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INTRODUCTION: Three-dimensional surgical planning software provides virtual reconstructions of the shoulder with automated joint indices for a preoperative case assessment. The aim of this single center study was to evaluate the concordance between the preoperatively selected humeral components and the final implants used in shoulder arthroplasty. METHODS: 129 cases who had undergone anatomic (n = 16) or reverse shoulder arthroplasty (n = 117) using the same type of uncemented short stem implant and were included for review in this study. The type of arthroplasty, stem size, stem inclination, tray-offset and liner-thickness were noted preoperatively and compared to the final implant specifications used in surgery. RESULTS: The type of arthroplasty matched the surgical plan in 99.2% of cases, as one case was converted from RSA to TSA. The concordance of planned to implanted stem size was 44.2% and the planned size was in range of one adjacent size in 87.6% of cases. Stem inclination in TSA matched the surgical plan in 50% of cases. Tray offset in RSA was predicted correctly in 65% and liner-thickness matched the surgical plan in 98.3% of cases. CONCLUSION: Despite a low degree of concordance of planned to implanted stem sizes of 44.2%, the choice of stem size was found to be in range of one adjacent size in 87.6% of cases. Further investigations of other contributing factors are necessary to increase the accuracy of the preoperative selection of humeral implants. LEVEL OF EVIDENCE: level IV, retrospective case study.
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Artroplastía de Reemplazo de Hombro , Articulación del Hombro , Humanos , Artroplastía de Reemplazo de Hombro/métodos , Articulación del Hombro/cirugía , Estudios Retrospectivos , Programas Informáticos , Diseño de PrótesisRESUMEN
INTRODUCTION: Radiographic stress shielding is a common finding in uncemented convertible short-stem shoulder arthroplasty (UCSSSA). The distal filling ratio (DFR) has been described as a predictor for the occurrence of stress shielding. A DFR > 70% was mentioned as a risk factor for the occurrence of stress shielding for some UCSSSA. However, measurements were only performed on conventional radiographs and no validation exists for 3D automated planning tools. METHODS: DFR was manually measured on postoperative true ap radiographs of 76 shoulder arthroplasties using a standardized protocol and were compared to preoperative CT scans with an automated calculation of the DFR after virtual implantation of the stem. RESULTS: The mean DFR measured on X-rays was 75.9% (SD = 8.7; 95% CI = 74-78) vs. 78.9% (SD = 9.1; 95% CI = 76.8-83) automatically measured on CT scans. This difference was significant (p < 0.001). In 7 out of 76 cases (9%) the difference between manual measurement on radiographs and computerized measurement on CT scans was > 10%. CONCLUSION: Manual measurement of the DFR is underestimated on conventional radiographs compared to automated calculation on CT scans be a mean of 3%. Therefore, automated measurement of the DFR on CT scans seems to be beneficial, especially in cases with osteopenic cortices. Manual measurement of the DFR on conventional ap radiographs in cases without CT scans, however, is still a viable alternative. LEVEL OF EVIDENCE: Level IV, retrospective study.
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Artroplastía de Reemplazo de Hombro , Articulación del Hombro , Humanos , Artroplastía de Reemplazo de Hombro/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Radiografía , Tomografía Computarizada por Rayos X/métodos , Articulación del Hombro/cirugíaRESUMEN
INTRODUCTION: Shorter humeral reverse total shoulder arthroplasty (RTSA) stems may reduce stress shielding, however, potentially carry the risk of varus/valgus malalignment. This radiographic study's purpose was to measure the incidence of stem malalignment and thus the realized neck-shaft angle (NSA). The hypothesis was that malalignment of the stem is a frequent postoperative radiographic finding. METHODS: Radiographs of an uncemented curved short stem RTSA with a 145° NSA were reviewed. The study group included 124 cases at a mean age of 74 (range 48-91) years. The humeral stem axis was measured and defined as neutral if the value fell within ± 5° of the longitudinal humeral axis. Angular values > 5° were defined as malaligned in valgus or varus. The filling ratio of the implant within the humeral shaft was measured at the level of the metaphysis (FRmet) and diaphysis (FRdia). RESULTS: The average humeral stem axis angle was 4 ± 3° valgus, corresponding to a true mean NSA of 149 ± 3°. Stem axis was neutral in 73% (n = 90) of implants. Of the 34 malaligned implants, 82% (n = 28) were in valgus (NSA = 153 ± 2°) and 18% (n = 6) in varus (NSA = 139 ± 1°). The average FRmet and FRdia were 0.68 ± 0.11 and 0.72 ± 0.11, respectively. A low positive association was found between stem diameter and filling ratios (r = 0.39; p < 0.001); indicating smaller stem sizes were more likely to be misaligned. CONCLUSION: Uncemented short stem implants may decrease stress shielding; however, approximately one quarter were implanted > 5° malaligned. The majority of malaligned components (86%) were implanted in valgus, corresponding to an NSA of > 150°. As such, surgeons must be aware that shorter and smaller stems may lead to axial malalignment influencing the true SA. LEVEL OF EVIDENCE: Level IV, retrospective study.
