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1.
Artículo en Inglés | MEDLINE | ID: mdl-39154849

RESUMEN

BACKGROUND: Reduced bone density is recognized as a predictor for potential complications in reverse shoulder arthroplasty (RSA). While humeral and glenoid planning based on preoperative computed tomography (CT) scans assist in implant selection and position, reproducible methods for quantifying the patients' bone density are currently not available. The purpose of this study was to perform bone density analyses including patient specific calibration in an RSA cohort based on preoperative CT imaging. It was hypothesized that preoperative CT bone density measures would provide objective quantification of the patients' humeral bone quality. METHODS: This study consisted of three parts, (1) analysis of a patient-specific calibration method in cadaveric CT scans, (2) retrospective application in a clinical RSA cohort, and (3) clustering and classification with machine learning models. Forty cadaveric shoulders were scanned in a clinical CT and compared regarding calibration with density phantoms, air muscle, and fat (patient-specific) or standard Hounsfield unit. Post-scan patient-specific calibration was used to improve the extraction of three-dimensional regions of interest for retrospective bone density analysis in a clinical RSA cohort (n=345). Machine learning models were used to improve the clustering (Hierarchical Ward) and classification (Support Vector Machine (SVM)) of low bone densities in the respective patients. RESULTS: The patient-specific calibration method demonstrated improved accuracy with excellent intraclass correlation coefficients (ICC) for cylindrical cancellous bone densities (ICC>0.75). Clustering partitioned the training data set into a high-density subgroup consisting of 96 patients and a low-density subgroup consisting of 146 patients, showing significant differences between these groups. The SVM showed optimized prediction accuracy of low and high bone densities compared to conventional statistics in the training (accuracy=91.2%; AUC=0.967) and testing (accuracy=90.5 %; AUC=0.958) data set. CONCLUSION: Preoperative CT scans can be used to quantify the proximal humeral bone quality in patients undergoing RSA. The use of machine learning models and patient-specific calibration on bone mineral density demonstrated that multiple 3D bone density scores improved the accuracy of objective preoperative bone quality assessment. The trained model could provide preoperative information to surgeons treating patients with potentially poor bone quality.

2.
JSES Int ; 8(4): 851-858, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39035663

RESUMEN

Background: Several studies have reported proximal bone resorption in stemless and press-fit short-stem humeral implants for anatomic total shoulder arthroplasty. The purpose of this biomechanical study was to evaluate implant and cortical bone micromotion of a cortical rim-supported stemless implant compared to a press-fit short stem implant during cyclic loading and static compression testing. Methods: Thirty cadaveric humeri were assigned to 3 groups based on a previously performed density analysis, adopting the metaphyseal and epiphyseal and inferior supporting bone densities for multivariate analyses. Implant fixation was performed in stemless implant in low bone density (SL-L, n = 10) or short stem implant in low bone density (Stem-L, n = 10) and in stemless implant in high bone density (SL-H, n = 10). Cyclic loading with 220 N, 520 N, and 820 N over 1000 cycles at 1.5 Hz was performed with a constant valley load of 25 N. Optical recording allowed for spatial implant tracking and quantification of cortical bone deformations in the medial calcar bone region. Implant micromotion was measured as rotational and translational displacement. Load-to-failure testing was performed at a rate of 1.5 mm/s with ultimate load and stiffness measured. Results: The SL-H group demonstrated significantly reduced implant micromotion compared to both low-density groups (SL-L: P = .014; Stem-L: P = .031). The Stem-L group showed significantly reduced rotational motion and variance in the test results at the 820-N load level compared to the SL-L group (equal variance: P = .012). Implant micromotion and reversible bone deformation were significantly affected by increasing load (P < .001), metaphyseal cancellous (P = .023, P = .013), and inferior supporting bone density (P = .016, P = .023). Absolute cortical bone deformation was significantly increased with stemless implants in lower densities and percentage reversible bone deformation was significantly higher for the SL-H group (21 ± 7%) compared to the Stem-L group (12 ± 6%, P = .017). Conclusion: A cortical rim-supported stemless implant maintained proximally improved dynamic bone loading in variable bone densities compared to a press-fit short stem implant. Biomechanical time-zero implant micromotion in lower bone densities was comparable between short stem and stemless implants at rehabilitation load levels (220 N, 520 N), but with higher cyclic stability and reduced variability for stemmed implantation at daily peak loads (820 N).

