New opto-electro-mechanical sensor for two-dimensions dosimetry based on radiochromic films.

This work presents the validation of a new Opto‒Electro-Mechanical (MOEM) system consisting of a matrix of photodetectors for two-dimensional dosimetry evaluation with radiochromic films. The proposed system is based on a 5 × 10 matrix of photodetectors controlled by both in-house electronic circuit and graphical user interface, which enables optical measurements directly. We present the first tests performed in an X-ray machine and 137Cs source with that array by using Gafchromic EBT3 films. We obtained similar results than with a standard method (e.g. flat-bed scanner). Results were compared with Monte Carlo simulations and very good agreement was found. Results show the feasibility of using this system for dose evaluations. To the best of our knowledge, this is the first MOEM sensor for radiotherapy. Further developments are ongoing to create an advanced 16 × 16 LDRs system covering 1.6 cm × 1.6 cm with a 1 mm of spatial resolution. We point to develop a portable dosimetry tool delivering dose maps in real time to improve the clinical application of radiochromic films.

Reversal of indoleamine 2,3-dioxygenase-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme.

Increased tryptophan (Trp) catabolism in the tumor microenvironment (TME) can mediate immune suppression by upregulation of interferon (IFN)-γ-inducible indoleamine 2,3-dioxygenase (IDO1) and/or ectopic expression of the predominantly liver-restricted enzyme tryptophan 2,3-dioxygenase (TDO). Whether these effects are due to Trp depletion in the TME or mediated by the accumulation of the IDO1 and/or TDO (hereafter referred to as IDO1/TDO) product kynurenine (Kyn) remains controversial. Here we show that administration of a pharmacologically optimized enzyme (PEGylated kynureninase; hereafter referred to as PEG-KYNase) that degrades Kyn into immunologically inert, nontoxic and readily cleared metabolites inhibits tumor growth. Enzyme treatment was associated with a marked increase in the tumor infiltration and proliferation of polyfunctional CD8+ lymphocytes. We show that PEG-KYNase administration had substantial therapeutic effects when combined with approved checkpoint inhibitors or with a cancer vaccine for the treatment of large B16-F10 melanoma, 4T1 breast carcinoma or CT26 colon carcinoma tumors. PEG-KYNase mediated prolonged depletion of Kyn in the TME and reversed the modulatory effects of IDO1/TDO upregulation in the TME.

Design and validation of a neuroprosthesis for the treatment of upper limb tremor.

Pathological tremor is the most prevalent movement disorder. In spite of the existence of various treatments for it, tremor poses a functional problem to a large proportion of patients. This paper presents the design and implementation of a novel neuroprosthesis for tremor management. The paper starts by reviewing a series of design criteria that were established after analyzing users needs and the expected functionality of the system. Then, it summarizes the design of the neuroprosthesis, which was built to meet the criteria defined previously. Experimental results with a representative group of 12 patients show that the neuroprosthesis provided significant (p < 0.001) and systematic tremor attenuation (in average 52.33 ± 25.48 %), and encourage its functional evaluation as a potential new treatment for tremor in a large cohort of patients.

Epigenetic biomarkers: A new perspective in laboratory diagnostics.

Epigenetics comprises the study of chemical modifications in the DNA and histones that regulates the gene expression or cellular phenotype. However, during the last decade this term has evolved after the elucidation of different mechanisms (microRNAs and nuclear organization of the chromosomes) involved in regulating gene expression. Epigenetics and the new designed technologies capable to analyze epigenetic changes (e.g., methylated DNA, miRNAs expression, post-translational modifications on histones among others) have disclosed an appealing scenario that will offer for the biomedical sciences new biomarkers for the study of neurodegenerative diseases, multifactorial complex diseases, rare diseases and cancer. Moreover, new technologies adapted for epigenetic studies will offer promising applications that in the next years will be common technologies in clinical laboratories. In this review we discuss epigenetic modifications used as possible biomarkers in several diseases. We also present the potential of methodologies to purify histones, and high throughput technologies as candidates to be set in clinical laboratories for their high potential analyzing epigenetic processes.

Dietary and botanical anxiolytics.

Drugs used to treat anxiety have many negative side effects including addiction, depression, suicide, seizures, sexual dysfunction, headaches and more. Anxiolytic medications do not restore normal levels of neurotransmitters but instead manipulate the brain chemistry. For example, selective serotonin reuptake inhibitors (SSRIs) prevent the reuptake of serotonin from the synapse allowing serotonin to remain in the area of activity for a longer period of time but does not correct the lack of serotonin production. Benzodiazepines, such as Valium and Xanax®, stimulate GABA receptors, thus mimicking the calming effects of GABA but again do not fix the lack of GABA production. Often, the brain becomes accustomed to these medications and they often lose their effectiveness, requiring higher doses or different drugs. In contrast to anxiolytic drugs, there are herbs and nutrients which can stimulates neurotransmitter synthesis and more naturally effect and even adjust brain chemistry in the absence of many of the side effects experienced with drugs. Therefore this paper explores several herbal and nutritional approaches to the treatment of anxiety.

[Can tobacco companies be good corporate citizens?]. / Les entreprises du tabac peuvent-elles être citoyennes?

Tobacco companies have jumped on the Corporate social responsibility (CSR) bandwagon as a tentative to be societally accepted as responsible actors and good corporate citizens. This is however not possible for two reasons. First, the product they sell is lethal and thus not compatible with the precondition of doing no harm to be a good corporate citizen. Second, the behavior of tobacco firms is not responsible, being illustrated by four examples: junk science versus sound science strategy, seducing young smokers, political lobbying and getting customers on new markets. To conclude, three implications for regulating the activities of the tobacco industry are given.

