Fructose 1,6-bisphosphate inhibits osteoclastogenesis by attenuating RANKL-induced NF-κB/NFATc-1.

BACKGROUND: Although some glycolytic intermediates have been shown to modulate several cell type formation and activation, the functional role of fructose 1,6-bisphosphate (FBP) on osteoclastogenesis is still unknown. METHODS: Osteoclastogenesis was evaluated on bone marrow preosteoclasts cultured with M-CSF - 30 ng/ml, RANKL - 10 ng/ml, and two concentrations of FBP (100 and 300 µM). TRAP-positive stained cells were counted, and osteoclastogenic marker genes expression were evaluated by qPCR. Osteoclasts resorption capacity was evaluated by the expression of specific enzymes and capacity to resorb a mineralized matrix. The NF-κB activation was detected using RAW 264.7, stably expressing luciferase on the NF-κB responsive promoter. RESULTS: We show that FBP, the product of the first stage of glycolysis, inhibited RANKL-induced osteoclasts differentiation and TRAP activity. The treatment of preosteoclasts with FBP attenuated osteoclast fusion and formation, without affecting cell viability. Moreover, the inhibition of several osteoclastogenic marker genes expression (TRAP, OSCAR, DC-STAMP, Integrin αv, NFATc1) by FBP correlates with a reduction of mineralized matrix resorption capacity. The mechanism underlying FBP-inhibition of osteoclastogenesis involves NF-κB/NFATc1 signaling pathway inhibition. CONCLUSION: Altogether these data show a protective role of a natural glycolytic intermediate in bone homeostasis that may have therapeutic benefit for osteolytic diseases.

Anoxic photocatalytic treatment of synthetic mining wastewater using TiO2 and scavengers for complexed cyanide recovery.

The wastewater from gold exploitation is well known for the toxic nature of recalcitrant cyanide metallic complexes. In this work the selectivity in the photocatalytic degradation of gold mining wastewater (Fe(CN)63-) using suspended TiO2 with alcoholic and organic acid scavengers in a mini-CPC photoreactor with a 30 W UV-A LED as an artificial source of light was evaluated. The study was done in four stages: 1. load catalyst determination, 2. combination of scavengers in a typical photocatalytic degradation, 3. evaluation of scavenger concentration and 4. kinetic study. The decomposition into CN- and Fe removal of the cyanocomplex were tracked. It was observed that formic acid (FA) and t-butanol (t-ButOH) were the best scavengers for the photocatalytic degradation under anoxic conditions. The best concentrations of acceptors used in the study were 10 mM FA and 10 mM t-ButOH at 20 W m-2 of UV-A power, reaching 80% degradation of Fe(CN)63-, 40% Fe removal and 18 ppm of free cyanide CN release to the liquid phase. The electrical efficiency of oxidation per order (EEo) was increased by about 50% with the addition of scavengers instead of traditional anoxic photocatalytic treatment. It was proved that the photocatalytic decomposition of the Fe cyanocomplex was done through the photoreduction path of the metal complex.

Tau and amyloid-related pathologies in the entorhinal cortex have divergent effects in the hippocampal circuit.

The entorhinal cortex (EC) is affected early in Alzheimer's disease, an illness defined by a co-occurrence of tau and amyloid-related pathologies. How the co-occurrence of these pathologies in the EC affects the hippocampal circuit remains unknown. Here we address this question by performing electrophysiological analyses of the EC circuit in mice that express mutant human amyloid precursor protein (hAPP) or tau (hTau), or both in the EC. We show that the alterations in the hippocampal circuit are divergent, with hAPP increasing but hTau decreasing neuronal/circuit excitability. Most importantly, mice co-expressing hAPP and hTau show that hTau has a dominant effect, dampening the excitatory effects of hAPP. Additionally, compensatory synaptic downscaling, in response to increased excitability in EC was observed in subicular neurons of hAPP mice. Based on simulations, we propose that EC interneuron pruning can account for both EC hyperexcitability and subicular synaptic downscaling found in mice expressing hAPP.

An approach to utilize the artificial high power LED UV-A radiation in photoreactors for the degradation of methylene blue.

Utilization of UV LED light is trending in the development of photoreactors for pollutant treatment. In this study, two different geometries were studied in the degradation of methylenebBlue (MB) using high power UVA LED as a source of light. The dosage, initial concentration, electric power, and H2O2 addition were evaluated in the two geometries: a mini CPC (Cilindrical Parabolic Collector) and a vertical cylindrical with external irradiation both coupled with LED UVA. Best degradation was obtained for 0.3 g L-1 TiO2, 40 min, and 15 ppm of MB of initial concentration in the standard batch reactor. It was found that the best system was a cpc geometry. Also, hydrogen peroxide was used as an electron acceptor and 97% degradation was obtained in 30 min with 10 mM H2O2 and 0.4 g TiO2/L. Power of the LEDs was also evaluated and it was found that 20 W m-2 is the best operational condition to achieve the best MB degradation avoiding the oxidant species recombination.

