Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 87
Filtrar
1.
J Stroke Cerebrovasc Dis ; 33(6): 107701, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38561169

RESUMO

OBJECTIVES: Post-stroke fatigue (PSF) is common and often disabling. Sleep-disordered breathing (SDB) is highly prevalent among stroke survivors and can cause fatigue. We explored the relationship between SDB and PSF over time. MATERIALS AND METHODS: Ischemic stroke (IS) patients within the BASIC project were offered SDB screening with a well-validated cardiopulmonary sleep apnea test at 0, 3-, 6-, and 12-months post-stroke. The primary exposure was the respiratory event index (REI; sum of apneas plus hypopneas per hour). The primary outcome was PSF, measured by the SF-36 vitality scale. Associations between REI and PSF were evaluated using linear regression including time-by-REI interactions, allowing the effect of REI to vary over time. RESULTS: Of the 411 IS patients who completed at least one outcome interview, 44 % were female, 61 % Mexican American (MA), 26 % non-Hispanic white, with a mean age of 64 (SD 10). Averaged across timepoints, REI was not associated with PSF. In a time-varying model, higher REI was associated with greater PSF at 3-months (ß = 1.75, CI = 0.08, 3.43), but not at 6- or 12-months. Across timepoints, female sex, depressive symptoms, and comorbidity burden were associated with greater PSF, whereas MA ethnicity was associated with less PSF. CONCLUSIONS: Higher REI was associated with modestly greater PSF in the early post-stroke period, but no association was observed at 6 months and beyond. SDB may be a modest modifiable risk factor for early PSF, but its treatment is unlikely to have a substantial impact on long-term PSF. MA ethnicity seems to be protective against PSF.


Assuntos
Fadiga , AVC Isquêmico , Síndromes da Apneia do Sono , Humanos , Feminino , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Síndromes da Apneia do Sono/etnologia , Masculino , Pessoa de Meia-Idade , Idoso , Fadiga/etiologia , Fadiga/epidemiologia , Fadiga/fisiopatologia , Fadiga/diagnóstico , Fadiga/psicologia , AVC Isquêmico/epidemiologia , AVC Isquêmico/diagnóstico , AVC Isquêmico/etnologia , Fatores de Risco , Fatores de Tempo , Medição de Risco , Sono , Respiração , Prognóstico
2.
Arch Orthop Trauma Surg ; 144(6): 2665-2671, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38801533

RESUMO

INTRODUCTION: Open book injuries are challenging injuries that oftentimes require surgical treatment. Currently, treatment is performed with symphyseal plating requiring extensive surgery and entirely limiting physiological movement of the symphyseal joint, frequently resulting in implant failure. Therefore, we investigated the biomechanical properties of a minimally invasive tape suture construct (modified SpeedBridge™) as an alternative stabilization technique for the treatment of open book injuries in human cadaver pelvic rings. MATERIALS AND METHODS: The symphysis of 9 human cadaver pelvises was dissected and dilated to 3 cm creating an open book injury. Next, the two osteosynthesis methods (plating, modified SpeedBridge™) were applied. All specimens then underwent cyclic horizontal and vertical loading, simulating biomechanical forces while sitting, standing and walking. For statistical analysis, 3D dislocation (mm) was calculated. RESULTS: Total displacement (mm) of the pubic symphysis displayed the following means and standard deviations: native group 1.34 ± 0.62 mm, open book group 3.01 ± 1.26 mm, tape group 1.94 ± 0.59 mm and plate group 1.37 ± 0.41 mm. Comparison between native and open book (p = 0.029), open book and plate (p = 0.004), open book and tape (p = 0.031), as well as tape and plate group (p = 0.002) showed significant differences. No significant differences were found when comparing the native and tape (p = 0.059), as well as the native and plate (p = 0.999) group. CONCLUSION: While both osteosynthesis techniques sufficiently stabilized the injury, symphyseal plating displayed the highest rigidity. The modified SpeedBridge™ as a tape suture construct provided statistically sufficient biomechanical stability while maintaining symphyseal micro mobility, consequently allowing ligamental healing of the injured joint without iatrogenic arthrodesis.


