Control of proton transport and hydrogenation in double-gated graphene.

The basal plane of graphene can function as a selective barrier that is permeable to protons1,2 but impermeable to all ions3,4 and gases5,6, stimulating its use in applications such as membranes1,2,7,8, catalysis9,10 and isotope separation11,12. Protons can chemically adsorb on graphene and hydrogenate it13,14, inducing a conductor-insulator transition that has been explored intensively in graphene electronic devices13-17. However, both processes face energy barriers1,12,18 and various strategies have been proposed to accelerate proton transport, for example by introducing vacancies4,7,8, incorporating catalytic metals1,19 or chemically functionalizing the lattice18,20. But these techniques can compromise other properties, such as ion selectivity21,22 or mechanical stability23. Here we show that independent control of the electric field, E, at around 1 V nm-1, and charge-carrier density, n, at around 1 × 1014 cm-2, in double-gated graphene allows the decoupling of proton transport from lattice hydrogenation and can thereby accelerate proton transport such that it approaches the limiting electrolyte current for our devices. Proton transport and hydrogenation can be driven selectively with precision and robustness, enabling proton-based logic and memory graphene devices that have on-off ratios spanning orders of magnitude. Our results show that field effects can accelerate and decouple electrochemical processes in double-gated 2D crystals and demonstrate the possibility of mapping such processes as a function of E and n, which is a new technique for the study of 2D electrode-electrolyte interfaces.

Gate-controlled suppression of light-driven proton transport through graphene electrodes.

Recent experiments demonstrated that proton transport through graphene electrodes can be accelerated by over an order of magnitude with low intensity illumination. Here we show that this photo-effect can be suppressed for a tuneable fraction of the infra-red spectrum by applying a voltage bias. Using photocurrent measurements and Raman spectroscopy, we show that such fraction can be selected by tuning the Fermi energy of electrons in graphene with a bias, a phenomenon controlled by Pauli blocking of photo-excited electrons. These findings demonstrate a dependence between graphene's electronic and proton transport properties and provide fundamental insights into molecularly thin electrode-electrolyte interfaces and their interaction with light.

Proton and molecular permeation through the basal plane of monolayer graphene oxide.

Two-dimensional (2D) materials offer a prospect of membranes that combine negligible gas permeability with high proton conductivity and could outperform the existing proton exchange membranes used in various applications including fuel cells. Graphene oxide (GO), a well-known 2D material, facilitates rapid proton transport along its basal plane but proton conductivity across it remains unknown. It is also often presumed that individual GO monolayers contain a large density of nanoscale pinholes that lead to considerable gas leakage across the GO basal plane. Here we show that relatively large, micrometer-scale areas of monolayer GO are impermeable to gases, including helium, while exhibiting proton conductivity through the basal plane which is nearly two orders of magnitude higher than that of graphene. These findings provide insights into the key properties of GO and demonstrate that chemical functionalization of 2D crystals can be utilized to enhance their proton transparency without compromising gas impermeability.

Forgotten giants: Robust climate signal in pollarded trees.

Tree ring records are among the most valuable resources to create high-resolution climate reconstructions. Most climate reconstructions are based on old trees growing in inaccessible mountainous areas with low human activity. Therefore, reconstruction of climate conditions in lowlands is usually based on data from distant mountains. Albeit old trees can be common in humanized areas, they are not used for climate reconstructions. Pollarding was a common traditional management in Europe that enabled trees to maintain great vitality for periods exceeding the longevity of unmanaged trees. We evaluate the potential of pollarded deciduous oaks to record past climate signal. We sampled four pollarded woodlands in Central Spain under continental Mediterranean climate. We hypothesized that pollarded trees have a strong response to water availability during current period without pollarding management, but also in the period under traditional management if pruning was asynchronous among trees. Moreover, we hypothesized that if climate is a regional driver of oak secondary growth, chronologies from different woodlands will be correlated. Pollard oaks age exceeded 500 years with a strong response to Standardized Precipitation-Evapotranspiration Index (SPEI) from 9 to 11 months. Climate signal was exceptionally high in three of the sites (r2 = 0.443-0.655) during low management period (1962-2022). The largest fraction of this climate signal (≈70 %) could be retrieved during the traditional management period (1902-1961) in the three sites where pollarding was asynchronous. Chronologies were significantly correlated since the 19th century for all the studied period, highlighting a shared climate forcing. We identified critical points to optimize pollard tree sampling schema. Our results show the enormous potential of pollarded woodlands to reconstruct hydroclimate conditions in the Mediterranean with a fine spatial grain. Studying pollarded trees is an urgent task, since the temporal window to retrieve the valuable information in pollarded trees is closing as these giants collapse and their wood rots.

