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Background: The determination of kinetic parameters and the development of mathematical models are of great interest to predict the growth of microalgae, the consumption of substrate and the design of photobioreactors focused on CO2 capture. However, most of the models in the literature have been developed for CO2 concentrations below 10%. Results: A nonaxenic microalgal consortium was isolated from landfill leachate in order to study its kinetic behavior using a dynamic model. The model considered the CO2 mass transfer from the gas phase to the liquid phase and the effect of light intensity, assimilated nitrogen concentration, ammonium concentration and nitrate concentration. The proposed mathematical model was adjusted with 13 kinetic parameters and validated with a good fit obtained between experimental and simulated data. Conclusions: Good results were obtained, demonstrating the robustness of the proposed model. The assumption in the model of DIC inhibition in the ammonium and nitrate uptakes was correct, so this aspect should be considered when evaluating the kinetics with microalgae with high inlet CO2 concentrations. Keywords: Dynamic model, Nonaxenic consortium, Photon flux density, Mass transfer, Leachate, Landfill, Ammonium, Nitrate, Carbon dioxide

Background: Refractory chronic cough (RCC) and unexplained chronic cough (UCC) adversely affect patients' quality of life (QoL). This multicenter, non-interventional study evaluates the relationship between cough severity and QoL and other patient-reported outcomes (PROs) in Spanish outpatients., Methods: RCC/UCC patients self-administered a printed survey comprising the cough-severity visual analog scale (VAS), adapted Cough Severity Diary (CSD), and Leicester Cough Questionnaire (LCQ), plus purpose-designed items regarding the physical and everyday-life impact of cough. Patients were stratified into VAS score tertiles. The impact of cough on QoL and other PROs in each tertile, and relationships between LCQ scores and the tertiles, were assessed., Results: The VAS was completed by 189 patients, and VAS score tertiles were identified as 0-50, 60-70, and 80-100 mm. The only between-tertile difference in demographic or cough characteristics was cough duration. VAS score tertiles were linearly associated with mean LCQ domain and total scores, as well as the proportion of patients with the highest scores on all adapted CSD items, and almost all physical and everyday-life impact items. In multiple linear-regression models, an increase of one tertile in the VAS score was associated with a decrease of 2.23 points in the LCQ total score, indicating poorer cough-related QoL., Conclusion: As self-assessed in patients with RCC/UCC, cough-severity VAS scores were strongly associated with the impact of cough on QoL and everyday life. Patients with VAS scores of 60-100 mm reported the greatest impact and thus may benefit the most from targeted cough therapies., Competing Interests: Declaration of competing interest Christian Domingo has received consultant and speaker's honoraria from MSD, Novartis, Boehringer, Sanofi, TEVA, AstraZeneca, ALK, Allergy Therapeutics. Santiago Quirce has received speaking, lecture and consulting fees from Allergy Therapeutics, AstraZeneca, GSK, Mundipharma, Novartis, Sanofi, and Teva. Ignacio Dávila has received consulting fees from Allergy Therapeutics, AstraZeneca, GSK, MSD, Novartis, and Sanofi. Lectures for Allergy Therapeutics, AstraZeneca, Chiesi, Diater, GSK, LETI, Novartis, and Sanofi. Grants to his institution from ISCIII (public entity), Junta de Castilla de León (public entity), and ThermoFisher. Astrid Crespo-Lessman has received consultant's honoraria from AstraZeneca, Sanofi, GlaxoSmithKline, and her institution has received grants from AstraZeneca and GlaxoSmithKline. Luis Puente-Maestu declares no conflict of interest. Ebymar Arismendi declares no conflict of interest. Alfredo De Diego declares no conflict of interest. Francisco Javier González-Barcala has received consulting fees and speaker's honoraria from ALK, AstraZeneca, Bial, Chiesi, GebroPharma, GlaxoSmithKline, Menarini, Novartis, Rovi, Roxall, Sanofi, Stallergenes-Greer and Teva. Luis Pérez De Llano has received consulting fees and speaker's honoraria from AstraZeneca, Chiesi, GlaxoSmithKline, FAES, MSD, Sanofi, Techdow Pharma and Teva, and his institution has received grants from AstraZeneca, FAES and Sanofi. Luis Cea-Calvo, Marta Sánchez-Jareño, and Pilar López-Cotarelo are full-time employees of MSD Spain. Assessed using an 11-point Likert scale, where higher numbers indicate greater severity/impact. Results pertain to the day before the study visit. Not all patients responded to all items. The total number of respondents is specified for each item. Percentages in each cough-severity VAS tertile are calculated based on the number of respondents in that tertile., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Introduction: Patient adherence to maintenance medication is critical for improving clinical outcomes in asthma and is a recommended guiding factor for treatment strategy. Previously, the APPaRENT studies assessed patient and physician perspectives on asthma care; here, a post-hoc analysis aimed to identify patient factors associated with good adherence and treatment prescription patterns., Methods: APPaRENT 1 and 2 were cross-sectional online surveys of 2866 adults with asthma and 1883 physicians across Argentina, Australia, Brazil, Canada, China, France, Italy, Mexico, and the Philippines in 2020-2021. Combined data assessed adherence to maintenance medication, treatment goals, use of asthma action plans, and physician treatment patterns and preferences. Multivariable logistic regression models assessed associations between patient characteristics and