Spontaneous bilayer wrapping of virus particles by a phospholipid Langmuir monolayer.

We report here the spontaneous formation of lipid-bilayer-wrapped virus particles, following the injection of "naked" virus particles into the subphase of a Langmuir trough with a liquid monolayer of lipids at its air-water interface. The virus particles are those of the well-studied cowpea chlorotic mottle virus, CCMV, which are negatively charged at the pH 6 of the subphase; the lipids are a 9:1 mix of neutral DMPC and cationic CTAB molecules. Before adding CCMV particles to the subphase we establish the mixed lipid monolayer in its liquid-expanded state at a fixed pressure (17.5 mN/m) and average area-per-molecule of (41Å2). Keeping the total area fixed, the surface pressure is observed to decrease at about 15 h after adding the virus particles in the subphase; by 37 h it has dropped to zero, corresponding to essentially all the lipid molecules having been removed from the air-water interface. By collecting particles from the subphase and measuring their sizes by atomic force microscopy, we show that the virus particles have been wrapped by lipid bilayers (or by two lipid bilayers). These results can be understood in terms of thermal fluctuations and electrostatic interactions driving the wrapping of the anionic virus particles by the cationic lipids. Spontaneous acquisition by a virus particle of, first, a hydrophobic lipid monolayer envelope and, then, a hydrophilic lipid bilayer envelope, as it interacts from the subphase with an oppositely charged Langmuir monolayer.

Characterization of proteases in the seminal plasma and spermatozoa of llama.

Camelids' semen has peculiar characteristics that differentiate it from other species, including the highly viscous aspect of seminal plasma that greatly difficult sperm manipulation and the development of techniques such as cryopreservation, artificial insemination, and/or in vitro fertilization. The presence of proteases in the seminal plasma is responsible for semen liquefaction, and sperm functionality to achieve fertilization. The enzymatic and molecular composition of the semen of llama remains unknown. Therefore, the goal of the study was to characterize the protease activity and composition of the seminal plasma and sperm of llama semen. The proteolytic activity was performed using gelatine zymography and the composition by mass-spectrometry. Metallo-proteases were the major source of gelatinolytic activity in seminal plasma, while serine-peptidases were the main enzymes of sperm cells. Matrix Metalloproteinase 2 (MMP2) was the most prominent metallo-protease of llama seminal plasma characterized under the exposure of different inhibitors (EDTA and benzamidine) and by a specific immunodetection. Moreover, the prostate and epididymis were identified as potential sites of its synthesis and secretion. Outstandingly, this metalloproteinase was undetectable in llama sperm. Regarding, the molecular composition of semen by mass-spectrometry, 4 metallo-, 9 serine-, 8 threonine-, and 1 aspartic-peptidases were identified alongside 15 regulators in the sperm cell; where 24 were directly or indirectly interacting. Whereas 6 metallo-, 12 serine-, 3 cysteine-, and 1 aspartic-peptidases were identified, besides 7 inhibitors and 5 regulators in llama seminal plasma where 30 of them were directly or indirectly interconnected. This is the first study describing a partial degradome of llama seminal plasma and spermatozoa suggesting significant differences especially the absence of MMP2 in spermatozoa in contrast to data observed in other species. The characterization of proteases in llama semen will provide a better understanding of the molecular mechanisms involved in the in vivo or in vitro fertilization process in this species.

Spanish validation of the Stigma of Occupational Stress Scale for Doctors (SOSS-D) and factors associated with physician burnout.