Six-month Follow-up of Cervical Composite Restorations Placed With a New Universal Adhesive System: A Randomized Clinical Trial.

PURPOSE: The objective of this double-blind, randomized clinical trial was to evaluate the six-month clinical performance of a new universal adhesive (Xeno Select, Dentsply) in noncarious cervical lesions (NCCLs) using two evaluation criteria: World Dental Federation (FDI) and the US Public Health Service (USPHS). METHODS AND MATERIALS: A total of 124 restorations were randomly placed in 31 patients according to the following groups: ER-D = etch-and-rinse/dry dentin; ER-M = etch-and-rinse/moist dentin; SE-et = selective enamel etching; and SET = self-etch. The composite resin EVOLUX (Dentsply) was placed incrementally. The restorations were evaluated after one week (baseline) and at six months using the FDI and USPHS criteria. Statistical analyses were performed using appropriate tests (α=0.05). RESULTS: Fifteen restorations were lost or fractured at six months (one for ER-D, three for ER-M, five for SE-et, and six for SET) (p>0.05 at six-month recall). When ER (ER-D and ER-M) was compared with SE (SE-et and SET) there was a significant difference in the retention rate after six months (p=0.001). Marginal staining and postoperative sensitivity to air were only observed in three (one for ER-M and two for SET) and two restorations (two for ER-D) in both evaluation criteria (p>0.05), respectively. Forty-seven restorations were considered to have minor discrepancies in marginal adaptation at the six-month recall using the FDI criteria (13 for ER-D, 10 for ER-M, 11 for SE-et, and 13 for SET; p>0.05 between groups). However, for all groups, a significant difference was detected when baseline and six-month data were compared (p<0.05). CONCLUSIONS: The six-month clinical behavior of Xeno Select Universal Adhesive depends on the bonding strategy used. The universal adhesive did not fulfill the American Dental Association criteria for full approval when used in the self-etch mode.

Tau pathology-mediated presynaptic dysfunction.

Brain tauopathies are characterized by abnormal processing of tau protein. While somatodendritic tau mislocalization has attracted considerable attention in tauopathies, the role of tau pathology in axonal transport, connectivity and related dysfunctions remains obscure. We have previously shown using the squid giant synapse that presynaptic microinjection of recombinant human tau protein (htau42) results in failure of synaptic transmission. Here, we evaluated molecular mechanisms mediating this effect. Thus, the initial event, observed after htau42 presynaptic injection, was an increase in transmitter release. This event was mediated by calcium release from intracellular stores and was followed by a reduction in evoked transmitter release. The effect of htau42 on synaptic transmission was recapitulated by a peptide comprising the phosphatase-activating domain of tau, suggesting activation of phosphotransferases. Accordingly, findings indicated that htau42-mediated toxicity involves the activities of both GSK3 and Cdk5 kinases.

Predicción de resultados de cistoscopias en la práctica / Predicting Results of Daily-practice Cystoscopies

Objetivo: Elaborar un modelo predictivo de cáncer de vejiga en una población clínica no seleccionada derivada a cistoscopia. Materiales y métodos: Pacientes consecutivos sometidos a cistoscopia debida a sospecha o seguimiento de un cáncer de vejiga previamente diagnosticado. Todos los pacientes fueron sometidos a citología urinaria y un BTA-stat®-test (BTA). Para evitar sesgos de evaluación, BTA, citologías y cistoscopias fueron realizados de forma ciega. Usamos regresión logística para predecir los resultados de la cistoscopia a partir de citología, BTA y variables clínicas. Resultados: Entre agosto de 2011 y julio de 2012 seleccionamos 244 pacientes y 237 fueron válidos para el análisis. Un 13% fueron de nuevo diagnóstico y un 87% de seguimiento. Las sensibilidades de la citología y el BTA fueron 57,9% (IC 95%: 42,2-72,1) y 63,2% (IC 95%: 47,3-76,6) con especificidades de 84,4% (IC 95%: 78,7- 88,8) y 82,9% (IC 95%: 77,1-87,5). El modelo predictivo incluyó BTA, citología, tiempo transcurrido desde el diagnóstico del tumor previo y tratamiento con mitomicina o BGC en los últimos 3 meses. La precisión del modelo (AUC) fue 0,85 (0,78-0,92), y bajó a 0,79 al excluir el BTA (p = 0,026). En los casos de seguimiento, un umbral de 10% en las probabilidades predichas por el modelo resultó en un valor predictivo negativo de 95,7%, y 95,0% en los tumores de bajo grado. Conclusión: En un contexto de contención de costes nuestro modelo puede usarse para espaciar las cistoscopias en pacientes con tumores de bajo grado previos, resultando en un uso más eficiente de recursos del sistema de salud

