Hypothalamic hormone deficiency enables physiological anorexia.

Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5-7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24-48-hour periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger during IBAs. These squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons exhibit reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.

microRNA-33 controls hunger signaling in hypothalamic AgRP neurons.

AgRP neurons drive hunger, and excessive nutrient intake is the primary driver of obesity and associated metabolic disorders. While many factors impacting central regulation of feeding behavior have been established, the role of microRNAs in this process is poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical role in the regulation of AgRP neurons, and that loss of miR-33 leads to increased feeding, obesity, and metabolic dysfunction in mice. These effects include the regulation of multiple miR-33 target genes involved in mitochondrial biogenesis and fatty acid metabolism. Our findings elucidate a key regulatory pathway regulated by a non-coding RNA that impacts hunger by controlling multiple bioenergetic processes associated with the activation of AgRP neurons, providing alternative therapeutic approaches to modulate feeding behavior and associated metabolic diseases.

Molecularly stratified hypothalamic astrocytes are cellular foci for obesity.

Astrocytes safeguard the homeostasis of the central nervous system1,2. Despite their prominent morphological plasticity under conditions that challenge the brain's adaptive capacity3-5, the classification of astrocytes, and relating their molecular make-up to spatially devolved neuronal operations that specify behavior or metabolism, remained mostly futile6,7. Although it seems unexpected in the era of single-cell biology, the lack of a major advance in stratifying astrocytes under physiological conditions rests on the incompatibility of 'neurocentric' algorithms that rely on stable developmental endpoints, lifelong transcriptional, neurotransmitter, and neuropeptide signatures for classification6-8 with the dynamic functional states, anatomic allocation, and allostatic plasticity of astrocytes1. Simplistically, therefore, astrocytes are still grouped as 'resting' vs. 'reactive', the latter referring to pathological states marked by various inducible genes3,9,10. Here, we introduced a machine learning-based feature recognition algorithm that benefits from the cumulative power of published single-cell RNA-seq data on astrocytes as a reference map to stepwise eliminate pleiotropic and inducible cellular features. For the healthy hypothalamus, this walk-back approach revealed gene regulatory networks (GRNs) that specified subsets of astrocytes, and could be used as landmarking tools for their anatomical assignment. The core molecular censuses retained by astrocyte subsets were sufficient to stratify them by allostatic competence, chiefly their signaling and metabolic interplay with neurons. Particularly, we found differentially expressed mitochondrial genes in insulin-sensing astrocytes and demonstrated their reciprocal signaling with neurons that work antagonistically within the food intake circuitry. As a proof-of-concept, we showed that disrupting Mfn2 expression in astrocytes reduced their ability to support dynamic circuit reorganization, a time-locked feature of satiety in the hypothalamus, thus leading to obesity in mice. Overall, our results suggest that astrocytes in the healthy brain are fundamentally more heterogeneous than previously thought and topologically mirror the specificity of local neurocircuits.

Size Matters: A Computational Study of Hydrogen Absorption in Ionic Liquids.

We combined both density functional theory and classical molecular dynamics simulations to investigate the molecular mechanisms governing hydrogen solvation in a total of 12 ionic liquids. Overall, the analysis of the structural properties under high temperature and pressure conditions revealed weak interactions between hydrogen and the ionic liquids, with a slight preference of this gas to be placed at the apolar domains. Interestingly, those ionic liquids comprising nitrate anions allow the accommodation of hydrogen molecules also in the polar areas. The study of the hydrogen velocity autocorrelation functions supports this observation. In addition, the structure of all of the tested ionic liquids was almost insensitive to the addition of hydrogen, so the available free volume and cavity formation are presumably the most important factors affecting solubility.

CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.

Dysregulation of hypothalamic ceramides has been associated with disrupted neuronal pathways in control of energy and glucose homeostasis. However, the specific ceramide species promoting neuronal lipotoxicity in obesity have remained obscure. Here, we find increased expression of the C16:0 ceramide-producing ceramide synthase (CerS)6 in cultured hypothalamic neurons exposed to palmitate in vitro and in the hypothalamus of obese mice. Conditional deletion of CerS6 in hypothalamic neurons attenuates high-fat diet (HFD)-dependent weight gain and improves glucose metabolism. Specifically, CerS6 deficiency in neurons expressing pro-opiomelanocortin (POMC) or steroidogenic factor 1 (SF-1) alters feeding behavior and alleviates the adverse metabolic effects of HFD feeding on insulin sensitivity and glucose tolerance. POMC-expressing cell-selective deletion of CerS6 prevents the diet-induced alterations of mitochondrial morphology and improves cellular leptin sensitivity. Our experiments reveal functions of CerS6-derived ceramides in hypothalamic lipotoxicity, altered mitochondrial dynamics, and ER/mitochondrial stress in the deregulation of food intake and glucose metabolism in obesity.

