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1.
Recent Results Cancer Res ; 214: 129-151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473851

RESUMO

The adoptive cell transfer (ACT) of genetically engineered T cell receptor (TCR) T cells is one of the burgeoning fields of immunotherapy, with promising results in current clinical trials. Presently, clinicaltrials.gov has over 200 active trials involving adoptive cell therapy. The ACT of genetically engineered T cells not only allows the ability to select for TCRs with desired properties such as high-affinity receptors and tumor reactivity but to further enhance those receptors allowing for better targeting and killing of cancer cells in patients. Moreover, the addition of genetic material, including cytokines and cytokine receptors, can increase the survival and persistence of the T cell allowing for complete and sustained remission of cancer targets. The potential for improvement in adoptive cell therapy is limitless, with genetic modifications targeting to improve weaknesses of ACT and to thus enhance receptor affinity and functional avidity of the genetically engineered T cells.


Assuntos
Engenharia Genética , Imunoterapia , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T , Linfócitos T/citologia , Humanos
2.
Artigo em Inglês | MEDLINE | ID: mdl-31638326

RESUMO

A transseptal puncture is critical for "left-sided" structural heart interventions. Procedures such as transcatheter edge-to-edge repair (MitraClip) and left atrial appendage (LAA) closure (Watchman) require precise puncture of the interatrial septum (IAS), and the presence of a prior atrial septal defect (ASD) closure device poses a challenge. We aim to present a successfully completed case of MitraClip and Watchman in the presence of ASD closure device in two different patients. A review of the literature will be reported, and pertinent clinical and technical considerations will be discussed in depth to achieve procedural success. In summary, transseptal puncture for left heart structural interventions is feasible in the presence of a prior ASD/patent foramen ovale closure device. A detailed understanding of the anatomical considerations as well as the use of multimodality imaging to evaluate the IAS will aid in improving procedural success rates.

3.
Anal Chem ; 91(20): 13096-13104, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525022

RESUMO

We introduce and compare two powerful new techniques for headspace gas analysis above bacterial batch cultures by spectroscopy, Raman spectroscopy enhanced in an optical cavity (CERS), and photoacoustic detection in a differential Helmholtz resonator (DHR). Both techniques are able to monitor O2 and CO2 and its isotopomers with excellent sensitivity and time resolution to characterize bacterial growth and metabolism. We discuss and show some of the shortcomings of more conventional optical density (OD) measurements if used on their own without more sophisticated complementary measurements. The spectroscopic measurements can clearly and unambiguously distinguish the main phases of bacterial growth in the two media studied, LB and M9. We demonstrate how 13C isotopic labeling of sugars combined with spectroscopic detection allows the study of bacterial mixed sugar metabolism to establish whether sugars are sequentially or simultaneously metabolized. For E. coli, we have characterized the shift from glucose to lactose metabolism without a classic diauxic lag phase. DHR and CERS are shown to be cost-effective and highly selective analytical tools in the biosciences and in biotechnology, complementing and superseding existing conventional techniques. They also provide new capabilities for mechanistic investigations and show a great deal of promise for use in stable isotope bioassays.

4.
Ann Hepatol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31543466

RESUMO

Management of symptomatic polycystic liver disease (PLD) has remained primarily unchanged since the early 20th century when multiple case reports described management of non-parasitic liver cysts. In 1968, Lin et al. described the fenestration procedure, "aspiration of the cysts, incision, partial excision with or without external drainage, or marsupilization and anastomosis to the gastrointestinal tract". Further surgical options have included cyst sclerotherapy, laparoscopic cyst aspiration, partial hepatectomy, and orthotopic liver transplant (OLT). Recently there has been discussion of medical management with somatostatin analogs to reduce hepatomegaly in PLD with varying success. There is no current consensus on treatment or standard of care for symptomatic PLD, it is largely up to surgeon preference and ability; however, there has been a movement toward early OLT with Model for End-Stage Liver Disease (MELD) score exception points. This case series reviews two female patients with normal renal and hepatic function with symptomatic PLD treated with transverse hepatectomy. We propose that patients suffering from symptomatic PLD, with retained renal and hepatic function, can be treated with transverse hepatectomy conserving limited donor livers for decompensated patients; moreover, transverse hepatectomy does not disrupt the major suprahepatic vena cava preserving potential surgical access for future OLT.

