Entorno inflamatorio diferencial en pacientes con osteoporosis y diabetes mellitus tipo 2 / Differential inflammatory environment in patients with osteoporosis and type 2 diabetes mellitus

Objetivo: La diabetes mellitus tipo 2 (DM2) y la osteoporosis son enfermedades asociadas con un entorno pro-inflamatorio, cuya prevención mediante nuevas estrategias terapéuticas podría evitar su desarrollo. Sin embargo, existe un escaso número de estudios que evalúen el perfil inflamatorio de la osteoporosis en pacientes con DM2.El objetivo de este estudio se centró en evaluar la respuesta inflamatoria inmunitaria mediante concentraciones séricas de nueve citocinas, dos de ellas de carácter anti-inflamatorio (IL-10, IL-5) y seis pro-inflamatorias (IL-2, IL-6, IL-12 (p70), IL-17A, TNFα e IFNɣ) en 163 individuos con DM2 y 47 controles. Una subpoblación, formada por 43 pacientes DM2 sin osteoporosis, y 33 con osteoporosis, fue analizada en más profundidad a nivel de parámetros óseos. Además, hemos evaluado las hormonas calciotropas, los marcadores de remodelado óseo, densidad mineral ósea y fracturas vertebrales en la población, y hemos analizado la relación de las citocinas ensayadas con la DM2, la osteoporosis y las fracturas vertebrales prevalentes.Los pacientes con DM2 tenían concentraciones séricas significativamente más altas de IL-10 en comparación con el grupo control (0,5±1 vs. 0,14±0,3 pg/ml; p=0,016) y los niveles de IL-12 p70 se mostraron más bajos en pacientes con DM2 respecto a los controles (2,9±1,6 vs. 3,9±3,1 pg/ml; p=0,027).En el grupo de pacientes con DM2 y osteoporosis, los niveles de la citocina IL-6 resultaron elevados respecto al grupo de DM2 sin osteoporosis (10,9±14,6 vs. 4,5±7,0; p=0,017). También se observó una asociación de IL-5, siendo sus niveles más bajos en el grupo DM2 con osteoporosis (1,7±0,2 vs. 3,8±0,6; p=0,032). Además, la IL-5 mostró una correlación directa con los niveles del biomarcador de formación ósea fosfatasa alcalina ósea (r=0,277, p=0,004) en la subpoblación de pacientes con DM2. El resto de citocinas no mostraron diferencias significativas. (AU)

Luminescent determination of propineb fungicide by using a carbon quantum dots-europium ions system.

We propose a modification of lanthanide-sensitized luminescence (LSL) to increase the selectivity and sensitivity of analytical methods based on this detection. LSL consists in the formation of complexes of lanthanide ions and organic compounds. Then, an intramolecular energy transfer occurs from the excited state of the ligand (organic analyte) to the emitting level of the lanthanide. The utilization of luminescent nanoparticles (carbon quantum dots, CQDs) in LSL systems can enhance their sensitivity and selectivity. CQDs can react with lanthanide ions through their carboxylic groups. These systems can thus be used as time-resolved luminescent probes. Propineb (PPN), a well-known dithiocarbamate fungicide, has been selected as the target analyte to show the advantages of using CQDs in LSL systems. The method proposed is based on the quenching produced by PPN in europium-CQDs luminescence, obtaining a detection limit of 0.03 µg mL-1 PPN and a method detection limit of 3 mg kg-1 in capers (bud and fruit), fulfilling the maximum residue limit in these samples (25 mg kg-1). The results showed that the use of nanoparticles in LSL systems may provide novel and simple analytical methods for the screening of contaminants in the agri-food sector.

Multidisciplinary approach to orbital embryonic rhabdomyosarcoma: About a case.

Of the head and neck tumoral lesions in children and adolescents, 5%-10% are primary malignant tumors. Among these tumors, orbital rhabdomyosarcoma stands out, which is the most common primary soft tissue sarcoma in children. Its diagnosis requires a high degree of clinical suspicion, and it can be corroborated with a series of examinations, in order to stage it and carry out the appropriate treatment. Currently, surgery and chemotherapy are the primary treatments, and the use of conventional radiotherapy is limited to cases where previous treatments fail or there is a risk of recurrence. The following case report aims to expose the clinical picture, diagnosis, staging and integral treatment of orbital rhabdomyosarcoma, as well as the interdisciplinary management that was performed to improve the patient's prognosis.