Deep learning estimation of modified Zernike coefficients and recovery of point spread functions in turbulence.

Recovering the turbulence-degraded point spread function from a single intensity image is important for a variety of imaging applications. Here, a deep learning model based on a convolutional neural network is applied to intensity images to predict a modified set of Zernike polynomial coefficients corresponding to wavefront aberrations in the pupil due to turbulence. The modified set assigns an absolute value to coefficients of even radial orders due to a sign ambiguity associated with this problem and is shown to be sufficient for specifying the intensity point spread function. Simulated image data of a point object and simple extended objects over a range of turbulence and detection noise levels are created for the learning model. The MSE results for the learning model show that the best prediction is found when observing a point object, but it is possible to recover a useful set of modified Zernike coefficients from an extended object image that is subject to detection noise and turbulence.

Differences in clinical outcomes, health care resource utilization and costs in heart failure patients according to left ventricular ejection fraction.

INTRODUCTION AND OBJECTIVES: The impact of left ventricular ejection fraction (LVEF) on health care resource utilization (HCRU) and cost in heart failure (HF) patients is not well known. We aimed to compare outcomes, HCRUs and costs according to LVEF groups. METHODS: Retrospective, observational study of all patients with an emergency department (ED) visit or admission to a tertiary hospital in Spain 2018 with a primary HF diagnosis. We excluded patients with newly diagnosed heart failure. One-year clinical outcomes, costs and HCRUs were compared according to LVEF (reduced [HFrEF], mildly reduced [HFmrEF], and preserved [HFpEF]). RESULTS: Among 1287 patients with a primary diagnosis of HF in the ED, 365 (28.4%) were discharged to home (ED group), and 919 (71.4%) were hospitalized (hospital group [HG]). In total, 190 patients (14.7%) had HFrEF, 146 (11.4%) HFmrEF, and 951 (73.9%) HFpEF. The mean age was 80.1±10.7 years; 57.1% were female. The median [interquartile range] of costs per patient/y was €1889 [259-6269] in the ED group and €5008 [2747-9589] in the HG (P <.001). Hospitalization rates were higher in patients with HFrEF in the ED group. The median costs of HFrEF per patient/y were higher in patients in both groups: €4763 [2076-17 155] vs €3900 [590-8013] for HFmrEF vs €3812 [259-5486] for HFpEF in the ED group, and €6321 [3335-796] vs €6170 [3189-10484] vs €4636 [2609-8977], respectively, in the hospital group (all P <.001). This difference was driven by the more frequent admission to intensive care units, and greater use of diagnostic and therapeutic tests among HFrEF patients. CONCLUSIONS: In HF, LVEF significantly impacts costs and HCRU. Costs were higher in patients with HFrEF, especially those requiring hospitalization, than in those with HFpEF.

A Cross-Sectional, Retrospective, and Comparative Study between Delirium and Non-Delirium Psychiatric Disorders in a Psychogeriatric Inpatient Population Referred to Consultation-Liaison Psychiatry Unit.

