VEGF expression disparities in brainstem motor neurons of the SOD1G93A ALS model: Correlations with neuronal vulnerability.

Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease characterized by severe muscle weakness mainly due to degeneration and death of motor neurons. A peculiarity of the neurodegenerative processes is the variable susceptibility among distinct neuronal populations, exemplified by the contrasting resilience of motor neurons innervating the ocular motor system and the more vulnerable facial and hypoglossal motor neurons. The crucial role of vascular endothelial growth factor (VEGF) as a neuroprotective factor in the nervous system is well-established since a deficit of VEGF has been related to motoneuronal degeneration. In this study, we investigated the survival of ocular, facial, and hypoglossal motor neurons utilizing the murine SOD1G93A ALS model at various stages of the disease. Our primary objective was to determine whether the survival of the different brainstem motor neurons was linked to disparate VEGF expression levels in resilient and susceptible motor neurons throughout neurodegeneration. Our findings revealed a selective loss of motor neurons exclusively within the vulnerable nuclei. Furthermore, a significantly higher level of VEGF was detected in the more resistant motor neurons, the extraocular ones. We also examined whether TDP-43 dynamics in the brainstem motor neuron of SOD mice was altered. Our data suggests that the increased VEGF levels observed in extraocular motor neurons may potentially underlie their resistance during the neurodegenerative processes in ALS in a TDP-43-independent manner. Our work might help to better understand the underlying mechanisms of selective vulnerability of motor neurons in ALS.

La nueva era de las enfermedades neurodegenerativas. La base de los nuevos abordajes / The new age of neurodegenerative diseases. The basis of the new approaches

La detección por biomarcadores de los procesos fisiopatológicos y moleculares implicados en las enfermedades cerebrales por plegamiento anormal de proteínas está permitiendo delinear la historia natural de estos procesos. La gran mayoría de ellos tiene una fase preclínica prolongada, en la que los cambios biológicos son patentes. Las manifestaciones clínicas (fenotipos) no tienen una correspondencia unívoca con la patología subyacente, a pesar de que se han utilizado los epónimos anatomopatológicos para la descripción de los síndromes clínicos, lo que ha favorecido la imprecisión diagnóstica. Para realizar un adecuado manejo clínico debemos conocer los tres planos que definen actualmente los procesos neurodegenerativos más frecuentes. La precisión diagnóstica será un prerrequisito para las nuevas terapias dirigidas a modificar el curso de las enfermedades por plegamiento proteico cerebrales. (AU)

The detection by biomarkers of the pathophysiological and molecular processes involved in misfolding protein diseases making it possible to delineate the natural history of these processes. The great majority of protein misfolding diseases have a prolonged preclinical phase, in which the biological changes are patent. The clinical manifestations (i.e., phenotypes) do not have a univocal correspondence with the underlying pathology, despite the fact that pathological eponyms have been used for the description of the clinical syndromes, which has favored diagnostic inaccuracy. In order to perform an adequate clinical management, we must know the 3 planes that currently define the most common neurodegenerative processes. Diagnostic accuracy will be a prerequisite for new therapies aimed at modifying the course of brain protein misfolding diseases. (AU)

[The new age of neurodegenerative diseases. The basis of the new approaches]. / La nueva era de las enfermedades neurodegenerativas. La base de los nuevos abordajes.

The detection by biomarkers of the pathophysiological and molecular processes involved in misfolding protein diseases making it possible to delineate the natural history of these processes. The great majority of protein misfolding diseases have a prolonged preclinical phase, in which the biological changes are patent. The clinical manifestations (i.e., phenotypes) do not have a univocal correspondence with the underlying pathology, despite the fact that pathological eponyms have been used for the description of the clinical syndromes, which has favored diagnostic inaccuracy. In order to perform an adequate clinical management, we must know the 3 planes that currently define the most common neurodegenerative processes. Diagnostic accuracy will be a prerequisite for new therapies aimed at modifying the course of brain protein misfolding diseases.

TITLE: La nueva era de las enfermedades neurodegenerativas. La base de los nuevos abordajes.La detección por biomarcadores de los procesos fisiopatológicos y moleculares implicados en las enfermedades cerebrales por plegamiento anormal de proteínas está permitiendo delinear la historia natural de estos procesos. La gran mayoría de ellos tiene una fase preclínica prolongada, en la que los cambios biológicos son patentes. Las manifestaciones clínicas (fenotipos) no tienen una correspondencia unívoca con la patología subyacente, a pesar de que se han utilizado los epónimos anatomopatológicos para la descripción de los síndromes clínicos, lo que ha favorecido la imprecisión diagnóstica. Para realizar un adecuado manejo clínico debemos conocer los tres planos que definen actualmente los procesos neurodegenerativos más frecuentes. La precisión diagnóstica será un prerrequisito para las nuevas terapias dirigidas a modificar el curso de las enfermedades por plegamiento proteico cerebrales.

