioration of renal function, 80% with the initial GFR <60 and late worsening, and 60% with the initial GFR <60 and no worsening. Late AKI was observed in 10% of patients and mortality in this group was 79.2%. Mortality in the entire group with AKI was 88.0% versus 24.5%. CONCLUSIONS The frequent occurrence of AKI, especially early, worsens the prognosis for survival. Assessment of renal function should be included in the prognostic scales for burned patients.

HIV Triggers a cGAS-Dependent, Vpu- and Vpr-Regulated Type I Interferon Response in CD4+ T Cells.

Several pattern-recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4+ T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection requires proviral integration and is regulated by newly expressed viral accessory proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction. Furthermore, Vpr also amplifies innate sensing of HIV-1 infection in Vpx-treated dendritic cells. Our results identify cGAS as mediator of an IFN-I response to HIV-1 infection in CD4+ T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cells of HIV-1.

Experimental Comparison of Efficiency of First Aid Dressings in Burning White Phosphorus on Bacon Model.

BACKGROUND: The aim of this study was to determine effectiveness of first aid dressings in extinguishing burning white phosphorous (WP), eliminating WP pieces from the surface, inhibiting re-ignition on the model (fresh bacon covered with military uniform), and preventing from late re-ignition caused by persistent WP pieces. MATERIAL AND METHODS: Burning WP was extinguished with several dressings: tactical Military Dressing (WJ10), wet gauze, 2 hydrocolloids, and 3 prototypes of hydrocolloids developed by the authors. RESULTS: All examined dressings were effective in extinguishing WP provided that the entire area of the burning substance was completely covered. Moist gauze was especially effective in extinguishing WP, and also removed and absorbed the majority of the WP mass, preventing deeper penetration of WP particles. The immediate re-ignition was observed when all the remaining examined dressings were removed from the bacon. A stream of water was dangerous, as it splashed and transferred pieces of WP around. CONCLUSIONS: Moist gauze placed on burning WP for approximately 3 min was most effective in extinguishing WP and removing most of the WP pieces. We recommend moist gauze, used once or twice, as the best primary means for WP elimination and preventing tissue penetration. As a dressing used for medical evacuation (MEDEVAC), or as a second step after complete removal of visible WP, innovative hydrocolloid or hydrogel dressings should be used.

Vpx-Independent Lentiviral Transduction and shRNA-Mediated Protein Knock-Down in Monocyte-Derived Dendritic Cells.

The function of dendritic cells (DCs) in the immune system is based on their ability to sense and present foreign antigens. Powerful tools to research DC function and to apply in cell-based immunotherapy are either silencing or overexpression of genes achieved by lentiviral transduction. To date, efficient lentiviral transduction of DCs or their monocyte derived counterparts (MDDCs) required high multiplicity of infection (MOI) or the exposure to the HIV-2/SIV protein Vpx to degrade viral restriction factor SAM domain and HD domain-containing protein 1 (SAMHD1). Here we present a Vpx-independent method for efficient (>95%) transduction of MDDCs at lower MOI. The protocol can be used both for ectopic gene expression and knock-down. Introducing shRNA targeting viral entry receptor CD4 and restriction factor SAMHD1 into MDDCs resulted in down-regulation of targeted proteins and, consequently, expected impact on HIV infection. This protocol for MDDCs transduction is robust and free of the potential risk arising from the use of Vpx which creates a virus infection-prone environment, potentially dangerous in clinical setting.

Influence of meniscus shape in the cross sectional plane on the knee contact mechanics.

We present a three dimensional finite element analysis of stress distribution and menisci deformation in the human knee joint. The study is based on the Open Knee model with the geometry of the lateral meniscus which shows some degenerative disorders. The nonlinear analysis of the knee joint under compressive axial load is performed. We present results for intact knee, knee with complete radial posterior meniscus root tear and knee with total meniscectomy of medial or lateral meniscus. We investigate how the meniscus shape in the cross sectional plane influences knee-joint mechanics by comparing the results for flat (degenerated) lateral and normal medial meniscus. Specifically, the deformation of the menisci in the coronal plane and the corresponding stress values in cartilages are studied. By analysing contact resultant force acting on the menisci in axial plane we have shown that restricted extrusion of the torn lateral meniscus can be attributed to small slope of its cross section in the coronal plane. Additionally, the change of the contact area and the resultant force acting on the menisci as the function of compressive load are investigated.