Binary MoS2 nanostructures as nanocarriers for amplification in multiplexed electrochemical immunosensing: simultaneous determination of B cell activation factor and proliferation-induced signal immunity-related cytokines.

A dual immunosensor is reported for the simultaneous determination of two important immunity-related cytokines: BAFF (B cell activation factor) and APRIL (a proliferation-induced signal). Sandwich-type immunoassays with specific antibodies (cAbs) and a strategy for signal amplification based on labelling the detection antibodies (dAbs) with binary MoS2/MWCNTs nanostructures and using horseradish peroxidase (HRP) were implemented. Amperometric detection was carried out at screen-printed dual carbon electrodes (SPdCEs) through the hydroquinone HQ/H2O2 system. The developed dual immunosensor provided limit of detection (LOD) of 0.08 and 0.06 ng mL-1 for BAFF and APRIL, respectively, and proved to be useful for the determination of both cytokines in cancer cell lysates and serum samples from patients diagnosed with autoimmune diseases and cancer. The obtained results agreed with those found using ELISA methodologies.

Redox Cycling Amplified Electrochemical Lateral-Flow Immunoassay: Toward Decentralized Sensitive Insulin Detection.

While paper-based lateral-flow immunoassays (LFA) offer considerable promise for centralized diagnostic applications, the analytical capability of conventional LFA remains constrained due to the low sensitivity of its common optical detection strategy. To address these issues, we report a simple electrochemical LFA (eLFA) with nanocatalytic redox cycling for decentralized insulin detection. Simultaneous binding of insulin with detection antibodies and capture antibodies through the capillary flow at the LFA platform and signal amplification through the rapid nanocatalytic reduction of [Fe(CN)6]3- (Fe3+) with Au nanoparticles (AuNP) and ammonia-borane (AB), coupled to electrochemical redox cycling reactions involving Fe3+, AuNP, and AB on the carbon working electrode, offer higher sensitivity than conventional colorimetric LFA and enzymatic redox cycling. The resulting integrated eLFA strip allows the detection of low insulin concentrations (LOD = 12 pM) and offers considerable promise for highly sensitive decentralized assays of different biological fluids (saliva and serum) without additional pretreatment or washing steps.

Anti-double stranded DNA antibodies: Electrochemical isotyping in autoimmune and neurological diseases.

This work reports the first amperometric biosensor for the simultaneous determination of the single or total content of the most relevant human immunoglobulin isotypes (hIgs) of anti-dsDNA antibodies, dsDNA-hIgG, dsDNA-hIgM, dsDNA-hIgA and dsDNA-three hIgs, which are considered relevant biomarkers in prevalent autoimmune diseases such as systemic lupus erythematosus (SLE) as well as of interest in neurodegenerative diseases such as Alzheimer's disease (AD). The bioplatform involves the use of neutravidin-functionalized magnetic microparticles (NA-MBs) modified with a laboratory-prepared biotinylated human double-stranded DNA (b-dsDNA) for the efficient capture of specific autoantibodies that are enzymatically labeled with horseradish peroxidase (HRP) enzyme using specific secondary antibodies for each isotype or a mixture of secondary antibodies for the total content of the three isotypes. Transduction was performed by amperometry (-0.20 V vs. the Ag pseudo-reference electrode) using the H2O2/hydroquinone (HQ) system after trapping the resulting magnetic bioconjugates on each of the four working electrodes of a disposable quadruple transduction platform (SP4CEs). The bioplatform demonstrated attractive operational characteristics for clinical application and was employed to determine the individual or total hIgs classes in serum from healthy individuals and from patients diagnosed with SLE and AD. The target concentrations in AD patients are provided for the first time in this work. In addition, the results for SLE patients and control individuals agree with those obtained by applying ELISA tests as well as with the clinical ranges reported by other authors, using individual detection methodologies restricted to centralized settings or clinical laboratories.

Unraveling autoimmune and neurodegenerative diseases by amperometric serological detection of antibodies against aquaporin-4.

