Radiological characterization of the tailings of an abandoned copper mine using a neural network and geostatistical analysis through the Co-Kriging method.

The radiological characterization of soil contaminated with natural radionuclides enables the classification of the area under investigation, the optimization of laboratory measurements, and informed decision-making on potential site remediation. Neural networks (NN) are emerging as a new candidate for performing these tasks as an alternative to conventional geostatistical tools such as Co-Kriging. This study demonstrates the implementation of a NN for estimating radiological values such as ambient dose equivalent (H*(10)), surface activity and activity concentrations of natural radionuclides present in a waste dump of a Cu mine with a high level of natural radionuclides. The results obtained using a NN were compared with those estimated by Co-Kriging. Both models reproduced field measurements equivalently as a function of spatial coordinates. Similarly, the deviations from the reference concentration values obtained in the output layer of the NN were smaller than the deviations obtained from the multiple regression analysis (MRA), as indicated by the results of the root mean square error. Finally, the method validation showed that the estimation of radiological parameters based on their spatial coordinates faithfully reproduced the affected area. The estimation of the activity concentrations was less accurate for both the NN and MRA; however, both methods gave statistically comparable results for activity concentrations obtained by gamma spectrometry (Student's t-test and Fisher's F-test).

Aptamers: A Feasible Technology in Cancer Immunotherapy.

Aptamers are single-chained RNA or DNA oligonucleotides (ODNs) with three-dimensional folding structures which allow them to bind to their targets with high specificity. Aptamers normally show affinities comparable to or higher than that of antibodies. They are chemically synthesized and therefore less expensive to manufacture and produce. A variety of aptamers described to date have been shown to be reliable in modulating immune responses against cancer by either blocking or activating immune receptors. Some of them have been conjugated to other molecules to target the immune system and reduce off-target side effects. Despite the success of first-line treatments against cancer, the elevated number of relapsing cases and the tremendous side effects shown by the commonly used agents hinder conventional treatments against cancer. The advantages provided by aptamers could enhance the therapeutic index of a given strategy and therefore enhance the antitumor effect. Here we recapitulate the provided benefits of aptamers with immunomodulatory activity described to date in cancer therapy and the benefits that aptamer-based immunotherapy could provide either alone or combined with first-line treatments in cancer therapy.

Brote de Stenotrophomonas maltophilia en una UCI médica asociado a la contaminación de los grifos. Hallazgo casual de jabones contaminados con Raoultella planticola / No disponible

INTRODUCCIÓN: Stenotrophomonas maltophilia origina raramente brotes nosocomiales. MÉTODOS: Descripción de un brote y la intervención realizada. Se comparó la incidencia acumulada (IA) en el periodo epidémico (PE) y preepidémico (PPE). Se realizaron cultivos ambientales. RESULTADOS: Ocurrieron 5 casos durante el PE con una IA de 3% (IC 95% 0,4-6), 4,8 veces superior a la del PPE. S. maltophilia creció en 6 grifos y el brote se controló tras su retirada. CONCLUSIÓN: desde el punto de vista de la prevención, es importante controlar determinados reservorios para evitar brotes nosocomiales

INTRODUCTION: Stenotrophomonas maltophilia is an infrequent cause of nosocomial outbreaks. METHODS: Outbreak report and intervention study. The accumulated incidence (AI) of the epidemic period (EP) was compared with AI of the pre-epidemic period (PEP). RESULTS: During EP, five cases were identified. AI was 3% (IC 95% 0,4-6), 4,8 times higher than the AI of PEP. S. maltophilia was isolated from the tap water faucets. The outbreak was controlled after removing the faucets. CONCLUSION: It is important to control environmental reservoirs to prevent outbreaks

XV Aniversario de Cuadernos de Medicina Forense / The XVth Anniversary of Cuadernos de Medicina Forense

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Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma.

