An in vitro neurogenetics platform for precision disease modeling in the mouse.

The power and scope of disease modeling can be markedly enhanced through the incorporation of broad genetic diversity. The introduction of pathogenic mutations into a single inbred mouse strain sometimes fails to mimic human disease. We describe a cross-species precision disease modeling platform that exploits mouse genetic diversity to bridge cell-based modeling with whole organism analysis. We developed a universal protocol that permitted robust and reproducible neural differentiation of genetically diverse human and mouse pluripotent stem cell lines and then carried out a proof-of-concept study of the neurodevelopmental gene DYRK1A. Results in vitro reliably predicted the effects of genetic background on Dyrk1a loss-of-function phenotypes in vivo. Transcriptomic comparison of responsive and unresponsive strains identified molecular pathways conferring sensitivity or resilience to Dyrk1a1A loss and highlighted differential messenger RNA isoform usage as an important determinant of response. This cross-species strategy provides a powerful tool in the functional analysis of candidate disease variants identified through human genetic studies.

Predicting spatio-temporal radiofrequency ablation temperature using deep neural networks.

Radiofrequency ablation (RFA) of the medial branch nerve is a widely used therapeutic intervention for facet joint pain. However, denervation of the multifidus muscle is an inevitable consequence of RFA. New ablation techniques with the potential to prevent muscle denervation can be designed using computational simulations. However, depending on the complexity of the model, they could be computationally expensive. As an alternative approach, deep neural networks (DNNs) can be used to predict tissue temperature during RFA procedure. The objective of this paper is to predict the tissue spatial and temporal temperature distributions during RFA using DNNs. First, finite element (FE) models with a range of distances between the probes were run to obtain the temperature readings. The measured temperatures were then used to train the DNNs that predict the spatio-temporal temperature distribution within the tissue. Finally, a separate data obtained from FE simulations were used to test the efficacy of the network. The results presented in this paper demonstrate that the network can achieve an error rate as low as 0.05%, accompanied by a 92% reduction in time compared to FE simulations. The approach proposed in this study will play a major role in the design of new RFA treatments for facet joint pain.

Regional healing trajectory of the patellar tendon after bone-patellar tendon-bone autograft harvest for anterior cruciate ligament reconstruction.

Graft site morbidities after bone-patellar tendon-bone (BPTB) autograft harvest for anterior cruciate ligament reconstruction (ACLR) negatively impacts rehabilitation. The purpose of this study was to establish tendon structural properties 1-month after BPTB autograft harvest compared to the uninvolved patellar tendon, and subsequently to quantify the healing trajectory of the patellar tendon over the course of rehabilitation. Patellar tendon morphology (ultrasound) and mechanical properties (continuous shear wave elastography) from 3 regions of the tendon (medial, lateral, central) were measured in 34 participants at 1 month, 3-4 months, and 6-9 months after ACLR. Mixed models were used to compare tendon structure between limbs at 1 month, and quantify healing over 3 timepoints. The involved patellar tendon had increased cross-sectional area and thickness in all regions 1-month after ACLR. Thickness reduced uniformly over time. Possible tendon elongation was observed and remained stable over time. Tendon viscosity was uniform across the three regions in the involved limb while the medial region had higher viscosity in the uninvolved limb, and shear modulus was elevated in all three regions at 1 month. Viscosity and shear modulus in only the central region reduced over time. Statement of Clinical Significance: The entire patellar tendon, and not just the central third, is altered after graft harvest. Tendon structure starts to normalize over time, but alterations remain especially in the central third at the time athletes are returning to sport. Early rehabilitation consisting of tendon loading protocols may be necessary to optimize biologic healing at the graft site tendon.