5.
JACC Cardiovasc Interv ; 12(11): 1018-1026, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31171276

RESUMO

OBJECTIVES: This study sought to compare patients with and without long-standing persistent atrial fibrillation (LSPAF) undergoing Watchman left atrial appendage (LAA) occlusion. BACKGROUND: An increased burden of atrial fibrillation is associated with progressive left atrial remodeling and enlargement. METHODS: Transesophageal echocardiography (TEE) measures of LAA ostial diameter and depth, device compression, and residual leak were evaluated in 101 consecutive Watchman cases. The patients were categorized into LSPAF (n = 48) or non-LSPAF (n = 53) groups and compared. RESULTS: The average LAA ostial diameter for LSPAF versus non-LSPAF by TEE omniplane at 0° was 21.1 ± 4.1 mm versus 18.2 ± 3.6 mm (p = 0.0002); at 45° was 18.7 ± 3.4 mm versus 16.3 ± 3.1 mm (p = 0.0004); at 90° was 19.6 ± 3.8 mm versus 16.2 ± 3.4 mm (p = 0.00001); and at 135° was 21.0 ± 4.1 mm versus 18.0 ± 4.1 mm (p = 0.0005). The average LAA depth for LSPAF versus non-LSPAF by TEE at 0° was 28.1 ± 6.4 mm versus 25.2 ± 4.9 mm (p = 0.02); at 45° was 27.9 ± 5.8 mm versus 25.1 ± 4.3 mm (p = 0.007); at 90° was 27.2 ± 5.2 mm versus 22.8 ± 3.7 mm (p = 0.0001); and at 135° was 25.6 ± 5.4 mm versus 21.5 ± 3.8 mm (p = 0.0001). In successfully treated patients, 77% of the LSPAF group received larger device (27, 30, or 33 mm) implants versus only 46% in the non-LSPAF group (p = 0.003). While both groups had similar rates of moderate (3 to 5 mm) leaks at implant (2% vs. 0%; p = 0.14), 27% of the LSPAF vs. 4% of the non-LSPAF group had moderate leaks (p = 0.04) on 6-week follow-up TEE. CONCLUSIONS: Patients with LSPAF have significantly larger LAA sizes, require larger devices, and have more residual leak on follow-up TEE. LSPAF may represent a higher risk group that warrants more stringent long-term follow-up.

6.
Interv Cardiol Clin ; 8(3): 261-267, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31078181

RESUMO

Mitral valve ring annuloplasty is a surgical gold standard and is used routinely during surgical mitral valve repair of primary or secondary mitral regurgitation. The Millipede IRIS annuloplasty ring is the first transcatheter, transfemoral, transseptal, semirigid, complete annuloplasty ring to be delivered to the mitral valve annulus. Initial results in humans demonstrate that the Millipede IRIS ring is safe, and can effectively reduce the mitral annular diameter leading to a clinically significant reduction or elimination of mitral regurgitation.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31001927