BACKGROUND: Animal and clinical studies with plant-produced single-chain variable fragment lymphoma vaccines have demonstrated specific immunogenicity and safety. However, the expression levels of such fragments were highly variable and required complex engineering of the linkers. Moreover, the downstream processing could not be built around standard methods like protein A affinity capture. DESIGN: We report a novel vaccine manufacturing process, magnifection, devoid of the above-mentioned shortcomings and allowing consistent and efficient expression in plants of whole immunoglobulins (Igs). RESULTS: Full idiotype (Id)-containing IgG molecules of 20 lymphoma patients and 2 mouse lymphoma models were expressed at levels between 0.5 and 4.8 g/kg of leaf biomass. Protein A affinity capture purification yielded antigens of pharmaceutical purity. Several patient Igs produced in plants showed specific cross-reactivity with sera derived from the same patients immunized with hybridoma-produced Id vaccine. Mice vaccinated with plant- or hybridoma-produced Igs showed comparable protection levels in tumor challenge studies. CONCLUSIONS: This manufacturing process is reliable and robust, the manufacturing time from biopsy to vaccine is <12 weeks and the expression and purification of antigens require only 2 weeks. The process is also broadly applicable for manufacturing monoclonal antibodies in plants, providing 50- to 1000-fold higher yields than alternative plant expression methods.

Idiotype vaccines for human B-cell malignancies.

After twenty years of use in humans, customized idiotypic vaccination yet remains a non-approved, experimental therapeutic option for patients with lymphoma and myeloma. Potentially applicable to all B-cell malignancies whose cells express a clonal immunoglobulin or its epitopes on their surface, this treatment is designed to prevent disease recurrence or progression. Mostly used in follicular lymphoma patients so far, idiotype vaccines have clearly shown biological efficacy, clinical efficacy and clinical benefit in this setting, although no study aiming at regulatory approval of the procedure has been able to meet its main clinical endpoints. In mantle cell lymphoma, only biological efficacy has been proven for idiotypic vaccination, while in multiple myeloma a limited number of studies support the notion of biological and perhaps even clinical efficacy, although no credible evidence of clinical benefit has still emerged. Idiotype vaccines have been produced and administered in a number of substantially different manners. Therefore, the results of most clinical trials cannot be easily compared, and even less pooled together in meaningful meta-analyses. A more creative and yet scientifically sound way to design clinical trials of customized active immunotherapies will be key to the future development of idiotype vaccines, particularly considering that we currently lack any clinical or biological indicator to possibly predict which patients are more likely to respond to idiotypic vaccination from an immunologic point of view. This review aims at summarizing the multifaceted success achieved by idiotype vaccines, as well as at outlining the challenges awaiting them in the near future: how to improve feasibility, immunogenicity and efficacy, as well as how to confirm benefit and gain regulatory approval.

[Idiotype vaccines in the treatment of follicular lymphoma: current status and future perspectives]. / Vacuna idiotípica en el tratamiento del linfoma folicular: situación actual y perspectivas futuras.

Follicular lymphoma is the second most prevalent non-Hodgkin lymphoma, representing 20% of all lymphomas. Follicular lymphoma is an indolent disease with a slow progression in which, although exhibiting a good response to treatment, relapse is very frequent and complete remission is not easy to maintain. Therefore, the disease is regarded as incurable. The search for new therapeutic strategies, together with a better understanding of the immune system, has led to the emergence of a new treatment named immunotherapy. Follicular lymphoma is a malignancy suitable for this kind of treatment given the fact that it is characterized by presenting a unique tumour-specific antigen: the idiotype of the monoclonal immunoglobulin displayed on the membrane of tumour cells. Several studies have been conducted to test immunotherapy as complementary to conventional treatment. In a previous study by our group, a clear benefit was evident is obtained after idiotypic vaccination, when an adequate immunization of the patient is obtained, in comparison to chemotherapy alone. In this sense, analysis is needed of whether idiotypic vaccination can produce not only long-lasting and complete remission, but even cure. It would be of great interest to consider an optimisation of the experimental design of clinical trials, an improvement of vaccine production, and the study of the molecular mechanisms of the tumour cell which modify the target immunoglobulin.

Vacuna idiotípica en el tratamiento del linfoma folicular: situación actual y perspectivas futuras / Idiotype vaccines in the treatment of follicular lymphoma: current status and future perspectives

