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Abstract Background Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). Methods In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. Results Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P

In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.

Frontal ablation is responsible for a large fraction of the mass loss from tidewater glaciers. The main contributors to frontal ablation are iceberg calving and submarine melting, with calving often being the largest. However, submarine melting, in addition to its direct contribution to mass loss, also promotes calving through the changes induced in the stress field at the glacier terminus, so both processes should be jointly analysed. Among the factors influencing submarine melting, the formation of a buoyant plume due to the emergence of fresh subglacial water at the glacier grounding line plays a key role. In this study we used Elmer/Ice to develop a 3D glacier dynamics model including calving and subglacial hydrology coupled with a line plume model to calculate the calving front position at every time step. We applied this model to the Hansbreen–Hansbukta glacier–fjord system in southern Spitsbergen, Svalbard, where a large set of data are available for both the glacier and the fjord from September 2008 to March 2011. We found that our 3D model reproduced the expected seasonal cycle of advance–retreat. Besides, the modelled front positions were in good agreement with the observed front positions at the central part of the calving front, with longitudinal differences, on average, below 15 m for the period from December 2009 to March 2011. But there were regions of the front, especially the eastern margin, that presented major differences.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD (''Chronic Kidney Disease-Mineral and Bone Disorders'') complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism. Resumen: La valoración del riesgo de fractura del paciente con enfermedad renal crónica (ERC) ha sido incluida en el complejo CKD-MBD («Chronic Kidney Disease-Mineral and Bone Disorders») en guías nefrológicas internacionales y nacionales, sugiriéndose por primera vez la evaluación de la densidad mineral ósea (DMO) si los resultados pueden condicionar la toma de decisiones terapéuticas. Sin embargo, existe muy poca información en práctica clínica real en esta población. El objetivo principal del estudio ERCOS (ERC-Osteoporosis) es describir el perfil de los pacientes con ERC G 3-5 D con osteoporosis (OP) y/o fracturas por fragilidad atendidos en consultas especializadas de nefrología, reumatología y medicina interna en España. Participaron 15 centros y se incluyeron 162 pacientes (siendo en su mayoría mujeres [71,2%] postmenopáusicas [98,3%]) con una mediana de edad de 77 años. La mediana del filtrado glomerular estimado (FGe) fue de 36 mL/min/1,73m2 y 38% de pacientes incluidos estaban en diálisis. Destacamos la elevada frecuencia de fracturas por fragilidad prevalentes [37,7%), principalmente vertebrales (52,5%) y de cadera (24,6%)], el antecedente desproporcionado de pacientes con patología glomerular en comparación a series puramente nefrológicas (corticoides) y el infratratamiento para la prevención de fracturas, fundamentalmente en consultas nefrológicas. Este estudio supone una inmediata llamada a la acción con la difusión de las nuevas guías clínicas, más proactivas, y subraya la necesidad de homogeneizar el enfoque asistencial/terapéutico multidisciplinar coordinado de estos pacientes de un modo eficiente para evitar las actuales discrepancias y el nihilismo terapéutico.

Hyperkalaemia is a common electrolyte imbalance with potentially serious short-, medium- and long-term consequences on morbidity and mortality rates and the use of national health service resources. The fact that different medical specialities can manage hyperkalaemia makes it important to have a unified approach, and the recent availability of new specific drug treatments means that the approach needs to be updated. This consensus document from the scientific societies most directly involved in the management of hyperkalaemia (Sociedad Española de Cardiología [Spanish Society of Cardiology], Sociedad Española de Endocrinología y Nutrición [Spanish Society of Endocrinology and Nutrition], Sociedad Española de Medicina Interna [Spanish Society of Internal Medicine], Sociedad Española de Medicina de Urgencias y Emergencias [Spanish Society of Accident and Emergency Medicine] and Sociedad Española de Nefrología [Spanish Society of Nephrology]) first of all reviews basic aspects of potassium balance and blood potassium. Then it goes on to focus on the concept, epidemiology, pathophysiology and diagnostic and therapeutic approaches to hyperkalaemia. The available evidence and the main published studies have been reviewed with the aim of providing a useful tool in the multidisciplinary approach to patients with hyperkalaemia. Resumen: La hiperpotasemia es una alteración electrolítica frecuente con consecuencias potencialmente graves a corto, medio y largo plazo, tanto en términos de morbilidad y mortalidad como de consumo de recursos del Sistema Nacional de Salud. El abordaje de la hiperpotasemia por diversas especialidades médicas y la reciente disponibilidad de nuevos tratamientos farmacológicos específicos hace necesaria una acción unificada y actualizada. El presente documento de consenso entre las sociedades científicas más directamente implicadas en el abordaje de la hiperpotasemia (Sociedad Española de Cardiología, Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Medicina Interna, Sociedad Española de Medicina de Urgencias y Emergencias y Sociedad Española de Nefrología) repasa, en primer lugar, aspectos básicos del balance de potasio y de la potasemia, centrándose posteriormente en el concepto, epidemiología, fisiopatología, y abordaje diagnóstico y terapéutico de la hiperpotasemia. Se han revisado las evidencias y los principales estudios publicados con el objetivo de que sea una herramienta útil en el abordaje multidisciplinar del paciente con hiperpotasemia.

