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1.
Curr Opin Pediatr ; 36(1): 105-111, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37991009

RESUMEN

PURPOSE OF REVIEW: The aim of this review is to provide the reader with the most updated available information so that it can be helpful in the approach of patients with early-onset scoliosis (EOS). RECENT FINDINGS: While confirming the efficacy and safety of classic techniques for the treatment of EOS such as traditional growing rods or Mehta casting, recent research suggests that there is room for improvement with less invasive techniques. SUMMARY: The most important goal when treating patients with EOS should be to promote rib cage expansion and lung development. Different techniques have been described and may be used depending on the specific patient's characteristics.


Asunto(s)
Procedimientos Ortopédicos , Escoliosis , Humanos , Escoliosis/terapia , Escoliosis/cirugía , Procedimientos Ortopédicos/métodos , Estudios Retrospectivos , Resultado del Tratamiento
2.
Curr Opin Pediatr ; 34(1): 71-75, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34845153

RESUMEN

PURPOSE OF REVIEW: The aim of this study was to review the most recent available evidence about lateral-extra articular tenodesis (LET) and anterolateral ligament (ALL) reconstruction in young patients treated for anterior cruciate ligament (ACL) injury. RECENT FINDINGS: The ALL of the knee acts as a secondary stabilizer of the knee preventing anterior translation and internal rotation. In vitro and in vivo biomechanical studies as well as prospective clinical trials have shown the importance of the ALL in knee biomechanics. The ALL injury has a synergetic impact on the knee stability in patients with acute ACL injury. ALL augmentation of ACL provides reduction of knee instability and graft failure and higher return to sport rates in high-risk patients. It has not been demonstrated that extra-articular procedures increase the risk of knee osteoarthritis secondary to knee over-constriction. Both Iliotibial band (ITB) ALL reconstruction and modified Lemaire LET have been shown safe and effective. Minimal biomechanical or clinical differences have been found between the two reconstruction methods. SUMMARY: Young patients with ACL tears and risk factors such as laxity or pivot shift willing to return to sports may benefit from ALL augmentation. Therefore, it is essential to identify these high-risk patients to individualize treatment.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Inestabilidad de la Articulación , Tenodesis , Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/métodos , Fenómenos Biomecánicos , Cadáver , Humanos , Inestabilidad de la Articulación/etiología , Inestabilidad de la Articulación/prevención & control , Inestabilidad de la Articulación/cirugía , Articulación de la Rodilla/cirugía , Ligamentos/cirugía , Estudios Prospectivos , Rango del Movimiento Articular , Tenodesis/métodos
3.
Rev Panam Salud Publica ; 46: e207, 2022.
Artículo en Español | MEDLINE | ID: mdl-36519067

RESUMEN

Objective: To develop a tool that measures levels of adherence to antiretroviral treatment (ART) in resource-poor settings, based on a combination of four methods for measuring adherence. Methods: Retrospective review of 500 medical records of people living with HIV, randomly selected from October 2017 to January 2020. Adherence to ART was measured by combining four measurement methods (coverage of prescribed ART, ART picked up at pharmacies, viral load, and self-reported adherence). Chi-squared tests were performed with p<0.05 for statistically significant differences and logistic binary regression to identify the probability of optimal and suboptimal adherence. Spearman tests were performed for correlation of categories, and Cronbach's alpha was used to measure the internal consistency of the tool. Results: We obtained 497 adherence scores. Of these, 307 (61.8%) users qualified as adherent, 141 (28.4%) as semi-adherent, and 49 (9.8%) as non-adherent. A higher probability of optimal adherence was found in groups aged 60 years and older (odds ratio [OR]: 1.6; CI95%: 0.8-3.5), with no difference between men and women (OR: 0.9; CI95%: 0.7-1.4). Spearman's test reported a relationship (r = 0.8) between viral load levels and final score, and Cronbach's alpha yielded modest internal consistency (α = 0.7). Conclusions: A tool was developed to measure adherence to ART in a resource-poor environment. The tool shows modest levels of internal consistency and a strong correlation between viral load and adherence.