both treatment prescription (by physicians) and patient treatment adherence., Results: Patient and physician assessments of treatment goals and adherence differed, as did reporting of short-acting β 2 -agonist (SABA) prescriptions alongside maintenance and reliever therapy (MART). Older age and greater patient-reported severity and reliever use were associated with better adherence. Patient-reported prescription of SABA with MART was associated with household smoking, severe or poorly controlled asthma, and living in China or the Philippines., Conclusions: Results revealed an important disconnect between patient and physician treatment goals and treatment adherence, suggesting that strategies for improving patient adherence to maintenance medication are needed, focusing on younger patients with milder disease. High reliever use despite good adherence may indicate poor disease control. Personalised care considering patient characteristics alongside physician training in motivational communication and shared decision-making could improve patient management and outcomes., Competing Interests: Declaration of competing interest Giorgio Walter Canonica reports having received research grants as well as being a lecturer or having received advisory board fees from A. Menarini, Alk-Abello, Allergy Therapeutics, AstraZeneca, Chiesi Farmaceutici, Firma, Genentech, Guidotti-Malesci, GSK, Hal Allergy, Mylan, Novartis, Regeneron, Roche, Sanofi-Aventis, Sanofi-Genzyme, Stallergenes Greer, Valeas, and OM Pharma, outside the submitted work. Christian Domingo has received funding for travel or speaker fees from ALK, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis, Stallergenes, Takeda, and Pfizer, and declares no specific conflicts of interest to report regarding this paper. Kim L. Lavoie reports investigator-initiated research support and speaking fees from AbbVie, consulting fees and speaking fees from Astellas, Boehringer Ingelheim, GSK, X-Factor, Respiplus, and Novartis, consulting fees from Janssen, Sojecci Inc., and AstraZeneca, and speaking fees from Bayer and Mundipharma, outside the submitted work. Amrit Kaliasethi is an employee of Fishawack Communications Ltd, part of Avalere Health. Shireen Quli Khan, Anurita Majumdar, and Sourabh Fulmali are full-time employees of GSK and hold shares in GSK., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Clinical trials have shown treatment benefits of dupilumab in patients with uncontrolled asthma for up to 1 year. This study aimed to evaluate the long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma, as data for extended treatment with dupilumab beyond 1 year are not available., Methods: TRAVERSE was an open-label extension study in 362 hospitals and clinical centres across 27 countries that assessed the safety and efficacy of dupilumab 300 mg every 2 weeks up to 96 weeks in adults and adolescents (aged 12-84 years) with moderate-to-severe or oral-corticosteroid-dependent severe asthma who had completed a previous dupilumab asthma study (phase 2A EXPEDITION, phase 2B DRI [P2b], phase 3 QUEST, or VENTURE). The primary endpoint was the number and percentage of patients with any treatment-emergent adverse events. Secondary endpoints included annualised exacerbation rate (AER) over the treatment period and change from parent study baseline in pre-bronchodilator FEV 1 , the five-item asthma control questionnaire (ACQ-5), the asthma quality of life questionnaire (AQLQ), type 2 biomarkers (blood eosinophils and serum total IgE), and anti-drug antibodies (ADAs). Statistical analyses were descriptive. We report safety in all enrolled patients, and efficacy in patients with non-oral-corticosteroid-dependent asthma and in subgroups, including patients with a type 2 inflammatory phenotype who received 148 weeks of treatment. This study is registered with ClinicalTrials.gov, NCT02134028., Findings: Between Aug 5, 2014, and Oct 11, 2019, of 2302 patients assessed for eligibility, 2282 adults and adolescents were enrolled (median age 50 years, 62·1% female and 37·9% male). Safety during TRAVERSE was consistent with the known dupilumab safety profile. The proportion of patients reporting treatment-emergent adverse events throughout the study duration was similar to that observed in the parent studies and ranged from 76·3% to 94·7%. The most frequently reported treatment-emergent adverse events were nasopharyngitis (17·5-25·9%), injection-site erythema (2·2-23·4%), and bronchitis (9·3-19·0%). Serious asthma exacerbations (0·5-3·6%) and pneumonia (0·7-2·7%) were the most frequently reported serious adverse events. There were four treatment-emergent adverse events leading to death. Efficacy during TRAVERSE was also consistent with the results of parent studies. In patients who were non-oral-corticosteroid-dependent, AER remained low (0·277-0·327) across parent study and treatment groups, pre-bronchodilator FEV 1 improvements were sustained to the end of treatment at week 96 (mean changes from parent study baseline ranged from 0·22 L [SD 0·44] to 0·33 L [0·44] across parent study and treatment groups), and improvements in ACQ-5 and AQLQ scores were sustained to the last timepoint assessed at week 48. Rapid improvements were observed in pre-bronchodilator FEV 1 and sustained improvements were seen in all outcome measures for patients given dupilumab who previously received placebo in parent studies; further improvements in AER, asthma control, and health-related quality of life were observed in patients who continued receiving dupilumab. Blood eosinophils and serum total IgE decreased progressively. ADA status had no effect on safety or efficacy. In the subgroup of patients with a type 2 inflammatory phenotype followed-up for 148 weeks, AER decreased progressively, and initial lung function improvements were sustained over 148 