Mediterranean springs: Keystone ecosystems and biodiversity refugia threatened by global change.

Mediterranean spring ecosystems are unique habitats at the interface between surface water and groundwater. These ecosystems support a remarkable array of biodiversity and provide important ecological functions and ecosystem services. Spring ecosystems are influenced by abiotic, biotic, and anthropogenic factors such as the lithology of their draining aquifers, their climate, and the land use of their recharge area, all of which affect the water chemistry of the aquifer and the spring discharges. One of the most relevant characteristics of spring ecosystems is the temporal stability of environmental conditions, including physicochemical features of the spring water, across seasons and years. This stability allows a wide range of species to benefit from these ecosystems (particularly during dry periods), fostering an unusually high number of endemic species. However, global change poses important threats to these freshwater ecosystems. Changes in temperature, evapotranspiration, and precipitation patterns can alter the water balance and chemistry of spring water. Eutrophication due to agricultural practices and emergent pollutants, such as pharmaceuticals, personal care products, and pesticides, is also a growing concern for the preservation of spring biodiversity. Here, we provide a synthesis of the main characteristics and functioning of Mediterranean spring ecosystems. We then describe their ecological value and biodiversity patterns and highlight the main risks these ecosystems face. Moreover, we identify existing knowledge gaps to guide future research in order to fully uncover the hidden biodiversity within these habitats and understand the main drivers that govern them. Finally, we provide a brief summary of recommended actions that should be taken to effectively manage and preserve Mediterranean spring ecosystems for future generations. Even though studies on Mediterranean spring ecosystems are still scarce, our review shows there are sufficient data to conclude that their future viability as functional ecosystems is under severe threat.

COVID-19 vaccines reduce mortality in hospitalized patients with oxygen requirements: Differences between vaccine subtypes. A multicontinental cohort study.

The aim of this study was to analyze whether the coronavirus disease 2019 (COVID-19) vaccine reduces mortality in patients with moderate or severe COVID-19 disease requiring oxygen therapy. A retrospective cohort study, with data from 148 hospitals in both Spain (111 hospitals) and Argentina (37 hospitals), was conducted. We evaluated hospitalized patients for COVID-19 older than 18 years with oxygen requirements. Vaccine protection against death was assessed through a multivariable logistic regression and propensity score matching. We also performed a subgroup analysis according to vaccine type. The adjusted model was used to determine the population attributable risk. Between January 2020 and May 2022, we evaluated 21,479 COVID-19 hospitalized patients with oxygen requirements. Of these, 338 (1.5%) patients received a single dose of the COVID-19 vaccine and 379 (1.8%) were fully vaccinated. In vaccinated patients, mortality was 20.9% (95% confidence interval [CI]: 17.9-24), compared to 19.5% (95% CI: 19-20) in unvaccinated patients, resulting in a crude odds ratio (OR) of 1.07 (95% CI: 0.89-1.29; p = 0.41). However, after considering the multiple comorbidities in the vaccinated group, the adjusted OR was 0.73 (95% CI: 0.56-0.95; p = 0.02) with a population attributable risk reduction of 4.3% (95% CI: 1-5). The higher risk reduction for mortality was with messenger RNA (mRNA) BNT162b2 (Pfizer) (OR 0.37; 95% CI: 0.23-0.59; p < 0.01), ChAdOx1 nCoV-19 (AstraZeneca) (OR 0.42; 95% CI: 0.20-0.86; p = 0.02), and mRNA-1273 (Moderna) (OR 0.68; 95% CI: 0.41-1.12; p = 0.13), and lower with Gam-COVID-Vac (Sputnik) (OR 0.93; 95% CI: 0.6-1.45; p = 0.76). COVID-19 vaccines significantly reduce the probability of death in patients suffering from a moderate or severe disease (oxygen therapy).

Pro-arrhythmogenic effects of Trypanosoma cruzi conditioned medium proteins in a model of bovine chromaffin cells.