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Artroplastía de Reemplazo de Hombro , Húmero/cirugía , Prótesis Articulares , Adulto , Anciano , Anciano de 80 o más Años , Artroplastía de Reemplazo de Hombro/efectos adversos , Artroplastía de Reemplazo de Hombro/instrumentación , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
Adenosine triphosphate (ATP)-binding cassette subfamily A member 3 (ABCA3), a phospholipid transporter in lung lamellar bodies (LBs), is essential for the assembly of pulmonary surfactant and LB biogenesis. Mutations in the ABCA3 gene are an important genetic cause for respiratory distress syndrome in neonates and interstitial lung disease in children and adults, for which there is currently no cure. The aim of this study was to prove that disease causing misfolding ABCA3 mutations can be corrected in vitro and to investigate available options for correction. We stably expressed hemagglutinin (HA)-tagged wild-type ABCA3 or variants p.Q215K, p.M760R, p.A1046E, p.K1388N or p.G1421R in A549 cells and assessed correction by quantitation of ABCA3 processing products, their intracellular localization, resembling LB morphological integrity and analysis of functional transport activity. We showed that all mutant proteins except for M760R ABCA3 were rescued by the bithiazole correctors C13 and C17. These variants were also corrected by the chemical chaperone trimethylamine N-oxide and by low temperature. The identification of lead molecules C13 and C17 is an important step toward pharmacotherapy of ABCA3 misfolding-induced lung disease.
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Transportadoras de Casetes de Unión a ATP/genética , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/genética , Metilaminas/farmacología , Mutación Missense/efectos de los fármacos , Deficiencias en la Proteostasis/tratamiento farmacológico , Deficiencias en la Proteostasis/genética , Células A549 , Transportadoras de Casetes de Unión a ATP/metabolismo , Humanos , Enfermedades Pulmonares Intersticiales/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Prueba de Estudio Conceptual , Pliegue de Proteína , Deficiencias en la Proteostasis/metabolismoRESUMEN
INTRODUCTION: Preoperative 3D planning programs for anatomic (TSA) and reverse total shoulder arthroplasty (RSA) allow the analysis of glenohumeral joint pathoanatomy and templating for implant size selection and placement. The aim of this multicenter study was to compare the preoperative glenoid implant type and size planned to the final glenoid implant type and size used intraoperatively. METHODS: Two hundred patients (100 TSA and 100 RSA) with a mean age of 72 years who had undergone preoperative planning and subsequent shoulder arthroplasty (100 TSA and 100 RSA) were included. All preoperative plans were saved and were analyzed for arthroplasty type (TSA vs. RSA), implant type (augment vs. nonaugment), and size (ie, polyethylene size, polyethylene radius of curvature, glenoid baseplate diameter, baseplate post length, and baseplate lateralization). The preoperative plan was available during surgery and was compared to the final implants inserted by the surgeon. RESULTS: There were no intraoperative conversions of TSA to RSA or vice versa. In patients planned for a TSA, complete concordance between the preoperative plan and final implant selection was 85%. A complete mismatch for TSA glenoid size, backside radius of curvature, and augmentation occurred in 2%. For RSA, complete concordance was found in 90% of cases. A complete mismatch for implant type, size, post length, and glenosphere size occurred in 3%. CONCLUSION: A high concordance was found between preoperative 3D planning implant selection and the glenoid component inserted at surgery for TSA and RSA. This high concordance may assist with surgical preparedness, implant stocks, and possibly future implant production.
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Artroplastía de Reemplazo de Hombro/instrumentación , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugía , Prótesis de Hombro , Anciano , Anciano de 80 o más Años , Artroplastía de Reemplazo de Hombro/métodos , Toma de Decisiones Asistida por Computador , Femenino , Cavidad Glenoidea , Humanos , Imagenología Tridimensional , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Planificación de Atención al Paciente , Periodo Preoperatorio , Cirugía Asistida por ComputadorRESUMEN
BACKGROUND: Several short-stemmed press-fit humeral components have been developed in recent years for anatomic total shoulder arthroplasty (TSA) as well as reverse shoulder arthroplasty (RSA). Varying radiographic outcomes have been reported, with some studies reporting concerning rates of aseptic loosening. This study analyzed the radiographic findings of a press-fit convertible short-stemmed humeral component in both TSA and RSA. METHODS: There were 150 anatomic TSAs (group 1) and 77 RSAs (group 2) analyzed radiographically at a minimum follow-up of 2 years postoperatively. Plain radiographs were reviewed for stem loosening, alignment, signs of stress shielding, and the filling ratio. RESULTS: At final follow-up, 49% of group 1 and 65% of group 2 had no evidence for radiographic changes. In those with radiographic changes, low bone adaptions were found in 83% and high adaptions in 17% in both groups. Larger stem sizes with higher filling ratios were associated with high radiographic adaptions in both groups (P = .02). The overall filling ratios were higher in group 2 (P = .002). Cortical contact of the stem led to higher bone adaptions (P = .014). CONCLUSIONS: The short humeral component analyzed in this study showed encouraging survival rates without aseptic loosening. Radiographic changes are associated with a higher filling ratio and cortical contact of the stem. Surgeons should aim to achieve fixation with the minimal required canal filling to minimize radiographic changes with the uncemented humeral component used in this study.
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Artroplastía de Reemplazo de Hombro/instrumentación , Articulación del Hombro/diagnóstico por imagen , Prótesis de Hombro , Adulto , Anciano , Anciano de 80 o más Años , Artroplastía de Reemplazo de Hombro/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Diseño de Prótesis , Falla de Prótesis , Radiografía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: The aim of the study was to evaluate the short-term clinical results of anatomic total shoulder arthroplasty with a short-stem prosthesis in primary osteoarthritis. MATERIALS AND METHODS: 65 shoulders with a mean age of 70 years (range 47-85 years) were available for minimum follow-up of 24 months. Clinical outcome was determined by range of motion, Constant score (CS) age and sex-adjusted Constant score (CS%), and subjective shoulder value (SSV). The influence of six different factors (high bone adaptations, age > 65 years, female gender, dominant side, atrophy of the supraspinatus tendon ≥ grade 2, glenoid type B2/B3) on the clinical outcome was assessed. RESULTS: At mean follow-up of 37 months (range 24-58 months), the CS improved from 36 ± 8 to 75 ± 12 (p < 0.001). The shoulder flexion (100° ± 21° to 159° ± 19°) as well as the external rotation (3° ± 11° to 43° ± 18°) improved significantly (p < 0.001). Three complications were noted (transient neuropraxia of the radial nerve, subjective instability, hematoma with superficial wound infection) leading to one revision surgery (wound debridement). No stem loosening was observed. High bone adaptation was present in 19 out of 65 shoulders (29%). The clinical outcome was not influenced by high bone adaptations (p ≥ 0.095). Age > 65 years (n = 44) and female gender (n = 38) were associated with worse clinical outcome (p ≤ 0.043). CONCLUSIONS: In the short term, the clinical results of this anatomical short-stem shoulder prosthesis are encouraging. A low prevalence of high bone adaptations was found without any influence on the clinical outcome and stem loosening was not observed.