weeks., Interpretation: Data show that safety and efficacy of dupilumab in adult and adolescent patients with moderate-to-severe asthma are sustained when treatment is extended up to 148 weeks. These findings therefore support the long-term use of dupilumab in this patient population., Funding: Sanofi and Regeneron Pharmaceuticals., Competing Interests: Declaration of interests MEW reports personal fees from AstraZeneca, Boehringer Ingelheim, Equillium, Gala Therapeutics, Genentech, Genzyme, Mylan, Novartis, Pulmatrix, ResTORbio, Regeneron Pharmaceuticals, Sentien Biotechnologies, and Teva; and grants and personal fees from GSK and Sanofi. LBF reports grant support through the Asthma & Allergy Center, Bellevue, NE, USA, from 3M, Aimmune, AstraZeneca, DBV Technologies, Genentech, Glenmark, GSK, Hoffmann-La Roche, Novartis, Pearl, Sanofi, and Teva; and has served as a national consultant for Sanofi. JFM has served as a consultant for AstraZeneca and Sanofi; received speaker fees from Boehringer Ingelheim, GSK, Menarini, Novartis, and Uriach; and received research grants from Novartis. IDP reports speaker fees from Aerocrine AB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Regeneron Pharmaceuticals, Sanofi, and Teva; payments for organisation of educational events from AstraZeneca, GSK, Regeneron Pharmaceuticals, Sanofi, and Teva; consultant fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, RespiVert, Sanofi, Schering-Plough, and Teva; international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Napp Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi, and Teva; and a research grant from Chiesi. AP reports grants, personal fees, and non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, and Teva; personal fees and non-financial support from Menarini, Novartis, and Zambon; and grants from Sanofi. AB reports non-financial support during the conduct of the study from GSK; serving as an investigator on clinical trials promoted by Acceleron Pharma, Actelion, Galapagos, MSD, Nuvaira, Pulmonx, United Therapeutic, and Vertex Pharmaceuticals; grants and personal fees from Boehringer Ingelheim; and personal fees from AstraZeneca, Chiesi, GSK, Regeneron Pharmaceuticals, and Sanofi. HW reports serving as a consultant and receiving travel and speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Novartis, Sanofi, and Takeda. MC reports research support from the American Lung Association, AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, Patient-Centered Outcomes Research Institute, and Sanofi; serving as a consultant for 4D Pharma, Aviragen Therapeutics, Boston Scientific, Genentech, Nuvaira, Sanofi, Teva, Therabron Therapeutics, Theravance Biopharma, Vectura, and Vida Pharma; speaker fees from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Genentech, Regeneron Pharmaceuticals, Sanofi, and Teva; and royalties from Elsevier. NMN reports speaker fees from ALK, AstraZeneca, Boehringer Ingelheim, Glenmark, MSD, Novartis, Sanofi, Stallergenes Greer, and Teva. YT has served as a consultant for AstraZeneca, Kyorin Pharmaceuticals, and Sanofi. DL has received research funding from Sanofi. CD reports travel and speaker fees from Allergy Therapeutics, ALK, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GSK, HAL Allergy, Inmunotek, Menarini, Novartis, Pfizer, Sanofi-Aventis, Stallergenes Greer, Takeda, and Teva. KRC reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Genentech, Grifols, Kamada, Mereo BioPharma, Novartis, Roche, and Sanofi; grants from Amgen, Baxter, and GSK; and personal fees from the GSK-Canadian Institutes of Health Research chair in Respiratory Health Care Delivery at the University Health Network, and Merck. XM, AHK, PJR, UK, LPM, EL, and MH are Sanofi employees and hold stock or stock options in the company. YZ, YD, FAK, MR, and NA are employees and shareholders at Regeneron Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: We lack the rationale on which to base the development of a yellow fever (YF) vaccination schedule for people living with human immunodeficiency virus (PLWHIV)., Objectives: To report on the current evidence regarding the seroconversion rate and the duration of humoral protection after YF vaccine, as well as the impact of revaccination in PLWHIV., Data Sources: MEDLINE, Google Scholar, LILACS and Cochrane CENTRAL were searched., Methods: We selected studies on PLWHIV of all ages (including perinatally HIV-infected patients) and all settings (YF endemic and non-endemic zones). Intervention investigated was vaccination against YF, at least once after the HIV diagnosis. The research questions were the seroconversion rate, duration of humoral immunity after YF vaccine and impact of revaccination in PLWHIV. Selected studies were assessed for quality using the Newcastle-Ottawa scale., Results: Ten, six and six studies were selected for the systematic review of each question, respectively. Only one study addressed the first question in perinatally HIV-infected children. The quality of the studies was assessed as Poor (n = 16), Fair (n = 2) or Good (n = 4). A meta-analysis demonstrated that 97.6% (95% CI 91.6%-100%) of the included population seroconverted. Between 1 and 10 years after YF vaccine, reported persistence of neutralizing antibodies was 72% (95% CI 53.6%-91%), and it was 62% (95% CI 45.4%-78.6%) more than 10 years after YF vaccine. No conclusions could be drawn on impact of revaccination because of the small number of patients., Conclusions: The current evidence regarding seroconversion rate, duration of humoral protection after YF vaccine and impact of revaccination in PLWHIV is limited by the low number and quality of studies. Based on the presently available data, it is difficult to rationally develop yellow fever vaccination guidelines for PLWHIV., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