Assuntos
Cadáver , Sínfise Pubiana , Humanos , Sínfise Pubiana/lesões , Sínfise Pubiana/cirurgia , Fenômenos Biomecânicos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Masculino , Placas Ósseas , Feminino , Fraturas Ósseas/cirurgia
3.
Arch Orthop Trauma Surg ; 143(6): 3111-3117, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35831608

RESUMO

INTRODUCTION: Current gold standard for the treatment of symphyseal disruptions includes anterior plating, almost entirely prohibiting symphyseal mobility and resulting in an iatrogenic arthrodesis followed by high rates of implant failure. Minimally invasive tape suture constructs have been found to maintain the micro mobility of ligamentous injuries, yet still providing sufficient biomechanical stability. Recently, this technique has been primarily investigated for symphyseal disruptions on synthetic pelvic models. Therefore, the aim of this study was to examine the feasibility of this novel flexible osteosynthesis on cadaveric pelvic models based on the following hypothesis: tape suture constructs ensure sufficient biomechanical stability without inhibiting micro mobility of the pubic symphysis for the treatment of symphyseal disruptions and maintain stability during long-term loading. MATERIALS AND METHODS: 9 cadaveric anterior pelvic rings were used in this study and a symphyseal disruption was created in every specimen. The specimens were then exposed to short- and long-term vertical and horizontal cyclic loading after treatment with a tape suture construct in criss-cross technique. The mean maximum displacement (mm) during cyclic loading and the corresponding stiffness (N/mm) were measured and compared. RESULTS: Regarding both displacement (mm) and corresponding stiffness (N/mm), the tape sutures displayed a significant difference between short- and long-term loading for cranial and caudal vertical loading (p < 0.01) but differences remained non-significant for horizontal loading (p > 0.05). No tape suture suffered from implant failure during long-term loading. CONCLUSIONS: The tape suture construct displayed sufficient biomechanical stability without exceeding the physiological mobility of 2 mm of the pubic symphysis; however, also maintained the desired micro mobility of the affected joint necessary to prevent an iatrogenic arthrodesis. Further, all tape sutures maintained stability throughout long-term loading.


Assuntos
Sínfise Pubiana , Humanos , Sínfise Pubiana/cirurgia , Sínfise Pubiana/lesões , Fenômenos Biomecânicos , Cadáver , Suturas , Doença Iatrogênica , Técnicas de Sutura
4.
Eur J Orthop Surg Traumatol ; 33(6): 2497-2503, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36544078

RESUMO

PURPOSE: The incidence of atlanto-axial injuries is continuously increasing and often requires surgical treatment. Recently, Harati developed a new procedure combining polyaxial transarticular screws with polyaxial atlas massae lateralis screws via a rod system with promising clinical results, yet biomechanical data is lacking. This biomechanical study consequently aims to evaluate the properties of the Harati technique. METHODS: Two groups, each consisting of 7 cervical vertebral segments (C1/2), were formed and provided with a dens axis type 2 fracture according to Alonzo. One group was treated with the Harms and the other with the Harati technique. The specimen was loaded via a lever arm to simulate extension, flexion, lateral flexion and rotation. For statistical analysis, dislocation (°) was measured and compared. RESULTS: For extension and flexion, the Harati technique displayed a mean dislocation of 4.12° ± 2.36° and the Harms technique of 8.48° ± 1.49° (p < 0.01). For lateral flexion, the dislocation was 0.57° ± 0.30° for the Harati and 1.19° ± 0.25° for the Harms group (p < 0.01). The mean dislocation for rotation was 1.09° ± 0.48° for the Harati and 2.10° ± 0.31° for the Harms group (p < 0.01). No implant failure occurred. CONCLUSION: This study found a significant increase in biomechanical stability of the Harati technique when compared to the technique by Harms et al. Consequently, this novel technique can be regarded as a promising alternative for the treatment of atlanto-axial instabilities.