Electrochemical sensing platform with gold nanoparticles capped by PDDA for benzyl alcohol determination.

An electrochemical sensor has been developed, by modifying screen-printed carbon devices (SPCE) with photochemically synthesized gold nanoparticles (AuNP), to determine benzyl alcohol, a preservative widely used in the cosmetic industry. To obtain the AuNP with the best properties for electrochemical sensing applications, the photochemical synthesis was optimized using chemometric tools. A response surface methodology based on central composite design was used to optimize the synthesis conditions, as irradiation time, and the concentrations of metal precursor and the capping/reducing agent (poly(diallyldimethylammonium) chloride, PDDA). The anodic current of benzyl alcohol on SPCE modified with the AuNP was used as response of the system. The best electrochemical responses were obtained using the AuNP generated by irradiating for 18 min a 7.20 [Formula: see text] 10-4 mol L-1 AuCl4--1.7% PDDA solution. The AuNP were characterized by transmission electron microscopy, cyclic voltammetry and dynamic light scattering. The nanocomposite-based sensor formed by the optimal AuNP (AuNP@PDDA/SPCE) was used to determine benzyl alcohol by linear sweep voltammetry in 0.10 mol L-1 KOH. The anodic current at + 0.017 ± 0.003 V (vs. AgCl) was used as analytical signal. Detection limit obtained under these conditions was 2.8 µg mL-1. The AuNP@PDDA/SPCE was applied to determine benzyl alcohol  in cosmetic samples.

Cáncer de testículo asociado a microlitiasis testicular / Association between testicular cancer and microlithiasis

Introducción: En la actualidad no existe evidencia que determine de forma concreta la relación entre microlitiasis testicular sola o en relación con otros factores como elemento de riesgo para el desarrollo de tumores testiculares, además de no existir recomendaciones claras sobre el seguimiento de esta condición. El objetivo de esta revisión es aportar con una guía para el seguimiento de estos pacientes basado en la evidencia de la literatura. Métodos: Se realizó una revisión de literatura durante diciembre de 2021 en PubMed, base de datos Cochrane y TRIP Database, la selección de los artículos se realizó por medio de las recomendaciones de PRISMA 2020. Resultados: Un total de 4 revisiones sistemáticas fueron seleccionadas para el trabajo final. Se logró determinar que la asociación de microlitiasis testicular a otros factores de riesgo incrementa aún más el riesgo de desarrollo de cáncer, sin embargo, en ausencia de estos factores el riesgo el riesgo de cáncer testicular es similar al de la población general. Conclusiones: En pacientes con riesgo de desarrollo de cáncer testicular se recomienda un seguimiento individualizado dependiendo de la edad, de los factores de riesgo asociados, de la infertilidad y del síndrome de disgenesia testicular, para poder determinar la necesidad de seguimiento versus realización de biopsia testicular. (AU)

Introduction: Currently, no evidence determines the relationship between testicular microlithiasis by itself, or in relation with other factors, as a risk factor for the development of testicular tumors. There are no clear recommendations regarding the follow-up of this medical condition. Therefore, this review aims to provide a guide to monitoring these patients, supported by the literature. Methodology: A literature review was carried out in December 2021 in PubMed, Cochrane, and TRIP Database, and the selection of the articles was made following the PRISMA 2020 recommendations. Results: Overall, the four systematic reviews chosen to conduct the final study determined that the combination of microlithiasis testicular with other risk factors further increased cancer development. However, the likelihood of testicular cancer risk is similar to that of the general population. Conclusions: Patients at risk of developing testicular cancer should undergo personalized monitoring according to their age, associated risk factors, infertility, and testicular dysgenesis syndrome to determine their follow-up needs or perform a testicular biopsy. (AU)

A MWCNTs-COOH/PSS nanocomposite-modified screen-printed electrode for the determination of synthetic phenolic antioxidants by HPLC with amperometric detection.