For bone tissue engineering applications, scaffolds that mimic the porous structure of the extracellular matrix are highly desirable. Herein, we employ a PCL/HA-based scaffold with a double-scaled architecture of small pores coupled to larger ones. To improve the osteoinductivity of the scaffold, we incorporate two different growth factors via polydopamine (PDA) coating. As a first step, we identify the maximum amount of PDA that can be deposited onto the scaffold. Next, to allow for the deposition of a second PDA layer which, in turn, will allow to increase the loading of growth factors, we incorporate a dithiol connecting layer. The thiol groups covalently react with the first PDA coating through Michael addition while also allowing for the incorporation of a second PDA layer. We load the first and second PDA layers with bone morphogenic protein-2 (BMP2) and vascular endothelial growth factor (VEGF), respectively, and evaluate the osteogenic potential of the functionalised scaffold by cell viability, alkaline phosphatase activity and the expression of three different osteogenesis-related genes of pre-seeded human mesenchymal stem cells. Through these studies, we demonstrate that the osteogenic activity of the scaffolds loaded with both BMP2 and VEGF is greater than scaffolds loaded only with BMP2. Importantly, the osteoinductivity is higher when the scaffolds are loaded with BMP2 and VEGF in two different PDA layers. Taken together, these results indicate that the as-prepared scaffolds could be a useful construct for bone-tissue applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study describes a new preparation method, which combines freeze drying and supercritical CO 2 foaming approaches, for the preparation of drug delivery scaffolds of polycaprolactone loaded with 5-fluorouracil, an anti-cancer drug, with low solubility in scCO 2 . It is a principal objective of this work to design a scCO 2 strategy to reduce 5-Fu solubility limitations in its homogeneous distribution into a PCL scaffold through the design of an innovative processing method. The design of this process is considered valuable for the development of clean technology in pharmacy and medicine, since most of the active agents have a null solubility in scCO 2 ·Supercritical CO 2 is used as a blowing agent to induce polymer foaming by means of the low temperature pressure quench process. The resulting samples have been prepared under different operational conditions focused on enhancing the performance of the release process. In this case, design of experiments (DOE) was considered for a more comprehensive and systematic optimization of the product. In particular, drug amount, equals to 4.8 or 9.1wt%, process temperature, of 45 or 50°C and depressurization rate, equals to 0.1MPas -1 or 2MPas -1 were selected as the factors to be investigated by a three-factor at two-level full factorial design. Samples were characterized to establish porosity data, drug loading percentage and, especially, release profile chromatographically monitored. Results from DOE have concluded which are the best samples providing a sustained drug release for several days, which may be of great interest to develop materials for tissue engineering and sustained release applications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Specific features of a silica-gelatin aerogel (3 wt.% gelatin content) in relation to drug delivery has been studied. It was confirmed that the release of both ibuprofen (IBU) and ketoprofen (KET) is about tenfold faster from loaded silica-gelatin aerogel than from pure silica aerogel, although the two matrices are structurally very similar. The main goal of the study was to understand the mechanistic background of the striking difference between the delivery properties of these closely related porous materials. Hydrated and dispersed silica-gelatin aerogel has been characterized by NMR cryoporometry, diffusiometry and relaxometry. The pore structure of the silica aerogel remains intact when it disintegrates in water. In contrast, dispersed silica-gelatin aerogel develops a strong hydration sphere, which reshapes the pore walls and deforms the pore structure. The drug release kinetics was studied on a few minutes time scale with 1s time resolution. Simultaneous evaluation of all relevant kinetic and structural information confirmed that strong hydration of the silica-gelatin skeleton facilitates the rapid desorption and dissolution of the drugs from the loaded aerogel. Such a driving force is not operative in pure silica aerogels., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this study, the design and fabrication of porous scaffolds, made of blends of polylactic-co-caprolactone (PLC) and polylactic acid (PLA) polymers, for tissue engineering applications is reported. The scaffolds are prepared by means of a bio-safe thermally induced phase separation (TIPS) approach with or without the addition of NaCl particles used as particulate porogen. The scaffolds are characterized to assess their crystalline structure, morphology and mechanical properties, and the texture of the pores and the pore size distribution. Moreover, in vitro human mesenchymal stem cells (hMSCs) culture tests have been carried out to demonstrate the biocompatibility of the scaffolds. The results of this study demonstrate that all of the scaffold materials processed by means of TIPS process are semi-crystalline. Furthermore, the blend composition affected polymer crystallization and, in turn, the nano and macro-structural properties of the scaffolds. Indeed, neat PLC and neat PLA crystallize into globular and randomly arranged sub micro-size scale fibrous conformations, respectively. Concomitantly, the addition of NaCl particles during the fabrication route allows for the creation of an interconnected network of large pores inside the primary structure while resulted in a significant decrease of scaffolds mechanical response. Finally, the results of cell culture tests demonstrate that both the micro and macro-structure of the scaffold affect the in vitro hMSCs adhesion and proliferation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Open-pore biodegradable microparticles are object of considerable interest for biomedical applications, particularly as cell and drug delivery carriers in tissue engineering and health care treatments. Furthermore, the engineering of microparticles with well definite size distribution and pore architecture by bio-safe fabrication routes is crucial to avoid the use of toxic compounds potentially harmful to cells and biological tissues. To achieve this important issue, in the present study a straightforward and bio-safe approach for fabricating porous biodegradable microparticles with controlled morphological and structural features down to the nanometer scale is developed. In particular, ethyl lactate is used as a non-toxic solvent for polycaprolactone particles fabrication via a thermal induced phase separation technique. The used approach allows achieving open-pore particles with mean particle size in the 150-250 μm range and a 3.5-7.9 m(2)/g specific surface area. Finally, the combination of thermal induced phase separation and porogen leaching techniques is employed for the first time to obtain multi-scaled porous microparticles with large external and internal pore sizes and potential improved characteristics for cell culture and tissue engineering. Samples were characterized to assess their thermal properties, morphology and crystalline structure features and textural properties., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In this study, the reaction of widely used artist's pigments in raw form to pulsed laser radiation of different wavelengths and pulse duration was investigated. Vermilion, lead chromate and malachite (in the form of pellets) were irradiated using laser pulses of 500 fs at 248 nm, and pulses of 150 ps and 15 ns at 1064 and 213 nm. Optical microscopy, colorimetry, spectrofluorimetry, micro-Raman spectroscopy and X-ray photoelectron spectroscopy were employed to characterize the physicochemical changes induced to the pigments. Change of crystalline phase was identified for vermilion while reduction processes take place for lead chromate and malachite. It was found that these effects were minimized by application of ultraviolet ultrashort pulses (of femtosecond and picosecond duration) as compared with changes occurring by pulsed infrared irradiation (of both picosecond and nanosecond duration). The results presented are discussed in relation to previous research on painted mock-ups in order to elucidate the role and significance of the binding media in the laser induced discoloration of painted surfaces and thus to propose optimum laser cleaning practices., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The analytical characterization of drug delivery systems prepared by means of green manufacturing technologies using CO(2) as a processing fluid is here reviewed. The assessment of the performance of nanopharmaceuticals designed for controlled drug release may result in a complex analytical issue and multidisciplinary studies focused on the evaluation of physicochemical, morphological and textural properties of the products may be required. The determination of the drug content as well as the detection of impurities and solvent residues are often carried out by chromatography. Assays on solid state samples relying on X-ray, vibrational and nuclear magnetic resonance spectroscopies are of great interests to study the composition and structure of pharmaceutical forms. The morphology and size of particles are commonly checked by microscopy and complementary chemical information can be extracted in combination with spectroscopic accessories. Regarding the thermal behavior, calorimetric and thermogravimetric techniques are applied to assess the thermal transitions and stability of the samples. The evaluation of drug release profiles from the nanopharmaceuticals can be based on various experimental set-ups depending on the administration route to be considered. Kinetic curves showing the evolution of the drug concentration as a function of time in various physiological conditions (e.g., gastric, plasmatic or topical) are recorded commonly by UV-vis spectroscopy and/or chromatography. Representative examples are commented in detail to illustrate the characterization strategies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Dengue fever (DF) remains one of the most important emerging infectious diseases. Whereas DF is well recognized in endemic countries, there are indications that the disease is underdiagnosed among travellers to endemic regions. Here, we present the first descriptive survey on cases of travel-acquired DF imported to Denmark diagnosed at the national reference laboratory for dengue virus diagnostics during a 9-year period. In our study, 16 - 46 travel-acquired dengue virus infections were diagnosed per year. DF is mainly imported by adults, mostly men, returning from Southeast Asian countries. The minimum incidence of dengue virus infection among Danish travellers is estimated to be 4.9 per 100,000 travellers. Our results confirm and expand studies from other European countries, and underline the importance of surveillance based on relevant diagnostic analyses., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

