Multidisciplinary virtual management of pulmonary nodules.

INTRODUCTION AND OBJECTIVES: Multidisciplinary nodule clinics provide high-quality care and favor adherence to guidelines. Virtual care has shown savings benefits along with patient satisfaction. Our aim is to describe the first year of operation of a multidisciplinary virtual lung nodule clinic, the population evaluated and issued decisions. Secondarily, among discharged patients, we aimed to analyze their follow-up prior to the existence of our consultation, evaluating its adherence to guidelines. MATERIALS AND METHODS: Observational study including all patients evaluated at the Virtual Lung Nodule Clinic (VLNC) (March 2018- March 2019). Clinical and radiological data were recorded. Recommendations, based on 2017 Fleischner Society guidelines, were categorized into follow-up, discharge or referral to lung cancer consultation. Discharged patients were classified according to adherence to guidelines of their previous management, into adequate, prolonged and non-indicated follow-up. RESULTS: A total of 365 patients (58.9% men; median age 64.0 years) were included. Sixty-four percent had smoking history and 23% had chronic obstructive pulmonary disease (COPD). Most nodules were solid (87.4%) and multiple (57.5%). The median diameter was 6.00 mm. 43.8% of patients were discharged following first VLNC evaluation. Among them, 27.5% had received appropriate follow-up, but 66.9% had received poor management. Patients with prolonged follow-up (33.1%) were older (67.0 vs 60.5 years) and had larger nodules (6.00 mm vs 5.00). Non-indicated follow-up patients (33.8%) were more non-smokers (77.8% vs 31.8%) and presented smaller nodules (4.00 vs 5.00 mm). CONCLUSIONS: During its first year of operation, the VLNC has evaluated a population with a relevant risk profile for lung cancer development, management of which should be cautious and adhere to guidelines. After the first VLNC assessment, approximately one-half of this population was discharged. It was noticeable that previous follow-up of discharged patients was found poorly adherent to guidelines, with a marked tendency to overmanagement.

Development of Technologies for Local Composting of Food Waste from Universities.

The amount of biowaste generated by university canteens (BWUC) in the faculties of the University of A Coruña (UDC) varies between 6 and 100 kg/day. In addition, the gardening services of the campus generate even higher amounts of garden waste (GrW), including pruning, which, once crushed, serves as bulking material for composting the biowaste from the canteens. Decentralized composting has been chosen with the aim of producing high quality organic fertilizers for university urban gardens while reducing the environmental burdens of both waste management and agricultural practice. Small static home composters of 340 L (SHC) for smaller amounts of generation (up to 20 kg BWUC/day) were used, while, for faculties of higher generation (up to 40 kg BWUC/day on average), the first composting stage was carried out in a closed and dynamic composter (DC). The dynamic composter was designed and built specifically for this project and its features were improved and optimized throughout the study. The pilot project was carried out in two centers of the UDC, which are known as the Philology Faculty (PF) and the School of Architecture (SA). All the organic waste generated by the canteens of these two colleges from January 2011 to July 2011 (approximately 3000 kg) was treated. Composting in SHC included a thermophilic phase that extended one month beyond the loading period for which thermophilic temperatures were also recorded. The use of the DC as the first stage in combination with static composters (SC) for the maturation stage reduced the overall thermophilic phase to 6-8 weeks. The complete maturation (Rottegrade class IV-V) was achieved after about four months in SHC and after two months when using the combined DC-SC system, if the right conditions of moisture were maintained. The chemical quality of the compost produced was compatible with Class A of Spanish legislation (equivalent to organic farmer quality) and the C/N ratio ranged from 9 to 15 depending on the relation BWUC:GrW.

Nitrogen losses and chemical parameters during co-composting of solid wastes and liquid pig manure.