Background and objectives: Delirium is the most prevalent psychiatric disorder in inpatient older people. Its presence is associated with higher rates of institutionalization, functional disability and mortality. This study aims to evaluate delirium in a hospitalized psychogeriatric population, focusing on which factors predict the appearance of delirium, the impact it generates and the diagnostic concordance between non-psychiatric physicians and psychiatrists. Material and methods: This is an observational, cross-sectional, retrospective, and comparative study. We obtained data from a sample of 1017 patients (≥65 years) admitted to general hospital and referred from different services to the consultation-liaison psychiatry (CLP) unit. Logistic regression was performed using delirium as the dependent variable. To estimate the concordance of the diagnoses, the Kappa coefficient was used. To assess the impact of delirium, an ordinal regression, Wilcoxon median test and Fisher's test were performed. Results: Delirium is associated with a higher number of visits, OR 3.04 (95% CI 2.38-3.88), longer length of stay and mortality, OR 2.07 (95% CI, 1.05 to 4.10). The model to predict delirium shows that being >75 years old has an OR of 2.1 (95% CI, 1.59-2.79), physical disability has an OR of 1.66 (95% CI, 1.25-2.20), history of delirium has an OR of 10.56 (95% CI, 5.26-21.18) and no use of benzodiazepines has an OR of 4.24 (95% CI, 2.92-6.14). The concordance between the referring physician's psychiatric diagnosis and the psychiatrist CLP unit showed a kappa of 0.30. When analysing depression and delirium, the concordance showed Kappa = 0.46. Conclusions: Delirium is a highly prevalent psychiatric disorder, but it is still underdiagnosed, with low diagnostic concordance between non-psychiatric doctors and psychiatrists from CLP units. There are multiple risk factors associated with the appearance of delirium, which must be managed to reduce its appearance.

Influence of Metal Salts Addition on Physical and Electrochemical Properties of Ethyl and Propylammonium Nitrate.

In this work, we deepen in the characterization of two protic ionic liquids (PILs), ethylammonium nitrate (EAN) and propylammonium nitrate (PAN). With this aim, we determined the influence of inorganic nitrate salts addition on their physical properties and their electrochemical potential window (EPW). Thus, experimental measurements of electrical conductivity, density, viscosity, refractive index and surface tension of mixtures of {EAN or PAN + LiNO3, Ca(NO3)2, Mg(NO3)2 or Al(NO3)3} at a temperature range between 5 and 95 °C are presented first, except for the last two properties which were measured at 25 °C. In the second part, the corresponding EPWs were determined at 25 °C by linear sweep voltammetry using three different electrochemical cells. Effect of the salt addition was associated mainly with the metal cation characteristics, so, generally, LiNO3 showed the lower influence, followed by Ca(NO3)2, Mg(NO3)2 or Al(NO3)3. The results obtained for the EAN + LiNO3 mixtures, along with those from a previous work, allowed us to develop novel predictive equations for most of the presented physical properties as functions of the lithium salt concentration, the temperature and the water content. Electrochemical results showed that a general order of EPW can be established for both PILs, although exceptions related to measurement conditions and the properties of the mixtures were found.

Paraventricular glia drive circuit function to control metabolism.

The role of glia as active participants in brain functions has become increasingly evident. In this issue of Cell Metabolism, Herrera Moro Chao et al. reveal that astrocytes in the hypothalamic paraventricular nucleus (PVN) bidirectionally control neuronal behavior in response to metabolic cues and that this control is disrupted in obesity.

Healthcare resource utilization and costs among patients with heart failure with preserved, mildly reduced, and reduced ejection fraction in Spain.

AIMS: To describe healthcare resource utilization (HCRU) of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain.  METHODS: Adults with ≥ 1 HF diagnosis and ≥ 1 year of continuous enrolment before the corresponding index date (1/January/2016) were identified through the BIG-PAC database. Rate per 100 person-years of all-cause and HF-related HCRU during the year after the index date were estimated using bootstrapping with replacement. RESULTS: Twenty-one thousand two hundred ninety-seven patients were included, of whom 48.5% had HFrEF, 38.6% HFpEF and 4.2% HFmrEF, with the rest being of unknown EF. Mean age was 78.8 ± 11.8 years, 53.0% were men and 83.0% were in NYHA functional class II/III. At index, 67.3% of patients were taking renin angiotensin system inhibitors, 61.2% beta blockers, 23.4% aldosterone antagonists and 5.2% SGLT2 inhibitors. Rates of HF-related outpatient visits and hospitalization were 968.8 and 51.6 per 100 person-years, respectively. Overall, 31.23% of patients were hospitalized, mainly because of HF (87.88% of total hospitalizations); HF hospitalization length 21.06 ± 17.49 days (median 16; 25th, 75th percentile 9-27). HF hospitalizations were the main cost component: inpatient 73.64%, pharmacy 9.67%, outpatient 9.43%, and indirect cost 7.25%. Rates of all-cause and HF-related HCRU and healthcare cost were substantial across all HF subgroups, being higher among HFrEF compared to HFmrEF and HFpEF patients. CONCLUSIONS: HCRU and cost associated with HF are high in Spain, HF hospitalizations being the main determinant. Medication cost represented only a small proportion of total costs, suggesting that an optimization of HF therapy may reduce HF burden.