This paper describes the evaluation of a new pharmaceutical formulation based on ketoprofen entrapment in a solid lipid particle (SLP) matrix. The drug-SLP samples, which were elaborated using a processing technology based on supercritical CO(2) , consisted of a model of a controlled-release system for topical applications. Some of the samples contained silanized TiO(2) as an additional ingredient to increase the interaction between drug and lipid matrix. The study of the sample features relied on reversed-phase high-performance liquid chromatography with a C(18) column and ultraviolet spectroscopic detection at 266 nm. Characterization assays comprised the determination of the overall amount of ketoprofen in the samples, the assessment of the release-permeation kinetic profiles, and the evaluation of impurities and decomposition products. The release and permeation of encapsulated ketoprofen were assayed at 32°C and pH 6.8 by using a static diffusion cell. Results showed a sustained drug delivery for at least 24 h. Besides, no degradation species were detected throughout the release-permeation processes, which indicated that the stability of the drug in the SLP system was preserved., (Copyright © 2011 Wiley-Liss, Inc.)

Several techniques have been proposed for producing porous structures or scaffolds for tissue engineering but, as yet, with no optimal solution. With regard to this topic, this paper focuses on the preparation of biocompatible nanometric filler-polymer composites organized in a network of fibers. Titanium dioxide (TiO2) or hydroxyapatite (HAP) nanopowders as the guest particles and poly(lactic acid) (L-PLA) or the blend poly(methylmethacrylate)/poly(epsilon-caprolactone) (PMMA/PCL) as the polymer carrier were selected as model systems for this purpose. A supercritical antisolvent technique was used to produce the composites. In the process developed, the non-soluble particulate filler was suspended in a polymer solution, and both components were sprayed simultaneously into supercritical carbon dioxide (scCO2). Using this technique, polymeric matrices were loaded with approximately 10-20 wt.% of inorganic phase distributed throughout the composite. Two different hybrid materials were prepared: a PMMA/PCL+TiO2 system where either fibers or microparticles were prepared by varying the molecular weight of the used PMMA; and fibers in the case of L-PLA+HAP system. After further post-processing in a three-dimensional network, these nanofibers can potentially be used as scaffolds for tissue engineering.