El linfoma folicular (LF) está considerado como elsegundo tipo de linfoma no-Hodgkin más común, representandomás del 20% del total de los linfomas. Es unaenfermedad de progresión lenta y curso indolente enla que, a pesar de la buena respuesta al tratamiento,las recaídas son muy frecuentes y cada vez es más difícilconseguir respuestas completas. Por ello, se puedeconsiderar que hasta el momento, el LF es incurable.La búsqueda continua de nuevas estrategias terapéuticasen enfermedades neoplásicas, junto con un mejorconocimiento del sistema inmunitario, ha llevado ala aparición de una nueva disciplina, conocida con elnombre de inmunoterapia, que aprovecha la capacidaddel sistema inmunitario de atacar lo extraño sin dañarlo propio. El LF es un tumor muy apropiado para estetipo de tratamiento por presentar un antígeno específicode tumor: el idiotipo de la inmunoglobulina monoclonalexpresada en la membrana de todas las célulastumorales. Se han realizado diversos estudios en losque se ha probado la inmunoterapia como tratamientocomplementario al tratamiento convencional. Recientemente,nuestro grupo ha publicado un estudio en el quese observa claramente que los resultados que se obtienentras la vacunación idiotípica, cuando se consigue lainmunización adecuada del paciente, son mejores quelos obtenidos con quimioterapia sola. En este sentido,es necesario seguir investigando para aclarar si la vacunaciónidiotípica pudiera no sólo mantener remisionescompletas duraderas en los pacientes vacunados, sinoincluso conseguir la curación de los mismos. Por ello,resulta interesante abordar un mejor planteamiento delos ensayos clínicos, la mejora de la producción de lavacuna y el estudio de mecanismos de la célula tumoralcapaces de modificar la inmunoglobulina específica del tumor(AU)

Follicular lymphoma is the second most prevalentnon-Hodgkin lymphoma, representing 20% of all lymphomas.Follicular lymphoma is an indolent diseasewith a slow progression in which, although exhibitinga good response to treatment, relapse is very frequentand complete remission is not easy to maintain. Therefore,the disease is regarded as incurable. The searchfor new therapeutic strategies, together with a betterunderstanding of the immune system, has led to theemergence of a new treatment named immunotherapy.Follicular lymphoma is a malignancy suitable for thiskind of treatment given the fact that it is characterizedby presenting a unique tumour-specific antigen: theidiotype of the monoclonal immunoglobulin displayedon the membrane of tumour cells. Several studies havebeen conducted to test immunotherapy as complementaryto conventional treatment. In a previous study byour group, a clear benefit was evident is obtained afteridiotypic vaccination, when an adequate immunizationof the patient is obtained, in comparison to chemotherapyalone. In this sense, analysis is needed of whetheridiotypic vaccination can produce not only long-lastingand complete remission, but even cure. It would be ofgreat interest to consider an optimisation of the experimentaldesign of clinical trials, an improvementof vaccine production, and the study of the molecularmechanisms of the tumour cell which modify the targetimmunoglobulin(AU)

Improving outcomes of transported newborns in Panama: impact of a nationwide neonatal provider education program.

OBJECTIVE: To determine whether national distribution of a neonatal provider education program (the S.T.A.B.L.E. Program) positively impacts the health of ill newborns that require transport in Panama. STUDY DESIGN: The investigation used a prospective, pre- and postintervention study design with a double pretest. The 10 birthing centers in Panama that routinely transport the greatest number of newborns received the education program intervention. Primary outcomes were body temperature and serum glucose level on arrival at the referral facility. Length of stay and mortality were evaluated as secondary outcomes. Variation in outcome indicators was compared for 7 months before and after the intervention. Data from all live newborns transported from outlying birthing center study sites during the study dates were included in the investigation. RESULT: A total of 136 and 146 newborns were transported during the observation and postintervention periods, respectively. Significantly more patients in the postintervention group had temperatures within the normal range (56% in postintervention group vs 34% in observation group; P<0.01). No statistical difference was observed in serum glucose levels, length of stay or mortality. CONCLUSION: Distribution of a neonatal provider educational program was associated with improved thermal management of transported newborns in Panama. Further study will help to confirm this association and determine the extent to which these findings are generalizable to other resource-constrained settings.

A DnaJ protein, apobec-1-binding protein-2, modulates apolipoprotein B mRNA editing.

