Agreement for Recovery: First Spanish Consensus on the Concept of Alcohol Addiction Recovery.

INTRODUCTION: Current literature does not dispose from a widely accepted definition of recovery in alcohol use disorder (AUD), and most proposals originate from anglophone countries. This study introduces a pioneering consensus in Spain on the definition of recovery in AUD. METHOD: The Delphi method was used. The expert panel, comprising 54 multidisciplinary professionals from the Community of Madrid. RESULTS: A high level of consensus (≥80% agreement) was reached for 45% of the items and majority (≥60%) for 84%. Recovery is understood as a dynamic, personalized, and voluntary process, potentially enduring throughout one's lifespan. It entails a transformative lifestyle shift aimed at achieving a significant improvement in overall quality of life, encompassing physical and mental health, interpersonal relationships, and environmental factors. The journey of recovery is marked by heightened psychological well-being, is characterized by empowerment, personal growth, existential purpose, and positive identity reconstruction. Recovery is supported by substance use management, requires proactive individual agency and involves both personal and societal responsibilities. CONCLUSIONS: This study represents a milestone as it is the first consensus in the Community of Madrid on the meaning of recovery in AUD. The proposed definition of recovery could be a potential reference for similar regions within Spain or even for other countries with cultural similarities. The elucidation of a clear framework of recovery provides a solid basis for future research efforts and clinical interventions in the Spanish AUD landscape.

Methanogenic symbionts of anaerobic ciliates are host- and habitat-specific.

The association between anaerobic ciliates and methanogenic archaea has been recognized for over a century. Nevertheless, knowledge of these associations is limited to a few ciliate species, and so the identification of patterns of host-symbiont specificity has been largely speculative. In this study, we integrated microscopy and genetic identification to survey the methanogenic symbionts of 32 free-living anaerobic ciliate species, mainly from the order Metopida. Based on Sanger and Illumina sequencing of the 16S rRNA gene, our results show that a single methanogenic symbiont population, belonging to Methanobacterium, Methanoregula, or Methanocorpusculum, is dominant in each host strain. Moreover, the host's taxonomy (genus and above) and environment (i.e., endobiotic, marine/brackish, or freshwater) are linked with the methanogen identity at the genus level, demonstrating a strong specificity and fidelity in the association. We also established cultures containing artificially co-occurring anaerobic ciliate species harboring different methanogenic symbionts. This revealed that the host-methanogen relationship is stable over short timescales in cultures without evidence of methanogenic symbiont exchanges, though, our intraspecific survey indicated that metopids also tend to replace their methanogens over longer evolutionary timescales. Therefore, anaerobic ciliates have adapted a mixed transmission mode to maintain and replace their methanogenic symbionts, allowing them to thrive in oxygen-depleted environments.

Stabilizing Pure Water-Fed Anion Exchange Membrane Water Electrolyzers through Membrane-Electrode Interface Engineering.

Nickel-iron (oxy)hydroxide (NiFeOxHy) stands as a cutting-edge nonprecious electrocatalyst for the oxygen evolution reaction (OER). However, the intrinsic thermodynamic instability of nickel and iron as anode materials in pure water-fed electrolyzers poses a significant durability challenge. In this study, an anion exchange ionomer coating was applied to NiFeOxHy to modify the local pH between a membrane and an electrode. This effectively extended the diffusion length of hydroxide anions toward the electrode, establishing an alkaline local pH environment. Stability tests with the ionomer coating showed reduced Ni dissolution. Moreover, locally resolved current density measurements were used to demonstrate a notably lower degradation rate during stability testing, revealing a 6-fold increase in stability with the ionomer on NiFeOxHy. In situ Raman spectroscopy in a neutral pH electrolyte confirmed inhibited Ni oxidation with the ionomer, mitigating Ni dissolution and enhancing stability of state-of-the-art NiFeOxHy catalysts in pure water-fed water electrolyzers.

Superlubric Sliding of Graphene Auto-Kirigami with Interfaces Containing Self-Assembled Stripe-Pattern Adsorbates.

Van der Waals heterostructures formed by stacked 2D materials show exceptional electronic, mechanical, and optical properties. Superlubricity, a condition where atomically flat, incommensurate planes of atoms result in ultra-low friction, is a prime example enabling, for example, self-assembly of optically visible graphene nanostructures in air via a sliding auto-kirigami process. Here, it is demonstrated that a subtle but ubiquitous adsorbate stripe structure found on graphene and graphitic surfaces in ambient conditions remains stable within the interface between twisted graphene layers as they slide over each other. Despite this contamination, the interface retains an exceptional superlubricious state with an estimated upper bound frictional shear strength of 10 kPa, indicating that direct atomic incommensurate contact is not required to achieve ambient superlubricity for 2D materials. The results suggest that any phenomena depending on 2D heterostructure interfaces such as exotic electronic behavior may need to consider the presence of stripe adsorbate structures that remain intercalated.