New sensing platforms based on screen-printed carbon electrodes modified with composites based on polystyrene sulfonate and oxidized multi-walled carbon nanotubes (PSS/MWCNTs-COOH/SPCE) have been used to develop a novel HPLC method with electrochemical detection (ECD) for the determination of the most used synthetic phenolic antioxidants in cosmetics: butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), tert-butylhydroquinone (TBHQ) and propyl gallate (PG). Optimal separation conditions were achieved using methanol: 0.10 mol L-1 acetate solution at pH 6 as mobile phase with a gradient elution program from 60 to 90% of methanol percentage in 15 min. The electrochemical detection was carried out in amperometric mode using the PSS/MWCNTs-COOH/SPCE at + 0.80 V vs. Ag. Under these optimal separation and detection conditions, the limits of detection (LOD) were between 0.11 and 0.25 mg L-1. These LOD values were better, especially for BHT, than those previously published in other HPLC methods. Linear ranges from 0.37 mg L-1, 0.83 mg L-1, 0.69 mg L-1 and 0.56 mg L-1 to 10 mg L-1 were obtained for PG, TBHQ, BHA and BHT, respectively. RSD values equal or lower than 5% and 8% were achieved for repeatability and reproducibility, respectively. The HPLC-ECD method was successfully applied to analyze different cosmetic samples. Recovery values within 83-109% were obtained in the validation studies.

Association between testicular cancer and microlithiasis.

INTRODUCTION: Currently, no evidence determines the relationship between testicular microlithiasis by itself, or in relation with other factors, as a risk factor for the development of testicular tumors. There are no clear recommendations regarding the follow-up of this medical condition. Therefore, this review aims to provide a guide to monitoring these patients, supported by the literature. METHODOLOGY: A literature review was carried out in December 2021 in PubMed, Cochrane, and Trip databases, and the selection of the articles was made following the PRISMA 2020 recommendations. RESULTS: Overall, the four systematic reviews chosen to conduct the final study determined that the combination of microlithiasis testicular with other risk factors further increased cancer development. However, the likelihood of testicular cancer risk is similar to that of the general population. CONCLUSIONS: Patients at risk of developing testicular cancer should undergo personalized monitoring according to their age, associated risk factors, infertility, and testicular dysgenesis syndrome to determine their follow-up needs or perform a testicular biopsy.

Validación de los modelos de impresión 3D paciente-específicos para cirugía ortopédica oncológica pélvica / Validation of patient-specific 3D impression models for pelvic oncological orthopedic surgery

Introducción: Los tumores del anillo pélvico suponen un reto por la dificultad de obtener márgenes quirúrgicos adecuados. Herramientas como la navegación quirúrgica o la impresión 3D para la fabricación de plantillas de posicionamiento quirúrgico paciente-específicas ayudan en la planificación preoperatoria y la ejecución intraoperatoria. Su correcta colocación es fundamental en localizaciones complejas como la pelvis, por lo que es necesario identificar los errores de posicionamiento. El objetivo de este estudio es demostrar la fiabilidad en la colocación de plantillas 3D para la realización de osteotomías en el anillo pélvico. Material y métodos: Estudio experimental en cadáver con 10 hemipelvis. Se realiza TC para la obtención del modelo tridimensional, planificación de osteotomías, diseño de plantillas de posicionamiento en rama isquiopubiana (I), iliopubiana (P), supracetabular (S) y cresta iliaca (C); y un marcador de posicionamiento (rigid-body) sobre las plantillas C y S para la navegación. Las plantillas y el rigid-body son impresos en 3D y se colocan según planificación previa. La navegación permite comprobar la posición final de las plantillas y de las osteotomías. Resultados: El posicionamiento de las plantillas respecto a la planificación preoperatoria varió dependiendo de la localización, siendo mayor el error en las de cresta iliaca. Utilizando la navegación, la media de error de distancia al plano de corte está en 3,5mm, excepto en pubis (5-8mm), estando condicionado por la posición del rigid body. Conclusión: El uso de plantillas paciente-específicas impresas en 3D es una herramienta fiable para la realización de osteotomías en cirugía oncológica pélvica.(AU)