Resumen: La hiperpotasemia es una alteración electrolítica frecuente con consecuencias potencialmente graves a corto, medio y largo plazo, tanto en términos de morbilidad y mortalidad como de consumo de recursos del Sistema Nacional de Salud. El abordaje de la hiperpotasemia por diversas especialidades médicas y la reciente disponibilidad de nuevos tratamientos farmacológicos específicos hace necesaria una acción unificada y actualizada. El presente documento de consenso entre las sociedades científicas más directamente implicadas en el abordaje de la hiperpotasemia (Sociedad Española de Cardiología, Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Medicina Interna, Sociedad Española de Medicina de Urgencias y Emergencias y Sociedad Española de Nefrología) repasa, en primer lugar, aspectos básicos del balance de potasio y de la potasemia, centrándose posteriormente en el concepto, epidemiología, fisiopatología, y abordaje diagnóstico y terapéutico de la hiperpotasemia. Se han revisado las evidencias y los principales estudios publicados con el objetivo de que sea una herramienta útil en el abordaje multidisciplinar del paciente con hiperpotasemia. Abstract: Hyperkalaemia is a common electrolyte imbalance with potentially serious short-, medium- and long-term consequences on morbidity and mortality rates and the use of national health service resources. The fact that different medical specialities can manage hyperkalaemia makes it important to have a unified approach, and the recent availability of new specific drug treatments means that the approach needs to be updated. This consensus document from the scientific societies most directly involved in the management of hyperkalaemia (Sociedad Española de Cardiología [Spanish Society of Cardiology], Sociedad Española de Endocrinología y Nutrición [Spanish Society of Endocrinology and Nutrition], Sociedad Española de Medicina Interna [Spanish Society of Internal Medicine], Sociedad Española de Medicina de Urgencias y Emergencias [Spanish Society of Emergency Medicine and Emergencies] and Sociedad Española de Nefrología [Spanish Society of Nephrology]) first of all reviews basic aspects of potassium balance and blood potassium. Then it goes on to focus on the concept, epidemiology, pathophysiology and diagnostic and therapeutic approaches to hyperkalaemia. The available evidence and the main published studies have been reviewed with the aim of providing a useful tool in the multidisciplinary approach to patients with hyperkalaemia.

Abstract Motivation Quantitative descriptions of multi-cellular structures from optical microscopy imaging are prime to understand the variety of three-dimensional (3D) shapes in living organisms. Experimental models of vertebrates, invertebrates and plants, such as zebrafish, killifish, Drosophila or Marchantia, mainly comprise multilayer tissues, and even if microscopes can reach the needed depth, their geometry hinders the selection and subsequent analysis of the optical volumes of interest. Computational tools to “peel” tissues by removing specific layers and reducing 3D volume into planar images, can critically improve visualization and analysis. Results We developed VolumePeeler, a versatile FIJI plugin for virtual 3D “peeling” of image stacks. The plugin implements spherical and spline surface projections. We applied VolumePeeler to perform peeling in 3D images of spherical embryos, as well as non-spherical tissue layers. The produced images improve the 3D volume visualization and enable analysis and quantification of geometrically challenging microscopy datasets. Availability ImageJ/FIJI software, source code, examples, and tutorials are openly available in https://cimt.uchile.cl/mcerda

Abstract INTRODUCTION Age‐related hearing loss is an important risk factor for cognitive decline. However, audiogram thresholds are not good estimators of dementia risk in subjects with normal hearing or mild hearing loss. Here we propose to use distortion product otoacoustic emissions (DPOAEs) as an objective and sensitive tool to estimate the risk of cognitive decline in older adults with normal hearing or mild hearing loss. METHODS We assessed neuropsychological, brain magnetic resonance imaging, and auditory analyses on 94 subjects > 64 years of age. RESULTS We found that cochlear dysfunction, measured by DPOAEs—and not by conventional audiometry—was associated with Clinical Dementia Rating Sum of Boxes (CDR‐SoB) classification and brain atrophy in the group with mild hearing loss (25 to 40 dB) and normal hearing (

The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present study is to assess the long-term effect of omeprazole on cobalamin and serum gastrin levels in healthy dogs. Eighteen healthy dogs were included: 10 in the control group and 8 in the omeprazole group. Three samples were collected: before starting the treatment (T0), 30 days after the start of treatment (T1), and at 60 days (T2). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T0, 481.4 (±170.21) at T1, and 513.2 (±174.50) at T2. In the omeprazole group, the values were 424.62 (±161.57) at T0, 454.5 (±160.96) at T1, and 414.87 (±127.90) at T2. No statistically significant changes were detected in cobalamin levels between the three-time period in both study groups. These results agree with previous findings in felines but contrast with human medicine studies. The median gastrin values (pg/mL) in the control group were 62.45 [30.17–218.75] at T0, 76.06 [30.67–199.87] at T1, and 63.02 [35.81–176.06] at T2. The median gastrin value in the omeprazole group was 67.59 [55.96–101.60] at T0, 191.77 [75.31–1901.77] at T1, and 128.16 [43.62–1066.46] at T2. Statistically significant differences were detected (p = 0.008), indicating an increase in gastrin levels after initiating treatment with omeprazole. In conclusion, the increased levels of gastrin observed in this population underscore the importance of conducting a comprehensive clinical assessment to identify potential gastrointestinal disorders, particularly in consideration of the usage of omeprazole as a preventive treatment.

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43−), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43− in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43− on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43- on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43− overload not only for the pathophysiology of SHPT but also in its systemic pathogenic role. Resumen: Aunque el fósforo es un elemento indispensable para la vida, en la naturaleza no se encuentra en estado nativo sino combinado en forma de fosfatos inorgánicos (PO43−), con niveles plasmáticos estrechamente regulados que se asocian a efectos deletéreos y mortalidad cuando estos se encuentran fuera de la normalidad. El interés creciente sobre el acúmulo de PO43- en la fisiopatología humana se originó en el papel que se le atribuyó en la patogenia del hiperparatiroidismo secundario a la enfermedad renal crónica. En este artículo revisamos los mecanismos por los cuales se justificaba dicho efecto y conmemoramos la importante contribución de un grupo español liderado por el Dr. M. Rodríguez, ahora hace justo 25 años, cuando demostraron por primera vez el efecto directo del PO43− sobre la regulación de la síntesis y secreción de hormona paratiroidea, manteniendo la integridad estructural de las glándulas paratiroides en su nuevo modelo experimental. Además de demostrar la importancia del ácido araquidónico (AA) y la vía de fosfolipasa A2-AA como mediadora de respuestas en la glándula paratiroidea, estos hallazgos fueron predecesores de la reciente descripción del importante papel del PO43- sobre la actividad del receptor-sensor de calcio y alimentaron asimismo diversas líneas de investigación sobre la importancia de la sobrecarga de PO43− no sólo en la fisiopatología del HPTS sino también en su papel patogénico sistémico.