This work reports the first electroanalytical bioplatform to date for the determination of antibodies against aquaporin-4 (AQP4-Abs), whose serum level is considered as relevant biomarker for certain autoimmune diseases. The bioplatform relies on the use of magnetic microparticles modified with the biotinylated protein for the capture of specific antibodies. The captured IgGs are enzymatically labelled with a secondary antibody conjugated to the horseradish peroxidase (HRP) enzyme. Amperometric transduction is performed using the H2O2/hydroquinone (HQ) system, which results in a cathodic current variation directly proportional to the concentration of the target antibodies. The evaluation of the analytical and operational characteristics of the developed bioplatform shows that it is competitive in terms of sensitivity with the only biosensor reported to date as well as with the commercially available ELISA kits. The achieved limit of detection value is 8.8 pg mL-1. In addition, compared to ELISA kits, the developed bioplatform is advantageous in terms of cost and point of care operation ability. The bioplatform was applied to the analysis of control serum samples with known AQP4-Abs contents as well as of sera from healthy individuals and patients diagnosed with Systemic Lupus Erythematosus (SLE) and Alzheimer (AD) diseases, providing results in agreement with the ELISA methodology.

Ultrasensitive detection of soy traces by immunosensing of glycinin and ß-conglycinin at disposable electrochemical platforms.

This work reports the first electrochemical bioplatform for the determination of soy traces in food. The bioplatform involves sandwich-type immunoassays using specific antibodies for ß-conglycinin and glycinin, which are the main allergenic soy proteins, and carboxylic acid-modified magnetic microbeads. Amperometric detection at -0.20 V (vs. an Ag pseudo-reference electrode) was performed using single or dual screen-printed carbon electrodes and the H2O2/hydroquinone (HQ) system. The measured variation in the cathodic current was directly proportional to the concentration of target allergenic proteins. The developed bioplatforms exhibit a good selectivity and sensitivity providing limits of detection (LOD) values of 0.03 and 0.02 ng mL-1 for ß-conglycinin and glycinin, respectively. The determination of both proteins can be carried out in only 1.5 h. The electrochemical bioplatforms allow their accurate determinations (with results statistically comparable to those provided by ELISA methodologies) in raw cookie dough and baked cookies enriched with soy flour. The results obtained confirm, in a pioneering way with electrochemical biosensors, the possibility of discriminating samples incurred with as little as 0.0005 ppm of a food allergen in model cookie extracts.

Simultaneous determination of four fertility-related hormones in saliva using disposable multiplexed immunoplatforms coupled to a custom-designed and field-portable potentiostat.

This work reports the first amperometric immunosensor for the simultaneous determination of four fertility-related hormones in saliva: progesterone (P4), luteinizing hormone (LH), estradiol (E2), and prolactin (PRL). The immune platform involves direct competitive (P4 and E2), and sandwich (LH and PRL) assays implemented onto functionalized magnetic microbeads (MBs). The amperometric transduction was performed upon placing the MBs-immunoconjugates onto each of the four working electrodes of the SPCE array (SP4CEs) and applying a detection potential of -0.20 V (vs. Ag pseudo-reference electrode) using the H2O2/hydroquinone (HQ) system. The achieved analytical and operational characteristics of the developed multiplexed immunoplatform showed a sensitivity that allows the determination of these hormones in saliva, and an adequate selectivity to analyse complex clinical samples. The bioplatform was employed for the determination of the set of four hormones in human saliva samples collected from individuals with different hormonal profiles. The results obtained using a conventional potentiostat were compared with those provided employing a novel low-cost custom-designed and field-portable quadruple potentiostat. Similar results were found which also agreed with those obtained by applying ELISA methods for the determination of single hormones.

Electrochemical immunoplatform to assist in the diagnosis and classification of breast cancer through the determination of matrix-metalloproteinase-9.

Matrix metalloproteinase 9 (MMP-9) is a zinc-dependent endopeptidase that promotes angiogenesis, tumor growth, metastasis and cell invasion through the degradation of extracellular matrix. This work reports a magnetic microbeads (MBs)-based sandwich immunoassay for the amperometric determination of MMP-9 at screen-printed carbon electrodes (SPCEs). The suitable capture antibody (cAb) is immobilized onto carboxylic MBs to selectively capture the antigen which is sandwiched with a biotinylated detector antibody (biotin-dAb) further conjugated with a commercial streptavidin-horseradish peroxidase (Strep-HRP) polymer. This immunoplatform provides great analytical characteristics in terms of selectivity and sensitivity, achieving a LOD value of 2.4 pg mL-1 for standards in buffered solutions. Although this value is similar to those reported for some other approaches described so far, the method described here is simpler involving a single 30 min incubation step which makes it ideal for automation or implementation in POC devices. Moreover, the method was assayed for the accurate determination of endogenous MMP-9 in both cancer cell lysates and serum samples of patients diagnosed with different subtypes of breast cancer (BC) after a simple dilution. The results obtained show that the disposable and affordable immunoplatform developed is able not only to discriminate BC patients from healthy individuals but also to do it for the worst outcome triple negative (TNBC) subtype.