Prevalence, Characteristics, Management and Outcomes of Patients with Heart Failure with Preserved, Mildly Reduced, and Reduced Ejection Fraction in Spain.

Objective: To estimate the prevalence, incidence, and describe the characteristics and management of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain. Methods: Adults with ≥1 inpatient or outpatient HF diagnosis between 1 January 2013 and 30 September 2019 were identified through the BIG-PAC database. Annual incidence and prevalence by EF phenotype were estimated. Characteristics by EF phenotype were described in the 2016 and 2019 HF prevalent cohorts and outcomes in the 2016 HF prevalent cohort. Results: Overall, HF incidence and prevalence were 0.32/100 person-years and 2.34%, respectively, but increased every year. In 2019, 49.3% had HFrEF, 38.1% had HFpEF, and 4.3% had HFmrEF (in 8.3%, EF was not available). Compared with HFrEF, patients with HFpEF were largely female, older, and had more atrial fibrillation but less atherosclerotic cardiovascular disease. Among patients with HFrEF, 76.3% were taking renin-angiotensin system inhibitors, 69.5% beta-blockers, 36.8% aldosterone antagonists, 12.5% sacubitril/valsartan and 6.7% SGLT2 inhibitors. Patients with HFpEF and HFmrEF took fewer HF drugs compared to HFrEF. Overall, the event rates of HF hospitalization were 231.6/1000 person-years, which is more common in HFrEF patients. No clinically relevant differences were found in patients with HFpEF, regardless EF (50- < 60% vs. ≥60%). Conclusions: >2% of patients have HF, of which around 50% have HFrEF and 40% have HFpEF. The prevalence of HF is increasing over time. Clinical characteristics by EF phenotype are consistent with previous studies. The risk of outcomes, particularly HF hospitalization, remains high, likely related to insufficient HF treatment.

Risk of outcomes in a Spanish population with chronic kidney disease.

Objectives: To assess mortality and cardiovascular and renal outcomes among patients with chronic kidney disease (CKD) (primary objective), with a particular focus on heart failure (HF) risk following diagnosis of CKD (secondary objective) in Spain. Methods: We conducted an observational study comprising cross-sectional and longitudinal retrospective analyses using secondary data from electronic health records. For the primary objective, adults with prevalent CKD [estimated glomerular filtration rate (eGFR) <60 or ≥60 mL/min/1.73 m2 with a urine albumin:creatinine ratio (UACR) ≥30 mg/g at the index date (1 January 2017)] were included. For the secondary objective, adults with incident CKD in 2017 were enrolled. Results: In the prevalent population, 46 786 patients with CKD without HF [75.8 ± 14.4 years, eGFR 51.4 ± 10.1 mL/min/1.73 m2; 75.1% on renin-angiotensin system inhibitors (RASis)] and 8391 with CKD and HF (79.4 ± 10.9 years, eGFR 46.4 ± 9.8 mL/min/1.73 m2) were included. In the prevalent population, the risk of all-cause death {hazard ratio [HR] 1.107 [95% confidence interval (CI) 1.064-1.153]}, HF hospitalization [HR 1.439 (95% CI 1.387-1.493)] and UACR progression [HR 1.323 (95% CI 1.182-1.481)] was greater in those patients with CKD and HF versus CKD only. For the incident population, 1594 patients with CKD without HF and 727 with CKD and HF were included. Within 24 months from the CKD diagnosis (with/without HF at baseline), 6.5% of patients developed their first HF hospitalization. Although 60.7% were taking RASis, only 3.4% were at maximal doses and among diabetics, 1.3% were taking sodium-glucose cotransporter-2 inhibitors. Conclusions: The presence of HF among CKD patients markedly increases the risk of outcomes. CKD patients have a high risk of HF, which could be partially related to insufficient treatment.

Primary vs. Secondary Heart Failure Diagnosis: Differences in Clinical Outcomes, Healthcare Resource Utilization and Cost.