Current Perspectives on the Clinical Research and Medicalization of Psychedelic Drugs for Addiction Treatments: Safety, Efficacy, Limitations and Challenges.

Mental health disorders and substance use disorders (SUDs) in particular, contribute greatly to the global burden of disease. Psychedelics, including entactogens and dissociative substances, are currently being explored for the treatment of SUDs, yet with less empirical clinical evidence than for other mental health disorders, such as depression or post-traumatic stress disorder (PTSD). In this narrative review, we discuss the current clinical research evidence, therapeutic potential and safety of psilocybin, lysergic acid diethylamide (LSD), ketamine, 3,4-methylenedioxymethamphetamine (MDMA) and ibogaine, particularly in the context of the SUD treatment. Our aim was to provide a balanced overview of the current research and findings on potential benefits and harms of psychedelics in clinical settings for SUD treatment. We highlight the need for more clinical research in this particular treatment area and point out some limitations and challenges to be addressed in future research.

The moderating role of sex in the relationship between cannabis use treatment admission profile and treatment processes and outcomes: A gender perspective.

BACKGROUND: Gender-specific interventions are crucial in addressing substance use disorders -particularly cannabis use disorder - as they allow for tailored therapeutic approaches and increase the likelihood of successful outcomes. However, differences in therapeutic processes and outcomes between males and females are often not observed, making the prognosis and development of such interventions more difficult. OBJECTIVE: This study aimed to examine the moderating role of sex in the relationship between treatment admission profile characterized by indicators of cannabis use and sociodemographic sources of gender inequality (e.g., employment status) and adherence and outcome at discharge. METHOD: A multicentric retrospective observational study was conducted with a sample of 3,814 outpatients diagnosed with cannabis use disorder. Electronic health records were used for data analysis. RESULTS: The interaction between sex and the number of children, as well as pre-treatment cannabis use, predicted lower treatment adherence, particularly among females. Additionally, the interaction between sex and the number of children predicted outcomes at discharge, with females showing a higher likelihood of dropout compared to males. DISCUSSION AND CONCLUSION: Enhanced comprehensive treatment with intensified contingency management programs should be prioritized for females (especially those with children) who have consumed cannabis in the month before treatment. Adopting a treatment policy framework incorporating sex/gender-sensitive therapist training and evaluative measures is essential for optimizing treatment outcomes for all patients.

Distinctive clinical traits of lupus-related myocarditis: a multicentre retrospective study.

OBJECTIVES: Cardiovascular involvement in systemic lupus erythematosus (SLE) is frequent but little is known about possible distinctive traits of SLE-related myocarditis (myoSLE) in comparison to patients with SLE (onlySLE) or myocarditis alone (onlyMyo). METHODS: A retrospective analysis was performed comparing patients with myoSLE (n = 25) from three centres with consecutive patients with onlySLE (n = 279) and onlyMyo (n = 88). SLE patients were dichotomised by disease duration ≤1 vs >1 year into recent onlySLE/early myoSLE vs longstanding onlySLE/late myoSLE. Further stratification into disease duration of 1-5, 5-10 and >10 years was also performed. SLE disease activity index 2000 (SLEDAI-2K) was used to estimate disease activity. Myocarditis was diagnosed through biopsy or magnetic resonance. RESULTS: Women were significantly more frequent among myoSLE than among onlyMyo (72% vs 43%; p= 0.013). Compared with onlyMyo, myoSLE patients had a higher frequency of conduction abnormalities (22% vs 5%; p= 0.046) and presented with numerically higher frequencies of left ventricular function compromise (48% vs 30%), along with higher pro-brain natriuretic peptide levels. Inflammation markers were higher in myoSLE compared with onlyMyo and to patients with onlySLE with >10 years of disease duration. SLEDAI-2K was significantly higher in late myoSLE than in longstanding onlySLE. Antiphospholipid syndrome was more frequent in myoSLE than in onlySLE. Multivariate analysis showed an association among myoSLE, anti-beta-2-glycoprotein I antibodies (aB2GPI, p= 0.014) and a higher number of involved British Isles Lupus Assessment Group domains in patient history (p= 0.003). CONCLUSION: myoSLE has unique clinical traits compared with other forms of myocarditis and is associated with aB2GPI and a more severe SLE course.

Multidisciplinary medication review during older patient hospitalization according to STOPP/START criteria reduces potentially inappropriate prescriptions: MoPIM cohort study.

PURPOSE: Multimorbidity and polypharmacy in older adults converts the detection and adequacy of potentially inappropriate drug prescriptions (PIDP) in a healthcare priority. The objectives of this study are to describe the clinical decisions taken after the identification of PIDP by clinical pharmacists, using STOPP/START criteria, and to evaluate the degree of accomplishment of these decisions. METHODS: Multicenter, prospective, non-comparative cohort study in patients aged 65 and older, hospitalized because of an exacerbation of their chronic conditions. Each possible PIDP was manually identified by the clinical pharmacist at admission and an initial decision was taken by a multidisciplinary clinical committee. At discharge, criteria were re-applied and final decisions recorded. RESULTS: From all patients (n = 674), 493 (73.1%) presented at least one STOPP criteria at admission, significantly reduced up to 258 (38.3%) at discharge. A similar trend was observed for START criteria (36.7% vs. 15.7%). Regarding the top 10 most prevalent STOPP criteria, the clinical committee initially agreed to withdraw 257 (34.2%) prescriptions and to modify 93 (12.4%) prescriptions. However, the evaluation of final clinical decisions revealed that 503 (67.0%) of those STOPP criteria were ultimately amended. For the top 10 START criteria associated PIDP, the committee decided to initiate 149 (51.7%) prescriptions, while a total of 198 (68.8%) were finally introduced at discharge. CONCLUSIONS: The clinical committee, through a pharmacotherapy review, succeeded in identifying and reducing the degree of prescription inadequacy, for both STOPP and START criteria, in older patients with high degree of multimorbidity and polypharmacy. TRIAL REGISTRATION: NCT02830425.

Diagnostic Performance of Point-of-Care High-Sensitivity Troponin in the Exclusion of Non-ST-Elevation Myocardial Infarction in the Emergency Department.

BACKGROUND: This study evaluates the diagnostic performance of high-sensitivity troponin using point-of-care testing (POCT) devices compared with main laboratory measurements for ruling out non-ST-elevation myocardial infarction (NSTEMI) in emergency department (ED) patients presenting with non-traumatic chest pain. METHODS: This multicenter, observational, prospective, non-interventional study was conducted in two Spanish hospitals from 1 June to 31 December 2023 and included adult patients presenting with non-traumatic chest pain admitted to the ED. High-sensitivity troponin levels were measured using both the Siemens Atellica® VTLi POCT device and main laboratory testing, with data collected on analytical results and measurement times. RESULTS: Of the 201 patients who met the inclusion criteria, a significant correlation was observed between the POCT and laboratory assays. The area under the curve (AUC) of the ROC curve was consistently greater than 0.9, indicating a high diagnostic accuracy for ruling out NSTEMI. In addition, measurement times were significantly reduced using POCT compared to the core laboratory. CONCLUSION: These results suggest that high-sensitivity troponin POCT devices offer comparable diagnostic performance to traditional laboratory methods for the diagnosis of NSTEMI in the emergency department, potentially speeding up clinical decisions and optimizing resource utilization.

Nirsevimab immunization's real-world effectiveness in preventing severe bronchiolitis: A test-negative case-control study.

BACKGROUND: Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. METHODS: In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. RESULTS: Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay. CONCLUSIONS: This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted.

Bit by bit toward the diversity of metopids: Description of the genus Pidimetopus n. gen. (Ciliophora: Armophorea).

While metopids (Armophorea: Metopida) represent the most species-rich group of free-living anaerobic ciliates thriving in hypoxic environments, our understanding of their true diversity remains incomplete. Most metopid species are still characterized only morphologically. Particularly, the so-called IAC clade (named in the past after some of the taxa included, Idiometopus, Atopospira, and Clevelandellida), comprising free-living members as well as the endosymbiotic ones (order Clevelandellida), is in serious need of revision. In our study, we establish a new free-living genus in the IAC clade, Pidimetopus n. gen., with descriptions of two new species, P. nanus n. sp., and P. permonicus n. sp., using up-to-date molecular and morphologic methods. The genus is characterized by small cells (up to 75 µm long), not more than 10 adoral membranelles and eight somatic kineties, and usually, four long caudal cilia that can stiffen. In addition to morphologic and molecular characterizations, we also conducted a statistical morphotype analysis of the polymorphic species P. nanus n. sp. We discuss the relevance of the earlier morphologically described species Metopus minor as a putative collective taxon for several small metopids less than 50 µm long.

Impact of universal immunization program with monoclonal antibody nirsevimab on reducing the burden of serious bronchiolitis that need pediatric intensive care.

