Telematic Interview in Telepharmacy: a comprehensive guide for pharmacotherapeutic follow-up and and informed drug delivery. / [Artículo traducido] Entrevista telemática en telefarmacia: documento de consenso para el seguimiento farmacoterapéutico y la entrega informada de medicamentos.

Telepharmacy is defined as the practice of remote pharmaceutical care, using information and communication technologies. Given its growing importance in outpatient pharmaceutical care, the Spanish Society of Hospital Pharmacy developed a consensus document, Guía de entrevista telemática en atención farmacéutica, as part of its strategy for the development and expansion of telepharmacy, with key recommendations for effective pharmacotherapeutic monitoring and informed dispensing and delivery of medications through telematic interviews. The document was developed by a working group of hospital pharmacists with experience in the field. It highlights the benefits of telematic interviewing for patients, hospital pharmacy professionals, and the healthcare system as a whole, reviews the various tools for conducting telematic interviews, and provides recommendations for each phase of the interview. These recommendations cover aspects such as tool/platform selection, patient selection, obtaining authorization and consent, assessing technological skills, defining objectives and structure, scheduling appointments, reviewing medical records, and ensuring humane treatment. Telematic interview is a valuable complement to face-to-face consultations but its novelty requires a strategic and formal framework that this consensus document aims to cover. The use of appropriate communication tools and compliance with recommended procedures ensure patient safety and satisfaction. By implementing telematic interviews, healthcare institutions can improve patient care, optimize the use of resources and promote continuity of care.

Development of Flame-Retardant Polylactic Acid Formulations for Additive Manufacturing.

Polymeric materials, renowned for their lightweight attributes and design adaptability, play a pivotal role in augmenting fuel efficiency and cost-effectiveness in railway vehicle development. The tailored formulation of compounds, specifically designed for additive manufacturing, holds significant promise in expanding the use of these materials. This study centers on poly(lactic acid) (PLA), a natural-based biodegradable polymeric material incorporating diverse halogen-free flame retardants (FRs). Our investigation scrutinizes the printability and fire performance of these formulations, aligning with the European railway standard EN 45545-2. The findings underscore that FR in the condensed phase, including ammonium polyphosphate (APP), expandable graphite (EG), and intumescent systems, exhibit superior fire performance. Notably, FR-inducing hydrolytic degradation, such as aluminum hydroxide (ATH) or EG, reduces polymer molecular weight, significantly impacting PLA's mechanical performance. Achieving a delicate balance between fire resistance and mechanical properties, formulations with APP as the flame retardant emerge as optimal. This research contributes to understanding the fire performance and printability of 3D-printed PLA compounds, offering vital insights for the rail industry's adoption of polymeric materials.

Telematic interview in telepharmacy: consensus document for farmacotherapeutic monitoring and informed drug delivery.

Telepharmacy is defined as the practice of remote pharmaceutical care, using information and communication technologies. Given its growing importance in outpatient pharmaceutical care, the Spanish Society of Hospital Pharmacy developed a consensus document, "Guía de entrevista telemática en atención farmacéutica," as part of its strategy for the development and expansion of telepharmacy, with key recommendations for effective pharmacotherapeutic monitoring and informed dispensing and delivery of medications through telematic interviews. The document was developed by a working group of hospital pharmacists with experience in the field. It highlights the benefits of telematic interviewing for patients, hospital pharmacy professionals, and the healthcare system as a whole, reviews the various tools for conducting telematic interviews, and provides recommendations for each phase of the interview. These recommendations cover aspects such as tool/platform selection, patient selection, obtaining authorization and consent, assessing technological skills, defining objectives and structure, scheduling appointments, reviewing medical records, and ensuring humane treatment. Telematic interview is a valuable complement to face-to-face consultations but its novelty requires a strategic and formal framework that this consensus document aims to cover. The use of appropriate communication tools and compliance with recommended procedures ensure patient safety and satisfaction. By implementing telematic interviews, healthcare institutions can improve patient care, optimize the use of resources and promote continuity of care.

Pembrolizumab-induced agranulocytosis.

