A registration strategy to characterize DTI-observed changes in skeletal muscle architecture due to passive shortening.

Skeletal muscle architecture is a key determinant of muscle function. Architectural properties such as fascicle length, pennation angle, and curvature can be characterized using Diffusion Tensor Imaging (DTI), but acquiring these data during a contraction is not currently feasible. However, an image registration-based strategy may be able to convert muscle architectural properties observed at rest to their contracted state. As an initial step toward this long-term objective, the aim of this study was to determine if an image registration strategy could be used to convert the whole-muscle average architectural properties observed in the extended joint position to those of a flexed position, following passive rotation. DTI and high-resolution fat/water scans were acquired in the lower leg of seven healthy participants on a 3T MR system in +20° (plantarflexion) and -10° (dorsiflexion) foot positions. The diffusion and anatomical images from the two positions were used to propagate DTI fiber-tracts from seed points along a mesh representation of the aponeurosis of fiber insertion. The -10° and +20° anatomical images were registered and the displacement fields were used to transform the mesh and fiber-tracts from the +20° to the -10° position. Student's paired t-tests were used to compare the mean architectural parameters between the original and transformed fiber-tracts. The whole-muscle average fiber-tract length, pennation angle, curvature, and physiological cross-sectional areas estimates did not differ significantly. DTI fiber-tracts in plantarflexion can be transformed to dorsiflexion position without significantly affecting the average architectural characteristics of the fiber-tracts. In the future, a similar approach could be used to evaluate muscle architecture in a contracted state.

Discovery and Preclinical Activity of BMS-986351, an Antibody to SIRPα That Enhances Macrophage-mediated Tumor Phagocytosis When Combined with Opsonizing Antibodies.

In normal cells, binding of the transmembrane protein CD47 to signal regulatory protein-α (SIRPα) on macrophages induces an antiphagocytic signal. Tumor cells hijack this pathway and overexpress CD47 to evade immune destruction. Macrophage antitumor activity can be restored by simultaneously blocking the CD47-SIRPα signaling axis and inducing a prophagocytic signal via tumor-opsonizing antibodies. We identified a novel, fully human mAb (BMS-986351) that binds SIRPα with high affinity. BMS-986351 demonstrated broad binding coverage across SIRPα polymorphisms and potently blocked CD47-SIRPα binding at the CD47 binding site in a dose-dependent manner. In vitro, BMS-986351 increased phagocytic activity against cell lines from solid tumors and hematologic malignancies, and this effect was markedly enhanced when BMS-986351 was combined with the opsonizing antibodies cetuximab and rituximab. A phase I dose-escalation/-expansion study of BMS-986351 for the treatment of advanced solid and hematologic malignancies is underway (NCT03783403). SIGNIFICANCE: Increasing the phagocytotic capabilities of tumor-associated macrophages by modulating macrophage-tumor cell surface signaling via the CD47-SIRPα axis is a novel strategy. Molecules targeting CD47 have potential but its ubiquitous expression necessitates higher therapeutic doses to overcome potential antigen sink effects. The restricted expression pattern of SIRPα may limit toxicities and lower doses of the SIRPα antibody BMS-986351 may overcome target mediated drug disposition while maintaining the desired pharmacology.

A 12-month follow-up study of patients with systemic lupus erythematosus after immunization against SARS-CoV-2.