Proton transport through nanoscale corrugations in two-dimensional crystals.

Defect-free graphene is impermeable to all atoms1-5 and ions6,7 under ambient conditions. Experiments that can resolve gas flows of a few atoms per hour through micrometre-sized membranes found that monocrystalline graphene is completely impermeable to helium, the smallest atom2,5. Such membranes were also shown to be impermeable to all ions, including the smallest one, lithium6,7. By contrast, graphene was reported to be highly permeable to protons, nuclei of hydrogen atoms8,9. There is no consensus, however, either on the mechanism behind the unexpectedly high proton permeability10-14 or even on whether it requires defects in graphene's crystal lattice6,8,15-17. Here, using high-resolution scanning electrochemical cell microscopy, we show that, although proton permeation through mechanically exfoliated monolayers of graphene and hexagonal boron nitride cannot be attributed to any structural defects, nanoscale non-flatness of two-dimensional membranes greatly facilitates proton transport. The spatial distribution of proton currents visualized by scanning electrochemical cell microscopy reveals marked inhomogeneities that are strongly correlated with nanoscale wrinkles and other features where strain is accumulated. Our results highlight nanoscale morphology as an important parameter enabling proton transport through two-dimensional crystals, mostly considered and modelled as flat, and indicate that strain and curvature can be used as additional degrees of freedom to control the proton permeability of two-dimensional materials.

Ferrozoles: Ferrocenyl derivatives of letrozole with dual effects as potent aromatase inhibitors and cytostatic agents.

In the treatment of hormone-dependent cancers, aromatase inhibitors (AI) are receiving increased attention due to some undesirable effects such as the risk of endometrial cancer and thromboembolism of SERMs (selective estrogen receptor modulators). Letrozole is the most active AI with 99% aromatase inhibition. Unfortunately, this compound also exhibits some adverse effects such as hot flashes and fibromyalgias. Therefore, there is an urgent need to explore new types of AIs that retain the same-or even increased-antitumor ability. Inspired by the letrozole structure, a set of new derivatives has been synthesized that include a ferrocenyl moiety and different heterocycles. The derivative that contains a benzimidazole ring, namely compound 6, exhibits a higher aromatase inhibitory activity than letrozole and it also shows potent cytostatic behavior when compared to other well-established aromatase inhibitors, as demonstrated by dose-response, cell cycle, apoptosis and time course experiments. Furthermore, 6 promotes the inhibition of cell growth in both an aromatase-dependent and -independent fashion, as indicated by the study of A549 and MCF7 cell lines. Molecular docking and molecular dynamics calculations on the interaction of 6 or letrozole with the aromatase binding site revealed that the ferrocene moiety increases the van der Waals and hydrophobic interactions, thus resulting in an increase in binding affinity. Furthermore, the iron atom of the ferrocene fragment can form a metal-acceptor interaction with a propionate fragment, and this results in a stronger coupling with the heme group-a possibility that is consistent with the strong aromatase inhibition of 6.

MAPK11 (p38ß) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study.

Background and purpose: MAPKs are among the most relevant signalling pathways involved in coordinating cell responses to different stimuli. This group includes p38MAPKs, constituted by 4 different proteins with a high sequence homology: MAPK14 (p38α), MAPK11 (p38ß), MAPK12 (p38γ) and MAPK13 (p38δ). Despite their high similarity, each member shows unique expression patterns and even exclusive functions. Thus, analysing protein-specific functions of MAPK members is necessary to unequivocally uncover the roles of this signalling pathway. Here, we investigate the possible role of MAPK11 in the cell response to ionizing radiation (IR). Materials and methods: We developed MAPK11/14 knockdown through shRNA and CRISPR interference gene perturbation approaches and analysed the downstream effects on cell responses to ionizing radiation in A549, HCT-116 and MCF-7 cancer cell lines. Specifically, we assessed IR toxicity by clonogenic assays; DNA damage response activity by immunocytochemistry; apoptosis and cell cycle by flow cytometry (Annexin V and propidium iodide, respectively); DNA repair by comet assay; and senescence induction by both X-Gal staining and gene expression of senescence-associated genes by RT-qPCR. Results: Our findings demonstrate a critical role of MAPK11 in the cellular response to IR by controlling the associated senescent phenotype, and without observable effects on DNA damage response, apoptosis, cell cycle or DNA damage repair. Conclusion: Our results highlight MAPK11 as a novel mediator of the cellular response to ionizing radiation through the control exerted onto IR-associated senescence.

Timing and duration of nutrient restriction and its impacts on placental development and umbilical blood flow in adolescent sheep.

We hypothesized that nutrient restriction from day 50-90 of gestation decreases umbilical blood flow and that umbilical blood flow would recover to control values upon realimentation during late gestation (d 90 to 130) or remain reduced in ewes that continued to be nutrient restricted. On d 50 of gestation, young nulliparous whiteface ewes (6-8 mo; n = 41) carrying singletons were randomly assigned to two dietary treatments: 100% of NRC recommendations (CON) or 60% of CON (RES). On d 90 of gestation, ewes either remained on CON or RES until d 130, or CON ewes were RES from d 90 to 130, or RES ewes were realimented to CON from d 90 to 130. This resulted in 4 treatment groups on day 130: CON-CON, CON-RES, RES-RES, RES-CON. Umbilical blood flow and fetal and placental measurements were obtained via ultrasonography every 10 days from day 50-110. Non-survival surgeries were performed on days 50, 90, and 130 (n = 6-7 ewes/group) where uterine artery and umbilical blood flows were measured during surgery via ultrasonography. Conceptus weights were recorded and placentomes collected to determine binucleate cell numbers. The study was conducted as a completely randomized design arrangement with repeated measures. Data were analyzed using the MIXED procedure of SAS. There was a nutritional treatment by day interaction (P < 0.01) with CON ewes having greater umbilical blood flow compared with RES by d 90. Fetal biparietal distance, abdominal width, and kidney area increased (P < 0.05) in CON-RES with all these measurements increasing during late gestation. We partially accept our hypothesis as nutrient restriction during mid gestation decreased umbilical blood flow. However, blood flow did not return to control levels upon realimentation. By d 130, fetal and placental weights were similar between RES-RES and CON-CON. Binucleate cell numbers in the fetal trophoblast were not influenced by nutritional treatments. Our findings suggest that refeeding previously nutrient restricted pregnant adolescent ewes to control levels does not reestablish umbilical blood flow. Adequate placental development during mid gestation could protect the fetus from a decreased umbilical blood flow later in gestation when nutrients were limited by 40%.

['Wait and see' in paediatric epilepsy. Our experience]. / Wait and see en epilepsia pediátrica. Nuestra experiencia.