Assuntos
Articulação Atlantoaxial , Instabilidade Articular , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Vértebras Cervicais/cirurgia , Articulação Atlantoaxial/cirurgia , Amplitude de Movimento Articular , Fenômenos Biomecânicos , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia
5.
Stroke ; 53(11): 3394-3400, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35959679

RESUMO

BACKGROUND: The association between stroke and dementia is well established. Less is known about this association in underrepresented ethnic groups. In a large ethnically diverse cohort, we examined whether history of stroke was associated with cognitive impairment, and whether this relationship differed by ethnicity (Mexican American [MA] versus non-Hispanic White). METHODS: This was a population-based cohort study conducted in Nueces County, TX, a biethnic community with a large and primarily nonimmigrant MA population. Residents aged ≥65 were recruited door-to-door or by telephone between May 2018 and December 2021. The primary exposure was history of stroke, obtained by self-report. Demographic, medical, and educational histories were also obtained. The primary outcome was the Montreal Cognitive Assessment (MoCA), a scale that evaluates multiple domains of cognitive performance. Scores were divided into 3 ordinal categories, roughly corresponding to normal cognition (MoCA 26-30), mild cognitive impairment (MoCA 20-25), or probable dementia (MoCA 0-19). RESULTS: One thousand eight hundred one participants completed MoCA screening (55% female; 50% MA, 44% Non-Hispanic White, 6% other), of whom 12.4% reported history of stroke. Stroke prevalence was similar across ethnicities (X2 2.1; P=0.34). In a multivariable cumulative logit regression model for the ordinal cognition outcome, a stroke by ethnicity interaction was observed (P=0.01). Models stratified by ethnicity revealed that stroke was associated with cognitive impairment across ethnicities, but had greater impact on cognition in non-Hispanic Whites (cumulative odds ratio=3.81 [95% CI, 2.37-6.12]) than in MAs (cumulative odds ratio=1.58 [95% CI, 1.04-2.41]). Increased age and lower educational attainment were also associated with cognitive impairment, regardless of ethnicity. CONCLUSIONS: History of stroke was associated with increased odds of cognitive impairment after controlling for other factors in both MA and Non-Hispanic White participants. The magnitude of the impact of stroke on cognition was less in MA than in Non-Hispanic White participants.


Assuntos
Disfunção Cognitiva , Demência , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Americanos Mexicanos , Estudos de Coortes , Acidente Vascular Cerebral/diagnóstico , Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Demência/diagnóstico
6.
Arch Orthop Trauma Surg ; 142(9): 2235-2243, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34052913

RESUMO

INTRODUCTION: Open book fractures are challenging injuries oftentimes requiring surgical treatment. The current treatment of choice is symphyseal plating, which requires extensive surgery and entirely limits physiological movement of the symphyseal joint, frequently resulting in implant failure. Therefore, we investigated the biomechanical properties of a semi-rigid implant (modified SpeedBridge™) as a minimally invasive tape suture construct for the treatment of open book fractures and evaluated the superiority of two techniques of implementation: criss-cross vs. triangle technique. MATERIALS AND METHODS: Nine synthetic symphyseal joints were dissected creating an open book fracture. The different osteosynthesis methods (plating, modified SpeedBridge™ in criss-cross/triangle technique) were then applied. All constructs underwent horizontal and vertical loading, simulating biomechanical forces while sitting, standing and walking. For statistical analysis, dislocation (mm) and stiffness (N/mm) were calculated. RESULTS: Symphyseal plating for the treatment of open book fractures proved to be a rigid osteosynthesis significantly limiting the physiological mobility of the symphyseal joint (dislocation: 0.08 ± 0.01 mm) compared to the tape sutures (dislocation: triangle technique 0.27 ± 0.07 mm, criss-cross technique 0.23 ± 0.05 mm) regarding horizontal tension (p < 0.01). Both modified SpeedBridge™ techniques showed sufficient biomechanical stability without one being superior to the other (p > 0.05 in all directions). Considering vertical loading, no statistical difference was found between all osteosynthesis methods (caudal: p = 0.41; cranial: p = 0.61). CONCLUSIONS: Symphyseal plating proved to be the osteosynthesis method with the highest rigidity. The modified SpeedBridge™ as a semi-rigid suture construct provided statistically sufficient biomechanical stability while maintaining a minimum of symphyseal movement, consequently allowing ligamental healing of the injured joint without iatrogenic arthrodesis. Furthermore, both the criss-cross and the triangle technique displayed significant biomechanical stability without one method being superior.


