Mutational Activation of ras Genes is Absent in Pediatric Osteosarcoma

Activation of ras oncogenes is found in human cancers; overall it is observed in 15% of all neoplasms. The purpose of this study was to assess the extent of involvement of ras oncogenes in osteosarcoma. Tumor samples from a series of 49 pediatric patients diagnosed with osteosarcoma and treated at our institution were evaluated. Paraffin-embedded tumor samples from diagnostic biopsies, from tumor en bloc resection tissue after neoadjuvant chemotherapy, and samples from metastases were examined in search of point mutations in H, K, and N-ras genes at codons 12 and 61 by means of polymerase chain reaction (PCR), slot-blotting, and radioactive labeled specific DNA probes. A total of 92 archival samples were studied. No point mutations activating these genes were found. These findings suggest that the activation by point mutations at codons 12 and 61 of the H, K, and N-ras genes does not play a role in the pathogenesis of human osteosarcoma. Since no point mutations in codons 12 and 61 were detected, it was not possible to establish any correlation between the ras genes and clinical or histologic finding

Successful strategies implemented towards the elimination of canine rabies in the Western Hemisphere

Almost all cases of human rabies result from dog bites, making the elimination of canine rabies a global priority. During recent decades, many countries in the Western Hemisphere have carried out large-scale dog vaccination campaigns, controlled their free-ranging dog populations and enforced legislation for responsible pet ownership. This article reviews progress in eliminating canine rabies from the Western Hemisphere. After briefly summarizing the history of control efforts and describing the approaches listed above, we note that programs in some countries have been hindered by societal attitudes and severe economic disparities, which underlines the need to discuss measures that will be required to complete the elimination of canine rabies throughout the region. We also note that there is a constant threat for dog-maintained epizootics to re-occur, so as long as dog-maintained rabies "hot spots" are still present, free-roaming dog populations remain large, herd immunity becomes low and dog-derived rabies lyssavirus (RABLV) variants continue to circulate in close proximity to rabies-naïve dog populations. The elimination of dog-maintained rabies will be only feasible if both dog-maintained and dog-derived RABLV lineages and variants are permanently eliminated. This may be possible by keeping dog herd immunity above 70% at all times, fostering sustained laboratory-based surveillance through reliable rabies diagnosis and RABLV genetic typing in dogs, domestic animals and wildlife, as well as continuing to educate the population on the risk of rabies transmission, prevention and responsible pet ownership. Complete elimination of canine rabies requires permanent funding, with governments and people committed to make it a reality. An accompanying article reviews the history and epidemiology of canine rabies in the Western Hemisphere, beginning with its introduction during the period of European colonization, and discusses how spillovers of viruses between dogs and various wild carnivores will affect future eradication efforts (Velasco-Villa et al., 2017)

Wideband Epidermal Antenna for Medical Radiometry

Microwave thermometry is a noninvasive and passive technique for measuring internal body temperature. Wearable compact antennas, matched to the specific body area, are required for this method. We present a new epidermal wideband antenna for medical radiometry. The double asymmetric H-shaped slot antenna was designed to be matched to different parts of the body without fat layers. The slots are fed by a short-circuited microstrip line in order to decrease size and back radiation, thus reducing potential interferences. In this way, contribution to radiometric temperature due to back radiation is lower than 4%, versus the 20% of the volume under investigation, over the whole operating frequency band. The designed prototype was manufactured on a flexible substrate. The antenna is a very small size, to make it comfortable and suitable for being used by patients with different body mass indexes. The double H-shaped antenna shows good wideband matching results from around 1.5 GHz up to 5 GHz, in different body locations such as the neck, foot instep and foot sole

Pattern recognition in data as a diagnosis tool

Medical data often appear in the form of numerical matrices or sequences. We develop mathematical tools for automatic screening of such data in two medical contexts: diagnosis of systemic lupus erythematosus (SLE) patients and identification of cardiac abnormalities. The idea is first to implement adequate data normalizations and then identify suitable hyperparameters and distances to classify relevant patterns. To this purpose, we discuss the applicability of Plackett-Luce models for rankings to hyperparameter and distance selection. Our tests suggest that, while Hamming distances seem to be well adapted to the study of patterns in matrices representing data from laboratory tests, dynamic time warping distances provide robust tools for the study of cardiac signals. The techniques developed here may set a basis for automatic screening of medical information based on pattern comparison

