Advanced Breast Cancer Guidelines in Latin America: Assessment, Adaptation, and Implementation of Fifth Advanced Breast Cancer Consensus Guidelines.

PURPOSE: As the fifth international consensus on advanced breast cancer (ABC5) established guidelines for the management of this disease, the aim of this article was to present the applicability of the consensus recommendations and to generate knowledge to improve access. METHODS: Sixty-one recommendation statements were selected and discussed by 15 breast cancer experts from Latin America (LA). After the discussion, the level of consensus was determined through a vote. In addition to this, the level of access to each of the recommendations presented, according to the country and health system, was exposed. RESULTS: Latin American experts had a high level of agreement with the ABC5 consensus recommendations (range, 83%-100%). Twelve of 61 statements are not available for all patients in LA. Among the limitations to access, the following ones are described: limited access to certain technologies (stereotactic body radiotherapy, positron emission tomography-computed tomography), the high costs of drugs that limits access to treatment with CDK4/6 inhibitors, pertuzumab, or poly(ADP-ribose) polymerase inhibitors, and the lack of molecular tests for access to therapeutic targets, as well as the difficult geography and cultural diversity of our continent. CONCLUSION: Despite the great relevance of the recommendations of the ABC5 consensus guidelines, we highlight that we still need to improve access for all patients, regardless of the country or health system they are in, for which we call to action to policy makers and patient groups to improve clinical outcomes of patients with advanced breast cancer in our region.

Mama supranumeraria: resección mediante técnica abierta con dren versus sin dren / Supranumerary breast: resection by open technique with drain vs without drain

Introducción. El tejido mamario accesorio es una anomalía congénita que se presenta en el 2-6 % de la población femenina. En este tejido se pueden desarrollar las mismas patologías que en la mama normal. El manejo curativo es la resección quirúrgica. El objetivo de este estudio fue comparar los resultados de la técnica de resección vía abierta de tejido mamario accesorio con dren vs sin dren. Métodos. Se realizó un estudio observacional tipo cohorte retrospectivo, teniendo en cuenta dos grupos de pacientes con tejido mamario accesorio: a uno de ellos se les realizó resección quirúrgica mediante técnica abierta con dren y al otro grupo sin dren. Además, se incluyó un brazo prospectivo donde se evaluó la calidad de vida y la satisfacción de las pacientes con el resultado posoperatorio mediante el uso de la herramienta Breast-Q. Resultados. Se recolectó la información de 82 pacientes, la mayoría mujeres; 22 se intervinieron con técnica con dren y 60 con técnica sin dren. 13,6 % de los pacientes presentaron complicaciones tempranas, siendo la infección de sitio operatorio la más frecuente (36,4 %). En general, las complicaciones fueron más comunes en el grupo con dren (40,9 % vs 3,4 %), con una diferencia estadísticamente significativa (p=0,000). La calidad de vida fue similar en ambos grupos. Conclusiones. Los pacientes a quienes se les realizó resección de mama supernumeraria y se dejó un sistema de drenaje en el lecho de disección presentaron más complicaciones posoperatorias que las pacientes a quienes no se les dejó dren

Introduction. Accessory breast tissue is a congenital anomaly that occurs in 2-6% of the female population. It can develop the same pathologies that in the normal breast. The curative management of this pathology is surgical resection. The objective of this study was to compare the results of the accessory breast tissue open resection technique with a drain vs without a drain. Methods. An observational retrospective cohort study was conducted considering two groups of patients with accessory breast tissue: one of them underwent surgical resection using an open technique with a drain and the other group without a drain. In addition, a prospective arm where the quality of life and satisfaction of the patients with the postoperative result was evaluated by the Breast-Q tool. Results. Eighty-two patients were included, most of them women; 22 were operated with open technique with drain and 60 without drain. 13.6% of patients presented early complications, with surgical site infection being the most frequent (36.4%) and, in general, complications were more common in the group with drain (40.9% vs 3.4%) with a statistically significant difference (p=0.000). Quality of life was similar in both groups.Conclusions. Patients who undergo supernumerary breast resection and leaving drainage in the dissection bed present more postoperative complications compared to those without drain

Clinical and molecular description of two cases of neonatal diabetes secondary to mutations in PDX1.

Summary: Pancreatic dysgenesis (PD) is a rare congenital disease, with less than 100 cases reported in the literature. In most cases, patients are asymptomatic and the diagnosis is made incidentally. In this report, we present the case of two brothers with a history of intrauterine growth retardation, low birth weight, hyperglycemia, and poor weight gain. The diagnosis of PD and neonatal diabetes mellitus was made by an interdisciplinary team composed of an endocrinologist, a gastroenterologist, and a geneticist. Once the diagnosis was made, treatment with an insulin pump, pancreatic enzyme replacement therapy, and supplementation with fat-soluble vitamins was decided. The use of the insulin infusion pump facilitated the outpatient treatment of both patients. Learning points: Pancreatic dysgenesis is a relatively rare congenital anomaly; most of the time, patients are asymptomatic and are diagnosed incidentally. The diagnosis of pancreatic dysgenesis and neonatal diabetes mellitus should be made with an interdisciplinary team. Due to its flexibility, the use of an insulin infusion pump facilitated the management of these two patients.

Animal-substrate interactions preserved in ancient lagoonal chalk.

Trace-fossil assemblages reflect the response of the benthos to sets of paleoenvironmental conditions during and immediately after sedimentation. Trace fossils have been widely studied in pelagic shelf and deep-sea chalk deposits from around the globe but never documented from ancient lagoonal chalk successions. Here we report the first detailed ichnologic analysis of a lagoonal chalk unit, using as an example the Upper Cretaceous Buda Formation from the Texas Gulf Coast Basin. In this unit, variable interconnection with the open ocean, accompanied by marked fluctuations in physicochemical parameters inherent to lagoonal circulation (e.g., salinity, hydrodynamic energy, bottom-water oxygenation), highly influenced the resultant trace-fossil content of the chalk. These lagoonal chalk deposits contain twenty ichnotaxa, displaying a clear dominance of Thalassinoides isp. and Chondrites isp., which are present in most of the bioturbated strata. The dominance of Thalassinoides isp., both in softgrounds as an element of the Cruziana Ichnofacies and in firmgrounds as a component of the Glossifungites Ichnofacies, highlights similarities with trace-fossil assemblages from shallow-water shelf-sea chalks. In contrast to both (open) shallow-water shelf-sea chalks and deep-sea chalks, the Buda Formation chalk exhibits more diverse assemblages and sharp fluctuations in ichnodiversity and ichnodisparity during relatively short periods of time. The increased ichnodiversity and ichnodisparity in this lagoonal chalk (in comparison with its open ocean counterparts) may reflect a complex interplay of taphonomic (i.e., incomplete bioturbation allowing preservation of shallow-tier trace fossils and ecologic (i.e., increased spatial environmental heterogeneity in the carbonate lagoonal setting) factors.

Tabernaemontana arborea and ibogaine induce paroxysmal EEG activity in freely moving mice: Involvement of serotonin 5-HT1A receptors.

Several Apocynaceae species, most notably Tabernanthe iboga, Voacanga africana and many Tabernaemontana species, produce ibogan-type alkaloids. Although a large amount of information exists about the Tabernaemontana genus, knowledge concerning chemistry and biological activity remains lacking for several species, especially related to their effects on the central nervous system (CNS). The aim of this study was to evaluate the effect of Tabernaemontana arborea Rose ex J.D.Sm. (T. arborea) hydroalcoholic extract (30, 56.2 and 100 mg/kg, i.p.) and two of its main alkaloids (ibogaine and voacangine, 30 mg/kg, i.p.) on electroencephalographic (EEG) activity alone and in the presence of the chemical convulsant agent pentylenetetrazole (PTZ, 85 mg/kg, i.p.) in mice. EEG spectral power analysis showed that T. arborea extract (56.2 and 100 mg/kg) and ibogaine (30 mg/kg, i.p.) promoted a significant increase in the relative power of the delta band and a significant reduction in alpha band values, denoting a CNS depressant effect. Voacangine (30 mg/kg, i.p.) provoked an EEG flattening pattern. The PTZ-induced seizures were not modified in the presence of T. arborea, ibogaine, or voacangine. However, sudden death was observed in mice treated with T. arborea extract at 100 mg/kg, i.p., combined with PTZ. Because T. arborea extract (100 mg/kg, i.p.) and ibogaine (30 mg/kg, i.p.), but not voacangine (30 mg/kg, i.p.), induced paroxysmal activity in the EEG, both were explored in the presence of a serotonin 5-HT1A receptor antagonist (WAY100635, 1 mg/kg, i.p.). The antagonist abolished the paroxysmal activity provoked by T. arborea (100 mg/kg, i.p.) but not that observed with ibogaine, corroborating the participation of serotonin neurotransmission in the T. arborea effects. In conclusion, high doses of the T. arborea extract induced abnormal EEG activity due in part to the presence of ibogaine and involving serotonin 5-HT1A receptor participation. Nevertheless, other possible constituents and mechanisms might participate in this complex excitatory activity that would be interesting to explore in future studies.