Fracture Resistance of Chairside CAD/CAM Molar Crowns Fabricated with Different Lithium Disilicate Ceramic Materials

PURPOSE: To compare the fracture resistance of five different groups of chairside CAD/CAM molar crowns fabricated from various lithium disilicate ceramic materials (LDC): one conventional precrystallized CAD/CAM LDC, two novel precrystallized LDCs, and one fully crystallized LDC tested both with and without optional sintering. MATERIALS AND METHODS: A total of 60 chairside CAD/CAM lithium disilicate molar crowns (n = 12 per group) with 1.5-mm occlusal thickness and a 1.0-mm chamfer finish were designed and fabricated with a chairside CAD/CAM system (CEREC, Dentsply Sirona). The restorations were divided into five groups: (1) IPS e.max CAD; (2) Amber Mill; (3) Straumann n!ce; (4) Straumann n!ce with optional sintering; and (5) Supreme CAD. Restorations were cemented using conventional resin luting cement and primer system to 3D-printed resin dies. Bonded restorations were loaded for 100,000 cycles with 275-N force, and the load at break (LB) and peak load (PL) until fracture were measured. SEM images of fracture surfaces on the printed dies were obtained. RESULTS: Fracture resistance was significantly different depending on the material. Supreme CAD showed the highest fracture resistance (LB: 1,557.2 N; PL: 1,785.8 N), followed by Amber Mill (LB: 1,393.0 N; PL: 1,604.2 N) and IPS e.max CAD (LB: 1,315.7 N; PL: 1,461.9 N). Straumann n!ce without (LB: 862.4 N; PL: 942.9 N) and with the optional sintering (LB: 490.4 N; PL: 541.0 N) showed significantly lower fracture resistance than the others. CONCLUSION: The fracture resistance of chairside CAD/CAM lithium disilicate molar crowns varied depending on the material, and the novel materials did not perform as well as the conventional equivalents. Fully crystallized lithium disilicate ceramic block materials showed lower fracture resistance than precrystallized counterparts and should be used with caution in the clinic, especially with optional sintering.

Superscan on 68Ga PSMA PET/CT in patients with metastatic prostate carcinoma: A case series.

Prostate cancer is the second most common malignancy in men worldwide, with a good prognosis when is detected and treated in early stages, but, when it presents progression to castration-resistant metastatic prostate cancer, most of the cases will have bone metastasis, decreasing the quality of life and life expectancy. For the evaluation of the disease in the routinary clinical practice, 68Ga-PSMA PET/CT, among others is a valuable tool for the evaluation of the disease extension. 68Ga-PSMA PET/CT detects the presence of PSMA receptor in the tumoral tissue, but also has physiologic uptake in certain organs, such as liver, spleen, intestine, kidneys, lacrimal and salivary glands. Total or partial absence of uptake in those organs is rare and may be due to a high metastatic tumor burden, a phenomenon originally described in bone scintigraphy as super scan. We describe a case series of seven patients with prostate cancer from the National Institute of Cancerology in Colombia, in which a super scan pattern was found in the evaluation with 68Ga-PSMA PET/CT, proposing the suppression of uptake in the intestine, liver, spleen, lacrimal and salivary glands as the main criteria for its definition, and showing that renal uptake persists in most cases, considering that, unlike the super scan in conventional bone scintigraphy, this is not a criterion necessary for its definition in the study with 68Ga-PSMA.

Experiences of grief and moral sentiments in survivors of the armed conflict in Medellín, Colombia.

The objective of the study is to understand the experience of grief and moral sentiments in survivors of the armed conflict in the city of Medellín, Colombia, through qualitative research. In total, 32 people affected by different victimising acts in the context of the armed conflict participated. There is a direct relationship between moral sentiments and the processes of handling and processing loss. Moral sentiments frame the experience of emotions in the victim, after the events have occurred, which influence the way in which the pain experienced is processed. These sentiments permeate the processes of dealing with the incident in survivors, the ways in which they perceive themselves and the perpetrators, and the social stances they adopt to face life. We conclude that moral factors play a role in the emotional recovery of victims and are indicative the possibility or difficulty of processing the events that occurred.

Multifidus Denervation After Radiofrequency Ablation of the Medial Nerve Alters the Biomechanics of the Spine-A Computational Study.