3.
J Shoulder Elbow Surg ; 33(7): 1503-1511, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38182017

RESUMEN

BACKGROUND: Reproducible methods for determining adequate bone densities for stemless anatomic total shoulder arthroplasty (aTSA) are currently lacking. The purpose of this study was to evaluate the utility of preoperative computed tomography (CT) imaging for assessing the bone density of the proximal humerus for supportive differentiation in the decision making for stemless humeral component implantation. It was hypothesized that preoperative 3-dimensional (3-D) CT bone density measures provide objective classifications of the bone quality for stemless aTSA. METHODS: A 3-part study was performed that included the analysis of cadaveric humerus CT scans followed by retrospective application to a clinical cohort and classification with a machine learning model. Thirty cadaveric humeri were evaluated with clinical CT and micro-CT (µCT) imaging. Phantom-calibrated CT data were used to extract 3-D regions of interest and defined radiographic scores. The final image processing script was applied retrospectively to a clinical cohort (n = 150) that had a preoperative CT and intraoperative bone density assessment using the "thumb test," followed by placement of an anatomic stemmed or stemless humeral component. Postscan patient-specific calibration was used to improve the functionality and accuracy of the density analysis. A machine learning model (Support vector machine [SVM]) was utilized to improve the classification of bone densities for a stemless humeral component. RESULTS: The image processing of clinical CT images demonstrated good to excellent accuracy for cylindrical cancellous bone densities (metaphysis [ICC = 0.986] and epiphysis [ICC = 0.883]). Patient-specific internal calibration significantly reduced biases and unwanted variance compared with standard HU CT scans (P < .0001). The SVM showed optimized prediction accuracy compared with conventional statistics with an accuracy of 73.9% and an AUC of 0.83 based on the intraoperative decision of the surgeon. The SVM model based on density clusters increased the accuracy of the bone quality classification to 87.3% with an AUC of 0.93. CONCLUSIONS: Preoperative CT imaging allows accurate evaluation of the bone densities in the proximal humerus. Three-dimensional regions of interest, rescaling using patient-specific calibration, and a machine learning model resulted in good to excellent prediction for objective bone quality classification. This approach may provide an objective tool extending preoperative selection criteria for stemless humeral component implantation.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Densidad Ósea , Húmero , Imagenología Tridimensional , Tomografía Computarizada por Rayos X , Humanos , Artroplastía de Reemplazo de Hombro/métodos , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Masculino , Femenino , Húmero/diagnóstico por imagen , Húmero/cirugía , Anciano , Persona de Mediana Edad , Cadáver , Cuidados Preoperatorios/métodos , Aprendizaje Automático , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugía , Anciano de 80 o más Años
4.
bioRxiv ; 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38106144

RESUMEN

Predicting the effects of mutations in proteins is critical to many applications, from understanding genetic disease to designing novel proteins that can address our most pressing challenges in climate, agriculture and healthcare. Despite a surge in machine learning-based protein models to tackle these questions, an assessment of their respective benefits is challenging due to the use of distinct, often contrived, experimental datasets, and the variable performance of models across different protein families. Addressing these challenges requires scale. To that end we introduce ProteinGym, a large-scale and holistic set of benchmarks specifically designed for protein fitness prediction and design. It encompasses both a broad collection of over 250 standardized deep mutational scanning assays, spanning millions of mutated sequences, as well as curated clinical datasets providing high-quality expert annotations about mutation effects. We devise a robust evaluation framework that combines metrics for both fitness prediction and design, factors in known limitations of the underlying experimental methods, and covers both zero-shot and supervised settings. We report the performance of a diverse set of over 70 high-performing models from various subfields (eg., alignment-based, inverse folding) into a unified benchmark suite. We open source the corresponding codebase, datasets, MSAs, structures, model predictions and develop a user-friendly website that facilitates data access and analysis.

5.
Pneumologie ; 77(11): 907-915, 2023 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-37963480

RESUMEN

Care of patients with pulmonary arterial hypertension (PAH) needs a multi-facetet concept and measures, including management of adverse reactions, right heart insufficiency as well as information on pregnancy, travels by air, psychosocial support, physical exercise training and prophylaxis by vaccination.Positive study results led to an higher recommendation of specialized exercise training in pulmonary hypertension. Also, the recommendation on iron substitution was amended according to the current evidence.In the current guidelines, special focus was given to the elaboration of recommendations regarding pregnancy, including patient information, contraception and patient management in case of pregnancy.This article aims to provide an overview on the recommendations of general measuremes, special circumstances and patient management according to the ESC/ERS guidelines. Amendments to the guideline recommendations are given as comments from the authors of this article.


Asunto(s)
Insuficiencia Cardíaca , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Embarazo , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Ejercicio Físico
6.
Orthop J Sports Med ; 11(9): 23259671231201462, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37786477

RESUMEN

Background: A knotless, tensionable primary anterior cruciate ligament (ACL) repair system preloaded with an internal brace has been released. Currently, there is no biomechanical data on the stabilization and gap formation behavior of the adjustable system when compared with fixed repairs in human ACL tissue. Hypothesis: That knotless adjustable suture repair with an internal brace would provide overall higher construct stability and greater load share on the ACL with less gap formation compared with fixed repair. Study Design: Controlled laboratory study. Methods: Human cadaveric knees were utilized for internal braced ACL repair constructs (each group n = 16). Two fixed groups consisting of a single-cinch loop (SCL), cortical button (SCL group), and knotless suture-anchor (anchor group) were compared with an SCL-adjustable loop device (SCL-ALD) group. Testing was performed at 4 different peak loads (50, 150, 250, 350 N) over 4000 cycles at 0.75 Hz including suture repair preconditioning (10 cycles at 0.5 Hz) for SCL-ALD. Specimens were ultimately pulled to failure with a cut internal brace. The final loading situation of the construct and ACL repair with gap formation and ultimate strength were evaluated. Results: Peak elongation at various peak loads showed a significantly higher (P < .001) stabilization of SCL-ALD when compared with both fixed groups. There was a significantly higher (P < .001) load share of SCL-ALD, especially at lower loads (48% of 50 N), and the gap formation remained restricted up to 250 N. With only a little load share on the fixed constructs (<6%) at lower loads (50, 150 N), gap formation in these groups started at a load of 150 N, leading to significantly higher gaps (P < .001). The ultimate failure load for SCL-ALD and anchor groups was significantly increased (P < .001) as compared with SCL. The stiffness of SCL-ALD (62.9 ± 10.6 N/mm) was significantly increased (P < .001). Conclusion: Internal braced knotless adjustable fixation for ACL repair with preconditioning of the suture repaired ligament increased the overall stabilization with higher load share on the ACL and restricted gap formation (<0.5 mm up to 350 N) compared with fixed suture repair. All internal braced repairs restored stability according to native ACL function. Clinical Relevance: Adjustable ACL repair improved the mechanical characteristics and reduced gap formation, but the overall clinical significance on healing remains unclear.

7.
Nature ; 622(7984): 818-825, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37821700

RESUMEN

Effective pandemic preparedness relies on anticipating viral mutations that are able to evade host immune responses to facilitate vaccine and therapeutic design. However, current strategies for viral evolution prediction are not available early in a pandemic-experimental approaches require host polyclonal antibodies to test against1-16, and existing computational methods draw heavily from current strain prevalence to make reliable predictions of variants of concern17-19. To address this, we developed EVEscape, a generalizable modular framework that combines fitness predictions from a deep learning model of historical sequences with biophysical and structural information. EVEscape quantifies the viral escape potential of mutations at scale and has the advantage of being applicable before surveillance sequencing, experimental scans or three-dimensional structures of antibody complexes are available. We demonstrate that EVEscape, trained on sequences available before 2020, is as accurate as high-throughput experimental scans at anticipating pandemic variation for SARS-CoV-2 and is generalizable to other viruses including influenza, HIV and understudied viruses with pandemic potential such as Lassa and Nipah. We provide continually revised escape scores for all current strains of SARS-CoV-2 and predict probable further mutations to forecast emerging strains as a tool for continuing vaccine development ( evescape.org ).


Asunto(s)
Evolución Molecular , Predicción , Evasión Inmune , Mutación , Pandemias , Virus , Humanos , Diseño de Fármacos , Infecciones por VIH , Evasión Inmune/genética , Evasión Inmune/inmunología , Gripe Humana , Virus Lassa , Virus Nipah , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Vacunas Virales/inmunología , Virus/genética , Virus/inmunología
8.
Am J Sports Med ; 51(11): 2858-2868, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37656204

RESUMEN

BACKGROUND: Reconstruction techniques for anterior glenoid bone loss have seen a trend from screws to suture-based fixations. However, comparative biomechanical data, including primary fixation and glenoid-graft contact pressure mapping, are limited. HYPOTHESIS: Suture-based bone block cerclage (BBC) and suspensory suture button (SB) techniques provide similar primary fixation and cyclic stability to double-screw fixation but with higher contact loading at the bony interface. STUDY DESIGN: Controlled laboratory study. METHODS: In total, 60 cadaveric scapulae were prepared to simulate anterior glenoid bone loss with coracoid autograft reconstruction. Graft fixation was performed with 3 different techniques: (1) an interconnected all-suture BBC, (2) 2 SB suspensions, and (3) 2 screws. Initial compression was analyzed during primary fixation. Cyclic peak loading with 50 N and 100 N over 250 cycles at 1 Hz was performed with a constant valley load of 25 N. Optical recording and pressure foils allowed for spatial bone block tracking and contact pressure mapping at the glenoid-graft interface. Load-to-failure testing was performed at a rate of 1.5 mm/s with ultimate load and stiffness measured. RESULTS: Initial graft compression was higher with screw fixation (141 ± 5 N) compared with suture-based fixations (P < .001), with BBC fixation providing significantly higher compression than SB fixation (116 ± 7 N vs. 91 ± 5 N; P < .001). Spatial bone block migration and ultimate failure load were similar between the BBC and screw groups. The SB group showed significantly increased bone block translation (3.1 ± 1.0 mm; P≤ .014) and rotation (2.5°± 1.4°; P≤ .025) and significantly lower ultimate failure load (180 ± 53 N) compared with the BBC (P = .046) and screw (P = .002) groups. Both suture-based fixations provided significantly increased graft-glenoid contact loading with higher pressure amplitudes (P≤ .032) and contact pressure after cyclic loading (+13%; SB: P = .007; BBC: P = .004) compared with screw fixation. CONCLUSION: Both SB and interconnected cerclage fixation improved dynamic contact loading compared with screw fixation in a biomechanical glenoid bone loss model. Cerclage fixation was biomechanically comparable with screw fixation but with a greater variability. SB fixation showed significantly lower primary fixation strength and greater bone block rotation and migration. CLINICAL RELEVANCE: Suture-based bone block fixations improved graft-glenoid contact loading, but the overall clinical consequence on healing remains unclear.


Asunto(s)
Procedimientos Ortopédicos , Escápula , Humanos , Escápula/cirugía , Suturas , Tornillos Óseos , Técnicas Histológicas
9.
Am J Sports Med ; 50(10): 2705-2713, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35787211

RESUMEN

BACKGROUND: Primary device fixation and the resistance against gap formation during repetitive loading influence the quality of meniscal repair. There are limited biomechanical data comparing primary tensioning and cyclic behavior of all-inside versus inside-out repair. HYPOTHESIS: All-inside devices provide higher initial load on the meniscal repair than inside-out fixation, and stiffer constructs show higher resistance against gap formation during cyclic loading. STUDY DESIGN: Controlled laboratory study. METHODS: In total, 60 longitudinal bucket-handle tears in human cadaveric menisci were created and repaired with a single stitch and randomly assigned to 4 all-inside groups (TrueSpan, FastFix 360, Stryker AIR, FiberStich) and 2 inside-out groups (suture repair [IO-S], suture tape [IO-ST]). Residual load after repair tensioning (50 N) and relief displacement were measured. Constructs underwent cyclic loading between 2 and 20 N over 500 cycles (0.75 Hz) with cyclic stiffness, gap formation, and final peak elongation measured. Ultimate load and stiffness were analyzed during pull to failure (3.15 mm/s). RESULTS: All-inside repair demonstrated significantly higher primary fixation strength than inside-out repair. The significantly highest load (mean ± SD; 20.1 ± 0.9 N; P < .037) and relief displacement (-2.40 ± 0.32 mm; P < .03) were for the knotless soft anchoring FiberStich group. The lowest initial load (9.0 ± 1.5 N; P < .001) and relief displacement (-1.39 ± 0.26 mm; P < .045) were for the IO-S repair group. The final gap formation (500th cycle) of FiberStich (0.75 ± 0.37 mm; P < .02) was significantly smaller than others and that of the IO-S (1.47 ± 0.33 mm; P < .045) significantly larger. The construct stiffness of the FiberStich and IO-ST groups was significantly greater at the end of cyclic testing (16.7 ± 0.80 and 15.5 ± 1.42 N/mm; P < .042, respectively) and ultimate failure testing (23.4 ± 3.6 and 20.6 ± 2.3 N/mm; P < .005). The FastFix 360 (86.4 ± 4.8 N) and Stryker AIR (84.4 ± 4.6 N) groups failed at a significantly lower load than the IO-S group (P < .02) with loss of anchor support. The FiberStich (146.8 ± 23.4 N), TrueSpan (142.0 ± 17.8 N), and IO-ST (139.4 ± 7.3 N) groups failed at significantly higher loads (P < .02) due to suture tearing. CONCLUSION: Overall, primary fixation strength of inside-out meniscal repair was significantly lower than all-inside repair in this cadaveric tissue model. Although absolute differences among groups were small, meniscal repairs with higher construct stiffness (IO-ST, FiberStich) demonstrated increased resistance against gap formation and failure load. CLINICAL RELEVANCE: Knotless single-stitch all-inside meniscal repair with a soft anchor resulted in less gapping, but the overall clinical significance on healing rates remains unclear.


