[Active surveillance for patients with localized prostate cáncer. Adherence and protocol drop analysis.] / La vigilancia activa en pacientes con cáncer de próstata localizado. Análisis de adherencia y salida del protocolo.

OBJECTIVE: VA is currently considered the treatment of choice for patients with low and very low risk prostate cancer. We analyzed the evolution of this treatment strategy in our series and adherence to the protocol. MATERIAL AND METHODS: Ambispective study of patients in VA in our center between 2014- 2019. 237 meet inclusion criteria, of which 142 (60%) have a minimum of 12 months of follow- up. Mean age: 68.5 (4678), median PSA 6.37 ng / ml (1-33). 229 (96.6%) are ISUP 1 and 8 (3.4%) ISUP 2. Objectives are proposed to assess our adherence to the protocol. Descriptive statistics are used to communicate the results. RESULTS: According to the classification by risk groups of the NCCN, 145 (61.2%), 49 (20.7%) and 42 (17.7%) were very low risk, low risk and favorable intermediate risk patients, respectively. The median of follow-up is 14 months (0-66). Of the patients with a minimum follow-up of 12 months, 107 (75.4%) were re-biopsied. 80 (33.8%) leave the protocol in these 5 years, 31.3% (25) by their own decision, 55% (44) due to medical criteria, and 11.3% (9) go to WW. After 5 years of follow-up, 99.2% of patients are still alive, 0.8% died of specific non-cancer causes. Of the objectives to assess adherence, 8 are achieved, 1 partially and 1 is not evaluable. CONCLUSIONS: VA in our center is already the treatment of choice for very low-risk patients, with a constant increase from year to year. Adherence to the protocol has been favorable during the period of time studied.

OBJETIVO: La VA se ha convertido en uno de los tratamientos de elección del CP localizado de bajo y muy bajo riesgo. Analizamos la evolución de esta estrategia de tratamiento en nuestra serie, así como la adherencia al protocolo.MATERIAL Y MÉTODOS: Estudio ambispectivo de los pacientes incluidos en VA en nuestro centro entre los años 2014-2019. 237 pacientes cumplen los criterios de inclusión en VA, de los cuales 142 (60%) tienen un seguimiento mínimo de 12 meses. Edad media: 68,5(46-78), mediana PSA 6,37 ng/ml (1-33). 229 pacientes (96,6%) son ISUP 1 y 8 (3,4%) ISUP 2. Se proponen unos objetivos para valorar nuestra adherencia al protocolo. Se utiliza estadística descriptiva y contraste de hipótesis para comunicar los resultados.RESULTADOS Y DISCUSIÓN: Atendiendo a la clasificación por grupos de riesgo de la NCCN, 145 (61,2%), 49 (20,7%) y 42 (17,7%) eran pacientes muy bajo riesgo, bajo riesgo y riesgo intermedio favorable respectivamente. El tiempo (mediana) de permanencia en el programa es de 14 meses (0-66). De los pacientes con un seguimiento mínimo de 12 meses, 107 (75,4%) son re ­ biopsiados. 80 pacientes (33,8%) salen del protocolo en estos 5 años, 31,3% (25) por decisión propia, 55% (44) por criterios médicos, y 11,3% (9) pasan a WW. Tras 5 años de seguimiento, el 99,2% de los pacientes continúan vivos, el 0,8% falleció por causas no cáncer específicas. De los objetivos para evaluar la adherencia, 8 de ellos se alcanzan, 1 parcialmente y 1 no es evaluable. CONCLUSIONES: La VA en nuestro centro constituye actualmente el tratamiento de elección para los pacientes con muy bajo riesgo. La adherencia al protocolo ha sido favorable durante el periodo de tiempo estudiado.

We Are Very Similar but Not Really: The Moderating Role of Cultural Identification for Refugee Resettlement of Venezuelans in Colombia.

This study aims to test the theoretical model of career adaptability of refugees to investigate the dynamics of successful resettlement. The theoretical model is grounded on career construction and social network theory. We employ quantitative and qualitative methodologies to test the model in a sample of Venezuelans living and working in Colombia. The quantitative results provide partial support for Campion's model. However, we test an alternative model and find that career adaptability has a direct relationship with subjective resettlement (i.e., life satisfaction and psychological health). In addition, cultural identification plays a buffering role on the harmful effects of discrimination on subjective resettlement. Qualitative results from eight in-depth interviews shed light on the process of refugee resettlement, thus revealing the role of social networks. Our study contributes to previous research on refugees by testing, adapting, and expanding a novel model of work resettlement and focusing on a group of refugees transitioning from one emerging country to another emerging country.