Abordaje multidisciplinario de un rabdomiosarcoma embrionario orbitario: a propósito de un caso / Multidisciplinary approach to orbital embryonic rhabdomyosarcoma: about a case

De las lesiones tumorales de cabeza y cuello en niños y adolescentes, un 5 a un 10% son tumores malignos primarios. Dentro de estos tumores destaca el rabdomiosarcoma orbitario infantil, que es el sarcoma primario de tejido blando más común en niños. Su diagnóstico requiere de un alto grado de sospecha clínica, que puede corroborarse con una serie de exámenes, para así estadificarlo e indicar el tratamiento adecuado. Actualmente se utiliza de primera intención cirugía y quimioterapia; el uso de la radioterapia convencional se limita a casos en los que fracasan los tratamientos anteriores o existe riesgo de recurrencia. El siguiente trabajo tiene como propósito exponer el cuadro clínico, diagnóstico, la estadificación y tratamiento integral de un rabdomiosarcoma embrionario orbitario, así como el manejo interdisciplinario que se realizó para mejorar el pronóstico de la paciente (AU)

Of the head and neck tumoral lesions in children and adolescents, 5 to 10% are primary malignant tumors. Among these tumors, orbital rhabdomyosarcoma stands out, which is the most common primary soft tissue sarcoma in children. Its diagnosis requires a high degree of clinical suspicion, and it can be corroborated with a series of examinations, in order to stage it and carry out the appropriate treatment. Currently, surgery and chemotherapy are the primary treatments, and the use of conventional radiotherapy is limited to cases where previous treatments fail or there is a risk of recurrence. The following case report aims to expose the clinical picture, diagnosis, staging and integral treatment of orbital rhabdomyosarcoma, as well as the interdisciplinary management that was performed to improve the patient's prognosis (AU)

Multidisciplinary approach to orbital embryonic rhabdomyosarcoma: about a case. / Abordaje multidisciplinario de un rabdomiosarcoma embrionario orbitario: a propósito de un caso.

Of the head and neck tumoral lesions in children and adolescents, 5 to 10% are primary malignant tumors. Among these tumors, orbital rhabdomyosarcoma stands out, which is the most common primary soft tissue sarcoma in children. Its diagnosis requires a high degree of clinical suspicion, and it can be corroborated with a series of examinations, in order to stage it and carry out the appropriate treatment. Currently, surgery and chemotherapy are the primary treatments, and the use of conventional radiotherapy is limited to cases where previous treatments fail or there is a risk of recurrence. The following case report aims to expose the clinical picture, diagnosis, staging and integral treatment of orbital rhabdomyosarcoma, as well as the interdisciplinary management that was performed to improve the patient's prognosis.

Sensitive fluorometric determination of quinclorac residues in rice.

Rice is one of the most important foods in the world due to its high nutritional value and production. Quinclorac, a selective herbicide, is one of the most detected pesticide residues in rice crops according to pesticide monitoring studies. Common methods for the determination of quinclorac in rice are very time-consuming and labour-intensive, so it is important to develop alternative sensitive and simple analytical methods able to detect quinclorac in food samples. Here we propose a fluorometric method for the screening of this herbicide at excitation/emission wavelengths of 238/358 nm/nm, respectively. A modified QuEChERS method was selected for sample treatment due to its simplicity and high recovery yields. The proposed method presents a detection limit of 2.5 ng mL-1 and satisfactory precision. Recovery experiments were performed in different kinds of rice (white and brown) at or below the Maximum Residue Limit established in European Union (5 mg kg-1), obtaining values close to 100%. All these characteristics ensure that the proposed method fulfils the requirements for its application in food control.

Graphene quantum dots-silver nanoparticles as a novel sensitive and selective luminescence probe for the detection of glyphosate in food samples.