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Artroplastía de Reemplazo de Hombro , Osteoartritis , Complicaciones Posoperatorias , Articulación del Hombro , Prótesis de Hombro , Anciano , Anciano de 80 o más Años , Artroplastía de Reemplazo de Hombro/efectos adversos , Artroplastía de Reemplazo de Hombro/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/diagnóstico , Osteoartritis/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Diseño de Prótesis , Radiografía/métodos , Rango del Movimiento Articular , Reoperación/métodos , Estudios Retrospectivos , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugía , Resultado del TratamientoRESUMEN
The ABCA3 lipid transporter is located in the limiting membrane of lamellar bodies (LBs) in type-II-pneumocytes. Mutations within the ABCA3 gene may functionally impair the transporter, causing lung diseases in newborns, children and adults. Assays to quantify volume and lipid filling of the LBs on the level of the vesicular structures and thereby assess the function of ABCA3 are still lacking. In the present study human influenza haemagglutinin- (HA-) tagged wild type and mutant ABCA3 proteins were stably expressed in lung A549 cells. Fluorescently-labelled TopFluor phosphatidylcholine (TopF-PC) incorporated in surfactant-like liposomes was delivered to the cells and visualized by confocal microscopy. Subsequently, a comprehensive image analysis method was applied to quantify volume and fluorescence intensity of TopF-PC in ABCA3-HA-positive vesicles. TopF-PC accumulated within the vesicles in a time and concentration-dependent manner, whereas the volume remained unchanged, suggesting active transport into preformed ABCA3 containing vesicles. Furthermore, this finding was supported by a decrease of the fluorescence intensity within the vesicles when either the ATPase of the transporter was inhibited by vanadate, or when a disease-causing mutation (K1388N) close to the ABCA3-nucleotide binding domain 2 was introduced. Conversely, a mutation (E292V) located in the first cytoplasmic loop of ABCA3 did not significantly affect lipid transport, but rather resulted in smaller vesicles. In addition to these findings, the assay used in this work for analysing the PC-lipid transport into ABCA3 positive vesicles will be useful to screen for compounds susceptible to restore function in mutated ABCA3 protein.
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Transportadoras de Casetes de Unión a ATP/genética , Transporte Biológico/genética , Lípidos/química , Pulmón/metabolismo , Células A549 , Transportadoras de Casetes de Unión a ATP/metabolismo , Adenosina Trifosfatasas/genética , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Humanos , Lectinas/genética , Pulmón/patología , Microscopía Confocal , MutaciónRESUMEN
Mutations in the ATP-binding cassette subfamily A member 3 (ABCA3) gene are the most common monogenetic cause of surfactant dysfunction disorders in newborns and interstitial lung diseases in children and young adults. Although the effect of mutations resulting in truncated or incomplete proteins can be predicted, the consequences of missense variants cannot be as easily. Our aim was to investigate the intracellular handling and disturbance of the cellular surfactant system in a stable cell model with several different clinically relevant ABCA3 missense mutations. We found that the investigated missense mutations within the ABCA3 gene affect surfactant homeostasis in different ways: first by disrupting intracellular ABCA3 protein localization (c.643C > A, p.Q215K; c.2279T > G, p.M760R), second by impairing the lipid transport of ABCA3 protein (c.875A > T, p.E292V; c.4164G > C, p.K1388N), and third by yet undetermined mechanisms predisposing for the development of interstitial lung diseases despite correct localization and normal lipid transport of the variant ABCA3 protein (c.622C > T, p.R208W; c.863G > A, p.R288K; c.2891G > A, p.G964D). In conclusion, we classified cellular consequences of missense ABCA3 sequence variations leading to pulmonary disease of variable severity. The corresponding molecular pathomechanisms of such ABCA3 variants may specifically be addressed by targeted treatments.
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Transportadoras de Casetes de Unión a ATP/genética , Predisposición Genética a la Enfermedad , Enfermedades Pulmonares Intersticiales/genética , Células A549 , Humanos , Enfermedades Pulmonares Intersticiales/fisiopatología , Mutación Missense/genética , FenotipoRESUMEN
Understanding host-guest interactions is one of the key requirements for adjusting properties in metal-organic frameworks (MOFs). In particular, systems with coordinatively unsaturated Lewis acidic metal sites feature highly selective adsorption processes. This is attributed to strong interactions with Lewis basic guest molecules. Here we show that a combination of 13C MAS NMR spectroscopy with state-of-the-art density functional theory (DFT) calculations allows one to unravel the interactions of water, 2-aminopyridine, 3-aminopyridine, and diethylamine with the open metal sites in Cr-MIL-101. The 13C MAS NMR spectra, obtained with ultrafast magic-angle spinning, are well resolved, with resonances distributed over 1000 ppm. They present a clear signature for each guest at the open metal sites. Based on competition experiments this leads to the following binding preference: water < diethylamine ≈ 2-aminopyridine < 3-aminopyridine. Assignments were done by exploiting distance sum relations derived from spin-lattice relaxation data and 13C{1H} REDOR spectral editing. The experimental data were used to validate NMR shifts computed for the Cr-MIL-101 derivatives, which contain Cr3O clusters with magnetically coupled metal centers. While both approaches provide an unequivocal assignment and the arrangement of the guests at the open metal sites, the NMR data offer additional information about the guest and framework dynamics. We expect that our strategy has the potential for probing the binding situation of adsorbate mixtures at the open metal sites of MOFs in general and thus accesses the microscopic interaction mechanisms for this important material class, which is essential for deriving structure-property relationships.