Background: There is scarce information on patients with secondary heart failure diagnosis (sHF). We aimed to compare the characteristics, burden, and outcomes of sHF with those with primary HF diagnosis (pHF). Methods: Retrospective, observational study on patients ≥18 years with emergency department (ED) visits during 2018 with pHF and sHF in ED or hospital (ICD-10-CM) diagnostic codes. Baseline characteristics, 30-day and 1-year mortality, readmission and re-ED visit rates, and costs were compared between sHF and pHF. Results: Out of the 797 patients discharged home from the ED, 45.5% had sHF, and these presented lower 1-year hospitalization, re-ED visit rates, and costs. In contrast, out of the 2,286 hospitalized patients, 55% had sHF and 45% pHF. Hospitalized sHF patients had significantly (p < 0.01) greater comorbidity, lower use of recommended HF therapies, longer length of stay (10.8 ± 10.1 vs. 9.7 ± 7.9 days), and higher in-hospital and 1-year mortality (32 vs. 25.8%) with no significant differences in readmission rates and lower 1-year re-ED visit rate. Hospitalized sHF patients had higher total costs (€12,262,422 vs. €9,144,952, p < 0.001), mean cost per patient-year (€9,755 ± 13,395 vs. €8,887 ± 12,059), and average daily cost per patient. Conclusion: Hospitalized sHF patients have a worse initial prognosis, greater use of healthcare resources, and higher costs.

Oncogenic Pathways in Neurodegenerative Diseases.

Cancer and neurodegenerative diseases are two of the leading causes of premature death in modern societies. Their incidence continues to increase, and in the near future, it is believed that cancer will kill more than 20 million people per year, and neurodegenerative diseases, due to the aging of the world population, will double their prevalence. The onset and the progression of both diseases are defined by dysregulation of the same molecular signaling pathways. However, whereas in cancer, these alterations lead to cell survival and proliferation, neurodegenerative diseases trigger cell death and apoptosis. The study of the mechanisms underlying these opposite final responses to the same molecular trigger is key to providing a better understanding of the diseases and finding more accurate treatments. Here, we review the ten most common signaling pathways altered in cancer and analyze them in the context of different neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), and Huntington's (HD) diseases.

Universal healthcare coverage for first episode of schizophrenia-spectrum disorders in Chile: analysis of the administrative database.

Aim of the study was to analyse the Ministry of Health's (MINSAL) administrative database of the Universal Health Coverage (UHC) program for First Episode of Schizophrenia Spectrum Disorders (FEP-SSD). The database included every case registered in the program between 2004 and 2017. According to the timeframes established for permanence in the program, cases were defined as Suspected, FEP in diagnostic observation and FEP-SSD. Only first registers were analysed. We compared gender, age at entry, level of care and region where the case was registered. Denominator data for estimation of incidence rates were obtained from the last census. We adjusted incidence rate ratios by age, gender, and region. During the studied period, 33.207 suspected cases were registered. 27.006 (81%) were confirmed as FEP and after 6-month follow-up, 22.701 (68%) were confirmed as FEP-SSD. The median age at entry was 24 years, males entering at younger age. Male proportion was higher than female in all groups. 46.9% of all cases were detected in primary care. FEP-SSD cases were six years younger and had a higher proportion of males than discarded cases (62.6 vs 53.2%). During 169.4 million person-years at risk, crude incidence for suspected cases was 19.58 per 100.000 person-years; for FEP, 15.92 per 100.000 person-years and for FEP-SSD, 13.38 per 100.000 person-years. Chile has lower incidence of FEP-SSD compared to current world estimations but gender proportions are comparable. This UHC program has allowed early access through the integration of mental health to the health network at all levels of care.

Al3+ solvation in solutions of aluminum nitrate in a protic ionic liquid: Nuclear magnetic resonance verification of the solvation shell composition.

The closest environment of Al3+ cations was analyzed in detail in solutions of aluminum nitrate in the prototypical protic ionic liquid ethyl ammonium nitrate (EAN) using 1 H and 14 N nuclear magnetic resonance (NMR) spectra. For Al (NO3 )3 -EAN mixtures with different water content, a quantitative analysis of the integral intensities of the 1 H and 14 N signals was carried out and the composition of the first solvation shell of the aluminum cation was refined.

Epidemiology and treatment of heart failure in Spain: the HF-PATHWAYS study.