Force-dependent activation of actin elongation factor mDia1 protects the cytoskeleton from mechanical damage and promotes stress fiber repair.

Plasticity of cell mechanics underlies a wide range of cell and tissue behaviors allowing cells to migrate through narrow spaces, resist shear forces, and safeguard against mechanical damage. Such plasticity depends on spatiotemporal regulation of the actomyosin cytoskeleton, but mechanisms of adaptive change in cell mechanics remain elusive. Here, we report a mechanism of mechanically activated actin polymerization at focal adhesions (FAs), specifically requiring the actin elongation factor mDia1. By combining live-cell imaging with mathematical modeling, we show that actin polymerization at FAs exhibits pulsatile dynamics where spikes of mDia1 activity are triggered by contractile forces. The suppression of mDia1-mediated actin polymerization increases tension on stress fibers (SFs) leading to an increased frequency of spontaneous SF damage and decreased efficiency of zyxin-mediated SF repair. We conclude that tension-controlled actin polymerization acts as a safety valve dampening excessive tension on the actin cytoskeleton and safeguarding SFs against mechanical damage.

Cyclophosphamide, Thalidomide, and Dexamethasone as Initial Therapy for Patients With Newly Diagnosed Multiple Myeloma in a Middle-Income Country: 7-Year Follow-Up.

PURPOSE: Major progress has occurred in multiple myeloma (MM) treatment in recent years, but this is not seen in low- and middle-income countries. MATERIALS AND METHODS: We retrospectively assessed the efficacy and safety of cyclophosphamide, thalidomide, and dexamethasone (cyclophosphamide 400 mg/m2 for 5 days, thalidomide 100 mg once daily, if tolerated, and dexamethasone 40 mg once weekly; in 28-day cycles) in patients with newly diagnosed MM treated at our institution between April 2008 and December 2012. Survival outcomes were estimated by the Kaplan-Meier method. RESULTS: Fifty-nine patients were found to meet the selection criteria. Median age was 56 years (27-78). Fifty-nine percent (n = 35) were male. International Staging System three was found in 24%. The median number of treatment cycles was 11 (range 4-12). After a median of 81-month follow-up (range 5-138 months), the overall response rate was 69.5%. The complete response and very good partial response were 5% and 32%, respectively. Median progression-free survival (PFS) was 35 months (95% CI, 18 to 41). The 3-year PFS was 47.4% (95% CI, 34.5 to 59.6) and 5-year PFS was 24.9% (95% CI, 14.4 to 36.9). The median of overall survival (OS) was 81 months (95% CI, 33 to not reached). The 3-year OS was 63.4% (95% CI, 49.2 to 74.6), and 5-year OS was 57.5% (95% CI, 43.2 to 69.4). The most common adverse event was neutropenia (grade 3 and 4, 30.5%). Out of 23 patients eligible for stem-cell transplantation, 10 (43.5%) proceeded with autologous transplantation. Treatment-related deaths occurred in four patients (6.7%). CONCLUSION: Cyclophosphamide, thalidomide, and dexamethasone achieves good response rates with tolerable toxicity, especially in patients age 65 years or younger representing a feasible approach for patients with MM in low-income health care settings.

Quantitative Analysis of Myofibroblast Contraction by Traction Force Microscopy.

Myofibroblasts play important roles in physiological processes such as wound healing and tissue repair. While high contractile forces generated by the actomyosin network enable myofibroblasts to physically contract the wound and bring together injured tissue, prolonged and elevated levels of contraction also drive the progression of fibrosis and cancer. However, quantitative mapping of these forces has been difficult due to their extremely low magnitude ranging from 100 pN/µm2 to 2 nN/µm2. Here, we provide a protocol to measure cellular forces exerted on two-dimensional compliant elastic hydrogels. We describe the fabrication of polyacrylamide hydrogels labeled with fluorescent fiducial markers, functionalization of substrates with ECM proteins, setting up the experiment, and imaging procedures. We demonstrate the application of this technique for quantitative analysis of traction forces exerted by myofibroblasts.

