Use of Gene Therapy in a Subcutaneous Murine Model of Lung Cancer

OBJECTIVE: To assess the effectiveness of in vivo gene therapy to treat subcutaneous tumors generated from murine lung cancer cells. MATERIAL AND METHODS: C57BL/6 mice received subcutaneus injections of 5×105 cells from the murine Lewis lung cancer cell line. By 10 days, subcutaneous tumors of approximately 5 mm diameter were formed. At that point, treatment was provided by intratumor injection of a replication-defective recombinant adenovirus carrying the gene for thymidine kinase (AdCMV-Tk) or interleukin (IL) 12 (AdCMV-IL12), or by injection of syngeneic dendritic cells previously transduced with adenovirus containing the IL-12 gene (DC-IL12). Control groups were treated with saline or adenovirus containing the gene for β-galactosidase (AdCMV-LacZ), which functions as a reporter gene and does not have a therapeutic effect. The number of animals in each group ranged from 14 to 25 in experiments using adenovirus and from 10 to 12 in experiments using dendritic cells. Tumor size was followed for 3 weeks in the case of treatment with adenovirus and 4 weeks for treatment with dendritic cells. RESULTS: A significant reduction in subcutaneous tumor growth was observed in the groups treated with AdCMVTk, AdCMV-IL12, and DC-IL12 compared with control groups treated with saline or AdCMV-LacZ. The difference was statistically significant from day 7 of treatment in the AdCMV-Tk group, from day 9 in the AdCMV-IL12 group, and from day 10 in the DC-IL12 group, and in all cases it was maintained until the end of the follow-up period. CONCLUSIONS: Gene therapy with AdCMV-Tk, AdCMVIL12, or DC-IL12 is effective in our model of subcutaneous tumors arising from cells of the Lewis lung cancer cell line. The treatment leads to a significant reduction in tumor growth compared with control groups

Cirugía percutánea de la litiasis renal en la era de la litotripsia extracorpórea: Experiencia en 301 pacientes

Indexación: ScieloIntroduction: Percutaneous renal surgery was introduced more than 20 years ago in urological practice. Extracorporeal Shock Wave Lithotripsy (ESWL) enter the urological scene shortly after. Our objective is to show our experience in percutaneous renal surgery after the introduction of the ESWL in our institution. Material and Methods: Surgical outcomes of 301 patients who underwent percutaneous renal surgery as treatment of renal stones were analyzed. This series begins just before the introduction of ESWL in our unit. Results: Renal pelvis was the most frequent localization with 142 cases (47.2%). There were 51 patients with straghorn calculi. 255 (84.7%) were stone free after one single procedure. Residual fragments were managed with many methods, until only 16 patients (5.4%) had residual fragments. Complications occurred in 26 patients (8.9%). There was no mortality. Conclusions: Percutaneous surgery is an important tool in the management of renal stones. In general, renal stones managed with this procedure, are more complex, however the achievement of good results is possible.La cirugía percutánea (CP) de la litiasis renal fue introducida en la urología hace más de 20 años. Poco después lo hizo la litotripsia extracorpórea (LEC). Nuestro objetivo es mostrar la experiencia en CP luego de la introducción de la LEC en nuestro servicio. Material y Métodos: Se analizan en forma retrospectiva los resultados de 301 pacientes operados por CP por litiasis renal. La serie comienza con la adquisición de un litotriptor extracorpóreo en nuestro servicio. Resultados: La localización más frecuente fue la pelvis renal con 142 casos (47,2%). Se observó litiasis coraliforme en 51 pacientes. Doscientos cincuenta y cinco (84,7%), quedaron libres de litiasis con un procedimiento. La litiasis residual fue tratada con diversos métodos, para un total final de 16 pacientes con fragmentos residuales (5,4%). Ocurrieron complicaciones en 26 pacientes (8,9%). No hubo mortalidad. Conclusiones: La cirugía percutánea de la litiasis renal es un procedimiento que debe formar parte importante en la resolución de la litiasis renal. En general las litiasis tratadas son más complejas, sin embargo, los resultados son excelentes.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0718-40262010000500013&nrm=is

Nefrectomía simple laparoscópica NOTES y LESS con el uso de instrumentos laparoscópicos estándar: Experiencia inicial en 3 casos

Indexación: ScieloIntroduction: Natural orifice transluminal endoscopic surgery (NOTES) and Laparoendoscopic Single Site Surgery (LESS) are emerging technologies, which allows to performed surgical procedures avoiding any surgical scars. However there are some problems due to the lack of equipment available for these procedures. The aim of these study is to present our initial experience with the transvaginal nephrectomy NOTES and LESS using standard laparoscopic instruments. Material and Methods: Two female patients (23 and 26 years old) with diagnosis of recurrent urinary tract infection and renal atrophy. A laparoscopic simple nephrectomy with transvaginal NOTES assistance was performed, using one access port for the camera and two abdominal work ports of 10 and 3mm. In a third patient (15 years old) a transumbilical LESS nephrectomy was preformed with the use of standard laparoscopic instruments. Results: Average operative time was 110 min (40-200), with an estimated blood loss of 200 cc. There were no perioperative complications and all patients were discharged 36 hours after surgery. Conclusion: Laparoscopic simple nephrectomy with transvaginal NOTES assistance and LESS are technically feasible with the use of standard laparoscopic instruments. Special access trocars and instruments development for this procedure will allow to performed a pure technique without the use of abdominal incisions.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0718-40262010000300016&nrm=is

Atrial fibrillation signatures on intracardiac electrograms identified by deep learning

Automatic detection of atrial fibrillation (AF) by cardiac devices is increasingly common yet suboptimally groups AF, flutter or tachycardia (AT) together as 'high rate events'. This may delay or misdirect therapy. Objective: We hypothesized that deep learning (DL) can accurately classify AF from AT by revealing electrogram (EGM) signatures. Methods: We studied 86 patients in whom the diagnosis of AF or AT was established at electrophysiological study (25 female, 65 ± 11 years). Custom DL architectures were trained to identify AF using N = 29,340 unipolar and N = 23,760 bipolar EGM segments. We compared DL to traditional classifiers based on rate or regularity. We explained DL using computer models to assess the impact of controlled variations in shape, rate and timing on AF/AT classification in 246,067 EGMs reconstructed from clinical data. Results: DL identified AF with AUC of 0.97 ± 0.04 (unipolar) and 0.92 ± 0.09 (bipolar). Rule-based classifiers misclassified ∼10-12% of cases. DL classification was explained by regularity in EGM shape (13%) or timing (26%), and rate (60%; p 15% timing variation, <0.48 correlation in beat-to-beat EGM shapes and CL < 190 ms (p < 0.001). Conclusions: Deep learning of intracardiac EGMs can identify AF or AT via signatures of rate, regularity in timing or shape, and specific EGM shapes. Future work should examine if these signatures differ between different clinical subpopulations with AF

Identification of new hot subdwarf binary systems by means of Virtual Observatory tools

The estimation of the binary fraction of hot subdwarfs is key to shed light on the different evolution scenarios proposed to explain the loss of the hydrogen envelope during the red giant branch phase. In this paper, we analyse the spectral energy distribution of the hot subdwarfs included in a recent and comprehensive catalogue with the aim of identifying companions. Our methodology shows a performance superior to the photometric criteria used in that study, identifying 202 objects wrongly classified as binaries according to their spectral energy distributions, and finding 269 new binaries. Out of an initial sample of 3186 objects, we classified 2469 as single and 615 as binary hot subdwarfs. The rest of the objects (102) were not classified because of their inadequate spectral energy distribution fitting due, in turn, to poor quality photometry. Effective temperatures, luminosities, and radii were computed for 192 singles and 42 binaries. They, in particular the binary sample, constitute an excellent data set to further perform a more careful spectroscopic analysis that could provide detailed values for the chemical composition, masses, ages, rotation properties, or reflection effects for the shortest period systems. The results obtained in this paper will be used as a reference for a forthcoming work where we aim to generalize binary and single hot subdwarf classification using Artificial Intelligence-based techniques.Agencia Estatal de Investigación | Ref. RTI2018-095076-B-C22Agencia Estatal de Investigación | Ref. PID2020-112949GB-I00Agencia Estatal de Investigación | Ref. MDM-2017-0737Xunta de Galicia | Ref. ED431G 2019/01Xunta de Galicia | Ref. ED481A-2019/155Gobierno de la Comunidad de Madrid | Ref. 2018-T2/TIC-1169

Three dimensional reconstruction to visualize atrial fibrillation activation patterns on curved atrial geometry

Background: The rotational activation created by spiral waves may be a mechanism for atrial fibrillation (AF), yet it is unclear how activation patterns obtained from endocardial baskets are influenced by the 3D geometric curvature of the atrium or 'unfolding' into 2D maps. We develop algorithms that can visualize spiral waves and their tip locations on curved atrial geometries. We use these algorithms to quantify differences in AF maps and spiral tip locations between 3D basket reconstructions, projection onto 3D anatomical shells and unfolded 2D surfaces. Methods: We tested our algorithms in N = 20 patients in whom AF was recorded from 64-pole baskets (Abbott, CA). Phase maps were generated by non-proprietary software to identify the tips of spiral waves, indicated by phase singularities. The number and density of spiral tips were compared in patient-specific 3D shells constructed from the basket, as well as 3D maps from clinical electroanatomic mapping systems and 2D maps. Results: Patients (59.4±12.7 yrs, 60% M) showed 1.7±0.8 phase singularities/patient, in whom ablation terminated AF in 11/20 patients (55%). There was no difference in the location of phase singularities, between 3D curved surfaces and 2D unfolded surfaces, with a median correlation coefficient between phase singularity density maps of 0.985 (0.978-0.990). No significant impact was noted by phase singularities location in more curved regions or relative to the basket location (p>0.1). Conclusions: AF maps and phase singularities mapped by endocardial baskets are qualitatively and quantitatively similar whether calculated by 3D phase maps on patient-specific curved atrial geometries or in 2D. Phase maps on patient-specific geometries may be easier to interpret relative to critical structures for ablation planning

