Membrane-Less Ethanol Electrooxidation over Pd-M (M: Sn, Mo and Re) Bimetallic Catalysts

The effect of the addition of three oxophilic co-metals (Sn, Mo and Re) on the electrochemical performance of Pd in the ethanol oxidation reaction (EOR) was investigated by performing half-cell and membrane-less electrolysis cell experiments. While the additions of Sn and Re were found to improve significantly the EOR performance of Pd, Mo produced no significant promotional effect. When added in significant amounts (50:50 ratio), Sn and Re produced a 3–4 fold increase in the mass-normalized oxidation peak current as compared to the monometallic Pd/C material. Both the electrochemical surface area and the onset potential also improved upon addition of Sn and Re, although this effect was more evident for Sn. Cyclic voltammetry (CV) measurements revealed a higher ability of Sn for accommodating OH- species as compared to Re, which could explain these results. Additional tests were carried out in a membrane-less electrolysis system. Pd50Re50/C and Pd50Sn50/C both showed higher activity than Pd/C in this system. Chronopotentiometric measurements at constant current were carried out to test the stability of both catalysts in the absence of a membrane. Pd50Sn50/C was significantly more stable than Pd50Re50/C, which showed a rapid increase in the potential with time. Despite operating in the absence of a membrane, both catalysts generated a high-purity (e.g., 99.99%) hydrogen stream at high intensities and low voltages. These conditions could lead to significant energy consumption savings compared to commercial water electrolyzerSe investigó el efecto de la adición de tres cometales oxófilos (Sn, Mo y Re) en el rendimiento electroquímico de Pd en la reacción de oxidación de etanol (EOR) realizando experimentos de celdas de electrólisis sin membrana y de media celda. Si bien se encontró que las adiciones de Sn y Re mejoraban significativamente el rendimiento EOR de Pd, Mo no produjo un efecto promocional significativo. Cuando se agregaron en cantidades significativas (proporción 50:50), Sn y Re produjeron un aumento de 3 a 4 veces en la corriente máxima de oxidación de masa normalizada en comparación con el material monometálico Pd/C. Tanto el área de superficie electroquímica como el potencial de inicio también mejoraron con la adición de Sn y Re, aunque este efecto fue más evidente para Sn. Las mediciones de voltamperometría cíclica (CV) revelaron una mayor capacidad de Sn para acomodar especies de OH- en comparación con Re, lo que podría explicar estos resultados. Se llevaron a cabo pruebas adicionales en un sistema de electrólisis sin membrana. PD50 Re 50 /C y Pd 50 Sn 50 /C mostraron una mayor actividad que Pd/C en este sistema. Se realizaron medidas cronopotenciométricas a corriente constante para probar la estabilidad de ambos catalizadores en ausencia de membrana. El Pd 50 Sn 50 /C fue significativamente más estable que el Pd 50 Re 50 /C, que mostró un rápido aumento del potencial con el tiempo. A pesar de operar en ausencia de una membrana, ambos catalizadores generaron una corriente de hidrógeno de alta pureza (por ejemplo, 99,99%) a intensidades altas y voltajes bajos. Estas condiciones podrían conducir a un ahorro significativo en el consumo de energía en comparación con los electrolizadores de agua comerciale

Investigaciones dendrogeomorfológicas aplicadas a la gestión de los impactos por erosión hídrica acelerada de suelos en las sendas del parque nacional de Monfragüe