OBJECTIVES: The aim of this study was to investigate the psychometric properties of the Spanish version of the Stigma of Occupational Stress Scale for Doctors (SOSS-D) and the factors associated with Physician Burnout in Paraguay. METHODS: Participants included 747 Paraguayan healthcare workers, aged 24-77 years old, of both sexes. SOSS-D was translated into Spanish and validated through an exploratory and confirmatory factor analysis. Participants were also scored with the Oldenburg Burnout Inventory (OLBI), the CAGE questionnaire, and the stigma subscale of the Perceived Barriers to Psychological Treatment (PBPT) measure. RESULTS: Three factors had a raw eigenvalue greater than 1, and explained 61.7% of total variance. The confirmatory analysis confirmed that the scale is three-dimensional. The model adjustment was good, according to all fit indices. OLBI results indicate clinically significant disengagement in 85.9% and clinically significant exhaustion in 91.6% of participants. Of the 747 participants, 57.6% reported alcoholic beverage consumption and among those, 19.3% had problematic alcohol consumption according to the CAGE questionnaire. The correlation between SOSS-D and the stigma subscale of the PBPT was statistically significant (r = 0.245, p < 0.001). CONCLUSIONS: The Spanish version of the SOSS-D was found to have good psychometric properties and adequately reproduces the three-dimensional model of the original English version.

Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.

Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines.

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.

Impact of Hurricane Maria on mold levels in the homes of Piñones, Puerto Rico.

Hurricane Maria struck Puerto Rico on September 20, 2017, severely impacting the island. In order to quantify the impact of the hurricane on the indoor air quality, we evaluated the fungal levels in households (n = 20) of the Piñones community for the period of 2018 and 2019. For each dust sample collected, the 36 Environmental Relative Moldiness Index (ERMI) molds were quantified using qPCR assays, and then Shannon Diversity Index (SDI) values for the fungal populations were calculated. Homes were in five separate regions, regarding their proximity in the studied area. We found that for regions with reported least water damage, the SDI values were similar for both sampled years, but for regions that reported mid-to-high level of damage region, the SDI values were significantly higher. Households that reported remediation actions between the two sampled years showed similar values for the second year as those that did not report any major impact. Our preliminary data provides insights into the significant impacts of hurricanes into indoor fungal environment.

Socio-academic Factors Influencing Knowledge About Organ Donation among Medical Students in Paraguay, 2018.

Organ donation currently is an extremely important issue in public health. Proper information about the details of this topic is extremely important, but is not yet widespread among the public. This study was carried out with the aim to determine the level of knowledge about organ donation among medical students in Paraguay and associated socio-academic factors influencing their level of knowledge. This was an analytical cross-sectional study, based on a multicenter survey among university medical students. About 68.7% (235) of the respondents were preclinical students doing basic sciences. Two aspects were evaluated, the knowledge regarding the donation of the organs and the socio-academic factors, then both the aspects were evaluated through bivariate and multivariate analyses. There were 342 respondents with a median age of 22 years (interquartile range: 20-23 years) of which 263 (77%) were women. One hundred and eighty-eight (55%) reported not knowing the law that protects and regulates the activities of organ and tissue donation in Paraguay. In the multivariate analysis, the highest frequency of a good level of knowledge of organ donation occurred in those who were older [RPA: 1.07, 95% confidence interval (CI): 1.02-1.12, P = 0.007] and in two of the universities evaluated (both with values P <0.012). On the contrary, those who were preclinical students, in general, had a lower level of knowledge of organ donation (RPa: 0.61, 95% CI: 0.46-0.79; value P <0.001). Our findings denote relatively a poor knowledge of organ donation in some socio-academic subsets. Therefore, it is important to develop strategies to increase the knowledge about the subject, by creating opportunities by way of discussions and debates among the students at all academic levels and also by conducting academic conferences on the subject.

Correction to: Human Papillomavirus and Factors Associated with Recurrence in Sinonasal Inverted Papillomas from Poland and Spain.

The original version of this article unfortunately contained a mistake. Three values in Table 1 were incorrect. In "months of recurrence", range row, the intervals should be in numbers. They should read as 3-83 instead of Mar-83, 9-83 instead of Sep-83 and 3-36 instead of Mar-36. The corrected Table 1 is given below. The original article has been corrected.

Human Papillomavirus and Factors Associated with Recurrence in Sinonasal Inverted Papillomas from Poland and Spain.

