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Author(s): Qin Liang [sup.1] [sup.2] , Claudio Monetti [sup.1] , Maria V. Shutova [sup.1] , Eric J. Neely [sup.1] [sup.2] , Sabiha Hacibekiroglu [sup.1] [sup.2] , Huijuan Yang [sup.1] [sup.3] [...], Human pluripotent cell lines hold enormous promise for the development of cell-based therapies. Safety, however, is a crucial prerequisite condition for clinical applications. Numerous groups have attempted to eliminate potentially harmful cells through the use of suicide genes.sup.1, but none has quantitatively defined the safety level of transplant therapies. Here, using genome-engineering strategies, we demonstrate the protection of a suicide system from inactivation in dividing cells. We created a transcriptional link between the suicide gene herpes simplex virus thymidine kinase (HSV-TK) and a cell-division gene (CDK1); this combination is designated the safe-cell system. Furthermore, we used a mathematical model to quantify the safety level of the cell therapy as a function of the number of cells that is needed for the therapy and the type of genome editing that is performed. Even with the highly conservative estimates described here, we anticipate that our solution will rapidly accelerate the entry of cell-based medicine into the clinic.Introduction of a suicide gene together with a linked cell-division gene to generate a safe-cell system enables the selective elimination of proliferating cells after cell transplantation in mouse models of cell therapy.

Francesca Guerriero, Valentina Orlando, Valeria Marina Monetti, Veronica Russo, Enrica Menditto Center of Pharmacoeconomics (CIRFF), University of Naples Federico II, Naples, Italy Purpose: The aim was to describe the current use of biological therapies among patients affected by psoriasis and to analyze a drug utilization profile in naïve patients in terms of switching and treatment costs in a Local Health Unit (LHU) of Southern Italy. Methods: We conducted an observational retrospective cohort analysis using the health-related administrative databases of a LHU in Southern Italy covering a population of about one million inhabitants. All subjects with a main or secondary diagnosis of psoriasis who received at least one prescription of biological therapies between January 1, 2010 and December 31, 2014 were analyzed. Switching rate was evaluated in naïve patients within the first year of treatment. Drug cost was calculated for all drugs prescribed and comprised both costs for psoriasis drugs and costs for other treatments. Results: About 20% of patients identified with a diagnosis of psoriasis were under treatment with biological drugs. Among 385 subjects treated with biological therapy, 51.2% were in treatment with etanercept and 33% with adalimumab. Among naïve patients, switching rate to a different biological drug, within the first year of treatment, was 7.3%. The per patient yearly drug cost was €10,536: 96.8% for psoriasis-related drugs and 3.2% for other pharmaceutical treatments. The annual average cost per patient switching from the initial treatment was €13,021, while for those who did not switch from the initial treatment, the annual average cost was €10,342, with a significant difference of about €2,680 per patient per year (p=0.002). Conclusion: Our data may be useful in exploring the dynamics that characterize the use of biological therapy within a specific context and to optimize the use of resources for a better management of the disease. Keywords: drug utilization, biological drugs, psoriasis, administrative databases, treatment cost, switch therapies

Abstract Pixuna virus (PIXV) is an enzootic member of the Venezuelan Equine Encephalitis Virus complex and belongs to the New World cluster of alphaviruses. Herein we explore the role of the cellular cytoskeleton during PIXV replication. We first identified that PIXV undergoes an eclipse phase consisting of 4 h followed by 20 h of an exponential phase in Vero cells. The infected cells showed morphological changes due to structural modifications in actin microfilaments (MFs) and microtubules (MTs). Cytoskeleton-binding agents, that alter the architecture and dynamics of MFs and MTs, were used to study the role of cytoskeleton on PIXV replication. The virus production was significantly affected (p