Introduction: Pelvic ring tumors pose a challenge due to the difficulty in obtaining adequate surgical margins. Tools such as surgical navigation or 3D printing for the fabrication of patient-specific surgical positioning templates help in preoperative planning and intraoperative execution. Their correct positioning is essential in complex locations such as the pelvis, so it is necessary to identify positioning errors. The aim of this study is to demonstrate the reliability of 3D template placement for pelvic ring osteotomies. Material and methods: Experimental study in cadaver with 10 hemipelvis. CT was performed to obtain the three-dimensional model, planning of osteotomies, design of positioning templates in ischiopubic (I), iliopubic (P), supracetabular (S) and iliac crest (C) branches; and a positioning marker (rigid-body) on the C and S templates for navigation. The templates and rigid-body are 3D printed and positioned according to pre-planning. Navigation allows the final position of the inserts and osteotomies to be checked. Results: The positioning of the templates with respect to the preoperative planning varied depending on the location, being greater the error in those of the iliac crest. Using navigation the mean error of distance to the cutting plane is 3.5mm, except in pubis 5-8mm), being conditioned by the position of the rigid body. Conclusion: The use of patient-specific templates printed in 3D is a reliable tool for performing osteotomies in pelvic cancer surgery.(AU)

[Translated article] Validation of patient-specific 3D impression models for pelvic oncological orthopedic surgery / Validación de los modelos de impresión 3D paciente-específicos para cirugía ortopédica oncológica pélvica

Introducción: Los tumores del anillo pélvico suponen un reto por la dificultad de obtener márgenes quirúrgicos adecuados. Herramientas como la navegación quirúrgica o la impresión 3D para la fabricación de plantillas de posicionamiento quirúrgico paciente-específicas ayudan en la planificación preoperatoria y la ejecución intraoperatoria. Su correcta colocación es fundamental en localizaciones complejas como la pelvis, por lo que es necesario identificar los errores de posicionamiento. El objetivo de este estudio es demostrar la fiabilidad en la colocación de plantillas 3D para la realización de osteotomías en el anillo pélvico. Material y métodos: Estudio experimental en cadáver con 10 hemipelvis. Se realiza TC para la obtención del modelo tridimensional, planificación de osteotomías, diseño de plantillas de posicionamiento en rama isquiopubiana (I), iliopubiana (P), supracetabular (S) y cresta iliaca (C); y un marcador de posicionamiento (rigid-body) sobre las plantillas C y S para la navegación. Las plantillas y el rigid-body son impresos en 3D y se colocan según planificación previa. La navegación permite comprobar la posición final de las plantillas y de las osteotomías. Resultados: El posicionamiento de las plantillas respecto a la planificación preoperatoria varió dependiendo de la localización, siendo mayor el error en las de cresta iliaca. Utilizando la navegación, la media de error de distancia al plano de corte está en 3,5mm, excepto en pubis (5-8mm), estando condicionado por la posición del rigid body. Conclusión: El uso de plantillas paciente-específicas impresas en 3D es una herramienta fiable para la realización de osteotomías en cirugía oncológica pélvica.(AU)

Introduction: Pelvic ring tumors pose a challenge due to the difficulty in obtaining adequate surgical margins. Tools such as surgical navigation or 3D printing for the fabrication of patient-specific surgical positioning templates help in preoperative planning and intraoperative execution. Their correct positioning is essential in complex locations such as the pelvis, so it is necessary to identify positioning errors. The aim of this study is to demonstrate the reliability of 3D template placement for pelvic ring osteotomies. Material and methods: Experimental study in cadaver with 10 hemipelvis. CT was performed to obtain the three-dimensional model, planning of osteotomies, design of positioning templates in ischiopubic (I), iliopubic (P), supracetabular (S) and iliac crest (C) branches; and a positioning marker (rigid-body) on the C and S templates for navigation. The templates and rigid-body are 3D printed and positioned according to pre-planning. Navigation allows the final position of the inserts and osteotomies to be checked. Results: The positioning of the templates with respect to the preoperative planning varied depending on the location, being greater the error in those of the iliac crest. Using navigation the mean error of distance to the cutting plane is 3.5mm, except in pubis 5-8mm), being conditioned by the position of the rigid body. Conclusion: The use of patient-specific templates printed in 3D is a reliable tool for performing osteotomies in pelvic cancer surgery.(AU)

[Translated article] Validation of patient-specific 3D impression models for pelvic oncological orthopedic surgery.

INTRODUCTION: Pelvic ring tumours pose a challenge due to the difficulty in obtaining adequate surgical margins. Tools such as surgical navigation or 3D printing for the fabrication of patient-specific surgical positioning templates help in preoperative planning and intraoperative execution. Their correct positioning is essential in complex locations such as the pelvis, so it is necessary to identify positioning errors. The aim of this study is to demonstrate the reliability of 3D template placement for pelvic ring osteotomies. MATERIAL AND METHODS: Experimental study in cadaver with 10 hemipelvis. CT was performed to obtain the three-dimensional model, planning of osteotomies, design of positioning templates in ischiopubic (I), iliopubic (P), supracetabular (S) and iliac crest (C) branches; and a positioning marker (rigid-body) on the C and S templates for navigation. The templates and rigid-body are 3D printed and positioned according to pre-planning. Navigation allows the final position of the inserts and osteotomies to be checked. RESULTS: The positioning of the templates with respect to the preoperative planning varied depending on the location, being greater the error in those of the iliac crest. Using navigation the mean error of distance to the cutting plane is 3.5mm, except in pubis (5-8mm), being conditioned by the position of the rigid body. CONCLUSION: The use of patient-specific templates printed in 3D is a reliable tool for performing osteotomies in pelvic cancer surgery.