Objetivo: Desenvolver uma ferramenta para medir os níveis de adesão à terapia antirretroviral (TARV) em um ambiente de poucos recursos, com base na combinação de quatro métodos de medição de adesão. Métodos: Revisão retrospectiva de 500 prontuários de pessoas que vivem com HIV, selecionadas aleatoriamente de outubro de 2017 a janeiro de 2020. A adesão à TARV foi medida pela combinação de quatro métodos (porcentagem de cobertura da TARV prescrita, coleta de TARV na farmácia, nível de carga viral e adesão autorrelatada). Foram realizados testes de qui-quadrado com P < 0,05 para diferenças estatisticamente significativas e regressão logística binária para identificar probabilidades de adesão ótima e subótima. Foram realizados testes de Spearman para a correlação de categorias e alfa de Cronbach para medir a consistência interna do instrumento. Resultados: Foram obtidos 497 índices de adesão. Entre eles, 307 (61,8%) usuários foram classificados como aderentes, 141 (28,4%) como semiaderentes e 49 (9,8%) como não aderentes. Foi encontrada maior probabilidade de adesão ótima nos grupos de 60 anos ou mais (odds ratio [OR]: 1,6; IC95%: 0,8-3,5), sem diferença entre homens e mulheres (OR: 0,9; IC95%: 0,7-1,4). O teste de Spearman constatou uma relação (r = 0,8) entre os níveis de carga viral e a pontuação final, e o teste alfa de Cronbach mostrou uma consistência interna modesta (α = 0,7). Conclusões: Foi desenvolvida uma ferramenta para medir a adesão em um ambiente de poucos recursos. A ferramenta apresenta níveis modestos de consistência interna e forte correlação de categoria entre carga viral e adesão.

4.
Int J Mol Sci ; 23(13)2022 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-35806197

RESUMEN

Trans-sialidases (TS) are important constitutive macromolecules of the secretome present on the surface of Trypanosoma cruzi (T. cruzi) that play a central role as a virulence factor in Chagas disease. These enzymes have been related to infectivity, escape from immune surveillance and pathogenesis exhibited by this protozoan parasite. In this work, atomic force microscopy (AFM)-based single molecule-force spectroscopy is implemented as a suitable technique for the detection and location of functional TS on the surface of extracellular vesicles (EVs) released by tissue-culture cell-derived trypomastigotes (Ex-TcT). For that purpose, AFM cantilevers with functionalized tips bearing the anti-TS monoclonal antibody mAb 39 as a sense biomolecule are engineered using a covalent chemical ligation based on vinyl sulfonate click chemistry; a reliable, simple and efficient methodology for the molecular recognition of TS using the antibody-antigen interaction. Measurements of the breakdown forces between anti-TS mAb 39 antibodies and EVs performed to elucidate adhesion and forces involved in the recognition events demonstrate that EVs isolated from tissue-culture cell-derived trypomastigotes of T. cruzi are enriched in TS. Additionally, a mapping of the TS binding sites with submicrometer-scale resolution is provided. This work represents the first AFM-based molecular recognition study of Ex-TcT using an antibody-tethered AFM probe.


Asunto(s)
Vesículas Extracelulares , Parásitos , Trypanosoma cruzi , Animales , Vesículas Extracelulares/metabolismo , Glicoproteínas , Microscopía de Fuerza Atómica , Neuraminidasa/metabolismo , Parásitos/metabolismo , Trypanosoma cruzi/metabolismo
5.
Curr Opin Pediatr ; 33(1): 90-96, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33278106

RESUMEN

PURPOSE OF REVIEW: The aim of this article is to review recent findings regarding the diagnosis and treatment of chronic recurrent multifocal osteomyelitis (CRMO). RECENT FINDINGS: An adequate understanding of pathophysiology along with the new advances in MRI imaging make it possible to determine the extent of disease and establish early treatment. TNF-α inhibitors and bisphosphonates have shown to be a well-tolerated and efficient treatment for CRMO providing both symptomatic relief and normalization of bone morphology. SUMMARY: The results of recent studies suggest that a better knowledge of the genetic and molecular factors will allow early diagnosis and the development of more effective individualized treatments in the future.


Asunto(s)
Osteomielitis , Enfermedad Crónica , Difosfonatos , Humanos , Imagen por Resonancia Magnética , Osteomielitis/diagnóstico por imagen , Osteomielitis/terapia , Recurrencia , Inhibidores del Factor de Necrosis Tumoral
6.
Mikrochim Acta ; 187(7): 421, 2020 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-32617684