Reconocimiento automatizado de patrones como herramienta diagnostica en el Lupus Eritematoso Sistemico (LES)

La inteligencia artificial (IA) es útil para el aprendizaje automático en contextos clínicos con grandes cantidades de datos. Se emplean técnicas de clasificación supervisada y no supervisada en el estudio de la expresión/transcripción génica en la enfermedad y de respuesta terapéutica. Sin embargo, la cantidad de datos disponibles en muchas situaciones médicas es escasa, por lo que es preciso calibrar muy bien la técnica de análisis a emplear para que el rendimiento sea adecuado. Dada la complejidad, el polimorfismo clínico del LES y sus diversas complicaciones, el reconocimiento automatizado de patrones evolutivos de variables puede ser de ayuda en la clínica

Mejora de la precisión de la herramienta Frax mediante la adición de una capa de análisis basada en medición de la densidad radiológica con la técnica 'Earth Mover's distance' (EMD)

La herramienta de cálculo FRAX determina la probabilidad a 10 años de que un individuo entre 40 y 90 años sufra una fractura osteoporótica mayor o de cadera computando los factores de riesgo del individuo y, opcionalmente, la densidad mineral ósea determinada por absorciometría de fotón dual (DEXA), en comparación con los de una cohorte de la que se conoce la prevalencia de fractura. Por otra parte, hay datos que sugieren que la medida de la densidad radiológica mediante la técnica Earth Mover’s Distance (EMD) puede mejorar la precisión diagnostica en mamografías y radiología osteoarticular, entre otras

Heart transplantation using allografts from older donors: multicenter study results

33rd Annual Meeting and Scientific Session of the International Society for Heart and Lung Transplantation, April 24–27, 2013, Montreal, Canada.[Abstract] Background. The lengthy waiting time for heart transplantation is associated with high mortality. To increase the number of donors, new strategies have emerged, including the use of hearts from donors ≥50 years old. However, this practice remains controversial. The aim of this study was to evaluate outcomes of patients receiving heart transplants from older donors. Methods. We retrospectively analyzed 2,102 consecutive heart transplants in 8 Spanish hospitals from 1998 to 2010. Acute and overall mortality were compared in patients with grafts from donors ≥50 years old versus grafts from younger donors. Results. There were 1,758 (84%) transplanted grafts from donors < 50 years old (Group I) and 344 (16%) from donors ≥50 years old (Group II). Group I had more male donors than Group II (71% vs 57%, p = 0.0001). The incidence of cardiovascular risk factors was higher in older donors. There were no differences in acute mortality or acute rejection episodes between the 2 groups. Global mortality was higher in Group II (rate ratio, 1.40; 95% confidence interval, 1.18–1.67; p = 0.001) than in Group I. After adjusting for donor cause of death, donor smoking history, recipient age, induction therapy, and cyclosporine therapy, the differences lost significance. Group II had a higher incidence of coronary allograft vasculopathy at 5 years (rate ratio, 1.67; 95% confidence interval, 1.22–2.27; p = 0.001). Conclusions. There were no differences in acute and overall mortality after adjusting for confounding factors. However, there was a midterm increased risk of coronary allograft vasculopathy with the use of older donors. Careful selection of recipients and close monitoring of coronary allograft vasculopathy are warranted in these patients.Instituto de Salud Carlos III; RD12/0042/00

Impact of short-term mechanical circulatory support with extracorporeal devices on postoperative outcomes after emergency heart transplantation: data from a multi-institutional Spanish cohort