RESUMO

OBJECTIVES: Review indications and outcomes for transcatheter iatrogenic atrial septal defect (iASD) closure in patients undergoing MitraClip or transseptal (TS) mitral valve-in-valve/ring (ViV/ViR) procedures. BACKGROUND: Mitral valve transcatheter interventions require large-diameter TS sheaths that can result in iASDs that necessitate post-procedure transcatheter closure. Although the presence of iASD has been well-described, indications for closure and outcomes after TS mitral valve interventions have not been reported. METHODS: Patients undergoing MitraClip repair and ViV or ViR transcatheter mitral valve replacement (TMVR) from February 14, 2014, to January 16, 2018, were studied retrospectively in this single center study. RESULTS: Seventeen patients had iASD closure: 11 MitraClip and 6 TMVR (5 ViV, 1 ViR). Indications for iASD closure included large iASD (n = 7), large left-to-right shunt (n = 9), pulmonary hypertension (n = 8), large right-to-left shunt (n = 1), severe RV dysfunction (n = 2), thin/aneurysmal septum (n = 2), and mobile material on pacemaker leads (n = 2). Closures were performed without complications using Amplatzer septal occluders. At 30 days, 94% of subjects (n = 16) were alive with one patient deceased from unknown causes. There were no myocardial infarctions or strokes. At 12 months, follow-up was available for 14 of 17 patients, and 71% of patients (10/14) were alive. One patient died due to cardiac causes, two from noncardiac causes and one for unknown reasons. There was one myocardial infarction, one intraparenchymal hemorrhage, and no ischemic strokes. CONCLUSIONS: The most common reasons for iASD closure after TS MV procedures are: large ASD unlikely to spontaneously close, large left-to-right shunt, and pulmonary hypertension. Patients who required iASD closure had low 30-day mortality but higher one-year mortality potentially reflecting a population with substantial comorbidities.

8.
J Echocardiogr ; 17(2): 53-63, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30771213

RESUMO

Percutaneous intervention for mitral valve disease has been established as an alternative to open surgical repair in high risk and inoperable candidates. Edge-to-edge leaflet plication with Mitraclip (Abbott, Menlo Park, CA, USA) is indicated for primary and secondary mitral valve diseases. Echocardiography provides a better understanding of mitral valve anatomy and allows us to classify and quantify mitral regurgitation. Transesophageal echocardiography is essential in patient screening, intraprocedural guidance, and post-procedure evaluation for patients undergoing edge-to-edge plication with MitraClip.

9.
Catheter Cardiovasc Interv ; 94(1): 165-170, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30588751

RESUMO

OBJECTIVES: This study investigates the correlation of occlusive wedge pressure (WP) with direct left atrial (LA) pressure in patients with severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVr) with MitraClip. BACKGROUND: There is interest in acquiring objective hemodynamic parameters for intraprocedural guidance in patients undergoing MitraClip. METHODS: The study included 94 patients with severe MR at prohibitive surgical risk who underwent MitraClip at the University of California Davis Medical Center between 2014 and 2016. RESULTS: An average of 1.8 ± 0.7 clips were used to achieve MR grade of 2+ or less in 99% of patients. Correlation analysis of all (n = 236) pre-clip, inter-clip, and final-clip WP and LA pressures yielded a Pearson's R (r) of 0.85 and 0.79 for mean WP vs mean LA and WP V vs LA V, respectively. Median LA V to mean LA ratio (LAV:mLA) was 1.75 (IQR 1.5-1.9). 79% (n = 74) of patients had LAV:mLA ratio ≥ 1.5 with associated WP V vs LA V correlation (r) of 0.83. In patients with LAV:mLA ratio < 1.5, the correlation (r) was 0.69. Baseline characteristics were not significantly different between patients with LAV:mLA ratio ≥ 1.5 and patients with LAV:mLA ratio < 1.5. Post-procedure, median LA V: mean LA ratio decreased from 1.75 to 1.4, P = 0.0001. CONCLUSIONS: Correlation between WP and direct LA pressure in patients with severe MR undergoing Mitraclip is modest. Caution is advised when using WP to approximate LA pressure intraprocedurally, especially in patients with baseline low LAV:mLA ratios.

10.
Artigo em Inglês | MEDLINE | ID: mdl-30311343

RESUMO

OBJECTIVES: To compare left atrial appendage (LAA) angiography to transesophageal echocardiography (TEE) for assessing usable LAA depth. BACKGROUND: TEE is typically employed for procedural measurement of LAA ostial diameter and depth. Since angiography enhances distal LAA anatomy, we sought to compare angiography to TEE for determining usable LAA depth. METHODS: Seventy five Watchman device cases were retrospectively evaluated. Two independent cardiologists measured intraoperative LAA ostial diameter and depth at standard 0°, 45°, 90°, and 135° TEE omniplane views and in the right anterior oblique (RAO) 30°, caudal (CAUD) 30° angiographic view. RESULTS: The average age and CHA2 DS2 VASc score were 74 (±7.2) years and 4.6 (±1.3), respectively. The average ostial diameter and depth (mm) by TEE were 0°: 19.6 and 26.5; 45°: 17.5 and 26.6; 90°: 18.3 and 25.1; 135°: 19.5 and 23.3. The ostial diameter and depth (mm) by RAO 30° CAUD 30° angiography were 21.1 and 29.7. This angiographic view corresponds to a TEE view between 90° and 135°. In comparison to angiography, TEE 90° underestimated the LAA ostial diameter by 2.9 ± 3.7 mm (P < 0.001) and by 1.9 ± 4.0 mm at TEE 135° (P < 0.01); Pearson's r 0.53 angiography/TEE 90° and 0.50 angiography/TEE 135°. More importantly, TEE 90° underestimated the true usable LAA depth by 5.4 ± 5.8 mm (P < 0.001) and by 7.3 ± 6.1 mm at TEE 135° (P < 0.001); Pearson's r 0.39 angiography/TEE 90° and 0.30 angiography/TEE 135°. CONCLUSIONS: Compared to TEE, LAA angiography provides additional depth information and may be particularly valuable when patients have insufficient depth for Watchman by TEE measures.

11.
Catheter Cardiovasc Interv ; 92(4): 792-796, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30019833

RESUMO

OBJECTIVES: The purpose of this study is to describe the initial clinical experience with a steerable transseptal needle (STSN) for left-sided structural heart procedures. BACKGROUND: Targeted transseptal (TS) puncture is required for many structural heart procedures, and the use of a steerable needle has not previously been described. METHODS: Consecutive patients undergoing structural heart interventions with targeted TS puncture under transesophageal echocardiographic (TEE) and fluoroscopic guidance were studied. The STSN was used in all patients with a standard commercial TS sheath. Deflection of the needle was performed "real time" to achieve localization of the TS puncture site. RESULTS: Twenty-seven patients underwent STSN puncture of the interatrial septum. In all cases, the needle could be deflected in vivo to achieve optimal tenting and localization of the puncture site without having to remove or reshape the needle. The needle was deflected to match a wide range of right atrial diameters (width 4.3 ± 0.9 cm and length 6.0 ± 0.9 cm in the 4-chamber view). In two patients with prior mitral valve surgery and a fibrotic septum, assisted crossing was achieved using the piercing stylet in one patient, and Bovie energy in the other. There were no procedural complications, and all patients had successful completion of the intended structural heart procedure. CONCLUSIONS: The STSN needle can be used to target the intended puncture location on the interatrial septum with real-time adjustable deflection without the need to remove and reshape the needle. In all cases crossing was successful and there were no complications.

12.
Redox Biol ; 18: 114-123, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30007887

RESUMO

Carbon monoxide (CO)-releasing molecules (CORMs), mostly metal carbonyl compounds, are extensively used as experimental tools to deliver CO, a biological 'gasotransmitter', in mammalian systems. CORMs are also explored as potential novel antimicrobial drugs, effectively and rapidly killing bacteria in vitro and in animal models, but are reportedly benign towards mammalian cells. Ru-carbonyl CORMs, exemplified by CORM-3 (Ru(CO)3Cl(glycinate)), exhibit the most potent antimicrobial effects against Escherichia coli. We demonstrate that CORM-3 releases little CO in buffers and cell culture media and that the active antimicrobial agent is Ru(II), which binds tightly to thiols. Thus, thiols and amino acids in complex growth media - such as histidine, methionine and oxidised glutathione, but most pertinently cysteine and reduced glutathione (GSH) - protect both bacterial and mammalian cells against CORM-3 by binding and sequestering Ru(II). No other amino acids exert significant protective effects. NMR reveals that CORM-3 binds cysteine and GSH in a 1:1 stoichiometry with dissociation constants, Kd, of about 5 µM, while histidine, GSSG and methionine are bound less tightly, with Kd values ranging between 800 and 9000 µM. There is a direct positive correlation between protection and amino acid affinity for CORM-3. Intracellular targets of CORM-3 in both bacterial and mammalian cells are therefore expected to include GSH, free Cys, His and Met residues and any molecules that contain these surface-exposed amino acids. These results necessitate a major reappraisal of the biological effects of CORM-3 and related CORMs.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Monóxido de Carbono/farmacologia , Escherichia coli/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Rutênio/farmacologia , Antibacterianos/química , Antineoplásicos/química , Monóxido de Carbono/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Neoplasias/tratamento farmacológico , Compostos Organometálicos/química , Rutênio/química
13.
Respir Med ; 137: 55-60, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29605213