RESUMEN

A microfluidic paper-based analytical device integrating carbon dot (CDs) is fabricated and used for a fluorometric off-on assay of biothiols. Vinyl sulfone (VS) click immobilization of carbon dots (CDs) on paper was accomplished by a one-pot simplified protocol that uses divinyl sulfone (DVS) as a homobifunctional reagent. This reagent mediated both the click oxa-Michael addition to the hydroxyl groups of cellulose and ulterior covalent grafting of the resulting VS paper to NH2-functionalized CDs by means of click aza-Michael addition. The resulting cellulose nanocomposite was used to engineer an inexpensive and robust microfluidic paper-based analytical device (µPAD) that is used for a reaction-based off-on fluorometric assay of biothiols (GSH, Cys, and Hcy). The intrinsic blue fluorescence of CDs (with excitation/emission maxima at 365/450 nm) is turned off via the heavy atom effect of an introduced iodo group. Fluorescence is turned on again due to the displacement of iodine by reaction with a biothiol. The increase in fluorescence is related to the concentration over a wide range (1 to 200 µM for GSH and 5-200 µM for Cys and Hcy, respectively), and the assay exhibits a low detection limit (0.3 µM for GSH and Cys and 0.4 µM for Hcy). The method allows for rapid screening and can also be used in combination with a digital camera readout. Graphical abstract Schematic representation of a µPAD based on click immobilized carbon dots and used for a reaction-based fluorometric off-on assay of biothiols. The intrinsic blue fluorescence of carbon dots is turned off via the heavy atom effect of an introduced iodo group and turned on by the displacement of this atom by reaction with a biothiol.


Asunto(s)
Cisteína/orina , Glutatión/orina , Homocisteína/orina , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/métodos , Puntos Cuánticos/química , Carbono/química , Química Clic , Humanos , Técnicas Analíticas Microfluídicas/instrumentación , Papel , Espectrometría de Fluorescencia/métodos , Sulfonas/química
7.
Haemophilia ; 25(3): e165-e173, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30994246

RESUMEN

INTRODUCTION: The joint range of motion (ROM) is an important clinical parameter used to assess the loss of functionality resulting from joint bleedings in people with haemophilia. These episodes require a close follow-up and, to decrease patients' hospital dependence, telemedicine tools are needed. Therefore, this study is aimed to analyse the validity of the Microsoft Kinect V2 sensor with corrected angle measurement to be used in the monitoring of elbow ROM in people with haemophilia. METHODS: A convenience sample of 10 healthy controls (CG) and 10 patients with haemophilia with elbow arthropathy (HG) participated in this study. Full ROM of elbow joints was measured in the frontal view with a 10-degree sweep using: (a) a clinical goniometer; (b) the Kinect V2; (c) the Kinect V2 with angle correction; and (d) using a photograph. Bland-Altman graphs (mean and 95% Limits of Agreement [LOA]) and Wilcoxon test were used to determine differences between measurements and groups. RESULTS: The angle-corrected Kinect V2 measurement removed the skew in the original data, reducing the average errors from 7.9° (LoA = -10.3°; 26.0°; CG) and 9.5° (LoA = -7.9°; 26.9°; HG) to -0.1° (LoA = -8.1°; 7.9°; CG) and -0.7° (LoA = -10.7°; 9.3°; HG). CONCLUSIONS: These error levels allow the use of Kinect V2 in the clinical practice. Kinect V2 with angle correction can complement the classical goniometry allowing an efficient and touchless measurement of ROM.


Asunto(s)
Articulación del Codo/fisiopatología , Hemartrosis/complicaciones , Hemartrosis/fisiopatología , Hemofilia A/complicaciones , Modelos Estadísticos , Rango del Movimiento Articular , Adulto , Femenino , Humanos , Masculino
8.
Bioconjug Chem ; 29(8): 2561-2575, 2018 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-29953208

RESUMEN

Polymer-based nanotheranostics are appealing tools for cancer treatment and diagnosis in the fast-growing field of nanomedicine. A straightforward preparation of novel engineered PEI-based nanotheranostics incorporating NIR fluorescence heptamethine cyanine dyes (NIRF-HC) to enable them with tumor targeted gene delivery capabilities is reported. Branched PEI-2 kDa (b2kPEI) is conjugated with IR-780 and IR-783 dyes by both covalent and noncovalent simple preparative methodologies varying their stoichiometry ratio. The as-prepared set of PEI-NIR-HC nanocarriers are assayed in vitro and in vivo to evaluate their gene transfection efficiency, cellular uptake, cytotoxicity, internalization and trafficking mechanisms, subcellular distribution, and tumor specific gene delivery. The results show the validity of the approach particularly for one of the covalent IR783-b2kPEI conjugates that exhibit an enhanced tumor uptake, probably mediated by organic anion transporting peptides, and favorable intracellular transport to the nucleus. The compound behaves as an efficient nanotheranostic transfection agent in NSG mice bearing melanoma G361 xenographs with concomitant imaging signal and gene concentration in the targeted tumor. By this way, advanced nanotheranostics with multifunctional capabilities (gene delivery, tumor-specific targeting, and NIR fluorescence imaging) are generated in which the NIRF-HC dye component accounts for simultaneous targeting and diagnostics, avoiding additional incorporation of additional tumor-specific targeting bioligands.