Glyphosate (Gly) is the most widely used herbicide at the moment. It presents a broad spectrum of action, hence its use for many different crops. Regulatory agencies have constantly mentioned the low hazard potential of Gly to mammals. However, the International Agency for Research on Cancer concluded in 2015 that glyphosate is "probably carcinogenic to humans". For this reason, it is important to develop reliable analytical methods to quantify Gly in food samples. Here, we propose an analytical method that makes use of graphene quantum dots (GQDs) and cysteine-capped silver nanoparticles (AgNPs) for the screening of glyphosate, using QuEChERS as sample treatment. Gly quenched the luminescence of GQDs-AgNPs system, achieving an excellent sensitivity (detection limit of 9 ng mL-1) and selectivity. The method developed was applied to different types of pulses (peas and lupins), obtaining recoveries close to 100% and relative standard deviations lower than 4% in all cases. Its simplicity and rapidity make this method an interesting alternative to other existing methodologies for the analysis of this pesticide in food samples.

Ultra-early continuous cardiac monitoring improves atrial fibrillation detection and prognosis of patients with cryptogenic stroke.

BACKGROUND AND PURPOSE: Subclinical atrial fibrillation (AF) is known to underlie a number of cases of cryptogenic stroke (CrS). However, there is need to define the most effective strategy for AF detection. The diagnostic usefulness was analysed of a strategy based on ultra-early continuous monitoring in patients with CrS in terms of AF detection, oral anticoagulation treatment and stroke recurrence, in comparison to a standard outpatient strategy. METHODS: Patients with ischaemic stroke of undetermined origin and confirmed to be cryptogenic after extensive work-up were searched for AF with (i) a conventional strategy (historical cohort, n = 101) with serial electrocardiograms and 24-h Holter monitoring or (ii) an ultra-early monitoring strategy with insertable cardiac monitor (ICM) implanted before discharge (prospective cohort, n = 90). AF episodes lasting >1 min, anticoagulant treatment and stroke recurrence were recorded. RESULTS: During admission, AF was similarly detected in both cohorts (24% of patients). After discharge (mean follow-up 30 ± 10 months), AF detection rates were 17/80 (21.3%) and 38/65 (58.5%) for patients in the conventional versus the ultra-early ICM group (P < 0.001). Up to 41% of AF cases in the ICM cohort were detected within the first month. Oral anticoagulation was initiated in 37.6% versus 65.5% (P < 0.001) and stroke recurrence was recorded in 10.9% versus 3.3% (P 0.04) in the conventional versus the ICM cohort. CONCLUSIONS: Pre-discharge ICM implant allows detection of AF during follow-up in up to 58% of selected patients with CrS. Compared to a conventional strategy, ultra-early ICM implant results in higher anticoagulation rates and a decrease in stroke recurrence.

Automated Photochemically Induced Method for the Quantitation of the Neonicotinoid Thiacloprid in Lettuce.

In this work, we present an automated luminescence sensor for the quantitation of the insecticide thiacloprid, one of the main neonicotinoids, in lettuce samples. A simple and automated manifold was constructed, using multicommutated solenoid valves to handle all solutions. The analyte was online irradiated with UV light to produce a highly fluorescent photoproduct (λexc/λem = 305/370 nm/nm) that was then retained on a solid support placed in the flow cell. In this way, the pre-concentration of the photoproduct was achieved in the detection area, increasing the sensitivity of the analytical method. A method-detection limit of 0.24 mg kg-1 was achieved in real samples, fulfilling the Maximum Residue Limit (MRL) of The European Union for thiacloprid in lettuce (1 mg kg-1). A sample throughput of eight samples per hour was obtained. Recovery experiments were carried out at values close to the MRL, obtaining recovery yields close to 100% and relative standard deviations lower than 5%. Hence, this method would be suitable for routine analyses in quality control, as an alternative to other existing methods.

Exploiting the fluorescence resonance energy transfer (FRET) between CdTe quantum dots and Au nanoparticles for the determination of bioactive thiols.

This work focused the implementation of FRET processes between CdTe quantum dots (QDs), acting as donors, and gold nanoparticles (AuNPs), behaving as acceptors, for the determination of several bioactive thiols such as captopril, glutathione, l-cysteine, thiomalic acid and coenzyme M. The surface chemistry of the QDs and AuNPs was adjusted with adequate capping ligands, i.e. mercaptopropionic acid and cysteamine, respectively, to guarantee the establishment of strong electrostatic interaction between them and promoting the formation of stable FRET assemblies. Under these circumstances the fluorescence emission of the QDs was completely suppressed by the AuNPs. The assayed target analytes were capable of disrupting the donor-acceptor assemblies yielding a concentration-related reversion of the FRET process and restoring QDs fluorescence emission. Distinct mechanisms, involving enhancing of the QDs quantum yield (QY), AuNPs agglomeration, nanoparticles detachment, etc., could be proposed to explain the referred FRET reversion. The developed approach assured good analytical working ranges and demonstrate adequate sensitivity for the assayed compounds, anticipating great prospective for implementing rapid, simple and reliable sensing methodologies for the monitoring of pharmaceutical, food and environmental species. However, selectivity could be a hindrance in the detection of these bioactive thiols in more complex matrices such as environmental and food samples. This problem could be circumvented through the employment of multivariate chemometric methods for the analysis and processing of whole fluorometric response. Moreover, the proposed methodology shows a great analytical versatility since it is possible to easily adapt the surface chemistry, of both QDs and AuNPs, to the chemical nature of the target analyte.

Phytochemical profile and antioxidant activity of caper berries (Capparis spinosa L.): Evaluation of the influence of the fermentation process.

In this work, we report the phytochemical profile and antioxidant activity of caper berries (Capparis spinosa L.) before and after a fermentation process. The phytochemical profiles were evaluated by high-performance liquid chromatography with UV and electrospray ionization mass spectrometry detection (HPLC-DAD-ESI-MSn). Twenty-one compounds were characterized, and seven of them quantified. The main component of non-fermented berries was glucocapparin, which was degraded upon the fermentation process. Most of the compounds were quercetin and kaempferol glycosides, epicatechin, and proanthocyanidins. The main differences observed upon the fermentation process were a decrease in epicatechin concentration, the hydrolysis of quercetin glycosides, and the degradation of glucosinolates. Total phenolic and flavonoid contents, as well as the antioxidant activities by the in vitro antioxidant assays DPPH and ABTS+, were determined, observing that the values were slightly higher after the fermentation process.

Ole e 13 is the unique food allergen in olive: Structure-functional, substrates docking, and molecular allergenicity comparative analysis.

Thaumatin-like proteins (TLPs) are enzymes with important functions in pathogens defense and in the response to biotic and abiotic stresses. Last identified olive allergen (Ole e 13) is a TLP, which may also importantly contribute to food allergy and cross-allergenicity to pollen allergen proteins. The goals of this study are the characterization of the structural-functionality of Ole e 13 with a focus in its catalytic mechanism, and its molecular allergenicity by extensive analysis using different molecular computer-aided approaches covering a) functional-regulatory motifs, b) comparative study of linear sequence, 2-D and 3D structural homology modeling, c) molecular docking with two different ß-D-glucans, d) conservational and evolutionary analysis, e) catalytic mechanism modeling, and f) IgE-binding, B- and T-cell epitopes identification and comparison to other allergenic TLPs. Sequence comparison, structure-based features, and phylogenetic analysis identified Ole e 13 as a thaumatin-like protein. 3D structural characterization revealed a conserved overall folding among plants TLPs, with mayor differences in the acidic (catalytic) cleft. Molecular docking analysis using two ß-(1,3)-glucans allowed to identify fundamental residues involved in the endo-1,3-ß-glucanase activity, and defining E84 as one of the conserved residues of the TLPs responsible of the nucleophilic attack to initiate the enzymatic reaction and D107 as proton donor, thus proposing a catalytic mechanism for Ole e 13. Identification of IgE-binding, B- and T-cell epitopes may help designing strategies to improve diagnosis and immunotherapy to food allergy and cross-allergenic pollen TLPs.

Development of an semi-automatic and sensitive photochemically induced fluorescence sensor for the determination of thiamethoxam in vegetables.

The determination of thiamethoxam (TMX), a widely known neonicotinoid pesticide, by a multicommutated optosensing device implemented with photochemically induced fluorescence (PIF) has been developed. The combination of both methodologies allows, on one hand a quick on-line photodegradation of TMX and, on the other hand, the preconcentration, quantification and desorption of the fluorescent photoproduct generated once retained on C18 silica gel filling the flow-cell which was monitored at 353 and 407nm for excitation and emission wavelengths, respectively. The proposed analytical method presents a detection limit of 3.6ngmL(-1) by using Multicommutated Flow Injection Analysis (MCFIA) as flow methodology. Recovery experiments have been carried out in different kinds of vegetables at levels same or below the legislated maximum residue limit, demonstrating that this method combines advantages such as simplicity, high sensibility and high selectivity, in addition to fulfill the requirements for its applications in quality control. The obtained results in the analysis of real samples were in good agreement with those provided by a reference liquid chromatography (HPLC) method.