Radiofrequency ablation of the medial branch is commonly used to treat chronic low back pain involving facet joints, which accounts for 12% to 37% of the total cases of chronic low back pain. An adverse effect of this procedure is the denervation of the multifidus muscle, which may lead to its atrophy which can affect the spine and possibly disc degeneration. This study aims to quantify changes in joint angles and loading caused by multifidus denervation after radiofrequency ablation. AnyBody model of the torso was used to evaluate intervertebral joints in flexion, lateral bending, and torsion. Force-dependent kinematics was used to calculate joint angles and forces. These dependent variables were investigated in intact multifidus, unilateral, and bilateral ablations of L3L4, L4L5, and L5S1 joints. The results showed pronounced angular joint changes, especially in bilateral ablations in flexion, when compared with other cases. The same changes' trend from intact to unilaterally then bilaterally ablated multifidus occurred in joint angles of lateral bending. Meanwhile, joint forces were not adversely affected. These results suggest that multifidus denervation after radiofrequency ablation affects spinal mechanics. Such changes may be associated with abnormal tissue deformations and stresses that can potentially alter their mechanobiology and homeostasis, thereby possibly affecting the health of the spine.

Health benefits of Open Streets programmes in Latin America: a quantitative health impact assessment.

BACKGROUND: To improve physical activity in Latin American cities, several interventions have been promoted, such as Open Streets programmes. Our study aims to quantify the health and economic effects of Open Streets-related physical activity in 15 Latin American cities. METHODS: We used a quantitative health impact assessment approach to estimate annual premature deaths and disease incidence (ischaemic heart disease, ischaemic stroke, type 2 diabetes, colon cancer, breast cancer, and dementia) avoided, the disability-adjusted life-years (DALYs) gained, and the cost saving (from reduced premature mortality) related to increased physical activity from Open Streets programmes in 15 Latin American cities. Input data were obtained from scientific publications, reports, and open street city surveys spanning 2017 to 2019. Physical activity data were converted to metabolic equivalent of the task. Exposure-response relationship functions were applied to estimate relative risk and population-attributable fraction, enabling the assessment of premature deaths and disease incidence. FINDINGS: The percentage of male users of the Open Streets programmes ranged from 55% (27 500 of 50 000 in Guatemala) to 75% (2250 of 3000 in El Alto, Bolivia), and female users ranged from 25% (750; El Alto) to 45% (22 500; Guatemala). We estimated that the current Open Streets programmes in the 15 Latin American cities studied could prevent 363 (95% CI 271-494) annual premature deaths due to increased physical activity, with an annual economic impact of US$194·1 million (144·9 million-263·9 million) saved and an annual reduction of 1036·7 DALYs (346·7-1778·3). If one Open Streets event is added per week in each of those cities, the potential benefit could increase to 496 (370 to 677) premature deaths prevented each year. INTERPRETATION: Open Streets programmes in Latin America can provide health and economic benefits related to increased physical activity and can be used as a health promotion and disease prevention tool. FUNDING: EU's Horizon 2020 research and innovation programme.

[The impact of COVID-19 in a cohort of patients with systemic sclerosis]. / El impacto de COVID-19 en una cohorte de pacientes con esclerosis sistémica.

Background: COVID-19 brought with it unknowns related to systemic sclerosis. Objective: To know the clinical evolution and prognosis of COVID-19 in a cohort of patients with systemic sclerosis. Methods: During the pandemic, we had digital contact with a cohort of 197 patients with SSc. If they had any condition that met the suspected definition of COVID-19, they underwent polymerase chain reaction testing for SARS-CoV-2; they were treated on an outpatient or hospital basis without interfering with their treatment. They followed their evolution every 24 hours until they became asymptomatic or died. Results: Thirteen patients (6.6%), nine diffuse cutaneous (dcSSc), and four limited cutaneous (lcSSc) developed COVID-19 during nine months of follow-up. The immunosuppressants used at the time of the disease were: mycophenolate mofetil, methotrexate, and prednisone, in low doses. Seven patients had interstitial lung disease (ILD). The main symptoms were chest pain, cough, dyspnea, dysgeusia, and anosmia, 1 with mild symptoms without pneumonia, 11 with mild pneumonia, and one with severe pneumonia that required hospital management. Only one (7.7%) presented severe pneumonia, was hospitalized, and died. Conclusions: COVID-19 disease in patients with SSc can be overcome in most cases, even when they are ILD and were using immunosuppressants at the time of infection with the SARS-CoV-2 virus.