Fast and sensitive diagnosis of autoimmune disorders through amperometric biosensing of serum anti-dsDNA autoantibodies.

This work reports the first amperometric biosensor involving the use of neutravidin-functionalized magnetic microbeads (NA-MBs) modified with a biotinylated-anti-dsDNA (b-dsDNA) as efficient magnetic microcarriers to selectively capture anti-dsDNA autoantibodies (IgG, IgA and IgM AAbs) present in the sera of patients with rheumatoid arthritis (RA). Subsequently, the attached anti-dsDNA AAbs are detected with a mixture of conventional HRP-labeled secondary antibodies (HRP-anti-human IgG/IgM/IgA mixture). The biorecognition event is monitored by amperometric transduction using the hydroquinone (HQ)/H2O2 system upon capturing the modified MBs on the surface of screen-printed carbon electrodes (SPCEs). The developed bioplatform exhibits a linear calibration plot ranging from 1 to 200 IU mL-1 with a LOD of 0.3 IU mL-1 for anti-dsDNA AAbs standards. In addition, the biosensor allows performing the determination of the anti-dsDNA AAbs levels directly in 100-times diluted serum samples from patients diagnosed with RA and in just 75 min. The obtained results are in agreement with those provided by an ELISA kit and allow discrimination between positive and negative samples.

Structural and theoretical characterization of a new twisted 4'-substituted terpyridine compound: 4'-(isoquinolin-4-yl)-2,2':6',2''-terpyridine.

4'-Substituted derivatives of 2,2':6',2''-terpyridine with N-containing heteroaromatic substituents, such as pyridyl groups, might be able to coordinate metal centres through the extra N-donor atom, in addition to the chelating terpyridine N atoms. The incorporation of these peripheral N-donor sites would also allow for the diversification of the types of noncovalent interactions present, such as hydrogen bonding and π-π stacking. The title compound, C24H16N4, consists of a 2,2':6',2''-terpyridine nucleus (tpy), with a pendant isoquinoline group (isq) bound at the central pyridine (py) ring. The tpy nucleus deviates slightly from planarity, with interplanar angles between the lateral and central py rings in the range 2.24 (7)-7.90 (7)°, while the isq group is rotated significantly [by 46.57 (6)°] out of this planar scheme, associated with a short Htpy...Hisq contact of 2.32 Å. There are no strong noncovalent interactions in the structure, the main ones being of the π-π and C-H...π types, giving rise to columnar arrays along [001], further linked by C-H...N hydrogen bonds into a three-dimensional supramolecular structure. An Atoms In Molecules (AIM) analysis of the noncovalent interactions provided illuminating results, and while confirming the bonding character for all those interactions unquestionable from a geometrical point of view, it also provided answers for some cases where geometric parameters are not informative, in particular, the short Htpy...Hisq contact of 2.32 Što which AIM ascribed an attractive character.

Linfoma de células del manto con presentación radiológica atípica: Presentación de caso / Mantle Cell Lymphoma with Atypical Radiologic Presentation

El linfoma de células del manto hace parte del subgrupo de linfomas no Hodgkin (LNH). Este se manifiesta con adenopatías, esplenomegalia, síntomas B y compromiso cutáneo asociado a enfermedad diseminada. El compromiso esplénico se presenta como: Esplenomegalia sin lesión focal; lesiones sólidas únicas o múltiples e infiltración del bazo sin cambios morfológicos ni lesiones focales. La aparición de linfoma con lesiones quísticas es extremadamente rara, se encuentran solo unos cuantos casos en la literatura, ninguno de ellos en el bazo. Se expone el caso de una paciente de 59 años de edad, quien consultó por dolor abdominal intermitente. En los estudios diagnósticos se observó esplenomegalia con lesiones sólidas y quísticas. Se realizó esplenectomía con estudio histopatológico que confirmó compromiso por linfoma de células del manto.

