Glucose Control in Acute Myocardial Infarction: A Pilot Randomized Study Controlled by Continuous Glucose Monitoring System Comparing the Use of Insulin Glargine with Standard of Care

Background: This pilot study aimed to verify if glycemic control can be achieved in type 2 diabetes patients after acute myocardial infarction (AMI), using insulin glargine (iGlar) associated with regular insulin (iReg), compared with the standard intensive care unit protocol, which uses continuous insulin intravenous delivery followed by NPH insulin and iReg (St. Care). Patients and Methods: Patients (n = 20) within 24 h of AMI were randomized to iGlar or St. Care. Therapy was guided exclusively by capillary blood glucose (CBG), but glucometric parameters were also analyzed by blinded continuous glucose monitoring system (CGMS). Results: Mean glycemia was 141 +/- 39 mg/dL for St. Care and 132 +/- 42 mg/dL for iGlar by CBG or 138 +/- 35 mg/dL for St. Care and 129 +/- 34 mg/dL for iGlar by CGMS. Percentage of time in range (80-180 mg/dL) by CGMS was 73 +/- 18% for iGlar and 77 +/- 11% for St. Care. No severe hypoglycemia (<= 40 mg/dL) was detected by CBG, but CGMS indicated 11 (St. Care) and seven (iGlar) excursions in four subjects from each group, mostly in sulfonylurea users (six of eight patients). Conclusions: This pilot study suggests that equivalent glycemic control without increase in severe hyperglycemia may be achieved using iGlar with background iReg. Data outputs were controlled by both CBG and CGMS measurements in a real-life setting to ensure reliability. Based on CGMS measurements, there were significant numbers of glycemic excursions outside of the target range. However, this was not detected by CBG. In addition, the data indicate that previous use of sulfonylurea may be a potential major risk factor for severe hypoglycemia irrespective of the type of insulin treatment.

Leukocyte- and Platelet-Rich Fibrin (L-PRF) for Long-Term Delivery of Growth Factor in Rotator Cuff Repair: Review, Preliminary Results and Future Directions

Surgical repair of the rotator cuff repair is one of the most common procedures in orthopedic surgery. Despite it being the focus of much research, the physiological tendon-bone insertion is not recreated following repair and there is an anatomic non-healing rate of up to 94%. During the healing phase, several growth factors are upregulated that induce cellular proliferation and matrix deposition. Subsequently, this provisional matrix is replaced by the definitive matrix. Leukocyte- and platelet-rich fibrin (L-PRF) contain growth factors and has a stable dense fibrin matrix. Therefore, use of LPRF in rotator cuff repair is theoretically attractive. The aim of the present study was to determine 1) the optimal protocol to achieve the highest leukocyte content; 2) whether L-PRF releases growth factors in a sustained manner over 28 days; 3) whether standard/gelatinous or dry/compressed matrix preparation methods result in higher growth factor concentrations. 1) The standard L-PRF centrifugation protocol with 400 x g showed the highest concentration of platelets and leukocytes. 2) The L-PRF clots cultured in medium showed a continuous slow release with an increase in the absolute release of growth factors TGF-β1, VEGF and MPO in the first 7 days, and for IGF1, PDGF-AB and platelet activity (PF4=CXCL4) in the first 8 hours, followed by a decrease to close to zero at 28 days. Significantly higher levels of growth factor were expressed relative to the control values of normal blood at each culture time point. 3) Except for MPO and the TGFβ-1, there was always a tendency towards higher release of growth factors (i.e., CXCL4, IGF-1, PDGF-AB, and VEGF) in the standard/gelatinous- compared to the dry/compressed group. L-PRF in its optimal standard/gelatinous-type matrix can store and deliver locally specific healing growth factors for up to 28 days and may be a useful adjunct in rotator cuff repair.

Scale Up of PLA Nanoparticle Synthesis by Solvent Displacement and Functionalization of the Particles with a Silica Shell for Targeted Drug Delivery Applications

Biodegradable polymer nanoparticles have the properties necessary to address many of the issues associated with current drug delivery techniques including targeted and controlled delivery. A novel drug delivery vehicle is proposed consisting of a poly(lactic acid) nanoparticle core, with a functionalized, mesoporous silica shell. In this study, the production of PLA nanoparticles is investigated using solvent displacement in both a batch and continuous manner, and the effects of various system parameters are examined. Using Pluronic F-127 as the stabilization agent throughout the study, PLA nanoparticles are produced through solvent displacement with diameters ranging from 200 to 250 nm using two different methods: dropwise addition and in an impinging jet mixer. The impinging jet mixer allows for easy scale-up of particle production. The concentration of surfactant and volume of quench solution is found to have minimal impact on particle diameter; however, the concentration of PLA is found to significantly impact the diameter mean and polydispersity. In addition, the stability of the PLA nanoparticles is observed to increase as residual THF is evaporated. Lastly, the isolated PLA nanoparticles are coated with a silica shell using the Stöber Process. It is found that functionalizing the silica with a phosphonic silane in the presence of excess Pluronic F-127 decreases coalescence of the particles during the coating process. Future work should be conducted to fine-tune the PLA nanoparticle synthesis process by understanding the effect of other system parameters and in synthesizing mesoporous silica shells.

Analysis, monitoring, and management of quality of experience in video delivery services over IP

Esta tesis estudia la monitorización y gestión de la Calidad de Experiencia (QoE) en los servicios de distribución de vídeo sobre IP. Aborda el problema de cómo prevenir, detectar, medir y reaccionar a las degradaciones de la QoE desde la perspectiva de un proveedor de servicios: la solución debe ser escalable para una red IP extensa que entregue flujos individuales a miles de usuarios simultáneamente. La solución de monitorización propuesta se ha denominado QuEM(Qualitative Experience Monitoring, o Monitorización Cualitativa de la Experiencia). Se basa en la detección de las degradaciones de la calidad de servicio de red (pérdidas de paquetes, disminuciones abruptas del ancho de banda...) e inferir de cada una una descripción cualitativa de su efecto en la Calidad de Experiencia percibida (silencios, defectos en el vídeo...). Este análisis se apoya en la información de transporte y de la capa de abstracción de red de los flujos codificados, y permite caracterizar los defectos más relevantes que se observan en este tipo de servicios: congelaciones, efecto de “cuadros”, silencios, pérdida de calidad del vídeo, retardos e interrupciones en el servicio. Los resultados se han validado mediante pruebas de calidad subjetiva. La metodología usada en esas pruebas se ha desarrollado a su vez para imitar lo más posible las condiciones de visualización de un usuario de este tipo de servicios: los defectos que se evalúan se introducen de forma aleatoria en medio de una secuencia de vídeo continua. Se han propuesto también algunas aplicaciones basadas en la solución de monitorización: un sistema de protección desigual frente a errores que ofrece más protección a las partes del vídeo más sensibles a pérdidas, una solución para minimizar el impacto de la interrupción de la descarga de segmentos de Streaming Adaptativo sobre HTTP, y un sistema de cifrado selectivo que encripta únicamente las partes del vídeo más sensibles. También se ha presentado una solución de cambio rápido de canal, así como el análisis de la aplicabilidad de los resultados anteriores a un escenario de vídeo en 3D. ABSTRACT This thesis proposes a comprehensive approach to the monitoring and management of Quality of Experience (QoE) in multimedia delivery services over IP. It addresses the problem of preventing, detecting, measuring, and reacting to QoE degradations, under the constraints of a service provider: the solution must scale for a wide IP network delivering individual media streams to thousands of users. The solution proposed for the monitoring is called QuEM (Qualitative Experience Monitoring). It is based on the detection of degradations in the network Quality of Service (packet losses, bandwidth drops...) and the mapping of each degradation event to a qualitative description of its effect in the perceived Quality of Experience (audio mutes, video artifacts...). This mapping is based on the analysis of the transport and Network Abstraction Layer information of the coded stream, and allows a good characterization of the most relevant defects that exist in this kind of services: screen freezing, macroblocking, audio mutes, video quality drops, delay issues, and service outages. The results have been validated by subjective quality assessment tests. The methodology used for those test has also been designed to mimic as much as possible the conditions of a real user of those services: the impairments to evaluate are introduced randomly in the middle of a continuous video stream. Based on the monitoring solution, several applications have been proposed as well: an unequal error protection system which provides higher protection to the parts of the stream which are more critical for the QoE, a solution which applies the same principles to minimize the impact of incomplete segment downloads in HTTP Adaptive Streaming, and a selective scrambling algorithm which ciphers only the most sensitive parts of the media stream. A fast channel change application is also presented, as well as a discussion about how to apply the previous results and concepts in a 3D video scenario.

Chronic control of high blood pressure in the spontaneously hypertensive rat by delivery of angiotensin type 1 receptor antisense.

The renin-angiotensin system plays a crucial role in the development and establishment of the hypertensive state in the spontaneously hypertensive (SH) rat. Interruption of this system's activity by pharmacological means results in the lowering of blood pressure (BP) and control of hypertension. However, such means are temporary and require the continuous use of drugs for the control of this pathophysiological state. Our objective in this investigation was to determine if a virally mediated gene-transfer approach using angiotensin type 1 receptor antisense (AT1R-AS) could be used to control hypertension on a long-term basis in the SH rat model of human essential hypertension. Injection of viral particles containing AT1R-AS (LNSV-AT1R-AS) in 5-day-old rats resulted in a lowering of BP exclusively in the SH rat and not in the Wistar Kyoto normotensive control. A maximal anti-hypertensive response of 33 +/- 5 mmHg was observed, was maintained throughout development, and still persisted 3 months after administration of LNSV-AT1R-AS. The lowering of BP was associated with the expression of AT1R-AS transcript and decreases in AT1-receptor in many peripheral angiotensin II target tissues such as mesenteric artery, adrenal gland, heart, and kidney. Attenuation of angiotensin II-stimulated physiological actions such as contraction of aortic rings and increase in BP was also observed in the LNSV-AT1R-AS-treated SH rat. These observations show that a single injection of LNSV-AT1R-AS normalizes BP in the SH rat on a long-term basis. They suggest that such a gene-transfer strategy can be successfully used to control the development of hypertension on a permanent basis.

Irreversible inactivation of interleukin 2 in a pump-based delivery environment.

The physical stability of pharmaceutical proteins in delivery environments is a critical determinant of biological potency and treatment efficacy, and yet it is often taken for granted. We studied both the bioactivity and physical stability of interleukin 2 upon delivery via continuous infusion. We found that the biological activity of the delivered protein was dramatically reduced by approximately 90% after a 24-hr infusion program. Only a portion of these losses could be attributed to direct protein deposition on the delivery surfaces. Analysis of delivered protein by size exclusion chromatography gave no indication of insulin-like, surface-induced aggregation phenomena. Examination of the secondary and tertiary structure of both adsorbed and delivered protein via Fourier-transform infrared spectroscopy, circular dichroism, and fluorescence spectroscopy indicated that transient surface association of interleukin 2 with the catheter tubing resulted in profound, irreversible structural changes that were responsible for the majority of the biological activity losses.

Alginates as therapeutic and drug delivery systems

Alginate is widely used as a viscosity enhancer in many different pharmaceutical formulations. The aim of this thesis is to quantitatively describe the functions of this polyelectrolyte in pharmaceutical systems. To do this the techniques used were Viscometry, Light Scattering, Continuous and Oscillatory Shear Rheometry, Numerical Analysis and Diffusion. Molecular characterization of the Alginate was carried out using Viscometry and Light Scattering to determine the molecular weight, the radius of gyration, the second virial coefficient and the Kuhn statistical segment length. The results showed good agreement with similar parameters obtained in previous studies. By blending Alginate with other polyelectrolytes, Xanthan Gum and 'Carbopol', in various proportions and with various methods of low and high shear preparation, a very wide range of dynamic rheological properties was found. Using oscillatory testing, the parameters often varied over several decades of magnitude. It was shown that the determination of the viscous and elastic components is particularly useful in describing the rheological 'profiles' of suspending agent blends and provides a step towards the non-empirical formulation of pharmaceutical disperse systems. Using numerical analysis of equations describing planar diffusion, it was shown that the analysis of drug release profiles alone does not provide unambiguous information about the mechanism of rate control. These principles were applied to the diffusion of Ibuprofen in Calcium Alginate gels. For diffusion in such non-Newtonian systems, emphasis was placed on the use of the elastic as well as the viscous component of viscoelasticity. It was found that the diffusion coefficients were relatively unaffected by increases in polymer concentration up to 5 per cent, yet the elasticities measured by oscillatory shear rheometry were increased. This was interpreted in the light of several theories of diffusion in gels.

Functionalised particles using dry powder coating in pharmaceutical drug delivery:promises and challenges

Introduction: Production of functionalised particles using dry powder coating is a one-step, environmentally friendly process that paves the way for the development of particles with targeted properties and diverse functionalities. Areas covered: Applying the first principles in physical science for powders, fine guest particles can be homogeneously dispersed over the surface of larger host particles to develop functionalised particles. Multiple functionalities can be modified including: flowability, dispersibility, fluidisation, homogeneity, content uniformity and dissolution profile. The current publication seeks to understand the fundamental underpinning principles and science governing dry coating process, evaluate key technologies developed to produce functionalised particles along with outlining their advantages, limitations and applications and discusses in detail the resultant functionalities and their applications. Expert opinion: Dry particle coating is a promising solvent-free manufacturing technology to produce particles with targeted functionalities. Progress within this area requires the development of continuous processing devices that can overcome challenges encountered with current technologies such as heat generation and particle attrition. Growth within this field requires extensive research to further understand the impact of process design and material properties on resultant functionalities.

Strumenti DevOps per Applicazioni Web con Federazione di Identità basata su SSO

Pratiche agili come CI, CD e movimenti come DevOps sono ora più che mai rilevanti nel settore del software. Il mercato del software, le esigenze aziendali e gli utenti finali richiedono rilasci sempre più rapidi e non sono più disposti ad aspettare mesi o anni per nuove funzionalità. Le pratiche citate hanno lo scopo di aiutare l'organizzazione a riuscire a lungo termine a soddisfare le esigenze degli utenti, rivendicando vantaggi in molti aspetti del processo di consegna. Sfortunatamente, molte aziende, pur adottando pratiche più agili, incontrano sfide che possono essere difficili da superare, a volte richiedono uno sforzo aggiuntivo e una ristrutturazione dell'organizzazione. Questa tesi è inserita in un contesto di adozione DevOps di un'azienda di consulenza informatica, che cerca di migliorare il proprio processo di delivery rendendolo più fluido e introducendo pratiche di automazione. Lo studio è stato condotto come etnografia, con il laureando che è entrato in azienda per un periodo di sei mesi lavorando fianco a fianco con le persone coinvolte nel processo. Il processo aziendale è stato studiato e analizzato, individuando le problematiche che rallentavano il processo di consegna e pianificando i successivi miglioramenti pratici.

Influence Of Delivery Method On Neuroprotection By Bone Marrow Mononuclear Cell Therapy Following Ventral Root Reimplantation With Fibrin Sealant.

The present work compared the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion (VRA) and reimplantation. For that, female adult Lewis rats were divided into the following groups: avulsion only, reimplantation with fibrin sealant; root repair with fibrin sealant associated with mononuclear cells; and repair with fibrin sealant and injected mononuclear cells. Cell therapy resulted in greater survival of spinal motoneurons up to four weeks post-surgery, especially when mononuclear cells were added to the fibrin glue. Injection of mononuclear cells to the lateral funiculus yield similar results to the reimplantation alone. Additionally, mononuclear cells added to the fibrin glue increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. Regarding the motor recovery, evaluated by the functional peroneal index, as well as the paw print pressure, cell treated rats performed equally well as compared to reimplanted only animals, and significantly better than the avulsion only subjects. The results herein demonstrate that mononuclear cells therapy is neuroprotective by increasing levels of brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF). Moreover, the use of fibrin sealant mononuclear cells delivery approach gave the best and more long lasting results.

Beliefs And Misbeliefs About Current Interventions During Labor And Delivery In Brazil.

30 Suppl 1

[gestational Diabetes: Follow-up After Delivery.]

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Solid Lipid Nanoparticles As Nucleic Acid Delivery System: Properties And Molecular Mechanisms.

Solid lipid nanoparticles (SLNs) have been proposed in the 1990s as appropriate drug delivery systems, and ever since they have been applied in a wide variety of cosmetic and pharmaceutical applications. In addition, SLNs are considered suitable alternatives as carriers in gene delivery. Although important advances have been made in this particular field, fundamental knowledge of the underlying mechanisms of SLN-mediated gene delivery is conspicuously lacking, an imperative requirement in efforts aimed at further improving their efficiency. Here, we address recent advances in the use of SLNs as platform for delivery of nucleic acids as therapeutic agents. In addition, we will discuss available technology for conveniently producing SLNs. In particular, we will focus on underlying molecular mechanisms by which SLNs and nucleic acids assemble into complexes and how the nucleic acid cargo may be released intracellularly. In discussing underlying mechanisms, we will, when appropriate, refer to analogous studies carried out with systems based on cationic lipids and polymers, that have proven useful in the assessment of structure-function relationships. Finally, we will give suggestions for improving SLN-based gene delivery systems, by pointing to alternative methods for SLNplex assembly, focusing on the realization of a sustained nucleic acid release.

Chronic Continuous Exenatide Infusion Does Not Cause Pancreatic Inflammation And Ductal Hyperplasia In Non-human Primates.

In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67-positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67-positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67-positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30-positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates.

Delivery Of A Urology Online Course Using Moodle Versus Didactic Lectures Methods.

To subjectively and objectively compare an accessible interactive electronic library using Moodle with lectures for urology teaching of medical students. Forty consecutive fourth-year medical students and one urology teacher were exposed to two teaching methods (4 weeks each) in the form of problem-based learning: - lectures and - student-centered group discussion based on Moodle (modular object-oriented dynamic learning environment) full time online delivered (24/7) with video surgeries, electronic urology cases and additional basic principles of the disease process. All 40 students completed the study. While 30% were moderately dissatisfied with their current knowledge base, online learning course delivery using Moodle was considered superior to the lectures by 86% of the students. The study found the following observations: (1) the increment in learning grades ranged from 7.0 to 9.7 for students in the online Moodle course compared to 4.0-9.6 to didactic lectures; (2) the self-reported student involvement in the online course was characterized as large by over 60%; (3) the teacher-student interaction was described as very frequent (50%) and moderately frequent (50%); and (4) more inquiries and requisitions by students as well as peer assisting were observed from the students using the Moodle platform. The Moodle platform is feasible and effective, enthusing medical students to learn, improving immersion in the urology clinical rotation and encouraging the spontaneous peer assisted learning. Future studies should expand objective evaluations of knowledge acquisition and retention.