RSV bronchiolitis remains the leading cause of hospitalization in children under 1 year of age. It is estimated that 2-6% of cases will be hospitalized on pediatric intensive care units (PICUs). In October 2023, a universal immunization program with the monoclonal antibody nirsevimab was implemented in Catalonia. The aim of the study was to analyze the impact of the nirsevimab immunization on the burden of bronchiolitis admitted to a PICU and resulting changes in epidemiological, clinical, and microbiological characteristics comparing the pre-nirsevimab (pre-N) with the post-nirsevimab (post-N) period. This was a prospective, descriptive, and observational study. Patients with severe bronchiolitis admitted to reference children's hospital PICU, between September 2010 and February 2024 were included. Demographic and clinical data were collected and viral laboratory etiological diagnosis was carried out. 1531 patients were recruited, 1458 in the pre-N seasons and 73 after its introduction (58% males, median age 52 days), of which 67% were immunized with nirsevimab. The total number of PICU bronchiolitis admissions, the ratio, and the RSV etiology were significantly lower in the post-N period (p = 0.03, p < 0.001, and p = 0.039, respectively). Significant higher age at admission (p < 0.001) and lower hospital length of stay (p < 0.001) was observed comparing pre-N vs. post-N period. CONCLUSION: Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis. WHAT IS KNOWN: • Bronchiolitis is the most common viral infection of the lower respiratory tract in infants. • It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world. WHAT IS NEW: • In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain. • Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing.

Control compounds for preclinical drug-induced liver injury assessment: Consensus-driven systematic review by the ProEuroDILI network.

BACKGROUND & AIMS: Idiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by drugs, and herbal or dietary supplements. Early identification of human hepatotoxicity at preclinical stages remains a major challenge, in which the selection of validated in vitro systems and test drugs has a significant impact. In this systematic review, we analyzed the compounds used in hepatotoxicity assays and established a list of DILI-positive and -negative control drugs for validation of in vitro models of DILI, supported by literature and clinical evidence and endorsed by an expert committee from the COST Action ProEuroDILI Network (CA17112). METHODS: Following 2020 PRISMA guidelines, original research articles focusing on DILI which used in vitro human models and performed at least one hepatotoxicity assay with positive and negative control compounds, were included. Bias of the studies was assessed by a modified 'Toxicological Data Reliability Assessment Tool'. RESULTS: A total of 51 studies (out of 2,936) met the inclusion criteria, with 30 categorized as reliable without restrictions. Although there was a broad consensus on positive compounds, the selection of negative compounds lacked clarity. 2D monoculture, short exposure times and cytotoxicity endpoints were the most tested, although there was no consensus on drug concentrations. CONCLUSIONS: Extensive analysis highlighted the lack of agreement on control compounds for in vitro DILI assessment. Following comprehensive in vitro and clinical data analysis together with input from the expert committee, an evidence-based consensus-driven list of 10 positive and negative control drugs for validation of in vitro models of DILI is proposed. IMPACT AND IMPLICATIONS: Prediction of human toxicity early in the drug development process remains a major challenge, necessitating the development of more physiologically relevant liver models and careful selection of drug-induced liver injury (DILI)-positive and -negative control drugs to better predict the risk of DILI associated with new drug candidates. Thus, this systematic study has crucial implications for standardizing the validation of new in vitro models of DILI. By establishing a consensus-driven list of positive and negative control drugs, the study provides a scientifically justified framework for enhancing the consistency of preclinical testing, thereby addressing a significant challenge in early hepatotoxicity identification. Practically, these findings can guide researchers in evaluating safety profiles of new drugs, refining in vitro models, and informing regulatory agencies on potential improvements to regulatory guidelines, ensuring a more systematic and efficient approach to drug safety assessment.

Spatially resolved tissue imaging to analyze the tumor immune microenvironment: beyond cell-type densities.

INTRODUCTION: The tissue immune microenvironment is associated with key aspects of tumor biology. The interaction between the immune system and cancer cells has predictive and prognostic potential across different tumor types. Spatially resolved tissue-based technologies allowed researchers to simultaneously quantify different immune populations in tumor samples. However, bare quantification fails to harness the spatial nature of tissue-based technologies. Tumor-immune interactions are associated with specific spatial patterns that can be measured. In recent years, several computational tools have been developed to increase our understanding of these spatial patterns. TOPICS COVERED: In this review, we cover standard techniques as well as new advances in the field of spatial analysis of the immune microenvironment. We focused on marker quantification, spatial intratumor heterogeneity analysis, cell‒cell spatial interaction studies and neighborhood analyses.

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care.

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

Two new HLA-DQB1*03:02:01 variants with substitutions in intron 2: HLA-DQB1*03:02:01:19 and -DQB1*03:02:01:21.

Two different single nucleotide substitutions in intron 2 give rise to novel HLA-DQB1*03:02:01 alleles.