Asunto(s)
Carbocianinas/administración & dosificación , Nanomedicina , Polietileneimina/química , Espectroscopía Infrarroja Corta/métodos , Nanomedicina Teranóstica , Animales , Línea Celular , Fluorescencia , Técnicas de Transferencia de Gen , Ratones
9.
J Shoulder Elbow Surg ; 27(11): 2021-2029, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29803503

RESUMEN

BACKGROUND: Nonoperative management of proximal humeral fractures (PHFs) is the most common treatment, but its functional outcome may improve with early mobilization. In frail osteoporotic patients, quick recovery of prefracture independency is mandatory. This study assessed fracture displacement in PHFs managed with conservative treatment after early mobilization and a home-based self-exercise program. METHODS: We retrospectively analyzed the radiologic displacement of fracture fragments of PHFs treated conservatively with early mobilization and a home-based self-exercise program. RESULTS: Included were 99 patients with 26 one-part, 32 two-part, 32 three-part, and 9 four-part PHFs managed conservatively, followed by early mobilization and a home-based self-exercise program. In the x-ray examinations, the head displaced from varus into valgus 55° ± 23° to 42° ± 22°, in the normal range of anatomic values. The medial hinge displaced from medial to the diaphysis (+1 ± 6 mm) to lateral to the head (-0.6 ± 6 mm). The greater tuberosity displaced cranially from -1 ± 7 mm to 2 ± 5 mm. The Constant score at the 1-year follow-up was 79.69 ± 16.3. DISCUSSION AND CONCLUSIONS: The home-based self-exercise program for conservative treatment of PHFs displaces the head-diaphysis angle and the medial hinge toward anatomic reduction, but there is a risk of greater tuberosity cranial displacement. Functional results are fairly good, allowing frail patients to keep on with their independency and life style. Because a large number of patients might need further physiotherapy, the quality of the home-based self-exercises should be supervised.


Asunto(s)
Tratamiento Conservador , Ambulación Precoz , Terapia por Ejercicio , Servicios de Atención de Salud a Domicilio , Autocuidado , Fracturas del Hombro/terapia , Anciano , Anciano de 80 o más Años , Diáfisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Fracturas del Hombro/diagnóstico por imagen , Resultado del Tratamiento
10.
Sensors (Basel) ; 18(8)2018 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-30050026

RESUMEN

Patients with hemophilia need to strictly follow exercise routines to minimize their risk of suffering bleeding in joints, known as hemarthrosis. This paper introduces and validates a new exergaming software tool called HemoKinect that intends to keep track of exercises using Microsoft Kinect V2's body tracking capabilities. The software has been developed in C++ and MATLAB. The Kinect SDK V2.0 libraries have been used to obtain 3D joint positions from the Kinect color and depth sensors. Performing angle calculations and center-of-mass (COM) estimations using these joint positions, HemoKinect can evaluate the following exercises: elbow flexion/extension, knee flexion/extension (squat), step climb (ankle exercise) and multi-directional balance based on COM. The software generates reports and progress graphs and is able to directly send the results to the physician via email. Exercises have been validated with 10 controls and eight patients. HemoKinect successfully registered elbow and knee exercises, while displaying real-time joint angle measurements. Additionally, steps were successfully counted in up to 78% of the cases. Regarding balance, differences were found in the scores according to the difficulty level and direction. HemoKinect supposes a significant leap forward in terms of exergaming applicability to rehabilitation of patients with hemophilia, allowing remote supervision.


Asunto(s)
Terapia por Ejercicio , Ejercicio Físico/fisiología , Hemartrosis/etiología , Hemartrosis/prevención & control , Hemofilia A/complicaciones , Programas Informáticos , Adulto , Codo/fisiología , Femenino , Hemartrosis/rehabilitación , Humanos , Rodilla/fisiología , Masculino
11.
Bioconjug Chem ; 27(3): 549-61, 2016 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-26841323

RESUMEN

Gene transfection mediated by the cationic polymer polyethylenimine (PEI) is considered a standard methodology. However, while highly branched PEIs form smaller polyplexes with DNA that exhibit high transfection efficiencies, they have significant cell toxicity. Conversely, low molecular weight PEIs (LMW-PEIs) with favorable cytotoxicity profiles display minimum transfection activities as a result of inadequate DNA complexation and protection. To solve this paradox, a novel polyelectrolyte complex was prepared by the ionic cross-linking of branched 1.8 kDa PEI with citric acid (CA). This system synergistically exploits the good cytotoxicity profile exhibited by LMW-PEI with the high transfection efficiencies shown by highly branched and high molecular weight PEIs. The polyectrolyte complex (1.8 kDa-PEI@CA) was obtained by a simple synthetic protocol based on the microwave irradiation of a solution of 1.8 kDa PEI and CA. Upon complexation with DNA, intrinsic properties of the resulting particles (size and surface charge) were measured and their ability to form stable polyplexes was determined. Compared with unmodified PEIs the new complexes behave as efficient gene vectors and showed enhanced DNA binding capability associated with facilitated intracellular DNA release and enhanced DNA protection from endonuclease degradation. In addition, while transfection values for LMW-PEIs are almost null, transfection efficiencies of the new reagent range from 2.5- to 3.8-fold to those of Lipofectamine 2000 and 25 kDa PEI in several cell lines in culture such as CHO-k1, FTO2B hepatomas, L6 myoblasts, or NRK cells, simultaneously showing a negligible toxicity. Furthermore, the 1.8 kDa-PEI@CA polyelectrolyte complexes retained the capability to transfect eukaryotic cells in the presence of serum and exhibited the capability to promote in vivo transfection in mouse (as an animal model) with an enhanced efficiency compared to 25 kDa PEI. Results support the polyelectrolyte complex of LMW-PEI and CA as promising generic nonviral gene carriers.


Asunto(s)
Ácido Cítrico/química , Electrólitos/química , Polietileneimina/química , Transfección , Línea Celular , Humanos , Técnicas In Vitro , Peso Molecular
12.
Molecules ; 20(3): 3716-29, 2015 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-25719741

RESUMEN

Bile acid sequestrants (BAS) represent a therapeutic approach for the management of hypercholesterolemia that relies on the cationic polymeric nature of BAS to selectively bind negatively charged bile acids. We hypothesized that the cross-linking of ß-cyclodextrin (ß-CD) and saccharides such as starch or dextrin with divinyl sulfone (DVS) yields homo- and hetero-polymeric materials with the ability to trap sterols. Our hypothesis was put to test by synthesizing a library of 22 polymers that were screened to evaluate their capability to sequester both cholesterol (CHOL) and cholic and deoxycholic acids (CA and DCA). Three polymers synthesized in high yield were identified as promising. Two were neutral hetero-polymers of ß-CD and starch or dextrin and the third was a weakly cationic homo-polymer of starch, highlighting the importance of the cavity effect. They were tested in hypercholesterolemic male Wistar rats and their ability to regulate hypercholesterolemia was similar to that for the reference BAS cholestyramine, but with two additional advantages: (i) they normalized the TG level and (ii) they did not increase the creatinine level. Neither hepatotoxicity nor kidney injury was detected, further supporting them as therapeutical candidates to manage hypercholesterolemia.


Asunto(s)
Ácidos y Sales Biliares/aislamiento & purificación , Hipercolesterolemia/prevención & control , Polímeros/química , Almidón/química , Sulfonas/química , beta-Ciclodextrinas/química , Animales , Ácidos y Sales Biliares/metabolismo , Reactivos de Enlaces Cruzados , Hipercolesterolemia/metabolismo , Técnicas In Vitro , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Wistar
13.
Molecules ; 20(3): 3565-81, 2015 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-25706758

RESUMEN

The aim of this study was to evaluate the crosslinking abilities of divinyl sulfone (DVS) for the preparation of novel water-insoluble cyclodextrin-based polymers (CDPs) capable of forming inclusion complexes with different guest molecules. Reaction of DVS with native α-cyclodextrin (α-CD), ß-cyclodextrin (ß-CD) and/or starch generates a variety of homo- and hetero-CDPs with different degrees of crosslinking as a function of the reactants' stoichiometric ratio. The novel materials were characterized by powder X-ray diffraction, electron microscopy and for their sorption of phenol and 4-nitrophenol. They were further evaluated as sorbents with phenolic pollutants (bisphenol A and ß-naphthol) and bioactive compounds (the hormone progesterone and curcumin). Data obtained from the inclusion experiments show that the degree of cross-linking has a minor influence on the yield of inclusion complex formation and highlight the important role of the CDs, supporting a sorption process based on the formation of inclusion complexes. In general, the inclusion processes are better described by a Freundlich isotherm although an important number of them can also be fitted to the Langmuir isotherm with R2 ≥ 0.9, suggesting a sorption onto a monolayer of homogeneous sites.