INTRODUCTION: With the widespread use of anti-programmed death-1 monoclonal antibodies, such as pembrolizumab, rare side effects appear in clinical practice. CASE REPORT: We report the case of a man diagnosed with non-keratinizing squamous lung carcinoma stage IVB with programmed death-ligand 1 70% who developed agranulocytosis 10 days after a single dose of pembrolizumab as monotherapy. MANAGEMENT AND OUTCOME: Pembrolizumab was discontinued immediately. Grade 4 neutrophil decrease is mentioned in the product information sheet as a rare side effect. The patient was admitted in poor physical condition with grade 4 neutropenic fever, mucositis and anemia. Agranulocytosis did not improve despite treatment with granulocyte colony-stimulating factor, intravenous corticosteroids and intravenous immunoglobulins. He experienced a rapid worsening and died 3 weeks after admission. The causal relationship between pembrolizumab and the appearance of agranulocytosis was determined as possible according to Naranjo's modified Karch and Lasagna's imputability algorithm. DISCUSSION: Hematologic immune-related adverse events are uncommon but important side effects among patients treated with immune checkpoint inhibitors. Agranulocytosis and neutropenia are infrequently reported but can be life-threatening. The main approach for agranulocytosis consists of intravenous corticosteroids, granulocyte colony-stimulating factors and blood products. Depending on bone marrow characteristics, treatments for refractory patients include intravenous immunoglobulins or cyclosporine. After an immune-related adverse event, benefits and risks must be considered before continuation with an immune checkpoint inhibitor. Detection and communication of adverse drug reactions to the Pharmacovigilance Systems have special relevance for rare side effects.

The Role of Ribosomal Proteins eL15 and eL36 in the Early Steps of Yeast 60S Ribosomal Subunit Assembly.

Ribosomal proteins have important roles in maintaining the structure and function of mature ribosomes, but they also drive crucial rearrangement reactions during ribosome biogenesis. The contribution of most, but not all, ribosomal proteins to ribosome synthesis has been previously analyzed in the yeast Saccharomyces cerevisiae. Herein, we characterize the role of yeast eL15 during 60S ribosomal subunit formation. In vivo depletion of eL15 results in a shortage of 60S subunits and the appearance of half-mer polysomes. This is likely due to defective processing of the 27SA3 to the 27SBS pre-rRNA and impaired subsequent processing of both forms of 27SB pre-rRNAs to mature 25S and 5.8S rRNAs. Indeed, eL15 depletion leads to the efficient turnover of the de novo formed 27S pre-rRNAs. Additionally, depletion of eL15 blocks nucleocytoplasmic export of pre-60S particles. Moreover, we have analyzed the impact of depleting either eL15 or eL36 on the composition of early pre-60S particles, thereby revealing that the depletion of eL15 or eL36 not only affects each other's assembly into pre-60S particles but also that of neighboring ribosomal proteins, including eL8. These intermediates also lack most ribosome assembly factors required for 27SA3 and 27SB pre-rRNA processing, named A3- and B-factors, respectively. Importantly, our results recapitulate previous ones obtained upon eL8 depletion. We conclude that assembly of eL15, together with that of eL8 and eL36, is a prerequisite to shape domain I of 5.8S/25S rRNA within early pre-60S particles, through their binding to this rRNA domain and the recruitment of specific groups of assembly factors.

Testing the performance, adequacy, and applicability of an artificial intelligence model for pediatric pneumonia diagnosis.

BACKGROUND: Community-acquired Pneumonia (CAP) is a common childhood infectious disease. Deep learning models show promise in X-ray interpretation and diagnosis, but their validation should be extended due to limitations in the current validation workflow. To extend the standard validation workflow we propose doing a pilot test with the next characteristics. First, the assumption of perfect ground truth (100% sensitive and specific) is unrealistic, as high intra and inter-observer variability have been reported. To address this, we propose using Bayesian latent class models (BLCA) to estimate accuracy during the pilot. Additionally, assessing only the performance of a model without considering its applicability and acceptance by physicians is insufficient if we hope to integrate AI systems into day-to-day clinical practice. Therefore, we propose employing explainable artificial intelligence (XAI) methods during the pilot test to involve physicians and evaluate how well a Deep Learning model is accepted and how helpful it is for routine decisions as well as analyze its limitations by assessing the etiology. This study aims to apply the proposed pilot to test a deep Convolutional Neural Network (CNN)-based model for identifying consolidation in pediatric chest-X-ray (CXR) images already validated using the standard workflow. METHODS: For the standard validation workflow, a total of 5856 public CXRs and 950 private CXRs were used to train and validate the performance of the CNN model. The performance of the model was estimated assuming a perfect ground truth. For the pilot test proposed in this article, a total of 190 pediatric chest-X-ray (CXRs) images were used to test the CNN model support decision tool (SDT). The performance of the model on the pilot test was estimated using extensions of the two-test Bayesian Latent-Class model (BLCA). The sensitivity, specificity, and accuracy of the model were also assessed. The clinical characteristics of the patients were compared according to the model performance. The adequacy and applicability of the SDT was tested using XAI techniques. The adequacy of the SDT was assessed by asking two senior physicians the agreement rate with the SDT. The applicability was tested by asking three medical residents before and after using the SDT and the agreement between experts was calculated using the kappa index. RESULTS: The CRXs of the pilot test were labeled by the panel of experts into consolidation (124/176, 70.4%) and no-consolidation/other infiltrates (52/176, 29.5%). A total of 31/176 (17.6%) discrepancies were found between the model and the panel of experts with a kappa index of 0.6. The sensitivity and specificity reached a median of 90.9 (95% Credible Interval (CrI), 81.2-99.9) and 77.7 (95% CrI, 63.3-98.1), respectively. The senior physicians reported a high agreement rate (70%) with the system in identifying logical consolidation patterns. The three medical residents reached a higher agreement using SDT than alone with experts (0.66±0.1 vs. 0.75±0.2). CONCLUSIONS: Through the pilot test, we have successfully verified that the deep learning model was underestimated when a perfect ground truth was considered. Furthermore, by conducting adequacy and applicability tests, we can ensure that the model is able to identify logical patterns within the CXRs and that augmenting clinicians with automated preliminary read assistants could accelerate their workflows and enhance accuracy in identifying consolidation in pediatric CXR images.

