Dysfunction of proprioceptive sensory synapses is a pathogenic event and therapeutic target in mice and humans with spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by a varying degree of severity that correlates with the reduction of SMN protein levels. Motor neuron degeneration and skeletal muscle atrophy are hallmarks of SMA, but it is unknown whether other mechanisms contribute to the spectrum of clinical phenotypes. Here, through a combination of physiological and morphological studies in mouse models and SMA patients, we identify dysfunction and loss of proprioceptive sensory synapses as key signatures of SMA pathology. We demonstrate that SMA patients exhibit impaired proprioception, and their proprioceptive sensory synapses are dysfunctional as measured by the neurophysiological test of the Hoffmann reflex (H-reflex). We further show that loss of excitatory afferent synapses and altered potassium channel expression in SMA motor neurons are conserved pathogenic events found in both severely affected patients and mouse models. Lastly, we report that improved motor function and fatigability in ambulatory SMA patients and mouse models treated with SMN-inducing drugs correlate with increased function of sensory-motor circuits that can be accurately captured by the H-reflex assay. Thus, sensory synaptic dysfunction is a clinically relevant event in SMA, and the H-reflex is a suitable assay to monitor disease progression and treatment efficacy of motor circuit pathology.

Validación de test de flexión-relajación para definir un déficit lumbar con electrodos tetrapolares / Validation of the flexion-relaxation test to define a lumbar deficit with tetrapolar electrodes

Introducción y objetivo: Obtener un nuevo punto de corte (PC) para un test de flexión-relajación (FR) lumbar efectuado con electrodos (e.) tetrapolares, desde valores ya definidos con dispositivos bipolares.Materiales y métodosLa muestra del estudio consta de 47 pacientes en situación de incapacidad temporal por dolor lumbar (DL). Fueron evaluados mediante un test de dinamometría isométrica, una prueba cinemática y una valoración del fenómeno FR.Se plantean dos experimentos con curvas ROC. El primero, con 47 pacientes que efectuaron de modo consecutivo el test FR con ambos tipos de electrodos, utilizándose como variable de clasificación el punto de corte conocido para los e. bipolares (2,49uV). En el segundo, con los datos de la EMGs registrados con e. tetrapolares en 17 pacientes, se efectúa un test de DeLong que compara las 2 curvas ROC que construimos, por un lado, al clasificar la muestra desde pruebas de dinamometría y cinemática, y por el otro, al clasificarlos con los valores de la EMGs bipolar.ResultadosUn total de 34 pacientes completaron adecuadamente las valoraciones del primer experimento y 17 pacientes el segundo. El primer estudio arroja un punto de corte de 1,2uV, con un AUC del 87,7%; sensibilidad 84,2% y especificidad 80%. El segundo muestra un PC para los e. bipolares de 1,21uV (AUC 87,5%) y para los e. tetrapolares de 1,43 (AUC 82,5%) con un test de DeLong sin diferencias significativas entre ambas curvas (p>0,4065).ConclusionesLa metodología de validación con curvas ROC ha permitido obtener un nuevo PC para la prueba FR de modo práctico, simplemente simultaneando ambos test sobre el mismo grupo de pacientes hasta obtener una muestra significativa. (AU)

Introduction and objective: To obtain a new cut-off point (CP) for a lumbar flexion-relaxation (RF) test established with tetrapolar (e.) electrodes, from values already defined with bipolar devices.Materials and methodsThe study sample consists of 47 patients in a situation of temporary disability due to low back pain (DL). They were evaluated by means of an isometric dynamometry test, a kinematic test and an assessment of the FR phenomenon.Two experiments with ROC curves are proposed. The first, with 47 patients who consecutively performed the RF test with both types of electrodes, using the cut-off point (CP) known for the e. bipolar (2.49μV). In the second, with the EMG data recorded with e. tetrapolar in 17 patients, a DeLong test was performed that compares the 2 ROC curves that were constructed on the one hand, by classifying the sample from dynamometry and kinematic tests, and on the other, by classifying them with the bipolar EMG values.ResultsA total of 34 patients adequately completed the evaluations of the first experiment and 17 patients the second. The first study shows a cut-off point of 1.2μV, with an AUC of 87.7%; Sensitivity 84.2% and Specificity 80%. The second shows a PC for e. bipolars of 1.21μV (AUC 87.5%) and for e. tetrapolar values of 1.43 (AUC 82.5%) with a DeLong test without significant differences between both curves (p>0.4065).ConclusionsThe validation methodology with ROC curves has made it possible to obtain a new PC for the RF test in a practical way, simply by simultaneously performing both tests on the same group of patients until a significant sample is obtained. (AU)

