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Orthogonal frequency-division multiplexing with random multiple access (OFDRMA) is discussed for down-link communications, whereby a single base-station transmits information towards several active users. Current methods for down-link communication partition the frequency resources among the active users in an orthogonal fashion, i.e. a central unit (typically the base-station itself) dynamically allocates the resources such that each user is allocated a fixed and exclusive set of sub-bands (a.k.a. bins, or subcarriers). The task and overhead required for orchestrating the frequency sub-bands allocations among the users in an optimal fashion can be quite cumbersome, and typically involves increased computational complexity, latency and bandwidth resources. The main purpose we address in this paper is to avoid the task and overhead required in the state-of-the-art OFDM systems in both the base-station and the users, while sacrificing as little as possible in terms of users side error rate performance. This is of particular importance in multi-user multiple-input multiple-output systems, which become increasingly popular these recent years. In OFDRMA a user is assumed to be allocated with a predetermined, randomly selected frequency bins. A multi-antenna multi-user delivery approach is presented based on pre-coding and multi-cast transmission. It is shown to provide robustness against the forced randomness of the scheme. Simulation results are provided for demonstrating the performance attainable with OFDRMA and the proposed transmission scheme.

Background Benznidazole and nifurtimox are effective drugs used to treat Chagas’ disease; however, their administration in patients in the chronic phase of the disease is still limited, mainly due to their limited efficacy in the later chronic stage of the disease and to the adverse effects related to these drugs. Objectives To evaluate the effect of low doses of nanoformulated benznidazole using a chronic model of Trypanosoma cruzi Nicaragua infection in C57BL/6J mice. Methods Nanoformulations were administered in two different schemes: one daily dose for 30 days or one dose every 7 days, 13 times. Results Both treatment schemes showed promising outcomes, such as the elimination of parasitaemia, a reduction in the levels of T. cruzi-specific antibodies and a reduction in T. cruzi-specific IFN-γ-producing cells, as well as an improvement in electrocardiographic alterations and a reduction in inflammation and fibrosis in the heart compared with untreated T. cruzi-infected animals. These results were also compared with those from our previous work on benznidazole administration, which was shown to be effective in the same chronic model. Conclusions In this experimental model, intermittently administered benznidazole nanoformulations were as effective as those administered continuously; however, the total dose administered in the intermittent scheme was lower, indicating a promising therapeutic approach to Chagas’ disease.

Background and Objectives: Congenital heart defects (CHD) and growth restriction at birth are two major causes of childhood and adult morbidity and mortality. The aim of this study was to assess the overall risk of growth restriction at birth, as measured by its imperfect proxy small (< 10th percentile) for gestational age (SGA), for newborns with CHD.Methods: Using data from a population-based cohort of children born with CHD, we assessed the risk of growth restriction at birth using SGA and severe SGA (3rd percentile). To compare the odds of SGA and severe SGA across five specific major CHD, we used ordinal logistic regression using isolated, minor (non-operated) ventricular septal defect (VSD) as the control group.Results: The overall proportion of SGA for “isolated” CHD (i.e., those not associated with other anomalies) was 13% (95% CI, 12–15%), which is 30% higher than what would be expected in the general population (i.e., 10%). The risk of severe SGA was 5% (95% CI, 4–6%) as compared with the expected 3% in the general population. There were substantial differences in the risk of overall SGA and more so severe SGA across the different CHD. The highest risk of SGA occurred for Tetralogy of Fallot (adjusted OR 2.7, 95% CI, 1.3–5.8) and operated VSD (adjusted OR 2.1, 95% CI, 1.1–3.8) as compared with the control group of minor (non-operated) VSD.Conclusion: The overall risks of both SGA and severe SGA were higher in isolated CHD than what would be expected in the general population with substantial differences across the subtypes of CHD. These results may provide a clue for understanding the underlying mechanisms of the relation between alterations in fetal circulation associated with different types of CHD and their effects on fetal growth.

Summary Background Preterm birth is a major global health challenge, the leading cause of death in children under 5 years of age, and a key measure of a population's general health and nutritional status. Current clinical methods of estimating fetal gestational age are often inaccurate. For example, between 20 and 30 weeks of gestation, the width of the 95% prediction interval around the actual gestational age is estimated to be 18–36 days, even when the best ultrasound estimates are used. The aims of this study are to improve estimates of fetal gestational age and provide personalised predictions of future growth. Methods Using ultrasound-derived, fetal biometric data, we developed a machine learning approach to accurately estimate gestational age. The accuracy of the method is determined by reference to exactly known facts pertaining to each fetus—specifically, intervals between ultrasound visits—rather than the date of the mother's last menstrual period. The data stem from a sample of healthy, well-nourished participants in a large, multicentre, population-based study, the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). The generalisability of the algorithm is shown with data from a different and more heterogeneous population (INTERBIO-21st Fetal Study). Findings In the context of two large datasets, we estimated gestational age between 20 and 30 weeks of gestation with 95% confidence to within 3 days, using measurements made in a 10-week window spanning the second and third trimesters. Fetal gestational age can thus be estimated in the 20–30 weeks gestational age window with a prediction interval 3–5 times better than with any previous algorithm. This will enable improved management of individual pregnancies. 6-week forecasts of the growth trajectory for a given fetus are accurate to within 7 days. This will help identify at-risk fetuses more accurately than currently possible. At population level, the higher accuracy is expected to improve fetal growth charts and population health assessments. Interpretation Machine learning can circumvent long-standing limitations in determining fetal gestational age and future growth trajectory, without recourse to often inaccurately known information, such as the date of the mother's last menstrual period. Using this algorithm in clinical practice could facilitate the management of individual pregnancies and improve population-level health. Upon publication of this study, the algorithm for gestational age estimates will be provided for research purposes free of charge via a web portal. Funding Bill & Melinda Gates Foundation, Office of Science (US Department of Energy), US National Science Foundation, and National Institute for Health Research Oxford Biomedical Research Centre.