INTRODUCTION: Pharmacological treatment of epilepsy is not healing; it tries to avoid seizures, as far as possible, in children who probably would still have them. PATIENTS AND METHODS: Our purpose is to analyse our experience with epileptic children and those who have a first non-symptomatic seizure without pharmacological treatment. Patients seen in a paediatric neurology consultation, from 2017 to 2021, who had suffered one or more acute non-symptomatic crises and who had not been treated pharmacologically, were analysed. RESULTS: Sixty-five patients meet the selection criteria. Twenty-four patients had had a single crisis with a mean duration of 12 minutes (1-60). In 66.7% it was nocturnal. 41.7% presented pathological electroencephalogram, and 21% pathological findings in neuroimaging. The mean control time was 2.7 years (0.003-13.6 years). Forty-one presented more than one crisis, with a mean duration of nine minutes (1-60). Five patients presented more than 20 seizures, the rest between two and 17. Twenty-four (58.5%) presented only nocturnal seizures. An electroencephalogram was performed in all: epileptiform graphoelements in 63.4%; and neuroimaging in all: pathological in 4.9%. Mean control time was 3.8 years (0.01-9.1 years). CONCLUSIONS: Seizure frequency, underlying pathology or test results should not be the only variables to take into consideration when starting antiepileptic drug treatment. The repercussion on their quality of life and neurodevelopment should prevail, agreeing on this decision with the parents.

TITLE: Wait and see en epilepsia pediátrica. Nuestra experiencia.El tratamiento farmacológico de la epilepsia no es curativo; pretende, en lo posible, evitar crisis en niños que probablemente van a seguir teniéndolas. Pacientes y métodos. El objeto es analizar nuestra experiencia en niños con epilepsia y con primera crisis no sintomática aguda no tratados con antiepilépticos. Se analizó a pacientes atendidos en una consulta de neuropediatría, desde 2017 hasta 2021, que habían sufrido una o más crisis no sintomáticas agudas y a los que no se les había tratado farmacológicamente. Resultados. Sesenta y cinco pacientes cumplieron los criterios de selección. Veinticuatro habían tenido una única crisis, con un tiempo medio de duración de 12 minutos (1-60). En un 66,7% fue nocturna. Un 41,7% presentó electroencefalograma patológico, y un 21%, hallazgos patológicos en la neuroimagen. El tiempo medio de control fue de 2,7 años (0,003-13,6 años). Cuarenta y uno presentaron más de una crisis, con una duración media de nueve minutos (1-60). Cinco pacientes presentaron más de 20 crisis, y el resto, entre dos y 17. Veinticuatro (58,5%) presentaron únicamente crisis nocturnas. Se realizó un electroencefalograma en todos: grafoelementos epileptiformes en el 63,4%; y neuroimagen en todos: patológica en el 4,9%. El tiempo medio de control fue de 3,8 años (0,01-9,1 años). Conclusiones. La frecuencia de las crisis, la patología de base o los resultados de las pruebas complementarias no deberían ser las únicas variables que habría que considerar para iniciar el tratamiento farmacológico antiepiléptico en los niños. Debería prevalecer, por encima de aquéllos, el potencial perjuicio sobre la calidad de vida y el neurodesarrollo, las funciones atencionales y el comportamiento del niño, y siempre consensuar esta decisión con los padres.

Carbon footprint, economic benefits and sustainable fishing: Lessons for the future from the Western Mediterranean.

Ensuring an economically viable, sustainable and low CO2 emission extractive fishery is critical in order to achieve the life below water UN sustainable development goals and the climate change commitments of Paris agreement. This challenge is even more relevant in the most overexploited region of the world: The Mediterranean Sea. Here, we use the socio-ecological system of the Spanish Mediterranean commercial fisheries (Northern Alboran Sea, Northern Spain and the Balearic Islands) to develop an integrative impact assessment, including detailed socio-economic, ecosystem indices of the trophic structure of extractive fishery and CO2 emission analyses combining different gear, vessel size classes as well as a wide range estimation of carbon release from the seafloor by bottom trawling. Northern Alboran Sea preferentially requires reduction in purse seine fishery while in Northern Spain bottom trawling should be reduced first to reach sustainable exploitation. Fuel CO2 footprint of purse seine and bottom trawling are among the lowest footprints of animal protein production, but considering sweeping released CO2 from the seafloor the bottom trawling footprint becomes the animal protein production with the highest footprint. Moreover, the lowest bottom released CO2 estimation overrides 2.7-10 times the CO2 buried in the seafloor through the biological pump in trawled areas potentially turning the continental shelf from a CO2 sink to a CO2 source. Net profit per fuel derived CO2 emission for all fleets is lower than 1€ kgCO2-1, being lowest for large bottom trawler (0.025 € kgCO2-1). Thus, urgent mitigation and adaptation measures are necessary to obtain sustainable fishery in terms of net profit, sustainable seafood extraction and CO2 emission reduction. Our study provides scientific bases to develop these measures such as the restriction of harmful fishing gear in carbon rich river influenced areas, reduction of bottom contact of the fishing gear, favouring purse seine fishery and smaller bottom trawlers.