Background: The steady increase in type 2 diabetes prevalence and the availability of new antidiabetic drugs (AD) have risen the use of these drugs with a change in the patterns of specific drug utilization. The complexity of this treatment is due to successive treatment initiation, switching and addition in order to maintain glycaemic control. The aim of this study was to describe the utilization patterns of ADs at initiation, treatment addition, and switching profiles and to measure factors influencing persistence to therapy.Methods: Retrospective observational study. Data were retrieved from the Campania Regional Database for Medication Consumption. Population consisted of patients receiving at least one prescription of ADs between January 1 and December 31, 2016. We calculated time to treatment switching or add-on as median number of days and interquartile range (IQR). Persistence rates were estimated using the Kaplan–Meier method. We used Cox regression models to estimate the likelihood of non-persistence over 1 year of follow-up. Hazard ratios and 95% confidence intervals were calculated.Results: Of 14,679 patients, 86.9% started with monotherapy and 13.1% with combination therapy. Most common initial treatment was metformin in both monotherapy and combination therapy. First-line prescription of sulfonylurea was observed in 6.9% of patients aged 60–79 years and in 10.8% of patients aged ≥80 years. Patients starting with metformin showed fewer treatment modifications (10.4%) compared to patients initiating with sulfonylureas (35.2%). Newer ADs were utilized during treatment progression. Patients who initiated with sulfonylurea were approximately 70% more likely to discontinue treatment compared to those initiated on metformin. Oldest age group (≥80 years) was more likely to be non-persistent, and likelihood of non-persistence was highest in polymedicated patients. Patients changing therapy were more likely to be persistent.Conclusions: Our results show that treatment of T2D in Italy is consistent with clinical guidelines. Even if newer ADs were utilized during disease progression, they seem not to be preferred in patients with a higher comorbidity score, although these patients could benefit from this kind of treatment. Our study highlights patients’ characteristics that might help identify those who would benefit from counselling from their health-care practitioner on better AD usage.

L'articolo presenta e riesamina criticamente i risultati centrali di una ricerca di etnografia aziendale sulla comunicazione sul posto di lavoro condotta in Germania fra il 2007 e il 2009 allo scopo di individuare i requisiti linguistico-comunicativi richiesti da mansioni non necessariamente specializzate. Scopo ultimo dell’indagine è di fornire una base empirica per lo sviluppo dell’apprendimento e insegnamento della lingua due (in questo caso il tedesco) ad adulti immigrati per un’inclusione sostenibile nel lavoro e nella società. La comunicazione è oggi parte integrante del lavoro per tutti i dipendenti, a tutti i livelli, in tutti i settori. La competenza linguistico-comunicativa è una componente di base della competenza professionale, necessaria per interagire adeguatamente per la produzione di prodotti e servizi nelle reti sociali in questione (colleghi, superiori, clienti, ecc.). Il lavoro offre possibilità non ancora sufficientemente sfruttate per l’apprendimento formale, non formale e informale della lingua due, che è al tempo stesso motivante, efficace ed efficiente. Language is work and work is language This article presents and critically reviews the main results of a study on corporate ethnography on communication in the workplace carried out in Germany between 2007 and 2009 in order to identify the linguistic and communicative requirements for not necessarily specialized tasks. The underlying aim of the study was to provide an empirical basis for the development of learning and teaching of the two languages (in this case German) to adult immigrants for sustainable inclusion in the workplace and in society. Communication is an integral part of work for employees at all levels, in all areas. Linguistic and communicative competence is a basic professional skill, necessary to manufacture products and offer services in the social networks being examined (colleagues, superiors, clients, etc.). Work offers opportunities that have not been sufficiently exploited in terms of formal, non-formal and informal learning of the two languages, which is simultaneously motivating, effective and efficient.

A novel vesicular drug delivery system has been created using only cholesteryl esters. The uncharged nature of the esters requires a formulation process that uses energy, in the form of sonication, to facilitate the cholesteryl esters formation into vesicles. The nature of the material choices renders the vesicles resistant to pH degradation between a pH of 2 and 10. Storage condition at 4°C for 9 months shows a stability of encapsulated materials as well as vesicles. The formulation process is a modified reverse phase method in which the esters are dissolved in an organic solvent, which is then removed and the aqueous component is then added with sonication in a temperature‐controlled water bath. A wide variety of materials can be encapsulated in these vesicles, which are called cholestosomes. Delivery of the cholestosome‐encapsulated materials is a function of the ester component structure and not the encapsulated molecule. Once encapsulated, the vesicles deliver the materials into cells. The potential for oral availability was explored using chylomicrons. Successful delivery of the cholestosome encapsulated into chylomicrons has enhanced the effectiveness of delivery to cells. Analytical methods have been developed to analyze the materials chosen from the cholesteryl esters as well as the encapsulated materials. Practical Applications: The creation of the cholestosome vesicle opens up completely new areas for encapsulating and delivering materials. The cholesteryl ester structure that makes up the vesicles is impervious to pH and bile salts, making cholestosomes ideal for oral delivery of drugs, such as oral insulin. Intracellular delivery of cholestosome vesicles enables multiple applications, from killing latent infections to preventing viral replication (irrespective of the virus) and delivering nucleic acid therapeutics to cure genetic disease. These vesicles pass the blood–brain barrier and could be used for treatments of Alzheimer's and related neurodegenerative disease. Cholestosomes can also be used in cosmetic formulations as the vesicles pass the dermis. They even could be used in food applications as the materials are considered generally regarded as safe. [ABSTRACT FROM AUTHOR]

In current telerobotics and telemanipulator applications, operators must perform a wide variety of tasks, often with a high risk associated with failure. A system designed to generate data-based behavioural estimations using observed operator features could be used to reduce risks in industrial teleoperation. This paper describes a non-invasive bio-mechanical feature capture method for teleoperators used to trial novel human-error rate estimators which, in future work, are intended to improve operational safety by providing behavioural and postural feedback to the operator. Operator monitoring studies were conducted in situ using the MASCOT teleoperation system at UKAEA RACE; the operators were given controlled tasks to complete during observation. Building upon existing works for vehicle-driver intention estimation and robotic surgery operator analysis, we used 3D point-cloud data capture using a commercially available depth camera to estimate an operator's skeletal pose. A total of 14 operators were observed and recorded for a total of approximately 8 h, each completing a baseline task and a task designed to induce detectable but safe collisions. Skeletal pose was estimated, collision statistics were recorded, and questionnaire-based psychological assessments were made, providing a database of qualitative and quantitative data. We then trialled data-driven analysis by using statistical and machine learning regression techniques (SVR) to estimate collision rates. We further perform and present an input variable sensitivity analysis for our selected features. [ABSTRACT FROM AUTHOR]

This article presents experiences of psychoanalytic work with open groups of children carried out in a health institution in Montevideo. The characteristics of the device used, the most common indications, the coordination style adopted, and the therapeutic effects of playing with others are detailed. [ABSTRACT FROM AUTHOR]

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BackgroundChlamydia trachomatis causes the most prevalent bacterial Sexual Transmitted Infection. In pregnant women, untreated chlamydial infections are associated with abortions, premature rupture of membranes, postpartum endometritis, low birth weight and transmission to the newborn. In Córdoba, Argentina, there is little knowledge about the prevalence of Chlamydia trachomatis in women in their third trimester of pregnancy, so, the aim of this study was to evaluate Chlamydia trachomatis prevalence and genotypes present in Cordovan pregnant women with different age and socioeconomic status.Methods and findingsDesign: prospective study. Settings: Women population from Cordoba city, Argentina. Population: Pregnant women having 35 to 37 weeks of gestation. Methods: Five hundred and nine cervical swabs were collected. Each sample was subjected to DNA extraction and PCR for Chlamydia trachomatis using primers NRO/NLO and CTP1/CTP2. Positives samples were sequenced to determine genotype. Main outcome measures: Demographic data of the patients were collected to detect a population at risk for this infection.ResultsA prevalence of 6.9% (35/509) for Chlamydia trachomatis infection was detected, with 32/295 and 3/214 from pregnant women with low or better economic resources respectively (p = 0,0001). Results showed a significantly increased rate of 11.6% (30/258) in women under 25 years compared with 2% (5/251) in patients over that age (p = 0,00003). Genotype E was the most prevalent.ConclusionsWith these results, we can say that pregnant women under 25 years old and low economic resources are one of the populations in which the screening programs of Chlamydia trachomatis should focus.