Retrospective evaluation of toceranib phosphate (Palladia) use in the treatment of feline pancreatic carcinoma.

Objective: To retrospectively assess the biological response in cats with pancreatic carcinoma treated with toceranib phosphate. Animals: Twenty-six client-owned cats. Procedure: Patient information from multiple institutions was solicited via an emailed REDCap survey. For inclusion, cats were required to have a confirmed diagnosis of exocrine pancreatic carcinoma either by histopathology, cytology, or both; to have received treatment with toceranib phosphate; and to have adequate follow-up data for analysis. Results: Twenty cats were treated for gross disease and 6 for microscopic disease/incomplete margins. Clinical benefit (complete response, partial response, or stable disease ≥ 10 wk) was observed in 9/20 cats treated in the gross disease setting (45%; complete response: n = 1, stable disease: n = 8). The remaining 11 cats with gross disease did not respond to toceranib phosphate. In the cats with microscopic disease, response was mixed. The median survival time for all cats was 97 d (range: 1 to 1666 d). Conclusion: Toceranib phosphate was well-tolerated and provided modest clinical benefit to a subset of cats treated. Clinical relevance: Although feline exocrine pancreatic carcinoma continues to be a challenging disease to treat, toceranib phosphate appeared to provide potential clinical benefit.

Évaluation rétrospective de l'utilisation du phosphate de tocéranib (Palladia) dans le traitement du carcinome pancréatique félin. Objectif: Évaluer rétrospectivement la réponse biologique chez les chats atteints d'un carcinome pancréatique traités par le phosphate de tocéranib. Animaux: Vingt-six chats appartenant à des clients. Procédure: Les informations sur les patients de plusieurs institutions ont été sollicitées via une enquête REDCap envoyée par courriel. Pour être inclus, les chats devaient avoir un diagnostic confirmé de carcinome pancréatique exocrine, soit par histopathologie, soit par cytologie, soit par les deux; avoir reçu un traitement par phosphate de tocéranib; et disposer de données de suivi adéquates pour l'analyse. Résultats: Vingt chats ont été traités pour une maladie macroscopique et six pour une maladie microscopique/marges incomplètes. Un bénéfice clinique (réponse complète, réponse partielle ou maladie stable ≥ 10 semaines) a été observé chez 9 chats sur 20 traités dans le cadre d'une maladie macroscopique (45 %; réponse complète: n = 1, maladie stable: n = 8). Les 11 chats restants atteints d'une maladie macroscopique n'ont pas répondu au phosphate de tocéranib. Chez les chats atteints d'une maladie microscopique, la réponse était mitigée. La durée médiane de survie pour tous les chats était de 97 jours (écart: 1 à 1666 jours). Conclusion: Le phosphate de tocéranib a été bien toléré et a apporté un bénéfice clinique modeste à un sous-ensemble de chats traités. Pertinence clinique: Bien que le carcinome pancréatique exocrine félin continue d'être une maladie difficile à traiter, le phosphate de tocéranib semble offrir un bénéfice clinique potentiel.(Traduit par Dr Serge Messier).

Spatially-Resolved Thermometry of Filamentary Nanoscale Hot Spots in TiO2 Resistive Random Access Memories to Address Device Variability.

Resistive random access memories (RRAM), based on the formation and rupture of conductive nanoscale filaments, have attracted increased attention for application in neuromorphic and in-memory computing. However, this technology is, in part, limited by its variability, which originates from the stochastic formation and extreme heating of its nanoscale filaments. In this study, we used scanning thermal microscopy (SThM) to assess the effect of filament-induced heat spreading on the surface of metal oxide RRAMs with different device designs. We evaluate the variability of TiO2 RRAM devices with area sizes of 2 × 2 and 5 × 5 µm2. Electrical characterization shows that the variability indicated by the standard deviation of the forming voltage is ∼2 times larger for 5 × 5 µm2 devices than for the 2 × 2 µm2 ones. Further knowledge on the reason for this variability is gained through the SThM thermal maps. These maps show that for 2 × 2 µm2 devices the formation of one filament, i.e., hot spot at the device surface, happens reliably at the same location, while the filament location varies for the 5 × 5 µm2 devices. The thermal information, combined with the electrical, interfacial, and geometric characteristics of the device, provides additional insights into the operation and variability of RRAMs. This work suggests thermal engineering and characterization routes to optimize the efficiency and reliability of these devices.

