RESUMEN

Abstract Introduction: Aquatic birds (AB) are usually associated with wetlands, which provide refuge, food, and/or nesting sites for resident and migratory species. Despite their ecological importance, there is little knowledge on AB in some tropical environments, such as those found on the Colima coast. Objective: To investigate the spatial and temporal composition of the AB community in Juluapan Lagoon, Colima, Central Mexican Pacific. Methods: Monthly counts were conducted between June 2017 and May 2018 during low-tide conditions to record habitat use by AB. Species richness and bird counts were obtained to compare sampling areas; mean richness and number of individuals were compared between seasons. Results: We detected 53 species and 5 750 individuals. The highest species richness and relative abundance values were obtained in winter at the lagoon area farthest from the connection with the marine system, where anthropogenic activity is lower. Diversity was greater in zones 2 and 3 in spring, summer, and fall. Muddy flats were the most used environment, and the most frequent activity was resting. Nesting activity was only recorded in the middle of the lagoon at the mangrove during spring. "Shorebirds" and "waders" were the most dominant groups in the bird community of the Juluapan lagoon. Conclusions: This coastal wetland is a site of great biological importance for aquatic birds; thus, conservation measures should be implemented, and there should be a continuous study of the effects of anthropogenic pressure.

Resumen Introducción: Las aves acuáticas (AA) son usualmente relacionadas a los humedales debido a que éstos funcionan como sitios de refugio, alimentación y anidación de diferentes especies residentes y migratorias. Sin embargo, el conocimiento sobre las aves acuáticas en algunos humedales es nulo. Objetivo: Investigar la composición espacio-temporal de la comunidad de AA en la laguna Juluapan, Colima, en el Pacífico Central Mexicano. Métodos: Entre junio de 2017 y mayo de 2018 se llevaron a cabo conteos mensuales en condiciones de marea baja para registrar el uso de hábitat de las AA. Se obtuvieron valores de riqueza de especies y número de individuos para realizar comparaciones entre zonas de muestreo, así como el promedio del número de especies y número de individuos para comparaciones entre temporadas. Resultados: Se registraron un total de 53 especies y 5 750 individuos. Los valores de riqueza de especies y densidad de individuos fueron más altos durante invierno, en la zona más alejada al ambiente marino, donde la actividad antropogénica es menor. La diversidad tuvo valores más altos en la zona 2 y 3, durante primavera, verano y otoño. El ambiente más explotado por las aves fueron las planicies lodosas; y el descanso fue la actividad más frecuente. Asimismo, la actividad de anidación sólo se registró en el manglar de la zona media durante primavera. Las "aves playeras" y "aves zancudas" fueron los grupos más predominantes en la comunidad de aves de la laguna Juluapan. Conclusiones: Este humedal costero es un sitio de gran importancia biológica para aves acuáticas, por lo que resulta necesario la implementación de medidas de conservación, así como el estudio de los efectos por la presión antropogénica.

Asunto(s)

RESUMEN

Las percepciones de olvidos recurrentes o episodios de distracción en la vida diaria se denominan quejas subjetivas de memoria (QSM). Su naturaleza se ha estudiado ampliamente en adultos mayores, pero su importancia y relación con el rendimiento neurocognitivo no se han abordado por completo en adultos más jóvenes. Se han sugerido algunos rasgos psicológicos como posibles moderadores de la asociación entre el rendimiento de la memoria objetiva y subjetiva. El primer objetivo de este estudio fue analizar la correspondencia entre la percepción objetiva y subjetiva de los fallos de memoria en jóvenes. En segundo lugar, estudiamos si el rasgo psicológico del neuroticismo podría estar influyendo en esta relación. Para ello, medimos QSM, diferentes dominios cognitivos (memoria episódica y de trabajo y funciones ejecutivas) y neuroticismo en 80 hombres y mujeres jóvenes. Los resultados mostraron que solo la memoria episódica inmediata estaba estadísticamente relacionada con los QSM. Curiosamente, las relaciones negativas entre el rendimiento de la memoria objetiva y subjetiva solo aparecieron en participantes con mayor neuroticismo. Por lo tanto, las quejas de memoria reportadas por los jóvenes podrían reflejar un peor rendimiento de la memoria episódica inmediata, mientras que el neuroticismo jugaría un papel principal en la asociación entre los déficits de memoria y las QSM. Este estudio proporciona datos que pueden ayudar a comprender mejor las QSM en los jóvenes.(AU)