Asymptomatic sudden death is the principal cause of mortality in Chagas disease. There is little information about molecular mechanisms involved in the pathophysiology of malignant arrhythmias in Chagasic patients. Previous studies have involved Trypanosoma cruzi secretion proteins in the genesis of arrhythmias ex vivo, but the molecular mechanisms involved are still unresolved. Thus, the aim was to determine the effect of these secreted proteins on the cellular excitability throughout to test its effects on catecholamine secretion, sodium-, calcium-, and potassium-conductance and action potential (AP) firing. Conditioned medium was obtained from the co-culture of T. cruzi and Vero cells (African green monkey kidney cells) and ultra-filtered for concentrating immunogenic high molecular weight parasite proteins. Chromaffin cells were assessed with the parasite and Vero cells control medium. Parasite-secreted proteins induce catecholamine secretion in a dose-dependent manner. Additionally, T. cruzi conditioned medium induced depression of both calcium conductance and calcium and voltage-dependent potassium current. Interestingly, this fact was related to the abolishment of the hyperpolarization phase of the AP produced by the parasite medium. Taken together, these results suggest that T. cruzi proteins may be involved in the genesis of pro-arrhythmic conditions that could influence the appearance of malignant arrhythmias in Chagasic patients.

Effect of antenatal betamethasone administration on rat cerebellar expression of type la metabotropic glutamate receptors (mGluRla) and anxiety-like behavior in the elevated plus maze.

Preclinical studies indicate that endogenous or exogenous glucocorticoids acting during the pre- or postnatal periods produce a significant Purkinje cell dendritic atrophy, especially during late postnatal ages. The present authors hypothesized that the underlying sub- strate that may contribute in part to this morphological change is the under-expression of the metabotropic glutamate la receptor (mGluRl a) because its expression is correlated with Purkinje cell dendritic outgrowth. Therefore, in the current study, they analyzed the impact of antenatal betamethasone on the immunoreactive expression of the mGluR 1 a and on anxiety-like behavior in the elevated plus maze (EPM). Pregnant rats were randomly divided into two experimental groups: control (CONT) and betamethasone-treated (BET). At gestational day 20 (G20), BET rats were subcutaneously injected with a solution of 170 µg.kg(-1) of betamethasone, and CONT animals received a similar volume of saline. At postnatal days 22 (P22) and P52, BET and CONT offspring were evaluated behaviorally in the EPM, and their cerebella were immunohistochemically processed. Contrary to the uthors' expected results, animals that were prenatally treated with a single course of betamethasone did not exhibit under-expression of mGluRl a or behavioral changes consistent with anxiety-like behaviors.

Changes in spinal alignment. / Alteraciones de la alineación vertebral.

Spinal misalignments are a common reason for consultation at primary care centers and specialized departments. Misalignment has diverse causes and is influenced by multiple factors: in adolescence, the most frequent misalignment is scoliosis, which is idiopathic in 80% of cases and normally asymptomatic. In adults, the most common cause is degenerative. It is important to know the natural history and to detect factors that might predict progression. The correct diagnosis of spinal deformities requires specific imaging studies. The degree of deformity determines the type of treatment. The aim is to prevent progression of the deformity and to recover the flexibility and balance of the body.

Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.