Assuntos
Fraturas Ósseas , Sínfise Pubiana , Fenômenos Biomecânicos , Placas Ósseas , Parafusos Ósseos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Humanos , Sínfise Pubiana/lesões , Suturas
7.
Biomed Eng Online ; 18(1): 38, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925898

RESUMO

BACKGROUND: Operative procedures for unstable pelvic ring fractures remain controversially discussed. Minimally invasive treatment options for pelvic ring fractures have several benefits for the patient. But they can also provide disadvantages. Anterior subcutaneous pelvic fixation (INFIX) has shown promising biomechanical results in pelvic ring fractures, but there is a high complication rate of nerve injuries. An additional screw to the INFIX seems to be more stable. The aim of this study is to compare biomechanical stability of a new modified unilateral INFIX fixing the unilateral injured pelvic ring with the standard INFIX. METHODS: 24 composite synthetic full pelvises were used in this study. 4 groups each with a number of six pelvic specimens were randomly assigned. A C1.3-type pelvic fracture was made with an osteotomy of the sacrum and an osteotomy of the anterior pelvic ring. Fracture fixation was performed within the four groups: (1) unilateral INFIX, (2) "extended" unilateral INFIX + additional pubic ramus pedicle screw, (3) bilateral INFIX, (4) "extended" bilateral INFIX + additional pubic ramus pedicle screw. All specimens were cyclic loaded with 200 N until maximum of 300 N. Distance/dislocation of the fracture fragments were detected with 3D-ultrasound measuring system. Stiffness was calculated. RESULTS: Extended unilateral INFIX showed the lowest mean dislocation. Lowest rotational stability was displayed by the standard bilateral INFIX. A significant difference (P = 0.04) was shown between the extended unilateral INFIX and the "standard" bilateral INFIX in terms of rotational stability. Extended unilateral INFIX showed significantly improved stability of anterior fracture dislocation (P = 0.01) and unilateral INFIX showed the highest rotational stiffness. Anterior fixation stiffness of the unilateral INFIX was significantly improved using an additional symphysis/pubic ramus screw (P = 0.002). CONCLUSION: Extended unilateral INFIX (+ additional pubic ramus pedicle screw) is a feasible minimally invasive treatment for anterior pelvic ring fractures. Higher stability and lower probability of bilateral nerve damage is provided by the extended unilateral INFIX compared to the standard bilateral INFIX.


Assuntos
Fixação de Fratura/instrumentação , Fraturas Ósseas/cirurgia , Fenômenos Mecânicos , Ossos Pélvicos/lesões , Fenômenos Biomecânicos , Teste de Materiais , Ossos Pélvicos/cirurgia , Estresse Mecânico
8.
Unfallchirurg ; 122(6): 444-451, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31053925

RESUMO

The 3D printing technology enables precise fracture models to be generated from volumetric digital imaging and communications in medicine (DICOM) computed tomography (CT) data. Apart from patient treatment, in the future this technology could potentially play a significant role in education and training in the field of orthopedic and trauma surgery. Preliminary results show that the understanding and classification of fractures can be improved when teaching medical students. The use of life-size and haptic models of real fractures for education is particularly interesting. Even experienced surgeons show an improved classification and treatment planning with the help of 3D printed models when compared to plain CT data. Especially for complex articular fractures, such as those of the acetabulum and tibial plateau, initial evidence shows patient benefits in terms of reduced surgery time and blood loss with the help of 3D models. The use of 3D printing on-site at the hospital is of particular interest in orthopedic and trauma surgery as it promises to provide products within a short time. The low investment and running costs and the increasing availability of convenient software solutions will spur increasing dissemination of this technology in the coming years.


Assuntos
Fraturas Ósseas/cirurgia , Ortopedia/educação , Impressão Tridimensional , Traumatologia/educação , Simulação por Computador , Educação Médica/métodos , Avaliação Educacional , Humanos , Ortopedia/métodos , Traumatologia/métodos
9.
J Proteome Res ; 17(4): 1340-1347, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29480007

RESUMO

To extend proteome coverage obtained from bottom-up mass spectrometry approaches, three complementary ion activation methods, higher energy collision dissociation (HCD), ultraviolet photodissociation (UVPD), and negative mode UVPD (NUVPD), are used to interrogate the tryptic peptides in a human hepatocyte lysate using a high performance Orbitrap mass spectrometer. The utility of combining results from multiple activation techniques (HCD+UVPD+NUVPD) is analyzed for total depth and breadth of proteome coverage. This study also benchmarks a new version of the Byonic algorithm, which has been customized for database searches of UVPD and NUVPD data. Searches utilizing the customized algorithm resulted in over 50% more peptide identifications for UVPD and NUVPD tryptic peptide data sets compared to other search algorithms. Inclusion of UVPD and NUVPD spectra resulted in over 600 additional protein identifications relative to HCD alone.