Leisure-time physical activity, sedentary behavior, and risk of breast cancer: Results from the SUN (‘Seguimiento Universidad De Navarra’) project

Evidence is still limited on the influence of sedentary lifestyles on breast cancer (BC) risk. Also, prospective information on the combined effects of both sedentariness and leisure-time physical activity (LTPA) is scarce. We aimed to assess the association of higher sedentary behavior and LTPA (separately and in combination) with the risk of BC in a middle-aged cohort of university graduates. The SUN Project is a follow-up study initiated in 1999 with recruitment permanently open. Baseline assessments included a validated questionnaire on LTPA and sedentary habits. Subsequently, participants completed biennial follow-up questionnaires. Multivariable adjusted Cox models were used to estimate the hazard ratios (HR) for incident BC according to LTPA, TV-watching, the joint classification of both, and a combined 8-item multidimensional active lifestyle score. We included 10,812 women, with 11.8 years of median follow-up of. Among 115,802 women-years of follow-up, we confirmed 101 incident cases of BC. Women in the highest category of LTPA (>16.5 MET-h/week) showed a significantly lower risk of BC (HR = 0.55; 95% CI: 0.34–0.90) compared to women in the lowest category (≤6 MET/h-week). Women watching >2 h/d of TV sh owed a higher risk (HR = 1.67; 95% CI:1.03–2.72) than those who watched TV 2 h/d may substantially increase BC risk, independently of each other

Non-invasive Spatial Mapping of Frequencies in Atrial Fibrillation: Correlation With Contact Mapping

Introduction: Regional differences in activation rates may contribute to the electrical substrates that maintain atrial fibrillation (AF), and estimating them non-invasively may help guide ablation or select anti-arrhythmic medications. We tested whether non-invasive assessment of regional AF rate accurately represents intracardiac recordings. Methods: In 47 patients with AF (27 persistent, age 63 ± 13 years) we performed 57-lead non-invasive Electrocardiographic Imaging (ECGI) in AF, simultaneously with 64-pole intracardiac signals of both atria. ECGI was reconstructed by Tikhonov regularization. We constructed personalized 3D AF rate distribution maps by Dominant Frequency (DF) analysis from intracardiac and non-invasive recordings. Results: Raw intracardiac and non-invasive DF differed substantially, by 0.54 Hz [0.13 - 1.37] across bi-atrial regions (R2 = 0.11). Filtering by high spectral organization reduced this difference to 0.10 Hz (cycle length difference of 1 - 11 ms) [0.03 - 0.42] for patient-level comparisons (R2 = 0.62), and 0.19 Hz [0.03 - 0.59] and 0.20 Hz [0.04 - 0.61] for median and highest DF, respectively. Non-invasive and highest DF predicted acute ablation success (p = 0.04). Conclusion: Non-invasive estimation of atrial activation rates is feasible and, when filtered by high spectral organization, provide a moderate estimate of intracardiac recording rates in AF. Non-invasive technology could be an effective tool to identify patients who may respond to AF ablation for personalized therapy

Complexes of Silver(I) Ions and Silver Phosphate Nanoparticles with Hyaluronic Acid and/or Chitosan as Promising Antimicrobial Agents for Vascular Grafts

Polymers are currently widely used to replace a variety of natural materials with respect to their favourable physical and chemical properties, and due to their economic advantage. One of the most important branches of application of polymers is the production of different products for medical use. In this case, it is necessary to face a significant disadvantage of polymer products due to possible and very common colonization of the surface by various microorganisms that can pose a potential danger to the patient. One of the possible solutions is to prepare polymer with antibacterial/antimicrobial properties that is resistant to bacterial colonization. The aim of this study was to contribute to the development of antimicrobial polymeric material ideal for covering vascular implants with subsequent use in transplant surgery. Therefore, the complexes of polymeric substances (hyaluronic acid and chitosan) with silver nitrate or silver phosphate nanoparticles were created, and their effects on gram-positive bacterial culture of Staphylococcus aureus were monitored. Stages of formation of complexes of silver nitrate and silver phosphate nanoparticles with polymeric compounds were characterized using electrochemical and spectrophotometric methods. Furthermore, the antimicrobial activity of complexes was determined using the methods of determination of growth curves and zones of inhibition. The results of this study revealed that the complex of chitosan, with silver phosphate nanoparticles, was the most suitable in order to have an antibacterial effect on bacterial culture of Staphylococcus aureus. Formation of this complex was under way at low concentrations of chitosan. The results of electrochemical determination corresponded with the results of spectrophotometric methods and verified good interaction and formation of the complex. The complex has an outstanding antibacterial effect and this effect was of several orders higher compared to other investigated complexes