Resumen: Aunque el fósforo es un elemento indispensable para la vida, en la naturaleza no se encuentra en estado nativo sino combinado en forma de fosfatos inorgánicos (PO43−), con niveles plasmáticos estrechamente regulados que se asocian a efectos deletéreos y mortalidad cuando estos se encuentran fuera de la normalidad. El interés creciente sobre el acúmulo de PO43− en la fisiopatología humana se originó en el papel que se le atribuyó en la patogenia del hiperparatiroidismo secundario a la enfermedad renal crónica. En este artículo revisamos los mecanismos por los cuales se justificaba dicho efecto y conmemoramos la importante contribución de un grupo español liderado por el Dr. M. Rodríguez, ahora hace justo 25 años, cuando demostraron por primera vez el efecto directo del PO43− sobre la regulación de la síntesis y secreción de hormona paratiroidea (manteniendo la integridad estructural de las glándulas paratiroides en su nuevo modelo experimental. Además de demostrar la importancia del ácido araquidónico (AA) y la vía de la fosfolipasa A2-AA como mediadora de respuestas en la glándula paratiroidea, estos hallazgos fueron predecesores de la reciente descripción del importante papel del PO43− sobre la actividad del receptor-sensor de calcio y alimentaron asimismo diversas líneas de investigación sobre la importancia de la sobrecarga de PO43−, no solo en la fisiopatología del hiperparatiroidismo secundario sino también en su papel patogénico sistémico. Abstract: Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43−), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43− in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43− on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43− on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43− overload not only for the pathophysiology of secondary hyperparathyroidism but also of its systemic pathogenic role.

Abstract The black aphid Aphis craccivora Koch is one of the main pests of the caupi-bean crop Vigna unguiculata (L.) Walp. Due to the need to find effective and safe methods of control, there has been an increase in research seeking natural alternatives. Thus, the objective of this work was to evaluate the potential of essential oils from jatoba Hymenaea courbaril, copaiba Copaifera langsdorffii and aroeira Schinus terebinthifolius to control nymphs and adults of A. craccivora. The oils were extracted from the leaves by the hydrodistillation method, diluted to 0.1% in distilled water with 2% dimethyl sulfoxide (DMSO). Each treatment had four repetitions, plus a control with distilled water + 2% DMSO. The biotests were conducted in two stages: the first was conducted in the laboratory, under controlled conditions of temperature, relative humidity and photophase, and the second was conducted in the greenhouse, using only the treatment with the best laboratory test results. After 24, 48, 72, 96 and 120 hours of exposure, the insect mortalities were checked. In the first phase of the experiment, the aroeira oil showed 83.33% and 75.75% efficiency of mortality in nymphs and adults, respectively. In the greenhouse tests, this same oil showed 73.52% in nymphs and 62.85% in adults, opening new perspectives regarding its use as a natural insecticide for the control of the black aphid of the bean.

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO2 (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m2 (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23.

Observations with the Five-hundred-meter Aperture Spherical Telescope recently detected H i 21 cm emission near M94, revealing an intriguing object, Cloud-9, without an optical counterpart. Subsequent analysis suggests that Cloud-9 is consistent with a gas-rich ( M _H I ≈ 10 ^6 M _⊙ ), starless, dark matter (DM) halo of mass M _200 ≈ 5 × 10 ^9 M _⊙ . Using the Karl G. Jansky Very Large Array in D-array configuration, we present interferometric observations of Cloud-9, revealing it as a dynamically cold ( W _50 ≈ 12 km s ^−1 ), nonrotating, and spatially asymmetric system, exhibiting gas compression on one side and a tail-like structure toward the other—features likely originating from ram pressure. Our observations suggest Cloud-9 is consistent with a starless ΛCDM DM halo if the gas is largely isothermal. If interpreted as a faint dwarf, Cloud-9 is similar to Leo T, a nearby gas-rich galaxy that would fall below current optical detection limits at Cloud-9's distance ( d ≈ 5 Mpc). Further observations with the Hubble Space Telescope reaching magnitudes m _g ≈ 30 would help identify such a galaxy or dramatically lower the current limits on its stellar mass ( M _gal ≲ 10 ^5 M _⊙ ). Cloud-9 thus stands as the firmest starless DM halo candidate to date or the faintest galaxy known at its distance.

A fundamental prediction of the Lambda cold dark matter cosmology is the centrally divergent cuspy density profile of dark matter haloes. Density cusps render cold dark matter haloes resilient to tides, and protect dwarf galaxies embedded in them from full tidal disruption. The hierarchical assembly history of the Milky Way may therefore give rise to a population of “microgalaxies”; i.e., heavily stripped remnants of early accreted satellites, which can reach arbitrarily low luminosity. Assuming that the progenitor systems are dark matter dominated, we use an empirical formalism for tidal stripping to predict the evolution of the luminosity, size, and velocity dispersion of such remnants, tracing their tidal evolution across multiple orders of magnitude in mass and size. The evolutionary tracks depend sensitively on the progenitor distribution of stellar binding energies. We explore three cases that likely bracket most realistic models of dwarf galaxies: one where the energy distribution of the most tightly bound stars follows that of the dark matter, and two where stars are defined by either an exponential density or surface brightness profile. The tidal evolution in the size–velocity dispersion plane is quite similar for these three models, although their remnants may differ widely in luminosity. Microgalaxies are therefore best distinguished from globular clusters by the presence of dark matter; either directly, by measuring their velocity dispersion, or indirectly, by examining their tidal resilience. Our work highlights the need for further theoretical and observational constraints on the stellar energy distribution in dwarf galaxies.