Mantle cell lymphoma is a Non-Hodgkin Lymphoma (NHL). In cases of disseminated disease, lymphadenopathy, splenomegaly, B-symptoms and skin disease are present. Lymphoma affecting the spleen has several radiologic presentations, ranging from normal appearance, to splenomegaly or multiples focal solid lesions. Cystic presentation of lymphoma is rare and few cases have been reported, none of them involving the spleen. We report a case of a 59-year old female patient with cystic spleen lesions that after splenectomy were diagnosed as Mantle cell lymphoma.

Ecografía Doppler en la evaluación de trasplante del hígado / US Doppler in Liver Transplantation

El trasplante de hígado es un método terapéutico efectivo para el tratamiento de múltiples enfermedades hepáticas terminales irreversibles, tanto agudas como crónicas. Los avances en la terapia inmunosupresora, la técnica quirúrgica y el cuidado perioperatorio han mejorado el pronóstico de los pacientes sometidos a este procedimiento. La ecografía con evaluación Doppler es el método de imagen más utilizado para valorar a estos pacientes, tanto en la etapa inicial como en el seguimiento a largo plazo. Tiene como ventajas estar ampliamente disponible, la posibilidad de volverse portátil, no generar efectos secundarios y no asociarse con efectos por radiación ionizante. Permite realizar una valoración anatómica en escala de grises y funcional con la evaluación del flujo de las diferentes anastomosis vasculares. Es el método diagnóstico ideal ante la sospecha de complicaciones vasculares. Las complicaciones más comunes y con más importancia clínica son las vasculares: trombosis arterial, trombosis venosa, estenosis, fístulas. También se encuentran complicaciones de la anastomosis biliar, las colecciones, las neoplasias y el rechazo. En este artículo se revisan los hallazgos normales y anormales en el Doppler de los pacientes sometidos a trasplante de hígado.

Liver transplantation is an effective therapeutic method for treatment of multiple irreversible terminal liver disease, both acute and chronic. Advances in immunosuppressive therapy, surgical technique and post-surgical care have improved the prognosis of patients undergoing this procedure. The ultrasound with Doppler assessment is the image method which is most commonly used to assess these patients, both in the initial phase and during long-term follow-up. The advantages of ultrasound Doppler are the following: It is widely available, it can be portable, it does not cause sideeffects, and it is not associated with ionizing radiation effects. In addition, it also allows an anatomical assessment of grey and functional scales, with flow evaluation of different vascular complications. The most common complications during liver transplantation, as well as the ones with the highest clinical importance are vascular complications: arterial thrombosis, venous thrombosis, stenosis, fistulas. In addition, one can find complications of biliary anastomosis, as well as collections, neoplasms and rejection. Normal and abnormal Doppler findings in patients undergoing liver transplantation are reviewed in this article.

Aspectos imaginológicos del sarcoma granulocítico en la cara y el cráneo de niños y jóvenes: informe de cinco casos y revisión de la literatura / Radiological findings of granulocytic sarcoma in the face and skull of children and young persons: report of five cases and literature review

Introducción: el sarcoma granulocítico (SG) es una neoplasia maligna cuya incidencia es de 2,9% a3,1% en pacientes con leucemia mieloide (LM) o enfermedades mieloproliferativas. Se presentahabitualmente en hombres y en población africana, asiática y suramericana. Objetivo: describir las características imaginológicas del SG en la cara y el cráneo de cinco niños y jóvenes. Pacientes y métodos: presentamos cinco pacientes con SG en la cara y la base del cráneo. A cuatro de ellos se les hizo tomografía computarizada (TC) y a tres, resonancia magnética (RM) cerebral. Cuatro presentaron una masa de tejido blando en la órbita, dos tenían afectación ósea y otro reveló lesión en el sistema nervioso central. En cuatro se diagnosticó leucemia mieloide aguda (LMA) .Conclusión: el SG puede manifestarse con invasión orbitaria y craneofacial en niños y adultos jóvenes. Usualmente los pacientes consultan por proptosis y edema orbitario. Con este cuadro clínico el SG es la primera probabilidad diagnóstica en el contexto de la LMA o las mielodisplasias. En otras situaciones clínicas se debe hacer diagnóstico diferencial con complicaciones de sinusitis, rabdomiosarcoma, linfoma de la órbita y otras neoplasias. La imaginología demuestra invasión de tejidos blandos e infiltración ósea. Es muy característico del SG afectar en un comienzo la pared lateral o la superior de la órbita. En algunos casos simula abscesos. El diagnóstico se confirma por histopatología.