Asunto(s)
Reactivos de Enlaces Cruzados/farmacología , Ciclodextrinas/química , Polímeros/química , Almidón/química , Sulfonas/química , Adsorción , Compuestos de Bencidrilo/aislamiento & purificación , Compuestos de Bencidrilo/metabolismo , Curcumina/aislamiento & purificación , Curcumina/metabolismo , Concentración de Iones de Hidrógeno , Naftoles/aislamiento & purificación , Naftoles/metabolismo , Nitrofenoles/aislamiento & purificación , Nitrofenoles/metabolismo , Fenoles/aislamiento & purificación , Fenoles/metabolismo , Progesterona/aislamiento & purificación , Progesterona/metabolismo , Difracción de Rayos X
14.
Bioconjug Chem ; 25(6): 1151-61, 2014 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-24852962

RESUMEN

The receptor for advanced glycation end products (RAGE) is involved in diabetes or angiogenesis in tumors. Under pathological conditions, RAGE is overexpressed and upon ligand binding and internalization stimulates signaling pathways that promote cell proliferation. In this work, amino dendritic polymers PEI 25 kDa and alkylated derivatives of PAMAM-G2 were engineered by the nonenzymatic Maillard glycation reaction to generate novel AGE-containing gene delivery vectors targeting the RAGE. The glycated dendritic polymers were easily prepared and retained the capability to bind and protect DNA from endonucleases. Furthermore, while glycation decreased the transfection efficiency of the dendriplexes in CHO-k1 cells which do not express RAGE, glycated dendriplexes acted as efficient transfection reagents in CHO-k1 cells which stably express recombinant RAGE. In addition, preincubation with BSA-AGEs, a natural ligand of the RAGE, or dansyl cadaverine, an inhibitor of the RAGE internalization, blocked transfection, confirming their specificity toward RAGE. The results were confirmed in NRK and RAW264.7 cell lines, which naturally express the receptor. The glycated compounds retain their transfection efficiency in the presence of serum and promote in vivo transfection in a mouse model. Accordingly, RAGE is a suitable molecular target for the development of site-directed engineered glycated nonviral gene vectors.


Asunto(s)
Dendrímeros/química , Técnicas de Transferencia de Gen , Ingeniería Genética , Vectores Genéticos/química , Polímeros/química , Receptores Inmunológicos/química , Animales , Células CHO , Cadaverina/análogos & derivados , Cadaverina/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cricetulus , Dendrímeros/administración & dosificación , Dendrímeros/síntesis química , Dendrímeros/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Vectores Genéticos/síntesis química , Vectores Genéticos/farmacología , Ratones , Modelos Biológicos , Tamaño de la Partícula , Polímeros/síntesis química , Polímeros/farmacología , Ratas , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/antagonistas & inhibidores , Receptores Inmunológicos/metabolismo , Relación Estructura-Actividad , Propiedades de Superficie
15.
Artículo en Inglés | MEDLINE | ID: mdl-38943379

RESUMEN

BACKGROUND: During the last two decades, there has been a growing interest in spinal sagittal alignment. Most published studies have focused on the role of spinopelvic parameters in patients with adult spinal deformity or in those with previous spinal fusion. OBJECTIVE: The aim of this study was to explore possible association between disability related to back pain and spinopelvic parameters in the absence of coronal deformity or previous spinal surgery. METHODS: In the setting of a larger study involving patients with low back pain (LBP), those without previous surgery or spinal deformity in the coronal plane were selected. A total of 52 patients (mean age 59 years, range 21-86, 23 men and 29 women) were found. The visual analogic scale (VAS) and Oswestry Disability Index questionnaire (ODI) were recorded. Surgimap software was used to measure the sagittal vertical axis (SVA), pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), and lumbar lordosis (LL). Statistical analysis was performed with SPSS Statistics software. Pearson or Spearman correlation were the test of choice depending on the specific variables. RESULTS: A statistically significant association was found between SVA and ODI (r 0.59, p< 0.03). Increased pelvic tilt was also associated with more severe disability related to back pain (r 0.48, p< 0.03). PI-LL mismatch showed moderate association with disability and severity of back pain, although this association did not reach statistical significance (r 0.52, p< 0.08). CONCLUSION: Our findings suggest that sagittal misalignment may be related with more severe disability and back pain in patients with minor or null deformity in the coronal plane.