The aim of this research was to study nitrogen losses during the treatment of the liquid fraction (LF) of pig manure by co-composting and to establish the best conditions for compost production with higher nitrogen and low heavy metal contents. Windrows were constituted with the solid fraction (SF) of pig manure, different organic waste (SF of pig manure, sawdust and grape bagasse) as co-substrate and Populus spp. wood chips as bulking material and watered intensely with the LF. Results show that nitrogen losses ranged from 30% to 66% of initial nitrogen and were mainly governed by substrate to bulking mass ratio and liquid fraction to substrate (LF/S) ratio, and only secondarily by operational parameters. Nitrogen losses decreased from 55-65% at low LF/S ratios (1.7-1.9 m3/t total solids (TS)) to 30-39% at high LF/S ratios (4.4-4.7 m3/t TS). Therefore, integrating the LF in the composting process at high LF/S ratios favoured nitrogen recovery and conservation. Nitrogen in the fine fraction (ranging from 27% to 48% of initial nitrogen) was governed by operational parameters, namely pH and temperature. Final compost showed low content in most heavy metals, but Zn was higher than the limits for compost use in agriculture. Zn content in the obtained compost varied from 1863 to 3269 mg/kg dm, depending on several factors. The options for obtaining better quality composts from the LF of pig manure are selecting co-substrates with low heavy metal content and using them instead of the SF of pig manure.

Nanoscale characterization of the dielectric charging phenomenon in PECVD silicon nitride thin films with various interfacial structures based on Kelvin probe force microscopy.

This work presents a novel characterization methodology for the dielectric charging phenomenon in electrostatically driven MEMS devices using Kelvin probe force microscopy (KPFM). It has been used to study plasma-enhanced chemical vapor deposition (PECVD) silicon nitride thin films in view of application in electrostatic capacitive RF MEMS switches. The proposed technique takes the advantage of the atomic force microscope (AFM) tip to simulate charge injection through asperities, and then the induced surface potential is measured. The impact of bias amplitude, bias polarity, and bias duration employed during charge injection has been explored. The influence of various parameters on the charging/discharging processes has been investigated: dielectric film thickness, SiN(x) material deposition conditions, and under layers. Fourier transform infrared spectroscopy (FT-IR) and x-ray photoelectron spectroscopy (XPS) material characterization techniques have been used to determine the chemical bonds and compositions, respectively, of the SiN(x) films being investigated. The required samples for this technique consist only of thin dielectric films deposited over planar substrates, and no photolithography steps are required. Therefore, the proposed methodology provides a low cost and quite fast solution compared to other available characterization techniques of actual MEMS switches. Finally, the comparison between the KPFM results and the discharge current transients (DCT) measurements shows a quite good agreement.

Nanoscale characterization of different stiction mechanisms in electrostatically driven MEMS devices based on adhesion and friction measurements.

In this work, for the first time different stiction mechanisms in electrostatic micro-electromechanical systems (MEMS) switches were studied. In these devices stiction can be caused by two main mechanisms: dielectric charging and meniscus formation resulting from the adsorbed water film between the switch bridge and the dielectric layer. The effect of each mechanism and their interaction were investigated by measuring the adhesive and friction forces under different electrical stress conditions and relative humidity levels. An atomic force microscope (AFM) was used to perform force-distance and friction measurements on the nanoscale. A novel technique was proposed to measure the induced surface potential over the dielectric surface and was used to explain the obtained adhesive and friction results. The evolution of adhesive force with time was monitored in order to study the charging/discharging processes in the dielectric film. The assessment methodology is employed for application in RF-MEMS switches and could be extended to other electrostatic MEMS devices. The study provides an in-depth understanding of different stiction mechanisms, and explanation for the literature reported device level measurements for electrostatic capacitive MEMS switches.

On the influence of environment gases, relative humidity and gas purification on dielectric charging/discharging processes in electrostatically driven MEMS/NEMS devices.

In this paper, we investigate the impact of environment gases and relative humidity on dielectric charging phenomenon in electrostatically actuated micro- and nano-electromechanical systems (MEMS and NEMS). The research is based on surface potential measurements using Kelvin probe force microscopy (KPFM). Plasma-enhanced chemical vapor deposition (PECVD) silicon nitride films were investigated in view of applications in electrostatic capacitive RF MEMS switches. Charges were injected through the atomic force microscope (AFM) tip, and the induced surface potential was measured using KPFM. Experiments have been performed in air and in nitrogen environments, both under different relative humidity levels ranging from 0.02% to 40%. The impact of oxygen gas and hydrocarbon contaminants has been studied for the first time by using different gas purifiers in both air and nitrogen lines. Voltage pulses with different bias amplitudes have been applied during the charge injection step under all investigated environmental conditions in order to investigate the effect of bias amplitude. The investigation reveals a deeper understanding of charging and discharging processes and could further lead to improved operating environment conditions in order to minimize the dielectric charging. Finally, the nanoscale KPFM results obtained in this study show a good correlation with the device level measurements for capacitive MEMS switches reported in the literature.