Copper recovery through biohydrometallurgy route: chemical and physical characterization of magnetic (m), non-magnetic (nm) and mix samples from obsolete smartphones.

The more modern electronics are, the smaller and complex printed circuit boards are. Thus, these materials are continually changed (physicochemically), increasing the copper concentrations in smartphones. In this sense, it is challenging to set standardized recycling processes to improve metal recovery. In addition, biohydrometallurgy is a clean and cheap process to obtain critical metals from low-grade sources and waste electronic equipment. Therefore, the aim of this work was to characterize, physicochemically, 21 PCBs from smartphones manufactured from 2010 to 2015, and then to recover the copper by Acidithiobacillus ferrooxidans (biohydrometallurgy). The PCBs were comminuted and separated into Magnetic (M), Nonmagnetic (NM) and without magnetic separation (MIX) samples. It was identified 217.8; 560.3 and 401.3 mg Cu/g of PCBs for M, NM and MIX samples, respectively. Regarding biohydrometallurgy, the culture media iron-supplemented (NM + Fe and MIX + Fe) increased the copper content by 2.6 and 7.2%, respectively, and the magnetic separation step was insignificant.

Metallic filamentary conduction in valence change-based resistive switching devices: the case of TaOx thin film with x∼ 1.

The resistive switching in metal-oxide thin films typically occurs via modulation of the oxygen content in nano-sized conductive filaments. For Ta2O5-based resistive switching devices, the two current models consider filaments composed of oxygen vacancies and those containing metallic Ta clusters. The present work tries to resolve this dispute. The filaments in Ta2O5 were formerly shown to exhibit the same electrical transport mechanisms as TaOx thin films with x∼ 1.0. In this paper, sputtered thin films of pure ß-Ta and of TaOx with different oxygen concentrations are studied and compared in terms of their structure and electrical transport. The structural analysis reveals the presence of Ta clusters in the TaOx films. Identical electrical transport characteristics were observed in the TaOx films with x∼ 1.0 and in the ß-Ta film. Both show the same transport mechanism, a carrier concentration on the order of 1022 cm-3 and a positive magnetoresistance associated with weak antilocalization at T < 30 K. It is concluded that the electrical transport in the TaOx films with x∼ 1.0 is dominated by percolation through Ta clusters. This means that the transport in the filaments is also determined by percolation through Ta clusters, strongly supporting the metallic Ta filament model.

Structure-Performance Relationships of Temperature-Responsive PLGA-PEG-PLGA Gels for Sustained Release of Bone Morphogenetic Protein-2.

PLGA (poly(lactic-co-glycolic) acid)-PEG (polyethylene glycol)-PLGA synthesis conditions have an impact on the physicochemical features of the copolymer and its usefulness as biomaterial. This study reports on an analysis of the composition and structural properties of PLGA-PEG-PLGA copolymers applying a variety of analytical techniques. Viscoelastic properties and particularly the temperature-responsive behavior of PLGA-PEG-PLGA showed a marked dependence on copolymer structural features. Physicochemical and biological properties, such as bioadhesion, biocompatibility and cell viability, of the raw copolymers and their gels were also evaluated. The most promising copolymer was chosen to formulate the osteoinductive protein bone morphogenetic protein-2 (125I-BMP-2), and the ability of its gels to sustain the release both in vitro and in vivo was monitored in situ using a gamma counter. In vitro diffusion studies were carried out using a bioinspired set-up that included a biorelevant receptor medium. In vivo release tests after implantation in a critical-size calvarial defect model showed an important burst, but then the release fitted well to the square-root kinetics. Importantly, the release rate constants recorded in vitro and in vivo matched each other suggesting close in vitro-in vivo correlation. Overall, the information gathered opens new perspectives in the biomedical application of these temperature-sensitive materials.

Evaluation of the effectiveness of a bMSC and BMP-2 polymeric trilayer system in cartilage repair.

