Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Reconstructing baselines: use of habitat suitability modelling to predict pre-fishing condition of a Vulnerable Marine Ecosystem

As industrialized fishing activities have moved into deeper water, the recognition of Vulnerable Marine Ecosystems (VMEs) has become important for the protection of the deep-sea. Our limited knowledge on the past and present distribution of VMEs hinders our ability to manage bottom fisheries effectively. This study investigated whether accounting for bottom fishing intensity (derived from Vessel Monitoring System records) as a predictor in habitat suitability models can (1) improve predictions of, and (2) provide estimates for a pre-fishing baseline for the distribution and biomass of a VME indicator taxon. Random Forest models were applied to presence/absence and biomass of Geodia sponges and environmental variables with and without bottom fishing intensity. The models including fishing were further used to predict distribution and biomass of Geodia to a pre-fishing scenario. Inclusion of fishing pressure as a predictive term significantly improved model performance for both sponge presence and biomass. This study has demonstrated a way to produce a more accurate picture of the current distribution of VMEs in the study area. The pre-fishing scenario predictions also identified areas of suitable Geodia habitat that are currently impacted by fishing, suggesting that sponge habitat and biomass have been impacted by bottom trawling activities.1054-3139Versión del editor2,27

Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology DepartmentUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology and Pathology DepartmentsUNIFESP, EPM, Dermatology DepartmentUNIFESP, EPM, Dermatology and Pathology DepartmentsSciEL

Psychiatry and neurodevelopmental disorders: experts by experience, clinical care and research

People with neurodevelopmental disorders often present with challenging behaviours and psychiatric illnesses. Diagnosis and treatment require patients, families and healthcare professionals to work closely together in partnership, acknowledging their respective areas of expertise. Good treatment outcomes should also be underpinned by robust research evidence. Key research priorities are highlighted

Review of the Central and South Atlantic Shelf and Deep-Sea Benthos: Science, Policy, and Management

The Central and South Atlantic represents a vast ocean area and is home to a diverse range of ecosystems and species. Nevertheless, and similar to the rest of the global south, the area is comparatively understudied yet exposed to increasing levels of multisectoral pressures. To counteract this, the level of scientific exploration in the Central and South Atlantic has increased in recent years and will likely continue to do so within the context of the United Nations (UN) Decade of Ocean Science for Sustainable Development. Here, we compile the literature to investigate the distribution of previous scientific exploration of offshore (30 m+) ecosystems in the Central and South Atlantic, both within and beyond national jurisdiction, allowing us to synthesise overall patterns of biodiversity. Furthermore, through the lens of sustainable management, we have reviewed the existing anthropogenic activities and associated management measures relevant to the region. Through this exercise, we have identified key knowledge gaps and undersampled regions that represent priority areas for future research and commented on how these may be best incorporated into, or enhanced through, future management measures such as those in discussion at the UN Biodiversity Beyond National Jurisdiction negotiations. This review represents a comprehensive summary for scientists and managers alike looking to understand the key topographical, biological, and legislative features of the Central and South Atlantic

A Core Outcome Set for Stillbirth Care: An International Consensus Study

Objective: To develop a core outcome set for stillbirth care. Design: Consensus development study. Setting: International. Population: 542 participants from 29 countries, including 381 parents or family members who have experienced stillbirth, 192 care professionals and researchers (31 of which identified as both parent and professional). 95.6% of parents and 86.5% of professional stakeholders were from in high‐income countries. Methods: Modified Delphi method and consensus meetings. Results: Stakeholders agreed upon 8 core outcomes to measure in all stillbirth care studies; an additional 11 outcomes for specific interventions or care were also decided. Core outcomes for all stillbirth care studies were life‐threatening complications and maternal death, parents' experience of respectful and supportive care, grief, mental health and emotional wellbeing, isolation, stigma, impact on work, impact on relationship with immediate family. Outcomes for studies assessing interventions to understand the cause of stillbirth (investigations): cause of death identified and parents' understanding of the cause of death. Outcomes in studies assessing subsequent pregnancy after stillbirth: antenatal complications for mother, antenatal complications for baby, survival of baby, neonatal outcomes and attachment to baby. Outcomes for when a stillbirth occurs in a multiple pregnancy: survival of other baby/ies, preterm birth, pregnancy complications for baby/ies and neonatal outcomes. Conclusion: This core outcome set for stillbirth care can be used in future trials and systematic reviews to minimise outcome‐reporting bias, allow comparability of interventions in meta‐analyses and ultimately reduce research wastage

NT-proBNP or Self-Reported Functional Capacity in Estimating Risk of Cardiovascular Events After Noncardiac Surgery