INTRODUCTION AND OBJECTIVES: To describe the epidemiology and treatment of a large contemporary cohort of patients with heart failure (HF). METHODS: Observational, retrospective, population-based study using the BIG-PAC database, which includes people aged ≥ 18 years seeking care for HF between 2017 and 2019. The main variables were the prevalence/annual incidence rate, comorbidities, clinical variables, and medication administered. RESULTS: We identified 19 762 patients with HF from a total of 1 189 003 persons seeking medical attention from 2017 to 2019 (2019: mean age, 78.3 years; 53.0% men). Distribution by type of left ventricular ejection fraction (LVEF) was as follows: 51.7% reduced, 40.2% preserved, and 8.1% mid-range. In 2019, the prevalence was 1.89% (95%CI, 1.70-2.08), with an incidence rate of 2.78 new cases per 1000 persons/y. No statistically significant differences were observed in prevalence and/or incidence from 2017 to 2019. Among patients with HF with reduced ejection fraction (HFrEF), 64% received beta-blockers, 80.5% angiotensin-converting enzyme inhibitor/angiotensin receptor blockers or sacubitril-valsartan, and 29.8% an aldosterone antagonist. In addition, from the diagnosis (baseline) to 24 months of follow-up, there was discreet treatment optimization, which was notable in the first 3 to 6 months. CONCLUSIONS: Epidemiological data on HF remained stable during the study period, with a lower prevalence than that reported in non-population-based studies. There is wide room for improvement in the optimization of medical treatment of HFrEF.

A Differentiable Neural-Network Force Field for Ionic Liquids.

We present NeuralIL, a model for the potential energy of an ionic liquid that accurately reproduces first-principles results with orders-of-magnitude savings in computational cost. Built on the basis of a multilayer perceptron and spherical Bessel descriptors of the atomic environments, NeuralIL is implemented in such a way as to be fully automatically differentiable. It can thus be trained on ab initio forces instead of just energies, to make the most out of the available data, and can efficiently predict arbitrary derivatives of the potential energy. Using ethylammonium nitrate as the test system, we obtain out-of-sample accuracies better than 2 meV atom-1 (<0.05 kcal mol-1) in the energies and 70 meV Å-1 in the forces. We show that encoding the element-specific density in the spherical Bessel descriptors is key to achieving this. Harnessing the information provided by the forces drastically reduces the amount of atomic configurations required to train a neural network force field based on atom-centered descriptors. We choose the Swish-1 activation function and discuss the role of this choice in keeping the neural network differentiable. Furthermore, the possibility of training on small data sets allows for an ensemble-learning approach to the detection of extrapolation. Finally, we find that a separate treatment of long-range interactions is not required to achieve a high-quality representation of the potential energy surface of these dense ionic systems.

Ecotoxicity of binary mixtures of ILs and inorganic salts of electrochemical interest.

The applicability of ionic liquids (ILs) has increased over the last years, and even new opportunities are becoming a reality, i.e. mixtures of pure IL and inorganic salt as electrolytes for smart electrochemical devices, yet the effects on the environment are almost unknown. In this work, the ecotoxicity of two pure protic ILs (Ethylammonium nitrate and Ethylimidazolium nitrate) and two pure aprotic ILs (butylmethylpyrrolidinium bis(trifluoromethylsulfonyl)imide and butyldimethylimidazolium bis(trifluoromethylsulfonyl)imide) and that of their binary mixtures with inorganic salts with common cation was tested towards changes in the bioluminescence of the bacteria Aliivibrio fischeri, using the Microtox® standard toxicity test. EC50 of these mixtures was determined over three standard periods of time and compared with the corresponding values to pure ILs. Results indicate that the aprotic ILs are more toxic than protic and that aromatic are more toxic than non-aromatic. The addition of inorganic mono (LiNO3), di (Ca(NO3)2·4H2O, Mg(NO3)2·6H2O) and trivalent (Al(NO3)3·9H2O) salts in binary mixtures with EAN was analysed first. The latter was found to induce an important increase in toxicity. Finally, mixtures of IL-inorganic lithium salt (LiNO3, for the protic ILs and LiTFSI for the aprotic ILs) toxicity was also studied, which showed toxicity levels strongly dependent on the IL of the mixture.