RESUMO

BACKGROUND: Interstitial lung abnormality (ILA) is found in 5-10% of the general population and is associated with increased mortality risk. Risk factors for ILA, including advanced age and smoking history also increase the risk for aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become an increasingly utilized intervention for patients with severe AS, and requires a high-resolution computed tomography (HRCT) of the chest to assess aortic valve dimensions. OBJECTIVES: To determine the prevalence and clinical significance of ILA on HRCT performed in patients referred for TAVR. METHODS: Consecutive pre-TAVR HRCTs performed over a 5-year period were reviewed. ILA was defined as bilateral, nondependent reticular opacities. All-cause mortality among TAVR recipients was compared between ILA cases and non-ILA controls matched 2:1 by age and gender using Cox proportional hazards regression and the Kaplan Meier estimator. RESULTS: Of 623 HRCTs screened, ILA was detected in 92 (14.7%), including 62 patients that underwent TAVR. Among ILA cases, 17 (27.4%) had a typical or probable usual interstitial pneumonia pattern, suggesting a diagnosis of idiopathic pulmonary fibrosis. Survival was worse in ILA cases compared to non-ILA controls (p = 0.008) and ILA was an independent predictor of mortality after multivariable adjustment (HR 3.29, 95% CI 1.34-8.08; p = 0.009). CONCLUSIONS: ILA is a common finding among patients with severe AS and is associated with increased mortality in those undergoing TAVR. Further research is needed to elucidate the biology underpinning this observation and determine whether ILA evaluation and risk stratification modulates this mortality risk.

14.
Mol Ther ; 26(4): 996-1007, 2018 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-29503203

RESUMO

The use of T cell receptor (TCR) gene-modified T cells in adoptive cell transfer has had promising clinical success, but often, simple preclinical evaluation does not necessarily accurately predict treatment efficacy or safety. Preclinical studies generally evaluate one or a limited number of type 1 cytokines to assess antigen recognition. However, recent studies have implicated other "typed" T cells in effective anti-tumor/viral immunity, and limited functional evaluations may underestimate cross-reactivity. In this study, we use an altered peptide ligand (APL) model and multi-dimensional flow cytometry to evaluate polyfunctionality of TCR gene-modified T cells. Evaluating six cytokines and the lytic marker CD107a on a per cell basis revealed remarkably diverse polyfunctional phenotypes within a single T cell culture and among peripheral blood lymphocyte (PBL) donors. This polyfunctional assessment identified unexpected phenotypes, including cells producing both type 1 and type 2 cytokines, and highlighted interferon γneg (IFNγneg) antigen-reactive populations overlooked in our previous studies. Additionally, APLs skewed functional phenotypes to be less polyfunctional, which was not necessarily related to changes in TCR-peptide-major histocompatibility complex (pMHC) affinity. A better understanding of gene-modified T cell functional diversity may help identify optimal therapeutic phenotypes, predict clinical responses, anticipate off-target recognition, and improve the design and delivery of TCR gene-modified T cells.