In vitro activity of cefiderocol and other newly approved antimicrobials against multi-drug resistant Gram-negative pathogens recovered in intensive care units in Spain and Portugal.

OBJECTIVE: The antimicrobial resistance is a significant public health threat, particularly for healthcare-associated infections caused by carbapenem-resistant Gram-negative pathogens which are increasingly reported worldwide. The aim of this study was to provide data on the in vitro antimicrobial activity of cefiderocol and that of commercially available comparator antibiotics against a defined collection of recent clinical multi-drug resistant (MDR) microorganisms, including carbapenem resistant Gram-negative bacteria collected from different regions in Spain and Portugal. METHODS: A total of 477 clinical isolates of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia were prospectively (n=265) and retrospectively (n=212) included (2016-2019). Susceptibility testing was performed using standard broad microdilution and results were interpreted using CLSI-2021 and EUCAST-2021 criteria. RESULTS: Overall, cefiderocol showed a good activity against Enterobacterales isolates, being 99.5% susceptible by CLSI and 94.5% by EUCAST criteria. It also demonstrated excellent activity against P. aeruginosa and S. maltophilia isolates, all being susceptible to this compound considering CLSI breakpoints. Regarding A. baumannii (n=64), only one isolate was resistant to cefiderocol. CONCLUSIONS: Our results are in agreement with other studies performed outside Spain and Portugal highlighting its excellent activity against MDR gram-negative bacteria. Cefiderocol is a therapeutic alternative to those available for the treatment of infections caused by these MDR bacteria.

[Validation of the flexion-relaxation test to define a lumbar deficit with tetrapolar electrodes]. / Validación de test de flexión-relajación para definir un déficit lumbar con electrodos tetrapolares.

INTRODUCTION AND OBJECTIVE: To obtain a new cut-off point (CP) for a lumbar flexion-relaxation (RF) test established with tetrapolar (e.) electrodes, from values already defined with bipolar devices. MATERIALS AND METHODS: The study sample consists of 47 patients in a situation of temporary disability due to low back pain (DL). They were evaluated by means of an isometric dynamometry test, a kinematic test and an assessment of the FR phenomenon. Two experiments with ROC curves are proposed. The first, with 47 patients who consecutively performed the RF test with both types of electrodes, using the cut-off point (CP) known for the e. bipolar (2.49µV). In the second, with the EMG data recorded with e. tetrapolar in 17 patients, a DeLong test was performed that compares the 2 ROC curves that were constructed on the one hand, by classifying the sample from dynamometry and kinematic tests, and on the other, by classifying them with the bipolar EMG values. RESULTS: A total of 34 patients adequately completed the evaluations of the first experiment and 17 patients the second. The first study shows a cut-off point of 1.2µV, with an AUC of 87.7%; Sensitivity 84.2% and Specificity 80%. The second shows a PC for e. bipolars of 1.21µV (AUC 87.5%) and for e. tetrapolar values of 1.43 (AUC 82.5%) with a DeLong test without significant differences between both curves (p>0.4065). CONCLUSIONS: The validation methodology with ROC curves has made it possible to obtain a new PC for the RF test in a practical way, simply by simultaneously performing both tests on the same group of patients until a significant sample is obtained.

Analysis of the biological and chemical characteristics of cabbage (Brassica oleracea var. Capitata L.) Fed with compost based on sugarcane residues.