Perceptions of recurrent forgetfulness or episodes of distraction in daily life are referred to as subjective memory complaints (SMCs). Their nature has been extensively studied in older adults, but their significance and relationship with neurocognitive performance have not been fully ad-dressed in younger adults. Some psychological traits have been suggested as possible moderators of the association between objective and subjective memory performance. The first aim of this study was to analyze the corre-spondence between the objective and subjective perception of memory failures in young people. Second, we studied whether the psychological trait of neuroticism could be influencing this relationship. Todo this, we measured SMCs, different cognitive domains (episodic and working memory and executive functions), and neuroticism in 80 young men and women. Results showed that only immediate episodic memory was statisti-cally related to SMCs. Interestingly, the negative relationships between ob-jective and subjective memory performance only appeared in participants with higher neuroticism. Thus, memory complaints reported by young people could reflect poorer immediate episodic memory performance, whereas neuroticism would play a main role in the association between memory deficits and SMCs. This study provides data that can help to bet-ter understand SMCs in young people.(AU)

Asunto(s)

RESUMEN

El objetivo de la ruta es establecer las pautas formales, respecto a la atención integral en salud en las niñas, niños y adolescentes, ayudando a optimizar las acciones, disminuir costos, incrementar la satisfacción de los usuarios, así como mejorar la productividad y competitividad del personal de salud. En razón de lo anterior presentamos la ruta de trabajo, para la adecuación de la normativa técnica, producto del trabajo de las diferentes dependencias vinculadas directa e indirectamente a la atención en salud a niñas, niños y adolescentes

The objective of the route is to establish formal guidelines regarding comprehensive health care in the girls, boys and adolescents, helping to optimize actions, reduce costs, increase user satisfaction, as well as improving the productivity and competitiveness of health personnel. Due to the above, we present the work route, for the adaptation of the technical regulations, product of the work of the different agencies linked directly and indirectly to care in health for girls, boys and adolescents

Asunto(s)

RESUMEN

OBJECTIVE: To assess the effectiveness of a psychoeducational intervention program (PIP) compared to standard attention in reducing caregiver burden after the intervention (at 4 months) and at follow-up (at 8 months). METHODS: A multicenter, evaluator-blind, randomized controlled trial. The experimental group received a PIP intervention consisting of 10 weekly group sessions, while the control group received standard attention. The primary outcome was measured as the change scores from baseline on the caregiver's burden (ZBI). The secondary outcomes evaluated included caregiver mental health (GHQ-28), anxiety (STAI), and depression (CES-D). Trial registration: ISRCTN16513116. RESULTS: The sample comprised 76 informal caregivers (41 allocated in the intervention condition and 35 in the control). The caregiver's burden (ZBI) did not show significant differences between groups at 4 months or 8 months. There were favorable and significant changes in the caregiver's mental health (GHQ) and depression (CES-D) at 4 months in the PIP group. There were no significant differences between groups in anxiety during the trial. CONCLUSIONS: The PIP intervention group reported positive effects on general mental health and depression after the intervention but not at follow-up. We need more studies which interventions follow expert recommendations and can sustain positive results over time.

RESUMEN

Significance: Conventional ultrasound-guided vascular access procedures are challenging due to the need for anatomical understanding, precise needle manipulation, and hand-eye coordination. Recently, augmented reality (AR)-based guidance has emerged as an aid to improve procedural efficiency and potential outcomes. However, its application in pediatric vascular access has not been comprehensively evaluated. Aim: We developed an AR ultrasound application, HoloUS, using the Microsoft HoloLens 2 to display live ultrasound images directly in the proceduralist's field of view. We presented our evaluation of the effect of using the Microsoft HoloLens 2 for point-of-care ultrasound (POCUS)-guided vascular access in 30 pediatric patients. Approach: A custom software module was developed on a tablet capable of capturing the moving ultrasound image from any ultrasound machine's screen. The captured image was compressed and sent to the HoloLens 2 via a hotspot without needing Internet access. On the HoloLens 2, we developed a custom software module to receive, decompress, and display the live ultrasound image. Hand gesture and voice command features were implemented for the user to reposition, resize, and change the gain and the contrast of the image. We evaluated 30 (15 successful control and 12 successful interventional) cases completed in a single-center, prospective, randomized study. Results: The mean overall rendering latency and the rendering frame rate of the HoloUS application were 139.30 ms ( σ = 32.02 ms ) and 30 frames per second, respectively. The average procedure completion time was 17.3% shorter using AR guidance. The numbers of puncture attempts and needle redirections were similar between the two groups, and the number of head adjustments was minimal in the interventional group. Conclusion: We presented our evaluation of the results from the first study using the Microsoft HoloLens 2 that investigates AR-based POCUS-guided vascular access in pediatric patients. Our evaluation confirmed clinical feasibility and potential improvement in procedural efficiency.