The recently discovered stellar system Ursa Major III/UNIONS 1 (UMa3/U1) is the faintest known Milky Way satellite to date. With a stellar mass of ${16}_{-5}^{+6}\,{M}_{\odot }$ and a half-light radius of 3 ± 1 pc, it is either the darkest galaxy ever discovered or the faintest self-gravitating star cluster known to orbit the Galaxy. Its line-of-sight velocity dispersion suggests the presence of dark matter, although current measurements are inconclusive because of the unknown contribution to the dispersion of potential binary stars. We use N -body simulations to show that, if self-gravitating, the system could not survive in the Milky Way tidal field for much longer than a single orbit (roughly 0.4 Gyr), which strongly suggests that the system is stabilized by the presence of large amounts of dark matter. If UMa3/U1 formed at the center of a ∼10 ^9 M _⊙ cuspy LCDM halo, its velocity dispersion would be predicted to be of order ∼1 km s ^−1 . This is roughly consistent with the current estimate, which, neglecting binaries, places σ _los in the range 1–4 km s ^−1 . Because of its dense cusp, such a halo should be able to survive the Milky Way tidal field, keeping UMa3/U1 relatively unscathed until the present time. This implies that UMa3/U1 is plausibly the faintest and densest dwarf galaxy satellite of the Milky Way, with important implications for alternative dark matter models and for the minimum halo mass threshold for luminous galaxy formation in the LCDM cosmology. Our results call for multi-epoch high-resolution spectroscopic follow-up to confirm the dark matter content of this extraordinary system.

We present the discovery of Ursa Major III/UNIONS 1, the least luminous known satellite of the Milky Way, which is estimated to have an absolute V -band magnitude of $+{2.2}_{-0.3}^{+0.4}$ mag, equivalent to a total stellar mass of ${16}_{-5}^{+6}$ M _⊙ . Ursa Major III/UNIONS 1 was uncovered in the deep, wide-field Ultraviolet Near Infrared Optical Northern Survey (UNIONS) and is consistent with an old ( τ > 11 Gyr), metal-poor ([Fe/H] ∼ −2.2) stellar population at a heliocentric distance of ∼10 kpc. Despite its being compact ( r _h = 3 ± 1 pc) and composed of few stars, we confirm the reality of Ursa Major III/UNIONS 1 with Keck II/DEIMOS follow-up spectroscopy and identify 11 radial velocity members, eight of which have full astrometric data from Gaia and are co-moving based on their proper motions. Based on these 11 radial velocity members, we derive an intrinsic velocity dispersion of ${3.7}_{-1.0}^{+1.4}$ km s ^−1 but some caveats preclude this value from being interpreted as a direct indicator of the underlying gravitational potential at this time. Primarily, the exclusion of the largest velocity outlier from the member list drops the velocity dispersion to ${1.9}_{-1.1}^{+1.4}$ km s ^−1 , and the subsequent removal of an additional outlier star produces an unresolved velocity dispersion. While the presence of binary stars may be inflating the measurement, the possibility of a significant velocity dispersion makes Ursa Major III/UNIONS 1 a high-priority candidate for multi-epoch spectroscopic follow-ups to deduce the true nature of this incredibly faint satellite.

Chronic kidney disease (CKD) is a highly prevalent disease that has become a public health problem. Progression of CKD is associated with serious complications, including the systemic CKD-mineral and bone disorder (CKD-MBD). Laboratory, bone and vascular abnormalities define this condition, and all have been independently related to cardiovascular disease and high mortality rates. The “old” cross-talk between kidney and bone (classically known as “renal osteodystrophies”) has been recently expanded to the cardiovascular system, emphasizing the importance of the bone component of CKD-MBD. Moreover, a recently recognized higher susceptibility of patients with CKD to falls and bone fractures led to important paradigm changes in the new CKD-MBD guidelines. Evaluation of bone mineral density and the diagnosis of “osteoporosis” emerges in nephrology as a new possibility “if results will impact clinical decisions”. Obviously, it is still reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will be clinically useful (low versus high turnover-bone disease). However, it is now considered that the inability to perform a bone biopsy may not justify withholding antiresorptive therapies to patients with high risk of fracture. This view adds to the effects of parathyroid hormone in CKD patients and the classical treatment of secondary hyperparathyroidism. The availability of new antiosteoporotic treatments bring the opportunity to come back to the basics, and the knowledge of new pathophysiological pathways [OPG/RANKL (LGR4); Wnt-ß-catenin pathway], also affected in CKD, offers great opportunities to further unravel the complex physiopathology of CKD-MBD and to improve outcomes.

IntroductionKlotho protein is predominantly expressed in the kidneys and has also been detected in vascular tissue and peripheral blood circulating cells to a lesser extent. Carotid artery intima-media thickness (CIMT) burden, a marker of subclinical atherosclerosis, has been associated with reductions in circulating Klotho levels in chronic kidney disease patients, who show reduced levels of this protein at all stages of the disease. However, the contribution of serum Klotho and its expression levels in peripheral blood circulating cells and in the carotid artery wall on the CIMT in the absence of kidney impairment has not yet been evaluated.MethodsWe conducted a single-center study in 35 atherosclerotic patients with preserved kidney function (eGFR≥60 mL/min/1.73m2) subjected to elective carotid surgery. Serum levels of Klotho and cytokines TNFa, IL6 and IL10 were determined by ELISA and transcripts encoding for Klotho (KL), TNF, IL6 and IL10 from vascular segments were measured by qRT-PCR. Klotho protein expression in the intima-media and adventitia areas was analyzed using immunohistochemistry.ResultsAPatients with higher values of CIMT showed reduced Klotho levels in serum (430.8 [357.7-592.9] vs. 667.8 [632.5-712.9] pg/mL; p

Abstract Cardiovascular disease is the leading cause of death worldwide. New therapeutic strategies are aimed to modulate the athero-inflammatory process that partially orchestrates underlying vascular damage. Peripheral blood circulating cells include different immune cells with a central role in the development of the atherogenic inflammatory response. The anti-aging protein α-Klotho has been related to protective effects against CVD. KL is expressed in monocytes, macrophages, and lymphocytes where it exerts anti-inflammatory effects. In this work, we analyse the relationships of the levels of inflammatory markers with the expression of the KL gene in PBCCs and with the serum levels of soluble KL in atherosclerotic vascular disease. For this, we conducted a cross-sectional single-center case–control study including a study group of 76 CVD patients and a control group of 16 cadaveric organ donors without medical antecedent or study indicating CVD. Vascular artery fragments and whole blood and serum samples were obtained during elective or organ retrieval surgery. Serum levels of sKL, TNFα and IL10, and gene expression levels of KL, TNF, IL10, NFKB1, DNMT1, and DNMT3A in PBCCs were measured. In these cells, we also determined KL promoter methylation percentage. Histological and immunohistochemical analyses were employed to visualize atherosclerotic lesions and to measure IL10 and TNFα levels in vascular fragments. Patients with CVD presented higher values of proinflammatory markers both at systemic and in the vasculature and in the PBCCs, compared to the control group. In PBCCs, CVD patients also presented lower gene expression levels of KL gene (56.4% difference, P < 0.001), higher gene expression levels of DNMT1 and DNMT3A (P < 0.0001, for both) and a higher methylation status of in the promoter region of KL (34.1 ± 4.1% vs. 14.6 ± 3.4%, P < 0.01). In PBCCs and vasculature, KL gene expression correlated inversely with pro-inflammatory markers and directly with anti-inflammatory markers. sKL serum levels presented similar associations with the expression levels of pro- and anti-inflammatory markers in PBCCs. The differences in KL expression levels in PBCCs and in serum sKL levels with respect to control group was even greater in those CVD patients with macroscopically observable atheromatous plaques. We conclude that promoter methylation-mediated downregulation of KL gene expression in PBCCs is associated with the pro-inflammatory status in atherosclerotic vascular disease.