Samples resulting from reaction of TiO(2) with octyltriethoxysilane, developed using a supercritical carbon dioxide procedure, have been studied by infrared and Raman spectroscopies and thermogravimetric analysis. Different reaction conditions have been applied to the preparation of samples in order to study the influence of experimental factors on the sample properties. Vibrational techniques have first been used to verify the presence of silanized structures on the surface of TiO(2) through the detection of specific bands characteristic of the Si-O-Si cross-linking. Thermogravimetric profiles consisting of weight loss values as a function of temperature have been analyzed by principal component analysis to extract information about the characteristics of the linkage between silane and TiO(2) as well as the thermal stability of the prepared materials. The mathematical treatment of data has provided conclusions on the properties of the samples and analogies and differences with respect to the commercial material.

For understanding the phenomena associated with the discoloration observed in some cases of infrared laser cleaned stonework surfaces, a comparative study of three different types and morphologies of pollution encrustation and stone substrates was undertaken. Fragments originating from monuments with historic and/or artistic value, bearing homogeneous thin soiling on Pentelic marble (Athens, Greece), thick encrustation on Hontoria limestone (Burgos, Spain) and compact thin crust on gypsum decorations (Athens, Greece), have been studied on the basis of their composition and origin, together with the conditions that may induce yellowing effects upon their laser cleaning with IR wavelengths. While irradiation in the UV (i.e. at 355 nm) could not effectively remove the encrustations studied, irradiation at 1,064 nm was found efficient to remove all the studied pollution accumulations. Discoloration towards yellow was evident in all cases and at different levels, including the samples with intentional patination layer. To the limit of Raman detection no chemical alterations were detected on the irradiated areas while the presence of yellow polar compounds in all the pollution crusts studied supports the argument that the discoloration of the stone surfaces upon their IR irradiation may be due to the uncovering of existing yellow layers as result of the migration of these compounds inwards to the original stone surface. To correct and/or prevent such undesired coloration the use of IR and UV radiation both in sequential and synchronous mode was considered, with positive results.

Objective: To compare the effectiveness and efficiency of an initiation protocol for non-invasive home mechanical ventilation (NIHMV) carried out at a pulmonary outpatient clinic with the standard in-hospital model., Methods: Prospective, observational study., Population: 16 patients divided into two groups: (A) outpatient protocol (n=9); and (B) standard in-hospital initiation with an elective admission (n=7)., Instrumentation: at baseline condition and treatment starting, arterial blood gases and nocturnal pulse-oximetry were performed. At the end of follow-up, arterial blood gases and patient compliance (ventilator's built-in counter) was determined. Efficiency was evaluated by calculating cost savings per ventilated patient for the financier and accumulated days of hospitalization saved., Results: No differences in baseline conditions were observed. Ventilation was effective in the two groups: a significant decrease in PaCO(2) and an increase in mean nocturnal oxygen saturation were observed after initiating ventilation. (Group A: PaCO(2):42.9+/-1.5; SpO(2):91.9+/-1.9; Group B:PaCO(2):44.3+/-6; SpO(2):91.9+/-2.7). At three months the effectiveness of ventilation and the number of hours of ventilation was equivalent in all groups. The new model cut costs for the health care financier by 50%. The outpatient sessions saved 63 days of hospitalization., Conclusions: (1) Outpatient initiation is an effective and efficient alternative to the traditional in-hospital method for NIHMV. (2) The outpatient protocol represents a substantial saving for the financier.