Splenic abscess is septic collection which occurs after haematogenous spread or local dissemination. Splenic abscess is an uncommon and rare condition, more frequently affecting male and immunocompromised patients. There are no guidelines regarding its diagnosis and management. Computed tomography (CT) scan is highly sensitive and specific (95% and 92%, respectively) in the diagnosis of splenic abscess. Diagnosis is based on blood cultures which are positive in 24 to 80% of cases. Bacterial growth culture of abscess after drainage is more efficient (50-80%) and can be performed after surgery or percutaneous drainage under imaging, including CT scan. Microorganisms involved are frequently enterobacteriaceae, gram-positive cocci and anaerobes. This particular ecology leads to an empiric broad-spectrum antibiotic therapy, with a variable duration, from 10days to more than one month. Management remains very close to the one applied in case of liver abscesses. The role of splenectomy in the prevention of recurrence remains controversial. We reviewed the literature regarding splenic abscesses, from diagnosis to therapy.

Infection during pregnancy is common and the developing fetal brain is vulnerable to vertical transmission due to immaturity of the fetal immune system. Infection is a major cause of multiple organ abnormalities, including the neuraxis, due to the neurotropism of the infectious agents. This review sets out to give an overview of fetal infection, review the general principles of the nature and timing of the infectious insult with respect to outcomes, review the neuroimaging of infection by ultrasound and magnetic resonance imaging (MRI), and review the various pathogens involved, including the two most common, cytomegalovirus (CMV) and Toxoplasma, and also other common viral and nonviral infections.

Background Lyme borreliosis (LB) diagnosis currently relies mainly on serological tests and sometimes PCR or culture. However, other biological assays are being developed to try to improve Borrelia-infection diagnosis and/or monitoring. Objectives To analyse available data on these unconventional LB diagnostic assays through a systematic literature review. Methods We searched PubMed and Cochrane Library databases according to the PRISMA-DTA method and the Cochrane Handbook for Systematic Reviews of Interventions. We analysed controlled and uncontrolled studies (published 1983–2018) on biological tests for adults to diagnose LB according to the European Study Group for Lyme Borreliosis or the Infectious Diseases Society of America definitions, or identify strongly suspected LB. Two independent readers evaluated study eligibility and extracted data from relevant study reports; a third reader analysed full texts of papers to resolve disagreements. The quality of each included study was assessed with the QUADAS-2 evaluation scale. Results Forty studies were included: two meta-analyses, 25 prospective controlled studies, five prospective uncontrolled studies, six retrospective controlled studies and two case reports. These biological tests assessed can be classified as: (i) proven to be effective at diagnosing LB and already in use (CXCL-13 for neuroborreliosis), but not enough to be standardized; (ii) not yet used routinely, requiring further clinical evaluation (CCL-19, OspA and interferon-α); (iii) uncertain LB diagnostic efficacy because of controversial results and/or poor methodological quality of studies evaluating them (lymphocyte transformation test, interferon-γ, ELISPOT); (iv) unacceptably low sensitivity and/or specificity (CD57+ natural killer cells and rapid diagnostic tests); and (v) possible only for research purposes (microscopy and xenodiagnoses). Discussion QUADAS-2 quality assessment demonstrated high risk of bias in 25/40 studies and uncertainty regarding applicability for 32/40, showing that in addition to PCR and serology, several other LB diagnostic assays have been developed but their sensitivities and specificities are heterogeneous and/or under-evaluated or unassessed. More studies are warranted to evaluate their performance parameters. The development of active infection biomarkers would greatly advance LB diagnosis and monitoring.