Tumor recurrence and tumor-related mortality in endometrial cancer: Analysis in 276 patients.

BACKGROUND: In this manuscript, we assessed tumor recurrence and tumor-related mortality in a clinical series of endometrial cancer patients. MATERIALS AND METHODS: A retrospective evaluation of 276 patients (mean age 64 years) with histologically confirmed endometrial cancer treated at a single hospital in Madrid (Spain) was conducted. The median follow-up was estimated using the inverse Kaplan-Meier method. RESULTS: Salient findings were endometrioid carcinoma (84.8% of cases), grade G1 (48.9%) and stages IB (35.1%) and IC (23.2%). Myometrial infiltration >50% was documented in 31.2% of cases and lymphovascular space invasion in 11.9%. After surgery, 52.5% of patients were classified into the low risk group, 21.4% into the intermediate risk group and 26.1% into the high risk group. Tumor recurrence occurred in 14.5% of patients, with an estimated median follow-up of 45 months (95% confidence interval (CI): 41.2-48.8), locoregional recurrence in 42.5% and distant recurrences in 57.5%. Furthermore, 40% of tumor recurrences developed during the first year after primary treatment and 90% over the first 3 years of follow-up. The tumor-related mortality rate was 15.9%. The estimated median follow-up was 46 months (95% CI: 43.0-49.0). Furthermore, 5.07% of death because of tumor developed during the first year after primary treatment and 13.77% over the first 3 years of follow-up. CONCLUSION: The rates of tumor-related death and tumor recurrence in endometrial cancer patients are low, with the highest percentages occurring within 3 years of primary treatment. Most of the recurrences occur outside the pelvis.

Multi-commutated fluorometric optosensor for the determination of citrinin in rice and red yeast rice supplements.

Citrinin is a toxic secondary metabolite first isolated from Penicillium citrinum, although is also produced by other species of Penicillium and Aspergillus. It has highly toxic, mutagenic, teratogenic and carcinogenic properties and is often found in crops, vegetables and fruit. To our knowledge there is no specific legislation on maximum levels permitted for citrinin, so no official analytical method is currently available for its determination. Our laboratory developed a fluorometric flow-through optosensor using Sephadex SPC-25 as solid support. Multi-commutated flow injection analysis was used for the construction of the manifold and for handling solutions. In this way, we minimised waste generation and human intervention, which are critical aspects when dealing with highly toxic compounds such as citrinin. The optimum excitation/emission wavelengths were set at 330/494 nm; the calibration curve was linear in the concentration range 35-900 ng ml⁻¹. A detection limit of 10.5 ng ml⁻¹ and relative standard deviations (RSDs) lower than 3% were obtained. The developed optosensor was applied to the determination of citrinin in rice and dietary supplements containing red yeast rice.

Rentabilidad diagnóstica de la broncoscopia en la enfermedad neoplásica en la Unidad de Fibrobroncoscopias del Hospital General Universitario de Albacete / Diagnostic yield of bronchoscopy in neoplastic disease in Bronchofibroscopy Unit of Albacete General University Hospital