Assuntos
Biologia Computacional , Fotólise , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Algoritmos , Bases de Dados Factuais , Humanos , Peptídeos , Raios Ultravioleta
10.
J Proteome Res ; 17(3): 1216-1226, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29376659

RESUMO

Charge deconvolution infers the mass from mass over charge (m/z) measurements in electrospray ionization mass spectra. When applied over a wide input m/z or broad target mass range, charge-deconvolution algorithms can produce artifacts, such as false masses at one-half or one-third of the correct mass. Indeed, a maximum entropy term in the objective function of MaxEnt, the most commonly used charge deconvolution algorithm, favors a deconvolved spectrum with many peaks over one with fewer peaks. Here we describe a new "parsimonious" charge deconvolution algorithm that produces fewer artifacts. The algorithm is especially well-suited to high-resolution native mass spectrometry of intact glycoproteins and protein complexes. Deconvolution of native mass spectra poses special challenges due to salt and small molecule adducts, multimers, wide mass ranges, and fewer and lower charge states. We demonstrate the performance of the new deconvolution algorithm on a range of samples. On the heavily glycosylated plasma properdin glycoprotein, the new algorithm could deconvolve monomer and dimer simultaneously and, when focused on the m/z range of the monomer, gave accurate and interpretable masses for glycoforms that had previously been analyzed manually using m/z peaks rather than deconvolved masses. On therapeutic antibodies, the new algorithm facilitated the analysis of extensions, truncations, and Fab glycosylation. The algorithm facilitates the use of native mass spectrometry for the qualitative and quantitative analysis of protein and protein assemblies.


Assuntos
Algoritmos , Anticorpos Monoclonais Humanizados/análise , Cetuximab/análise , Glicoproteínas/análise , Imunoglobulina G/análise , Infliximab/análise , Properdina/análise , Daclizumabe , Entropia , Glicosilação , Humanos , Fragmentos de Peptídeos/análise , Mapeamento de Peptídeos , Proteólise , Soluções , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas por Ionização por Electrospray/métodos , Eletricidade Estática , Tripsina/química
11.
Nitric Oxide ; 77: 96-105, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29704568

RESUMO

Several recent reports suggest that HNO may be produced endogenously by reaction of H2S and S-nitrosoglutathione (GSNO). This hypothesis was tested using deoxymyoglobin (MbFeII) to trap the expected HNO released from the target reaction, which should generate the stable HNO adduct, HNO-Mb, under anaerobic conditions. Under numerous experimental conditions, the sole globin product was NO-Mb, as characterized by absorbance, EPR, and NMR spectroscopies. Analogous reactions of GSNO with other biological reductants such as ascorbic acid, dithiothreitol, glutathione, and dithionite also yielded NO-Mb as the sole globin product; however, whereas analogous reduction of GSNO using NaBH4 generates HNO-Mb in high yield. Quantitative GC/MS analyses of reactions of GS15NO with H2S showed that the main reaction product was 15NO, with 15N2 produced at a comparable level to 15N2O. Overall yield of N2O is unchanged by the presence of MbFeII, discounting the intermediacy of either NO or HNO in its formation. Taken together, these results argue against the generation of free HNO as a major pathway in the reactions of GSNO with H2S, and instead imply some as yet uncharacterized intermediates generate the nitrogenic gases.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Óxidos de Nitrogênio/metabolismo , Óxido Nitroso/metabolismo , S-Nitrosoglutationa/metabolismo , Animais , Cavalos , Humanos , Sulfeto de Hidrogênio/química , Mioglobina/metabolismo , Óxido Nítrico/química , Óxidos de Nitrogênio/química , Óxido Nitroso/química , S-Nitrosoglutationa/química
12.
Bioorg Med Chem ; 26(4): 957-969, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28919180

RESUMO

Synthetic modification of cyclosporin A at P3-P4 positions led to the discovery of NIM258, a next generation cyclophilin inhibitor with excellent anti-hepatitis C virus potency, with decreased transporter inhibition, and pharmacokinetics suitable for coadministration with other drugs. Herein is disclosed the evolution of the synthetic strategy to from the original medicinal chemistry route, designed for late diversification, to a convergent and robust development synthesis. The chiral centers in the P4 fragment were constructed by an asymmetric chelated Claisen rearrangement in the presence of quinidine as the chiral ligand. Identification of advanced crystalline intermediates enabled practical supply of key intermediates. Finally, macrocyclization was carried out at 10% weight concentration by a general and unconventional "slow release" concept.