Abstract Background Ischemic stroke is the most common cerebrovascular disease and is caused by interruption of blood supply to the brain. To date, recombinant tissue plasminogen activator (rtPA) has been the main pharmacological treatment in the acute phase. However, this treatment has some drawbacks, such as a short half-life, low reperfusion rate, risk of hemorrhagic transformations, and neurotoxic effects. To overcome the limitations of rtPA and improve its effectiveness, we recently designed sonosensitive sub-micrometric capsules (SCs) loaded with rtPA with a size of approximately 600 nm, synthesized using the layer-by-layer (LbL) technique, and coated with gelatine for clot targeting. In this study, we evaluated the rtPA release of ultrasound (US)-responsive SCs in healthy mice and the therapeutic effect in a thromboembolic stroke model. Results In healthy mice, SCs loaded with rtPA 1 mg/kg responded properly to external US exposure, extending the half-life of the drug in the blood stream more than the group treated with free rtPA solution. The gelatine coating also contributed to stabilizing the encapsulation and maintaining the response to US. When the same particles were administered in the stroke model, these SCs appeared to aggregate in the ischemic brain region, probably generating secondary embolisms and limiting the thrombolytic effect of rtPA. Despite the promising results of these thrombolytic particles, at least under the dose and size conditions used in this study, the administration of these capsules represents a risk factor for stroke. Conclusions This is the first study to report the aggregation risk of a drug carrier in neurological pathologies such as stroke. Biocompatibility analysis related to the use of nano-and microparticles should be deeply studied to anticipate the limitations and orientate the design of new nanoparticles for translation to humans. Graphical Abstract

The article is devoted to the study of the phenomenon of public memory about the civil war of 1936 – 1939 and the Francoist dictatorship in Spain. Another focus of the research is an analysis of the difficulties and contradictions associated with the transformations of the Spanish state historical policy, including the problems resulting from the adoption of a new law on democratic memory in the country. For twenty years, issues of memory have invariably been present in the Spanish political discourse and affect the daily life of Spaniards. This situation has been accompanied by significant media attention and wide media coverage. Numerous references to the themes of memory and the difficult past are often superficial and do not reveal the essence of the problem, forming a horizontal informational reflection that gives the illusion of saturation. The authors, analyzing the relationship of the Spaniards with their past, apply the comparative method in the context of four historical stages — the period of the Francoist dictatorship, the stage of democratic transition, democratic Spain in the 1980s – 1990s, and Spain of the 21st century. The conducted research allows us to assert that one important characteristic of the Spanish case is the lack of social consolidation and acceptance of the policy of public memory on a democratic basis. This reveals the difficulty of building a social and political consensus around the policy of memory. Turning to the history of the issue of the return of memory and noting the desire of the left political forces for a historical revenge, the authors of the article conclude that it is impossible to present a single correct presentation of democratic memory. Using the example of the denial of both the Francoist memory and the revolutionary memory of the anarchist movement, the article argues the specific character of democratic memory as a cultural phenomenon: democratic memory is multiple, it reflects and presents various interests of many social actors and does not have an exclusively liberal-democratic character.

This article analyzes the memory and representation of the Second Spanish Republic, particularly its years in peace (1931-1936), in Span-ish fiction cinema and made in this country, from 1939 to the present day. The most common ideas and images in this vision of the Second Republic present in cinematography are studied, and the continuity / evolution or change in them throughout the Franco dictatorship, the Democratic Transition and to this day, taking as an example some films. Finally, some general conclusions are addressed that highlight a lower visibility of this period in Spanish cinematography in general compared to the period of the Civil War (1936-1939), as well as the persistence of certain stereotypes around the Second Republic.

Abstract Chronic kidney disease (CKD) has been associated with a higher risk of cardiovascular disease (CVD). CKD patients present a decrease in the levels of the protein Klotho that accompanies the decrease in kidney function. This protein has been related to protective effects against CVD. However, it is unclear whether circulating Klotho, and its expression in peripheral blood cells (PBCs) are also associated with subclinical atherosclerosis in CKD. The present study aimed to study the relationship between Klotho and subclinical atherosclerosis in a population of patients with moderate to severe CKD. We determined the serum levels and gene expression in PBCs levels of Klotho and three inflammatory cytokines in 103 patients with CKD and investigated their relationship with two surrogate markers of subclinical atherosclerotis: ankle-brachial index (ABI) and carotid intima-media thickness (CIMT). Patients with subclinical atherosclerosis presented lower serum and PBCs expression levels of Klotho. Both variables were associated with the presence of subclinical atherosclerosis, being directly related with ABI and inversely with CIMT (P