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The sorption properties of metal-organic frameworks (MOFs) can be influenced by introducing covalently attached functional side chains, which make this subclass of porous materials promising for applications as diverse as gas storage and separation, catalysis, and drug delivery. The incorporation of side groups usually comes along with disorder, as the synthesis procedures rarely allow for one specific position among a larger group of equivalent sites to be selected. For a series of isoreticular CAU-1 frameworks, chosen as model compounds, one out of four positions at every linker is modified with equal probability. Here, we investigate the influence of this disorder on Ar sorption and 129Xe nuclear magnetic resonance spectroscopy using hyperpolarized 129Xe gas. Models used for predicting the pore dimensions as well as their distributions were derived from the unfunctionalized framework by replacing one proton at every linker with either an amino, an acetamide, or a methyl urea functionality. The resulting structures were optimized using density functional theory (DFT) calculations. Results from void analyses and Monte Carlo force field simulations suggest that for available Ar nonlocal DFT (NLDFT) kernels, neither the pore dimensions nor the distributions induced by the side-chain disorder are well-reproduced. By contrast, we found the 129Xe chemical shift analysis for the shift observed at high temperature to be well-suited to develop a detailed fingerprint of the porosity and side-chain disorder within the isoreticular CAU-1 series. After calibrating the 129Xe limiting shift of the amino-functionalized framework with DFT calculations, the downfield shifts for the other two derivatives are an excellent measure for the reduction of the accessible pore space and reveal a strong preference for the side chains toward the octahedral voids for both cases. We expect that the strategy presented here can be commonly applied to disorder phenomena within MOFs in the future.
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BACKGROUND: This study analyzed the radiographic results of a cemented all-polyethylene keeled glenoid component available in different sizes and multiple backside radiuses of curvature. METHODS: The study group consisted of 118 cases (114 patients). There were 63 women and 51 men. Mean age at the time of arthroplasty was 68 years (range, 51-85 years). True anterior-posterior radiographs obtained postoperatively and at the final follow-up were analyzed for implant seating and the occurrence of radiolucent lines. Glenoid morphology and fatty infiltration of the rotator cuff muscles were examined using computed tomography scans. Mean follow-up was 38 months (range, 24-70 months). RESULTS: The mean radiolucent line score after surgery was 0.54 points (range, 0-3 points), and 90% had no or only 1 radiolucent line. At the final follow-up, the mean score was 1.06 points (range, 0-3 points), and 74% had no or only 1 radiolucent line. The score increased significantly over time (P < .001). No component was at risk for loosening. No correlation was found between patient age, sex, hand dominance, glenoid morphology, or fatty infiltration of the rotator cuff muscles and the occurrence of radiolucent lines. CONCLUSION: In the short-term, the glenoid component analyzed in this study showed promising radiographic results, with a low number of radiolucent lines without failure. However, the mean radiolucent line score increased significantly over time, and long-term observations are necessary to confirm a possible advantage compared with older component designs.