Mammalian homologues of DnaJ proteins, also known as Hsp40 proteins, are co-chaperonins that complement Hsp70 chaperone function. Using the yeast two-hybrid system, we cloned an apolipoprotein (apo) B mRNA editing complementation protein, called apobec-1-binding protein-2 (ABBP-2), and found that it is a Class II DnaJ homologue. ABBP-2 binds to apobec-1, the mammalian apoB mRNA editase, via its J domain and neighboring G/F domain. It is a ubiquitously expressed protein, and, by transfection analysis of GFP-ABBP-2, we found that the protein is located in both the nucleus and cytosol of transfected cells, with predominance in the nucleus. Down-regulation of ABBP-2 expression in cultured cells inhibits endogenous apobec-1-mediated apoB mRNA editing. Like other Hsp40 proteins, ABBP-2 binds to Hsp70 and has ATPase-stimulating activity. Apobec-1-mediated apoB mRNA editing activity of in vitro tissue extracts requires the presence of Hsp70/ABBP-2. Although exogenously added ATP is not required for editing activity, removal of the endogenous ATP present in these extracts, which disrupts ABBP-2-Hsp70 interaction, completely inhibits editing. ABBP-2 differs from previously described auxiliary proteins (ABBP-1, ACF, and GRY-RBP) in that it does not contain any RNA recognition motifs. Not only is ABBP-2 required for efficient apoB mRNA editing, this newly discovered apobec-1-binding protein may help determine the subcellular distribution and trafficking of apobec-1 via its interaction with the chaperonin Hsp70.

New 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants.

A series of new 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives were synthesized in an attempt to find a new class of antidepressant drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter. Title compounds were evaluated for in vitro activity on 5-HT1A receptor and 5-HT transporter. They show high nanomolar affinity for both activities, and in particular, compounds 1-(5-chlorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (7) and 1-(5-fluorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (8) show values (nM) of K(i)=30 and 2.3 for 5-HT1A receptors and K(i)=30 and 12 for serotonin transporters, respectively. In GTPgammaS binding assays, compound 8 revealed antagonist properties to 5-HT1A receptors. Such a pharmacological profile could lead to potent antidepressant agents with new dual mechanism of action.

[Ongoing health management control by cost monitoring through tracer indicators]. / Control permanente de la gestión sanitaria por monitoreo de costos mediante acontecimientos indicadores.

OBJECTIVE: To determine the operational cost of a hospital's surgical unit, compare those results with standards, and determine the incidence of the costs; to produce an effective methodology for this purpose that can be applied to all kinds of medical units using any low-cost widely available computer database system, with that methodology being utilized for ongoing management control. METHODS: This study was carried out in 1999 in the Orthopedics and Traumatology Unit of the "Domingo Funes" Public Hospital, in the province of Córdoba, Argentina. Of the 817 patients who underwent diagnostic or therapeutic procedures in that unit during the year, we selected the 154 of them who were hospitalized and required surgical or instrumental procedures. The study used the tracer event method described by Kessner. Through a consensus process, medical specialists and health economists selected and defined these indicators, which were categorized in relation to their complexity (high, medium, limited, or none). Direct and indirect costs were assessed in order to study their contribution to total cost. Total cost was estimated using nine variables that were applied to the different tracer events. RESULTS: The largest portion of total cost, both real and standard, was based on the "bed-day" variable. Of this bed-day cost for all tracer events, 51.2% was due to an indirect cost of "social hospitalization" (keeping patients hospitalized for such reasons as transportation difficulties or delays in receiving requested medical supplies) and 48.8% to a direct cost of true therapeutic hospitalization. This bed-day cost was 117% higher for the real costs as compared to the standard costs. The indirect costs of social hospitalization and of therapeutic supplies made up nearly half of the total real cost. Excluding the indirect costs, the real cost of all the tracer events exceeded the standard cost by only 6.4%. Including the indirect costs of social hospitalization and of therapeutic supplies, the real cost exceeded the standard cost by 39.8%. The amount spent on medical staff and support personnel represented just 11.5% of the total cost. DISCUSSION: Suggestions are provided in various areas, including solutions for the high cost of social hospitalization and therapeutic supplies, the cost-control benefits of creating protocols for procedures and treatments, and the rational utilization of technology in order to improve efficiency and reduce risks. The wider application of this procedure is recommended for cost-management control in all hospital units carrying out surgery or other medical procedures.

[Evidence of cerebral involvement in the chronic stage of Chagas disease obtained using the P300 potential and quantified electroencephalography]. / Evidencias de compromiso cerebral en el estadio crónico de la enfermedad de Chagas obtenidas por medio del potencial P300 y de electroencefalografía cuantificada.