In this study a poly(lactide-co-glycolide) acid (PLGA) tri-layer scaffold is proposed for cartilage repair. The trilayer system consists of a base layer formed by a tablet of PLGA microspheres, a second layer composed of a microsphere suspension placed on top of the tablet, and the third layer, which constitutes an external electrospun PLGA thin polymeric membrane. Combinations of bone morphogenetic protein-2 (BMP-2) encapsulated in the microspheres of the suspension layer, and bone marrow mesenchymal stem cells (bMSC) seeded on the electrospun membrane, are evaluated by histologic analyses and immunohistochemistry in a critical size osteochondral defect in rabbits. Five experimental groups, including a control group (empty defect), a blank group (blank scaffold), a bMSC treated group, two groups treated with 2.5 µg or 8.5 µg of BMP-2 and another two groups implanted with bMSC-BMP-2 combination are evaluated. The repair area increases throughout the experimental time (24 weeks). The repair observed in the treated groups is statistically higher than in control and blank groups. However, the bMSC-BMP-2 combination does not enhance the BMP-2 response. In conclusion, BMP-2 and bMSC repaired effectively the osteochondral defect in the rabbits. The bMSC-BMP-2 combination did not produce synergism.

BMP-2, PDGF-BB, and bone marrow mesenchymal cells in a macroporous ß-TCP scaffold for critical-size bone defect repair in rats.

The aim of this work was to study the bone repair induced by bone morphogenetic protein-2 (BMP-2), rat mesenchymal stem cells (rMSCs), and platelet-derived growth factor (PDGF-BB) incorporated in a macroporous beta-tricalcium phosphate (ß-TCP) system fabricated by robocasting, and to identify the most beneficial combination in a critical rat calvaria defect. BMP-2 was formulated in microspheres to provide a prolonged, local concentration, whereas PDGF-BB, which acts during the initial stage of defect repair, was incorporated in a thin layer of crosslinked alginate. Approximately 80% of PDGF-BB and 90% of BMP-2 were released into the defect during the first 2 d and 3 weeks, respectively. Histological analyses indicated a minor synergistic effect in the BMP-2-MSC groups. In contrast, significant antagonism was found with combined BMP-2 and PDGF-BB defect treatment. The high-grade repair induced by BMP-2 rules out any advantage from combining BMP-2 with PDGF-BB or MSCs, at least with this scaffold and defect model.

Evaluation of nanostructure and microstructure of bone regenerated by BMP-2-porous scaffolds.

In this study, three systems containing BMP-2 were fabricated, including two electrospun sandwich-like-systems of PLGA 75:25 and PLGA 50:50 and a microsphere system of PLGA 50:50 to be implanted in a critical size defect in rat calvaria. The in vivo BMP-2 release profiles of the three systems were similar. The total dose was released during the first two weeks. To evaluate the nano and microstructure of the regenerated bone a multi-technique analysis was used, including stereo microscope, X-Ray; AFM, micro-CT, and histological analyses. The progression of bone regeneration was followed at 4, 8, and 12 weeks after the microsphere system implantation whereas the two electrospun systems were evaluated at fixed 12 weeks. All the techniques applied showed high bone regeneration. The average values of bone volume density, bone mineral density, Young's modulus, and the percent of bone repair were ∼70% of the values of the native bone. Besides, SEM-EDX analysis indicated that the main chemical elements in the new bone were oxygen, calcium, and phosphorus in a ratio similar to that of native bone. In comparison, the micro-CT may provide an alternative to histology for the evaluation of bone formation at the defect size.

Smurf1 knocked-down, mesenchymal stem cells and BMP-2 in an electrospun system for bone regeneration.