Background: Though several drugs have been tested, the choice of the ideal steroid-sparing agent in steroid-dependent asthmatic patients remains unclear. Our objective was to evaluate the efficacy and tolerance of methotrexate in low weekly doses in order to decrease chronic oral steroid requirements in asthmatic patients., Design: double blind randomized placebo-controlled study., Setting: The study was performed in a 760-bed teaching hospital., Patients: 46 steroid-dependent asthmatic patients were randomized., Interventions: PATIENTS received 10mg of methotrexate or placebo once weekly for a year. The 6-methylprednisolone was progressively tapered (2mg/day every two weeks) until FEV1 diminished by 5% or more; 6-methylprednisolone was then increased until the previous FEV1 was reached, and the procedure was repeated throughout follow-up., Measurements: Blood and urine analyses and bone densitometry were performed at entry and at the end of the study. Pulmonary function was tested monthly during the first three months and then every three months until the end., Results: Thirty-nine patients were evaluated at interim analysis. A 54.8% decrease (9.5+/-4.9 mg/day) in 6-methylprednisolone dose was observed in the methotrexate group and a 4.4% decrease (0.5+/-7.2 mg/day) in the placebo group (P<0.001). There was no significant decrease of FEV1 in either group. No changes in bone metabolism were observed except for a non-statistically significant increase in osteocalcin levels in the treated group compared to a decrease in the placebo group. Toxicity was mild., Conclusions: (1) Methotrexate is an effective steroid-sparing agent. (2) A dosage lower than the one recommended in the literature is effective. (3) Tolerance is good. (4) No benefit or detrimental effects in bone metabolism were observed after one year.

Background: Almitrine bismesylate (AB) is a peripheral chemoreceptor agonist which is believed to improve oxygenation of COPD patients with chronic hypoxaemia, probably by improving the ventilation perfusion mismatch. We studied the long-term effects of AB in COPD patients with chronic hypoxaemia., Design: Prospective, randomised, double-blind, placebo-controlled trial., Setting: Eight hundred bed teaching hospital with a catchment population of 350,000 inhabitants. PATIENT RECRUITMENT: COPD outpatients consulting between September 95 and September 99., Inclusion Criteria: (1) COPD (FEV1 < 50%). (2) PaO2 < or = 65 mmHg. (3) Stable arterial blood gases (ABG), spirometry (S) and clinical state., Exclusion Criteria: Asthma, restrictive disease, sleep apnoea syndrome, advanced renal or hepatic disease, peripheral neuropathy, use of respiratory stimulants or psychotrophic drugs., Treatment: AB 1 mg/kg/day (weight < 75 kg = 50 mg/day; weight > or = 75 kg = 100 mg/day) in an intermittent schedule with resting periods of 1 month after the third, 6th and 9th months during 1 year., Instrumentation: Stabilisation period: S, ABG. Run-in period: S, ABG, 6-min walking test (WT), nocturnal pulse oximetry (NP) and quality of life evaluation (CRQ). Third, 6th and 9th months: S, ABG. End of the study: S, ABG, WT, NP, CRQ., Statistics: ANOVA for repeated measurements., Results: Two hundred and eighty-nine patients were evaluated and 81 were included in the study. Sixty-six were followed for 6 months, 53 for 9 months and 42 for 1 year. Almitrine and placebo groups did not present significant differences in ABG and S in the 6th, 9th and 12th months. Evolution in WT, NP and CRQ were similar in the two groups. No relevant side-effects were detected: only two patients stopped treatment (one placebo and one AB)., Conclusion: In an intermittent schedule, although well tolerated, at doses of 1 mg/kg/day, AB was not effective in long-term treatment of chronic hypoxemia in COPD patients.

The application of a radon model is useful to understand the processes that drive the radon gas behaviour from its sources to its accumulation indoors. Since in a given inhabited house the detailed knowledge of the values of all the parameters that affect indoor radon levels is not available, the response of the model has to be explored in a reference site in which all the parameters are supposed to be known. We call this site the reference configuration. In this paper we report on the procedure followed to carry out uncertainty, sensitivity and variability analysis of the model response for a reference configuration that corresponds to a single family multi-zone house. We have obtained from the uncertainty analysis that, assuming a normal distribution of all the input parameters with a 10% relative standard deviation (R.S.D.), the model outputs present a R.S.D. in the range 17-22%. The sensitivity analysis reflects, in general, a good behaviour of the model, in the sense that its response describes a realistic behaviour of the system. The variability analysis has shown that the model is applicable to a wide range of situations, and that the most relevant parameters for the reference configuration are: the soil gas-permeability (obtained from the mean soil grain diameter); the ventilation rate of the rooms; the air-exchange rate between the basement and room 2; the soil-indoor pressure difference; the open area; and the concrete radium content.