BACKGROUND: South America's substance use profile, poverty, income inequality, and cocaine-supplier role make it a unique place for substance use research. This study investigated the burden of disease attributable to amphetamine use disorder, cannabis use disorder (CAD), cocaine use disorder, and opioid use disorder (OUD) in South America from 1990 to 2019, on the basis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: GBD 2019 estimated the incidence, prevalence, mortality, years of life lost (YLL), years of life lived with disability (YLD), and disability-adjusted life-years (DALYs) due to substance use disorders in each of the 12 South American countries (Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Guyana, Paraguay, Peru, Suriname, Uruguay, and Venezuela). Data were modelled using standardised tools (ie, the Cause of Death Ensemble model, spatio-temporal Gaussian process regression, and disease modelling meta-regression) to generate estimates of each quantity of interest by sex, location, and year. The analysis included comparisons by sex and country, and against regional and global estimates. FINDINGS: In 2019, the highest amphetamine use disorder burden per 100 000 population in South America was in Peru (66 DALYs). CAD DALY rates per 100 000 in South America were stable between 1990 and 2019, except in Chile and Colombia, which had the highest rates in 2019 (19 DALYs for Chile and 18 DALYs for Colombia). OUD DALYs per 100 000 increased during the period in Brazil and Peru, which in 2019 had the highest rates in South America (82 DALYs for Brazil and 70 DALYs for Peru). In 2019, Brazil had the highest cocaine use disorder DALYs per 100 000 (45 DALYs), nearly double its rate in 1990. DALY rates were higher in males than females for each substance use disorder, except in Paraguay. The overall burden of substance use disorders was higher in males than in females, mainly because of cocaine use disorder and CAD, whereas for amphetamine use disorder, the difference between sexes was minimal, and for OUD there was no difference. For males and females, the highest rate of substance use disorders DALYs per 100 000 was for OUD except in Argentina (in males, 58 DALYs for cocaine use disorder vs 52 DALYs for OUD) and in Paraguay (in females, 77 for amphetamine use disorder vs 50 for OUD). CAD DALY rates were generally the lowest among the substance use disorders for males and females. Amphetamine use disorder YLD rates were reasonably stable throughout the period and were highest in Peru, Paraguay, and Uruguay (>40 YLD per 100 000). For CAD, YLD rates were stable in all countries except Chile and Colombia. Cocaine use disorder YLD rates per 100 000 for the top four countries (Argentina, Uruguay, Chile, and Brazil) increased from 1990 to 2010 (eg, from 19 to 33 in Brazil), but decreased between 2010 and 2019 (eg, from 36 to 31 in Chile). For OUD, YLD rates showed a slight increase in most countries apart from Brazil, which increased from 52 in 1990 to 80 in 2019 and was top among the countries. Amphetamine use disorder YLL rates per 100 000 were highest in Suriname and Peru during the period, although in Suriname it increased from 2·7 in 2010 to 3·2 in 2019, whereas in Peru it decreased from 2·1 to 1·7. The highest YLL rate for cocaine use disorder was in Brazil, which increased from 3·7 in 1990 to 18·1 in 2019. Between 2000 and 2019, Chile and Uruguay showed the highest OUD YLL rates (11·6 for Chile and 10·9 for Uruguay). A high incidence of CAD was found in Chile, Colombia, Guyana, and Suriname. There were high incidences of amphetamine use disorder in Paraguay, cocaine use disorder in Argentina, and OUD in Ecuador. A decrease in annual prevalence for substance use disorders during the period was observed in Venezuela (amphetamine use disorder, CAD, and OUD), Brazil (CAD and amphetamine use disorder), Colombia (amphetamine use disorder and cocaine use disorder), Peru (amphetamine use disorder and cocaine use disorder), Chile and Suriname (amphetamine use disorder), Uruguay (CAD), and Bolivia (OUD). Overall, the cocaine use disorder burden stabilised then decreased. OUD was less prevalent than other substance use disorders but its burden was the highest. INTERPRETATION: The decrease in the burden of cocaine use disorder probably reflects the success of national standardised treatment programmes. Programmes for amphetamine use disorder, CAD, and OUD management should be improved. We did not find an increase in CAD burden in Uruguay, the country with the highest degree of cannabis decriminalisation in the region. Countries in South America should improve monitoring of substance use disorders, including regular surveys to provide more accurate data on which to base policy decisions. FUNDING: The Bill & Melinda Gates Foundation.

Retrospective look at change in brain natriuretic peptide values in ambulatory patients with chronic heart failure.