Patients with the dual burden of chronic kidney disease (CKD) and cardiovascular disease (CVD) experience unacceptably high rates of morbidity and mortality, which also entail unfavorable effects on healthcare systems. Currently, concerted efforts to identify, prevent and treat CVD in CKD patients are lacking at the institutional level, with emphasis still being placed on individual specialty views on this topic. The authors of this position paper endorse the need for a dedicated interdisciplinary team of subspecialists in cardio-nephrology that manages appropriate clinical interventions across the inpatient and outpatient settings. There is a critical need for training programs, guidelines and best clinical practice models, and research funding from nephrology, cardiology and other professional societies, to support the development of the subspecialty of cardio-nephrology. This position paper from the coordinating committee from the Working Group for Cardiorenal Medicine of the Spanish Society of Nephrology (S.E.N.) is intended to be the starting point to develop the subspecialty of cardio-nephrology within the S.E.N.. The implementation of the subspecialty in day-to-day nephrological practice will help to diagnose, treat, and prevent CVD in CKD patients in a precise, clinically effective, and health cost-favorable manner. Resumen: Los pacientes con enfermedad renal crónica (ERC) que presentan enfermedad cardiovascular (ECV) tienen índices de morbilidad y mortalidad inaceptablemente elevados, que impactan desfavorablemente sobre los sistemas de salud. En la actualidad, se requieren actuaciones multidisciplinares para identificar, prevenir y tratar la ECV en los pacientes con ERC, debiendo pues superarse la época de las actuaciones de las especialidades individuales. Los autores de este artículo respaldan la necesidad de un equipo interdisciplinar de subespecialistas en cardionefrología que gestione las intervenciones clínicas adecuadas en el entorno hospitalario y en el ambulatorio. Existe una gran necesidad de programas de formación, de guías y modelos de práctica clínica, y de fondos para la investigación en las sociedades de nefrología, cardiología y otras, para apoyar el desarrollo de la subespecialidad de cardio-nefrología. Este documento de opinión del comité coordinador del Grupo de Trabajo de Medicina Cardiorenal de la Sociedad Española de Nefrología (S.E.N.) pretende ser el inicio del desarrollo de la subespecialidad de Cardionefrología en el marco de la S.E.N. La implementación de la subespecialidad en la práctica nefrológica diaria contribuirá a diagnosticar, tratar y prevenir la ECV en los pacientes con ERC de una manera precisa, clínicamente efectiva y sanitariamente rentable.

El Grisón es uno de los mesocarnívoros más crípticos y poco estudiados a lo largo de su distribución. En Colombia, su presencia está limitada a registros anecdóticos y sin evidencias en ecosistemas circundantes a las ciudades. Aquí reportamos los primeros dos registros de la especie en hábitats con una alta influencia antrópica al norte y occidente del Valle de Aburrá, Colombia

We consider a Hamiltonian system associated with the two-well umbilical catastrophe potential D5, while the corresponding potential contains only one free parameter. We determine how this free parameter affects the equilibrium dynamics of the system by computing their coordinates on the configuration plane, along with their linear stability and type. Additionally, we discuss the influence of the same free parameter on the orbital dynamics of the system by performing a systematic and thorough orbit classification that allows us to reveal the bounded or escaping motion of the test particle.

Resumen: La interleuquina 17A (IL-17A) es una citoquina proinflamatoria producida por células del sistema inmune, sobre todo por los linfocitos Th17 y los linfocitos γδ. En este trabajo, revisamos el papel de IL-17A en la patogenia de la hipertensión y de la lesión en órganos diana. Estudios en ratones han demostrado que la IL-17A aumenta la presión arterial, probablemente por acciones a varios niveles. Además, las concentraciones plasmáticas de IL-17A están ya aumentadas en pacientes con hipertensión arterial ligera o moderada. Estudios preclínicos sobre hipertensión arterial han detectado células productoras de IL-17A en órganos diana, como corazón, vasos y riñón. En pacientes con nefroesclerosis hipertensiva existe infiltración del riñón por linfocitos Th17 y linfocitos γδ que expresan IL-17A. Además, en modelos experimentales de hipertensión el bloqueo de IL-17A, mediante estrategias génicas, o utilizando anticuerpos neutralizantes, disminuye la presión arterial por acciones sobre la pared vascular y el transporte tubular de sodio y disminuye la lesión en órganos diana. En conjunto, los datos presentados en esta revisión sugieren que la IL-17A participa en la regulación de la presión arterial y en la génesis y mantenimiento de la hipertensión arterial, pudiendo constituir una diana terapéutica en el futuro. Abstract: Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 lymphocytes and γδ lymphocytes. In this paper, we review the role of IL-17A in the pathogenesis of hypertension and target organ damage. Studies in mice have shown that IL-17A increases blood pressure, probably by acting on multiple levels. Furthermore, IL-17A plasma concentrations are already elevated in patients with mild or moderate hypertension. Preclinical studies on arterial hypertension have detected IL-17A-producing cells in target organs such as the heart, vessels and kidneys. Patients with hypertensive nephrosclerosis show kidney infiltration by Th17 lymphocytes and γδ lymphocytes that express IL-17A. In addition, in experimental models of hypertension, blocking IL-17A by genetic strategies, or using neutralising antibodies, lowers blood pressure by acting on the vascular wall and tubule sodium transport and reduces damage to target organs. As a whole, the data presented in this review suggest that IL-17A participates in the regulation of blood pressure and in the genesis and maintenance of arterial hypertension, and may constitute a therapeutic target in the future.

Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 and γδ lymphocytes. In this paper, we review the role of IL-17A in the pathogenesis of hypertension and in target organ damage. Preclinical studies in mice have shown that systemic adminstration of IL-17A increases blood pressure, probably by acting on multiple levels. Furthermore, IL-17A plasma concentrations are already elevated in patients with mild or moderate hypertension. Many studies in hypertensive mice models have detected IL-17A-producing cells in target organs such as the heart, vessels and kidneys. Patients with hypertensive nephrosclerosis show kidney infiltration by Th17 lymphocytes and γδ lymphocytes that express IL-17A. In addition, in experimental models of hypertension, the blockade of IL-17A by genetic strategies or using neutralizing antibodies, disminished blood pressure, probablyby acting on the small mesenteric arteries as well as in the regulation of tubule sodium transport. Moreover, IL-17A inhibition reduces end-organs damage. As a whole, the data presented in this review suggest that IL-17A participates in the regulation of blood pressure and in the genesis and maintenance of arterial hypertension, and may constitute a therapeutic target of hypertension-related pathologies in the future. Resume: La interleuquina 17A (IL-17A) es una citoquina proinflamatoria producida por células del sistema inmune, sobre todo por los linfocitos Th17 y los linfocitos γδ. En este trabajo, revisamos el papel de IL-17A en la patogenia de la hipertensión y de la lesión en órganos diana. Estudios en ratones han demostrado que la IL-17A aumenta la presión arterial, probablemente por acciones a varios niveles. Además, las concentraciones plasmáticas de IL-17A están ya aumentadas en pacientes con hipertensión arterial ligera o moderada. Estudios preclínicos sobre hipertensión arterial han detectado células productoras de IL-17A en órganos diana, como corazón, vasos y riñón. En pacientes con nefroesclerosis hipertensiva existe infiltración del riñón por linfocitos Th17 y linfocitos γδ que expresan IL-17A. Además, en modelos experimentales de hipertensión el bloqueo de IL-17A, mediante estrategias génicas, o utilizando anticuerpos neutralizantes, disminuye la presión arterial por acciones sobre la pared vascular y el transporte tubular de sodio y disminuye la lesión en órganos diana. En conjunto, los datos presentados en esta revisión sugieren que la IL-17A participa en la regulación de la presión arterial y en la génesis y mantenimiento de la hipertensión arterial, pudiendo constituir una diana terapéutica en el futuro.

Abstract The escape of a particle from a dynamical system depends on the intersection between the ingoing and outgoing asymptotic trajectories to certain periodic orbits placed at the openings of the curves of zero velocity of the system. Although many efforts have been devoted to the analysis of the escape from potentials presenting multiple openings, there are still few studies on potentials with only one opening. In this article, we clarify the way in which the energy affects the escape in this type of systems, showing that, contrary to what one could expect, there are several bifurcations for certain values of the energy.

Mountain glaciers have generally experienced an accelerated retreat over the last 3 decades as a rapid response to current global warming. However, the response to previous warm periods in the Holocene is not well-described for glaciers of the southern Europe mountain ranges, such as the Pyrenees. The situation during the Medieval Climate Anomaly (900–1300 CE) is particularly relevant since it is not certain whether the southern European glaciers just experienced significant ice loss or whether they actually disappeared. We present here the first chronological study of a glacier located in the Central Pyrenees (NE Spain), Monte Perdido Glacier (MPG), carried out by different radiochronological techniques and a comparison with geochemical proxies from neighbouring palaeoclimate records. The chronological model evidences that the glacier persisted during the Roman period and the Medieval Climate Anomaly. The apparent absence of ice in the past ∼ 600 years suggests that any ice accumulated during the Little Ice Age has since ablated. This interpretation is supported by measured concentrations of anthropogenic metals, including Zn, Se, Cd, Hg and Pb, which have concentrations well below those typical of industrial-age ice measured at other glaciers in Europe. This study strengthens the general understanding that warming of the past few decades has been exceptional for the past 2 millennia.

Background: Treatment quality is important in clinical hyperthermia. Guideline-based treatment protocols are used to determine system settings and treatment strategies to ensure effective tumor heating and prevent unwanted treatment-limiting normal tissue hot spots. Realizing both these goals can prove challenging using generic guideline-based and operator-dependent treatment strategies. Hyperthermia treatment planning (HTP) can be very useful to support treatment strategies. Although HTP is increasingly integrated into the standard clinical workflow, active clinical application is still limited to a small number of hyperthermia centers and should be further stimulated. Purpose: This paper aims to serve as a practical guide, demonstrating how HTP can be applied in clinical decision making for both superficial and locoregional hyperthermia treatments. HTP in clinical decision making: Seven problems that occur in daily clinical practice are described and we show how HTP can enhance insight to formulate an adequate treatment strategy. Examples use representative commercially available hyperthermia devices and cover all stages during the clinical workflow. Problems include selecting adequate phase settings, heating ability analysis, hot spot suppression, applicator selection, evaluation of target coverage and heating depth, and predicting possible thermal toxicity in case of an implant. Since we aim to promote a general use of HTP in daily practice, basic simulation strategies are used in these problems, avoiding a need for the application of dedicated advanced optimization routines that are not generally available. Conclusion: Even fairly basic HTP can facilitate clinical decision making, providing a meaningful and clinically relevant contribution to maintaining and improving treatment quality.

Cadmium (Cd) is a highly toxic heavy metal for humans and animals, which is associated with acute hepatotoxicity. Selenium (Se) confers protection against Cd-induced toxicity in cells, diminishing the levels of ROS and increasing the activity of antioxidant selenoproteins such as glutathione peroxidase (GPx). The aim of this study was to evaluate the antagonistic effect of selenomethionine (SeMet) against Cd toxicity in HepG2 cells, through the modulation of selenoproteins. To this end, the cells were cultured in the presence of 100 µM SeMet and 5 μM, 15 µM, and 25 µM CdCl2 and a combination of both species for 24 h. At the end of the experiment, cell viability was determined by MTT assay. The total metal content of Cd and Se was analyzed by triple-quadrupole inductively coupled plasma–mass spectrometry (ICP-QqQ-MS). To quantify the concentration of three selenoproteins [GPx, selenoprotein P (SELENOP), and selenoalbumin (SeAlb)] and selenometabolites, an analytical methodology based on column switching and a species-unspecific isotopic dilution approach using two-dimensional size exclusion and affinity chromatography coupled to ICP-QqQ-MS was applied. The co-exposure of SeMet and Cd in HepG2 cells enhanced the cell viability and diminished the Cd accumulation in cells. Se supplementation increased the levels of selenometabolites, GPx, SELENOP, and SeAlb; however, the presence of Cd resulted in a significant diminution of selenometabolites and SELENOP. These results suggested that SeMet may affect the accumulation of Cd in cells, as well as the suppression of selenoprotein synthesis induced by Cd.