Introducción: la COVID-19 trajo consigo incógnitas relacionadas con la esclerosis sistémica, enfermedad de baja prevalencia asociada a neumopatía intersticial difusa (NID). Objetivo: conocer la evolución clínica y el pronóstico de la COVID-19 en una cohorte de pacientes con esclerosis sistémica (ES). Métodos: se analizó una serie de 13 casos procedentes de una cohorte de 197 pacientes con ES en seguimiento vía digital. Cuando los pacientes cumplieron con la definición sospechosa de COVID-19 se solicitó prueba de reacción en cadena de polimerasa para SARS-CoV-2. Todos los pacientes recibieron seguimiento durante su atención ambulatoria u hospitalaria, sin interferir con su tratamiento cada 24 horas hasta quedar asintomáticos o fallecer. Resultados: de 197 pacientes, trece (6.6%) enfermaron de COVID-19 de edad 57 años (RIC: 52-63), cutáneos difusa (ESD) y 4 limitada (ESL) en lapso de 9 meses. Once presentaron neumonía leve (84%), una neumonía grave con fallecimiento intrahospitalario (7.7%). La oximetría media al ambiente se mantuvo en SO2 90% (88-92%). Casi todos usaban inmunosupresores (84%) al momento de enfermar: micofenolato de mofetilo, metotrexato, prednisona en dosis bajas. Siete (53%) tenían enfermedad pulmonar intersticial (EPI) previa. Principalmente manifestaron disnea (67.5%), dolor torácico, tos, disgeusia y anosmia. Conclusiones: es posible que al momento del contagio con el virus SARS-CoV-2 los inmunosupresores permitieran una menor respuesta inflamatoria sistémica, evitando un peor pronóstico, incluso en quienes tienen enfermedad intersticial previa.

Understanding Progestins: From Basics to Clinical Applicability.

Progestin is a term used to describe a synthetic progestogen. The activity and potency of synthetic progestins are mostly evaluated via parameters associated with their endometrial effects, which are related to their interactions with progesterone, estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. The chemical structure of progestins is the key to understanding their interactions with these receptors and predicting the other effects associated with these drugs. Due to their endometrial effect, progestins are used for different gynecological conditions, such as endometriosis, contraception, hormonal replacement therapy, and artificial reproduction techniques. This review is focused on improving our knowledge of progestins (from their history and biochemical effects related to their chemical structures to clinical applications in gynecological conditions) in order to improve clinical practice.

[Impact of hyperglycemia on the prognosis of patients hospitalized for severe pneumonia in COVID-19]. / Impacto de hiperglucemia en el pronóstico de hospitalizados por neumonía grave en COVID-19.

Background: Adequate glycemic control improves the prognosis of patients hospitalized for pneumonia associated with severe COVID-19. Objective: To evaluate the impact of hyperglycemia (HG) on the prognosis of patients hospitalized for severe pneumonia associated with COVID-19 in unvaccinated patients. Material and methods: Prospective cohort study. We included patients hospitalized from August 2020 to February 2021, with severe COVID-19 pneumonia, not vaccinated against SARS-CoV-2. Data was collected from admission to discharge. We used descriptive and analytical statistics according to the data distribution. ROC curves were used to determine the cut-off points with the highest predictive performance for HG and mortality, with the IBM SPSS program, version 25. Results: We included 103 patients, 32% women, 68% men, age 57 ± 13 years; 58% were admitted with HG (191, IQR 152-300 mg/dL) and 42% with normoglycemia (NG < 126 mg/dL). Mortality was higher in HG at admission 34 (56.7%) than in NG 13 (30.2%) (p = 0.008). HG was associated with diabetes mellitus 2 and neutrophilia (p < 0.05). The risk of death increases 1.558 times (95% CI 1.118-2.172) if HG is at admission and 1.43 times (95% CI 1.14-1.79) during hospitalization. Maintaining NG throughout the hospitalization contributed independently to survival (RR = 0.083 [95% CI 0.012-0.571], p = 0.011). Conclusion: HG significantly impacts prognosis by increasing mortality more than 50% during hospitalization for COVID-19.