Insulin-like Growth Factor I Couples Metabolism with Circadian Activity through Hypothalamic Orexin Neurons.

Uncoupling of metabolism and circadian activity is associated with an increased risk of a wide spectrum of pathologies. Recently, insulin and the closely related insulin-like growth factor I (IGF-I) were shown to entrain feeding patterns with circadian rhythms. Both hormones act centrally to modulate peripheral glucose metabolism; however, whereas central targets of insulin actions are intensely scrutinized, those mediating the actions of IGF-I remain less defined. We recently showed that IGF-I targets orexin neurons in the lateral hypothalamus, and now we evaluated whether IGF-I modulates orexin neurons to align circadian rhythms with metabolism. Mice with disrupted IGF-IR activity in orexin neurons (Firoc mice) showed sexually dimorphic alterations in daily glucose rhythms and feeding activity patterns which preceded the appearance of metabolic disturbances. Thus, Firoc males developed hyperglycemia and glucose intolerance, while females developed obesity. Since IGF-I directly modulates orexin levels and hepatic expression of KLF genes involved in circadian and metabolic entrainment in an orexin-dependent manner, it seems that IGF-I entrains metabolism and circadian rhythms by modulating the activity of orexin neurons.

Disposable screen-printed carbon-based electrodes in amperometric detection for simultaneous determination of parabens in complex-matrix personal care products by HPLC.

Parabens are chemicals widely used as preservatives in different types of industrial products. In recent years, the concern about the safety of these compounds has increased due to their endocrine disrupting activity. For this reason, their use is highly regulated and even some of them have already been banned. Thus, methods for the sensitive and selective detection of these compounds are required to control their presence in food, cosmetic, and pharmaceutical products. This paper presents an HPLC method with electrochemical detection using disposable screen-printed electrodes (SPE) for simultaneous determination of 6 different parabens in personal care products. Electrochemical behaviour of parabens was studied on SPE with different carbon-based materials as working electrode: carbon, ordered mesoporous carbon and graphene. From these studies, pH, detection potential, and the most adequate SPE were chosen. Due to the wide range of textures and viscosities (e.g., liquid, solid, and semi-solid) of personal care products, adequate sample pretreatments are required before chromatographic measurement. Here, a fast ultrasound-assisted extraction method was applied to simultaneously extract 6 parabens (methyl-, ethyl-, isopropyl-, propyl-, butyl-and benzyl-paraben) from different complex-matrix cosmetic products. Instrumental limits of detection between 20 and 115 µg L-1 were obtained applying +1.0 V (vs. Ag) as detection potential on carbon-based SPE. The total analysis time, including sample extraction and HPLC run, was shorter than 35 min. The proposed method is more versatile and faster than the current available methods and has been successfully applied to determine parabens in commercial samples such as shampoos, body creams, facial tonics, and toothpastes.

Insulin-like growth factor I mitigates post-traumatic stress by inhibiting AMP-kinase in orexin neurons.

Maladaptive coping behaviors are probably involved in post-traumatic stress disorders (PTSD), but underlying mechanisms are incompletely understood. We now report that mice lacking functional insulin-like growth factor I (IGF-I) receptors in orexin neurons of the lateral hypothalamus (Firoc mice) are unresponsive to the anxiolytic actions of IGF-I and develop PTSD-like behavior that is ameliorated by inhibition of orexin neurons. Conversely, systemic IGF-I treatment ameliorated PTSD-like behavior in a wild-type mouse model of PTSD (PTSD mice). Further, systemic IGF-I modified the GABA/Glutamate synaptic structure in orexin neurons of naïve wild-type mice by increasing the dephosphorylation of GABA(B) receptor subunit through inhibition of AMP-kinase (AMPK). Significantly, pharmacological inhibition of AMPK mimicked IGF-I, normalizing fear behavior in PTSD mice. Thus, we suggest that IGF-I enables coping behaviors by balancing E/I input onto orexin neurons in a context-dependent manner. These observations provide a novel therapeutic approach to PTSD through modulation of AMPK.