Writing simple RF electronic devices on paper with carbon nanotube ink.

This paper shows that we can print on paper simple high-frequency electronic devices such as resistances, capacitances or inductances, with values that can be changed in a controllable manner by an applied dc voltage. This tunability is achieved with the help of an ink containing functionalized carbon nanotubes and water. After the water is evaporated from the paper, the nanotubes remain steadily imprinted on paper, showing a semiconducting behavior and tunable electrical properties.

Mechanism of smooth muscle relaxation by tiropramide.

Experiments on rabbit isolated colon show that a carbachol-induced contraction is accompanied by a decrease in cAMP content of the smooth muscle. (+/-)-alpha-(Benzoylamino)-4-[2-(diethylamino)-ethoxy]-NN-di-propylbenzen-propanamid (tiropramide, CR 605), a new tyrosine derivative with antispastic properties, increases cAMP concentrations within the same dose range that produces smooth muscle relaxation with or without carbachol (0.1 microM). These effects are potentiated by 1 mM theophylline, a phosphodiesterase inhibitor. In a purified microsomal preparation from rabbit colon smooth muscle, corresponding to sarcoplasmic reticulum, tiropramide induced a dose-dependent increase Ca2+ binding in the presence of ATP and Mg2+. Tiropramide inhibited phosphodiesterase activity in rabbit colon homogenates in a range of doses about ten times that producing relaxation, cAMP content enhancement and increase Ca2+ binding to sarcoplasmic reticulum. The effects of tiropramide on the carbachol-stimulated rabbit colon in the presence of theophylline, indomethacin of PGE1 are more in agreement with an action of tiropramide as inhibitor of cAMP catabolism than as a result of a prostaglandin-mediated effect. These observations suggest that the smooth muscle relaxant activity of tiropramide arises from drug-induced increase of cAMP concentrations possibly because of inhibition of cAMP catabolism. This effect is accompanied by the binding to the sarcoplasmic reticulum of Ca2+, preventing its interaction with the contractile proteins of the smooth muscle. A direct effect of tiropramide-enhanced cAMP content on contractile proteins in the smooth muscle cannot be excluded.

[Glucosamine: its importance for the metabolism of articular cartilage. 2. Studies on articular cartilage]. / Glukosamin Seine Bedeutung für den Knorpelstoffwecusel der Gelenke 2. Gelenkknorpel-Untersuchungen.

In healthy individuals there exists a balance between cartilage proteoglycan synthesis and degradation. In arthrotic cartilage this metabolic balance is deteriorated in spite of a sometimes enhanced proteoglycan synthesis, since the catabolic rate exceeds the anabolic rate corresponding to the severity of the disease. The extracellular organic matrix of the cartilage is destroyed. With different experimental models it could be demonstrated, that the non steroidal anti-inflammatory drugs commonly used in the treatment of arthrosis inhibit the synthesis of mucopolysaccharides, intensify the already existing metabolic disorder, prevent a normalization of cartilage composition and thus impair the function of the cartilage. Glucosamine on the other hand increases in a dose-dependent way the ability of cartilage to synthesize both sulfated mucopolysaccharides and protein, thus restoring the catabolic-anabolic balance of the cartilage.

[Glucosamine: its value for the metabolism of articular cartilage. 1. Biochemistry of proteoglycans, studies on in-vitro cultures of embryonal mouse fibroblasts and bone germs]. / Glukosamin: Seine Bedeutung für den Knorpelstoffwechsel der Gelenke. 1. Biochemie der Proteoglykane, Untersuchungen an in vitro-Kulturen embryonaler Mäuse-Fibroblasten und Knochenanlagen.

Mucopolysaccharides (glycosaminoglycanes) are essential constituents of the cartilage (chondroitin sulfate) and the synovial fluid (hyaluronic acid). They are formed within the chondrocyte preferably from glucosamine or from glucose and bound to protein constituting proteoglycanes. Non steroidal anti-inflammatory drugs and corticosteroids inhibit this synthesis. Primary fibroblast cultures and in vitro cultured mouse embryo tibiae show a dose-dependent increased synthesis of mucopolysaccharides and an enhanced growth of the bones after addition of glucosamine to the culture medium. This finding underlines the importance of a sufficient supply of the joints with glucosamine.