ImportanceNearly 16 million surgical procedures are conducted in North America yearly, and postoperative cardiovascular events are frequent. Guidelines suggest functional capacity or B-type natriuretic peptides (BNP) to guide perioperative management. Data comparing the performance of these approaches are scarce.ObjectiveTo compare the addition of either N-terminal pro-BNP (NT-proBNP) or self-reported functional capacity to clinical scores to estimate the risk of major adverse cardiac events (MACE).Design, Setting, and ParticipantsThis cohort study included patients undergoing inpatient, elective, noncardiac surgery at 25 tertiary care hospitals in Europe between June 2017 and April 2020. Analysis was conducted in January 2023. Eligible patients were either aged 45 years or older with a Revised Cardiac Risk Index (RCRI) of 2 or higher or a National Surgical Quality Improvement Program, Risk Calculator for Myocardial Infarction and Cardiac (NSQIP MICA) above 1%, or they were aged 65 years or older and underwent intermediate or high-risk procedures.ExposuresPreoperative NT-proBNP and the following self-reported measures of functional capacity were the exposures: (1) questionnaire-estimated metabolic equivalents (METs), (2) ability to climb 1 floor, and (3) level of regular physical activity.Main Outcome and MeasuresMACE was defined as a composite end point of in-hospital cardiovascular mortality, cardiac arrest, myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care.ResultsA total of 3731 eligible patients undergoing noncardiac surgery were analyzed; 3597 patients had complete data (1258 women [35.0%]; 1463 (40.7%) aged 75 years or older; 86 [2.4%] experienced a MACE). Discrimination of NT-proBNP or functional capacity measures added to clinical scores did not significantly differ (Area under the receiver operating curve: RCRI, age, and 4MET, 0.704; 95% CI, 0.646-0.763; RCRI, age, and 4MET plus floor climbing, 0.702; 95% CI, 0.645-0.760; RCRI, age, and 4MET plus physical activity, 0.724; 95% CI, 0.672-0.775; RCRI, age, and 4MET plus NT-proBNP, 0.736; 95% CI, 0.682-0.790). Benefit analysis favored NT-proBNP at a threshold of 5% or below, ie, if true positives were valued 20 times or more compared with false positives. The findings were similar for NSQIP MICA as baseline clinical scores.Conclusions and relevanceIn this cohort study of nearly 3600 patients with elevated cardiovascular risk undergoing noncardiac surgery, there was no conclusive evidence of a difference between a NT-proBNP–based and a self-reported functional capacity–based estimate of MACE risk.Trial RegistrationClinicalTrials.gov Identifier: NCT0301693

TOI-663: A newly discovered multi-planet system with three transiting mini-Neptunes orbiting an early M star

We present the detection of three exoplanets orbiting the early M dwarf TOI-663 (TIC 54962195; V = 13.7 mag, J = 10.4 mag, R$_{★}$ = 0.512 ± 0.015 R$_{⊙}$, M$_{★}$ = 0.514 ± 0.012 M$_{⊙}$, d = 64 pc). TOI-663 b, c, and d, with respective radii of 2.27 ± 0.10 R$_{⊕}$, 2.26 ± 0.10 R$_{⊕}$, and 1.92 ± 0.13 R$_{⊕}$ and masses of 4.45 ± 0.65 M$_{⊕}$, 3.65 ± 0.97 M$_{⊕}$, and <5.2 M$_{⊕}$ at 99%, are located just above the radius valley that separates rocky and volatile-rich exoplanets. The planet candidates are identified in two TESS sectors and are validated with ground-based photometric follow-up, precise radial-velocity measurements, and high-resolution imaging. We used the software package juliet to jointly model the photometric and radial-velocity datasets, with Gaussian processes applied to correct for systematics. The three planets discovered in the TOI-663 system are low-mass mini-Neptunes with radii significantly larger than those of rocky analogs, implying that volatiles, such as water, must predominate. In addition to this internal structure analysis, we also performed a dynamical analysis that confirmed the stability of the system. The three exoplanets in the TOI-663 system, similarly to other sub-Neptunes orbiting M dwarfs, have been found to have lower densities than planets of similar sizes orbiting stars of different spectral types

Which patient will feel down, which will be happy? The need to study the genetic disposition of emotional states

Purpose In quality-of-life (QL) research, the genetic susceptibility of negative and positive emotions is frequently ignored, taken for granted, or treated as noise. The objectives are to describe: (1) the major findings of studies addressing the heritable and environmental causes of variation in negative and positive emotional states and (2) the major biological pathways of and genetic variants involved in these emotional states