16.
Polymers (Basel) ; 16(8)2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38675010

RESUMEN

Water recycling and reuse are cornerstones of water management, which can be compromised by the presence of pollutants. Among these, pharmaceuticals can overcome standard water treatments and require sophisticated approaches to remove them. Sorption is an economically viable alternative limited by the need for sorbents with a sorption coefficient (Kd) higher than 500 L/kg. The cross-linking of dextrin (Dx) with divinyl sulfone (DVS) in the presence of 1 mmol or 5 mmol of ibuprofen (IBU) yields the insoluble polymers pDx1 and pDx5 with improved affinity for IBU and high selectivity towards erythromycin (ERY) and ERY Kd higher than 4 × 103 L/kg, when tested against a cocktail of six drugs. Characterization of the polymers shows that both pDx1 and pDx5 have similar properties, fast sorption kinetics, and ERY Kd of 13.3 × 103 for pDx1 and 6.4 × 103 for pDx5, representing 26.6 and 12.0 times the 500 L/kg threshold. The fact that new affinities and improvements in Kd can be achieved by cross-linking Dx in the presence of other molecules that promote pre-organization expands the applications of DVS cross-linked polysaccharides as sustainable, scalable, and environmentally friendly sorbents with a potential application in wastewater treatment plants (WTPs).

17.
Org Biomol Chem ; 11(16): 2586-96, 2013 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-23429475

RESUMEN

The easy vinyl sulfone derivatization of ferrocene allows the preparation of some effective, versatile and valuable ferrocenylation reagents. The applicability of such compounds in conjugation and bioconjugation of amine and/or thiol containing molecules and biomolecules through Michael-type addition under mild conditions that preserve the biological function of the latter is described. The feasibility of the methodology is demonstrated by the preparation of a variety of conjugates and bioconjugates (ferrocenyl terminated dendrimers and ferrocene-sugar, ferrocene-cyclodextrin, ferrocene-peptide and ferrocene-protein conjugates).


Asunto(s)
Colorantes/química , Compuestos Ferrosos/química , Sulfonas/química , Animales , Carbohidratos/síntesis química , Carbohidratos/química , Bovinos , Colorantes/síntesis química , Ciclodextrinas/síntesis química , Ciclodextrinas/química , Dendrímeros/síntesis química , Dendrímeros/química , Técnicas Electroquímicas , Compuestos Ferrosos/síntesis química , Indicadores y Reactivos , Metalocenos , Modelos Moleculares , Péptidos/síntesis química , Péptidos/química , Albúmina Sérica Bovina/síntesis química , Albúmina Sérica Bovina/química , Sulfonas/síntesis química
18.
Int J Food Microbiol ; 387: 110054, 2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36525768

RESUMEN

The occurrence of fungi and mycotoxins in foods is a serious global problem. Most of the regulated mycotoxins in food are produced by Fusarium spp. This work aimed to assess the antifungal activity of selected lactic acid bacteria (LAB) strains against the main toxigenic Fusarium spp. isolated from cereals. Various machine learning (ML) algorithms such as neural networks (NN), random forest (RF), extreme gradient boosted trees (XGBoost), and multiple linear regression (MLR), were applied to develop models able to predict the percentage of fungal growth inhibition caused by the LAB strains tested. In addition, the ability of the assayed LAB strains to reduce/inhibit the production of the main mycotoxins associated with these fungi was studied by UPLC-MS/MS. All assays were performed at 20, 25, and 30 °C in dual culture (LAB plus fungus) on MRS agar-cereal-based media. All factors and their interactions very significantly influenced the percentage of growth inhibition compared to controls. The efficacy of LAB strains was higher at 20 °C followed by 30 °C and 25 °C. Overall, the order of susceptibility of the fungi to LAB was F. oxysporum > F. poae = F. culmorum ≥ F. sporotrichioides > F. langsethiae > F. graminearum > F. subglutinans > F. verticillioides. In general, the most effective LAB was Leuconostoc mesenteroides ssp. mesenteroides (T3Y6b), and the least effective were Latilactobacillus sakei ssp. carnosus (T3MM1 and T3Y2). XGBoost and RF were the algorithms that produced the most accurate predicting models of fungal growth inhibition. Mycotoxin levels were usually lower when fungal growth decreased. In the cultures of F. langsethiae treated with LAB, T-2 and HT-2 toxins were not detected except in the treatments with Pediococcus pentosaceus (M9MM5b, S11sMM1, and S1M4). These three strains of P. pentosaceus, L. mesenteroides ssp. mesenteroides (T3Y6b) and L. mesenteroides ssp. dextranicum (T2MM3) inhibited fumonisin production in cultures of F. proliferatum and F. verticillioides. In F. culmorum cultures, zearalenone production was inhibited by all LAB strains, except L. sakei ssp. carnosus (T3MM1) and Companilactobacillus farciminis (T3Y6c), whereas deoxynivalenol and 3-acetyldeoxynivalenol were only detected in cultures of L. sakei ssp. carnosus (T3MM1). The results show that an appropriate selection and use of LAB strains can be one of the most impacting tools in the control of toxigenic Fusarium spp. and their mycotoxins in food and therefore one of the most promising strategies in terms of efficiency, positive impact on the environment, food safety, food security, and international economy.