OBJECTIVE: To identify all post-BNT162b2 vaccination (BioNTech and Pfizer) events during the ensuing 12 months in patients with systemic lupus erythematosus (SLE) from the Immuno-Rheumatology Department at Cayetano Heredia Hospital's cohort, Lima, Perú. METHODS: A 12-month follow-up study was conducted from the first dose of immunization with the BNT162b2 vaccine, which was given between May and June 2021, to SLE patients from this cohort. RESULTS: The initial population was constituted by 100 patients (100 patients received the 1st dose, 90 the 2nd dose, and 85 the 3rd dose of this vaccine); 33 patients presented a SLE reactivation (flare), 9% (9/100) post 1st dose, 26.6% (24/90) post 2nd dose, and 16.4% (14/85) post 3rd dose. The most common types of flare were articular (26) and renal (14) with 5/33 (15.1%) requiring hospitalization for flare management. A negative association with flare occurrence was found between the use of hydroxychloroquine RR 0.43 (0.21-0.85) and the opposite was the case for azathioprine RR 2.70 (1.39-5.25). During follow-up, 26 patients developed SARS-CoV-2 infection of whom three required hospitalization, one of whom died. CONCLUSIONS: 33 of 100 SLE patients immunized with BNT162b2 vaccine against SARS-CoV-2, presented SLE flares (47 episodes in total); 5 of these patients required in-hospital management and all fully recovered; 26 patients had SARS-CoV-2 infection; three required hospitalization, one died.

Front instabilities in the presence of convection due to thermal and compositional gradients.

Reaction fronts separate fluids of different densities due to thermal and compositional gradients that may lead to convection. The stability of convectionless flat fronts propagating in the vertical direction depends not only on fluid properties but also in the dynamics of a front evolution equation. In this work, we analyze fronts described by the Kuramoto-Sivashinsky (KS) equation coupled to hydrodynamics. Without density gradients, the KS equation has a flat front solution that is unstable to perturbations of long wavelengths. Buoyancy enhances this instability if a fluid of lower density is underneath a denser fluid. In the reverse situation, with the denser fluid underneath, the front can be stabilized with appropriate thermal and compositional gradients. However, in this situation, a different instability develops for large enough thermal gradients. We also solve numerically the nonlinear KS equation coupled to the Navier-Stokes equations to analyze the front propagation in two-dimensional rectangular domains. As convection takes place, the reaction front curves, increasing its velocity.

Assessment of Mechanically Induced Changes in Helical Fiber Microstructure Using Diffusion Tensor Imaging.

Noninvasive methods to detect microstructural changes in collagen-based fibrous tissues are necessary to differentiate healthy from damaged tissues in vivo but are sparse. Diffusion Tensor Imaging (DTI) is a noninvasive imaging technique used to quantitatively infer tissue microstructure with previous work primarily focused in neuroimaging applications. Yet, it is still unclear how DTI metrics relate to fiber microstructure and function in musculoskeletal tissues such as ligament and tendon, in part because of the high heterogeneity inherent to such tissues. To address this limitation, we assessed the ability of DTI to detect microstructural changes caused by mechanical loading in tissue-mimicking helical fiber constructs of known structure. Using high-resolution optical and micro-computed tomography imaging, we found that static and fatigue loading resulted in decreased sample diameter and a re-alignment of the macro-scale fiber twist angle similar with the direction of loading. However, DTI and micro-computed tomography measurements suggest microstructural differences in the effect of static versus fatigue loading that were not apparent at the bulk level. Specifically, static load resulted in an increase in diffusion anisotropy and a decrease in radial diffusivity suggesting radially uniform fiber compaction. In contrast, fatigue loads resulted in increased diffusivity in all directions and a change in the alignment of the principal diffusion direction away from the constructs' main axis suggesting fiber compaction and microstructural disruptions in fiber architecture. These results provide quantitative evidence of the ability of DTI to detect mechanically induced changes in tissue microstructure that are not apparent at the bulk level, thus confirming its potential as a noninvasive measure of microstructure in helically architected collagen-based tissues, such as ligaments and tendons.

A Biomechanical Comparison of All-Inside Versus Transtibial Meniscus Root Repair Techniques.

BACKGROUND: Meniscus root tears are associated with chondral injury, early degenerative change, and a high conversion rate to total knee arthroplasty. It is well-established that meniscus root tears lead to decreased femorotibial contact area, increased peak contact pressures, and increased stress on the articular cartilage. PURPOSE: To evaluate the biomechanical characteristics of the all-inside meniscus root repair procedure and compare it with the previously described transtibial technique. STUDY DESIGN: Controlled laboratory study. METHODS: Nine paired cadaveric knees were prepared by removing skin, subcutaneous tissues, quadriceps muscles, patella, and patellar tendon, while leaving the capsule in place. Pressure-mapping sensors were inserted, and specimens underwent compressive loading to obtain peak pressures, mean pressures, and femorotibial contact area in the medial and lateral compartments. Tests were performed as static compression tests with the knee locked at 0° of flexion. Compression testing was performed in 3 states: meniscus intact, meniscus root cut, and after meniscus root repair with an all-inside repair technique. Additionally, testing was completed on 9 pairs of cadaveric knees to compare stiffness and maximal load to failure between the all-inside and transtibial meniscus root repair techniques. RESULTS: In the medial compartment, there were significant increases in median peak pressures and median mean pressures in the root cut state as compared with the intact state (+636 kPA [95% CI, 246 to 1026] and +190 kPA [95% CI, 49 to 330], respectively). All-inside meniscus root repair restored median peak pressures and median mean pressures to approach those of the intact meniscus (+311 kPA [95% CI, -79 to 701] and +137 kPA [95% CI, -3 to 277]). In the lateral compartment, there were also significant increases in median peak pressures and median mean pressures in the root cut state as compared with the intact state (+718 kPA [95% CI, 246 to 1191] and +203 kPA [95% CI, 51 to 355]). All-inside meniscus root repair restored median peak pressures and median mean pressures such that they were not significantly different from the intact state (+322 kPA [95% CI, -150 to 795] and +18 kPA [95% CI, -134 to 171]). There was no difference between repair techniques regarding load to failure (P = .896). Transtibial meniscus root repair had significantly more stiffness (mean ± SD, 24.8 ± 9.3 N/mm) as compared with the all-inside meniscus root repair technique (13.6 ± 3.8 N/mm, P = .015). CONCLUSION: All-inside meniscus root repair reduced median peak and mean pressures to those of the native intact meniscus with the knee in extension in the cadaveric model. When compared with a transtibial meniscus root repair technique, all-inside repair demonstrated decreased stiffness and a similar load to failure. CLINICAL RELEVANCE: All-inside meniscus root repair restored mean and peak femorotibial pressures to those of the intact meniscus. Additionally, it offers a technically easier technique for management of meniscus root tears.

Simulated tele-management for teaching medical students on primary health care managerial decision making

Introduction: Medical students are poorly prepared in health services management due to the use of traditional teaching methods, developed in theoretical environments with poor active participation. Virtual simulated training is an innovative alternative in the learning process. Objective: This study aimed to determine the knowledge improvement in managerial decision-making amongst medical students at the Universidad Nacional Mayor de San Marcos in Peru, after a virtual simulated training. Methods: A before-after cross-sectional design was undertaken among final year medical students to measure their improvement in management knowledge. The simulation methodology was used as a component of the Medical Externship clinical course in which the administrative dimension of a clinical case such as hypoacusis was considered. Results: Of the 79 participants, 48 (60.8%) were female and the median age was 25 years. There was a median satisfaction level of 3.8 and the performance median score was 17. The median post-test rank scores were higher and statistically significant than pre-test rank scores (p = 0.004); post-test scores for males (p-value = 0.05) and females (p = 0.03) were also statistically higher than pre-test scores. Conclusion: The non-clinical simulation experience improves the knowledge on managerial decision making. It also opens opportunities to work on management issues in clinical courses, providing a comprehensive learning experience. On the other hand, it is an innovative experience where a clinical course adopts a management component.

Introducción: Los estudiantes de medicina están poco preparados en gestión de servicios de salud debido al uso de métodos de enseñanza tradicionales, llevados a cabo en entornos teóricos y poco participativos. La formación virtual simulada es una alternativa innovadora en el proceso de aprendizaje. Objetivo: Determinar la mejora en conocimientos sobre la toma de decisiones gerenciales entre los estudiantes de medicina de la Universidad Nacional Mayor de San Marcos en Perú, tras un entrenamiento simulado virtual. Métodos: Estudio de diseño transversal de antes-después en estudiantes de último año de medicina. La metodología de simulación se utilizó como un componente del curso clínico de externado, en el que se consideró la dimensión administrativa de un caso clínico de hipoacusia. Resultados: De los 79 participantes, 48 (60,8%) eran mujeres y la edad media era de 25 años. La mediana del nivel de satisfacción fue de 3,8 y la mediana del rendimiento fue de 17. La mediana de las puntuaciones del post-test fue mayor y estadísticamente significativa en comparación a la del pre-test (p = 0,004); las puntuaciones post-test fueron más altas que las puntuaciones pre-test para los hombres (p = 0,05) y mujeres (p = 0,03). Conclusiones: La experiencia de simulación no clínica logra una mejora significativa en el conocimiento de los participantes. Además, abre oportunidades para trabajar los temas de gestión en los cursos clínicos, proporcionando una experiencia de aprendizaje integral. Por otro lado, es una experiencia innovadora en la que un curso clínico adopta un componente de gestión.

Keratinocyte Response to Infection with Sporothrix schenckii.

Sporotrichosis is a subacute, or chronic mycosis caused by traumatic inoculation of material contaminated with the fungus Sporothrix schenckii which is part of the Sporothrix spp. complex. The infection is limited to the skin, although its progression to more severe systemic or disseminated forms remains possible. Skin is the tissue that comes into contact with Sporothrix first, and the role of various cell lines has been described with regard to infection control. However, there is little information on the response of keratinocytes. In this study, we used the human keratinocyte cell line (HaCaT) and evaluated different aspects of infection from modifications in the cytoskeleton to the expression of molecules of the innate response during infection with conidia and yeast cells of Sporothrix schenckii. We found that during infection with both phases of the fungus, alterations of the actin cytoskeleton, formation of membrane protuberances, and loss of stress fibers were induced. We also observed an overexpression of the surface receptors MR, TLR6, CR3 and TLR2. Cytokine analysis showed that both phases of the fungus induced the production of elevated levels of the chemokines MCP-1 and IL-8, and proinflammatory cytokines IFN-α, IFN-γ and IL-6. In contrast, TNF-α production was significant only with conidial infection. In late post-infection, cytokine production was observed with immunoregulatory activity, IL-10, and growth factors, G-CSF and GM-CSF. In conclusion, infection of keratinocytes with conidia and yeast cells of Sporothrix schenckii induces an inflammatory response and rearrangements of the cytoskeleton.

Novel Techniques and Future Perspective for Investigating Critical-Size Bone Defects.

A critical-size bone defect is a challenging clinical problem in which a gap between bone ends will not heal and will become a nonunion. The current treatment is to harvest and transplant an autologous bone graft to facilitate bone bridging. To develop less invasive but equally effective treatment options, one needs to first have a comprehensive understanding of the bone healing process. Therefore, it is imperative to leverage the most advanced technologies to elucidate the fundamental concepts of the bone healing process and develop innovative therapeutic strategies to bridge the nonunion gap. In this review, we first discuss the current animal models to study critical-size bone defects. Then, we focus on four novel analytic techniques and discuss their strengths and limitations. These four technologies are mass cytometry (CyTOF) for enhanced cellular analysis, imaging mass cytometry (IMC) for enhanced tissue special imaging, single-cell RNA sequencing (scRNA-seq) for detailed transcriptome analysis, and Luminex assays for comprehensive protein secretome analysis. With this new understanding of the healing of critical-size bone defects, novel methods of diagnosis and treatment will emerge.

Applying deep learning to quantify empty lacunae in histologic sections of osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a disease in which inadequate blood supply to the subchondral bone causes the death of cells in the bone marrow. Decalcified histology and assessment of the percentage of empty lacunae are used to quantify the severity of ONFH. However, the current clinical practice of manually counting cells is a tedious and inefficient process. We utilized the power of artificial intelligence by training an established deep convolutional neural network framework, Faster-RCNN, to automatically classify and quantify osteocytes (healthy and pyknotic) and empty lacunae in 135 histology images. The adjusted correlation coefficient between the trained cell classifier and the ground truth was R = 0.98. The methods detailed in this study significantly reduced the manual effort of cell counting in ONFH histological samples and can be translated to other fields of image quantification.