Severe hepatotoxicity during treatment with capmatinib.

INTRODUCTION: Capmatinib is a mesenchymal-epithelial transition (MET) inhibitor authorized for metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutation treatment in adult patients. CASE REPORT: We report a case of an elderly female with a diagnosis of metastatic NSCLC with MET exon 14 skipping mutation who developed a severe hepatotoxicity after 7 weeks under treatment with capmatinib. MANAGEMENT & OUTCOME: Capmatinib was immediately discontinued. Hepatotoxicity is included as "warning and precautions" in the product information sheet. The patient was admitted with severe acute hepatitis, secondary hypocoagulability and acute deterioration of renal function. She experienced a rapid worsening with a fatal outcome three days after admission. The causal relationship between capmatinib and the appearance of hepatotoxicity was determined as probable according to Naranjo's modified Karch and Lasagna's imputability algorithm. DISCUSSION: The recognition and diagnosis of drug-induced liver injury (DILI) are often difficult and delayed. Molecularly targeted agents require careful assessment of liver function both prior to and during therapy. Capmatinib hepatotoxicity is an infrequent but severe adverse drug reaction (ADR). Prescribing information includes recommendations about liver function monitoring. The main approachment for DILI is the removal of the causative agent. Detection and communication of ADRs to the Pharmacovigilance Systems have special relevance for novel drugs, with little data in real life setting.

Adherencia y calidad de vida en los pacientes con leucemia linfocítica crónica tratados con antineoplásicos orales / Adherence and quality of life in patients with chronic lymphocytic leukemia treated with oral antineoplastic drugs

Objetivos: evaluar la adherencia y la calidad de vida de los pacientes con leucemia linfocítica crónica tratados con antineoplásicos orales. Comparar la adherencia y la calidad de vida según el fármaco recibido y según la línea de tratamiento.Métodoestudio descriptivo prospectivo realizado de junio a noviembre de 2021 en un hospital terciario. Se incluyeron pacientes con leucemia linfocítica crónica, atendidos en la consulta de Farmacia Oncológica y tratados con antineoplásicos orales desde al menos 6 meses antes de la inclusión en el estudio. Se estimó la adherencia mediante el cuestionario Morisky’s 8 item Medication Adherence Scale y el recuento de medicación sobrante, considerándose adherentes si su tasa de adherencia era ≥ 90%. Para evaluar la calidad de vida, se utilizó el cuestionario EQ-5D-3L del grupo EuroQol, la escala Functional Assessment of Chronic Illness Therapy – Fatigue y el QLQ-C30 de la European Organization for Research and Treatment of Cancer. Se programaron 2 entrevistas: en el momento de la inclusión y a los 3 meses. Se revisó la historia clínica, recogiéndose variables demográficas y clínicas. El análisis estadístico se realizó con el programa SPSS® 25.0.Resultadosse incluyeron 23 pacientes, todos fueron adherentes según el recuento de medicación, 20 presentaron adherencia alta, y 3 media, según Morisky’s 8 item Medication Adherence Scale. Los resultados del cuestionario EQ-5D-3L mostraron que los pacientes eran autónomos para su cuidado personal y sus actividades cotidianas, el 69,6% no tenían problemas de movilidad, el 78,3% no tenía ansiedad/depresión y el 56,5% presentaba algún tipo de dolor. (AU)

Objective: To evaluate adherence and quality of life to oral antineoplastic treatment in patients with chronic lymphocytic leukemia. To compare adherence and QoL according to treatment subgroups and treatment-line subgroups.MethodsWe conducted a descriptive prospective study from June to November 2021 in a tertiary care hospital. Patients treated at the Oncology Pharmacy with a diagnosis of chronic lymphocytic leukemia and treatment with oral antineoplastics for at least 6 months before inclusion in the study were included. Adherence was assessed using Morisky’s 8 item Medication Adherence Scale and leftover pills counts, considering adherents if their adherence rate was ≥ 90%. Quality of life was assessed with Euro-Qol EQ-5D-3L questionnaire, Functional Assessment of Chronic Illness Therapy – Fatigue scale and QLQ-C30 questionnaire from European Organization for Research and Treatment of Cancer. Two interviews were scheduled: at the time of inclusion and at 3 months. Variable collected: demographic data, clinical data (disease and treatment); and response (scores obtained from questionnaires and adherence rate). The data statistical analysis was carried out with SPSS® 25.0 software.ResultsTwenty three patients were included, all of them showed an adherence rate higher than 90%; 20 patients were considered high adherent, and 3 patients medium adherent to treatment according to Morisky’s 8 item Medication Adherence Scale. (AU)

Synthesis of Micro- and Mesoporous Carbon Foams with Nanodispersed Metals for Adsorption and Catalysis Applications.

This work focuses on carbon foams, whose peculiarity is a predominant open macroporous cellular network that can be provided with tailored texture and morphology by the modification of the preparation process. The goal was to obtain macroporous carbonaceous structures capable of being activated by following a simple thermo-foaming procedure using a few reagents. With this purpose in mind, carbon foams with different textural properties were synthesized from sucrose using two foaming processes: at atmospheric pressure and in a pressurized reactor. Iron and silver nitrates added to sucrose gave rise, after carbonization, to materials with iron oxides and elemental silver particles nano-dispersed in the carbon matrix and promoted microporosity in both cases and mesoporosity in the case of iron nitrate. Iron nitrate also catalyzes the graphitization of the carbon material during carbonization. All these findings show the potential of sucrose thermo-foaming process as a viable and sustainable path to produce versatile carbon materials, capable of being used in various applications.

Adherence and quality of life in patients with chronic lymphocytic leukemia treated with oral antineoplastic drugs. / Adherencia y calidad de vida en los pacientes con leucemia linfocítica crónica tratados con antineoplásicos orales.

OBJECTIVE: To evaluate adherence and quality of life to oral antineoplastic treatment in patients with chronic lymphocytic leukemia. To compare adherence and QoL according to treatment subgroups and treatment-line subgroups. METHODS: We conducted a descriptive prospective study from June to November 2021 in a tertiary care hospital. Patients treated at the Oncology Pharmacy with a diagnosis of chronic lymphocytic leukemia and treatment with oral antineoplastics for at least 6 months before inclusion in the study were included. Adherence was assessed using Morisky's 8 item Medication Adherence Scale and leftover pills counts, considering adherents if their adherence rate was ≥ 90%. Quality of life was assessed with Euro-Qol EQ-5D-3L questionnaire, Functional Assessment of Chronic Illness Therapy - Fatigue scale and QLQ-C30 questionnaire from European Organization for Research and Treatment of Cancer. Two interviews were scheduled: at the time of inclusion and at 3 months. Variable collected: demographic data, clinical data (disease and treatment); and response (scores obtained from questionnaires and adherence rate). The data statistical analysis was carried out with SPSS® 25.0 software. RESULTS: Twenty three patients were included, all of them showed an adherence rate higher than 90%; 20 patients were considered high adherent, and 3 patients medium adherent to treatment according to Morisky's 8 item Medication Adherence Scale. The results of the EQ-5D-3L questionnaire showed that the patients were all of them autonomous in their personal care and daily activities, 69.6% did not have any mobility problems and 78.3% did not have anxiety/depression; 56.5% had some type of pain. Eighteen patients had no fatigue, and 5 had mild/moderate fatigue according to Functional Assessment of Chronic Illness Therapy - Fatigue scale. The results of the EORTC QLQ-C30 questionnaire showed that patients had a high /healthy functional level, a good quality of life and a low level of symptoms. Analysis by treatment subgroups and by treatment-line subgroups did not show statistically significant differences in adherence or quality of life. CONCLUSIONS: Patients diagnosed with chronic lymphocytic leukemia and treated with oral antineoplastic therapies showed a high adherence rate and referred a good quality of life.

[Translated article] Adherence and quality of life in patients with chronic lymphocytic leukemia treated with oral antineoplastic drugs.

OBJECTIVE: To evaluate adherence and quality of life to oral antineoplastic treatment in patients with chronic lymphocytic leukemia. To compare adherence and quality of life according to treatment subgroups and treatment-line subgroups. METHODS: We conducted a descriptive prospective study from June to November 2021 in a tertiary care hospital.  Patients with chronic lymphocytic leukaemia, seen at the Oncology Pharmacy and treated with oral antineoplastic drugs for at least 6 months prior to inclusion in the study were included. Adherence was assessed using Morisky's 8 item Medication Adherence Scale and leftover pills counts, considering adherents if their adherence rate was ≥90%. Quality of life was assessed with Euro-Qol EQ-5D-3L questionnaire, Functional Assessment of Chronic Illness Therapy - Fatigue scale and QLQ-C30 questionnaire from European Organization for Research and Treatment of Cancer. Two interviews were scheduled: at the time of inclusion and at 3 months. The clinical history was reviewed and demographic and clinical variables were collected. The data statistical analysis was carried out with SPSS® 25.0 software. RESULTS: Twenty three patients were included, all of them showed an adherence rate higher than 90%; 20 patients were considered high adherent, and 3 patients médium adherent to treatment according to Morisky's 8 item Medication Adherence Scale. The results of the EQ-5D-3L questionnaire showed that the patients were all of them autonomous in their personal care and daily activities, 69.6% did not have any mobility problems and 78.3% did not have anxiety/depression; 56.5% had some type of pain. Eighteen patients had no fatigue, and 5 had mild/moderate fatigue according to Functional Assessment of Chronic Illness Therapy - Fatigue scale. The results of the EORTC QLQ-C30 questionnaire showed that patients had a high /healthy functional level, a good quality of life and a low level of symptoms. Analysis by treatment subgroups and by treatment-line subgroups did not show statistically significant differences in adherence or quality of life. CONCLUSIONS: Patients diagnosed with chronic lymphocytic leukemia and treated with oral antineoplastic therapies showed a high adherence rate and referred a good quality of life.

The Telepharmacy patient prioritisation model of the Spanish Society of Hospital Pharmacy.

The Spanish Society of Hospital Pharmacy Position Paper on Telepharmacy states that the inclusion of patients should take into account  ethical considerations and, therefore, be based on the concept of equity. Thus, it establishes that Telepharmacy should not be limited to specific  pathologies or medicines, but should be based on the individual needs of each patient: it also highlights the need to rely on selection or prioritisation models to help identify patients who can benefit from  Telepharmacy. The aim of this article is to present the Spanish Society of  Hospital Pharmacy Telepharmacy Patient Prioritisation Model, which establishes  key recommendations and a reference prioritisation model to guide  hospital pharmacists in the identification and prioritisation of patients  who are candidates for inclusion in Telepharmacy programmes. This model was  developed based on the experience of a group of experts in their clinical  practice as well as on a review of the main reference documents available in  this field. It comprises 25 criteria, grouped into 8 minimum inclusion criteria, 5 continuity criteria, and 12 recommended criteria. The latter criteria are divided  into high, medium, and low priority criteria. Patients are prioritised according  to their scores on meeting the recommended criteria, such that those with the  highest scores are given the highest priority. As stated in the Spanish Society  of Hospital Pharmacy Position Paper on Telepharmacy, pharmacotherapeutic  monitoring can be conducted via remote consultation without sending  medication, but not vice versa; thus, the 25 criteria defined apply to  Telepharmacy programmes in the area of the remote dispensing and informed  delivery of medicines, but only 19 of them apply to pharmacotherapeutic  monitoring programmes. The model presented is intended to be a reference  guide and should be adapted to the particular characteristics and  circumstances of each pharmacy service, depending on demand and available  resources.

La Sociedad Española de Farmacia Hospitalaria, en su Documento de  osicionamiento sobre Telefarmacia, establece que la inclusión de pacientes debe tener en cuenta consideraciones éticas y, por tanto, estar  basada en el concepto de equidad. Por ello, establece que la Telefarmacia no  debe restringirse por patologías ni medicamentos, sino en función de las  necesidades individuales de cada paciente, y destaca la necesidad de apoyarse en modelos de selección o priorización que ayuden en la  identificación de los pacientes que puedan beneficiarse de la Telefarmacia. El  objetivo de este artículo es presentar el "Modelo de priorización de pacientes  en Telefarmacia de la Sociedad Española de Farmacia Hospitalaria", que pretende establecer recomendaciones clave y un modelo de priorización de referencia que sirva de orientación a los farmacéuticos especialistas en farmacia hospitalaria para la identificación y priorización de pacientes candidatos a ser incluidos en programas de Telefarmacia. El modelo  a sido desarrollado en base a la experiencia de un grupo de expertos en su práctica clínica y a la revisión de los principales documentos de referencia disponibles en este ámbito y está conformado por un total de 25  criterios, agrupados en 8 criterios mínimos de inclusión, 5 criterios de  continuidad y 12 criterios recomendables. Estos últimos se dividen en criterios  de alta, media y baja prioridad. En función de las puntuaciones obtenidas del  cumplimiento de los criterios recomendables, se establece el orden de  prioridad de pacientes, de modo que aquellos que mayor puntuación obtengan  serán los más prioritarios. Tal como recoge el "Documento de Posicionamiento sobre Telefarmacia de la Sociedad Española de Farmacia Hospitalaria", puede  haber seguimiento farmacoterapéutico por teleconsulta sin envío de medicación, pero no al contrario, por lo que los 25 criterios definidos aplican a  programas de Telefarmacia en el ámbito de la dispensación y entrega informada de medicamentos a distancia, pero solamente 19 de ellos aplican para los programas de seguimiento farmacoterapéutico. El modelo que se  presenta ha sido concebido como un marco de referencia y deberá adaptarse a las características y circunstancias particulares de cada servicio de farmacia,  en función de la demanda y de los recursos disponibles.

Modelo de priorización de pacientes en Telefarmacia de la Sociedad Española de Farmacia Hospitalaria / The Telepharmacy patient prioritisation model of the Spanish Society of Hospital Pharmacy

La Sociedad Española de Farmacia Hospitalaria, en su Documento de Posicionamiento sobre Telefarmacia, establece que la inclusión de pacientesdebe tener en cuenta consideraciones éticas y, por tanto, estar basada enel concepto de equidad. Por ello, establece que la Telefarmacia no deberestringirse por patologías ni medicamentos, sino en función de las necesidades individuales de cada paciente, y destaca la necesidad de apoyarseen modelos de selección o priorización que ayuden en la identificaciónde los pacientes que puedan beneficiarse de la Telefarmacia. El objetivode este artículo es presentar el “Modelo de priorización de pacientes enTelefarmacia de la Sociedad Española de Farmacia Hospitalaria”, quepretende establecer recomendaciones clave y un modelo de priorizaciónde referencia que sirva de orientación a los farmacéuticos especialistas enfarmacia hospitalaria para la identificación y priorización de pacientescandidatos a ser incluidos en programas de Telefarmacia. El modelo hasido desarrollado en base a la experiencia de un grupo de expertos en supráctica clínica y a la revisión de los principales documentos de referenciadisponibles en este ámbito y está conformado por un total de 25 criterios,agrupados en 8 criterios mínimos de inclusión, 5 criterios de continuidad y 12 criterios recomendables. Estos últimos se dividen en criterios de alta,media y baja prioridad. En función de las puntuaciones obtenidas del cumplimiento de los criterios recomendables, se establece el orden de prioridadde pacientes, de modo que aquellos que mayor puntuación obtengan seránlos más prioritarios. (AU)

The Spanish Society of Hospital Pharmacy Position Paper on Telepharmacy states that the inclusion of patients should take into account ethicalconsiderations and, therefore, be based on the concept of equity. Thus,it establishes that Telepharmacy should not be limited to specific pathologies or medicines, but should be based on the individual needs of eachpatient: it also highlights the need to rely on selection or prioritisationmodels to help identify patients who can benefit from Telepharmacy. Theaim of this article is to present the Spanish Society of Hospital PharmacyTelepharmacy Patient Prioritisation Model, which establishes key recommendations and a reference prioritisation model to guide hospital pharmacists in the identification and prioritisation of patients who are candidatesfor inclusion in Telepharmacy programmes. This model was developedbased on the experience of a group of experts in their clinical practiceas well as on a review of the main reference documents available in thisfield. It comprises 25 criteria, grouped into 8 minimum inclusion criteria,5 continuity criteria, and 12 recommended criteria. The latter criteria aredivided into high, medium, and low priority criteria. Patients are prioritisedaccording to their scores on meeting the recommended criteria, such that those with the highest scores are given the highest priority. (AU)

The C-terminal tail of ribosomal protein Rps15 is engaged in cytoplasmic pre-40S maturation.

The small ribosomal subunit protein Rps15/uS19 is involved in early nucleolar ribosome biogenesis and subsequent nuclear export of pre-40S particles to the cytoplasm. In addition, the C-terminal tail of Rps15 was suggested to play a role in mature ribosomes, namely during translation elongation. Here, we show that Rps15 not only functions in nucleolar ribosome assembly but also in cytoplasmic pre-40S maturation, which is indicated by a strong genetic interaction between Rps15 and the 40S assembly factor Ltv1. Specifically, mutations either in the globular or C-terminal domain of Rps15 when combined with the non-essential ltv1 null allele are lethal or display a strong growth defect. However, not only rps15 ltv1 double mutants but also single rps15 C-terminal deletion mutants exhibit an accumulation of the 20S pre-rRNA in the cytoplasm, indicative of a cytoplasmic pre-40S maturation defect. Since in pre-40S particles, the C-terminal tail of Rps15 is positioned between assembly factors Rio2 and Tsr1, we further tested whether Tsr1 is genetically linked to Rps15, which indeed could be demonstrated. Thus, the integrity of the Rps15 C-terminal tail plays an important role during late pre-40S maturation, perhaps in a quality control step to ensure that only 40S ribosomal subunits with functional Rps15 C-terminal tail can efficiently enter translation. As mutations in the C-terminal tail of human RPS15 have been observed in connection with chronic lymphocytic leukaemia, it is possible that apart from defects in translation, an impaired late pre-40S maturation step in the cytoplasm could also be a reason for this disease.

Predictive value of immune-related adverse events during pembrolizumab treatment in non-small cell lung cancer.

OBJECTIVES: Several studies have reported the role of immune-related adverse events as a predictor of clinical benefit, but few have properly described these findings in advanced or metastatic non-small cell lung cancer treated with pembrolizumab. This study aimed to evaluate the association between immune-related adverse events development and clinical outcomes in the aforementioned group of patients. METHODS: We conducted a retrospective study in patients with advanced or metastatic non-small cell lung cancer treated with pembrolizumab. Overall response rate, progression-free survival and overall survival were evaluated according to the appearance, subtype and number of immune-related adverse events developed. We report the results of the immune-related adverse events analysis and the potential correlation between immune-related adverse events and clinical outcomes. Univariate and multivariate analyses were performed to evaluate this relationship. RESULTS: A total of 94 patients were analysed; 60 of them developed immune-related adverse events. Patients with immune-related adverse events had a significantly higher overall response rate compared with the non-immune-related adverse events group (34% vs 8.5%, χ2=0.005). Median progression-free survival was statistically significant in favour of patients with at least one immune-related adverse event (p=0.015). Median overall survival was not reached in patients with ≥1 immune-related adverse events, compared with 8 months (95% CI 0.6 to 15.4 months) in those without immune-related adverse events. Patients who developed ≥2 immune-related adverse events had longer median progression-free survival (11 vs 4 months, not statistically significant) and overall survival (not reached vs 11, p=0.022) compared with those with ≤1 immune-related adverse events. CONCLUSIONS: Obtained data showed that patients with immune-related adverse events occurrence had significantly better overall response rate and longer progression-free survival and overall survival. This study highlights the role of immune-related adverse events as a predictor of survival in a real-life setting.

Association of snR190 snoRNA chaperone with early pre-60S particles is regulated by the RNA helicase Dbp7 in yeast.

Synthesis of eukaryotic ribosomes involves the assembly and maturation of precursor particles (pre-ribosomal particles) containing ribosomal RNA (rRNA) precursors, ribosomal proteins (RPs) and a plethora of assembly factors (AFs). Formation of the earliest precursors of the 60S ribosomal subunit (pre-60S r-particle) is among the least understood stages of ribosome biogenesis. It involves the Npa1 complex, a protein module suggested to play a key role in the early structuring of the pre-rRNA. Npa1 displays genetic interactions with the DExD-box protein Dbp7 and interacts physically with the snR190 box C/D snoRNA. We show here that snR190 functions as a snoRNA chaperone, which likely cooperates with the Npa1 complex to initiate compaction of the pre-rRNA in early pre-60S r-particles. We further show that Dbp7 regulates the dynamic base-pairing between snR190 and the pre-rRNA within the earliest pre-60S r-particles, thereby participating in structuring the peptidyl transferase center (PTC) of the large ribosomal subunit.

Additive Manufactured Scaffolds for Bone Tissue Engineering: Physical Characterization of Thermoplastic Composites with Functional Fillers.

Thermoplastic polymer-filler composites are excellent materials for bone tissue engineering (TE) scaffolds, combining the functionality of fillers with suitable load-bearing ability, biodegradability, and additive manufacturing (AM) compatibility of the polymer. Two key determinants of their utility are their rheological behavior in the molten state, determining AM processability and their mechanical load-bearing properties. We report here the characterization of both these physical properties for four bone TE relevant composite formulations with poly(ethylene oxide terephthalate)/poly(butylene terephthalate (PEOT/PBT) as a base polymer, which is often used to fabricate TE scaffolds. The fillers used were reduced graphene oxide (rGO), hydroxyapatite (HA), gentamicin intercalated in zirconium phosphate (ZrP-GTM) and ciprofloxacin intercalated in MgAl layered double hydroxide (MgAl-CFX). The rheological assessment showed that generally the viscous behavior dominated the elastic behavior (G″ > G') for the studied composites, at empirically determined extrusion temperatures. Coupled rheological-thermal characterization of ZrP-GTM and HA composites showed that the fillers increased the solidification temperatures of the polymer melts during cooling. Both these findings have implications for the required extrusion temperatures and bonding between layers. Mechanical tests showed that the fillers generally not only made the polymer stiffer but more brittle in proportion to the filler fractions. Furthermore, the elastic moduli of scaffolds did not directly correlate with the corresponding bulk material properties, implying composite-specific AM processing effects on the mechanical properties. Finally, we show computational models to predict multimaterial scaffold elastic moduli using measured single material scaffold and bulk moduli. The reported characterizations are essential for assessing the AM processability and ultimately the suitability of the manufactured scaffolds for the envisioned bone regeneration application.

Effect of the reduced graphene oxide (rGO) compaction degree and concentration on rGO-polymer composite printability and cell interactions.

Graphene derivatives combined with polymers have attracted enormous attention for bone tissue engineering applications. Among others, reduced graphene oxide (rGO) is one of the preferred graphene-based fillers for the preparation of composites via melt compounding, and their further processing into 3D scaffolds, due to its established large-scale production method, thermal stability, and electrical conductivity. In this study, rGO (low bulk density 10 g L-1) was compacted by densification using a solvent (either acetone or water) prior to melt compounding, to simplify its handling and dosing into a twin-screw extrusion system. The effects of rGO bulk density (medium and high), densification solvent, and rGO concentration (3, 10 and 15% in weight) on rGO dispersion within the composite, electrical conductivity, printability and cell-material interactions were studied. High bulk density rGO (90 g L-1) occupied a low volume fraction within polymer composites, offering poor electrical properties but a reproducible printability up to 15 wt% rGO. On the other hand, the volume fraction within the composites of medium bulk density rGO (50 g L-1) was higher for a given concentration, enhancing rGO particle interactions and leading to enhanced electrical conductivity, but compromising the printability window. For a given bulk density (50 g L-1), rGO densified in water was more compacted and offered poorer dispersability within the polymer than rGO densified in acetone, and resulted in scaffolds with poor layer bonding or even lack of printability at high rGO percentages. A balance in printability and electrical properties was obtained for composites with medium bulk density achieved with rGO densified in acetone. Here, increasing rGO concentration led to more hydrophilic composites with a noticeable increase in protein adsorption. Moreover, scaffolds prepared with such composites presented antimicrobial properties even at low rGO contents (3 wt%). In addition, the viability and proliferation of human mesenchymal stromal cells (hMSCs) were maintained on scaffolds with up to 15% rGO and with enhanced osteogenic differentiation on 3% rGO scaffolds.

Ubiquitin and Ubiquitin-Like Proteins and Domains in Ribosome Production and Function: Chance or Necessity?

Ubiquitin is a small protein that is highly conserved throughout eukaryotes. It operates as a reversible post-translational modifier through a process known as ubiquitination, which involves the addition of one or several ubiquitin moieties to a substrate protein. These modifications mark proteins for proteasome-dependent degradation or alter their localization or activity in a variety of cellular processes. In most eukaryotes, ubiquitin is generated by the proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a polyubiquitin precursor, or as a single N-terminal moiety to ribosomal proteins, which are practically invariably eL40 and eS31. Herein, we summarize the contribution of the ubiquitin moiety within precursors of ribosomal proteins to ribosome biogenesis and function and discuss the biological relevance of having maintained the explicit fusion to eL40 and eS31 during evolution. There are other ubiquitin-like proteins, which also work as post-translational modifiers, among them the small ubiquitin-like modifier (SUMO). Both ubiquitin and SUMO are able to modify ribosome assembly factors and ribosomal proteins to regulate ribosome biogenesis and function. Strikingly, ubiquitin-like domains are also found within two ribosome assembly factors; hence, the functional role of these proteins will also be highlighted.