BACKGROUND: There is significant interest in the role of B-type natriuretic peptide (BNP) guided therapy for outpatient congestive heart failure (CHF) patients. The objective of this study was to see if the percentage change in BNP levels can predict CHF hospitalisations or death. METHODS: We retrospectively reviewed the records of CHF patients who had BNP levels drawn on two clinic visits. Patients were divided into two groups, those with a 70% or greater increase in the BNP values and those in whom the BNP value either decreased or did not increase by 70%. Primary outcome measured was the need for hospitalisation for CHF or death within 6 months of the second clinic visit. RESULTS: One hundred and fourteen (114) paired BNP measurements were included in the analysis. Of these, 26 had > 70% increase in BNP while 88 did not. Hospitalisations for CHF or death at 6 months were significantly higher in the former group than the latter (p = 0.04). On multivariate regression analysis significant change in BNP remained a predictor of adverse outcomes. CONCLUSIONS: In stable outpatients with CHF, > 70% increase in BNP is an independent risk factor for CHF hospitalisations or death at 6 months.

[Persistent hiccup as initial clinical manifestation of SARS-CoV-2 infection]. / Hipo (singulto) persistente como manifestación clínica inicial de infección por SARS-CoV-2.

SARS-CoV-2 infection usually manifests as an acute respiratory syndrome, characterized by fever, cough, sore throat and dyspnea. Nonetheless, since the beginning of the pandemic in December 2019, less frequent initial symptoms were reported, as the sudden appearance of hiccups (singultus). We describe a clinical case of a 62-year-old male with a medical history of arterial hypertension, diabetes and chronic cardiac insufficiency, who complained of persistent hiccups as initial manifestation of COVID-19, followed by respiratory symptoms. After the SARS-CoV-2 infection diagnosis was made, the patient was hospitalized, receiving the corresponding treatment. The singultus partially improved with dopaminergic antagonists and it disappeared on the sixth day of hospitalization. Glycemic correction with regular insulin was required. He presented a favorable outcome, being discharged after 14 days of hospitalization.

La infección por SARS-CoV-2 se presenta generalmente como un síndrome respiratorio agudo, caracterizado por fiebre, tos, odinofagia y disnea. Sin embargo, desde el comienzo de la pandemia, a fines del año 2019, fueron reportados otros síntomas menos frecuentes, como manifestación inicial de la enfermedad, entre ellos la aparición de hipo (singulto). Se describe el caso de un varón de 62 años de edad con antecedentes de hipertensión arterial, diabetes e insuficiencia cardiaca, que sufrió hipo persistente como primer síntoma de COVD-19, seguido de síntomas respiratorios. Luego de efectuado el diagnóstico de infección por SARS-CoV-2, el paciente fue hospitalizado y recibió el tratamiento correspondiente. El singulto mejoró parcialmente con el uso de fármacos anti-dopaminérgicos (metoclopramida) y desapareció al sexto día de internación. Se requirió la corrección de la glucemia con insulina corriente. Evolucionó favorablemente y fue externado luego de 14 días de hospitalización.

Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response.

The psychedelic 5-HT2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and in vivo acute mechanism of psilocin/psilocybin. Competition binding studies with psilocin were performed in brain and cell cultures. The role of 5HT2AR, 5-HT2C receptors (5HT2CR) and 5-HT1A receptors (5HT1AR) on the psychosis-like head-twitch response (HTR) and on body temperature in mice after psilocybin administration were evaluated. Psilocin showed similar affinities for 5HT2AR (Ki: 120-173 nM), 5HT2CR (Ki: 79-311 nM) and 5-HT1AR (Ki: 152-146 nM) in human and mice brain. Psilocybin induced a dose-dependent HTR (maximal effect 17.07 ± 1.31 at 1 mg/kg i.p.) that was completely suppressed by the 5HT2AR antagonist MDL11939 (1 mg/kg). Higher doses of psilocybin (3 mg/kg) induced lower HTR (9.00 ± 0.53). The 5HT2CR antagonist SB242084 (0.1 mg/kg) increased HTR exerted by psilocybin (3 mg/kg). Psilocybin significantly raised core body temperature at low dose (0.125 mg/kg) (Emax=0.67 ± 0.15 °C), whereas a significant decrease was induced by doses over 1 mg/kg (Emax = -1.31 ± 0.16 °C). Pre-treatment with the 5HT1AR antagonist WAY100635 reversed the decrease of body temperature after psilocybin (1 mg/kg), causing hyperthermia (Emax = 0.94 ± 0.26 °C). The present work provides key findings on the 5HT2AR, 5-HT2CR and 5HT1AR involvement in the acute central effects of psilocybin. The results may be relevant for understanding the mechanism of action underlying the therapeutic effects and side effects of this psychedelic drug.