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Artroplastía de Reemplazo de Hombro/métodos , Osteoartritis/cirugía , Polietileno , Articulación del Hombro/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/diagnóstico , Diseño de Prótesis , Articulación del Hombro/diagnóstico por imagen , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Knowledge about the clinical spectrum of lung disease caused by variations in the ATP binding cassette subfamily A member 3 (ABCA3) gene is limited. Here we describe genotype-phenotype correlations in a European cohort. METHODS: We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015. RESULTS: Of 22 homozygous (15 male) and 18 compound heterozygous patients (3 male), 37 presented with neonatal respiratory distress syndrome as term babies. At follow-up, two major phenotypes are documented: patients with (1) early lethal mutations subdivided into (1a) dying within the first 6â months or (1b) before the age of 5â years, and (2) patients with prolonged survival into childhood, adolescence or adulthood. Patients with null/null mutations predicting complete ABCA3 deficiency died within the 1st weeks to months of life, while those with null/other or other/other mutations had a more variable presentation and outcome. Treatment with exogenous surfactant, systemic steroids, hydroxychloroquine and whole lung lavages had apparent but many times transient effects in individual subjects. CONCLUSIONS: Overall long-term (>5â years) survival of subjects with two disease-causing ABCA3 mutations was <20%. Response to therapies needs to be ascertained in randomised controlled trials.
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Transportadoras de Casetes de Unión a ATP/genética , Enfermedades Pulmonares Intersticiales/genética , Mutación , Adolescente , Adulto , Biopsia , Líquido del Lavado Bronquioalveolar/química , Niño , Preescolar , Consanguinidad , Diagnóstico por Imagen , Femenino , Genotipo , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Microscopía Electrónica , Fenotipo , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Diffuse parenchymal lung diseases (DPLDs) are characterized by chronic inflammation and fibrotic remodeling of the interstitial tissue. A small fraction of DPLD cases can be genetically defined by mutations in certain genes, with ABCA3 being the gene most commonly affected. However, the pathomechanisms underlying ABCA3-induced DPLD are far from clear. To investigate whether ABCA3 plays a role in cellular cholesterol homeostasis, phospholipids, free cholesterol, and cholesteryl esters were quantified in cells stably expressing ABCA3 using mass spectrometry. Cellular free cholesterol and lipid droplets were visualized by filipin or oil red staining, respectively. Expression of SREBP regulated genes was measured using qPCR. Cell viability was assessed using the XTT assay. We found that wild type ABCA3 reduces cellular free cholesterol levels, induces the SREBP pathway, and renders cells more resistant to loading with exogenous cholesterol. Moreover, ABCA3 mutations found in patients with DPLD interfere with this protective effect of ABCA3, resulting in free cholesterol induced cell death. We conclude that ABCA3 plays a previously unrecognized role in the regulation of cellular cholesterol levels. Accumulation of free cholesterol as a result of a loss of ABCA3 export function represents a novel pathomechanism in ABCA3-induced DPLD.
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Transportadoras de Casetes de Unión a ATP/fisiología , Células Epiteliales Alveolares/efectos de los fármacos , Colesterol/farmacología , Citoprotección/genética , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/fisiología , Células Epiteliales Alveolares/fisiología , Muerte Celular/efectos de los fármacos , Células Cultivadas , Colesterol/metabolismo , Citoprotección/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/fisiología , Humanos , Metabolismo de los Lípidos/genética , Enfermedades Pulmonares Intersticiales/genética , Enfermedades Pulmonares Intersticiales/metabolismo , Enfermedades Pulmonares Intersticiales/patología , Fosfolípidos/metabolismo , Fosfolípidos/farmacología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/fisiologíaRESUMEN
The ABCA3 gene encodes a lipid transporter in type II pneumocytes critical for survival and normal respiratory function. The frequent ABCA3 variant R288K increases the risk for neonatal respiratory distress syndrome among term and late preterm neonates, but its role in children's interstitial lung disease has not been studied in detail. In a retrospective cohort study of 228 children with interstitial lung disease related to the alveolar surfactant system, the frequency of R288K was assessed and the phenotype of patients carrying a single R288K variant further characterized by clinical course, lung histology, computed tomography and bronchoalveolar lavage phosphatidylcholine PC 32:0. Cell lines stably transfected with ABCA3-R288K were analyzed for intracellular transcription, processing and targeting of the protein. ABCA3 function was assessed by detoxification assay of doxorubicin, and the induction and volume of lamellar bodies. We found nine children with interstitial lung disease carrying a heterozygous R288K variant, a frequency significantly higher than in the general Caucasian population. All identified patients had neonatal respiratory insufficiency, recovered and developed chronic interstitial lung disease with intermittent exacerbations during early childhood. In vitro analysis showed normal transcription, processing, and targeting of ABCA3-R288K, but impaired detoxification function and smaller lamellar bodies. We propose that the R288K variant can underlie interstitial lung disease in childhood due to reduced function of ABCA3, demonstrated by decelerated detoxification of doxorubicin, reduced PC 32:0 content and decreased lamellar body volume.
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BACKGROUND: Children's interstitial lung diseases (chILD) comprise a broad spectrum of diseases. Besides the genetically defined surfactant dysfunction disorders, most entities pathologically involve the alveolar surfactant region, possibly affecting the surfactant proteins SP-B and SP-C. Therefore, our objective was to determine the value of quantitation of SP-B and SP-C levels in bronchoalveolar lavage fluid (BALF) for the diagnosis of chILD. METHODS: Levels of SP-B and SP-C in BALF from 302 children with chILD and in controls were quantified using western blotting. In a subset, single-nucleotide polymorphisms (SNPs) in the SFTPC promoter were genotyped by direct sequencing. RESULTS: While a lack of dimeric SP-B was found only in the sole subject with hereditary SP-B deficiency, low or absent SP-C was observed not only in surfactant dysfunction disorders but also in patients with other diffuse parenchymal lung diseases pathogenetically related to the alveolar surfactant region. Genetic analysis of the SFTPC promoter showed association of a single SNP with SP-C level. CONCLUSION: SP-B levels may be used for screening for SP-B deficiency, while low SP-C levels may point out diseases caused by mutations in TTF1, SFTPC, ABCA3, and likely in other genes involved in surfactant metabolism that remain to be identified. We conclude that measurement of levels of SP-B and SP-C was useful for the differential diagnosis of chILD, and for the precise molecular diagnosis, sequencing of the genes is necessary.
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Líquido del Lavado Bronquioalveolar/química , Enfermedades Pulmonares Intersticiales/diagnóstico , Proteína B Asociada a Surfactante Pulmonar/análisis , Proteína C Asociada a Surfactante Pulmonar/análisis , Transportadoras de Casetes de Unión a ATP/genética , Adolescente , Bronquitis/genética , Estudios de Casos y Controles , Niño , Preescolar , Comorbilidad , Proteínas de Unión al ADN/genética , Discapacidades del Desarrollo/genética , Femenino , Heterogeneidad Genética , Genotipo , Humanos , Síndromes de Inmunodeficiencia/genética , Lactante , Enfermedades Pulmonares Intersticiales/genética , Masculino , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Precursores de Proteínas/genética , Proteolípidos/genética , Proteinosis Alveolar Pulmonar/diagnóstico , Proteinosis Alveolar Pulmonar/genética , Proteína B Asociada a Surfactante Pulmonar/deficiencia , Proteína B Asociada a Surfactante Pulmonar/genética , Proteína C Asociada a Surfactante Pulmonar/química , Proteína C Asociada a Surfactante Pulmonar/deficiencia , Proteína C Asociada a Surfactante Pulmonar/genética , Análisis de Secuencia de ADN , Factores de Transcripción , Adulto JovenRESUMEN
The resistance of metal-organic frameworks towards water is a very critical issue concerning their practical use. Recently, it was shown for microporous MOFs that the water stability could be increased by introducing hydrophobic pendant groups. Here, we demonstrate a remarkable stabilisation of the mesoporous MOF Al-MIL-101-NH2 by postsynthetic modification with phenyl isocyanate. In this process 86 % of the amino groups were converted into phenylurea units. As a consequence, the long-term stability of Al-MIL-101-URPh in liquid water could be extended beyond a week. In water saturated atmospheres Al-MIL-101-URPh decomposed at least 12-times slower than the unfunctionalised analogue. To study the underlying processes both materials were characterised by Ar, N2 and H2 O sorption measurements, powder X-ray diffraction, thermogravimetric and chemical analysis as well as solid-state NMR and IR spectroscopy. Postsynthetic modification decreased the BET equivalent surface area from 3363 to 1555â m(2) g(-1) for Al-MIL-101-URPh and reduced the mean diameters of the mesopores by 0.6â nm without degrading the structure significantly and reducing thermal stability. In spite of similar water uptake capacities, the relative humidity-dependent uptake of Al-MIL-101-URPh is slowed and occurs at higher relative humidity values. In combination with (1) H-(27) Al D-HMQCâ NMR spectroscopy experiments this favours a shielding mechanism of the Al clusters by the pendant phenyl groups and rules out pore blocking.