Introduction: Granulocytic sarcoma (GS) is a rare malignant neoplasia, with an incidence rate of 2.9% to 3.1% in patients with myeloid leukemia or myeloproliferative diseases. Usually it affects males, of African, Asian and South American populations. Objetive: To describe the radiological characteristics of GS in the face and skull of children and young people. Patients and methods: We report five patients with GS in the face and skull. Computerized tomography (CT) was carried out in four and orbital and brain magnetic resonance (MRI) in three. Out of the five, four had soft tissue masses in the orbit, two had bone infiltration, and in one there was a central nervous system lesion. In four patients acute myeloid leukemia was demonstrated. Conclusion: GS may affect the orbit, the face and the skull of children and young adults; it manifests with exophthalmia and orbital edema. It must be considered as a diagnostic possibility in the context of myeloid leukemia and myelodysplasias. Otherwise, differential diagnosis should be made with complications of sinusitis, orbital rhabdomyosarcoma, orbital lymphoma and other tumors. Imaging studies may help in the diagnosis by revealing soft tissue masses and areas of bone infiltration. In some cases GS may resemble abscesses. Diagnosis must be confirmed by histopathology.

Esplenosis torácica: presentación de caso / Thoracic splenosis: a case report

La esplenosis torácica se define como la presencia de implantes de tejido esplénico en la pleura parietal o visceral, secundaria a una rotura del bazo o traumatismo esplénico o diafragmático. Es una entidad rara, con síntomas poco específicos, que presenta un curso benigno. Entre las modalidades de imágenes para el diagnóstico se encuentran métodos convencionales, como el ultrasonido, la tomografía axial computarizada y la medicina nuclear, que son técnicas útiles para determinar tejido esplénico residual. En el artículo se presenta el caso de un hombre joven con antecedente de trauma esplénico, al cual se le diagnostica esplenosis torácica como parte del estudio de síndrome febril prolongado y síntomas respiratorios.

Utilidad de la colangiografía por TC con multidetectores en la evaluación de pacientes con obstrucción biliar / The utility of multidetector CT cholangiography in the evaluation of patients with biliar obstruction

Objetivos: establecer de la concordancia entre la colangiotomografía con multidetectores, con reconstrucciones MPR y MinIP, y la colangiopancreatografía endoscópica retrógrada (CPER), la colangiografía transparietohepática (CTPH) o la cirugía, para identificar el sitio y la causa de la obstrucción, en pacientes con dilatación biliar. Material y métodos: estudio de concordancia entre pruebas diagnósticas, descriptivo y prospectivo. Población de referencia: durante 24 meses se estudiaron 34 pacientes, con dilatación de la vía biliar, diagnosticada con colangiotomografia, en el hospital Universitario san vicente de paúl, y a quienes posteriormente se les realizó un estudio confirmatorio, como CPER, CTPH o cirugía. Resultados: de los 34 pacientes, 16 presentaban litiasis biliar, y de ellos 6 tuvieron como prueba confirmatoria la cirugía, y 10, la CPER. los 18 pacientes restantes tenían malignidad como la causa de la obstrucción y el diagnóstico fue confirmado por cirugía en 11, 3 con CPER y 4 con CTPH. se obtuvo un 91% de concordancia con la colangiografía TC para determinar el sitio y la causa de la obstrucción. Conclusión: nuestros resultados muestran muy buena concordancia de la colangiotomografía con multidetectores para identifir el sitio y la causa de la obstrucción, en pacientes con dilatación de la vía biliar; así mismo, puede ser una alternativa a la colangiorresonancia.

Apendicitis epiploica. Reporte de cuatro casos / Epiploic appendagitis. Report of four cases

La apendicitis epiploica es una entidad rara, benigna y autolimitada. Su principal sintomatología es dolor abdominal focal acompañado de un recuento de glóbulos blancos y velocidades de sedimentación normales o ligeramente elevadas. Usualmente simulan cuadros de abdomen agudo como apendicitis o diverticulitis. Esta entidad presenta hallazgos característicos en la tomografía computarizada que llevan al cirujano a evitar procedimientos innecesarios. Presentamos cuatro casos con una revisión y discusión de la literatura.