The pandemic and the geopolitical conflict between Russia and Ukraine are events that have caused economic instability in Peru. Reason that was investigated on the analysis of the biological and chemical characteristics of cabbage fed with compost based on sugarcane residues. The objective was to analyze the physical, chemical and biological characteristics of cabbage from the adequate dose of compost based on sugarcane residues and distance between plants. It is based on the methodology applied with an experimental approach, for which the Completely Random Block Design with a 4x 2 factorial arrangement was used, which consisted of 3 blocks and 8 treatments that were the combination: F1 with 0, F2 with 8, T3 with 10 and F4 with 12 t/ha and spacing (D1) with 0.30 m between plants and 0.60 m between rows and (D2) with 0.35 m between plants and 0.60 m between rows. The physical characteristics of cabbage were evaluated and processed by analysis of variance, nutrient concentrations in leaves and stomatal density were analyzed. The results determined that T7 stood out in plant height with 41.88 cm, yield with 26.76 tn/ha and T6 in root length with 20.22 cm. In chemical analysis of leaves T1 stood out in nitrogen, phosphorus, potassium and T4 in calcium, magnesium and sulfur. In T7 stomata density with 977 stomata/mm2. It concludes that at an adequate dose and greater distance that T7 stands out in the concentration of nutrients that are within normal values and high density of stomata; Therefore, these characteristics influenced the optimal biochemical reactions, which obtained good development and yield that differed at 51.39% and 32.17% with respect to the controls T1 and T5.

Order-chaos transition in correlation diagrams and quantization of period orbits.

Eigenlevel correlation diagrams has proven to be a very useful tool to understand eigenstate characteristics of classically chaotic systems. In particular, we showed in a previous publication [Phys. Rev. Lett. 80, 944 (1998)0031-900710.1103/PhysRevLett.80.944] how to unveil the scarring mechanism, a cornerstone in the theory of quantum chaos, using the Planck constant as the correlation parameter. By increasing the Planck constant, we induced a transition from order to chaos, in which scarred wave functions appeared as the interaction of pairs of eigenstates in broad avoided crossings, forming a well-defined frontier in the correlation diagram. In this paper, we demonstrate that this frontier can be obtained by means of the semiclassical quantization of the involved scarring periodic orbits. Additionally, in order to calculate the Maslov index of each scarring periodic orbit, which is necessary for the semiclassical quantization procedure, we introduce a straightforward method based on Lagrangian descriptors. We illustrate the theory using the vibrational eigenstates of the LiCN molecular system.

A comprehensive review on monitoring and purification of water through tunable 2D nanomaterials.

Instead of typical household trash, the heavy metal complexes, organic chemicals, and other poisons produced by huge enterprises threaten water systems across the world. In order to protect our drinking water from pollution, we must keep a close eye on the situation. Nanotechnology, specifically two-dimensional (2D) nanomaterials, is used in certain wastewater treatment systems. Graphene, g-C3N4, MoS2, and MXene are just a few examples of emerging 2D nanomaterials that exhibit an extraordinary ratio of surface (m3), providing material consumption, time consumption, and treatment technique for cleaning and observing water. In this post, we'll talk about the ways in which 2D nanomaterials may be tuned to perform certain functions, namely how they can be used for water management. The following is a quick overview of nanostructured materials and its possible use in water management: Also discussed in length are the applications of 2D nanomaterials in water purification, including pollutant adsorption, filtration, disinfection, and photocatalysis. Fluorescence sensors, colorimetric, electrochemical, and field-effect transistors are only some of the devices being studied for their potential use in monitoring water quality using 2D nanomaterials. Utilizing 2D content has its benefits and pitfalls when used to water management. New developments in this fast-expanding business will boost water treatment quality and accessibility in response to rising awareness of the need of clean, fresh water among future generations.

Estudio descriptivo sobre la satisfacción de las usuarias de Implanon® y los motivos para su retirada / Descriptive study on the satisfaction of Implanon users and their reasons for its removal

Introducción: Implanon®es un implante anticonceptivo subdérmico que se inserta de forma ambulatoria, contiene 68mg de etonogestrel y se incluye dentro de los métodos anticonceptivos de pauta larga reversible. Metodología: Estudio descriptivo longitudinal y retrospectivo, de las pacientes a las que se insertó Implanon® en nuestro centro entre los años 2015 y 2016. Las variables analizadas han sido: edad, motivo de inserción y retirada, tiempo hasta la retirada, grado de satisfacción de las pacientes, y embarazo no deseado durante el periodo de uso. Resultados: En el 97,3% de los casos el motivo de inserción fue la anticoncepción, pero hubo un caso de inserción para control del sangrado menstrual abundante. La edad media de inserción se situó en los 27,2 años. El porcentaje de continuidad con el método tras 3 años de seguimiento fue del 43,6%. Los motivos más frecuentes para solicitar retirada fueron sangrado uterino frecuente (16,2%) y deseo gestacional (13,5%). Respecto a la satisfacción, de forma global el 75,7% de las usuarias estaban satisfechas con el método. No se produjo ningún embarazo en las usuarias. Conclusiones: Implanon® es un método anticonceptivo de alta efectividad, principalmente utilizado por pacientes en torno a la tercera década de la vida. Los efectos secundarios más frecuentes observados son las relaciones con alteraciones del patrón de sangrado menstrual y suelen ser el uno de los motivos más frecuentes para solicitar retirada del dispositivo.(AU)

Introduction: Implanon® is a subdermal contraceptive implant that is inserted on an outpatient basis. It contains 68mg of etonogestrel, and is a long-acting reversible contraception method. Methodology: Longitudinal and retrospective descriptive study of the patients who had Implanon® inserted in our centre between 2015 and 2016. The variables analysed were age, reasons for insertion and removal, time until removal, degree of patient satisfaction, and unwanted pregnancy during the period of use. Results:In 97.3% of the cases, the reason for insertion was contraception, but there was one case of insertion to control heavy menstrual bleeding. The mean age of insertion was 27.2 years. The percentage continuing with the method after 3 years of follow-up was 43.6%. The most frequent reasons for requesting removal were frequent uterine bleeding (16.2%) and gestational desire (13.5%). Regarding satisfaction, overall 75.7% of the users were satisfied with the method. No pregnancy occurred in the users. Conclusions: Implanon® is a highly effective contraceptive method, mainly used by patients around the third decade of life. The most frequent side effects observed relate to alterations in the menstrual bleeding pattern, and are among the most frequent reasons for requesting removal of the device.(AU)

Are GES carbapenemases underdiagnosed? An allelic discrimination assay for their accurate detection and differentiation.

GES (Guiana Extended Spectrum) carbapenemases belong to "minor class A carbapenemases" and its prevalence could be underestimated due to the lack of specific tests. The aim of this study was to develop an easy PCR method to differentiate between GES ß-lactamases with or without carbapenemase activity, based on an allelic discrimination system of SNPs that encode E104K and G170S mutations, without need of sequencing. Two pair of primers and Affinity Plus probes, labeled with different fluorophores; FAM/IBFQ and YAK/IBFQ, were designed for each one of the SNPs. This allelic discrimination assay allows to detect in real time the presence of all type of GES- ß-lactamases, being able to differentiate between carbapenemases and extended-spectrum ß-lactamase (ESBL), through a quick PCR test that avoid costly sequencing approaches and could help to decrease the current underdiagnosis of minor carbapenemases that scape of phenotypic screenings.

Tendencia de egresos hospitalarios con diagnóstico de accidente cerebrovascular agudo entre los años 2018-2021 en Chile: análisis descriptivo / Hospital discharge trend with diagnosis of acute stroke between the years 2018 and 2021 in Chile: descriptive analysis

Introducción: El accidente cerebrovascular (ACV) es una afección con alta morbimortalidad, producida por la interrupción de la perfusión cerebral. Este artículo tiene como objetivo analizar la tendencia de egresos hospitalarios por ACV agudo en el periodo 2018-2021 en Chile. Metodología: Estudio descriptivo observacional, que incluyó egresos hospitalarios con diagnóstico de ACV agudo en el periodo 2018-2021, en Chile (n=19.274), según datos del Departamento de Estadísticas e Información de Salud de Chile. Se calculó la tasa de egreso hospitalario (TEH) según variable, utilizando datos del censo chileno 2017. No requirió comité de ética. Resultados: El 2018 tuvo la mayor TEH por ACV agudo (28,99) y el 2021 la menor (26,39). El grupo de "80 años y más" presenta la mayor TEH, mientras que el de "5-9 años" la menor. La mayor y menor TEH las tienen las regiones de Ñuble (263,00) y Tarapacá (10,29), respectivamente. Discusión: La disminución de TEH durante dicho periodo podría deberse al fortalecimiento de la Ley de Urgencia, al Programa Nacional de Telesalud y el impacto de la reciente pandemia. A mayor edad, aumenta la prevalencia y gravedad de las comorbilidades, lo cual explicaría la mayor TEH en el grupo más longevo. La mayor TEH masculina podría ser porque los hombres presentan mayor cantidad y severidad de factores de riesgo. La mayor TEH en la región del Ñuble posiblemente sea por los elevados niveles de pobreza y ruralidad, y la menor TEH en Tarapacá podría relacionarse con la presencia de una población nacional más joven.

Introduction: Stroke (CVA) is a condition with high morbidity and mortality, produced by the interruption of cerebral perfusion. This article aims to analyze the trend of hospital discharges for acute stroke in the period 2018-2021 in Chile. Methodology: Descriptive observational study, which included hospital discharges with a diagnosis of acute stroke in the period 2018-2021, in Chile (n=19,274), according to data from the Chilean Department of Health Statistics and Information. The hospital discharge rate (HTE) was calculated according to variable, using data from the 2017 Chilean census. No ethics committee was required. Results: 2018 had the highest HTE for acute stroke (28.99) and 2021 the lowest (26.39). The group aged "80 years and older" had the highest TEH, while the group aged "5-9 years" had the lowest TEH. The regions of Ñuble (263.00) and Tarapacá (10.29) have the highest and lowest HTE, respectively. Discussion: The decrease in HTE during this period could be due to the strengthening of the emergency law, the National Telehealth Program and the impact of the recent pandemic. The higher the age, the higher the prevalence and severity of comorbidities, which would explain the higher HTE in the older group. The higher male HTE may be due to the fact that men have a greater number and severity of risk factors. The higher HTE in the Ñuble region is possibly due to the high levels of poverty and rurality, and the lower HTE in Tarapacá would be related to having a younger national population.

Percutaneous closure of a ruptured right coronary sinus of Valsalva aneurysm that mimics severe aortic regurgitation.

A 34-year-old male was admitted with presumed acute, severe aortic regurgitation. Multimodal imaging was performed and showed a ruptured right coronary sinus of Valsalva aneurysm into the right atrium. He underwent a percutaneous closure of the ruptured sinus of Valsalva aneurysm. The patient had major clinical improvement.

Salt marsh fragmentation in a mesotidal estuary: Implications for medium to long-term management.

During the last decades many salt marshes worldwide have suffered important losses in their extent and associated ecosystem services. The salt marshes of San Vicente de la Barquera estuary (N Spain) are a clear example of this, with a drastic reduction in vegetation surface over the last 60 years. This paper provides insights into the main factors controlling salt marsh functioning in sheltered estuarine areas. Regional and local factors have been disaggregated to identify the main drivers controlling the functioning of the salt marsh to develop appropriate management measures according to the evolution of the system. These factors have been studied in their spatial context through detailed maps of change in vegetation cover combined with topographic data obtained from UAV and RTK-DGPS surveys. The results demonstrate that in this estuary the salt marsh area is declining following a fragmentation process. No clear pattern of vegetation loss/gain with elevation has been identified. However, the results point to increased hydrodynamic stress in the area, with stronger currents inside the estuary. This is probably the major factor responsible for the decline of the salt marshes in the San Vicente de la Barquera estuary. Furthermore, several human interventions during the 20th century (local drivers) have also probably contributed to a lower resilience against SLR (regional driver). This work demonstrates that both natural and human drivers of change need to be considered when characterizing the evolution of salt marshes, wherever efficient management strategies need to be designed.