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Aluminio/química , Complejos de Coordinación/química , Compuestos Organometálicos/química , Agua/química , Complejos de Coordinación/síntesis química , Estructuras Metalorgánicas , Compuestos Organometálicos/síntesis química , Porosidad , Espectrometría por Rayos X , Termogravimetría , Difracción de Rayos XRESUMEN
Background: Higher bone or metal glenoid offset in reverse shoulder arthroplasty (RSA) reduces scapular notching, improves range of motion (ROM), and reduces postoperative instability. This retrospective multicenter study compared two implant designs to evaluate the short-term clinical and radiologic results of bone increased offset RSA (BIO-RSA) and metal increased offset RSA (MIO-RSA) in reverse shoulder. We hypothesized no difference between groups. Methods: This study analyzed n = 62 BIO-RSA and n = 90 MIO-RSA cases with a mean follow-up of 29.7 ± 6.0 months (BIO-RSA, range 24-49 months) and 24.0 ± 1.1 months (MIO-RSA, range 22-28 months). A 145°-onlay humeral stem was utilized in BIO-RSA cases, while a 135°-semi-inlay humeral stem was implanted in all MIO-RSA cases. Preoperative and postoperative radiologic imaging was reviewed to identify signs of scapular notching. Additionally, lateralization was evaluated according to Erickson et al. The constant score, subjective shoulder value, and ROM were evaluated during the baseline and follow-up consultations, and the findings of both groups were subsequently compared. Results: Scapular notching was observed in 7.0% (n = 8) of MIO-RSA cases and 8.1% (n = 5) of BIO-RSA cases (P = .801). MIO-group had a higher lateralization angle (P = .020) and the BIO-group had a higher distalization angle (P = .005). At baseline, mean constant score in the MIO-RSA group was higher than in the BIO-RSA group (P < .001), and it significantly increased to 67.8 ± 12.1P (MIO-RSA) and 69.5 ± 12.3P (BIO-RSA) to a similar level (P = .399). ROM improved in both groups with no significant difference between the two groups at follow-up. Conclusion: BIO-RSA and MIO-RSA in two distinct implant designs provide comparable short-term outcomes with a similar increase in shoulder function with notable variations in the lateralization and distalization angles between both implants. Scapular notching was rarely seen and unaffected by the method of glenoid lateralization. Follow-up investigations of both techniques are necessary to complement and track changes in the long-term outcome.
RESUMEN
The Latarjet procedure is a proven and effective operation to treat anterior shoulder instability. Especially in cases with anterior glenoid bone loss, the Latarjet operation is the most popular procedure to restore glenoid anatomy and avoid further dislocations. Next to the re-creation of the missing glenoid bone, the sling effect of the conjoint tendon transferred between a split in the subscapularis muscle is an important "soft tissue stabilizer" of the humeral head. However, it has been shown that the inferior part of the subscapularis muscle tends to degenerate, leading to fatty infiltration of the muscle itself. Also, exposure through the subscapularis split is technically demanding, and there is a risk of nerve damage due to the pulling forces of the retractors during open surgery. When performing the procedure arthroscopically, extremely low and medial portals are necessary to find a correct angle for the glenoid drilling when approaching from anterior. Neurovascular structures may be at risk during these surgical steps. The aim of the flipped Latarjet procedure is to facilitate a safe and reliable arthroscopic operation to anteriorly stabilize the shoulder by transferring the coracoid to the deficient glenoid without splitting the subscapularis muscle while keeping the benefits of a sling effect of the conjoined tendon.
RESUMEN
BACKGROUND: In recent years, the number of reverse shoulder arthroplasty implantations has increased continuously and a higher number of revision surgeries due to complications can be expected in the future. Current data show a mean complication rate for RSA of around 4%. The most common complications are instability, infection, component loosening, and periprosthetic fracture. TREATMENT OPTIONS: Revision surgery for RSA is challenging, and an individual treatment plan is necessary. For prosthetic instability, different operative or non-operative treatment options are available. Revision surgery for periprosthetic infection with replacement of the prosthesis is usually necessary for infection management. The treatment of periprosthetic fractures is based on techniques of general fracture treatment and depends on the fracture type. Knowledge of complications and risk factors may decrease complication rates in primary reverse shoulder arthroplasty in the future.