A sandwich-like system, fabricated with electrospun, poly(lactic-co-glycolic-acid) (PLGA) membranes incorporating either human recombinant bone morphogenetic protein 2 (BMP-2) enriched microspheres, rat bone marrow mesenchymal stem cells (rMSC), or rMSC with their Smurf1 (SMAD ubiquitin regulatory factor-1) expression knocked down by means of siRNA (rMSC573) at varying densities was evaluated in a rat calvarial, critical-size defect. The behavior of four membrane varieties, fabricated with different PLGA copolymers, was initially studied in rMSC cultures to decide on optimal membrane degradation and cell proliferation and differentiation characteristics. PLGA75:25 provided the most stable structure, and favored the cell environment. Radiological and histological analyses indicated bone repair in animals treated with the PLGA75:25 bioactivated systems. We found no synergist interaction between BMP-2 and rMSC 8 to 12 weeks postimplantation. By contrast, synergistic defect repair of around 85% was detected after 8 weeks of combined BMP-2 and rMSC573 treatment.

Lifelink: 3G-based mobile telemedicine system.

Current wired telemedicine systems encounter difficulties when implemented in archipelagic developing countries because of the high cost of fixed infrastructure. In this research, we devised Lifelink, a mobile real-time telemonitoring and diagnostic facility to command and control remote medical devices through mobile phones. The whole process is phone-based, effectively freeing offsite medical specialists from stationary monitoring consoles and endowing the system with the potential to increase the number participating consultants. The electrocardiogram (ECG) readings are analyzed using a detrended fluctuation technique and classified into pathological cases using an unassisted K-means clustering algorithm. We analyzed 30 batches of 2-hour ECG signals taken from cardiac patients (20 males, 10 females, mean age 46.7 years) with pre-diagnosed pathologies. The method successfully categorized the 30 subjects without user intervention into the following cases: normal (at 86.7% accuracy), congestive heart failure (86.7%), and atrial fibrillation (80.0%). The synergy of mobile monitoring and fluctuation analysis presents a powerful platform to reach remote, underserved communities with poor or nonexistent wired communication structures. It is likely to be essential in the development of new mobile diagnostic and prognostic measures.

Intestinal parasitic infection and associated symptoms in children attending day care centres in Trujillo, Venezuela.

OBJECTIVES: To examine the presence of intestinal protozoan and helminth infections and their association with clinical signs and symptoms in children in Trujillo, Venezuela. METHODS: Conventional microscopic methods (thick-smear, saline and iodine solutions) were used to identify parasites in stool samples of 301 children attending day care centres. A subgroup of 45 children was evaluated clinically and parasitologically five times during a 1-month period using conventional methods and the Kinyoun acid-fast stain for Cryptosporidium identification. RESULTS: The point prevalence of protozoan infections was 21% for Giardia duodenalis, 1.0% for Entamoeba histolytica/dispar, 4% for Entamoeba coli, 16% for Blastocystis hominis, and 89% for Cryptosporidium parvum. Prevalence of helminth infection was 11% for Ascaris lumbricoides, 10% for Trichuris trichiura, 0.3% for Strongyloides stercoralis, and 1.3% for Hymenolepis nana. Over a 1-month time frame, new infections were observed at a rate of 11% for G. duodenalis, 4% for E. histolytica/dispar, 7% for A. lumbricoides, 11% for T. trichiura, 0% for S. stercoralis, and 2% for H. nana. Intestinal symptoms (diarrhoea, vomiting, gas, stomach pain, and loss of appetite) were associated with presence of one or more of C. parvum or B. hominis organisms in stool samples. CONCLUSIONS: Intestinal parasitic infections contribute significantly to the enteric disease burden experienced by this group of children. The organisms most strongly implicated by this study are common and difficult-to-treat protozoan pathogens.

Mesofauna de criaderos naturales de anopheles spp. y las poblaciones depredadoras de sus larvas / Mesofauna of naturals breeding of anopheles spp. and the predator of larval population

Se estudia la flora, mesofauna y depredadores de larvas de 22 humedales criaderos de Anopheles albimanus ubicados en una transecta desde el estado Trujillo (9º34'N y 70º37'0) entre altitudes comprendidas desde los 547 hasta los 19 msnm. Se observó una relación inversa entre el número de larvas de An.albimanus y An.triannulatus en criaderos permanentes soleados, así como una relación directa entre hidrofilas y la presencia de an.albimanus. Se evidenció depredación natural de larvas Anopheles sp por larvas de Odonata mediante la técnica de Elisa. No se observó ninguna relación importante entre las características fisicoquímicas del agua y del suelo de los humedales, con la fauna culicida