Asunto(s)
Enfermedades de los Cartílagos , Traumatismos de la Rodilla , Lesiones de Menisco Tibial , Fenómenos Biomecánicos , Cadáver , Enfermedades de los Cartílagos/cirugía , Humanos , Traumatismos de la Rodilla/cirugía , Meniscos Tibiales/cirugía , Técnicas de Sutura , Lesiones de Menisco Tibial/cirugía
10.
Am J Nephrol ; 53(7): 552-564, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35675794

RESUMEN

INTRODUCTION: Chronic activation of the mineralocorticoid receptor (MR) leads to pathological processes like inflammation and fibrosis during cardiorenal disease. Modulation of immunological processes in the heart or kidney may serve as a mechanistic and therapeutic interface in cardiorenal pathologies. In this study, we investigated anti-inflammatory/-fibrotic and immunological effects of the selective nonsteroidal MR antagonists finerenone (FIN) in the deoxycorticosterone acetate (DOCA)-salt model. METHODS: Male C57BL6/J mice were uninephrectomized and received a DOCA pellet implantation (2.4 mg/day) plus 0.9% NaCl in drinking water (DOCA-salt) or received a sham operation and were orally treated with FIN (10 mg/kg/day) or vehicle in a preventive study design. Five weeks after the procedure, blood pressure (BP), urinary albumin/creatinine ratio (UACR), glomerular and tubulointerstitial damage, echocardiographic cardiac function, as well as cardiac/renal inflammatory cell content by FACS analysis were assessed. RESULTS: BP was significantly reduced by FIN. FACS analysis revealed a notable immune response due to DOCA-salt exposure. Especially, infiltrating renal RORγt γδ-positive T cells were upregulated, which was significantly ameliorated by FIN treatment. This was accompanied by a significant reduction of UACR in FIN-treated mice. In the heart, FIN reduced DOCA-salt-induced cardiac hypertrophy, cardiac fibrosis and led to an improvement of the global longitudinal strain. Cardiac actions of FIN were not associated with a regulation of cardiac RORγt γδ-positive T cells. DISCUSSION/CONCLUSION: The present study shows cardiac and renal protective effects of FIN in a DOCA-salt model. The cardiorenal protection was accompanied by a reduction of renal RORγt γδ T cells. The observed actions of FIN may provide a potential mechanism of its efficacy recently observed in clinical trials.


Asunto(s)
Hipertensión Renal , Hipertensión , Naftiridinas , Linfocitos T , Animales , Presión Sanguínea , Acetato de Desoxicorticosterona , Fibrosis , Hipertensión/tratamiento farmacológico , Hipertensión Renal/patología , Riñón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Naftiridinas/farmacología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/uso terapéutico
11.
Cardiovasc Res ; 118(11): 2488-2505, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-34061169

RESUMEN

AIMS: Heart failure (HF) is characterized by an overactivation of ß-adrenergic signalling that directly contributes to impairment of myocardial function. Moreover, ß-adrenergic overactivation induces adipose tissue lipolysis, which may further worsen the development of HF. Recently, we demonstrated that adipose tissue-specific deletion of adipose triglyceride lipase (ATGL) prevents pressure-mediated HF in mice. In this study, we investigated the cardioprotective effects of a new pharmacological inhibitor of ATGL, Atglistatin, predominantly targeting ATGL in adipose tissue, on catecholamine-induced cardiac damage. METHODS AND RESULTS: Male 129/Sv mice received repeated injections of isoproterenol (ISO, 25 mg/kg BW) to induce cardiac damage. Five days prior to ISO application, oral Atglistatin (2 mmol/kg diet) or control treatment was started. Two and twelve days after the last ISO injection cardiac function was analysed by echocardiography. The myocardial deformation was evaluated using speckle-tracking-technique. Twelve days after the last ISO injection, echocardiographic analysis revealed a markedly impaired global longitudinal strain, which was significantly improved by the application of Atglistatin. No changes in ejection fraction were observed. Further studies included histological-, WB-, and RT-qPCR-based analysis of cardiac tissue, followed by cell culture experiments and mass spectrometry-based lipidome analysis. ISO application induced subendocardial fibrosis and a profound pro-apoptotic cardiac response, as demonstrated using an apoptosis-specific gene expression-array. Atglistatin treatment led to a dramatic reduction of these pro-fibrotic and pro-apoptotic processes. We then identified a specific set of fatty acids (FAs) liberated from adipocytes under ISO stimulation (palmitic acid, palmitoleic acid, and oleic acid), which induced pro-apoptotic effects in cardiomyocytes. Atglistatin significantly blocked this adipocytic FA secretion. CONCLUSION: This study demonstrates cardioprotective effects of Atglistatin in a mouse model of catecholamine-induced cardiac damage/dysfunction, involving anti-apoptotic and anti-fibrotic actions. Notably, beneficial cardioprotective effects of Atglistatin are likely mediated by non-cardiac actions, supporting the concept that pharmacological targeting of adipose tissue may provide an effective way to treat cardiac dysfunction.