Neglected tropical diseases (NTDs) constitute a group of infectious diseases prevalent in countries with tropical and subtropical climate that affect the poorest individuals and produce high chronic disability associated with serious problems for the health system and socioeconomic development. Chagas disease or American trypanosomiasis is included on the NTDs list. However, even though this disease affects more than 10 million people, mostly in Latin America, causing the death of over 10,000 people every year, only two drugs are approved for its treatment, benznidazole and nifurtimox. These antiparasitic agents were developed almost half a century ago and present several biopharmaceutical disadvantages such as low aqueous solubility and permeability limiting their bioavailability. In addition, both therapeutic agents are available only as tablets and a liquid pediatric formulation is still lacking. Therefore, novel pharmaceutical strategies to optimize the pharmacotherapy of Chagas disease are urgently required. In this regard, nanotechnological approaches may be a crucial alternative for the delivery of both drugs ensuring an effective pharmacotherapy although the successful bench-to-bedside translation remains a major challenge. The present work reviews in detail the formulation and in-vitro/in-vivo analysis of different nanoformulations of nifurtimox and benznidazole in order to enhance their solubility, dissolution, bioavailability and trypanocidal activity. Fil: Arrua, Eva Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Farmacia; Argentina Fil: Seremeta, Katia Pamela. Universidad Nacional del Chaco Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina Fil: Bedogni, Giselle Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Farmacia; Argentina Fil: Okulik, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional del Chaco Austral; Argentina Fil: Salomon, Claudio Javier. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Chronic rhinosinusitis (CRS) is a characteristic feature of cystic fibrosis (CF) multiorgan disease and develops early in the life of patients with CF. The study aimed to correlate the inflammatory markers and the presence of structural abnormalities detected by MRI in the paranasal sinuses of patients with CF. Methods: Nasal lavage and MRI of the paranasal sinuses was performed in a cohort of 30 CF patients (median age 14 y, range 7–20 y). Morphological abnormalities characteristic of CF were evaluated with a dedicated CRS MRI scoring system and correlated with different inflammation parameters measured in nasal lavage. Inflammation of the paranasal sinuses was positively associated with structural abnormalities in MRI. The concentration of the pro-inflammatory markers neutrophil elastase (NE) and the neutrophil elastase/alpha1-antitrypsin (NE/A1AT) complex correlated significantly with CRS-MRI sum score (p &lt, 0.05, r = 0.416 and p &lt, 0.05, r = 0.366, respectively). S. aureus infection was associated with the increased pro-inflammatory cytokine activity of IL-6 and IL-8, and increased levels of NE/A1AT complex in our patients (p &lt, 0.05, respectively). CRS-MRI sum score and individual sinus MRI scores were positively associated with inflammatory activity as a sign of CRS pathology present in CF.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most common chronic disorders with limited therapeutic options. However, the pathogenesis of CRSwNP remains poorly understood. Objective We sought to determine the role of abnormalities in nasal epithelial ion transport in primary epithelial cultures and patients with CRSwNP. Methods We studied epithelial ion transport and transcript levels of the Cl− channels cystic fibrosis transmembrane conductance regulator and transmembrane protein 16A (TMEM16A) in human primary nasal epithelial cultures of patients with CRSwNP and healthy controls. Furthermore, we determined expression levels of proinflammatory cytokines that have been implicated in the regulation of epithelial ion channels (IL-1β, INF-γ, TNF-α, IL-13) and studied effects of the key TH2 signaling molecule IL-13 in CRSwNP and control nasal epithelial cultures. Finally, we measured in vivo nasal potential difference to compare epithelial ion transport in patients with CRSwNP and controls. Results Bioelectric studies demonstrated that Ca2+-activated Cl− secretion was reduced in CRSwNP versus control nasal epithelial cultures. Transcript levels of IL-13 and the Ca2+-activated Cl− channel TMEM16A were increased in CRSwNP cultures. Stimulation with IL-13 increased TMEM16A expression further and restored Ca2+-activated Cl− secretion in CRSwNP cultures. Nasal potential difference measurements demonstrated reduced Ca2+-activated Cl− transport in patients with CRSwNP versus controls. Conclusions This study demonstrates that TMEM16A-mediated Ca2+-activated Cl− secretion is reduced in primary nasal epithelial cultures and nasal epithelia of patients with CRSwNP. Our data suggest that the Ca2+-activated Cl− channel TMEM16A may be implicated in the pathogenesis and serve as a novel therapeutic target in patients with CRSwNP.

UWB microwave imaging has proven to be a promising technique for early-stage breast cancer detection. The extensive image reconstruction time can be accelerated by parallelizing the execution of the underlying beamforming algorithms. However, the efficiency of the parallelization will most likely depend on the grade of parallelism of the imaging algorithm and of the utilized hardware. This paper investigates the dependencies of two different beamforming algorithms on multiple hardware specification of several graphics boards. The parallel implementation is realized by using NVIDIA’s CUDA. Three conclusions are drawn about the behavior of the parallel implementation and how to efficiently use the accessible hardware.

La maladie de Lyme fait l’objet d’une mediatisation importante. De nombreux articles et emissions de radio et de television ont contribue a renforcer un sentiment d’etat d’alerte concernant cette maladie. L’une des demandes principales des patients est de beneficier d’une reconnaissance et d’une prise en charge adaptee de leur infection...

Objectives: To develop an alcohol-free solution suitable for children of benznidazole, the drug of choice for treatment of Chagas disease. Methods: In a quality-by-design approach, a systematic optimisation procedure was carried out to estimate the values of the factors leading to the maximum drug concentration. The formulations were analysed in terms of chemical and physical stability and drug content. The final preparation was subjected to an in vivo palatability assay. Mice were infected and treated orally in a murine model. Results: The results showed that benznidazole solubility increased up to 18.38 mg/ml in the optimised co-solvent system. The final formulation remained stable at all three temperatures tested, with suitable drug content and no significant variability. Palatability of the preparation was improved by taste masking of BZL. In vivo studies showed that both parasitaemia and mortality diminished, particularly at a dose of 40 mg/kg/day. Conclusion: Quality by design was a suitable approach to formulate a co-solvent system of benznidazole. The in vivo studies confirmed the suitability of the optimised such solutions to diminish both parasitaemia and mortality. Thus, this novel alternative should be taken into account for further clinical evaluation in all age ranges. Fil: Santos Souza, Higo Fernando. Universidade de Sao Paulo; Brasil Fil: Real, Daniel Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Area Técnica Farmacéutica; Argentina Fil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Area Técnica Farmacéutica; Argentina Fil: Rocha, Sandra Carla. Universidade de Sao Paulo; Brasil Fil: Alonso, Victoria Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Area Parasitología; Argentina Fil: Serra, Esteban Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Area Parasitología; Argentina Fil: Silber, Ariel Mariano. Universidade de Sao Paulo; Brasil Fil: Salomon, Claudio Javier. Universidad Nacional de Rosario. Area Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

Background: The caprazamycin derivative, CPZEN-45 has previously demonstrated antitubercular activity against Mycobacterium tuberculosis H37Rv. Here, the authors report a basic biopharmaceutical characterization of the compound focusing on in vitro permeability and cytotoxicity, with respect to the suitability of CPZEN-45 hydrochloride for inhalation treatment of tuberculosis. Results: MTT assays confirmed that CPZEN-45 HCl had no acute cytotoxic effects up to 3 mg/ml. In transport studies, apparent permeability coefficients of CPZEN-45 HCl across Calu-3 monolayers in absorptive and secretive directions were 0.43 ± 0.20 × 10-6 cm/s and 0.38 ± 0.12 × 10-6 cm/s, respectively. Across ATI-like monolayers, apparent permeability values were 12.10 ± 4.31 × 10-6 cm/s and 8.50 ± 1.83 × 10-6 cm/s. CPZEN-45 HCl formed colloidal complexes at concentrations above 0.38 mg/ml; however, these complexes were not micelles, as assessed by Orange OT encapsulation assay. Conclusion: CPZEN-45 is an interesting new drug candidate with potential to be used in aerosol therapy of tuberculosis.

Resume Les donnes de declaration obligatoire (DO) de tuberculose entre 2000 et 2007 en Bretagne ont ete analysees. La Bretagne avait la troisieme plus forte incidence francaise (1975 cas declares, huit cas pour 100 000). Une diminution significative de l’incidence a ete observee sur la periode d’etude. Elle refletait la diminution d’incidence a partir de 2001 par rapport aux annees 1990. La maladie touchait une population âgee de 55 ans en moyenne contre 45 ans pour le reste du pays (p

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, teaching and research for diagnostic imaging in women’s healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practices at the time at which they were issued. Although ISUOG has made every effort to ensure that guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. They are not intended to establish a legal standard of care because interpretation of the evidence that underpins the guidelines may be influenced by individual circumstances and available resources. Approved guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

Objectives To describe prospectively the normal abdominal and pelvic ultrasound features within 24 h following uneventful Cesarean section. Methods Transabdominal ultrasound examination was performed between 1 and 3 h, and again at 24 h, following lower-segment Cesarean section (LSCS). The myometrium, endometrium, and amount and distribution of free peritoneal fluid were studied in 30 women with singleton pregnancies who underwent LSCS delivery. Results Examinations were performed easily in all cases except one who was morbidly obese (body mass index > 40 kg/m2). At 1–3 h after delivery, mean ± SD endometrial thickness was 13 ± 2 mm. Mean uterine length, from the fundus to the cervical external os, was 160 ± 15 mm. Measurement of uterine length in the mid-sagittal plane of the pelvis was impossible in eight cases (27%) owing to pain. No abnormal intrauterine findings were observed. Mean uterine width was 110 ± 10 mm. Mean distance between the sacral promontory and uterine fundus was 104 ± 11 mm. Mean thicknesses of the anterior and posterior walls of the uterus were 40 ± 5 mm and 39 ± 7 mm, respectively. No fluid was seen in Morrison's or Douglas' pouches. There was a consistent and significant reduction between the measurements performed at 1–3 h and those at 24 h after LSCS, except for the distance between the fundus and external os. Conclusions Ultrasound examination is feasible after Cesarean section. Images are obtained easily, even when scanning through the scar. In normal pregnancies, there is no fluid in the abdomen or pelvis. These results could help clinicians in the decision-making process in cases of early postpartum hemorrhage or hemodynamic instability following LSCS. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.

Background Urinary tract infections (UTIs) are a major recurrent problem for spinal cord injury (SCI) patients. Repeated antibiotic treatments contribute to the emergence of multidrug-resistant bacteria (MDRB). We evaluated the use of weekly oral cycling antibiotics (WOCA) in the prevention of UTIs over a mean follow-up period of 53 months (median follow-up period: 57 months) and analyzed the risk of MDRB emergence. Methods We conducted a cross-sectional study of adult SCI patients with neurogenic bladder who were receiving the WOCA regimen. Results We included 50 patients, mainly men (60%), with a mean age of 51 ± 13.5 years. Overall, 66% of patients had been paraplegic or tetraplegic for 19.4 ± 14.3 years; 92% underwent intermittent catheterization; and 36% had no postvoid residual. The number of febrile and non-febrile UTIs significantly reduced after WOCA initiation (9.45 non-febrile UTIs before WOCA initiation vs . 1.57 after; 2.25 febrile UTIs before WOCA initiation vs . 0.18 after; P = 0.0001). Only one adverse event was reported during the follow-up period. The number of MDRB-colonized patients decreased from 9/50 to 4/50 during the follow-up period. Conclusion WOCA is an effective and safe strategy to prevent UTIs in SCI patients with neurogenic bladder. WOCA does not lead to the emergence of MDRB resistance and even seems to reduce MDRB carriage.

As the WHO stated, lower respiratory infections are the third leading cause of death. In addition, it is remarkable that antimicrobial resistance represents a huge threat. Thus, new therapeutic weapons are required. Among the possible alternatives, antibiotic encapsulation in nanoparticles has gained much attention in terms of improved tolerability, activity and ability to combat the resistance mechanisms of bacteria. In this regard, this reviewarticle focuses on the latest nanocarrier approaches for inhalatory therapy of antibiotics. First, the technology related to lung disposition will be reviewed. Then, nanocarrier systems will be introduced and the challenges required to perform adequate pulmonary deposition analysed. In the following part, drug delivery systems (DDSs) on the market or in clinical trials are described and, finally, new approaches of nanoparticles that have reached preclinical stage are enumerated. Altogether, this review aims at gathering together the novel nanosystems for anti-infectious therapy, underlining the potential of DDSs to improve and optimize currently available antibiotic therapies in the context of lung infections. Fil: Moreno Sastre, M.. Universidad del País Vasco; España. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine; España Fil: Pastor, M.. Universidad del País Vasco; España. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine; España Fil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Esquisabel, A.. Universidad del País Vasco; España. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine; España Fil: Pedraz, J. L.. Universidad del País Vasco; España. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine; España

Smoking is a major contributing factor for chronic obstructive pulmonary disease (COPD). Tobacco smoke exposure causes oxidative stress which results in alveolar wall destruction, mucus hyper secre...