Sinonasal inverted papilloma (SNIP) is a benign but locally aggressive tumor that has a tendency for recurrence and malignant transformation. The role of human papillomavirus (HPV) in SNIP is controversial. To determine the HPV-DNA prevalence and type distribution in SNIP in two different geographic areas and assess the association between SNIP recurrence and HPV infection, as well as additional potential etiologic factors. Two retrospective cohorts of SNIP patients from Poland and Spain were evaluated. Demographic, tobacco/alcohol use, clinical, and follow-up data were collected. All samples were subject to histopathologic evaluation, DNA quality control, and HPV-DNA detection by PCR. HPV-DNA positive samples and a random sample of HPV-DNA negative cases were further subject to p16INK4a analysis. Proportional-hazards models were used to evaluate the risk of recurrence by selected variables. Seventy-nine SNIP patients (46 from Spain diagnosed between 1995 and 2014, and 33 from Poland diagnosed between 2012 and 2017) were included in the study. HPV-DNA was detected in four patients (5.1%), two from each region, and all four were positive for the HPV11 subtype. Seventeen patients (21.5%) experienced recurrence, with a median time to recurrence of 14 months. No association was identified between lesional HPV-DNA positivity, toxic habits, Krouse stage, or malignant transformation and a higher risk of recurrence. The low prevalence of HPV-DNA in SNIPs suggests that HPV is not a main etiology for development of these lesions. With a lack of association between the evaluated factors and recurrence, further research with larger number of patients and additional biomarkers is warranted to further understand predisposing risk factors.

BOMET-QoL-10 questionnaire for breast cancer patients with bone metastasis: the prospective MABOMET GEICAM study.

BACKGROUND: Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. METHODS: Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. RESULTS: Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0-1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. CONCLUSIONS: BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients. TRIAL REGISTRATION: NCT03847220. Retrospectively registered on clinicaltrials.gov (February the 20th 2019).

Euploid blastocysts implant irrespective of their morphology after NGS-(PGT-A) testing in advanced maternal age patients.

PURPOSE: Does blastocyst morphology following euploid elective single embryo transfer (eSET) after preimplantation genetic testing for aneuploidies (PGT-A) via next generation sequencing impact clinical outcome? METHODS: Two hundred ninety-six patients underwent PGT-A. Of 1549 blastocysts, 1410 blastocysts had a conclusive result after PGT-A and were included for analysis. An eSET policy was followed in a frozen embryo replacement cycle. A total of 179 euploid blastocysts were thawed and transferred. Clinical outcomes were categorized in four different embryo quality groups: excellent, good, average and poor. RESULTS: Euploidy rate was 19/36 (52.7%, 95% CI 37-68), 199/470 (42.3%, 95% CI 38-47), 156/676 (23.0%, 95% CI 20-26) and 39/228 (17.1%, 95% CI 13-23) in the excellent, good, average and poor quality blastocyst groups, respectively. Fitted logistic regression analysis taking into account the following covariables: female, age, embryo chromosomal status and day of blastocyst development/biopsy showed that morphology was predictive of the comprehensive chromosome screening result (p < 0.05). A logistic regression analysis was also performed on clinical outcomes taking into account the effect of blastocyst morphology and day of blastocyst development/biopsy. None of the parameters were shown to be significant, suggesting morphology and day of blastocyst development/biopsy do not reduce the competence of euploid embryos (p > 0.05). CONCLUSIONS: After eSET, implantation rate was 80-86%; live birth rate per embryo transfer was 60-73% and clinical miscarriage rate was found to be < 10% and were not significantly affected by the embryo morphology. Results are concordant with those reported when using aCGH and highlights the competence of poor-quality euploid embryos.

Inadequate response to imatinib treatment in chronic myeloid leukemia due to a drug interaction with phenytoin.

Imatinib mesylate and the newer BCR-ABL tyrosine kinase inhibitors are the standard therapy for chronic myeloid leukemia. Although these are remarkably effective drugs, some mechanisms of resistance have been identified including drug-to-drug interactions. Here we present the case of a chronic myeloid leukemia patient with an inadequate response to imatinib due to concurrent phenytoin administration. Conspicuously low imatinib plasma trough levels were documented. Imatinib dose was increased from 400 to 800 mg with good response. In conclusion, drug-to-drug interactions should be ruled out in cases of resistance to tyrosine kinase inhibitor treatment. Potent inducers of cytochrome P450 isoenzyme CYP3A4, as phenytoin, could induce inadequate responses due to increased imatinib clearance and low imatinib trough plasma levels. Thus, this interaction should be avoided. When this is not possible, dose escalation of imatinib and measurement of plasma levels, if available, is recommended.

Metodología activa en el Estudio de Caso para desarrollo del pensamiento crítico y sentido ético / Case Study active methodology for the development of critical thinking and ethical sense skills / Metodologia ativa no Estudo de Caso para desenvolvimento do pensamento crítico e sentido ético

Introducción Un modelo centrado en la enseñanza-aprendizaje supone un cambio en la docencia universitaria, esto implica el uso de metodologías activas con enfoque en el desarrollo de habilidades como el pensamiento crítico (PC) y sentido ético (SE). Objetivo Evaluar el impacto de la implementación del estudio de caso (EC) en el desarrollo de habilidades de PC y SE en estudiantes de enfermería. Métodos Se realizó una intervención longitudinal en una muestra de 103 estudiantes, se aplicó la prueba estadística ANOVA. Resultados Se evaluó el desarrollo de PC al comparar los resultados obtenidos por los estudiantes en tres evaluaciones, se logró evidenciar un progreso en el desarrollo de las habilidades de PC, y SE. Con el análisis de varianza se estableció que el valor del estadístico F fue mayor al crítico (valor p < 0,05), para un nivel de confianza del 95%, se puede rechazar la hipótesis nula. Discusión La implementación de la metodología contribuyó favorablemente en el desarrollo de las habilidades PC y SE en los estudiantes, lo que les permitió identificar y resolver problemas, al fundamentar sus decisiones. Además, fomentó el aprendizaje colaborativo y el respeto, entre pares. Conclusiones La metodología EC promovió un aprendizaje activo y un cambio en la cultura del aula. Si bien, implementar la metodología de EC favoreció el desarrollo de habilidades de PC y SE en los estudiantes de enfermería, es necesario seguir investigando sobre factores que mejoren el proceso de enseñanza-aprendizaje con un enfoque activo.

Introduction A teaching-learning centered university model implies an evolution characterized by using active methodologies with a focus on the development of skills such as critical thinking (CT), and ethical sense (ES). Objective To assess the impact from the implementation of the Study Case (SC) in the development of critical thinking and ethical sense among nursing students. Methods A longitudinal intervention was conducted on a sample of 103 nursing students. ANOVA tests were performed. Results Critical thinking was assessed by comparing the corresponding results of the students in three evaluations. A progress is development of critical thinking and ethical sense was evidenced. From the ANOVA, it was shown that the F value was higher than the critical reference (p < 0.05) within a 95% confidence interval, and thus, the nil hypothesis was rejected. Discussion The implementation of this methodology favorably contributed for the development of critical thinking and ethical sense skills among the students, an improvement which allowed them to identify and solve problems based on their decision arguments. Moreover, the methodology fostered collaborative learning and respect among colleagues. Conclusions Although the Case Study methodology promoted active learning and a change in the culture of the classroom, it is necessary to continue studying the factors which could improve the teaching-learning processes under an active approach.

Introdução Um modelo centrado no ensino-aprendizagem supõe um câmbio na docência universitária, isto envolve o uso de metodologias ativas com enfoque no desenvolvimento de habilidades como o pensamento crítico (PC) e sentido ético (SE). Objetivo Avaliar o impacto da implementação do estudo de caso (EC) no desenvolvimento de habilidades de PC e SE em estudantes de enfermagem. Métodos Realizou-se uma intervenção longitudinal em uma mostra de 103 estudantes, aplicou-se a proba estatística ANOVA. Resultados Avaliou-se o desenvolvimento de PC ao comparar os resultados obtidos pelos estudantes em três avaliações, atingiu-se evidenciar um progresso no desenvolvimento das habilidades de PC, e SE. Com a análise de variância estabeleceu-se que o valor do estatístico F foi maior ao crítico (valor p < 0,05), para um nível de confiança do 95%, pode se rejeitar a hipótese nula. Discussão A implementação da metodologia contribuiu favoravelmente no desenvolvimento das habilidades PC e SE nos estudantes, o que lhes permitiu identificar e resolver problemas, ao fundamentar suas decisões. Além disso, fomentou a aprendizagem colaborativa e o respeito entre pares. Conclusões A metodologia EC promoveu uma aprendizagem ativa e um câmbio na cultura de aula. Embora, implementar a metodologia de EC favoreça o desenvolvimento de habilidades de PC e SE nos estudantes de enfermagem, é necessário seguir pesquisando sobre fatores que melhorem o processo de ensino-aprendizagem com um enfoque ativo.

Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions.

BACKGROUND: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). PATIENTS AND METHODS: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue. Serum and plasma were sent to a central laboratory, cfDNA purified and EGFR mutations analyzed and quantified using a real-time PCR assay. Response data from a subset of patients (n = 18) were retrospectively collected. RESULTS: Of 1033 NSCLC patients at presentation, 1026 were assessable; with a prevalence of males and former or current smokers. Sensitizing mutations were found in the cfDNA of 113 patients (11%); with a majority of females, never smokers and exon 19 deletions. Thirty-one patients were positive only in plasma and 11 in serum alone and mutation load was higher in plasma and in cases with exon 19 deletions. More than 50% of samples had <10 pg mutated genomes/µl with allelic fractions below 0.25%. Patients treated first line with TKIs based exclusively on EGFR positivity in blood had an ORR of 72% and a median PFS of 11 months. Of 105 patients screened after progression to EGFR-TKIs, sensitizing mutations were found in 56.2% and the p.T790M resistance mutation in 35.2%. CONCLUSIONS: Large-scale EGFR testing in the blood of unselected advanced NSCLC patients is feasible and can be used to select patients for targeted therapy when testing cannot be done in tissue. The characteristics and clinical outcomes to TKI treatment of the EGFR-mutated patients identified are undistinguishable from those positive in tumor.

[Cemented stems in revision total knee arthroplasty on patients older than 75 y/o. Clinical and radiological analysis]. / Vástagos cementados en recambios de prótesis total de rodilla en pacientes mayores de 75 años. Análisis clínico y radiológico.

BACKGROUND: The purpose of this study was to analyze the clinical and radiological evolution of the total knee revision arthroplasty with cemented stems in patients over 75 years. MATERIAL AND METHODS: A retrospective analysis was performed in all the subjects who underwent revision of total knee arthroplasty with cemented stems between 2008 and 2014 in our center. Twenty-seven individuals over 75 years met the inclusion criteria. We assessed the Knee Society Score and range of motion for clinical outcome. We evaluated the implant stability with radiographs through radiolucent lines according to the modified radiological scale of the Knee Society; we registered the complications and prosthetic survival. RESULTS: With an average age of our participants of 82.6 ± 4.4 years and a follow-up of 43 ± 14.4 months, we did not find any mechanical failure of the components. The functional average score was 115 ± 32 in the total KSS, of which 77 ± 17.5 points were in the KSS knee and 42 ± 24 in the KSS function. The average range of motion was 98º ± 17. Radiologically, 18 patients presented radiolucent lines, but only three needed follow-up using the modified Knee Society radiographic scoring system. CONCLUSIONS: The results revealed that cemented stems are a good method for fixation in the revision of total knee arthroplasty in people over 75 years. We observed acceptable medium-term clinical results with a low risk of radiological failure, despite the high number of radiolucencies.

Analizar la evolución funcional y radiológica de los pacientes mayores de 75 años intervenidos de cirugía de revisión de rodilla con vástagos cementados.

Synthesis and characterization of extremely small gold nanoshells, and comparison of their photothermal conversion capacity with gold nanorods.

The current methods for preparing gold nanoshells (AuNSs) produce shells with a diameter of approximately 40 nm or larger, with a relatively large polydispersity. However, AuNSs with smaller diameters and more monodispersity are better suited for biomedical applications. In this work, we present a modified method for the preparation of AuNSs, based on the use of sacrificial silver nanoparticles (AgNPs). We customized the Lee-Meisel method to prepare small and monodisperse AgNPs that were used as sacrificial nanoparticles to prepare extremely small monodispersed AuNSs with an average diameter from 17 to 25 ± 4 nm. We found that these AuNSs are faceted, and that the oxidized silver likely dissolves out of the nanoparticles through some of the facets on the AuNSs. This leads to a silver oxide plug on the surface of the AuNSs, which has not been reported before. The smaller AuNSs, prepared under the best conditions, absorb in the near infrared region (NIR) that is appropriate for applications, such as photothermal therapy or medical imaging. The AuNSs showed absorption peaks in the NIR similar to those of gold nanorods (AuNRs) but with better photothermal capacity. In addition, because of their negative charge, these AuNSs are more biocompatible than the positively charged AuNRs. The synthesis of small, monodisperse, stable and biocompatible nanoparticles, like the ones presented in this work, is of prime importance in biomedical applications.

Vástagos cementados en recambios de prótesis total de rodilla en pacientes mayores de 75 años. Análisis clínico y radiológico / Cemented stems in revision total knee arthroplasty on patients older than 75 y/o. Clinical and radiological analysis

Resumen: Antecedentes: Analizar la evolución funcional y radiológica de los pacientes mayores de 75 años intervenidos de cirugía de revisión de rodilla con vástagos cementados. Material y métodos: Mediante análisis retrospectivo, hemos revisado a 27 individuos mayores de 75 años a quienes se les ha implantado una prótesis total de rodilla de revisión con vástagos cementados en nuestro centro entre 2008-2014. Durante el seguimiento, se realizó un análisis clínico mediante la escala Knee Society Score y de movilidad de la rodilla, un análisis radiológico de la estabilidad de los implantes por medio de la escala radiológica modificada de la Knee Society, el registro de las complicaciones y la supervivencia protésica. Resultados: Con una edad media de los participantes de 82.6 ± 4.4 años y un seguimiento medio de 43 ± 14.4 meses, no hemos observado ningún caso de aflojamiento mecánico de los componentes. La valoración funcional ha sido de 115 ± 32 puntos en la escala total KSS, de los cuales 77 ± 17.5 puntos pertenecen al KSS rodilla y 42 ± 24 puntos al KSS función. El rango medio de movilidad fue de 98o ± 17. A nivel radiológico, 18 sujetos mostraron radiolucencias periprotésicas; según los criterios de la escala radiológica de la Knee Society, solo tres requirieron seguimiento clínico-radiológico estricto. Conclusiones: La cementación de los vástagos en prótesis totales de rodilla de revisión se trata de un buen sistema de fijación en personas mayores de 75 años, con elevada supervivencia del implante, buen resultado funcional y bajo porcentaje de aflojamiento radiológico a pesar de la aparición frecuente de radiolucencias.

Abstract: Background: The purpose of this study was to analyze the clinical and radiological evolution of the total knee revision arthroplasty with cemented stems in patients over 75 years. Material and methods: A retrospective analysis was performed in all the subjects who underwent revision of total knee arthroplasty with cemented stems between 2008 and 2014 in our center. Twenty-seven individuals over 75 years met the inclusion criteria. We assessed the Knee Society Score and range of motion for clinical outcome. We evaluated the implant stability with radiographs through radiolucent lines according to the modified radiological scale of the Knee Society; we registered the complications and prosthetic survival. Results: With an average age of our participants of 82.6 ± 4.4 years and a follow-up of 43 ± 14.4 months, we did not find any mechanical failure of the components. The functional average score was 115 ± 32 in the total KSS, of which 77 ± 17.5 points were in the KSS knee and 42 ± 24 in the KSS function. The average range of motion was 98o ± 17. Radiologically, 18 patients presented radiolucent lines, but only three needed follow-up using the modified Knee Society radiographic scoring system. Conclusions: The results revealed that cemented stems are a good method for fixation in the revision of total knee arthroplasty in people over 75 years. We observed acceptable medium-term clinical results with a low risk of radiological failure, despite the high number of radiolucencies.

The DEP-6D, a new preference-based measure to assess health states of dependency.

In medical literature there are numerous multidimensional scales to measure health states for dependence in activities of daily living. However, these scales are not preference-based and are not able to yield QALYs. On the contrary, the generic preference-based measures are not sensitive enough to measure changes in dependence states. The objective of this paper is to propose a new dependency health state classification system, called DEP-6D, and to estimate its value set in such a way that it can be used in QALY calculations. DEP-6D states are described as a combination of 6 attributes (eat, incontinence, personal care, mobility, housework and cognition problems), with 3-4 levels each. A sample of 312 Spanish citizens was surveyed in 2011 to estimate the DEP-6D preference-scoring algorithm. Each respondent valued six out of the 24 states using time trade-off questions. After excluding those respondents who made two or more inconsistencies (6% out of the sample), each state was valued between 66 and 77 times. The responses present a high internal and external consistency. A random effect model accounting for main effects was the preferred model to estimate the scoring algorithm. The DEP-6D describes, in general, more severe problems than those usually described by means of generic preference-based measures. The minimum score predicted by the DEP-6D algorithm is -0.84, which is considerably lower than the minimum value predicted by the EQ-5D and SF-6D algorithms. The DEP-6D value set is based on community preferences. Therefore it is consistent with the so-called 'societal perspective'. Moreover, DEP-6D preference weights can be used in QALY calculations and cost-utility analysis.

Impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome.

WHAT IS KNOWN AND OBJECTIVE: Regular blood transfusions in the management of myelodysplastic syndrome (MDS) often lead to iron overload. The main objective of this study was to evaluate the impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in patients with MDS. Secondary objectives were to describe treatment effectiveness and safety in daily clinical practice. METHODS: A longitudinal, retrospective, observational study was carried out in a university hospital. The inclusion criteria were age over 18 years, MDS diagnosis and treatment with deferasirox for transfusion-dependent iron overload during the period of study (from January 2011 to April 2015). Treatment effectiveness was estimated by serum ferritin (SF), and adherence was measured by medication possession ratio (MPR). Clinically relevant analytical alterations during the treatment and reasons for treatment discontinuation were also assessed. RESULTS: Thirty-five patients were included in the study. Median SF at baseline was 1636 µg/L, and it decreased to 1399 µg/L during follow-up. The median adherence rate was 92%, although only 54·8% of the patients maintained deferasirox adherence ≥90% during the whole duration of treatment. Adherence rate was inversely correlated to SF (r = -0·288, P = 0·004). The median (p25, p75) duration of treatment was 11 (3·0, 37·8) months. The most common reasons for treatment discontinuation were renal toxicity (35%) and patient's death (25%). WHAT IS NEW AND CONCLUSION: Deferasirox's effectiveness, measured by the decrease in SF, was significantly better in adherent patients. The most frequent reason for treatment discontinuation was renal toxicity. Developing strategies to improve deferasirox treatment adherence and monitoring renal function in those patients should be key points in pharmaceutical care.

New diplopic restrictive strabismus as a sequela after conjunctival surgery for conjunctival lesions: a series of 3 cases, management and outcome.

OBJECTIVE: To present three clinical cases of diplopia secondary to conjunctival surgery (for tumor of caruncle and recurrent pterygium surgery). PATIENTS AND METHODS: Clinical data of three patients with binocular diplopia and incomitant esotropia associated with compensatory torticollis and duction limitation are shown and discussed. In all cases, a complete ophthalmological examination was performed including ocular motility study, duction test and preoperative evaluation under general anesthesia. RESULTS: The forced duction test was positive in all cases, confirming the diagnosis of restrictive strabismus. Uneventful surgery was performed in all cases in which conjunctival adherences to eye orbit bones were eliminated and the involved extraocular muscle was isolated and freed. Furthermore, some additional treatments were applied to avoid recurrency (subconjunctival and topical corticosteroids, amniotic membrane and therapeutic contact lens). One case presented postoperatively a new conjunctival adherence in spite of such anti-recurrency treatment although with no significant motility alterations associated. CONCLUSIONS: Conjunctival surgery can cause fibrosis and conjunctival adherences leading to restrictive strabismus. The surgical procedure for solving this problem must be performed with special care to avoid complications and recurrencies. The use of antimetabolites or amniotic membrane seems to be recommendable to ensure a satisfactory postoperative outcome.