Asunto(s)
Catecolaminas , Insuficiencia Cardíaca , Tejido Adiposo/metabolismo , Adrenérgicos/metabolismo , Adrenérgicos/farmacología , Animales , Catecolaminas/metabolismo , Lipasa/genética , Lipasa/metabolismo , Lipólisis , Masculino , Ratones , Compuestos de Fenilurea
12.
J Am Heart Assoc ; 10(14): e019473, 2021 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-34227403

RESUMEN

Background It is known that dietary intake of polyunsaturated fatty acids may improve cardiac function. However, relatively high daily doses are required to achieve sufficient cardiac concentrations of beneficial omega-3 fatty acids. The liver X receptor (LXR) is a nuclear hormone receptor and a crucial regulator of lipid homeostasis in mammals. LXR activation has been shown to endogenously reprogram cellular lipid profiles toward increased polyunsaturated fatty acids levels. Here we studied whether LXR lipid reprogramming occurs in cardiac tissue and exerts cardioprotective actions. Methods and Results Male 129SV mice were treated with the LXR agonist AZ876 (20 µmol/kg per day) for 11 days. From day 6, the mice were injected with the nonselective ß-agonist isoproterenol for 4 consecutive days to induce diastolic dysfunction and subendocardial fibrosis while maintaining systolic function. Treatment with isoproterenol led to a marked impairment of global longitudinal strain and the E/e' ratio of transmitral flow to mitral annular velocity, which were both significantly improved by the LXR agonist. Histological examination showed a significant reduction in isoproterenol-induced subendocardial fibrosis by AZ876. Analysis of the cardiac lipid composition by liquid chromatography-high resolution mass spectrometry revealed a significant increase in cardiac polyunsaturated fatty acids levels and a significant reduction in saturated fatty acids by AZ876. Conclusions The present study provides evidence that the LXR agonist AZ876 prevents subendocardial damage, improves global longitudinal strain and E/e' in a mouse model of isoproterenol-induced cardiac damage, accompanied by an upregulation of cardiac polyunsaturated fatty acids levels. Cardiac LXR activation and beneficial endogenous cardiac lipid reprogramming may provide a new therapeutic strategy in cardiac disease with diastolic dysfunction.


Asunto(s)
Compuestos de Anilina/farmacología , Ácidos Grasos/metabolismo , Cardiopatías/prevención & control , Isoproterenol , Miocardio/metabolismo , Tiazoles/farmacología , Animales , Reprogramación Celular , Modelos Animales de Enfermedad , Fibrosis , Cardiopatías/inducido químicamente , Cardiopatías/patología , Receptores X del Hígado/agonistas , Masculino , Ratones , Ratones de la Cepa 129 , Miocardio/patología
13.
Orthop J Sports Med ; 8(1): 2325967119897421, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32064293

RESUMEN

BACKGROUND: Recently, there has been a resurgence of interest in primary repair of the anterior cruciate ligament (ACL), with fixation techniques evolving. However, to date, there have been no biomechanical studies comparing fixed to adjustable fixation repair techniques. HYPOTHESIS: Adjustable ACL repair provides for improved stabilization compared with fixed techniques with respect to both gap formation and residual load-bearing capability. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 4 different ACL repair techniques (n = 5 per group), including single- and double-cinch loop (CL) cortical button fixation as well as knotless single-suture anchor fixation, were tested using a porcine model. For adjustable single-CL loop fixation, additional preconditioning (10 cycles at 0.5 Hz) was performed. The force after fixation and the actuator displacement to achieve a time-zero preload of 10 N were measured for fixed techniques. Incrementally increasing cycling (1 mm/500 cycles) from 1 to 8 mm was performed for 4000 cycles at 0.75 Hz before pull to failure (50 mm/min). The final residual peak load and gap formation for each test block were analyzed as well as ultimate strength. RESULTS: Knot tying of a single-CL over a button (mean ± SD, 0.66 ± 0.23 mm) and knotless anchor fixation (0.20 ± 0.12 mm) resulted in significant time-zero gaps (P < .001) and significantly higher overall gap formation at reduced residual loading (analysis of covariance, P < .001) compared with both the double-CL loop and adjustable fixation techniques. The adjustable group showed the highest failure load and stiffness, at 305.7 N and 117.1 N/mm, respectively. The failure load of the knotted single-CL group was significantly reduced compared with all other groups (P < .001). CONCLUSION: Adjustable single-CL cortical button fixation with intraoperative preconditioning optimized time-zero ACL tension and led to significantly improved stabilization and reduced gap formation, with the highest ultimate strength. Single-CL loop knot tying over the button and knotless anchor fixation resulted in time-zero gaps to achieve slight tension on the ACL and significantly higher gap formation at reduced load-bearing capability. CLINICAL RELEVANCE: Although the clinical relevance of gap formation is uncertain, a biomechanical understanding of the stabilization potential of current ACL repair techniques is pertinent to the continued evolution of surgical approaches to enable better clinical outcomes.

14.
Orthop J Sports Med ; 8(1): 2325967119897423, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32064294

RESUMEN

BACKGROUND: The latest biomechanical studies on some form of internal bracing have shown improved stabilization for anterior cruciate ligament (ACL) repair, but gap formation and load-sharing function have not yet been reported. HYPOTHESIS: Internal bracing of an adjustable ACL repair construct provides improved stabilization with reduced gap formation and higher residual loading on the ACL. STUDY DESIGN: Controlled laboratory study. METHODS: Internally braced ACL repair constructs with single- and double-cinch loop (CL) cortical buttons, a knotless suture anchor, and a single-CL cortical button with adjustable loop fixation (CLS-ALD) were tested (n = 20 each) in a porcine model at 4 different loads (n = 5 each) over 4000 cycles at 0.75 Hz (n = 80 total). The CLS-ALD technique allowed for additional preconditioning (10 cycles at 0.5 Hz). Test results of the isolated internal brace groups served as a baseline for comparison. Lastly, specimens were pulled to failure (50 mm/min) with a cut internal brace. Final loading and gap formation on the ACL repair construct as well as ultimate strength were analyzed. RESULTS: A statistical significance for peak loads over peak elongation was found between the CLS-ALD and all other reinforced groups (analysis of covariance, P < .001). Accordingly, the adjustable repair technique showed improved load-bearing capability with the internal brace compared with all other fixed repair groups and revealed significantly higher loads than the knotted single-CL group. Also, significantly reduced gap formation was found for the CLS-ALD compared with all other groups (P < .001), with no gap formation up to 150 N with a final gap of 0.85 ± 0.31 mm at 350 N. A significantly higher ultimate failure load (866.2 ± 104.0 N; P < .001) was found for the button-fixed internal brace group compared with all other groups. CONCLUSION: Internal bracing had a crucial role in improving the stabilization potential of ACL repair at loads occurring during normal daily activity. The added strength of the internal brace allowed for reducing peak loads on the ACL repair construct as well as restricting gap formation to below 3 mm at loads up to 350 N. CLINICAL RELEVANCE: Improvements in the mechanical characteristics of current ACL repair techniques that enable reduced gap formation and allow for early range of motion and accelerated rehabilitation may strengthen the self-healing response with the formation of stable scar tissue.

16.
Clin Pract Cases Emerg Med ; 3(2): 137-139, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31061970

RESUMEN

Implantable collamer lenses (ICL) are phakic (natural lens remains in place) lenses that were first developed in the 1990s for correction of high myopia. The effectiveness and safety of ICLs are making them an increasingly popular option for vision correction in the myopic patient, competing with traditional options like glasses, contacts, and procedures such as laser-assisted in situ keratomileusis. Although generally safe, due to the position of the phakic ICL in the eye, pupillary block remains a rare but vision-threatening complication of ICL implantation. Pupillary block caused by phakic ICL is a serious complication that requires urgent recognition and intervention and is poorly described in emergency medicine literature. We describe a case of pupillary block five years after ICL implantation that was refractory to standard medical therapy, highlighting the importance of early diagnosis and referral for more definitive therapy.