Antecedentes: El cáncer de pulmón es la segunda causa de muerte después de las enfermedades cardiovasculares. El carcinoma broncogénico tiene una causa desencadenante fundamental, el tabaco. La fibrobroncoscopia es necesaria para el diagnóstico y la estadificación del cáncer pulmonar, lo que nos ayudará a estimar el pronóstico y decidir la actitud terapéutica a seguir. En este estudio analizamos la rentabilidad de las distintas técnicas de la broncoscopia en el diagnóstico del cáncer de pulmón. Métodos: En 181 pacientes a los que se realizó fibrobroncoscopia y que tuvieron un diagnóstico final de neoplasia, se analizó la comorbilidad previa, el hábito tabáquico, las diversas técnicas broncoscópicas a las que fueron sometidos y el estadio TNM en el que se hallaban en el momento del diagnóstico. También se valoró la rentabilidad de nuestras técnicas en relación con otros estudios de la bibliografía. Resultados: El 86,2% de los pacientes presentaba historia de tabaquismo; el 49,2%, diagnóstico de enfermedad pulmonar obstructiva crónica, y el 18,9%, otra neoplasia previa. La exploración endoscópica mostró lesión endobronquial en el 58% de los pacientes. El broncoaspirado fue positivo en el 53,6% de los procedimientos realizados; la biopsia bronquial, en el 81,9%; la biopsia transbronquial, en el 71,8% (en asociación con radioscopia positiva en el 81% y sin radioscopia, en el 61% de los casos), y la punción transbronquial, positiva en el 64,3% (con patólogo presente la rentabilidad diagnóstica ascendía al 72,7%). Conclusiones: La rentabilidad de las técnicas fibrobroncoscópicas que se utilizan en nuestro medio es similar a la de otros estudios importantes realizados hasta la fecha (AU)

Background: Lung cancer is the second leading cause of mortality after cardiovascular diseases. Bronchogenic carcinoma has a fundamental underlying cause, that is, tobacco. The bronchoscopy is required for lung cancer diagnosis and staging and will help us to estimate prognosis and determine the therapeutic approach to follow. In this study, the yield of the various techniques of bronchoscopy in the diagnosis of lung cancer has been analyzed. Methods: Previous comorbidity, smoking habit, the different bronchoscopic techniques the subject underwent and the patient's TNM stage at the time of diagnosis were analyzed in 181 patients who underwent bronchoscopy and whose final diagnosis was neoplasm. The performance of our techniques in relation to other studies in the literature was also evaluated. Results: A total of 86.2% of patients had a history of smoking, 49.2%, diagnosis of Chronic obstruction pulmonary disease and 18.9% had had another previous malignancy. The endoscopic examination showed endobronchial lesion in 58% of patients. BAS was positive in 53.6% of procedures performed, bronchial biopsy 81.9%, transbronchial biopsy in 71.8% (in association with positive fluoroscopy in 81% and without fluoroscopy in 61% of cases) and positive transbronchial needle aspiration in 64.3% (with pathologist present the diagnostic yield amounted to 72.7%). Conclusions: The yield of bronchoscopic techniques used in our environment is similar to that found in other major studies conducted to date (AU)

Olive pollen profilin (Ole e 2 allergen) co-localizes with highly active areas of the actin cytoskeleton and is released to the culture medium during in vitro pollen germination.

Pollen allergens offer a dual perspective of study: some of them are considered key proteins for pollen physiology, but they are also able to trigger allergy symptoms in susceptible humans after coming in contact with their tissues. Profilin (Ole e 2 allergen) has been characterized, to some extent, as one of the major allergens from Olea europaea L. pollen, a highly allergenic species in the Mediterranean countries. In order to obtain clues regarding the biological role of this protein, we have analyzed both its cellular localization and the organization of actin throughout pollen hydration and early pollen tube germination. The localization of the cited proteins was visualized by confocal laser scanning microscopy immunofluorescence using different antibodies. Upon pollen hydration and pollen germination, a massive presence of profilin was detected close to the site of pollen tube emergence, forming a ring-like structure around the 'effective' apertural region. Profilin was also detected in the pollen exine of the germinating pollen grains and in the germination medium. After using a permeabilization-enhanced protocol for immunolocalization, profilin was also localized in the cytoplasm of the pollen tube, particularly at both the proximal and apical ends. Noticeable accumulations of actin were observed in the cytoplasm of the pollen tube; particularly, in both the apical region and the area immediately close to the aperture. Actin filaments were not observed, probably due to the need of further enhanced fixation procedures. The ultrastructural localization of profilin showed the presence of the protein in the cytoplasm of both the mature pollen grain and the pollen tube. The results shown here could be interpreted as signs of a massive dissociation of the actin-profilin complexes, mobilization of actin monomers, and therefore, an intense activity of the actin cytoskeleton. The extensive release of allergenic proteins from the pollen grain into the surrounding aqueous media, as described here for profilin, may help us to understand the mechanisms by which these allergens might come in contact with the human mucosa, therefore triggering the symptoms of allergy.