Validation of patient-specific 3D impression models for pelvic oncological orthopedic surgery. / Validación de los modelos de impresión 3D paciente-específicos para cirugía ortopédica oncológica pélvica.

INTRODUCTION: Pelvic ring tumors pose a challenge due to the difficulty in obtaining adequate surgical margins. Tools such as surgical navigation or 3D printing for the fabrication of patient-specific surgical positioning templates help in preoperative planning and intraoperative execution. Their correct positioning is essential in complex locations such as the pelvis, so it is necessary to identify positioning errors. The aim of this study is to demonstrate the reliability of 3D template placement for pelvic ring osteotomies. MATERIAL AND METHODS: Experimental study in cadaver with 10 hemipelvis. CT was performed to obtain the three-dimensional model, planning of osteotomies, design of positioning templates in ischiopubic (I), iliopubic (P), supracetabular (S) and iliac crest (C) branches; and a positioning marker (rigid-body) on the C and S templates for navigation. The templates and rigid-body are 3D printed and positioned according to pre-planning. Navigation allows the final position of the inserts and osteotomies to be checked. RESULTS: The positioning of the templates with respect to the preoperative planning varied depending on the location, being greater the error in those of the iliac crest. Using navigation the mean error of distance to the cutting plane is 3.5mm, except in pubis (5-8mm), being conditioned by the position of the rigid body. CONCLUSION: The use of patient-specific templates printed in 3D is a reliable tool for performing osteotomies in pelvic cancer surgery.

Serotypes and Clonal Composition of Streptococcus pneumoniae Isolates Causing IPD in Children and Adults in Catalonia before 2013 to 2015 and after 2017 to 2019 Systematic Introduction of PCV13.

The goal of this study was to investigate the distribution of serotypes and clonal composition of Streptococcus pneumoniae isolates causing invasive pneumococcal disease (IPD) in Catalonia, before and after systematic introduction of PCV13. Pneumococcal strains isolated from normally sterile sites obtained from patients of all ages with IPD received between 2013 and 2019 from 25 health centers of Catalonia were included. Two study periods were defined: presystematic vaccination period (2013 and 2015) and systematic vaccination period (SVP) (2017 to 2019). A total of 2,303 isolates were analyzed. In the SVP, there was a significant decrease in the incidence of IPD cases in children 5 to 17 years old (relative risk [RR] 0.61; 95% confidence interval [CI] 0.38 to 0.99), while there was a significant increase in the incidence of IPD cases in 18- to 64-year-old adults (RR 1.33; 95% CI 1.16 to 1.52) and adults over 65 years old (RR 1.23; 95% CI 1.09 to 1.38). Serotype 8 was the major emerging serotype in all age groups except in 5- to 17-year-old children. In children younger than 5 years old, the main serotypes in SVP were 24F, 15A, and 3, while in adults older than 65 years they were serotypes 3, 8, and 12F. A significant decrease in the proportions of clonal complexes CC156, CC191, and ST306 and an increase in those of CC180, CC53, and CC404 were observed. A steady decrease in the incidence of IPD caused by PCV13 serotypes indicates the importance and impact of systematic vaccination. The increase of non-PCV13 serotypes highlights the need to expand serotype coverage in future vaccines and rethink vaccination programs for older adults. IMPORTANCE We found that with the incorporation of the PCV13 vaccine, the numbers of IPD cases caused by serotypes included in this vaccine decreased in all of the age groups. Still, there was an unforeseen increase of the serotypes not included in this vaccine causing IPD, especially in the >65-year-old group. Moreover, a significant increase of serotype 3 included in the vaccine has been observed; this event has been reported by other researchers. These facts call for the incorporation of more serotypes in future vaccines and a more thorough surveillance of the dynamics of this microorganism.

Genomic Prediction of Yield Traits in Single-Cross Hybrid Rice (Oryza sativa L.).

Hybrid rice varieties can outyield the best inbred varieties by 15 - 30% with appropriate management. However, hybrid rice requires more inputs and management than inbred rice to realize a yield advantage in high-yielding environments. The development of stress-tolerant hybrid rice with lowered input requirements could increase hybrid rice yield relative to production costs. We used genomic prediction to evaluate the combining abilities of 564 stress-tolerant lines used to develop Green Super Rice with 13 male sterile lines of the International Rice Research Institute for yield-related traits. We also evaluated the performance of their F1 hybrids. We identified male sterile lines with good combining ability as well as F1 hybrids with potential further use in product development. For yield per plant, accuracies of genomic predictions of hybrid genetic values ranged from 0.490 to 0.822 in cross-validation if neither parent or up to both parents were included in the training set, and both general and specific combining abilities were modeled. The accuracy of phenotypic selection for hybrid yield per plant was 0.682. The accuracy of genomic predictions of male GCA for yield per plant was 0.241, while the accuracy of phenotypic selection was 0.562. At the observed accuracies, genomic prediction of hybrid genetic value could allow improved identification of high-performing single crosses. In a reciprocal recurrent genomic selection program with an accelerated breeding cycle, observed male GCA genomic prediction accuracies would lead to similar rates of genetic gain as phenotypic selection. It is likely that prediction accuracies of male GCA could be improved further by targeted expansion of the training set. Additionally, we tested the correlation of parental genetic distance with mid-parent heterosis in the phenotyped hybrids. We found the average mid-parent heterosis for yield per plant to be consistent with existing literature values at 32.0%. In the overall population of study, parental genetic distance was significantly negatively correlated with mid-parent heterosis for yield per plant (r = -0.131) and potential yield (r = -0.092), but within female families the correlations were non-significant and near zero. As such, positive parental genetic distance was not reliably associated with positive mid-parent heterosis.

Density-functional-theory approach to the Hamiltonian adaptive resolution simulation method.

In the Hamiltonian adaptive resolution simulation method (H-AdResS) it is possible to simulate coexisting atomistic (AT) and ideal gas representations of a physical system that belong to different subdomains within the simulation box. The Hamiltonian includes a field that bridges both models by smoothly switching on (off) the intermolecular potential as particles enter (leave) the AT region. In practice, external one-body forces are calculated and applied to enforce a reference density throughout the simulation box, and the resulting external potential adds up to the Hamiltonian. This procedure suggests an apparent dependence of the final Hamiltonian on the system's thermodynamic state that challenges the method's statistical mechanics consistency. In this paper, we explicitly include an external potential that depends on the switching function. Hence, we build a grand canonical potential for this inhomogeneous system to find the equivalence between H-AdResS and density functional theory (DFT). We thus verify that the external potential inducing a constant density profile is equal to the system's excess chemical potential. Given DFT's one-to-one correspondence between external potential and equilibrium density, we find that a Hamiltonian description of the system is compatible with the numerical implementation based on enforcing the reference density across the simulation box. In the second part of the manuscript, we focus on assessing our approach's convergence and computing efficiency concerning various model parameters, including sample size and solute concentrations. To this aim, we compute the excess chemical potential of water, aqueous urea solutions and Lennard-Jones (LJ) mixtures. The results' convergence and accuracy are convincing in all cases, thus emphasising the method's robustness and capabilities.

Variabilidad en el registro de alergias entre niveles asistenciales / Variability in allergies registration between care levels

Objetivo: El objetivo del estudio es comparar el grado de coincidencia en el registro de alergias entre las aplicaciones informáticas de los distintos niveles asistenciales (atención primaria y hospitalaria).Métodos: Estudio observacional descriptivo retrospectivo de 2 meses de duración en el que participaron todas las unidades clínicas con prescripción electrónica. Se incluyó en el estudio a todos los pacientes ingresados con al menos una alergia registrada en la aplicación informática hospitalaria. Se cuantificó el porcentaje de alergias registradas en hospital, atención primaria o ambas.Resultados: Se incluyeron 723 pacientes en los que se registraron 1.280 alergias. El ratio de alergias por paciente fue 1,77. La media de edad fue 62±37 años y el 58,37% eran mujeres. El 80,47% de las alergias registradas fueron farmacológicas.De manera global el 42,11% de todas las alergias fueron registradas en ambas aplicaciones. El 21,20% de las alergias no farmacológicas y el 47,18% de las alergias farmacológicas fueron registradas en ambas aplicaciones. Del total de las alergias farmacológicas detectadas en el estudio, el 68,08% estaban registradas en atención primaria y el 79,13% en atención hospitalaria. Respecto al total de las alergias no farmacológicas el 37,20% estaban registradas en atención primaria y el 84% en la aplicación de atención hospitalaria. Conclusiones: En nuestro estudio hemos encontrado una gran variabilidad en el registro de alergias en los diferentes niveles asistenciales. En menos de la mitad de los casos se registra la alergia en ambos niveles. (AU)

This study aims at comparing the coincidence degree between different allergy-recording computer applications that can be found in distinct levels of the health care system (primary care and hospital care).Methods: Two-month retrospective descriptive and observational study for analyzed records in Clinical Units equipped by electronic prescription. All in-patients who had at least one allergy record registered in the hospital computer application were included in the study. The percentage of allergies registered in hospital, primary care or both applications was quantified.Results: 723 patients were included, among whom 1,280 allergies were recorded. The allergy ratio per patient was 1.77. The average age was 62±37 years and 58.37% were women. 80.47% of the recorded allergies were drug-related.42.11% of global allergies were registered in both applications. 21.20% of non-drug-related allergies and 47.18% of drug-related allergies were registered in both applications. According to the total of drug allergies detected in the study, 68.08% were registered in primary care and 79.13% in hospital care. Regarding to the total of non-drug-related allergies, 37.20% were registered in primary care and 84% in hospital care.Conclusions: Our study reported a high variability in the allergy registration between the different levels of the care health system. Less than the half of allergy cases are registered in both care levels studied. (AU)

Implantación y desarrollo de un programa de conciliación farmacoterapéutica en paciente prequirúrgico del Servicio de Otorrinolaringología: proyecto QonciliaX / Implantation and development of a pharmacotherapy reconciliation program in the presurgery otorhinolariyngology patient: QonciliaX program

Introducción: El objetivo del estudio es diseñar un procedimiento normalizado de trabajo (PNT) de conciliación prequirúrgica en paciente de otorrinolaringología (ORL) con hospitalización convencional. Material y métodos: El diseño del PNT se realizó en varias fases. Fase 1: revisión bibliográfica; Fase 2: selección de pacientes candidatos, definición de responsabilidades, establecimiento del circuito de trabajo y elaboración del PNT, planificación de la consulta de farmacia; Fase 3: aprobación del PNT; Fase 4: sesiones informativas/formativas a los servicios implicados. Resultados: 1. La selección de pacientes candidatos será realizada por ORL; 2. Citación de pacientes candidatos en la consulta de farmacia previa a la consulta de preanestesía; 3. Consulta de farmacia, se obtendrá el listado farmacoterapéutico y se valorará la adherencia junto con recomendaciones dirigidas al anestesista, otorrino y médico de primaria (MAP); 4. Elaboración de un informe de conciliación; 5. En la consulta de preanestesia, el anestesista podrá consultar el informe de farmacia; 6. Durante el ingreso del paciente en el hospital, el otorrino podrá consultar el informe de farmacia; 7. Alta del paciente, en la que se le entregará un informe con recomendaciones para el MAP y un plan horario con indicaciones sobre administración de medicación. Discusión: La elección de pacientes de otorrino se basa en el hecho de tratarse de pacientes con patologías crónicas y comorbilidades y podrían beneficiarse por tanto de una atención farmacéutica. La integración de diversos profesionales en un equipo multidisciplinar permite mejorar y protocolizar el procedimiento de trabajo. Integra el ámbito de primaria y especializada mejorando de este modo la continuidad asistencial. (AU)

Introduction: The main target of the proyect is to design a Standard Operational Process (SOP) of presurgery medication reconciliation on otorhinolaryngology patients with coventional hospitalization Material and methods: The SOP design was performed in several stages. Stage 1: bibliography review; Stage 2: candidate patient selection, responsability assignments, establishment of a working circuit, SOP elaboration, pharmacy consultory planification; Stage 3: SOP approval; Stage 4: informative/formative sessions directed to the involved departments. Results: 1. Otorhinolaringoloty department will carry candidate patient selection; 2. Candidate patients pharmacy consultory appointment previous to preanesthetic consultory; 3. Pharmacy consultory, in which it will be acquired the pharmacotherapy patient list and adherence evaluation along with pharmacology recommendations directed to the anesthesiologist, otolaryngologist and primary care physician; 4. Medication reconciliation report preparation; 5. In the preanesthesic consultory, the anesthesiologist will be able to consult the pharmacy report; 6. Patient admission, during this period, the otolaryngologist may use of the pharmacy report; 7. During patient hospital discharge, the patient will be delivered a report with recommendations for the primary care physician and a mediation schedule with medication administration indactions. Discussion: Otolaryngologist patients selection is based on the fact that it is a group of patients with chronic pathologies and comorbilities and therefore, they could benefit from a pharmaceutical care. Divers professionals integration in a multidisciplinary work team, allows to improve and protocolize a Standard Operational Process. It integrates primary and specialist care, improving care continuity. (AU)