16.
J Am Soc Echocardiogr ; 31(4): 434-453, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29482977

RESUMO

Percutaneous intervention for mitral valve (MV) disease has been established as an alternative to open surgical MV repair in patients with prohibitive surgical risk. Multiple percutaneous approaches have been described and are in various stages of development. Edge-to-edge leaflet plication with the MitraClip (Abbott, Menlo Park, CA) is currently the only Food and Drug Administration-approved device specifically for primary or degenerative lesions. Use of the edge-to-edge clip for secondary mitral regurgitation is currently under investigation and may result in expanded indications. Echocardiography has significantly increased our understanding of the anatomy of the MV and provided us with the ability to classify and quantify the associated mitral regurgitation. For percutaneous interventions of the MV, transesophageal echocardiography imaging is used for patient screening, intraprocedural guidance, and confirmation of the result. Optimal outcomes require the echocardiographer and the proceduralist to have a thorough understanding of intra-atrial septal and MV anatomy, as well as an appreciation for the key points and potential pitfalls of each of the procedural steps. With increasing experience, more complex valvular pathology can be successfully percutaneously treated. In addition to two-dimensional echocardiography, advances in three-dimensional echocardiography and fusion imaging will continue to support the refinement of current technologies, the expansion of clinical applications, and the development of novel devices.

18.
Catheter Cardiovasc Interv ; 91(6): 1159-1163, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28944572

RESUMO

OBJECTIVES: To describe a novel balloon sizing technique used during adult transcatheter patent ductus arteriosus (PDA) closure. In addition, to determine the clinical and procedural outcomes in six patients who underwent PDA balloon sizing with subsequent deployment of a PDA occluder device. BACKGROUND: Transcatheter PDA closure in adults has excellent safety and procedural outcomes. However, PDA sizing in adults can be challenging due to variable defect size, high flow state, or anatomical complexity. We describe a series of six cases where the balloon- pull through technique was successfully performed for PDA sizing prior to transcatheter closure. METHODS: Consecutive adult patients undergoing adult PDA closure at our institution were studied retrospectively. A partially inflated sizing balloon was pulled through the defect from the aorta into the pulmonary artery and the balloon waist diameter was measured. Procedural success and clinical outcomes were obtained. RESULTS: Six adult patients underwent successful balloon pull-through technique for PDA sizing during transcatheter PDA closure, since conventional angiography often gave suboptimal opacification of the defect. All PDAs were treated with closure devices based on balloon PDA sizing with complete closure and no complications. In three patients that underwent preprocedure computed tomography, the balloon size matched the CT derived measurements. CONCLUSION: The balloon pull-through technique for PDA sizing is a safe and accurate sizing modality in adults undergoing transcatheter PDA closure.

20.
Alzheimers Dement ; 13(12): 1389-1396, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28627379

RESUMO

INTRODUCTION: The mechanism triggering degeneration in Alzheimer's disease (AD) remains uncertain. Therapeutic failure following amyloid ß (Aß) removal casts doubt on amyloid neurotoxicity per se as the primary cause of AD. Impaired microvascular function has been suggested as an alternative etiology. People with Down syndrome (DS) develop Alzheimer's pathology, but whether microvascular impairment also occurs in DS (as in AD) is unknown. METHODS: We examined brain microvasculature in five DS subjects with AD-type histopathology, seven AD cases, and seven controls without AD-type pathology. We counted microvessels in five anatomic regions and assessed endothelial integrity by CD31 immunohistochemistry. RESULTS: Microvascular numbers and endothelial integrity were significantly diminished in DS brains compared with controls and were similar to AD brains. DISCUSSION: People with DS and trisomy 21 produce a large amount of Aß. If Alzheimer's pathology occurred in DS without microvascular loss or endothelial impairment, a direct neurotoxic Aß mechanism would be supported and microvascular impairment rejected. The observation of microvascular impairment in DS with Alzheimer's disease changes fails to reject the microvascular hypothesis and provides some support for this potential mechanism of injury.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Síndrome de Down/patologia , Microvasos/patologia , Adulto , Idoso , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/metabolismo , Síndrome de Down/complicações , Feminino , Humanos , Masculino , Microvasos/metabolismo , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo
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