Chaotic solitons in the quadratic-cubic nonlinear Schrödinger equation under nonlinearity management.

We analyze the response of rational and regular (hyperbolic-secant) soliton solutions of an extended nonlinear Schrödinger equation (NLSE) which includes an additional self-defocusing quadratic term, to periodic modulations of the coefficient in front of this term. Using the variational approximation (VA) with rational and hyperbolic trial functions, we transform this NLSE into Hamiltonian dynamical systems which give rise to chaotic solutions. The presence of chaos in the variational solutions is corroborated by calculating their power spectra and the correlation dimension of the Poincaré maps. This chaotic behavior (predicted by the VA) is not observed in the direct numerical solutions of the NLSE when rational initial conditions are used. The solitary-wave solutions generated by these initial conditions gradually decay under the action of the nonlinearity management. On the contrary, the solutions of the NLSE with exponentially localized initial conditions are robust solitary-waves with oscillations consistent with a chaotic or a complex quasiperiodic behavior.

South american geochronology: radiometric time scale for middle to late tertiary mammal-bearing horizons in patagonia.

Radiometric (potassium-argon) age determinations for basalts and tuffs associated with middle to late Tertiary mammal-bearing horizons in Patagonia, southern Argentina, permit refinement of boundaries and hiatuses between beds of Deseadan (early Oligocene) through Friasian (middle to late Miocene) age. At two localities beds of Deseadan age are overlain by basalts, which gave dates of 33.6 and 35.4 million years ago; 34.0 million years ago is tentatively accepted as a terminal date for known Deseadan. At several localities beds of Colhuehuapian age are underlain by basalts, which gave dates ranging from 28.8 to 24.3 million years ago; 25.0 million years is tentatively taken as a basal age for known Colhuehuapian. The paleontological hiatus between known Deseadan and known Colhuehuapian is thus in the order of 9.0 million years. Two tuffs from the Santa Cruz Formation (Santacrucian) gave ages of 21.7 and 18.5 million years. Plagioclase and biotite concentrates of an ignimbrite from the Collón Curá Formation (Friasian) gave ages ranging from 15.4 to 14.0 million years.

Fosfomycin in a single dose versus a 7-day course of amoxicillin-clavulanate for the treatment of asymptomatic bacteriuria during pregnancy.

The purpose of this paper was to compare the efficacy of a single dose of 3 g of fosfomycin to that of a 7-day regimen of amoxicillin-clavulanate in the treatment of asymptomatic bacteriuria during pregnancy. A randomised, prospective, interventional, analytical, longitudinal study was undertaken, in which the efficacy of two antibiotic regimens (one short and the other long) in the treatment of pregnant women with asymptomatic bacteriuria is compared. One hundred and nine patients were randomly assigned to two groups: 56 were treated with amoxicillin-clavulanate and 53 with fosfomycin. The two groups were similar in terms of co-morbidity, treatments received during pregnancy, obstetric, gynaecological and surgical history and laboratory data. The efficacy of the two regimens was similar and the eradication rate was over 80% in both groups (P = 0.720) (relative risk [RR] 1.195, 95% confidence interval [CI]: 0.451-3.165). The number of reinfections was greater in the amoxicillin-clavulanate group (P = 0.045). The secondary effects were lower in the fosfomycin group (P = 0.008). There were no significant differences in the number of persistences (P = 0.39), development of symptomatic urinary infections (P = 0.319) or recurrences (P = 0.96). Treatment with a single dose of fosfomycin is as effective as the standard course of treatment with amoxicillin-clavulanate and may be preferable due to its simpler administration and the smaller number of reinfections.