RESUMEN

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy. Most (80%) children with XLMTM have profound muscle weakness and hypotonia at birth resulting in severe respiratory insufficiency, the inability to sit up, stand or walk, and early mortality. At birth, 85-90% of children with XLMTM require mechanical ventilation, with more than half requiring invasive ventilator support. Historically, ventilator-dependent children with neuromuscular-derived respiratory failure of this degree and nature, static or progressive, are not expected to achieve complete independence from mechanical ventilator support. In the ASPIRO clinical trial (NCT03199469), participants receiving a single intravenous dose of an investigational gene therapy (resamirigene bilparvovec) started showing significant improvements in daily hours of ventilation support compared with controls by 24 weeks post-dosing, and 16 of 24 dosed participants achieved ventilator independence between 14 and 97 weeks after dosing. At the time, there was no precedent or published guidance for weaning chronically ventilated children with congenital neuromuscular diseases off mechanical ventilation. When the first ASPIRO participants started showing dramatically improved respiratory function, the investigators initiated efforts to safely wean them off ventilator support, in parallel with primary protocol respiratory outcome measures. A group of experts in respiratory care and physiology and management of children with XLMTM developed an algorithm to safely wean children in the ASPIRO trial off mechanical ventilation as their respiratory muscle strength increased. The algorithm developed for this trial provides recommendations for assessing weaning readiness, a stepwise approach to weaning, and monitoring of children during and after the weaning process.

Asunto(s)

RESUMEN

Previous studies have found direct associations between glycaemic index (GI) and glycaemic load (GL) with chronic diseases. However, this evidence has not been consistent in relation to mortality, and most data regarding this association come from high-income and low-carbohydrate-intake populations. The aim of this study was to evaluate the association between the overall GI and dietary GL and all-cause mortality, CVD and breast cancer mortality in Mexico. Participants from the Mexican Teachers' Cohort (MTC) study in 2006-2008 were followed for a median of 10 years. Overall GI and dietary GL were calculated from a validated FFQ. Deaths were identified by the cross-linkage of MTC participants with two national mortality registries. Cox proportional hazard models were used to estimate the impact of GI and GL on mortality. We identified 1198 deaths. Comparing the lowest and highest quintile, dietary GI and GL appeared to be marginally associated with all-cause mortality; GI, 1·12 (95 % CI: 0·93, 1·35); GL, 1·12 (95 % CI: 0·87, 1·44). Higher GI and GL were associated with increased risk of CVD mortality, GI, 1·30 (95 % CI: 0·82, 2·08); GL, 1·64 (95 % CI: 0·87, 3·07) and with greater risk of breast cancer mortality; GI, 2·13 (95 % CI: 1·12, 4·06); GL, 2·43 (95 % CI: 0·90, 6·59). It is necessary to continue the improvement of carbohydrate quality indicators to better guide consumer choices and to lead the Mexican population to limit excessive intake of low-quality carbohydrate foods.

RESUMEN

Loop-Mediated Isothermal Amplification (LAMP) is a useful technique for detecting infectious microorganisms in human fluids since it performs similarly to conventional PCR, the results are obtained faster and no thermocyclers or complex devices are required. Since only two isothermal blocks (95 °C to lyse cells and 65 °C for DNA amplification) are needed, LAMP is particularly suited for applications in Low- and Middle-Income Countries (LMICs). To validate such assumption, we first designed and tested Arduino-controlled LAMP thermoblocks to process a considerable number of samples simultaneously with a low-energy consumption to enable routine use under worst-case conditions (no main power source and low ambient temperatures). The thermoblocks were tested when battery-powered at temperature down to 5 °C, showing high stability in well temperatures (<0.8 °C). The charge required for both thermoblocks to simultaneously achieve the target temperatures after switching on and to keep their working temperatures were 4.1 A·h and 2.4 A·h/h, respectively. Second, we implemented a low-cost viewer with LEDs and filters to detect the fluorescent LAMP reaction. All the components required for the instrument are for general purpose and readily available by e-commerce. Thus, the LAMP device allows for considerable autonomy by using a typical car battery in rural and itinerant healthcare or field hospitals in LMICs, even under difficult environmental conditions.

RESUMEN

The aim of this study was to compare the levels of reactive oxygen species (ROS) in Bos taurus and Bos indicus in vitro embryos cryopreserved using either slow freezing or vitrification. Embryos were divided into four groups based on subspecies and freezing method: Bos indicus slow freezing (BiSF; n = 8), Bos indicus vitrification (BiVT; n = 10), Bos taurus slow freezing (BtSF; n = 9), and Bos taurus vitrification (BtVT; n = 6). After thawing, the embryos were incubated with CellRox Green and images were obtained using a confocal microscope. The fluorescence intensity of each cell was measured and expressed as arbitrary units of fluorescence (auf) and compared using a multiple regression and unpaired t-test with α = 0.05. Results showed that subspecies and the freezing method significantly affected auf (P < 0.001; R2 = 0.1213). Bos indicus embryos had higher auf than Bos taurus embryos, whether frozen by slow freezing (67.05 ± 23.18 vs 51.30 ± 16.84, P < 0.001) or vitrification (64.44 ± 23.32 vs 47.86 ± 17.53, P < 0.001). Slow freezing induced higher auf than vitrification in both Bos taurus (51.30 ± 16.84 vs 47.86 ± 17.53, P < 0.001) and Bos indicus (67.05 ± 23.18 vs 64.44 ± 23.32, P < 0.014). In conclusion, Bos taurus embryos had lower ROS levels when frozen using vitrification, while Bos indicus embryos had consistent ROS patterns regardless of the freezing method. However, Bos indicus embryos frozen by slow freezing tended to have a higher number of cells with elevated ROS levels.

RESUMEN

The biodegradation of therapeutic magnetic-oxide nanoparticles (MONPs) in the human body raises concerns about their lifespan, functionality, and health risks. Interactions between apoferritin proteins and MONPs in the spleen, liver, and inflammatory macrophages significantly accelerate nanoparticle degradation, releasing metal ions taken up by apoferritin. This can alter the protein's biological structure and properties, potentially causing health hazards. This study examines changes in apoferritin's shape, electrical surface potential (ESP), and protein-core composition after incubation with cobalt-ferrite (CoFe2O4) oxide nanoparticles. Using atomic force microscopy (AFM) and scanning Kelvin probe force microscopy (SKPFM), we observed changes in the topography and ESP distribution in apoferritin nanofilms over time. After 48 h, the characteristic apoferritin hole (∼1.35 nm) vanished, and the protein's height increased from ∼3.5 to ∼7.5 nm due to hole filling. This resulted in a significant ESP increase on the filled-apoferritin surface, attributed to the formation of a heterogeneous chemical composition and crystal structure (γ-Fe2O3, Fe3O4, CoO, CoOOH, FeOOH, and Co3O4). These changes enhance electrostatic interactions and surface charge between the protein and the AFM tip. This approach aids in predicting and improving the MONP lifespan while reducing their toxicity and preventing apoferritin deformation and dysfunction.

RESUMEN

This study investigated the molecular characteristics of urinary carbapenemase-producing Klebsiella pneumoniae isolates (n = 194) in Gauteng, South Africa, using simple, cost-effective PCR methodologies. Extensively drug resistant (XDR) ST307 with blaOXA-181 on IncX3 plasmids was endemic in Gauteng community hospitals leaving limited options for treating in- and outpatient urinary tract infections. High-level ceftazidime/avibactam resistance was detected among isolates harbouring blaOXA-48-like including blaOXA-181. These findings highlighted the need for genomic methodologies suitable for lower- and middle-income countries to track XDR clones and plasmids in community hospitals. Such results will aid with treatment and stewardship strategies.

RESUMEN

INTRODUÇÃO: Na cardiomiopatia hipertrófica (CMH) o achado mais típico na ressonância magnética é o realce tardio do mesocárdico, localizado principalmente na parede inferosseptal. Este realce não está presente em todos os casos e ocorre preferencialmente em paredes onde há maior hipertrofia. Apresentamos dois casos com fenótipo típico de CMH e padrão atípico de realce tardio. RELATO DE CASO: CASO 1-Assintomático, confirmou o diagnóstico de CMH durante a investigação de quadro recorrente de acidente vascular encefálico isquêmico. CASO 2- Histórico familiar de morte súbita, assintomático, feito diagnóstico de CMH por cascata familiar. Demais detalhes das características e achados podem ser avaliados na tabela 1. Na ressonância cardíaca: 1: hipertrofia ventricular esquerda com predomínio septal, com espessura máxima de 20 mm em septo ínfero-medial associado a presença de realce tardio miocárdico com predomínio subendocárdico difuso nos segmentos apicais. (Figura A/B). 2- aumento significativo da espessura do ápice do ventrículo direito causando redução da sua cavidade efetiva e dilatação do átrio direito. Função sistólica do ventrículo direito preservadas com presença de realce tardio subendocárdico no ápice. Espessura normal das paredes do ventrículo esquerdo com a presença de áreas de realce tardio subendocárdico circunferencial envolvendo as porções basal, médio e apical com pontos de infiltração gordurosa esparsos predominantemente na porção apical e média (Figura C/D). DISCUSSÃO E CONCLUSÃO: Na CMH, o padrão de realce tardio mais prevalente é o mesocárdico, geralmente nas paredes ventriculares onde há maior hipertrofia, e é puntiforme. Na presença de aneurisma apical na CMH, tem sido descrito o padrão transmural de realce. O realce subendocárdico circunferencial evidenciado no presente estudo, representa um achado radiológico atípico e infrequente da CMH. Suscitando amplo debate quanto a sua fisiopatologia. Após discussão, sua ocorrência foi atribuída a um possível infarto tipo 2, relacionado à isquemia na CMH por desproporção entre oferta e demanda. Assim sendo, propomos a consideração do realce tardio subendocárdico circunferencial como uma potencial apresentação da CMH e concluímos ser de suma importância clínica o reconhecimento dos diversos padrões de realce tardio, ainda que atípicos, para uma abordagem propedêutica mais precisa e eficaz.

RESUMEN

This study investigates the enhancement of polylactic acid (PLA) properties through the incorporation of graphene nanoplatelets (GNPs) and carbon black (CB) for applications in 3D printing and injection molding. The research reveals that GNPs and CB improve the electrical conductivity of PLA, although conductivity remains within the insulating range, even with up to 10% wt of nanoadditives. Mechanical characterization shows that nanoparticle addition decreases tensile strength due to stress concentration effects, while dispersants like polyethylene glycol enhance ductility and flexibility. This study compares the properties of materials processed by injection molding and 3D printing, noting that injection molding yields isotropic properties, resulting in better mechanical properties. Thermal analysis indicates that GNPs and CB influence the crystallization behavior of PLA with small changes in the melting behavior. Dynamic Mechanical Thermal Analysis (DMTA) results show how the glass transition temperature and crystallization behavior fluctuate. Overall, the incorporation of nanoadditives into PLA holds potential for enhanced performance in specific applications, though achieving optimal conductivity, mechanical strength, and thermal properties requires careful optimization of nanoparticle type, concentration, and dispersion methods.

RESUMEN

PURPOSE: To investigate the patient-reported outcomes (PROs), knee stability, and complications in prospective comparative studies of patients undergoing augmented anterior cruciate ligament (ACL) repair compared to ACL reconstruction (ACLR). METHODS: A literature search was performed according to the 2020 PRISMA guidelines. Human clinical studies of level I-II evidence comparing PROs, knee stability and complications following ACL repair and reconstruction were included, and a qualitative analysis was performed. Excluded studies included those lacking reporting outcomes, studies that performed open ACLR or repair, studies published prior to the year 2000 and studies with evidence levels III-IV. Study quality was assessed using the Cochrane Collaboration's risk of bias tool. RESULTS: Seven level of evidence I-II studies were retained including 190 ACLR and 221 repairs (75 Bridge-Enhanced ACL Repair (BEAR), 49 Suture Augmentation (SA), and 97 Dynamic Intraligamentary Stabilization (DIS)). At final follow-up, re-rupture rates varied between 0-14% (BEAR) vs 0-6% (ACLR) and mean side-to-side differences measured using KT-1000 testing ranged from 1.6-1.9mm (BEAR) vs 1.7-3.14mm (ACLR). For DIS vs ACLR, mean anterior tibial translation values at final follow-up were 1.7mm (DIS) vs. 1.4mm (ACLR), and re-rupture rates ranged from 20.8%-29% (DIS) vs. 17%-27.2% (ACLR). For SA vs ACLR, the mean side to side difference ranged from 0.2-0.39mm (SA) vs 0.33-0.4mm (ALCR), while the re-rupture rates were 10% (SA) vs. 0% (ACLR). International Knee Documentation Committee (IKDC), Tegner, Lysholm and Knee Injury and Osteoarthritis Outcome (KOOS) scores across both cohorts exhibited statistically significant, and comparable improvement, from baseline to final follow-up ranging from 1 to 5 years. CONCLUSION: Augmented ACL repair results in similar patient reported outcomes measures in comparison to ACL reconstruction. However, augmented ACL repair may be associated with higher rates of failure given re-rupture rates of up to 14%, 29% and 10% for BEAR, DIS and SA, respectively. LEVEL OF EVIDENCE: II; Systematic review of level I-II studies.

RESUMEN

Fly colonization patterns and development are crucial in estimating the post-mortem interval (PMI) of decomposing corpses. Understanding the potential effects of xenobiotics on species development in cadaveric entomofauna is essential for accurate PMI estimation, given their presence in decomposing bodies. Benzodiazepines, commonly prescribed for their anxiolytic, hypnotic, and muscle relaxant effects, are of forensic interest due to their potential for abuse, dependence, intoxication, and overdose-related deaths. This study aimed to explore the effect of clonazepam and its metabolites on Megaselia scalaris, a species commonly used to estimate PMI, the alteration of which could impact the accuracy of said estimation. The S9 biotransformation fraction, an in vitro model consisting of an array of metabolic enzymes, was used to generate phase I and II metabolites for evaluating their effect on M. scalaris development, representing an innovative approach to this type of study. Megaselia scalaris larvae were reared in synthetic growth media under controlled conditions. The study compared different groups: control, clonazepam, and clonazepam with S9 fraction. Larvae were measured daily to determine growth rate, and clonazepam concentrations were analyzed using HPLC-DAD. Results showed that larvae grown in media containing clonazepam or clonazepam with S9 fraction developed faster than control larvae, reaching their pupal stage earlier. Growth rates were also altered in treated groups. In conclusion, the presence of clonazepam and its metabolites accelerated the life cycle of M. scalaris, potentially impacting the accuracy of PMI estimation. These findings underscore the importance of considering xenobiotics in forensic entomological studies for precise post-mortem interval determination.

Asunto(s)

RESUMEN

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as volunteers challenged with ETEC, diarrheal severity is significantly increased in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of volunteers with ETEC. To understand how EtpA directs ETEC-blood group A interactions and stimulates adaptive immunity, we mutated EtpA, mapped its glycosylation by mass-spectrometry (MS), isolated polyclonal (pAbs) and monoclonal antibodies (mAbs) from vaccinated mice and ETEC-infected volunteers, and determined structures of antibody-EtpA complexes by cryo-electron microscopy. Both bgA and mAbs that inhibited EtpA-bgA interactions and ETEC adhesion, bound to the C-terminal repeat domain highlighting this region as crucial for ETEC pathogen-host interaction. MS analysis uncovered extensive and heterogeneous N-linked glycosylation of EtpA and cryo-EM structures revealed that mAbs directly engage these unique glycan containing epitopes. Finally, electron microscopy-based polyclonal epitope mapping revealed antibodies targeting numerous distinct epitopes on N and C-terminal domains, suggesting that EtpA vaccination generates responses against neutralizing and decoy regions of the molecule. Collectively, we anticipate that these data will inform our general understanding of pathogen-host glycan interactions and adaptive immunity relevant to rational vaccine subunit design.

RESUMEN

Background: Selumetinib is the first approved treatment for pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN) in the EU and US, as well as in multiple other countries. Evidence for the management of selumetinib-associated adverse events (AEs) is mostly limited to clinical trials and expanded-access programs. We gathered a panel of European healthcare practitioners with clinical experience prescribing selumetinib and/or managing pediatric patients with NF1-PN to provide recommendations on the prevention and management of AEs. Methods: A modified Delphi approach was used to develop the recommendations among the group of experts. Initial statements were developed from a literature review of current management recommendations and regulatory reports. The panel refined the statements and rated the extent to which they agreed with them in 2 sessions and a follow-up survey. The panel comprised 2 pediatric neuro-oncologists, 1 pediatric oncologist, 1 pediatrician, 1 neuropediatrician, 1 oncologist, 1 neurologist, 2 psychologists, and 1 dermatologist. Results: The experts agreed on the relative frequency and impact of AEs potentially associated with selumetinib. Consensus-level agreement was reached for 36 statements regarding the prevention and management of AEs potentially associated with selumetinib. Experts recommended treatments for AEs based on their experience. Conclusions: The development of a variety of consensus statements indicates expert agreement on best practices for the prevention and management of AEs potentially associated with selumetinib in pediatric patients with NF1-PN. These events are generally manageable and should be considered alongside treatment benefit. Information sharing is warranted as further experience is gained.