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).

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.

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.

[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.

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.

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.

[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.

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

La radioembolización hepática con 90Y es una terapia locorregional cada vez más ampliamente empleada en el tratamiento del carcinoma hepatocelular. Recientemente, se ha descrito su potencial beneficio como tratamiento de downstaging, logrando una disminución de la carga tumoral que permite rescatar a los pacientes para tratamientos más radicales como el trasplante hepático. Presentamos el caso de un paciente con el diagnóstico de carcinoma hepatocelular estadio intermedio de la Barcelona Clinic Liver Cancer (BCLC), multicéntrico y bilobar, en quien el tratamiento de radioembolización con 90Y consiguió una adecuada respuesta radiológica, reduciéndose de forma muy significativa la carga tumoral, permitiendo su rescate con trasplante hepático (AU)

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 (AU)

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.

Alteraciones de la alineación vertebral / Changes in spinal alignment

Las desalineaciones de la columna vertebral constituyen un motivo de consulta muy frecuente en atención primaria y servicios especializados. Las etiologías son diversas e influyen múltiples factores: en la adolescencia, la desalineación más frecuente es la escoliosis, de causa idiopática (80%) y normalmente asintomática. En la edad adulta, la causa más frecuente es la degenerativa. Es importante conocer la historia natural y detectar posibles factores predictivos de progresión. El correcto diagnóstico de las deformidades vertebrales requiere de estudios radiológicos concretos. El grado de deformidad determina el tipo de tratamiento. El objetivo es prevenir la progresión de la deformidad, recuperar la flexibilidad y el balance del cuerpo (AU)

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 (AU)

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.

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.