[Autism and intelligence quotient: stability?] / Autismo y cociente intelectual: estabilidad?

INTRODUCTION: Autism is a heterogeneous disorder. The possibility of determining its characteristics over time will have a great impact on the prognosis and predictions that can be made. In that regard, the intelligence quotient and its possible stability throughout the life cycle can help to better define the phenotype of the disorder and its associated needs. DEVELOPMENT: Longitudinal studies show a certain level of stability in intelligence quotient scores, especially starting from the school years. Before, in the preschool stage, there is greater variability, especially in those children who have a borderline intellectual functioning or moderate intellectual disability. CONCLUSION: More research should continue to be developed to know the cognitive profile of people with autism spectrum disorder and be able to make predictions based on their intellectual functioning.

TITLE: Autismo y cociente intelectual: estabilidad?Introduccion. El autismo es un trastorno heterogeneo. La posibilidad de determinar sus caracteristicas a lo largo del tiempo tendra una gran repercusion en el pronostico y las predicciones que se puedan hacer. En ese sentido, el cociente intelectual y su posible estabilidad a lo largo del ciclo vital pueden ayudar a definir mejor el fenotipo del trastorno y sus necesidades asociadas. Desarrollo. Los estudios longitudinales muestran cierta estabilidad en las puntuaciones del cociente intelectual, sobre todo a partir de los años escolares. Antes, en la etapa preescolar, existe mayor variabilidad, especialmente en aquellos niños que tienen un funcionamiento intelectual limite o discapacidad intelectual moderada. Conclusion. Debe seguirse desarrollando mas investigacion para conocer el perfil cognitivo de las personas con trastorno del espectro autista y poder realizar predicciones a partir de su funcionamiento intelectual.

Neuromodulation of the inferior thalamic peduncle for major depression and obsessive compulsive disorder.

Neuromodulation of the inferior thalamic peduncle is a new surgical treatment for major depression and obsessive-compulsive disorder. The inferior thalamic peduncle is a bundle of fibers connecting the orbito-frontal cortex with the non-specific thalamic system in a small area behind the fornix and anterior to the polar reticular thalamic nucleus. Electrical stimulation elicits characteristic frontal cortical responses (recruiting responses and direct current (DC)-shift) that confirm correct localization of this anatomical structure. A female with depression for 23 years and a male with obsessive-compulsive disorder for 9 years had stereotactic implantation of electrodes in the inferior thalamic peduncle and were evaluated over a long-term period. Initial OFF stimulation period (1 month) showed no consistent changes in the Hamilton Depression Scale (HAM-D), Yale Brown Obsessive Compulsive Scale (YBOCS), or Global Assessment of Functioning scale (GAF). The ON stimulation period (3-5 V, 130-Hz frequency, 450-msec pulse width in a continuous program) showed significant decrease in depression, obsession, and compulsion symptoms. GAF improved significantly in both cases. The neuropsychological tests battery showed no significant changes except from a reduction in the perseverative response of the obsessive-compulsive patient and better performance in manual praxias of the female depressive patient. Moderate increase in weight (5 kg on average) was observed in both cases.