Resume Objectif. – Le but de cette etude est d'etudier les caracteristiques de l'hysterectomie chez les patientes n'ayant jamais accouche par voie basse dans un service hospitalo-universitaire. Patientes et methodes. – Etude retrospective des dossiers medicaux d'hysterectomie sur huit ans. Les patientes nullipares vaginales ont ete separees en deux groupes : groupe 1 : patientes operees par voie haute de premiere intention, groupe 2 : patientes operees par abord vaginal sans (2a) ou avec (2b) assistance cœlioscopique. Les donnees per et postoperatoires ont ete analysees et comparees. Resultats. – Pendant la periode d'etude, 243 hysterectomies chez des nullipares vaginales ont ete realisees. Parmi ces patientes, l'hysterectomie a ete entreprise par abord vaginal dans 75 % des cas. Dans 13 cas (7,1 %), une laparoconversion a ete necessaire. Le poids moyen des uterus extraits par voie haute etait de 943 g contre 370 g en moyenne pour ceux extraits par voie vaginale. La voie haute (groupe 1) demandait plus de temps (105 minutes en moyenne) que la voie vaginale pure (groupe 2a ; 81 minutes) mais moins que la voie vaginale avec assistance cœlioscopique (2b ; 173 minutes). Il n'y avait pas de difference significative en ce qui concerne les pertes sanguines ou les complications entre les groupes 1 et 2. Le sejour hospitalier etait plus court dans le groupe 2. L'assistance cœlioscopique a la voie vaginale n'etait pas associee a un volume uterin moyen plus eleve, ni a une reduction des complications. Discussion et conclusion. – L'absence d'antecedent d'accouchement par voie basse ne devrait plus etre consideree comme une contre-indication a l'hysterectomie par voie basse. Chez ces patientes, la majorite des interventions devrait etre pratiquee par cette voie ; l'assistance cœlioscopique semble d'un interet limite.

Due to the development of many quality control systems in the industry, increasing demands for limited health care resources and rise of legal aspects in ultrasound practice, the need for quality has also emerged in the prenatal ultrasound field. Based on the literature, various approaches for quality control based on fetal detection rates, analysis of nuchal translucency measurements or biometric measurements are reviewed. Particular emphasis is put on the use of fetal biometry to develop quality control systems based on both a qualitative or a quantitative approach.

Resume La maladie de Creutzfeldt-Jakob est une maladie neurodegenerative principalement caracterisee par une demence. Elle se presente sous trois formes epidemiologiques : une forme sporadique, majoritaire, une forme familiale liee a une mutation dans le gene codant pour la proteine prion et des formes iatrogenes. Cette encephalopathie subaigue spongiforme transmissible est une maladie rare dont l’incidence est d’un cas par an et par million d’habitants. Elle se caracterise par une spongiose, une mort neuronale et une gliose astrocytaire ainsi que par l’accumulation d’une proteine de l’hote sous une forme partiellement resistante aux proteases. Le nouveau variant de la maladie de Creutzfeldt-Jakob a ete decrit en 1996 en Grande-Bretagne chez des sujets jeunes sans aucun antecedent familial ou iatrogene. Des signaux hyperdenses a l’imagerie par resonance magnetique cerebrale ont ete decrits dans les zones post-thalamiques et peuvent constituer une aide au diagnostic lorsque la clinique est evocatrice. Cette forme a rapidement ete suspectee d’etre la consequence de l’infection de l’homme par l’agent de l’encephalopathie spongiforme bovine. A ce jour, plus de 130 cas mondiaux ont ete repertories. L’agent responsable est largement distribue en peripherie, ce qui impose de reconsiderer la securite des greffes, des medicaments, de la transfusion et de reevaluer les regles de securite hospitaliere. En termes de sante publique, il est crucial que tous les cas soient identifies.

Background Chagas disease is a neglected parasitic infection caused by the protozoan Trypanosoma cruzi (T. cruzi) that affects more than 6 million people, mainly in Latin America. Benznidazole is still the drug of choice in many countries to treat it in spite of its dosage regimen and adverse side effects such as such as allergic dermatitis, peripheral neuropathy and anorexia. Thus, novel, safer, and more efficacious treatments for such neglected infection are urgently required. Methodology In this study, the efficacy of orally administered low doses of benznidazole (BNZ) nanoparticles was evaluated during the acute phase in mice infected with T. cruzi Nicaragua (TcN) that were immunosuppressed during the chronic stage of the disease. Moreover, the production of T. cruzi-specific antibodies, cardiac tissue inflammation and reactive oxygen species generation by Vero cells treated with both BNZ nanoparticles (BNZ-nps) and raw BNZ (R-BNZ) were also evaluated. Principal findings T. cruzi infected mice treated with 10, 25 or 50 mg/kg/day of BNZ-nps survived until euthanasia (92 days post infection (dpi)), while only 15% of infected untreated mice survived until the end of the experiment. PCR analysis of blood samples taken after induction of immunosuppression showed that a dosage of 25 mg/kg/day rendered 40% of the mice PCR-negative. The histological analysis of heart tissue showed a significant decrease in inflammation after treatments with 25 and 50 mg/kg/day, while a similar inflammatory damage was observed in both infected mice treated with R-BNZ (50 mg/kg/day) and untreated mice. In addition, only BNZ-nps treated mice led to lower levels of T. cruzi-specific antibodies to 50–100%. Finally, mammalian Vero cells treated with BNZ-nps or R-BNZ lead to a significant increase in ROS production. Conclusions Based on these findings, this research highlights the in-vitro/in-vivo efficacy of nanoformulated BNZ against T. cruzi acute infections in immunosuppressed and non-immunosuppressed mice and provides further evidence for the optimization of dosage regimens to treat Chagas disease., Author summary Chagas disease is a neglected parasitic infection caused by the protozoan Trypanosoma cruzi (T. cruzi) that affects more than 6 million people, mainly in Latin America. Benznidazole is still the drug of choice in many countries to treat it in spite of its dosage regimen and adverse side effects such as such as allergic dermatitis, peripheral neuropathy and anorexia. In this study, the efficacy of low doses of benznidazole, formulated as nanoparticles, against T. cruzi acute infections in immunosuppressed and non-immunosuppressed mice was investigated in order to establish future treatment strategies. In-vivo experiments showed that all infected mice treated with low doses of nanoformulated benznidazole survived until the end of the assay (92 dpi), while only 15% of infected untreated mice survived to the end of the same period of time. Moreover, such novel formulation was able to decrease the parasite burden and, consequently, heart inflammation and lesions were significantly reduced. Clearly, low doses of benznidazole exhibited, at least, the same efficacy in infected mice as the usual dose, confirming the usefulness of nanoformulated benznidazole for an improved treatment of Chagas disease.

Atypical teratoid/rhabdoid tumour is a rare and highly malignant tumour of the posterior fossae nervous system that occurs in children especially in the first few years of life. Cutaneous location is not previously reported. A newborn boy was referred for both aqueductal stenosis detected antenatally and skin tags mimicking hamartoma. The cerebral tumour increased in size during a few months leading to both skin and cerebral biopsies. Integrase Interactor-1 (INI-1) immunostaining and tumoural and leukocytes INI-1 gene sequencing confirmed the atypical teratoid/rhabdoid tumour nature of the cerebral tumour. INI-1 immunostaining in skin biopsy confirmed the dermal location of rhabdoid tumour. Thus, unusual cutaneous lesions may be part of atypical teratoid/rhabdoid tumour. The loss of Integrase INI-1 on immunohistochemical staining is characteristic.

PURPOSE To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) with recombinant human interferon alfa-2a (Roferon-A; Hoffman La-Roche AG, Basel, Switzerland) versus the combination of 5-FU with leucovorin (LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS A total of 496 previously untreated colorectal cancer patients were randomized to receive either Roferon-A (9 MIU) subcutaneously three times per week, with 5-FU (750 mg/m2/d) by continuous intravenous (i.v.) infusion (CIV) on days 1 to 5, then, after a 9-day hiatus, as a weekly i.v. bolus at the same dose (IFN/5-FU); or LV (200 mg/m2/d) by i.v. infusion plus 5-FU (370 mg/m2/d) by i.v. bolus on days 1 to 5, repeated every 4 weeks (LV/5-FU). RESULTS There were no significant differences between IFN/5-FU and LV/5-FU in the overall response rate (21% v 18%), duration of response (7.3 v 6.2 months), or survival time (median, 11.0 v 11.3 months). Toxicity profiles differed; constitutional symptoms and myelosuppression were more frequent and more severe with IFN/5-FU, and gastrointestinal symptoms with LV/5-FU. More patients interrupted treatment for adverse events (AEs) with IFN/5-FU than with LV/5-FU. Five treatment-related deaths occurred with each regimen. CONCLUSION The combination IFN/5-FU produced response rates, response durations, and survival times similar to those with LV/5-FU. Biochemical modulation of 5-FU by either IFN or LV appears to result in equivalent efficacy; however, fewer patients were able to tolerate the specified IFN/5-FU combination used in this study.

This study aimed to determine the prevalence of and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) carriage among patients newly admitted to rehabilitation centres. It is a prospective study examining MRSA carriage on admission to seven rehabilitation wards in four countries. Risk factors for MRSA carriage were analysed using univariate and multivariate analyses. A total of 1204 patients were studied. Among them, 105 (8.7%) had a positive admission MRSA screening result. The MRSA carriers were more likely to be male, to have had a recent stay in another long-term-care facility or >2 weeks acute-care hospital stay, history of colonization with MRSA, reduced level of consciousness, peripheral vascular disease and pressure sores. In multivariable logistic regression male gender (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.4-3.6, p 0.001), history of MRSA positivity (OR 6.8, 95% CI 3.8-12.3, p 2 weeks) acute-care hospital stay (OR 1.9, 95% CI 1.2-3, p 0.004), remained significant risk factors for MRSA carriage. MRSA carriage is common on admission to rehabilitation centres but less so, than previously described in long-term-care facilities. Male gender, history of MRSA positivity, previous hospitalization and peripheral vascular disease may predict MRSA carriage, and may serve as indicators for using pre-emptive infection control measures.

Hundred years after the discovery of Chagas' disease, there is a lack of effective treatment to control this neglected disease caused by the parasite Trypanosoma cruzi. The transmission is primarily through vector-borne blood transfusion or during pregnancy, producing high mortality and morbidity among poor people in many countries of Latin America. In the last decades, the efforts have been focused mainly on the elimination of vectors. At the same time, screening of blood donors in order to avoid transfusional transmission has been improved all over the world. However, Chagas' disease is still a major public health problem, with estimates of nearly 90 million people at risk of infection and more than eight million infected in 18 endemic countries. Despite the high incidence in endemic regions and the dissemination of neglected diseases in North America and Europe, to date, there are only two drugs developedn and prescribed for the treatment of Chagas' disease, nifurtimox (tablets of 120 mg) and benznidazole (tablets of 100 mg). In this review, different approaches carried out in the last decades for developing novel pharmaceutical formulations for the delivery of nifurtimox and benznidazole are discussed. Fil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

Knowledge of local MRSA epidemiology at both facility and ward level helps target control measures. This study aimed to determine the prevalence of and risk factors for MRSA colonisation on admission to different healthcare sectors in two European countries.

The 1st International Meeting on Pharmaceutical Sciences (RICiFA 2010) took place from the 23–25th of June 2010 in the National University of Cordoba, Cordoba, Argentina. The purpose of this conference was to bring together renowned scientists, researchers, and students in order to reflect upon recent advances in pharmaceutical sciences. The meeting offered a strong representation of all the disciplines including Phytopharmacy and Pharmacognosy, Pharmacology, Drug Quality Control, Microbiology, Pharmaceutical Technology and Biotechnology, Medicinal Chemistry, Clinical Pharmacy, and Pharmaceutical Education. The opening session began with a keynote lecture given by Dr. Ruben Manzo, President of the Scientific Committee (Argentina), entitled Research and Development of the Pharmaceutical Sciences and its Relationship with the Academic Education in Argentina. Three invited plenary lectures were given by internationally known researchers including Dr. Jean Pierre Benoit (France), Dr. Maria Esther Gil Alegre (Spain), and Dr. Lee Kirsch (U.S.A.). Professor Benoit's presentation was entitled A New Generation of Oncological Nanomedicines: The Lipidic Nanocapsules. Professor Benoit teaches pharmaceutical technology and biopharmacy at the Faculty of Pharmacy, Angers University. He is currently the director of a 50-strong research team, recognized and financed by INSERM. His dynamism has also led him to fulfill numerous administrative tasks within national and international institutions: for example, he has been made a member of the Board of Governors of the CRS (Controlled Release Society), and he has been vice-president then president of the International Microencapsulation Society from 1999 to 2003. His research activity has resulted in the publication of over 220 original refereed scientific articles and reviews, 25 patents and more than 110 contributions at conferences. He was recognized as an AAPS Fellow in 1994. His research, at the frontiers of physical chemistry, pharmaceutical technology, and biology, concerns both the development of new encapsulation methods for active ingredients without recourse to organic solvents, and drug targeting in tumors, particularly in the brain. In the area of drug targeting, Professor Benoit's research group was the first to demonstrate the biocompatibility and the biodegradability of poly(lactide-co-glycolide) microspheres implanted in the brain. Their studies have led to two phase I/II clinical trials and one phase IIb trial in patients suffering from glioblastoma; a significant increase in patient survival has been observed. Currently, his interest is directed towards the conception of bio-inspired nanocapsules (lipid nanocapsules) as new drug delivery systems to target tumors. Dr. Maria Esther Gil Alegre presented a lecture entitled Delivery Systems in Dermatocosmetics. Dr. Gil Alegre is Professor of Pharmaceutical Technology and Researcher of the Industrial Pharmaceutical Institute at the Complutense University of Madrid (UCM), Spain. Her research activity has resulted in the publication of many original refereed scientific articles and reviews, patents, and more than 100 contributions at conferences. She is the author of several book chapters and books. She was engaged with the Spanish Real Pharmacopeia for many years. Her research interests are based on drug delivery systems, microencapsulation of drugs for human and veterinary medicine. She has been involved in the development of new encapsulation methods for active ingredients applied particularly to cosmetic products. Professor Lee Kirsch's talk was entitled A Case Study on Linking Solid-State Stability to Manufacturing Design in the FDA's Quality-By-Design Pharmaceutical Development Paradigm. Dr. Kirsch is professor of Pharmaceutics and Chemical and Biochemical Engineering at The University of Iowa. The research he presented was part of a multi-institutional research project supported by the US-FDA and conducted by the National Institute for Pharmaceutical Technology and Education (NIPTE). Professor Kirsch is the editor-in-chief of AAPS PharmSciTech. An additional ten invited podium presentations were given by distinguished Argentinean scientists and educators including Dr. Maria E. Fatima Nader: Trends in the Design of Pharmaceutical Dosage Forms using Lactobacilli Strains; Dr. Carlos Lanusse: Pharmacology of the Antihelmintic Therapy in Veterinary Medicine; Dr. Juan Gallo: New Trends in Antiangiogenic Ophtalmology Treatment; Dr. Luis E. Bruno Blanch: Applied Methodology to the Design of Anticonvulsant Drugs; Dr. Julio A. Zygadlo: Essentials Oils and its Biological Activities; Dr. Marcelo Naccuchio: Pharmaceutical Technology and Regenerative Medicine; Dr. Virginia Rivero: Research and Development Applied to Novel Vaccines; Dr. Joaquin V. Rodriguez: Trends in Cryopreservation of Cells and Tissues; Dr. Claudia Balague: Advances and Evaluation of the Contents of the Pharmacy Profession; and Dr. Marcela Longhi: Advances of the Applied Analytical Chemistry and Drug Quality Control. Over 230 posters were presented at the meeting. The abstracts were selected and reviewed by the conference's Scientific Committee. We are sincerely grateful to the contributing authors for their outstanding cooperation and valuable support. All are experts in their respective fields and we are honored that each of them not only agreed to participate, but also clearly devoted a great deal of time and diligence to their efforts. Special thanks are also due to all the peer reviewers for their valuable comments, criticisms, and suggestions. This first annual meeting was attended by nearly 500 pharmacists, pharmaceutical scientists, academics, researchers, and students; it signified a major contribution to scientific exchange in Latin America. Although mainly from Argentina, the symposium attracted participants from neighboring South American countries. We thank the participants for submitting their contributions for publication. Please visit the following URL for a complete compilation of presentation titles, authors, and abstracts: www.fbioyf.unr.edu.ar/ricifa. In conjunction with the RICiFA 2010, a day-long pre-satellite symposium on pharmaceutical education took place wherein participants were exposed to topical issues on the role of the pharmacist in health care and its links to pharmaceutical education. The social side of RICiFA 2010—finding new friends and greeting old ones—was an excellent complement to the meeting program. The outstanding success of RICiFA 2010 was achieved by the joint effort of many coworkers and colleagues who worked very hard. Thanks, to all of them. The scientific committee of RICiFA 2010 is already looking forward to welcoming participants once again next year at the 2nd International Meeting on Pharmaceutical Sciences (RICiFA 2012) in Rosario, Argentina The organizing committee of RICiFA 2010 expresses its sincere appreciation to our Sponsors whose generous support has enabled us to present the 1st International Meeting on Pharmaceutical Sciences: Colorcom, Conicet, Damico Sistemas, Evonk, Jenk, Laboratorio de Hemoderivados-UNC, Laboratorios Gador, Laboratorios Monserrat and Eclair, Norces SA, Paam Instrumental and Taller Sancez.

This paper is an attempt to present the current status of VSAT systems in Europe, based on two aspects. 1. The first part describes the actions conducted by the European Telecommunications Standards Institute (ETSI) for issuing proper technical standards. It is also explained how these standards are included in the general framework of the European legislation, the purpose of which is to create the conditions for a really open telecommunications market all over Europe, and more particularly to favour the implementation of independent (private) satellite communications networks, mainly for corporate services on a free competition basis, both as concerns operators and manufacturers. 2. The second part gives an overview of the actual implementation of VSAT networks in Europe and of the expected market trends.

The features of programming languages can be evaluated according to how they affect programming-language independence in four dimensions. The four dimensions are: 1) machine independence, 2) problem independence, 3) human independence, and 4) time independence. This paper presents a definition of independence , and shows how that definition applies to each of the dimensions. By organizing language features in this way, the strengths and weaknesses of many language designs can be identified, and new directions for programming-language research become apparent. This paper also presents the advantages of, and methods of achieving, independence in these dimensions, and occasionally presents the disadvantages of independence.Each of the four dimensions is treated as a discrete domain, and the elements of each domain are classified according to their properties. The elements of the machine domain are classified according to (a) architecture, (b) machine size, (c) peripheral devices, and (d) operating system. The problem domain is classified according to (a) discipline, (b) problem context, (c) system mode, and (d) problem-solving methods. The human domain is classified according to (a) user qualifications, (b) natural language spoken, (c) the three classes designers, implementors , and users , and (d) independence in the class implementors is considered alone. Finally the time dimension is treated in three time scales: (a) program processing, (b) project development, and (c) language evolution.

The aim of this study is to report the authors' initial clinical experience of a 320-detector row computed tomography (CT) scanner in cerebrovascular disorders. Volumetric CT using the full 160-mm width of the 320 detector rows enables full brain coverage in a single rotation that allows for combined time-resolved whole-brain perfusion and four-dimensional CT angiography (CTA). The protocol for the combined dynamic CTA and CT perfusion (CTP) is presented, and its potential applications in stroke, stenoocclusive disease, arteriovenous malformations and dural shunts are reviewed based on clinical examples. The combined CTA/CTP data can provide visualization of dynamic flow and perfusion as well as motion of an entire volume at very short time intervals which is of importance in a variety of pathologies with altered cerebral hemodynamics. The broad coverage enabled by 320 detector rows offers z-axis coverage allowing for whole-brain perfusion and subtracted dynamic angiography of the entire intracranial circulation.

Background Atopic dermatitis (AD) is an inflammatory skin disease of a chronic course. The role of neuropeptides in pathogenesis of this disorder is probably not crucial; however, there is evidence that these substances influence the development and course of AD. Objective The aim of this study was to evaluate the plasma level of substance P, neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) in AD patients during exacerbation and remission of the disease. Material and methods Forty-nine patients with AD, aged 17 to 56 years, participated in the study. Among this group, there were 25 males (51%) and 24 females (49%). The disease lasted from 1 to 55 years. The severity of the disease was assessed with SCORAD index. The severity of pruritus was evaluated with Visual Analog Scale and a specially designed questionnaire. Neuropeptides plasma level was detected with radioimmunoassay. Results Substance P plasma level in AD patients during exacerbation and remission was significantly higher than in the control group. There was a negative correlation between substance P plasma level and total IgE level. CGRP plasma level during exacerbation of AD was significantly lower than in healthy controls and increased in the remission. Significantly higher CGRP concentration was observed in patients suffering from severe pruritus; however, both in patients with more and less severe pruritus, CGRP plasma level was lower than in controls. Higher CGRP plasma level was also observed in patients with more severe disease. NPY plasma level in patients with AD was significantly increased both during exacerbation and remission. During remission of AD, NPY concentration was higher than during exacerbation.

This paper discusses the main issues relating to the configuration and equipment which are to be provided in earth-stations for implementing satellite links with digital circuit multiplication (DCM). Such an implementation is possible using either FDMA/TDM/PSK (continuous) or TDMA/PSK (burst mode) carriers. The main accent will be put in the paper on earth-stations operating with FMDA/TDM/PSK carriers (called IDR carriers by INTELSAT). As regards the RF/IF subsystem, it is shown that IDR and TDMA are very effective in terms of earth-station equipment as compared with conventional FDM/FM operation. As regards the communication subsystem—independently of the DCM equipment proper—a compact terminal, integrating all the signal processing and baseband functions is described.

Objectives Previous findings in mice revealed that SLC26A9, a recently identified epithelial chloride channel, is essential for preventing airway obstruction associated with IL13-induced airway inflammation. These results suggest that SLC26A9 may be a promising alternative Cl − channel in mucoobstructive lung diseases [e.g. cystic fibrosis (CF)]. Thus, we functionally characterized a newly generated epithelial cell line with stable expression of SLC26A9 to investigate molecular regulation. Methods Fisher rat thyroid (FRT) cells were stably transduced with a HA-tagged SLC26A9 construct. Transepithelial Cl − currents were measured by applying a Cl − gradient in Ussing chambers. Whole-cell patch clamp experiments were performed. Results SLC26A9 expression in transduced FRT (FRT-SLC) cells was found at high levels. Transepithelial measurements revealed that the basal short circuit current (I sc ) was significantly increased in FRT-SLC (12.3±2.0 µA/cm 2 P 2 ) cell monolayers. CAMP (IBMX/forskolin)-stimulated Cl − secretion was significantly increased in FRT-SLC compared to FRT-CTL cells (ΔI sc = 4.9±0.5 vs. ΔI sc = 0.7±0.2 µA/cm 2 P − current in FRT-SLC cells and a similar inhibitor selectivity. Conclusion In FRT-SLC cells, SLC26A9 contributes to constitutive and cAMP-stimulated Cl − currents. This established epithelial cell model overexpressing SLC26A9 may be useful for further studies of the regulation and pharmacological activation of SLC26A9 as an alternative Cl − channel in CF.