Cambios en la masa ósea en una población infantil con diabetes mellitus tipo 1. Estudio longitudinal / Changes in bone mass in a paediatric population with type 1 diabetes mellitus. Longitudinal study

Objetivo: Evaluar, a lo largo de un seguimiento de 79,2 meses, el comportamiento de la densidad mineral ósea (DMO) determinada mediante Densitometría Axial Computarizada (DXA), la densidad mineral ósea volumétrica (DMOvol) y su relación con los datos antropométricos, junto con los parámetros relativos al metabolismo óseo (calcio, fósforo, fosfatasa alcalina, parathormona (PTH) y vitamina D (25-OH-D3)) en una población infantil con Diabetes Mellitus Tipo 1 (DM1) sin complicaciones microvasculares y un grupo control de referencia de similares características.Material y métodos: Inicialmente, se realizó un estudio transversal en 40 niños diabéticos (edad media 9,4±2,8 años) y 108 controles (9,3±1,5 años) para valorar las posibles diferencias entre ambas poblaciones. 26 pacientes del grupo diabético inicial, fueron reevaluados tras 79,2 meses de seguimiento.Resultados: Se observó que, al inicio, la masa ósea fue similar en los diabéticos y controles. Después del seguimiento, la DMO de los niños diabéticos era muy inferior a la esperada en población infantil no diabética.El peso, la altura y el Índice de Masa Corporal (IMC) siguieron el mismo patrón que la DMO. Los valores de calcio, fósforo, fosfatasa alcalina, PTH y vitamina D, aunque en rango de normalidad, fueron más bajos que en los controles. La fosfatasa alcalina no se incrementó en el periodo puberal.Conclusiones: El presente estudio demuestra que los niños y adolescentes con un diagnóstico reciente de DM1 tienen una DMO normal. Sin embargo, con el paso del tiempo, y sobre todo durante la adolescencia, muestran una menor ganancia de masa ósea y alteraciones en los parámetros de recambio óseo. (AU)

Lagrangian descriptors for the Bunimovich stadium billiard.

We apply the concept of Lagrangian descriptors to the dynamics on the Bunimovich stadium billiard, a two-dimensional ergodic system with singular families of trajectories, namely, the bouncing ball and the whispering gallery orbits. They play a central role in structuring the phase space, which is unveiled here by means of the Lagrangian descriptors applied to the associated map on the boundary. More interestingly, we also consider the open stadium, which in the optical case (Fresnel's laws) can be directly related to recent microlaser experiments. We find that the structure of the emission profile of these systems can be easily described thanks to the open version of the Lagrangian descriptors.

Microstructure, corrosion rate, and mechanical properties of unidirectionally and cross-rolled Mg-0.375Ga and Mg-0.750Ga alloys.

The effect of unidirectional and cross rolling on the corrosion rate, texture, tensile properties and hemolysis of the Mg-0.375Ga and Mg-0.750Ga alloys was evaluated. Pure Mg and as-cast alloys were processed by unidirectional and cross rolling at 400°C to obtain a total thickness reduction of 50%. The corrosion rate was measured by the weight loss method in simulated body fluid. Determination of the hemolysis percentage was carried out by direct contact of specimens with diluted blood. After hot rolling, the mechanical properties of the alloys were improved. The cross-rolled Mg-0.750Ga alloy showed the highest grain refinement (55 µm) and the highest ultimate tensile strength (240 MPa), however, lower elongation (13.9%) than the rolled Mg-0.375Ga alloy. While unidirectional rolling creates a strong basal texture, cross rolling weakens considerably this texture. The Ga addition weakens the basal texture. Corrosion rate of the Mg-Ga alloys was significantly reduced (<1 mm/yr) after heat treatment and hot rolling due the homogenization of the microstructure and the presence of gallium as alloying element. The cross-rolled samples showed higher corrosion than the heat-treated and unidirectionally rolled samples. After rolling, alloys showed hemolysis percentages between 7.1 and 9.3%, values lower than those presented by pure magnesium (>22.7%) and as-cast alloys (>24.2%); however, the alloys are still hemolytic (>5%).