Objective: Our objective was to elaborate a predictive model of bladder cancer, in an unselected clinical population submitted to cystoscopy. Materials and methods: We recruited consecutive patients who underwent cystoscopy due to suspicion of bladder cancer or surveillance of a previously diagnosed bladder cancer. Urine cytology and a BTA-stat® (BTA) test were carried out for all patients. To avoid an assessment bias, the BTA-tests, cytologies and cystoscopies were conducted in a blinded fashion. We used logistic regression to predict cystoscopy results from cytology, BTA-test and clinical variables. Results: From August 2011 to July 2012, we recruited 244 patients and 237 were valid for analysis. Newly diagnosed and surveillance cases were 13% and 87% respectively. Cytology and BTA-test sensitivities were 57.9% (CI 95: 42.2-72.1) and 63.2% (CI 95: 47.3-76.6) with specificities of 84.4% (CI 95: 78.7-88.8) and 82.9% (CI 95: 77.1-87.5). The predictive model included the BTA-test, cytology, time since previous tumor, and treatment with mitomicin or BGC during the last three months. The model predictive accuracy (AUC) was 0.85 (0.78-0.92), and dropped to 0.79 when excluding the BTA-test (p = 0.026). For the surveillance of bladder cancer, a 10% threshold on the model predicted probabilities resulted in an overall negative predictive value of 95.7%, and 95.0% in low grade tumors. Conclusion: In a cost containment environment, our prediction model could be used to space out cystoscopies in patients with previous, low grade tumors, resulting in a more efficient use of resources in the healthcare system

Predicting results of daily-practice cystoscopies.

OBJECTIVE: Our objective was to elaborate a predictive model of bladder cancer, in an unselected clinical population submitted to cystoscopy. MATERIALS AND METHODS: We recruited consecutive patients that underwent cystoscopy due to suspicion of bladder cancer or surveillance of a previously diagnosed bladder cancer. Urine cytology and a BTA-stat® (BTA) test were carried out for all patients. To avoid an assessment bias, the BTA-tests, cytologies and cystoscopies were conducted in a blinded fashion. We used logistic regression to predict cystoscopy results from cytology, BTA-test and clinical variables. RESULTS: From August 2011 to July 2012, we recruited 244 patients and 237 were valid for analysis. Newly diagnosed and surveillance cases were 13% and 87% respectively. Cytology and BTA-test sensitivities were 57.9% (CI 95: 42.2-72.1) and 63.2% (CI 95: 47.3-76.6) with specificities of 84.4% (CI 95: 78.7-88.8) and 82.9% (CI 95: 77.1-87.5). The predictive model included the BTA-test, cytology, time since previous tumour, and treatment with mitomicin or BGC during the last three months. The model predictive accuracy (AUC) was .85 (.78-.92), and dropped to 0.79 when excluding the BTA-test (P=.026). For the surveillance of bladder cancer, a 10% threshold on the model predicted probabilities resulted in an overall negative predictive value of 95.7%, and 95.0% in low grade tumours. CONCLUSION: In a cost containment environment, our prediction model could be used to space out cystoscopies in patients with previous, low grade tumours, resulting in a more efficient use of resources in the healthcare system.

[Conservative treatment of 2 tracheal lesions secondary to anesthetic intubation]. / Tratamiento conservador en dos lesiones traqueales secundarias a intubación anestésica.

This case report describes two patients admitted to our hospital for elective surgery, one for biliary disease and the other for vascular disease. Shortly after surgery each presented a clinical picture attributable to membranous tracheal pars rupture caused by anesthetic intubation. Airway lesions were diagnosed and, after patient status was evaluated, conservative medical treatment was prescribed in both cases. Outcome was excellent, with no complications, within a few days. These cases demonstrate the efficacy of this way of managing this potentially serious complication.

Intervención de enfermería en la discolisis percutánea con láser Holmium / Nurse's role in the use of Holmium laser for percutaneous discectomy

En el presente trabajo se presentan las bases cientificas y tecnologicas de un nuevo tratamiento sobre 40 discos intervertebrales patologicos en 22 pacientes (7 mujeres y 75 hombres), mediante la discolisis percutanea con laser Holmium, practicado en la Clinica Reina Sofia de Bogota, durante un lapso de 5 meses (del 29 de enero al 29 de junio de 1994). En la aplicacion de esta nueva terapeutica y en el desarrollo del procedimiento, se destaca la importancia y efectividad de la enfermera profesional como integrante del equipo de salud en esta especialidad. Las ventajas de la discolisis con laser frente a la disquectomia abierta convencional, pueden resumirse asi: ser una intervencion minimamente invasora y muy poco traumática; no requiere anestesia general ni hospitalizacion; exige menor tiempo de incapacidad postoperatoria; menor incidencia de complicaciones y menores costos. Vale anotar que la F.D.A. de los Estados Unidos, ya aprobo el uso del laser Ho-Yag (Holmium) y el KTP para la realizacion de la discolisis en los casos de hernia discal.