Introducción: el adecuado control glucémico mejora el pronóstico de pacientes hospitalizados por neumonía asociada a COVID-19 grave. Objetivo: evaluar el impacto de la hiperglucemia (HG) sobre el pronóstico de pacientes hospitalizados por neumonía grave asociada a COVID-19 en no vacunados. Material y métodos: estudio de cohorte prospectivo. Se incluyeron pacientes hospitalizados de agosto de 2020 a febrero de 2021, con neumonía grave por COVID-19, no vacunados contra SARS-CoV-2. Los datos fueron recolectados desde el ingreso hasta el egreso. Se empleó estadística descriptiva y analítica de acuerdo con la distribución de datos. Se construyeron curvas ROC para determinar los puntos de corte de mayor rendimiento predictivo para HG y mortalidad, con el programa IBM SPSS, versión 25. Resultados: se incluyeron 103 pacientes, 32% mujeres, 68% hombres, edad 57 ± 13 años; 58% ingresaron con HG (191, IQR 152-300 mg/dL) y 42% en normoglucemia (NG < 126 mg/dL). La mortalidad fue mayor en HG al ingreso 34 (56.7%) que en NG 13 (30.2%) (p = 0.008). La HG se asoció con diabetes mellitus 2 y neutrofilia (p < 0.05). El riesgo de muerte se incrementó 1.558 veces (IC 95% 1.118-2.172) si la HG fue al ingreso y 1.43 veces (IC 95% 1.14-1.79) durante la hospitalización. Mantener NG durante todo el internamiento contribuyó de manera independiente a la sobrevida (RR 0.083 [IC 95% 0.012-0.571], p = 0.011). Conclusión: la HG impacta significativamente el pronóstico al incrementar en más de 50% la mortalidad durante la hospitalización por COVID-19.

Challenging the assumption of uniformity in patellar tendon structure: Regional patellar tendon morphology and mechanical properties in vivo.

Patellar tendons are assumed to be uniform in morphology and mechanical properties despite a higher prevalence of tendinopathies observed in the medial region. The purpose of this study was to compare the thickness, length, viscosity, and shear modulus of the medial, central, and lateral regions of healthy patellar tendons of young males and females in vivo. B-mode ultrasound and continuous shear wave elastography were performed on 35 patellar tendons (17 females, 18 males) over three regions of interest. A linear mixed-effects model (α = 0.05) was used to determine differences between the three regions and sexes followed by pairwise comparisons for significant findings. The lateral region (mean [95% confidence interval] = 0.34 [0.31-0.37] cm) was thinner compared with the medial (0.41 [0.39-0.44] cm, p < 0.001), and central (0.41 [0.39-0.44] cm, p < 0.001) regions regardless of sex. Viscosity was lower in the lateral (19.8 [16.9-22.7] Pa-s) versus medial region (27.4 [24.7-30.2] Pa-s, p = 0.001). Length had a region-by-sex interaction (p = 0.003) characterized by a longer lateral (4.83 [4.54-5.13] cm) versus medial (4.42 [4.12-4.72] cm) region in males (p < 0.001), but not females (p = 0.992). Shear modulus was uniform between regions and sexes. The thinner, and less viscous lateral patellar tendon may reflect the lower load the tendon experiences explaining the differences in regional prevalence of developing tendon pathology. Statement of Clinical Significance: Healthy patellar tendons are not uniform in morphology or mechanical properties. Considering regional tendon properties may help guide targeted interventions for patellar tendon pathologies.

Hacia el diseño de Vida Saludable, un nuevo programa de estudios para la educación básica en México.

OBJETIVO: Describir el proceso de diseño de Vida Saludable, un nuevo programa de estudios para la educación básica en México. Material y métodos. Se conformó un equipo de trabajo entre especialistas en salud y la Secretaría de Educación Pública. Se establecieron las bases científicas de Vida Saludable, se seleccionaron y evaluaron materiales para Vida Saludable, y se revisaron contenidos vigentes de salud incluidos en otras asignaturas. RESULTADOS: Alimentación, actividad física e higiene y limpieza fueron definidos como los tres ejes temáticos para Vida Saludable. Se aprobaron 3 de 228 insumos para usarse en Vida Saludable y 71.7% de los con-tenidos vigentes en educación básica sobre salud requieren ediciones. CONCLUSIONES: Vida Saludable es un parteaguas hacia la alfabetización en materia de salud en educación básica en México, que se alinea con la agenda global para preservar la salud humana y planetaria.

Contractile ring composition dictates kinetics of in silico contractility.

Constriction kinetics of the cytokinetic ring are expected to depend on dynamic adjustment of contractile ring composition, but the impact of ring component abundance dynamics on ring constriction is understudied. Computational models generally assume that contractile networks maintain constant total amounts of components, which is not always true. To test how compositional dynamics affect constriction kinetics, we first measured F-actin, non-muscle myosin II, septin, and anillin during Caenorhabditis elegans zygotic mitosis. A custom microfluidic device that positioned the cell with the division plane parallel to a light sheet allowed even illumination of the cytokinetic ring. Measured component abundances were implemented in a three-dimensional agent-based model of a membrane-associated contractile ring. With constant network component amounts, constriction completed with biologically unrealistic kinetics. However, imposing the measured changes in component quantities allowed this model to elicit realistic constriction kinetics. Simulated networks were more sensitive to changes in motor and filament amounts than those of crosslinkers and tethers. Our findings highlight the importance of network composition for actomyosin contraction kinetics.

Reliability of Continuous Shear Wave Elastography in the Pathological Patellar Tendon.

OBJECTIVES: Patellar tendon injuries occur via various mechanisms such as overuse, or due to surgical graft harvest for anterior cruciate ligament reconstruction (ACLR). Quantified patellar tendon stiffness after injury may help guide clinical care. Continuous shear wave elastography (cSWE) allows for the assessment of viscosity and shear modulus in tendons. The reliability of the measure, however, has not been established in the patellar tendon. The purpose of this study was to investigate the interrater reliability, intrarater reliability, and between-day stability of cSWE in both healthy and pathological patellar tendons. METHODS: Participants with patellar tendinopathy (n = 13), history of ACLR using bone-patellar tendon-bone autograft (n = 9), and with no history of patellar tendon injury (n = 13) were recruited. cSWE was performed 4 times by multiple raters over 2 days. Intraclass correlations (ICC) and minimum detectable change (MDC95% ) were calculated. RESULTS: Good to excellent between-day stability were found for viscosity (ICC = 0.905, MDC95%  = 8.3 Pa seconds) and shear modulus (ICC = 0.805, MDC95%  = 27.4 kPa). The interrater reliability measures, however, were not as reliable (ICC = 0.591 and 0.532). CONCLUSIONS: cSWE is a reliable assessment tool for quantifying patellar tendon viscoelastic properties over time. It is recommended, however, that a single rater performs the measure as the interrater reliability was less than ideal.

ALCAM: A Novel Surface Marker on EpCAMlow Circulating Tumor Cells.

Background: Current strategies in circulating tumor cell (CTC) isolation in pancreatic cancer heavily rely on the EpCAM and cytokeratin cell status. EpCAM is generally not considered a good marker given its transitory change during Epithelial to Mesenchymal Transition (EMT) or reverse EMT. There is a need to identify other surface markers to capture the complete repertoire of PDAC CTCs. The primary objective of the study is to characterize alternate surface biomarkers to EpCAM on CTCs that express low or negligible levels of surface EpCAM in pancreatic cancer patients. Methods: Flow cytometry and surface mass spectrometry were used to identify proteins expressed on the surface of PDAC CTCs in culture. CTCs were grown under conditions of attachment and in co-culture with naïve neutrophils. Putative biomarkers were then validated in GEMMs and patient samples. Results: Surface proteomic profiling of CTCs identified several novel protein biomarkers. ALCAM was identified as a novel robust marker in GEMM models and in patient samples. Conclusions: We identified several novel surface biomarkers on CTCs expressed under differing conditions of culture. ALCAM was validated and identified as a novel alternate surface marker on EpCAMlow CTCs.

Fracture Resistance of Chairside CAD/CAM Molar Crowns Fabricated with Different Lithium Disilicate Ceramic Materials.