Boosting the photocatalytic properties of NaTaO3 by coupling with AgBr.

AgBr/NaTaO3 composites, with different molar % of NaTaO3 (Br/NTO(X%)), have been synthesized by simple precipitation methods; bare NaTaO3 was synthesized by hydrothermal procedure, while AgBr was synthesized by a precipitation procedure using cetyl-tri-methyl-ammonium bromide (CTAB) and AgNO3. Samples have been characterized by X-ray diffraction (XRD), N2 adsorption, UV-vis diffuse reflectance spectroscopy (DRS), Fourier-transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Photocatalytic activity of the as-prepared photo-catalysts was evaluated through photocatalytic degradation of rhodamine B (RhB), methyl orange (MO) and caffeic acid (CAFA) under UV and visible illumination. Single AgBr material and Br/NTO(X%) composites displayed the ability to absorb light in the visible region, while NaTaO3 is only photoactive under UV irradiation. Based on the position of conduction and valence bands of AgBr and NaTaO3, the heterojunction between these two photo-catalysts corresponds to a type II junction. In the case of photocatalytic degradation of RhB and CAFA, Br/NTO(x%) composites have highest photocatalytic activity than that obtained by both parental materials under the same operational conditions. AgBr and Br/NTO(x%) composites achieve a fast degradation of MO, together with a considerable adsorption capacity, attributed to the presence of a remaining amount of residual CTAB on the AgBr surface. In summary, coupling AgBr with NaTaO3 improves the photocatalytic activity under both UV and visible illumination with respect to the parental components, but the performance of the composites is highly dependent on the type of substrate to be degraded and the illumination conditions.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Wien effect in interfacial water dissociation through proton-permeable graphene electrodes.

Strong electric fields can accelerate molecular dissociation reactions. The phenomenon known as the Wien effect was previously observed using high-voltage electrolysis cells that produced fields of about 107 V m-1, sufficient to accelerate the dissociation of weakly bound molecules (e.g., organics and weak electrolytes). The observation of the Wien effect for the common case of water dissociation (H2O [Formula: see text] H+ + OH-) has remained elusive. Here we study the dissociation of interfacial water adjacent to proton-permeable graphene electrodes and observe strong acceleration of the reaction in fields reaching above 108 V m-1. The use of graphene electrodes allows measuring the proton currents arising exclusively from the dissociation of interfacial water, while the electric field driving the reaction is monitored through the carrier density induced in graphene by the same field. The observed exponential increase in proton currents is in quantitative agreement with Onsager's theory. Our results also demonstrate that graphene electrodes can be valuable for the investigation of various interfacial phenomena involving proton transport.

Sexual orientation, gender: Where is the problem? Nowhere! Correct self-identification and minority stigma.

PURPOSE: Self-concept, at the core of minority stress, is associated with negative mental health outcomes. METHODS: We aimed to assess the effectiveness of a one-shot third-wave CBT intervention targeting correct self-identification to address suffering related to minority stress. The study population included 172 participants (n = 98 heterosexuals, n=13 transgenders). The intervention consisted of a 90 minutes conference including overview of LGBT's suffering related to distal and proximal factors, a wisdom understanding of the root of suffering (mistaken self-identification) followed by a Questions & Answers session. Participants completed online self-questionnaires assessing sociodemographic data, acceptance by others (external) and oneself (internal) for sexual orientation and gender variables before the conference, immediately after the conference, and three months later. RESULTS: The conference helped to improve external acceptance of transgender for the whole sample, especially among the majority group. Those belonging to the minority (LGBT) had a positive benefit from the conference by reducing their fear of judgment. Adding a Q&A session to the conference failed to show any additional benefits. CONCLUSION: A specific wisdom-based self-identification conference appears to be an effective and low-cost intervention to target minority stigma, and therefore mental health and social integration of LGBT people.