Asunto(s)
Fusarium , Lactobacillales , Micotoxinas , Micotoxinas/análisis , Cromatografía Liquida , Espectrometría de Masas en Tándem , Grano Comestible/microbiología
19.
Polymers (Basel) ; 15(15)2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37571082

RESUMEN

Water use has been increasing globally by 1% per year, and recycling and re-use are critical issues compromised by the presence of pollutants. In this context, the design of novel materials and/or procedures for the large scale-removal of pollutants must be economically and environmentally feasible in order to be considered as part of the solution by emerging economies. We demonstrate that the cross-linking of biodegradable polysaccharides such as starch, dextrin, or dextrin and ß-cyclodextrin with divinyl sulfone is an innovative strategy for synthesizing insoluble and eco-friendly sorbent polymers, including pSt, pDx and pCD-Dx. The evaluation of these polymers' ability to remove ciprofloxacin (CIP), a prime example of antibiotic pollution, revealed that pSt, with a Kd of 1469 L/kg and a removal rate higher than 92%, is a favorable material. Its sorption is pH-dependent and enhanced at a mildly alkaline pH, allowing for the desorption (i.e., cleaning) and reuse of pSt through an environmentally friendly treatment with 20 mM AcONa pH 4.6. The facts that pSt (i) shows a high affinity for CIP even at high NaCl concentrations, (ii) can be obtained from affordable starting materials, and (iii) is synthesized and regenerated through organic, solvent-free procedures make pSt a novel sustainable material for inland water and seawater remediation, especially in less developed countries, due to its simplicity and low cost.

20.
J Spine Surg ; 9(3): 247-258, 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37841795

RESUMEN

Background: Surgical treatment of degenerative lumbar disease in the elderly is controversial. Elderly patients have an increased risk for medical and surgical complications commensurate with their comorbidities, and concerns over complications have led to frequent cases of insufficient decompression to avoid the need for instrumentation. The purpose of this study was to evaluate clinical outcome between older and younger patients undergoing lumbar instrumented arthrodesis. Methods: This is a retrospective, comparative study of prospectively collected outcomes. One hundred and fifty-four patients underwent 1- or 2-level posterolateral lumbar fusion. Patients were divided into two groups. Group 1: 87 patients ≤65 years of age who underwent decompression and posterolateral instrumented fusion; Group 2: 67 patients ≥75 years of age who underwent the same procedures with polymethylmethacrylate (PMMA) pedicle-screw augmentation. Mean follow-up 27.47 months (range, 76-24 months). Results: Mean age was 49.1 years old (range, 24-65) for the younger group and 77.8 (range, 75-86) in the elderly group. Patients ≥75 years of age showed higher preoperative comorbidity (American Society of Anesthesiology, ASA: 1.7 vs. 2.4), and ≥2 systemic diseases with greater frequency (12.5% vs. 44.7%). No significant differences were found between the two groups in terms of postoperative complications, fusion, or revision rate. During follow-up, adjacent disc disease and adjacent fracture occurred significantly more in Group 2 (P<0.05). At the end of follow-up, there were no significant differences between the two groups in any of the clinical and health-related quality of life scores or satisfaction with treatment received. Conclusions: Osteoporosis represents a major consideration before performing spine surgery. Despite an obvious increased risk of complications in elderly patients, PMMA-augmented fenestrated pedicle screw instrumentation in spine fusion represents a safe and effective surgical treatment option to elderly patients with poor bone quality. Age itself should not be considered a contraindication in otherwise appropriately selected patients.

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