Oral ulcers produced by mycophenolate mofetil in two liver transplant patients.

Oral ulcers are a frequent problem in transplant medicine. It is important to consider infectious etiologies, exacerbated by the immunosuppressive treatment, but other etiologies are also possible, like adverse drug reactions. Mycophenolate mofetil (MMF) is an immunosuppressive medication that has been used in combination with calcineurin inhibitors and steroids. Reports of renal transplant patients with oral ulcers related to MMF have appeared lately and herein we have described 2 cases in liver transplant patients. Their oral ulcers resolved quickly after suspension of the medication. Our 2 cases in liver transplant patients represented a unique setting for this type of complication.

Tratamiento videotoracoscópico del neumotórax espontáneo / Video-thoracoscopical treatment of spontaneous pneumothorax

Se presenta la experiencia, evaluada prospectivamente, del tratamiento por videotoracoscopia (VTC) del neumotórax espontáneo entre septiembre de 1994 y mayo de 1997. La indicación quirúrgica fue en el 36,5 por ciento por fístula aérea persistente, en 33,3 por ciento por recidiva, en 17,5 por ciento por bilateralidad, en 8 por ciento por tener certificado el diagnóstico de bulas y en 4,7 por ciento por petición del paciente para evitar recidiva. En 60 de los 63 pacientes se encontraron bulas, todas localizadas en los lóbulos superiores, en 7 de ellos habla además otras localizaciones. No hubo mortalidad, existieron 2 infecciones de herida operatoria, 2 recidivas precoces que se solucionaron por VTC y una fístula aérea prolongada que se resolvió con gel de fibrina. No hubo conversiones en la serie

Resección de nódulos pulmonares por videotoracoscopía / Pulmonary nodules resection by videothoracoscopy

El diagnóstico de nódulos pulmonares es difícil con técnicas no invasivas. El objetivo de este trabajo es analizar la experiencia en el diagnóstico y tratamiento de estas lesiones por videotoracoscopía. Se estudiaron 59 pacientes operados con esta técnica entre Enero de 1995 y Junio de 1997. En este período se intervinieron 25 nódulos benignos y 34 malignos, de los cuales 32 fueron metastásicos y 2 primarios pulmonares. El promedio de edad fue de 52 años (40 para las mujeres y 50 años los hombres). El tiempo operatorio promedio fue de 66 minutos con extremos de 20 a 150 minutos. Hubo 4 conversiones que corresponde al 6,7 por ciento de la casuístíca. El promedio de días hospitalarios postoperatorios fue de 3,74. En 4 pacientes (6,7 por ciento.) se presentaron complicaciones menores y no hubo mortalidad. La videotoracoscopía es un excelente método diagnóstico y en ocasiones terapéutico para el manejo de nódulos pulmonares, con baja morbilidad, corta estadía hospitalaria y sin mortalidad en este estudio

Embolización arterial bronquial en el tratamiento de la hemoptisis masiva / Bronchial artery embolization in the treatment of massive hemoptysis

Se evaluó retrospectivamente la eficacia de la embolización arterial bronquial en el tratamiento de la hemoptisis masiva. El procedimiento se efectuo en 16 pacientes (12 hombres y 4 mujeres de 16 a 66 años de edad) que ingresaron al INERyCT con el diagnóstico de hemoptisis masiva entre 1982 y 1986. La embolización arterial bronquial se practicó en 11 enfermos con hemorragia activa. En 9 de ellos el procedimiento controló la hemorragia en le curso de una semana. Los dos pacientes restantes murieron por recurrencia de la hemorragia. En otra serie cinco pacientes fueron embolizados sin hemorragia activa. Un período de 13 meses de seguimiento en los 14 pacientes en que se realizó embolización arterial bronquial demostró éxito del tratamiento en 11 enfermos y fracaso (recurrencia de la hemorragia) en tres de ellos. Estos resultados coinciden con estudios realizados con mayor número de enfermos en otros países y permiten señalar que la embolización arterial bronquial es una alternativa eficaz de tratamiento en pacientes con hemoptsis masiva y la única alternativa en enfermos con contraindicaciones quirúrgica

Aldosterone and the mobilization of energy.

Aldosterone diminishes the ability to endure starvation. Its exogenous administration to adrenalectomized rats advances the onset of hypothermia and death. The impairment seems to lie in an inability to mobilize energy stores fully: animals given the steroid are unable to lose weight at a normal rate. The findings help to establish the significance of mineralocorticoids in the regulation of energy exchange and solve some theoretical questions as to their general mode of action.

Environmental control of energy metabolism in rats.

Food availability was arranged so that episodes of feeding were separated by long periods of deprivation. Distinctly different contexts were associated with each condition. For other animals, relatively short periods of deprivation stood in contrast to relatively long opportunities to free-feed, and were also embedded in widely differing physical contexts. These temporal relationships among the conditions were adjusted to sharpen the saliency of each metabolic condition and thereby enhance its associability with the distinctive environment in which each occurred. To avoid the possibility of circadian entrainment, the feeding or deprivation episodes occurred at unpredictable times according to a variable-time schedule. Following several training cycles and an extended period of free-feeding in a neutral environment, the animals were reexposed to the various contexts and sacrificed for metabolite assays. The environment predictive of feeding elevated adipocyte lipoprotein lipase activity and lowered the levels of serum free fatty acids. The deprivation context boosted serum triglycerides and blood urea nitrogen. The conditioned responses were all of a compensatory nature: Feeding cues resulted in accelerated caloric deposition, deprivation cues elicited conditioned mobilization of stored energy. While protein catabolism and several indices of fat metabolism appear to be conditionable, no evidence of environmental control of glycemic responses was observed.