It is already known the involvement of the peripheral nervous system in chronic stages of Chagas disease. Tomographic and neuropsychological evidence of brain compromise has been included recently. In order to evaluate the neurophysiological counterpart of cerebral involvement, we studied P300 evoked potential and quantified EEG (qEEG) of 35 patients (26-55 years), and compared to an equal number of control subjects (29-55 years). We have found increased P300 latency compared to the control group (331.24 +/- 24. 02 vs 318.86 +/- 23.18) (p=0.01716). qEEG showed lower relative Beta 1 power in the patients group (p=1.6E5), and the principal frequency 1 Hz slower in the same group (p=0.01077). Multivariate analysis showed three subpopulations: a normal one, pathological one with higher Alpha power and pathological with Alpha decrement and DeltaTheta increment. Pathological findings represented 20% for the qEEG and 11.43% for cognitive potentials. Cardiac and neurologic involvement were not correlated. We conclude that there is clear electrophysiological evidence of cerebral involvement in chronic Chagas disease, thus reinforcing findings obtained by other methods.

Realtime ultrasound diagnosis over a wide-area network (WAN) using off-the-shelf components.

A trial system was developed for relaying realtime ultrasound images from an obstetric referral centre, the Maitland Hospital, to a tertiary-care centre, the John Hunter Hospital in Newcastle. The sites were approximately 30 km apart and connected by a microwave link at 2 Mbit/s. The pilot study demonstrated the feasibility of realtime ultrasound transmission using commonly available components.

Evidence that nicotine can acutely desensitize central nicotinic acetylcholinergic receptors.

Current concepts concerning nicotine's CNS mechanism(s) of action suggest that this drug produces its effects via an interaction at nicotinic-cholinergic receptors (nAChRs) sensitive to acetylcholine. In vitro research further suggests that, following its initial agonist effect, this cholinergic drug may also induce a rapid desensitization of the nAChR similar to that of acetylcholine, resulting in termination of its pharmacological effect. Research described in this paper provides evidence of this secondary desensitization process in vivo by demonstrating nicotine's ability to induce acute tolerance in a Discriminative Stimulus (DS) paradigm. The ability of nicotine (400 micrograms/kg, SC) to elicit DS control of behavior in a two-lever operant procedure was significantly reduced via a challenge dose (800 micrograms/kg, SC) of nicotine administered 15-180 min before the training dose. Twenty-three of 52 rats demonstrated this phenomenon. The time to develop acute tolerance varied, providing additional evidence that these effects may be contingent upon individual rat variability. In addition, physostigmine was also observed to induce a similar desensitization in a random population of desensitizing rats. Lastly, there were no differences between desensitizers and non-desensitizers in relation to the ability of mecamylamine (1000 micrograms/kg, SC) to antagonize the DS, while in both populations of rats scopolamine (100 micrograms/kg, SC) failed to antagonize the DS.

Differential tolerance to the behavioral effects of chronic pimozide and clozapine on multiple random interval responding in rats.

The behavioral effects of 10 days of chronic administration of the typical neuroleptic, pimozide, and the atypical neuroleptic, clozapine, were compared on a schedule of multiple random interval responding for food reinforcement and on photocell activity in rats. The low doses of both neuroleptics (0.125mg/kg pimozide, 1.25mg/kg clozapine) had little effect on any of the dependent variables measured. The high doses (1.0mg/kg pimozide, 10.0mg/kg clozapine) significantly disrupted response rates and reinforcement rates and significantly increased response duration when the drugs were first administered. Chronic administration, however, resulted in different profiles for the two drugs. While tolerance developed to the disruptive effects of clozapine, tolerance did not develop to the disruptive effects of pimozide and, on some dependent measures, an increased sensitivity developed. No tolerance developed to the disruptive effects of either drug on photocell activity. The effects of the drugs depended on the reinforcement density of the operant schedule.

A characterization of nicotine-induced tolerance: evidence of pharmacological tolerance in the rat.

The present studies were conducted in order to confirm and extend previous findings that the mechanisms of tolerance to the behaviorally disruptive effects of nicotine in a operant model were primarily pharmacological. Both the traditional methodology employing the determination of dose response curves before and after chronic drug administration and a methodology which omits the generation of dose response curves were utilized in these investigations of nicotine-induced tolerance. Rats developed tolerance to both pre- and post-session administration of nicotine, suggesting that the mechanisms of tolerance to the disruptive effects of nicotine are primarily pharmacological. The mechanisms underlying these effects, however, remain to be evaluated.