Thermoplastic Starch-Based Blends with Improved Thermal and Thermomechanical Properties.

This research focused on the development of biomaterials based on cassava starch and corn starch and on the effect of the incorporation of polycaprolactone (PCL) on the thermal and thermomechanical properties of the blends. The results indicated partial compatibility in the blends, especially with cassava starch at a content of 20 wt% as reflected by the maintenance of tensile strength and elongation. In addition, the changes in the crystal quality of PCL and the displacement of the absorption bands of the carbonyl groups of PCL in the infrared (989-1000 cm-1), attributed to the formation of hydrogen bonds between these groups and the hydroxyl groups of starches, were also associated with compatibility. It was observed that the crystallinity of PLC in the presence of cassava and corn starch was 38% and 62%, respectively; a crystallinity greater than that of PCL was related to an improved nucleation at the interface. Based on these properties, the blends are expected to be functional for the manufacture of short-term use products by conventional thermoplastic processing methods.

Release of Nanoparticles in the Environment and Catalytic Converters Ageing.

A Three-Way Catalyst (TWC) contains a cordierite ceramic monolith coated with a layer of Al2O3, CexZr1-xO2 and platinoids mixture. Under standard operation, the platinoid concentration decreases, exposing the remaining washcoat structure. After that particle release stage, the sintering process follows where the crystalline CexZr1-xO2 solution is broken and begins to separate into ZrO2 and CeO2 phases. ZrO2 is released to the environment as micro and nanoparticles, while a small amount of CeO2 generates a new AlxCe1-xO2 composite. The main effect of Ce capture is the growth in the size of the polycrystal structure from 86.13 ± 16.58 nm to 225.35 ± 69.51 nm. Moreover, a transformation of cordierite to mullite was identified by XRD analysis. Raman spectra showed that the oxygen vacancies (Vö) concentration decreased as CexZr1-xO2 phases separation occurred. The SEM-EDS revealed the incorporation of new spurious elements and microfractures favouring the detachment of the TWC support structure. The release of ultrafine particles is a consequence of catalytic devices overusing. The emission of refractory micro to nanocrystals to the atmosphere may represent an emerging public health issue underlining the importance of implementing strict worldwide regulations on regular TWCs replacement.

The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits.

BACKGROUND: Approximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH. METHODS: In vitro studies: Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20 mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed. RESULTS: In vitro studies: PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P < 0.001) and CMV-PDGF-BB-MSCs (P < 0.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (P < 0.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14 days (P < 0.01), and osteogenic differentiation at 28 days (P = 0.07) than CMV-PDGF-BB-MSCs. In vivo: The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P = 0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P < 0.001), greater osteoclast density (P < 0.01), and greater angiogenesis (P < 0.01) than the other treatment groups. CONCLUSION: The use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.

The efficacy of lapine preconditioned or genetically modified IL4 over-expressing bone marrow-derived mesenchymal stromal cells in corticosteroid-associated osteonecrosis of the femoral head in rabbits.

Cell-based therapy for augmentation of core decompression (CD) using mesenchymal stromal cells (MSCs) is a promising treatment for early stage osteonecrosis of the femoral head (ONFH). Recently, the therapeutic potential for immunomodulation of osteogenesis using preconditioned (with pro-inflammatory cytokines) MSCs (pMSCs), or by the timely resolution of inflammation using MSCs that over-express anti-inflammatory cytokines has been described. Here, pMSCs exposed to tumor necrosis factor-alpha and lipopolysaccharide for 3 days accelerated osteogenic differentiation in vitro. Furthermore, injection of pMSCs encapsulated with injectable hydrogels into the bone tunnel facilitated angiogenesis and osteogenesis in the femoral head in vivo, using rabbit bone marrow-derived MSCs and a model of corticosteroid-associated ONFH in rabbits. In contrast, in vitro and in vivo studies demonstrated that genetically-modified MSCs that over-express IL4 (IL4-MSCs), established by using a lentiviral vector carrying the rabbit IL4 gene under the cytomegalovirus promoter, accelerated proliferation of MSCs and decreased the percentage of empty lacunae in the femoral head. Therefore, adjunctive cell-based therapy of CD using pMSCs and IL4-MSCs may hold promise to heal osteonecrotic lesions in the early stage ONFH. These interventions must be applied in a temporally sensitive fashion, without interfering with the mandatory acute inflammatory phase of bone healing.