Assuntos
Antivirais/química , Ciclosporina/química , Hepacivirus/fisiologia , Antivirais/síntese química , Antivirais/farmacologia , Ciclização , Ciclosporina/síntese química , Ciclosporina/farmacologia , Dipeptídeos/síntese química , Dipeptídeos/química , Desenho de Fármacos , Quinidina/química , Estereoisomerismo , Replicação Viral/efeitos dos fármacos
14.
Anal Chem ; 89(9): 4838-4846, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28365979

RESUMO

In April 2016, the Food and Drug Administration approved the first biosimilar monoclonal antibody (mAb), Inflectra/Remsima (Celltrion), based off the original product Remicade (infliximab, Janssen). Biosimilars promise significant cost savings for patients, but the unavoidable differences between innovator and copycat biologics raise questions regarding product interchangeability. In this study, Remicade and Remsima were examined by native mass spectrometry, ion mobility, and quantitative peptide mapping. The levels of oxidation, deamidation, and mutation of individual amino acids were remarkably similar. We found different levels of C-terminal truncation, soluble protein aggregates, and glycation that all likely have a limited clinical impact. Importantly, we identified more than 25 glycoforms for each product and observed glycoform population differences, with afucosylated glycans accounting for 19.7% of Remicade and 13.2% of Remsima glycoforms, which translated into a 2-fold reduction in the level of FcγIIIa receptor binding for Remsima. While this difference was acknowledged in Remsima regulatory filings, our glycoform analysis and receptor binding results appear to be somewhat different from the published values, likely because of methodological differences between laboratories and improved glycoform identification by our laboratory using a peptide map-based method. Our mass spectrometry-based analysis provides rapid and robust analytical information vital for biosimilar development. We have demonstrated the utility of our multiple-attribute monitoring workflow using the model mAbs Remicade and Remsima and have provided a template for analysis of future mAb biosimilars.


Assuntos
Anticorpos Monoclonais/química , Medicamentos Biossimilares/química , Infliximab/química , Cromatografia em Gel , Glicosilação , Interferometria , Espectrometria de Massas/métodos , Mapeamento de Peptídeos
15.
J Am Chem Soc ; 137(34): 10922-10925, 2015 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-26280087

RESUMO

We report unexpected mass spectrometric observations of glycosylated human leukocyte antigen (HLA) class I-bound peptides. Complemented by molecular modeling, in vitro enzymatic assays, and oxonium ion patterns, we propose that the observed O-linked glycans carrying up to five monosaccharides are extended O-GlcNAc's rather than GalNAc-initiated O-glycans. A cytosolic O-GlcNAc modification is normally terminal and does not extend to produce a polysaccharide, but O-GlcNAc on an HLA peptide presents a special case because the loaded HLA class I complex traffics through the endoplasmic reticulum and Golgi apparatus on its way to the cell membrane and is hence exposed to glycosyltransferases. We also report for the first time natural HLA class I presentation of O- and N-linked glycopeptides derived from membrane proteins. HLA class I peptides with centrally located oligosaccharides have been shown to be immunogenic and may thus be important targets for immune surveillance.


Assuntos
Acetilglucosamina/química , Antígenos de Histocompatibilidade Classe I/química , Peptídeos/química , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Modelos Moleculares , Peptídeos/metabolismo
16.
Nat Methods ; 8(8): 691-6, 2011 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-21743460

RESUMO

The protein ubiquitin is an important post-translational modifier that regulates a wide variety of biological processes. In cells, ubiquitin is apportioned among distinct pools, which include a variety of free and conjugated species. Although maintenance of a dynamic and complex equilibrium among ubiquitin pools is crucial for cell survival, the tools necessary to quantify each cellular ubiquitin pool have been limited. We have developed a quantitative mass spectrometry approach to measure cellular concentrations of ubiquitin species using isotope-labeled protein standards and applied it to characterize ubiquitin pools in cells and tissues. Our method is convenient, adaptable and should be a valuable tool to facilitate our understanding of this important signaling molecule.