Hipo (singulto) persistente como manifestación clínica inicial de infección por SARS-COV-2 / Persistent hiccup as initial clinical manifestation of SARS-CoV-2 infection

Resumen La infección por SARS-CoV-2 se presenta generalmente como un síndrome respiratorio agudo, caracterizado por fiebre, tos, odinofagia y disnea. Sin embargo, desde el comienzo de la pandemia, a fines del año 2019, fueron reportados otros síntomas menos frecuentes, como manifestación inicial de la en fermedad, entre ellos la aparición de hipo (singulto). Se describe el caso de un varón de 62 años de edad con antecedentes de hipertensión arterial, diabetes e insuficiencia cardiaca, que sufrió hipo persistente como primer síntoma de COVD-19, seguido de síntomas respiratorios. Luego de efectuado el diagnóstico de infección por SARS-CoV-2, el paciente fue hospitalizado y recibió el tratamiento correspondiente. El singulto mejoró parcial mente con el uso de fármacos anti-dopaminérgicos (metoclopramida) y desapareció al sexto día de internación. Se requirió la corrección de la glucemia con insulina corriente. Evolucionó favorablemente y fue externado luego de 14 días de hospitalización.

Abstract SARS-CoV-2 infection usually manifests as an acute respiratory syndrome, characterized by fever, cough, sore throat and dyspnea. Nonetheless, since the beginning of the pandemic in December 2019, less frequent initial symptoms were reported, as the sudden appearance of hiccups (singultus). We describe a clinical case of a 62-year-old male with a medical history of arterial hypertension, diabetes and chronic cardiac insufficiency, who complained of persistent hiccups as initial manifestation of COVID-19, followed by respiratory symptoms. After the SARS-CoV-2 infection diagnosis was made, the patient was hospitalized, receiving the corresponding treat ment. The singultus partially improved with dopaminergic antagonists and it disappeared on the sixth day of hospitalization. Glycemic correction with regular insulin was required. He presented a favorable outcome, being discharged after 14 days of hospitalization.

Downstaging of bilobar hepatocellular carcinoma after radioembolization with 90Y microspheres as a bridge to liver transplantation. / Downstaging de carcinoma hepatocelular bilobar tras radioembolización con microesferas de 90Y como puente al trasplante hepático.

Hepatic radioembolization with 90Y is an increasingly widely used locoregional therapy in the treatment of hepatocellular carcinoma. Its potential benefit has recently been described as a downstaging treatment, achieving a decreased tumour burden and allowing patients to be rescued for more radical treatments, such as liver transplantation. The case is presented of a patient diagnosed with multifocal bilobar hepatocellular carcinoma, Barcelona Clinic Liver Cancer (BCLC) intermediate stage, in whom treatment with 90Y achieved a satisfactory radiological response with a very significant reduction of tumour burden, allowing rescue with liver transplantation.

[Anticholinesterases in the treatment of Alzheimer's disease]. / Anticolinesterásicos en el tratamiento de la enfermedad de Alzheimer.

INTRODUCTION: Among the numerous pathophysiological theories that attempt to explain the development of Alzheimer's disease (AD) there are two facts that stand out above the rest: on the one hand, the formation of neurofibrillary tangles inside cells and, on the other, the extra-cellular deposition of beta-amyloid protein. These two mechanisms lead to neurodegeneration and the death of cells by means of a process called 'apoptosis' or 'programmed cell death'. In the early stages of this neurodegenerative process it is more pronounced in cholinergic-type brain centres. This led to the formulation of the so-called cholinergic theory of Alzheimer, which provides the rationale behind the use of the drugs that are currently available to treat this disease, namely, acetylcholine esterase (AChE) inhibitors (rivastigmine, donepezil and galanthamine). DEVELOPMENT AND CONCLUSIONS: We review the possible pharmacological approaches that could help to prevent or delay cell death, and which act on the mechanisms involved in the production of neurofibrillary tangles or the deposition of beta-amyloid protein. We also review the main characteristics of cholinergic neurotransmission, which will help us to understand the therapeutic approaches that have been applied in an attempt to enhance deficient cholinergic neurotransmission. One of the most notable of these is the amount of attention recently being paid to the enzyme AChE, which increases the bioavailability of the neurotransmitter in the cholinergic synapses by preventing the hydrolysis of acetylcholine; these are the only drugs currently available for the symptomatic treatment of this disease.