International registry of dermatological manifestations secondary to COVID-19 infection in 347 Hispanic patients from 25 countries.

BACKGROUND: The infection by coronavirus disease 2019 (COVID-19) has been associated with multiple cutaneous manifestations, although characterization of them in Hispanic patients with darker skin phototypes is lacking. The objective of this study is to characterize the clinical dermatological manifestations associated with COVID-19 infection in cases with few or without general symptoms in patients from Latin America. METHODS: Cross-sectional study using a questionnaire that was made for health professionals (physicians with a specialty in dermatology) to investigate dermatological lesions associated with COVID-19 infection in patients from 25 countries of Latin America. The survey was active from June 9 to July 30, 2020. RESULTS: In this study, information was collected from a total of 347 patients. We found a female gender predominance: 179/347 (51.6%). The mean age at presentation was 40.87 years. The most frequent dermatological manifestations were maculopapular rash and urticarial lesions, followed by papulovesicular lesions, vesicular lesions, chilblain-like lesions, papular lesions, ecchymosis, petechial purpura, pityriasis rosea-like lesions, pruritus, palmoplantar dysesthesias, transient livedo, acral necrosis, palpable purpura, livedo racemosa, and retiform purpura. As far as we know, there are no previous reports of pruritus and palmoplantar dysesthesias. CONCLUSIONS: This registry emphasizes skin manifestations as an important criterion for establishing the diagnosis of COVID-19 infection in Latin American countries. This information will be useful for the early identification of suspected cases by health professionals (dermatologists and nondermatologists) and will allow contact tracing to mitigate the impact on health systems at different levels.

Effect of porosity of a functionally-graded scaffold for the treatment of corticosteroid-associated osteonecrosis of the femoral head in rabbits.

Background/Objective: Core decompression (CD) with scaffold and cell-based therapies is a promising strategy for providing both mechanical support and regeneration of the osteonecrotic area for early stage osteonecrosis of the femoral head (ONFH). We designed a new 3D printed porous functionally-graded scaffold (FGS) with a central channel to facilitate delivery of transplanted cells in a hydrogel to the osteonecrotic area. However, the optimal porous structural design for the FGS for the engineering of bone in ONFH has not been elucidated. The aim of this study was to fabricate and evaluate two different porous structures (30% or 60% porosity) of the FGSs in corticosteroid-associated ONFH in rabbits. METHODS: Two different FGSs with 30% or 60% porosity containing a 1-mm central channel were 3D printed using polycaprolactone and ß-tricalcium phosphate. The FGS was 3-mm diameter and 32-mm length and was composed of three segments: 1-mm in length for the non-porous proximal segment, 22-mm in length for the porous (30% versus 60%) middle segment, and 9-mm in length for the 15% porous distal segment. Eighteen male New Zealand White rabbits were given a single dose of 20 â€‹mg/kg methylprednisolone acetate intramuscularly. Four weeks later, rabbits were divided into three groups: the CD group, the 30% porosity FGS group, and the 60% porosity FGS group. In the CD group, a 3-mm diameter drill hole was created into the left femoral head. In the FGS groups, a 30% or 60% porosity implant was inserted into the bone tunnel. Eight weeks postoperatively, femurs were harvested and microCT, mechanical, and histological analyses were performed. RESULTS: The actual porosity and pore size of the middle segments were 26.4% â€‹± â€‹2.3% and 699 â€‹± â€‹56 â€‹µm in the 30% porosity FGS, and 56.0% â€‹± â€‹4.5% and 999 â€‹± â€‹71 â€‹µm in the 60% porosity FGS, respectively using microCT analysis. Bone ingrowth ratio in the 30% porosity FGS group was 73.9% â€‹± â€‹15.8%, which was significantly higher than 39.5% â€‹± â€‹13.0% in the CD group on microCT (p â€‹< â€‹0.05). Bone ingrowth ratio in the 60% porosity FGS group (61.3% â€‹± â€‹30.1%) showed no significant differences compared to the other two groups. The stiffness at the bone tunnel site in the 30% porosity FGS group was 582.4 â€‹± â€‹192.3 â€‹N/mm3, which was significantly higher than 338.7 â€‹± â€‹164.6 â€‹N/mm3 in the 60% porosity FGS group during push-out testing (p â€‹< â€‹0.05). Hematoxylin and eosin staining exhibited thick and mature trabecular bone around the porous FGS in the 30% porosity FGS group, whereas thinner, more immature trabecular bone was seen around the porous FGS in the 60% porosity FGS group. CONCLUSION: These findings indicate that the 30% porosity FGS may enhance bone regeneration and have superior biomechanical properties in the bone tunnel after CD in ONFH, compared to the 60% porosity FGS. TRANSLATION POTENTIAL STATEMENT: The translational potential of this article: This FGS implant holds promise for improving outcomes of CD for early stage ONFH.