Assuntos
Marcação por Isótopo/métodos , Espectrometria de Massas/métodos , Espectrometria de Massas/normas , Frações Subcelulares/metabolismo , Ubiquitina/metabolismo , Animais , Humanos , Estados Unidos
17.
Neurology ; 102(2): e207960, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38165320

RESUMO

BACKGROUND AND OBJECTIVES: During acute hospitalizations, physicians often focus on the stroke patient and not family who may be traumatized by this sudden change to their loved one. We investigated long-term psychological distress among family surrogate decision makers for Mexican American (MA) and non-Hispanic White (NHW) severe stroke patients. Previous work in other diseases suggested worse psychological outcomes in MA than NHW caregivers. METHODS: This was a population-based, prospective cohort study in Nueces County, TX. Stroke patient participants and their surrogate decision makers were enrolled soon after any stroke between April, 2016, and October, 2020, if surrogates had made decisions about life-sustaining treatments. Surrogates completed validated measures of posttraumatic stress, National Stressful Events Survey for Posttraumatic Stress Disorder Short Scale; anxiety, Generalized Anxiety Disorder-7; and depression, Patient Health Questionnaire-8 at discharge, 3, 6, and 12 months. Ethnic differences were assessed with multilevel linear mixed models, sequentially adjusted for prespecified patient and surrogate demographic, socioeconomic, and clinical covariates. RESULTS: There were 301 family surrogates for 241 severe stroke patients. The mean follow-up was 315 days. High scores on measures of psychological distress ranged between 17% and 28% of surrogates. One or more high levels of the psychological outcomes were found in 17%-43% of surrogates; 2 or more were found in 12%-27%; and all 3 were found in 5%-16% of surrogates. All psychological outcomes were worse among MAs on unadjusted analyses. In fully adjusted models, posttraumatic stress remained worse among MAs (0.36, 95% CI 0.17-0.56); ethnic differences were attenuated and no longer significant in the final model for anxiety (0.59, 95% CI -0.55 to 1.74) and depression (0.97, 95% CI -0.25 to 2.19). The trajectory for depression did differ by ethnicity (interaction p = 0.03), with depression score improving more rapidly over time among NHWs than MAs. Advance care plans did not seem to confound any ethnic differences. DISCUSSION: Psychological distress is common among family surrogate decision makers in the year after stroke and may be worse among MAs. Efforts are needed to support family members of all ethnic groups after severe stroke.


Assuntos
Cuidadores , Angústia Psicológica , Acidente Vascular Cerebral , Humanos , Tomada de Decisões , Etnicidade , Americanos Mexicanos , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Brancos , Cuidadores/psicologia
18.
Orthop Traumatol Surg Res ; 110(3): 103797, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38142779

RESUMO

BACKGROUND: The current rise in elderly patients with compromised bone quality complicates the surgical treatment of acetabular T-type fractures (AO type 62B2 fractures). There is on ongoing discussion about the treatment options, mostly consisting of an open reduction and internal fixation (ORIF) with or without primary or secondary total hip arthroplasty (THA). Yet, these patients are oftentimes unable to fulfil weight-bearing restrictions and mostly present with an unavailability of a stable anchor site. Consequently, this study investigates the feasibility of a cementless hip revision cup for acetabular T-type fractures and compares its biomechanical properties to ORIF. HYPOTHESIS: The cementless hip revision cup provides sufficient biomechanical stability under the simulation of full weight-bearing. PATIENTS AND METHODS: The study compared two groups of human cadaveric hip bones with T-type fractures, of whom 6 subjects were treated with ORIF (6 male; mean age: 62±17years; mean body weight: 75±15) versus 6 subjects treated with a cementless hip revision cup (2 male; 69±12 years; 73±15kg). The group-assignment was controlled for comparable BMD results (mean BMD: ORIF 110±37 mg Ca-Ha/mL versus hip revision cup 134±32 mg Ca-Ha/mL). To compare for biomechanical stability cyclic loading was applied measuring the force and dislocation of the fracture gap at standardized bone loci using an all-electric testing machine and a 3D-ultrasound measuring system. RESULTS: Comparing superior pubic ramus versus iliac wing (cementless hip revision cup versus ORIF [mean±standard deviation]: 5.8±2.0 versus 7.0±3.2; p=0.032) as well as sacral ala versus iliac wing (4.6±2.2 versus 6.4±3.7; p=0.002), the cementless revision cup achieved a significantly higher stability than the plate osteosynthesis. CONCLUSION: Revision cup and ORIF withstood biomechanical loading forces exceeding full weight-bearing in this biomechanical study. The results of our study suggest that the cementless hip revision cup might be promising alternative to the current standard care of ORIF with or without primary THA. LEVEL OF EVIDENCE: III; case control experimental study.