En muchos espacios naturales protegidos, el flujo peatonal de visitantes se concentra en determinados sectores del área de uso público, sobre todo en la proximidad de las principales vías de acceso (carreteras, núcleos de población...) y en un reducido número de sendas y caminos peatonales que comunican los elementos más visitados. Es el caso del camino hacia la Cola de Caballo en el parque nacional de Ordesa y Monte Perdido; el camino a la ermita de San Frutos en el parque natural de las Hoces del río Duratón; o la senda que comunica el Salto del Gitano con el castillo y la ermita en el parque nacional de Monfragüe, por citar algunos ejemplos. Esta concentración de actividades de senderismo produce en determinados tramos de estos caminos y sendas (zonas con suelos arenosos o limosos y altas pendientes) una erosión hídrica acelerada por el efecto físico del pisoteo, compactación y continua fricción. En ocasiones se llegan a formar regueros, pequeños barrancos y se pierden grandes cantidades de suelos fértiles, que además fosilizan y aterran aquéllas zonas donde va a parar la escorrentía, produciendo importantes impactos en estos espacios singulares. Existen numerosos ejemplos de ingentes partidas económicas que los gestores de estos espacios protegidos tienen que destinar a la reparación y recuperación de estas sendas y su entorno. Para ayudar a los gestores es básico disponer de metodologías y herramientas que cuantifiquen esta erosión hídrica (en mm/año) delimitando qué tramos de estas sendas y caminos tienen los mayores problemas erosivos, para así determinar cuáles deben ser prioritarios en su corrección, o qué acciones de restricción de paso o determinación de capacidad de acogida, son necesarias adoptar. Para esta cuantificación son muy útiles, desde hace décadas, las técnicas dendrogeomorfológicas aplicadas a las raíces de árboles que han quedado expuestas a la intemperie por la erosión acelerada en las sendas. En este trabajo se propone una nueva metodología de medición del suelo denudado en relación con la raíz, basado en el estudio microtopográfico de la superficie utilizando moldes y réplicas de alta resolución realizados en diferentes tipos de siliconas, latex y escayolas, y su posterior escaneo tridimensional. La zona piloto donde se ha ensayado esta metodología son los senderos y caminos del parque nacional de Monfragüe (Cáceres), que presentan raíces expuestas debido a la intensa erosión hídrica acelerada como consecuencia de la elevada concentración de visitantes. Los estudios son financiados por el proyecto de investigación IDEA-GesPPNN, del OAPN (MAGRAMA)

White matter cortico-striatal tracts predict apathy subtypes in Huntington's disease

Apathy is the neuropsychiatric syndrome that correlates most highly with Huntington's disease progression, and, like early patterns of neurodegeneration, is associated with lesions to cortico-striatal connections. However, due to its multidimensional nature and elusive etiology, treatment options are limited. To disentangle underlying white matter microstructural correlates across the apathy spectrum in Huntington's disease. Forty-six Huntington's disease individuals (premanifest (N = 22) and manifest (N = 24)) and 35 healthy controls were scanned at 3-tesla and underwent apathy evaluation using the short-Problem Behavior Assessment and short-Lille Apathy Rating Scale, with the latter being characterized into three apathy domains, namely emotional, cognitive, and auto-activation deficit. Diffusion tensor imaging was used to study whether individual differences in specific cortico-striatal tracts predicted global apathy and its subdomains. We elucidate that apathy profiles may develop along differential timelines, with the auto-activation deficit domain manifesting prior to motor onset. Furthermore, diffusion tensor imaging revealed that inter-individual variability in the disruption of discrete cortico-striatal tracts might explain the heterogeneous severity of apathy profiles. Specifically, higher levels of auto-activation deficit symptoms significantly correlated with increased mean diffusivity in the right uncinate fasciculus. Conversely, those with severe cognitive apathy demonstrated increased mean diffusivity in the right frontostriatal tract and left dorsolateral prefrontal cortex to caudate nucleus tract. The current study provides evidence that white matter correlates associated with emotional, cognitive, and auto-activation subtypes may elucidate the heterogeneous nature of apathy in Huntington's disease, as such opening a door for individualized pharmacological management of apathy as a multidimensional syndrome in other neurodegenerative disorders

Discordance Between SARS-CoV-2-specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients

Background: Severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) elicited by mRNA-based vaccines in solid organ transplant (SOT) recipients and its correlation with antibody responses remain poorly characterized. Methods: We included 44 (28 kidney, 14 liver, and 2 double organ) recipients who received the full series of the mRNA-1273 vaccine. SARS-CoV-2-CMI was evaluated at baseline, before the second dose, and at 2 wk after completion of vaccination by an ELISpot-based interferon-γ FluoroSpot assay using overlapping peptides covering the S1 domain. SARS-CoV-2 immunoglobulin G seroconversion and serum neutralizing activity against the spike protein were assessed at the same points by commercial ELISA and an angiotensin-converting enzyme-2/spike antibody inhibition method, respectively. Postvaccination SARS-CoV-2-CMI was compared with 28 healthcare workers who received the BNT162b2 vaccine. Results: Positive SARS-CoV-2-CMI increased from 6.8% at baseline to 23.3% after the first mRNA-1273 dose and 59.5% after the completion of vaccination (P < 0.0001). Lower rates were observed for immunoglobulin G seroconversion (2.3%, 18.6%, and 57.1%, respectively) and neutralizing activity (2.3%, 11.6%, and 31.0%). There was a modest correlation between neutralizing titers and the magnitude of SARS-CoV-2-CMI (Spearman's rho: 0.375; P = 0.015). Fifteen recipients (35.7%) mounted SARS-CoV-2-CMI without detectable neutralizing activity, whereas 3 (7.1%) did the opposite, yielding poor categorical agreement (Kappa statistic: 0.201). Rates of positive SARS-CoV-2-CMI among SOT recipients were significantly decreased compared with nontransplant controls (82.1% and 100.0% after the first dose and completion of vaccination, respectively; P < 0.0001). Kidney transplantation, the use of tacrolimus and prednisone, and the number of immunosuppressive agents were associated with lower cell-mediated responses. Results remained unchanged when 3 recipients with prevaccination SARS-CoV-2-CMI were excluded. Conclusions: Two-thirds of SOT recipients mounted SARS-CoV-2-CMI following vaccination with mRNA-1273. Notable discordance was observed between vaccine-induced cell-mediated and neutralizing humoral immunities. Future studies should determine whether these patients with incomplete responses are effectively protected.This work was supported by the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 Research Call COV20/00181) and cofinanced by the European Development Regional Fund “A way to achieve Europe.” M.F.R. holds a research contract “Miguel Servet” (CP18/00073) and R.L.G. a research contract “Rio Hortega” (CM19/00120), both from the Instituto de Salud Carlos III, Spanish Ministry of Science and InnovationS

Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis microenvironment

Brain metastases are the most common tumor of the brain with a dismal prognosis. A fraction of patients with brain metastasis benefit from treatment with immune checkpoint inhibitors (ICI) and the degree and phenotype of the immune cell infiltration has been used to predict response to ICI. However, the anatomical location of brain lesions limits access to tumor material to characterize the immune phenotype. Here, we characterize immune cells present in brain lesions and matched cerebrospinal fluid (CSF) using single-cell RNA sequencing combined with T cell receptor genotyping. Tumor immune infiltration and specifically CD8 + T cell infiltration can be discerned through the analysis of the CSF. Consistently, identical T cell receptor clonotypes are detected in brain lesions and CSF, confirming cell exchange between these compartments. The analysis of immune cells of the CSF can provide a non-invasive alternative to predict the response to ICI, as well as identify the T cell receptor clonotypes present in brain metastasis. The use of CSF for diagnosis of metastatic brain tumors could be of clinical and patient benefit. Here the authors undertake a single-cell RNA analysis of CSF and brain to determine whether the phenotype in the CSF is reflective of the phenotype in the tumo

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6&nbsp;years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P &lt; 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100&nbsp;years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school&#x2;aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

White matter cortico-striatal tracts predict apathy subtypes in Huntington's disease

Apathy is the neuropsychiatric syndrome that correlates most highly with Huntington's disease progression, and, like early patterns of neurodegeneration, is associated with lesions to cortico-striatal connections. However, due to its multidimensional nature and elusive etiology, treatment options are limited. To disentangle underlying white matter microstructural correlates across the apathy spectrum in Huntington's disease. Forty-six Huntington's disease individuals (premanifest (N = 22) and manifest (N = 24)) and 35 healthy controls were scanned at 3-tesla and underwent apathy evaluation using the short-Problem Behavior Assessment and short-Lille Apathy Rating Scale, with the latter being characterized into three apathy domains, namely emotional, cognitive, and auto-activation deficit. Diffusion tensor imaging was used to study whether individual differences in specific cortico-striatal tracts predicted global apathy and its subdomains. We elucidate that apathy profiles may develop along differential timelines, with the auto-activation deficit domain manifesting prior to motor onset. Furthermore, diffusion tensor imaging revealed that inter-individual variability in the disruption of discrete cortico-striatal tracts might explain the heterogeneous severity of apathy profiles. Specifically, higher levels of auto-activation deficit symptoms significantly correlated with increased mean diffusivity in the right uncinate fasciculus. Conversely, those with severe cognitive apathy demonstrated increased mean diffusivity in the right frontostriatal tract and left dorsolateral prefrontal cortex to caudate nucleus tract. The current study provides evidence that white matter correlates associated with emotional, cognitive, and auto-activation subtypes may elucidate the heterogeneous nature of apathy in Huntington's disease, as such opening a door for individualized pharmacological management of apathy as a multidimensional syndrome in other neurodegenerative disorders