Uterine kallikrein and arterial bradykinin activities and uterine arterial proliferation in response to acute estradiol-17ß exposure in ovariectomized ewes.

Estradiol-17ß (E2) increases kallikrein in rodent and human reproductive tissues. Kallikrein specific activity is increased in the porcine uterus when conceptus E2 is secreted at maternal recognition of pregnancy. When kallikrein acts on kininogen to liberate bradykinin, angiogenic and vasoactive factors are released. The uterus of ovariectomized ewes administered E2 undergoes rapid vascular changes via different patterns of angiogenic and vasoactive factors. Our hypothesis was that E2 would increase the specific activity and protein secretion of tissue kallikrein in endometrial explants culture media (ECM) and ewes exposed to E2 would have uterine arteries that would be more sensitive to the vasodilatory effects of bradykinin. Ovariectomized ewes received 100 mg of E2 implants for 0, 12, 24, or 48 h. After treatment, uterine weights were determined, and caruncles were processed for ECM. Uterine weights and uterine weight per ewe body weight were significantly greater in the 12 and 24 h ewes compared with the 0 h ewes, with the 48 h ewes being similar to the 24 h ewes. There were no statistically significant differences in caruncular tissue kallikrein protein secretion among the treatment groups. There was a tendency (P = 0.09) for duration of E2 exposure to influence tissue kallikrein specific activity where kallikrein activity was greater (P ≤ 0.05) in the 12 and 48 h ewes compared with the 0 h ewes, with 24 h ewes being intermediate (unprotected F test). Uterine arteries from ewes with E2 for 24 and 48 h had more sensitivity to bradykinin, via the bradykinin receptor 2, than uterine arteries from ewes with 0 or 12 h E2 exposure. We fail to reject our hypothesis as E2 did elicit a positive response in tissue kallikrein specific activity and bradykinin response. Further investigations are needed to determine how kallikrein and bradykinin may be involved in vascular remodeling of the ovine uterus.

Post-traumatic stress disorder prevalence and sleep quality in fire victims and rescue workers in southern Brazil: a cross-sectional study.

OBJECTIVES: This survey was conducted to evaluate the prevalence of post-traumatic stress disorder (PTSD) and the sleep quality in victims and rescue team of the third deadliest nightclub fire in the world. STUDY DESIGN: A cross-sectional study. METHODS: Participants were victims and rescue workers exposed to a fire at a nightclub, which occurred in January 2013 in Southern Brazil. The Pittsburgh Sleep Quality Index (PSQI), composed of seven subjective sleep variables (including daytime dysfunction), and PTSD Checklist - Civilian version (PCL-C) were applied to all people who sought medical attention at the local reference center in the first year after the event. Comprehensive information was obtained concerning sociodemographic factors, health status, and sleep complaints. RESULTS: A total of 370 individuals, 190 victims and 180 rescue workers, were included. Participants were 70% male, with an average age of 29 years. The prevalence of PTSD was 31.9%, ranging from 24.4% for rescue workers to 38.9% for victims. The prevalence of poor sleep quality was 65.9%, ranging from 56.1% for rescue workers to 75.3% for victims. Most of the participants with PTSD (91.5%) had PSQI scores >5 (poor sleepers), against 54.0% of the non-PTSD individuals. All seven PSQI subscores showed significant differences between PTSD and non-PTSD individuals, especially daytime dysfunction. Sex, shift work, previous psychiatric disease, and sleep quality remained associated with PTSD in adjusted models, with a prevalence ratio (95% CI) of 1.76 (1.28-2.43) in females, 1.73 (1.17-2.55) in shift workers, 1.36 (1.03-1.80) in individuals with psychiatric disease history, and 5.42 (2.55-11.52) in poor sleepers. CONCLUSIONS: The presence of daytime dysfunction increased by at least tenfold the prevalence of PTSD in this sample. Considering that daytime dysfunction was shown to be strongly associated with PTSD, sleep-related issues should be addressed in the assessment of individuals exposed to traumatic events, both victims and rescuers. Factors like shift work and female sex were also associated with PTSD, especially among victims.