17.
Hig. Aliment. (Online) ; 33(288/289): 2173-2176, abr.-maio 2019. tab
Artículo en Portugués | LILACS, VETINDEX | ID: biblio-1482293

RESUMEN

Coco ralado é o produto obtido do fruto do coqueiro (Cocos nucifera L.), podendo ser classificado quanto á umidade, adição de açúcar e caramelização. Por ser facilmente encontrado em comércios e amplamente utilizado, o objetivo desse trabalho foi avaliar a qualidade microbiológica de coco ralado úmido e adoçado comercializados nos estados do Rio de Janeiro e Mato Grosso. Das três amostras analisadas, apenas uma apresentou coliformes a 45° enquanto que duas apresentaram Staphylococcus coagulase positiva acima do limite estabelecido em legislação, além disso, duas das três amostras apresentaram suspeita de presença de Salmonella sp. De acordo com os resultados obtidos, duas amostras estavam impróprias para o consumo, pois estavam fora dos padrões exigidos pela legislação brasileira.


Asunto(s)
Alimentos de Coco , Contaminación de Alimentos/análisis , Contaminación de Alimentos/legislación & jurisprudencia , Microbiología de Alimentos , Cocos
18.
Hig. Aliment. (Online) ; 33(288/289): 2725-2728, abr.-maio 2019. tab
Artículo en Portugués | LILACS, VETINDEX | ID: biblio-1482325

RESUMEN

A couve manteiga (Brassica oleracea variedade acephala) é uma hortaliça pertencente à família Brassicaceae, rica em nutrientes, susceptível a contaminação e altamente consumida in natura pela população brasileira. O presente trabalho teve como objetivo avaliar a contaminação microbiológica de couve manteiga comercializada na cidade de Cuiabá-MT e analisar a redução da carga microbiana após sanitização desta. Foi realizado a pesquisa de Salmonella sp. e a contagem de bactérias heterotróficas aeróbias mesófilas (BHAM). Todas as amostras apresentaram ausência de Salmonella sp., estando aptas ao consumo e verificou-se que após a sanitização a quantidade de BHAM diminuiu, demonstrando a importância da sanitização para alimentos consumidos in natura.


Asunto(s)
Brassica/microbiología , Carga Bacteriana/efectos de los fármacos , Hipoclorito de Sodio/administración & dosificación , Microbiología de Alimentos/métodos , Salmonella/aislamiento & purificación
19.
Hig. Aliment. (Online) ; 33(288/289): 2823-2827, abr.-maio 2019. tab
Artículo en Portugués | LILACS, VETINDEX | ID: biblio-1482345

RESUMEN

A castanha-do-Brasil é um produto extrativista de grande relevância econômica. Condições ambientais, manipulação impertinente e características do fruto oferecem subsídios para o crescimento de microrganismos contaminantes. O objetivo desse trabalho foi avaliar a qualidade higiênico-sanitária de Castanha-do-Brasil comercializada na Amazônia Ocidental através da pesquisa de Salmonella sp. e quantificação de bactérias heterotróficas aeróbias mesófilas. Foram coletadas duas amostras de Castanha-do-Brasil de três diferentes locais de comercialização: Boca do Acre (AM), Cujubim e Ji-Paraná (RO), totalizando seis amostras. A partir das análises realizadas foi identificado a presença de Salmonella sp. em duas amostras demonstrando que o consumo deste produto poderia trazer risco a saúde do consumidor.


Asunto(s)
Bacterias Heterotróficas/análisis , Bertholletia/microbiología , Microbiología de Alimentos , Salmonella/aislamiento & purificación
20.
Hig. Aliment. (Online) ; 33(288/289): 2042-2045, abr.-maio 2019. tab
Artículo en Portugués | LILACS, VETINDEX | ID: biblio-1482458

RESUMEN

A busca por melhor qualidade de vida e hábitos alimentares saudáveis vem causando aumento no consumo do pescado devido ao seu alto valor nutritivo. Porém o pescado devido a suas características é susceptível a deterioração o que prejudica sua qualidade. O objetivo deste estudo foi verificar a qualidade microbiológica de filés de peixe pintado (Pseudoplatystoma fasciaum X Leiaurius marmoratus) comercializados em diferentes estabelecimentos na cidade de Cuiabá – MT. Das amostras analisadas, duas apresentaram contaminação por Salmonella sp. e presença de Staphylococcus coagulase positiva. Os resultados indicam que duas amostras estavam impróprias para consumo podendo acarretar riscos à saúde do consumidor.


Asunto(s)
Animales , Carne/microbiología , Contaminación de Alimentos/análisis , Microbiología de Alimentos , Bagres , Calidad de los Alimentos
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