[Abstract] Objectives. We sought to investigate the potential impact of preoperative short-term mechanical circulatory support (MCS) with extracorporeal devices on postoperative outcomes after emergency heart transplantation (HT). Methods. We conducted an observational study of 669 patients who underwent emergency HT in 15 Spanish hospitals between 2000 and 2009. Postoperative outcomes of patients bridged to HT on short-term MCS (n = 101) were compared with those of the rest of the cohort (n = 568). Short-term MCS included veno-arterial extracorporeal membrane oxygenators (VA-ECMOs, n = 23), and both pulsatile-flow (n = 53) and continuous-flow (n = 25) extracorporeal ventricular assist devices (VADs). No patient underwent HT on intracorporeal VADs. Results. Preoperative short-term MCS was independently associated with increased in-hospital postoperative mortality (adjusted odds-ratio 1.75, 95% CI 1.05–2.91) and overall post-transplant mortality (adjusted hazard-ratio 1.60, 95% CI 1.15–2.23). Rates of major surgical bleeding, cardiac reoperation, postoperative infection and primary graft failure were also significantly higher among MCS patients. Causes of death and survival after hospital discharge were similar in MCS and non-MCS candidates. Increased risk of post-transplant mortality affected patients bridged on pulsatile-flow extracorporeal VADs (adjusted hazard-ratio 2.21, 95% CI 1.48–3.30) and continuous-flow extracorporeal VADs (adjusted hazard-ratio 2.24, 95% CI 1.20–4.19), but not those bridged on VA-ECMO (adjusted hazard-ratio 0.51, 95% CI 0.21–1.25). Conclusions. Patients bridged to emergency HT on short-term MCS are exposed to an increased risk of postoperative complications and mortality. In our series, preoperative bridging with VA-ECMO resulted in comparable post-transplant outcomes to those of patients transplanted on conventional support

Preoperative INTERMACS profiles determine postoperative outcomes in critically ill patients undergoing emergency heart transplantation: analysis of the Spanish National Heart Transplant Registry

[Abstract] Background. Postoperative outcomes of patients with advanced heart failure undergoing ventricular assist device implantation are strongly influenced by their preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles. We sought to investigate whether a similar association exists in patients undergoing emergency heart transplantation. Methods and Results. By means of the Spanish National Heart Transplant Registry database, we identified 704 adult patients treated with emergency heart transplantation in 15 Spanish centers between 2000 and 2009. Post-transplant outcomes were analyzed pertaining to patient preoperative INTERMACS profiles, which were retrospectively assigned by 2 blinded cardiologists. Before transplantation, INTERMACS profile 1 (critical cardiogenic shock) was present in 207 patients, INTERMACS profile 2 (progressive decline) in 291, INTERMACS profile 3 (inotropic dependence) in 176, and INTERMACS profile 4 (resting symptoms) was present in 30 patients. In-hospital postoperative mortality rates were, respectively, 43%, 26.8%, and 18% in patients with profiles 1, 2, and 3 to 4 (P<0.001). INTERMACS 1 patients also presented the highest incidence of primary graft failure (1: 31.3%, 2: 22.3%, 3–4: 21.8%; P=0.03) and postoperative need for dialysis (1: 33.2%, 2: 18.9%, 3–4: 21.5%; P<0.001). Adjusted odds-ratios for in-hospital postoperative mortality were 4.38 (95% confidence interval, 2.51–7.66) for profile 1 versus 3 to 4, 2.49 (95% confidence interval, 1.56–3.97) for profile 1 versus 2, and 1.76 (95% confidence interval, 1.02–3.03) for profile 2 versus 3 to 4. Long-term survival after hospital discharge was not influenced by preoperative INTERMACS profiles. Conclusions. Preoperative INTERMACS profiles determine outcomes after emergency heart transplantation. Results call for a change in policies related to the management of heart transplant candidates presenting with INTERMACS profiles 1 and 2

Versatile Graphene-Based Platform for Robust Nanobiohybrid Interfaces

Technologically useful and robust graphene-based interfaces for devices require the introduction of highly selective, stable, and covalently bonded functionalities on the graphene surface, whilst essentially retaining the electronic properties of the pristine layer. This work demonstrates that highly controlled, ultrahigh vacuum covalent chemical functionalization of graphene sheets with a thiol-terminated molecule provides a robust and tunable platform for the development of hybrid nanostructures in different environments. We employ this facile strategy to covalently couple two representative systems of broad interest: metal nanoparticles, via S-metal bonds, and thiol-modified DNA aptamers, via disulfide bridges. Both systems, which have been characterized by a multi-technique approach, remain firmly anchored to the graphene surface even after several washing cycles. Atomic force microscopy images demonstrate that the conjugated aptamer retains the functionality required to recognize a target protein. This methodology opens a new route to the integration of high-quality graphene layers into diverse technological platforms, including plasmonics, optoelectronics, or biosensing. With respect to the latter, the viability of a thiol-functionalized chemical vapor deposition graphene-based solution-gated field-effect transistor array was assessed