Frecuencia de alexitimia y factores relacionados en pacientes con fibromialgia tratados en un hospital público de Lima, Perú / Frequency and related factors of alexithymia in patients with fibromyalgia treated at a public hospital in Lima, Peru

RESUMEN Objetivo : Determinar la frecuencia de alexitimia y factores relacionados en pacientes con fibromialgia, y la relación entre alexitimia y capacidad funcional, intensidad de dolor, depresión y variables generales (edad, sexo, tiempo de enfermedad, grado de instrucción y años de estudio) en fibromialgia. Material y métodos : Se realizó un estudio descriptivo transversal en pacientes con fibromialgia del Servicio de Reumatología de un hospital público de Lima, Perú. Se aplicó una ficha sociodemográfica, la TAS-20, el MD-HAQ y la CES-D. Resultados : De los 126 pacientes con fibromialgia, 60 (47,62 %) mostraron alexitimia, 24 de ellos presentaron depresión (40%) y 39, discapacidad funcional (65%). En el análisis bivariado la alexitimia se relacionó significativamente con mayor comorbilidad, menor grado de instrucción, mayor intensidad de dolor, mayor fatiga y más síntomas reportados. En el análisis multivariado, años de estudio (£11 años) fue el único factor relacionado a alexitimia (TAS-20) (p=0,010, OR: 2,589 [1,249 - 5,365]). Conclusiones : Se demuestra una frecuencia considerable de alexitimia en pacientes con fibromialgia y, en el análisis multivariado, este hallazgo se relaciona significativamente con un número menor de años de estudio.

SUMMARY Objective : To determine the frequency of alexithymia and associated factors in patients with fibromyalgia, and the relationship between alexithymia with functional capacity, pain intensity, depression and general variables (age, sex, time of illness, degree of instruction, and years of study) in fibromyalgia. Material and methods : Descriptive cross-sectional study of patients with fibromyalgia from the Rheumatology service of a public hospital in Lima, Perú. A sociodemographic record, TAS-20, MD-HAQ and CES-D were applied. Results . Of the 126 patients with fibromyalgia, 60 had alexithymia (47.62%); 24 alexithymic patients had depression (40 %), and 39 had functional disability (65 %). In the bivariate analysis, alexithymia was significantly related to greater comorbidity, less education, greater pain intensity, greater fatigue and more reported symptoms. In the multivariate analysis, years of study (£ 11 years) were the only factor related to alexithymia (TAS-20) (p=0.010, OR: 2.589 [1.249 - 5.365]). Conclusions : This study shows a considerable frequency of alexithymia in fibromyalgia patients and, in the multivariate analysis, the finding is significantly related to a lower number of years of study.