PURPOSE: To compare the fracture resistance of five different groups of chairside CAD/CAM molar crowns fabricated from various lithium disilicate ceramic materials (LDC): one conventional precrystallized CAD/CAM LDC, two novel precrystallized LDCs, and one fully crystallized LDC tested both with and without optional sintering. MATERIALS AND METHODS: A total of 60 chairside CAD/CAM lithium disilicate molar crowns (n = 12 per group) with 1.5-mm occlusal thickness and a 1.0-mm chamfer finish were designed and fabricated with a chairside CAD/CAM system (CEREC, Dentsply Sirona). The restorations were divided into five groups: (1) IPS e.max CAD; (2) Amber Mill; (3) Straumann n!ce; (4) Straumann n!ce with optional sintering; and (5) Supreme CAD. Restorations were cemented using conventional resin luting cement and primer system to 3D-printed resin dies. Bonded restorations were loaded for 100,000 cycles with 275-N force, and the load at break (LB) and peak load (PL) until fracture were measured. SEM images of fracture surfaces on the printed dies were obtained. RESULTS: Fracture resistance was significantly different depending on the material. Supreme CAD showed the highest fracture resistance (LB: 1,557.2 N; PL: 1,785.8 N), followed by Amber Mill (LB: 1,393.0 N; PL: 1,604.2 N) and IPS e.max CAD (LB: 1,315.7 N; PL: 1,461.9 N). Straumann n!ce without (LB: 862.4 N; PL: 942.9 N) and with the optional sintering (LB: 490.4 N; PL: 541.0 N) showed significantly lower fracture resistance than the others. CONCLUSION: The fracture resistance of chairside CAD/CAM lithium disilicate molar crowns varied depending on the material, and the novel materials did not perform as well as the conventional equivalents. Fully crystallized lithium disilicate ceramic block materials showed lower fracture resistance than precrystallized counterparts and should be used with caution in the clinic, especially with optional sintering.

Tendon loading in runners with Achilles tendinopathy: Relations to pain, structure, and function during return-to-sport.

We aimed to (1) compare pain, tendon structure, lower limb function, and Achilles tendon loads while running between limbs in runners with Achilles tendinopathy, and (2) explore the relations of pain, tendon structure, and lower limb function to Achilles tendon loads while running. Twenty runners with Achilles tendinopathy participated in this pilot study. Pain was assessed with questionnaires, quantitative sensory testing, and functional testing. Tendon morphology and mechanical properties were evaluated with ultrasound imaging, continuous shear wave elastography, and ultrasound imaging combined with dynamometry. Lower limb function was assessed with an established test battery. Achilles tendon loads were estimated from biomechanical data acquired during running. Compared to the least symptomatic limb, the most symptomatic limb had lower scores on the Victorian Institute of Sports Assessment - Achilles questionnaire and worse pain during drop countermovement jumping, hopping, and running. Tendon thickness and cross-sectional area were greater, and Young's modulus, drop countermovement jump height, and plyometric quotient during hopping were lower on the most symptomatic limb. Side-to-side differences in drop countermovement jump height were significantly associated with side-to-side differences in Achilles tendon peak forces and average loading rates during running. Various measures of pain, structure, and function differ between limbs in runners with Achilles tendinopathy during return-to-sport. Tendon forces, however, do not differ between limbs during comfortable running. In addition to measures that differ between limbs, measures of performance during drop countermovement jumping may aid in clinical decision-making during return-to-sport because they are associated with tendon forces while running.

Relationships between tendon structure and clinical impairments in patients with patellar tendinopathy.

The clinical relevance of altered tendon structure in patellar tendinopathy is contested since structural change persists after symptom resolution. The purpose of this study was to explore the relationships between tendon structure and clinical impairments in patellar tendinopathy. In this retrospective, secondary analysis of individuals with patellar tendinopathy (n = 41), tendon structure (thickness, cross-sectional area [CSA], shear modulus, and viscosity), symptom severity, lower extremity function (counter-movement jump [CMJ] height), and quadriceps muscle performance (knee extension force and central activation ratio [CAR]) were recorded for the symptomatic limb. Relationships among structure, symptom severity, lower extremity function, and quadriceps muscle performance were examined using sequential regression models. Adjusting for age, sex, body mass index, and pain levels, there were significant positive relationships for thickness (p < 0.001, ß = 0.718) and viscosity (p = 0.006, ß = 0.496) with CMJ height. There were significant negative relationships between CSA with both CMJ height (p = 0.001, ß = -0.538) and CAR (p = 0.04, ß = -0.517). This is the first study to demonstrate relationships between tendon structure and lower extremity function or quadriceps muscle performance in patients with patellar tendinopathy. Clinical significance: Since structural changes persist after symptom resolution, addressing these changes may assist in restoring lower extremity function and quadriceps muscle performance.