Effects of antigastrin drugs on the interaction of 125I-human gastrin with rat gastric mucosa membranes.

A method for studying the interaction of 125I-human gastrin with a rat gastric mucosal membrane fraction is described, and the saturability, high affinity and reversibility of the preparations, as well as the correlation of pharmacological responses to antigastrin-drugs with the observed binding are discussed. Proglumide and other antigastrin drugs inhibit gastrin binding in a dose-dependent way, and their activities in such a system are well correlated with the "in vivo" antisecretory activities of these drugs.

Studies on the mechanism of action of protacine (CR 604), a new non-steroidal anti-inflammatory agent.

3'-(4-[2-(1-P-Chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropyl-glutaramate(+/-)dimaleate (protacine, CR 604), a new non-steroidal compound active on experimental inflammation, in vitro inhibits prostaglandin synthesis from arachidonic acid and platelet aggregation. When administered p.o., it prevents ex vivo platelet aggregation and in vivo arachidonate-induced thrombosis in rabbits. The cAMP levels of rat leucocytes are significantly reduced after treatment in vivo with protacine, even under maximum PGE-mediated stimulation. These effects, the inhibition of the proteolytic activity of trypsin and the fibrinolytic properties evidenced on recalcified plasma clots, contribute to explain the anti-inflammatory activity of protacine.

Pharmacological study of a new non-steroidal anti-inflammatory drug: protacine (CR 604).

The pharmacological activities of 3'-(4-[2-(1-p-chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropylglutaramate(+/-)dimaleate (protacine, CR 604), a new indolyl derivative with strong anti-inflammatory, analgesic and antipyretic activities, are described. The dose-dependent activity of protacine on inflammation has been shown both in short-term experiments, like the hind paw edema induced by carrageenin and several other irritants, and long-term tests, like the aminoacetonitrile-induced osteolathyrism, the adjuvant-induced arthritis and the cotton pellet-induced granuloma. The analgesic activity of the drug has been evidenced in the phenylquinone-induced writhing and the Randall-Selitto tests, and the antipyretic effects in the yeast-induced hyperthermia in rats. Other general pharmacological effects have been studied, too. Contrarily to several other anti-inflammatory drugs, including indometacin, showing advers effects at doses which are in the same range of those active on experimental inflammation, protacine shows these effects to a minor degree and at doses which are much larger than those pharmacologically active. The therapeutic index of protacine therefore is superior to that of other anti-inflammatory drugs.

Studies on the safety of a new non-steroidal anti-inflammatory drug: protacine (CR 604).

The effects of 3'-(4-[2-(1-p-chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazinyl-1-yl)propyl-4-benzamido-N,N-dipropyl-glutaramate(+/-)dimaleate(protacine, CR 604) on gastrointestinal physiology and tolerance were investigated. The anti-inflammatory activities and the effects on the gastrointestinal tract showed a very good separation. Protacine showed a smaller influence on gastric prostaglandins and did not stimulate both basal and cAMP enhanced gastric acid output as did other antiinflammatory drugs. This may explain, at least in part, its gastrointestinal safety. Articular cartilage metabolism showed to remain practically unchanged by protacine both in in vitro and ex vivo experiments. All these results show that protacine has very good gastrointestinal safety indexes, that effects on articular cartilage metabolism are very low and that, from these points of view, it is superior to other non-steroidal anti-inflammatory drugs of similar potency.

The mechanism of action of nitro-heterocyclic antimicrobial drugs. Metabolic activation by micro-organisms.

Although the target of the antimicrobial drug 1-methyl-2-nitro-5-vinylimidazole (MEV) has been shown to be DNA (Goldstein et al., 1977) the drug was ineffective in cell-free systems because it was not activated. Both the rate of metabolic activation of MEV and its antibacterial activity were increased when bacteria were grown in limiting oxygen. Mutants of Escherichia coli which were conditionally resistant to nitroimidazoles and nitrofurans were defective in drug activation. The activities of these drugs against E. coli correlated with their rates of metabolism. The antimicrobial spectrum of the drugs appeared to be related to their reducibility by different species.