Replication of the tensile behavior of knee ligaments using architected acrylic yarn.

Knee ligament injury diagnosis is achieved by a comparison between the laxity levels sensed by a clinician in the injured and healthy limb. This is a difficult-to-learn task that requires hands-on practice to achieve proficiency. The inclusion of a physical knee simulator with biomechanically realistic passive components such as knee ligaments could provide consistent training for medical students and lead to improved care for knee injury patients. In this study, we developed a material construct that is both adaptable to a physical knee model and capable of replicating the non-linear mechanical behavior of knee ligaments with the use of helically arranged acrylic yarn. The microstructure of four different types of acrylic yarn were measured and then tested under uniaxial tension. While the fiber twist angle was similar amongst the four yarn types (range = 17.9-18.8°), one yarn was distinct with a low ply twist angle (15.2 ± 1.6°) and high packing fraction (Φ=0.32±0.08). These microstructural differences yielded a lower toe length and higher stiffness and best corresponded to ligament mechanical behavior. We then made looped-yarn constructs to modulate the sample's toe length and stiffness. We found that the load-displacement curve of the construct can be tuned by changing the loop length and loop number of the looped-yarn constructs, matching the load-displacement curve of specific knee ligaments. This study shows how spun yarn can be used to replicate the mechanical behavior of knee ligaments, creating synthetic ligament constructs that could enable the construction of biomechanically realistic joints.

Eritema nodoso necrosante en lepra lepromatosa asociada a infección mixta por Mycobacterium lepromatosis y Mycobacterium leprae. Reporte de caso / Necrotizing erythema nodosumin lepromatous leprosy associated with mixed infection by Mycobacterium lepromatosis and Mycobacterium leprae. Case report

RESUMEN La lepra es una enfermedad causada por Mycobacterium leprae. Su evolución crónica a veces se ve interrumpida por cuadros inmunológicos llamados reacción leprosa en pacientes con alta carga bacilar. Estos cuadros inmunológicos incrementan la morbilidad y pueden complicarse, volviéndose potencialmente mortales. En el espectro de estas reacciones, se han descrito algunas caracterizadas por lesiones vasculo necróticas, como el Fenómeno de Lucio y el eritema nodoso lepromatoso necrosante, que son asociadas a la lepra lepromatosa difusa y a la especie de bacilos recién descripta, Mycobacterium lepromatosis. Presentamos un paciente de sexo femenino de 21 años de edad, que duranteel tratamiento específico para lepra multibacilar presentó cuadros recidivantes de eritema nudoso que evolucionó a la forma necrosante. En este paciente se precisó a través de la biología molecular la presencia simultánea de M. leprae y M. lepromatosis como causantes de la enfermedad. Este caso representa la primera comunicación de M. lepromatosis en el Paraguay, y también la primera infección dual como agente causante de lepra, en asociación con el M. leprae.

ABSTRACT Leprosy is a disease caused by Mycobacterium leprae. Its chronic evolution is sometimes interrupted by immunological conditions called leprosy reaction in patients with high bacillary load. These immunological conditions increase morbidity and can be complicated, becoming life threatening. In the spectrum of these reactions, some characterized by vasculonecrotic lesions have been described, such as Lucio's Phenomenon and Necrotizing Lepromatous Nodus Erythem, which are associated with diffuse lepromatous leprosy and the species of bacilli just described, Mycobacterium lepromatosis. We present a 21-year-old female patient, who during specific treatment for multibacillary leprosy presented recurrent pictures of erythema nodosum that evolved to the necrotizing form. In this patient, the simultaneous presence of M. leprae and M. lepromatosis as the cause of the disease was determined through molecular biology. This case represents the first communication of M. lepromatosis in Paraguay, and also the first dual infection as a causative agent of leprosy, in association with M. leprae.