Uropatía obstructiva bilateral y microvejiga post-radioterapia / Bilateral obstructive uropathy and micro-bladder after

No disponible

Sorption behaviors of antimicrobial and antiparasitic veterinary drugs on subtropical soils.

Brazil is one of the world's largest producers of animal protein, requiring the large-scale use of veterinary drugs. The administration of antimicrobials and antiparasitics is a common practice. However, there is a lack of information on how these drugs impact the environment. Antimicrobials are capable of altering the soil microbial population and are responsible for the development of multidrug-resistant microbial strains. Therefore, it is important to evaluate the fate and transport of these compounds in the environment, and one parameter used for this purpose is the soil-water partition coefficient. In this work, an assessment was made of the soil sorption behaviors of 18 drugs from seven different families, including antimicrobials (sulfonamides, fluoroquinolones, amphenicols, and macrolides) and antiparasitic drugs (milbemycin, avermectins, and benzimidazoles). Seven subtropical soils of different textural classes were tested. The Freundlich sorption coefficients, expressed as µg1-1/n (cm3)1/n g-1, were in the following ranges: 0.45 to 19 (sulfonamides), 72 to 2410 (fluoroquinolones), 9 to 58 (thiabendazole), 0.03 to 0.48 (florfenicol), 105 to 424 (moxidectin), 14 to 184 (avermectins), and 1.5 to 74 (macrolides). The results showed that the drugs belonging to the same family, with chemical structures in common, presented similar behaviors regarding sorption and desorption, for the different soils tested and are generally in agreement with soils from temperate regions. The data set obtained in this work give an overview of the fate of the veterinary drugs in Brazilian subtropical soils with different textures and composition and can be very helpful for exposure risk assessments.

Sorption mechanism of enrofloxacin on humic acids extracted from Brazilian soils.

Veterinary antimicrobials are emerging environmental contaminants of concern. In this study, the sorption of enrofloxacin (ENR) onto humic acids (HAs) extracted from three Brazilian soils was evaluated. HAs were characterized by elemental analysis and solid 13C nuclear magnetic resonance spectroscopy. The sorption of ENR onto HAs was at least 20-fold higher than onto the soils from which they were separated. Ionic and cation bridging are the primary interactions involved. The interactions driven by cation exchange are predominant on HAs, which appear to have abundant carboxylic groups and a relatively high proportion of H-bond donor moieties with carbohydrate-like structures. Interactions explained by cation bridging and/or surface complexation on HAs are facilitated by moieties containing conjugated ligands, significant content of oxygen-containing functional groups, such as phenolic-OH or lignin-like structures. HAs containing electron-donating phenolic moieties and carboxylic acid ligand groups exhibit a sorption mechanism that is primarily driven by strong metal binding, favoring the formation of ternary complexes between functional groups of the organic matter and drugs.

Electrospinning of gelatin and SMPU with carbon nanotubes for tissue engineering scaffolds.

The nanofibres created by electrospinning technique are currently used for a variety of applications in tissue engineering; and Gelatin and Polyurethane Shape-Memory (SMPU) have important results in biomedicine. Similarly, carbon nanotubes combined with other biomaterials change important properties, opening new opportunities for biomedical applications. In this work, we constructed scaffold using electrospinning technique based in bovine-hide gelatin, SMPU and both materials hybrid with carbon nanotube. Morphology and cytotoxicity were evaluated and mechanical properties for two materials were obtained in scaffold building. Morphological, mechanical and citotoxic properties of the electrospun fibers were found to be dependent of alteration in materials concentration, electrospinning conditions and MWCNT concentration. According to morphological, cytotoxic and mechanical analysis, SMPU more MWCNT were the best material, with nanofibers of 451 nm, tensile strength of 1.912 MPa, and a high ratio surface volume.

Inhibition of cholinergic pathways in Drosophila melanogaster by α-conotoxins.

Nicotinic acetylcholine receptors (nAChRs) play a pivotal role in synaptic transmission of neuronal signaling pathways and are fundamentally involved in neuronal disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia. In vertebrates, cholinergic pathways can be selectively inhibited by α-conotoxins; we show that in the model organism Drosophila, the cholinergic component of the giant fiber system is inhibited by α-conotoxins MII, AuIB, BuIA, EI, PeIA, and ImI. The injection of 45 pmol/fly of each toxin dramatically decreases the response of the giant fiber to dorsal longitudinal muscle (GF-DLM) connection to 20 ± 13.9% for MII; 26 ± 13.7% for AuIB, 12 ± 9.9% for BuIA, 30 ± 11.3% for EI, 1 ± 1% for PeIA, and 34 ± 15.4% for ImI. Through bioassay-guided fractionation of the venom of Conus brunneus, we found BruIB, an α-conotoxin that inhibits Drosophila nicotinic receptors but not its vertebrate counterparts. GF-DLM responses decreased to 43.7 ± 8.02% on injection of 45 pmol/fly of BruIB. We manipulated the Dα7 nAChR to mimic the selectivity of its vertebrate counterpart by placing structurally guided point mutations in the conotoxin-binding site. This manipulation rendered vertebrate-like behavior in the Drosophila system, enhancing the suitability of Drosophila as an in vivo tool to carry out studies related to human neuronal diseases. .

Use of experimental design to optimize a triple-potential waveform to develop a method for the determination of streptomycin and dihydrostreptomycin in pharmaceutical veterinary dosage forms by HPLC-PAD.

An HPLC-PAD method using a gold working electrode and a triple-potential waveform was developed for the simultaneous determination of streptomycin and dihydrostreptomycin in veterinary drugs. Glucose was used as the internal standard, and the triple-potential waveform was optimized using a factorial and a central composite design. The optimum potentials were as follows: amperometric detection, E1=-0.15V; cleaning potential, E2=+0.85V; and reactivation of the electrode surface, E3=-0.65V. For the separation of the aminoglycosides and the internal standard of glucose, a CarboPac™ PA1 anion exchange column was used together with a mobile phase consisting of a 0.070 mol L(-1) sodium hydroxide solution in the isocratic elution mode with a flow rate of 0.8 mL min(-1). The method was validated and applied to the determination of streptomycin and dihydrostreptomycin in veterinary formulations (injection, suspension and ointment) without any previous sample pretreatment, except for the ointments, for which a liquid-liquid extraction was required before HPLC-PAD analysis. The method showed adequate selectivity, with an accuracy of 98-107% and a precision of less than 3.9%.

The effect of glass ionomer and adhesive cements on substance P expression in human dental pulp

OBJECTIVES: The purpose of this study was to quantify the effect of glass ionomer and adhesive cements on SP expression in healthy human dental pulp. Study DESIGN: Forty pulp samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. In thirty of these premolars a Class V cavity preparation was performed and teeth were equally divided in three groups: Experimental Group I: Glass Ionomer cement was placed in the cavity. Experimental Group II: Adhesive Cement was placed in the cavity. Positive control group: Class V cavities only. The remaining ten healthy premolars where extracted without treatment and served as a negative control group. All pulp samples were processed and SP was measured by radioimmunoassay. RESULTS: Greater SP expression was found in the adhesive cement group, followed by the glass ionomer and the positive control groups. The lower SP values were for the negative control group. ANOVA showed statistically significant differences between groups (p < 0.0001). Tukey HSD post hoc tests showed statistically significant differences in SP expression between negative control group and the 3 other groups (p < 0.01). Differences between the cavity-only group and the two experimental groups were also statistically significant (p < 0.05 and p < 0.01 respectively). There is also a statistically significant difference between the two experimental groups (p < 0.01). CONCLUSIONS: These findings suggest that adhesive cements provoke a greater SP expression when compared with glass ionomer

The effect of glass ionomer and adhesive cements on substance P expression in human dental pulp.

OBJECTIVES: The purpose of this study was to quantify the effect of glass ionomer and adhesive cements on SP expression in healthy human dental pulp. STUDY DESIGN: Forty pulp samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. In thirty of these premolars a Class V cavity preparation was performed and teeth were equally divided in three groups: Experimental Group I: Glass Ionomer cement was placed in the cavity. Experimental Group II: Adhesive Cement was placed in the cavity. Positive control group: Class V cavities only. The remaining ten healthy premolars where extracted without treatment and served as a negative control group. All pulp samples were processed and SP was measured by radioimmunoassay. RESULTS: Greater SP expression was found in the adhesive cement group, followed by the glass ionomer and the positive control groups. The lower SP values were for the negative control group. ANOVA showed statistically significant differences between groups (p<0.0001). Tukey HSD post hoc tests showed statistically significant differences in SP expression between negative control group and the 3 other groups (p<0.01). Differences between the cavity-only group and the two experimental groups were also statistically significant (p<0.05 and p<0.01 respectively). There is also a statistically significant difference between the two experimental groups (p<0.01). CONCLUSION: These findings suggest that adhesive cements provoke a greater SP expression when compared with glass ionomer.