Although worldwide inventories of glacier area have been coordinated internationally for several decades, a similar effort for glacier ice thicknesses was only initiated in 2013. Here, we present the third version of the Glacier Thickness Database (GlaThiDa v3), which includes 3 854 279 thickness measurements distributed over roughly 3000 glaciers worldwide. Overall, 14 % of global glacier area is now within 1 km of a thickness measurement (located on the same glacier) – a significant improvement over GlaThiDa v2, which covered only 6 % of global glacier area and only 1100 glaciers. Improvements in measurement coverage increase the robustness of numerical interpolations and model extrapolations, resulting in better estimates of regional to global glacier volumes and their potential contributions to sea-level rise. In this paper, we summarize the sources and compilation of glacier thickness data and the spatial and temporal coverage of the resulting database. In addition, we detail our use of open-source metadata formats and software tools to describe the data, validate the data format and content against this metadata description, and track changes to the data following modern data management best practices. Archived versions of GlaThiDa are available from the World Glacier Monitoring Service (e.g., v3.1.0, from which this paper was generated: https://doi.org/10.5904/wgms-glathida-2020-10; GlaThiDa Consortium, 2020), while the development version is available on GitLab (https://gitlab.com/wgms/glathida, last access: 9 November 2020).

Glaciers in Peru play a major role in water availability and they also have direct implications on natural hazards such as glacial lake outburst floods (GLOFs) and/or ice avalanches, which have caused a high number of fatalities and damage to infrastructure in the last decades. Despite a noticeable effort to quantify and understand the shrinking and thawing of glaciers in Peru, there are still regions where detailed assessment is still missing. In this work, a set of remote sensing images were used to map, for the first time, the evolution of the glaciated area (from 1970 to 2018) in the Pariacacá Mountains (11º5’ S, 76º0’ W) in the Cordillera Central of Peru. The results evidenced a marked decrease of the glaciated surface, with 55.3% shrinkage since 1970 and 40% since 1987. Faster glacier retreat occurred between 1985 and the end of the 1990s, and this period was followed by a significant slowdown in shrinking rates. The differential loss of ice, depending on elevation and exposure to incoming radiation, has led to changes in spatial distribution of the glaciers. Currently, they have almost completely thawed below 5000 m a.s.l. They are mostly located in south- to west-facing aspects. Ice melting in the last decades has even affected the summit areas. Finally, the development of ablation hollows has been identified as an important driver of glacier thaw. These features are formed mainly in gentle slopes and highly irradiated zones between 5000 and 5400 m a.s.l.

Meltwater and sediment-laden plumes at tidewater glaciers, resulting from the localized subglacial discharge of surface melt, influence submarine melting of the glacier and the delivery of nutrients to the fjord's surface waters. It is usually assumed that increased subglacial discharge will promote the surfacing of these plumes. Here, at a western Greenland tidewater glacier, we investigate the counterintuitive observation of a non-surfacing plume in July 2012 (a year of record surface melting) compared to the surfacing of the plume in July 2013 (an average melt year). We combine oceanographic observations, subglacial discharge estimates and an idealized plume model to explain the observed plumes' behavior and evaluate the relative impact of fjord stratification and subglacial discharge on plume dynamics. We find that increased fjord stratification prevented the plume from surfacing in 2012, show that the fjord was more stratified in 2012 due to increased freshwater content and speculate that this arose from an accumulation of ice sheet surface meltwater in the fjord in this record melt year. By developing theoretical scalings, we show that fjord stratification in general exerts a dominant control on plume vertical extent (and thus surface expression), so that studies using plume surface expression as a means of diagnosing variability in glacial processes should account for possible changes in stratification. We introduce the idea that, despite projections of increased surface melting over Greenland, the appearance of plumes at the fjord surface could in the future become less common if the increased freshwater acts to stratify fjords around the Greenland ice sheet. We discuss the implications of our findings for nutrient fluxes, trapping of atmospheric CO2 and the properties of water exported from Greenland's fjords.

Observations with the Five-hundred-meter Aperture Spherical Telescope have revealed the presence of a marginally resolved source of 21 cm emission from a location $\sim 50^{\prime} $ from the M94 galaxy, without a stellar counterpart down to the surface brightness limit of the DESI Imaging Legacy Survey (∼29.15 mag arcsec ^−2 in the g band). The system (hereafter Cloud-9) has round column density isocontours and a line width consistent with thermal broadening from gas at T ∼ 2 × 10 ^4 K. These properties are unlike those of previously detected dark H i clouds and similar to the expected properties of REionization-Limited-H i Clouds (RELHICs), namely, starless dark matter (DM) halos filled with gas in hydrostatic equilibrium and in thermal equilibrium with the cosmic ultraviolet background. At the distance of M94, d ∼ 4.7 Mpc, we find that Cloud-9 is consistent with being a RELHIC inhabiting a Navarro–Frenk–White (NFW) DM halo of mass M _200 ∼ 5 × 10 ^9 M _⊙ and concentration c _NFW ∼ 13. Although the agreement between the model and observations is good, Cloud-9 appears to be slightly, but systematically, more extended than expected for ΛCDM RELHICs. This may imply either that Cloud-9 is much closer than implied by its recessional velocity, v _CL9 ∼ 300 km s ^−1 , or that its halo density profile is flatter than NFW, with a DM mass deficit greater than a factor of 10 at radii r ≲ 1 kpc. Further observations may aid in constraining these scenarios better and help elucidate whether Cloud-9 is the first ever observed RELHIC, a cornerstone prediction of the ΛCDM model on the smallest scales.

Reducing oxidative stress stands at the center of a prevention and control strategy for mitigating cellular senescence and aging. Kidney disease is characterized by a premature aging syndrome, and to find a modulator targeting against oxidative stress, mitochondrial dysfunction, and cellular senescence in kidney cells could be of great significance to prevent and control the progression of this disease. This review focuses on the pathogenic mechanisms related to the appearance of oxidative stress damage and mitochondrial dysfunction in kidney disease. In this scenario, the anti-aging Klotho protein plays a crucial role by modulating signaling pathways involving the manganese-containing superoxide dismutase (Mn-SOD) and the transcription factors FoxO and Nrf2, known antioxidant systems, and other known mitochondrial function regulators, such as mitochondrial uncoupling protein 1 (UCP1), B-cell lymphoma-2 (BCL-2), Wnt/β-catenin, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), transcription factor EB, (TFEB), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Therefore, Klotho is postulated as a very promising new target for future therapeutic strategies against oxidative stress, mitochondria abnormalities, and cellular senescence in kidney disease patients.