During gastrulation, the vertebrate embryo is patterned and shaped by complex signaling pathways and morphogenetic movements. One of the first regions defined during gastrulation is the prospective notochord, which exhibits specific cell behaviors that drive the extension of the embryonic axis. To examine the signals involved in notochord formation in Xenopus laevis and the competence of cells to respond to these signals, we performed cell transplantation experiments during gastrulation. Labeled cells from the prospective notochord, somitic mesoderm, ventrolateral mesoderm, neural ectoderm, and epidermis, between stages 9 (pregastrulation) and 12 (late gastrulation), were grafted into the prospective notochord region of the early gastrula. We show that cells from each region are competent to respond to notochord-inducing signals and differentiate into notochordal tissue. Cells from the prospective neural ectoderm are the most responsive to notochord-inducing signals, whereas cells from the ventrolateral and epidermal regions are the least responsive. We show that at the end of gastrulation, while transplanted cells lose their competence to form notochord, they remain competent to form somites. These results demonstrate that at the end of gastrulation cell fates are not restricted within germ layers. To determine whether notochord-inducing signals are present throughout gastrulation, grafts were made into progressively older host embryos. We found that regardless of the age of the host, grafted cells from each region give rise to notochordal tissue. This indicates that notochord-inducing signals are present throughout gastrulation and that these signals overlap with somite-inducing signals at the end of gastrulation. We conclude that it is the change of competence that restricts cells to specific tissues rather than the regulation of the inducing signals., (Copyright 2000 Academic Press.)

Legionella often causes systemic manifestations. The clinical spectrum now includes cardiac legionellosis. The first case of myocarditis was reported by Gross in 1981. To date few additional cases have been described. Myocardial involvement might be more frequent than supposed in legionnaires' disease.

A previously healthy young man presented with breathlessness, diffuse pulmonary infiltrates on the chest x-ray film, and a high degree of peripheral blood eosinophilia. Analysis of bronchoalveolar lavage (BAL) fluid showed 64 percent eosinophils. A diagnosis of toxocariasis was eventually reached on the basis of a positive enzyme-linked immunosorbent assay (ELISA) for Toxocara canis. The routine performance of the ELISA test for Toxocara in the diagnostic approach to pulmonary infiltration with eosinophilia could reveal an undetermined, sometimes unsuspected, number of cases of adult toxocariasis with pulmonary involvement. A high degree of eosinophilia in the differential cell count of BAL fluid may eventually prove to be a useful clue in favor of such a diagnosis.

Sacrococcygeal teratoma is rarely diagnosed in adults. Pulmonary mass as the presenting clinical form of the malignant variety of this germ-cell tumor is exceptional. We report herein such a case with the noticeable peculiarity of showing the air meniscus sign on chest roentgenographic examination.

We studied, in a prospective way, the characteristics of definitively diagnosed nosocomially acquired pneumonias in our hospital over 36 months. Out of 55 cases, 27 were due to Legionella pneumophila and 28 to other, non-Legionella bacteria. The cases of legionellosis concentrated in July, August, and December. The only risk factors that showed significant differences (p less than 0.05) were general anesthesia and surgery and immunosuppressive disease, which were more frequent in the non-Legionella group, as were chronic liver disease and lowering of consciousness level. The absence of severe underlying disease, chronic or not, was uncommon in both groups, but more frequent in the Legionella group. We observed no differences in the clinical features of the two groups. Mean values of gamma-glutamyltranspeptidase and total bilirubin were higher (p less than 0.05) in the non-Legionella group. The only x-ray data that showed significant difference were pleural effusion, more frequent in the non-Legionella group (p less than 0.02). The mortality rate of legionellosis was 14.6 percent compared to 35.7 percent for the non-Legionella group (p less than 0.05). We conclude that a sure differential diagnosis based on clinical, roentgenographic and analytical features of both groups is not possible. The relatively low mortality rate of the Legionella group, when compared to other series of nosocomial legionellosis, could be due to the standard use of erythromycin in the therapeutic approach to nosocomial-acquired pneumonia in our hospital.

Nineteen diabetic patients with end-stage renal disease on CAPD were evaluated over a 2 year period. All but one patient was insulin-dependent, with a mean age of 47.7 years. Average time on CAPD was 16.1 months (range, 2-28 months). Thirteen patients were followed for more than 12 months, and nine for more than 18 months. The mean training period was 22.9 days. Good blood glucose control was obtained with intraperitoneal (IP) insulin in all of the patients. Mean blood glucose levels of 125 +/- 23.08 mg/dl were achieved with 103 +/- 38.5 U/day of regular IP insulin. Glycosalated hemoglobin decreased from a mean of 12.7 +/- 2.35% before CAPD to 10.08 +/- 0.97% during CAPD. Peritoneal creatinine clearance remained stable during the study period, with a concommitant decrease (P less than 0.001) in the mean residual renal creatinine clearance. The incidence of peritonitis was one episode per 7.8 patient-months. Average length of hospitalization was 33.24 days/year. Visual acuity remained stable after 1 year in 73% of the 26 eyes evaluated. No amputations were required in more than 2 years of follow-up. Actuarial survival was 100% at 1 year and 86% at 2 years, and the technique survival of CAPD was 91 and 79%, respectively. These results demonstrate that CAPD is a good dialysis procedure for treating diabetic patients with chronic renal failure, and it offers the advantage of controlling glycemia better than other dialysis methods.

Legionnella often causes systemic manifestations. The clinical spectrum now includes cardiac legionnellosis. The first case of pericardial effusion was reported in September, 1981. To date, few additional cases have been reported. We hereby report a case of asymptomatic pericardial effusion with simultaneous pulmonary involvement. Pericardial involvement, if sought, would probably be more frequent than supposed in Legionnaires' disease.