New tools for targeted disruption of cholinergic synaptic transmission in Drosophila melanogaster.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. The α7 subtype of nAChRs is involved in neurological pathologies such as Parkinson's disease, Alzheimer's disease, addiction, epilepsy and autism spectrum disorders. The Drosophila melanogaster α7 (Dα7) has the closest sequence homology to the vertebrate α7 subunit and it can form homopentameric receptors just as the vertebrate counterpart. The Dα7 subunits are essential for the function of the Giant Fiber circuit, which mediates the escape response of the fly. To further characterize the receptor function, we generated different missense mutations in the Dα7 nAChR's ligand binding domain. We characterized the effects of targeted expression of two UAS-constructs carrying a single mutation, D197A and Y195T, as well as a UAS-construct carrying a triple D77T, L117Q, I196P mutation in a Dα7 null mutant and in a wild type background. Expression of the triple mutation was able to restore the function of the circuit in Dα7 null mutants and had no disruptive effects when expressed in wild type. In contrast, both single mutations severely disrupted the synaptic transmission of Dα7-dependent but not glutamatergic or gap junction dependent synapses in wild type background, and did not or only partially rescued the synaptic defects of the null mutant. These observations are consistent with the formation of hybrid receptors, consisting of D197A or Y195T subunits and wild type Dα7 subunits, in which the binding of acetylcholine or acetylcholine-induced conformational changes of the Dα7 receptor are altered and causes inhibition of cholinergic responses. Thus targeted expression of D197A or Y195T can be used to selectively disrupt synaptic transmission of Dα7-dependent synapses in neuronal circuits. Hence, these constructs can be used as tools to study learning and memory or addiction associated behaviors by allowing the manipulation of neuronal processing in the circuits without affecting other cellular signaling.

Paired nanoinjection and electrophysiology assay to screen for bioactivity of compounds using the Drosophila melanogaster giant fiber system.

Screening compounds for in vivo activity can be used as a first step to identify candidates that may be developed into pharmacological agents. We developed a novel nanoinjection/electrophysiology assay that allows the detection of bioactive modulatory effects of compounds on the function of a neuronal circuit that mediates the escape response in Drosophila melanogaster. Our in vivo assay, which uses the Drosophila Giant Fiber System (GFS, Figure 1) allows screening of different types of compounds, such as small molecules or peptides, and requires only minimal quantities to elicit an effect. In addition, the Drosophila GFS offers a large variety of potential molecular targets on neurons or muscles. The Giant Fibers (GFs) synapse electrically (Gap Junctions) as well as chemically (cholinergic) onto a Peripheral Synapsing Interneuron (PSI) and the Tergo Trochanteral Muscle neuron (TTMn. The PSI to DLMn (Dorsal Longitudinal Muscle neuron) connection is dependent on Dα7 nicotinic acetylcholine receptors (nAChRs). Finally, the neuromuscular junctions (NMJ) of the TTMn and the DLMn with the jump (TTM) and flight muscles (DLM) are glutamatergic. Here, we demonstrate how to inject nanoliter quantities of a compound, while obtaining electrophysiological intracellular recordings from the Giant Fiber System and how to monitor the effects of the compound on the function of this circuit. We show specificity of the assay with methyllycaconitine citrate (MLA), a nAChR antagonist, which disrupts the PSI to DLMn connection but not the GF to TTMn connection or the function of the NMJ at the jump or flight muscles. Before beginning this video it is critical that you carefully watch and become familiar with the JoVE video titled "Electrophysiological Recordings from the Giant Fiber Pathway of D. melanogaster" from Augustin et al, as the video presented here is intended as an expansion to this existing technique. Here we use the electrophysiological recordings method and focus in detail only on the addition of the paired nanoinjections and monitoring technique.

A novel approach for in vivo screening of toxins using the Drosophila Giant Fiber circuit.

Finding compounds that affect neuronal or muscular function is of great interest as potential therapeutic agents for a variety of neurological disorders. Alternative applications for these compounds include their use as molecular probes as well as insecticides. We have developed a bioassay that requires small amounts of compounds and allows for unbiased screening of biological activity in vivo. For this, we paired administering compounds in a non-invasive manner with simultaneous electrophysiological recordings from a well-characterized neuronal circuit, the Giant Fiber System of Drosophila melanogaster, which mediates the escape response of the fly. The circuit encompasses a variety of neurons with cholinergic, glutamatergic, and electrical synapses as well as neuromuscular junctions. Electrophysiological recordings from this system allow for the detection of compound-related effects against any molecular target on these components. Here, we provide evidence that this novel bioassay works with small molecules such as the cholinergic receptor blocker mecamylamine hydrochloride and the potassium channel blocker tetraethylammonium hydroxide, as well as with venom from Conus brunneus and isolated conopeptides. Conopeptides have been developed into powerful drugs, such as the painkillers Prialt™ and Xen2174. However, most conopeptides have yet to be characterized, revealing the need for a rapid and straightforward screening method. Our findings show that mecamylamine hydrochloride, as well as the α-conotoxin ImI, which is known to be an antagonist of the human α7 nicotinic acetylcholine receptor, efficiently disrupted the synaptic transmission of a Drosophila α7 nicotinic acetylcholine receptor-dependent pathway in our circuit but did not affect the function of neurons with other types of synapses. This demonstrates that our bioassay is a valid tool for screening for compounds relevant to human health.

Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot-Marie-Tooth neuropathy.

Dominant-intermediate Charcot-Marie-Tooth neuropathy (DI-CMT) is characterized by axonal degeneration and demyelination of peripheral motor and sensory neurons. Three dominant mutations in the YARS gene, encoding tyrosyl-tRNA synthetase (TyrRS), have so far been associated with DI-CMT type C. The molecular mechanisms through which mutations in YARS lead to peripheral neuropathy are currently unknown, and animal models for DI-CMTC are not yet available. Here, we report the generation of a Drosophila model of DI-CMTC: expression of the 3 mutant--but not wild type--TyrRS in Drosophila recapitulates several hallmarks of the human disease, including a progressive deficit in motor performance, electrophysiological evidence of neuronal dysfunction and morphological signs of axonal degeneration. Not only ubiquitous, but also neuron-specific expression of mutant TyrRS, induces these phenotypes, indicating that the mutant enzyme has cell-autonomous effects in neurons. Furthermore, biochemical and genetic complementation experiments revealed that loss of enzymatic activity is not a common feature of DI-CMTC-associated mutations. Thus, the DI-CMTC phenotype is not due to haploinsufficiency of aminoacylation activity, but most likely to a gain-of-function alteration of the mutant TyrRS or interference with an unknown function of the WT protein. Our results also suggest that the molecular pathways leading to mutant TyrRS-associated neurodegeneration are conserved from flies to humans.

Axial and radial water transport and internal water storage in tropical forest canopy trees.

Heat and stable isotope tracers were used to study axial and radial water transport in relation to sapwood anatomical characteristics and internal water storage in four canopy tree species of a seasonally dry tropical forest in Panama. Anatomical characteristics of the wood and radial profiles of sap flow were measured at the base, upper trunk, and crown of a single individual of Anacardium excelsum, Ficus insipida, Schefflera morototoni, and Cordia alliodora during two consecutive dry seasons. Vessel lumen diameter and vessel density did not exhibit a consistent trend axially from the base of the stem to the base of the crown. However, lumen diameter decreased sharply from the base of the crown to the terminal branches. The ratio of vessel lumen area to sapwood cross-sectional area was consistently higher at the base of the crown than at the base of the trunk in A. excelsum, F. insipida and C. alliodora, but no axial trend was apparent in S. morototoni. Radial profiles of the preceding wood anatomical characteristics varied according to species and the height at which the wood samples were obtained. Radial profiles of sap flux density measured with thermal dissipation sensors of variable length near the base of the crown were highly correlated with radial profiles of specific hydraulic conductivity (k(s)) calculated from xylem anatomical characteristics. The relationship between sap flux density and k(s) was species-independent. Deuterium oxide (D(2)O) injected into the base of the trunk of the four study trees was detected in the water transpired from the upper crown after only 1 day in the 26-m-tall C. alliodora tree, 2 days in the 28-m-tall F. insipida tree, 3 days in the 38-m-tall A. excelsum tree, and 5 days in the 22-m-tall S. morototoni tree. Radial transport of injected D(2)O was detected in A. excelsum, F. insipida and S. morototoni, but not C. alliodora. The rate of axial D(2)O transport, a surrogate for maximum sap velocity, was positively correlated with the predicted sapwood k(s) and with tree height normalized by the relative diurnal water storage capacity. Residence times for the disappearance of the D(2)O tracer in transpired water ranged from 2 days in C. alliodora to 22 days in A. excelsum and were positively correlated with a normalized index of diurnal water storage capacity. Capacitive exchange of water between stem storage compartments and the transpiration stream thus had a profound influence on apparent rates of axial water transport, the magnitude of radial water movement, and the retention time in the tree of water taken up by the roots. The inverse relationship between internal water exchange capacity and k(s) was consistent with a trade-off contributing to stability of leaf water status through highly efficient water transport at one extreme and release of stored water at the other extreme.