AGING-ASSOCIATED COGNITIVE DECLINE IS REVERSED BY D-SERINE SUPPLEMENTATION.

Brain aging is a natural process that involves structural and functional changes that lead to cognitive decline, even in healthy subjects. This detriment has been associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction due to a reduction in the brain levels of D-serine, the endogenous NMDAR co-agonist. However, it is not clear if D-serine supplementation could be used as an intervention to reduce or reverse age-related brain alterations. In the present work, we aimed to analyze the D-serine effect on aging-associated alterations in cellular and large-scale brain systems that could support cognitive flexibility in rats. We found that D-serine supplementation reverts the age-related decline in cognitive flexibility, frontal dendritic spine density, and partially restored large-scale functional connectivity without inducing nephrotoxicity; instead, D-serine restored the thickness of the renal epithelial cells that were affected by age. Our results suggest that D-serine could be used as a therapeutic target to reverse age-related brain alterations.SIGNIFICANT STATEMENTAge-related behavioral changes in cognitive performance occur as a physiological process of aging. Then, it is important to explore possible therapeutics to decrease, retard or reverse aging effects on the brain. NMDA receptor hypofunction contributes to the aging-associated cognitive decline. In the aged brain, there is a reduction in the brain levels of the NMDAR co-agonist, D-Serine. However, it is unclear if chronic D-serine supplementation could revert the age-detriment in brain functions. Our results show that D-serine supplementation reverts the age-associated decrease in cognitive flexibility, functional brain connectivity, and neuronal morphology. Our findings raise the possibility that restoring the brain levels of D-serine could be used as a therapeutic target to recover brain alterations associated with aging.

Decreased mortality among patients with catheter-related bloodstream infections at Catalan hospitals (2010-2019).

BACKGROUND: The incidence of catheter-related bloodstream infections (CRBSIs) has fallen over the last decade, especially in intensive care units (ICUs). AIM: To assess the existence of concomitant trends in outcomes and to analyse the current risk factors for mortality. METHODS: A multicentre retrospective cohort study was conducted at 24 Catalan hospitals participating in the Surveillance of healthcare-associated infections in Catalonia (VINCat). All hospital-acquired CRBSI episodes diagnosed from January 2010 to December 2019 were included. A common protocol including epidemiological, clinical, and microbiological data was prospectively completed. Mortality at 30 days after bacteraemia onset was analysed using the Cox regression model. FINDINGS: Over the study period, 4795 episodes of CRBSI were diagnosed. Among them, 75% were acquired in conventional wards and central venous catheters were the most frequently involved (61%). The 30-day mortality rate was 13.8%, presenting a significant downward trend over the study period: from 17.9% in 2010 to 10.6% in 2019 (hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.92-0.98). The multivariate analysis identified age (HR: 1.03; 95% CI: 1.02-1.04), femoral catheter (1.78; 1.33-2.38), medical ward acquisition (2.07; 1.62-2.65), ICU acquisition (3.45; 2.7-4.41), S. aureus (1.59; 1.27-1.99) and Candida sp. (2.19; 1.64-2.94) as risk factors for mortality, whereas the mortality rate associated with episodes originating in peripheral catheters was significantly lower (0.69; 0.54-0.88). CONCLUSION: Mortality associated with CRBSI has fallen in recent years but remains high. Intervention programmes should focus especially on ICUs and medical wards, where incidence and mortality rates are highest.