Chronic loss of inhibition in piriform cortex following brief, daily optogenetic stimulation.

It is well established that seizures beget seizures, yet the cellular processes that underlie progressive epileptogenesis remain unclear. Here, we use optogenetics to briefly activate targeted populations of mouse piriform cortex (PCx) principal neurons in vivo. After just 3 or 4 days of stimulation, previously subconvulsive stimuli trigger massive, generalized seizures. Highly recurrent allocortices are especially prone to "optokindling." Optokindling upsets the balance of recurrent excitation and feedback inhibition. To understand how this balance is disrupted, we then selectively reactivate the same neurons in vitro. Surprisingly, we find no evidence of heterosynaptic potentiation; instead, we observe a marked, pathway-specific decrease in feedback inhibition. We find no loss of inhibitory interneurons; rather, decreased GABA synthesis in feedback inhibitory neurons appears to underlie weakened inhibition. Optokindling will allow precise identification of the molecular processes by which brain activity patterns can progressively and pathologically disrupt the balance of cortical excitation and inhibition.

A Combined Strategy of Additive Manufacturing to Support Multidisciplinary Education in Arts, Biology, and Engineering.

This research presents results for the design and creation of supporting teaching materials using additive manufacturing. The materials are inspired by selected artwork of four animal species, which belong to a collection from the museum of the University of Antioquia. The topic selected was fauna in Colombia, and the animals in question were chosen based on important roles they have in areas like health, the environment, and food. These animals will complement science education given to several age groups visiting the museum. In addition to the 3D-manufactured objects, a study was conducted using several age groups that are very relevant to the museum: children, teenagers, and first year undergraduate students. A video showing technical information cards about the manufacturing process was also developed. This project was multidisciplinary, involving collaboration between the engineering school, the museum, and a local high school. The results showed that young visitors want complete information on the animals and to have interaction with the animal models, which is not always possible. This project serves as a local strategy not only for taking arts and knowledge out of the museum but also for planning first year courses in the university and thus reducing problems like school dropout, low motivation, and poor performance in national exams.

ABC4 Consensus: First Latin American Meeting-Assessment, Comments, and Application of Its Recommendations.

Breast cancer accounts for a high burden among all the neoplasms in Latin America, with more-advanced stages at presentation, which could result in high mortality rates. The 4th International Consensus Conference for Advanced Breast Cancer (ABC4) is focused on standardizing therapy for advanced breast cancer (ABC) and has held 5 meetings so far. ABC4 took place in Lisbon, Portugal, from November 2 to 4, 2017; however, the first Latin American ABC conference was held in Lima, Peru, from 18 to 19 May, 2018, chaired by Fatima Cardoso, MD, PhD. During these 2 days, the ABC4 consensus recommendations for advanced and locally advanced breast cancer were presented. Local treatment and systemic therapy were discussed with local experts, mainly focusing on anti-human epidermal growth factor receptor 2 therapy and newly approved drugs for hormone receptor-positive breast cancer, such as as CDK4/6, mammalian target of rapamycin, and poly (ADP-ribose) polymerase inhibitors for triple-negative breast cancer. The discussion focused additionally on access to drugs and ABC4 consensus recommendations as regards Latin American patients.

Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Is Associated with Indigenous American Ancestry in Latin American Women.

Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (+) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2+ tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07-1.35; P = 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2+ tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer. SIGNIFICANCE: The positive association between Indigenous American genetic ancestry and HER2+ breast cancer suggests that the high incidence of HER2+ subtypes in Latinas might be due to population and subtype-specific genetic risk variants.

Temporally irregular electrical stimulation to the epileptogenic focus delays epileptogenesis in rats.

BACKGROUND: Variation in the temporal patterns of electrical pulses in stimulation trains has opened a new field of opportunity for the treatment of neurological disorders, such as pharmacoresistant temporal lobe epilepsy. Whether this novel type of stimulation affects epileptogenesis remains to be investigated. OBJECTIVE: The purpose of this study was to analyze the effects of temporally irregular deep brain stimulation on kindling-induced epileptogenesis in rats. METHODS: Temporally irregular deep brain stimulation was delivered at different times with respect to the kindling stimulation. Behavioral and electrographic changes on kindling acquisition were compared with a control group and a temporally regular deep brain stimulation-treated group. The propagation of epileptiform activity was analyzed with wavelet cross-correlation analysis, and interictal epileptiform discharge ratios were obtained. RESULTS: Temporally irregular deep brain stimulation delivered in the epileptogenic focus during the interictal period shortened the daily afterdischarge duration, slowed the progression of seizure stages, diminished the generalized seizure duration and interfered with the propagation of epileptiform activity from the seizure onset zone to the ipsi- and contralateral motor cortex. We also found a negative correlation between seizure severity and interictal epileptiform discharges in rats stimulated with temporally irregular deep brain stimulation. CONCLUSION: These results provide evidence that temporally irregular deep brain stimulation interferes with the establishment of epilepsy by delaying epileptogenesis by almost twice as long in kindling animals. Thus, temporally irregular deep brain stimulation could be a preventive approach against epilepsy.

Implementation of Computerized Physician Order Entry for Chemotherapy: A Latin American Experience.

PURPOSE: We describe the implementation process of a computerized physician order entry (CPOE) for outpatient chemotherapy at a Latin American hospital, with the intent of providing other institutions with general guidance and insight through our experience. METHODS: In 2012, under the direction of the Department of Medicine of the Instituto Nacional de Enfermedades Neoplásicas, a multidisciplinary team composed of oncologists, nurses, pharmacists, and informatics engineers was formed to develop software for a CPOE for chemotherapy within a preexistent homegrown electronic medical record system in various phases. This included mapping and redesigning processes in an entirely electronic format, integrating the needs of the user for the development of electronic order sets, developing a checkpoint and a warning system to minimize prescription errors, and finally, training all the staff in implementation of the system. RESULTS: A CPOE for outpatient chemotherapy was successfully implemented in 2016. We have successfully standardized 266 chemotherapy orders, including for both solid tumors and hematologic malignancies, on the basis of appropriate guidelines. The software is linked to laboratory results and allows entry of important details for the patient's safety, such as anthropometric information for an automatic dose calculation and ranges for safe prescription. In addition, it is linked to the nursing plan sheets. Finally, it is possible to assess and continuously monitor the complex process of chemotherapy prescription. CONCLUSION: This is the first report of implementation of a CPOE for chemotherapy in our region. The system was designed by a multidisciplinary team with its own resources. Our experience demonstrates the feasibility of computerizing the chemotherapy prescription process, constituting a tangible example for other institutions with potential impact on patient care.

Birds of Antioquia: Georeferenced database of specimens from the Colección de Ciencias Naturales del Museo Universitario de la Universidad de Antioquia (MUA).

The department of Antioquia, Colombia, lies in the northwestern corner of South America and provides a biogeographical link among divergent faunas, including Caribbean, Andean, Pacific and Amazonian. Information about the distribution of biodiversity in this area is of relevance for academic, practical and social purposes. This data paper describes the dataset containing all bird specimens deposited in the Colección de Ciencias Naturales del Museo Universitario de la Universidad de Antioquia (MUA). We curated all the information associated with the bird specimens, including the georeferences and taxonomy, and published the database through the Global Biodiversity Information Facility network. During this process we checked the species identification and existing georeferences and completed the information when possible. The collection holds 663 bird specimens collected between 1940 and 2011. Even though most specimens are from Antioquia (70%), the collection includes material from several other departments and one specimen from the United States. The collection holds specimens from three endemic and endangered species (Coeligena orina, Diglossa gloriossisima, and Hypopirrhus pyrohipogaster), and includes localities poorly represented in other collections. The information contained in the collection has been used for biodiversity modeling, conservation planning and management, and we expect to further facilitate these activities by making it publicly available.

Dietary iron concentration may influence aging process by altering oxidative stress in tissues of adult rats.

Iron is an essential element. However, in its free form, iron participates in redox-reactions, leading to the production of free radicals that increase oxidative stress and the risk of damaging processes. Living organisms have an efficient mechanism that regulates iron absorption according to their iron content to protect against oxidative damage. The effects of restricted and enriched-iron diets on oxidative stress and aging biomarkers were investigated. Adult Wistar rats were fed diets containing 10, 35 or 350 mg/kg iron (adult restricted-iron, adult control-iron and adult enriched-iron groups, respectively) for 78 days. Rats aged two months were included as a young control group. Young control group showed higher hemoglobin and hematocrit values, lower levels of iron and lower levels of MDA or carbonyl in the major studied tissues than the adult control group. Restricted-iron diet reduced iron concentrations in skeletal muscle and oxidative damage in the majority of tissues and also increased weight loss. Enriched-iron diet increased hematocrit values, serum iron, gamma-glutamyl transferase, iron concentrations and oxidative stress in the majority of tissues. As expected, young rats showed higher mRNA levels of heart and hepatic L-Ferritin (Ftl) and kidneys SMP30 as well as lower mRNA levels of hepatic Hamp and interleukin-1 beta (Il1b) and also lower levels of liver protein ferritin. Restricted-iron adult rats showed an increase in heart Ftl mRNA and the enriched-iron adult rats showed an increase in liver nuclear factor erythroid derived 2 like 2 (Nfe2l2) and Il1b mRNAs and in gut divalent metal transporter-1 mRNA (Slc11a2) relative to the control adult group. These results suggest that iron supplementation in adult rats may accelerate aging process by increasing oxidative stress while iron restriction may retards it. However, iron restriction may also impair other physiological processes that are not associated with aging.

Diseño y construcción de un espirómetro pitot computarizado para tratamientos con radioterapia de tumores que se mueven durante la respiración / Design and construction of a computerized spirometer pitot radiotherapy treatments for tumors that move during breathing

Introducción: Ciertos tumores se mueven junto con los movimientos respiratorios dificultando la del tratamiento con la radioterapia. El propósito de este estudio fue implementar una técnica adaptada a la respiración para minimizar el movimiento del tumor, utilizando tecnología desarrollada en nuestro medio. Métodos: Con la ayuda de sensores de caudal de aire que provienen de la respiración, se generaron señales que fueron transformadas en gráficos por medio de interfaces mediante un software diseñado por los investigadores. El procedimiento de utilización de esta técnica constó de tres fases (calibración, entrenamiento y tratamiento). Para demostrar la eficacia de la técnica, se requirió tomar varias series TAC de simulación de diferentes momentos y al mismo paciente para demostrar que el isocentro del tumor no variaba cuando la respiración era bloqueada en el mismo momento del ciclo respiratorio. Resultados: El trabajo de diseño y construcción del espirómetro pitot computarizado se prolongó por cerca de un año, posteriormente se realizaron las pruebas en el equipo de tomografía y un planificador CAT PLAN. La técnica fue fácilmente aprendida por los pacientes. El isocentro del tumor en las diferentes series no sufrió cambios mayores a los 2 mm, con una desviación aceptada y atribuida a la incertidumbre por contorno. El GTV fue mucho mayor en la respiración libre que en respiración bloqueada hasta el 32%. El PTV presentó cambios más drásticos (mayor en 62%). Se observó que cuando se bloquea la respiración en inspiración profunda, el volumen pulmonar aumenta hasta en un 30%, disminuyendo de esta manera el volumen de pulmón sao irradiado. Conclusión: la viabilidad de un diseño de espirómetros de este tipo amplía las posibilidades para el mejoramiento técnico de mayor envergadura, como la miniaturización del equipo, la comunicación inalámbrica de datos y la aplicación de otros sistemas médicos de imágenes como angiofluoroscopía y aplicación...

Introduction: Some tumors move along with the respiratory movements making it hard the treatment with radiotherapy. The aim of this study was to set up a technique adapted with respiration in order to minimize the tumor’s movement with respiration by using our own developed technology. Methods: With help o sensors of air volume which come from breathing, was generated signals that were transformed in graphics through interfaces by software, designed by our researchers. The method of utilization of this technique is listed of three stages (calibration, training and treatment). In order to show the efficacy of this technique, it was required to take several series of TAC of simulation, on different times and to the same patient, with the aim to show the tumor’s isocenter does not vary when the respiration was blocked at the same moment of the respiratory cycle. Results: The work design and construction of the computer pitot spirometer was prolonged near to a year. After that, tests were performed by the tomography equipment and the planner CAT PLAN. This technique was easily learned by patients. The tumor’s isocenter on the different series did not suffer mayor changes to 2 mm, with accepted deviation and attribute it to the uncertainty for contour. The GTV was much major in free respiration than blocked on 32%. The PTV presented more drastic changes (major on 62). We observed that when respiration in blocked on deep inspiration, the pulmonary volume grows about 30%, decreasing for this way the volume of the irradiated healthy lung. Conclusion: The viability of a design of espirometers of this type extend the possibilities to technical improvement of major magnitude, such as the miniaturization of the equipment, the wireless communication of data and the application in the other medical imaging systems as angiofluoroscopia the application to equipment of old generation without incorporated systems.

Vitamin A deficiency increases hepcidin expression and oxidative stress in rat.

OBJECTIVE: The interaction between vitamin A and iron status has been widely reported; however, the exact mechanism involved in this interaction has not been well characterized. The present study investigated the mechanism involved in tissue iron accumulation and changes in the oxidative status in vitamin A-deficient rats. METHODS: Rats were treated with a control diet, a vitamin A-deficient diet, or a vitamin A/iron-deficient diet for 57 d. The animals were sacrificed; the blood, liver, and spleen were collected for biochemical analysis. Analysis of variance or Mann-Whitney tests were used to compare groups and Pearson's or Spearman's tests to investigate the bivariate correlation. RESULTS: Vitamin A deficiency increased liver hepcidin mRNA and iron spleen concentrations; however, iron deficiency in vitamin A-deficient rats deeply inhibits liver hepcidin mRNA expression and significantly increases divalent metal transporter-1 mRNA levels. Liver ferroportin and hereditary hemochromatosis gene mRNA levels did not change in either treatment. In the vitamin A-deficient groups, liver carbonyl protein increased, whereas catalase and glutathione S-transferase activities decreased, suggesting that vitamin A protects the liver against protein oxidation. A significant positive correlation was found between lipid oxidative damage and iron concentration in the liver and spleen (r = 0.611, P = 0.007; r = 0.558, P = 0.025, respectively). CONCLUSION: These results suggest that vitamin A maintains iron homeostasis by the modulation of liver hepcidin expression. The increase of lipid peroxidation in vitamin A deficiency seems to be iron dependent, whereas protein oxidation is not.

Parallel measurement of Ca2+ binding and fluorescence emission upon Ca2+ titration of recombinant skeletal muscle troponin C. Measurement of sequential calcium binding to the regulatory sites.

Calcium binding to chicken recombinant skeletal muscle TnC (TnC) and its mutants containing tryptophan (F29W), 5-hydroxytryptophan (F29HW), or 7-azatryptophan (F29ZW) at position 29 was measured by flow dialysis and by fluorescence. Comparative analysis of the results allowed us to determine the influence of each amino acid on the calcium binding properties of the N-terminal regulatory domain of the protein. Compared with TnC, the Ca(2+) affinity of N-terminal sites was: 1) increased 6-fold in F29W, 2) increased 3-fold in F29ZW, and 3) decreased slightly in F29HW. The Ca(2+) titration of F29ZW monitored by fluorescence displayed a bimodal curve related to sequential Ca(2+) binding to the two N-terminal Ca(2+) binding sites. Single and double mutants of TnC, F29W, F29HW, and F29ZW were constructed by replacing aspartate by alanine at position 30 (site I) or 66 (site II) or both. Ca(2+) binding data showed that the Asp --> Ala mutation at position 30 impairs calcium binding to site I only, whereas the Asp --> Ala mutation at position 66 impairs calcium binding to both sites I and II. Furthermore, the Asp --> Ala mutation at position 30 eliminates the differences in Ca(2+) affinity observed for replacement of Phe at position 29 by Trp, 5-hydroxytryptophan, or 7-azatryptophan. We conclude that position 29 influences the affinity of site I and that Ca(2+) binding to site I is dependent on the previous binding of metal to site II.

Seudotumor inflamatorio de higado / Inflammatory pseudotumor of liver

Se estudia el caso de una niña de 6 años de edad, procedente del área rural del municipio de Chinchiná (Caldas), quien consultó por cuadro clínico consistente en ictericia de un mes de evolución, sin otros síntomas asociados. Las pruebas de funcionamiento hepático mostraron un patrón obstructivo de la vía biliar y la ultrasonografía y tomografía axial computarizada abdominal, evidenciaron la presencia de masa en el hilio hepático, con dilatación de las vías biliares. Se tomaron muestras de la lesión tumoral por laparotomía, las cuales fueron reportadas como proceso inflamatorio, hamartoma mesenquimal y seudotumor inflamatorio. La paciente se manejó con un tubo sinfín para drenaje de las vías biliares, que fue factor determinante en la recuperación. Después de revisar las características clínicas, radiológicas y anatomopatológicas, se llegó a la conclusión que se trataba de un seudotumor inflamatorio