Assuntos
Acetábulo , Artroplastia de Quadril , Cadáver , Prótese de Quadril , Humanos , Acetábulo/cirurgia , Acetábulo/lesões , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Artroplastia de Quadril/métodos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Desenho de Prótese , Reoperação , Fenômenos Biomecânicos , Suporte de Carga , Fraturas Ósseas/cirurgia , Idoso de 80 Anos ou mais
19.
Neurology ; 102(11): e209423, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38759136

RESUMO

BACKGROUND AND OBJECTIVES: Poverty is associated with greater stroke incidence. The relationship between poverty and stroke recurrence is less clear. METHODS: In this population-based study, incident strokes within the Greater Cincinnati/Northern Kentucky region were ascertained during the 2015 study period and followed up for recurrence until December 31, 2018. The primary exposure was neighborhood socioeconomic status (nSES), defined by the percentage of households below the federal poverty line in each census tract in 4 categories (≤5%, >5%-10%, >10%-25%, >25%). Poisson regression models provided recurrence rate estimates per 100,000 residents using population data from the 2015 5-year American Community Survey, adjusting for age, sex, and race. In a secondary analysis, Cox models allowed for the inclusion of vascular risk factors in the assessment of recurrence risk by nSES among those with incident stroke. RESULTS: Of 2,125 patients with incident stroke, 245 had a recurrent stroke during the study period. Poorer nSES was associated with increased stroke recurrence, with rates of 12.5, 17.5, 25.4, and 29.9 per 100,000 in census tracts with ≤5%, >5%-10%, >10%-25%, and >25% below the poverty line, respectively (p < 0.01). The relative risk (95% CI) for recurrent stroke among Black vs White individuals was 2.54 (1.91-3.37) before adjusting for nSES, and 2.00 (1.47-2.74) after adjusting for nSES, a 35.1% decrease. In the secondary analysis, poorer nSES (HR 1.74, 95% CI 1.10-2.76 for lowest vs highest category) and Black race (HR 1.31, 95% CI 1.01-1.70) were both independently associated with recurrence risk, though neither retained significance after full adjustment. Age, diabetes, and left ventricular hypertrophy were associated with increased recurrence risk in fully adjusted models. DISCUSSION: Residents of poorer neighborhoods had a dose-dependent increase in stroke recurrence risk, and neighborhood poverty accounted for approximately one-third of the excess risk among Black individuals. These results highlight the importance of poverty, race, and the intersection of the 2 as potent drivers of stroke recurrence.


Assuntos
Pobreza , Recidiva , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pobreza/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/economia , Idoso , Pessoa de Meia-Idade , Kentucky/epidemiologia , Fatores de Risco , Classe Social , Idoso de 80 Anos ou mais , Incidência , Ohio/epidemiologia
20.
Ann Neurol ; 71(5): 601-13, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22473675

RESUMO

Cerebrospinal fluid samples collected from children during initial presentation of central nervous system inflammation, who may or may not subsequently be diagnosed as having multiple sclerosis (MS), were subjected to large-scale proteomics screening. Unexpectedly, major compact myelin membrane proteins typically implicated in MS were not detected. However, multiple molecules that localize to the node of Ranvier and the surrounding axoglial apparatus membrane were implicated, indicating perturbed axon-glial interactions in those children destined for diagnosis of MS.


Assuntos
Axônios/metabolismo , Biomarcadores/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Proteínas do Tecido Nervoso/líquido cefalorraquidiano , Neuroglia/metabolismo , Autoantígenos/líquido cefalorraquidiano , Axônios/patologia , Criança , Diagnóstico Precoce , Feminino , Humanos , Immunoblotting , Masculino , Espectrometria de Massas , Esclerose Múltipla/patologia , Proteínas da Mielina/líquido cefalorraquidiano , Neuroglia/patologia , Nós Neurofibrosos/metabolismo , Nós Neurofibrosos/patologia
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa