Implantable controlled release devices for BMP-7 delivery and suppression of glioblastoma initiating cells

Designing therapeutic devices capable of manipulating glioblastoma initiating cells (GICs) is critical to stop tumor recurrence and its associated mortality. Previous studies have indicated that bone morphogenetic protein-7 (BMP-7) acts as an endogenous suppressor of GICs, and thus, it could become a treatment for this cancer. In this work, we engineer an implantable microsphere system optimized for the controlled release of BMP-7 as a bioinspired therapeutic device against GICs. This microsphere delivery system is based on the formation of a heparin- BMP-7 nanocomplex, first coated with Tetronic® and further entrapped in a biodegradable polyester matrix. The obtained microspheres can efficiently encapsulate BMP-7, and release it in a controlled manner with minimum burst effect for over two months while maintaining protein bioactivity. Released BMP-7 showed a remarkable capacity to stop tumor formation in a GICs cell culture model, an effect that could be mediated by forced reprogramming of tumorigenic cells towards a non-tumorigenic astroglial lineage.This work was financed by Ministerio de Ciencia e Innovación, Programa de Investigación en Salud (PS09/1786) and Xunta de Galicia (EM2013/042). ERN acknowledges a grant from Agencia Española de Cooperación Internacional. MF had a contract from Asociación Española contra el Cáncer. NC and MGF acknowledge their Isidro Parga Pondal contracts from Xunta de Galicia. Dr. Helena Mira and Dr. Pilar González advised us on the neurosphere culture model and the cell testing assays. Katrin Viertel and Ida Fejos provided technical help at the preformulation stages. Prof. Anxo Vidal and Erea Borrajo provided technical help for FACS analysis. We thank Prof. Maria J. Alonso for the supporting group infrastructure

Aortic perforation by active-fixation atrial pacing lead: an unusual but serious complication

Perforation of a cardiac chamber is an infrequent but serious sequela of pacemaker lead implantation. An even rarer event is the perforation of the aorta by a protruding right atrial wire. We present here the first case in the medical literature of aortic perforation as a sequela to the implantation of a cardiac resynchronization therapy defibrillator. The patient was a 54-year-old man with idiopathic dilated cardiomyopathy who underwent the implantation of a defibrillator, with no apparent sequelae. Six hours after the procedure, he experienced cardiac tamponade and required urgent open-chest surgery. The pericardial effusion was found to be caused by mechanical friction of a protruding right atrial wire on the aortic root. The aortic root and the atrial wall were both repaired with Prolene suture, which achieved complete control of the bleeding. There was no need to reposition the atrial wire. The patient had a good postoperative recovery

Therapeutic education and functional readaptation in obese patients on a waiting list for total knee replacement. A case-control study

Background Studies show patients with knee osteoarthritis (OA) on waiting list for total knee replacement (TKR) underused conservative treatment, did not adhere to clinical guidelines on knee OA management, and potentially had earlier surgery and a higher risk of revisions. Therapeutic education and functional readaptation (TEFR) plus conventional therapy in waiting list patients improved function and adherence. TKR patients are often obese, negatively influencing TKR results, many patients are dissatisfied after TKR, and around 14% of TKR are inappropriate..

Subjectivity and symptom in Uruguayan interior hospitals: scope of the role of the psychology resident

El presente trabajo pretende dar visibilidad al complejo y novedoso escenario en el que se inserta el Residente de Psicología en Uruguay, cuando ingresa a trabajar en un Hospital General, tomando las experiencias en cuatro hospitales del interior del país. Las experiencias a transmitir son fruto de nuestra inserción en ASSE (Administración de los Servicios de Salud del Estado) a través del Programa de Practicantes y Residentes de Psicología (PPRP) por el convenio entre ASSE y la Facultad de Psicología de la Universidad de la República (2009). Conjuntamente transitando la Especialización de Psicología en Servicios de Salud (Muniz, 2013) que se enmarca en el Sistema Nacional Integrado de Salud (2007) y la nueva Ley de Salud Mental (2017). Interesa problematizar acerca de los obstáculos y facilitadores para el ejercicio del rol de Residente de Psicología en los Servicios de Salud. Así como también intercambiar en relación al valioso aporte que podemos realizar desde nuestra disciplina en los equipos de salud hospitalarios, contribuyendo a un abordaje interdisciplinario. Se propone tomar como líneas de análisis de las subjetividades y presentaciones sintomáticas actuales, los efectos que produce la proximidad del fallecimiento de un paciente en la institución y quienes trabajan en ella, pero sobre todo en los usuarios y sus familias. ¿Cómo se transitan los procesos de enfermedad, la aceptación de un diagnóstico médico?, ¿Qué lugar se le da a la expresión y al trabajo sobre el sufrimiento, las emociones, la angustia, el dolor psíquico? ¿Cuál es el rol del Residente de Psicología ante estos nuevos escenarios en Uruguay?The present work aims to give visibility to the complex and novel scenario in which the Psychology Resident in Uruguay is inserted, when he enters to work in a General Hospital, taking the experiences in four hospitals of the interior of the country.The experiences to be transmitted are the result of our insertion in ASSE (Administration of State Health Services) through the Program of Practitioners and Residents of Psychology (PPRP) by the agreement between ASSE and the Faculty of Psychology of the University of the Republic (2009). Jointly transiting the Specialization of Psychology in Health Services (Muniz, 2013), that is part of the National Integrated Health System (2007) and the new Mental Health Law (2017). It is interesting to problematize about the obstacles and facilitators for the exercise of the role of Resident of Psychology in Health Services. As well as exchange in relation to the valuable contribution we can make from our discipline in hospital health teams, contributing to an interdisciplinary approach. It is proposed to take as a line of analysis the subjectivities and current symptomatic presentations, the effects produced by the proximity of the death of a patient in the institution and those who work in it, but especially in users and their families. How is the disease processes, the acceptance of a medical diagnosis transited? What place is given to the expression and work on suffering, emotions, anguish, psychic pain? What is the role of the Psychology Resident in these new scenarios in Uruguay?Facultad de Psicologí

Knee osteoarthritis and periarticular structure quantified by ultrasound. A case-control study

Background Assessment of pain and physical function is complex in patients with knee osteoarthritis (OA), as standard criteria are lacking.A previous study examining correlations between functional capacity and pain (WOMAC) and anthropometric characteristics and periarticular knee structure (quantified by ultrasound imaging) in females with knee OA found increased quadriceps muscle density was associated with higher functional disability and pain scores, suggesting that not only joint wear and symptom severity are involved and more objective measures are necessary..

Total knee replacement from the patient's perspective. A qualitative study

Total knee replacement (TKR) is effective in relieving pain and improving function in patients with severe osteoarthritis (OA) However, studies report that 14-30% of patients are dissatisfied with the result and do not achieve the expected benefits, especially in function. Objectives: To examine the factors influencing decision-making before TKR. Methods: We made a phenomenological study of the determinants that lead patients to accept, delay or reject TKR (this study is part of a larger study). Demographic and clinical data were collected and pain intensity measured by the WOMAC scale. Focus groups were conducted and the results transcribed and analysed using the 4-stage analysis of qualitative data according to Ritchie, Spencer and O'Connor (2003). Results: 12 patients (9 female, mean age 71.58 + 6.02 years, BMI 37.43 + 5.32, mean comorbidities 6.73 + 2.19 and mean WOMAC pain 14.9 + 8.89, function 15.77 + 8.6, total 15. 71 + 8. 22) were included: 6 had received, 4 were waiting for and 2 had rejected TKR. Focus groups identified widespread pain (pain intensity functional limitations), causal beliefs and perceptions (OA a natural process associated with age, obesity, physical work, sport) mood (importance of optimism), professional-user relationship (communication, experience of OA) expectations (need for surgery conditioned by pain, lost function, surgical risks), and social support (promotion of healthy habits and adherence conditioned by family and social support) as factors influencing attitudes to undergoing TKR. Conclusions: The process of deciding to undergo TKR is complex and influenced by multiple factors. TKR improves a small proportion of an aging painful body. Our results suggest the need of care before and after TKR, psychosocial support and preventive and educational programmes. References: Ritchie J, Spencer L, O'Connor W. Carrying out qualitative analysis. In Ritchie J. and Lewis J. (eds.) guide for social science students and researchers Oaks; New Delhi. Qualitative research practice: A. Sage: London; Thousand; 2003 Disclosure of Interest: None declare

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake