Disruption of neuronal chloride ion (Cl−) homeostasis has been linked to several pathological conditions, including substance use disorder, yet targeted pharmacotherapies are lacking. In this study, ...we explored the potential of serotonin 2A receptor (5‐HT2AR) agonism to reduce alcohol consumption in male wild‐type C57Bl/6J mice and to ameliorate alcohol‐induced inhibitory plasticity in the midbrain. We found that administration of the putative 5‐HT2AR agonist TCB‐2 attenuated alcohol consumption and preference but did not alter water or saccharin consumption. We hypothesized that the selective behavioural effects of TCB‐2 on alcohol drinking were due, at least in part, to effects of the agonist on ventral tegmental area (VTA) neurocircuitry. Alcohol consumption impairs Cl− transport in VTA GABA neurons, which acts as a molecular adaptation leading to increased alcohol self‐administration. Using ex vivo electrophysiological recordings, we found that exposure to either intermittent volitional alcohol drinking or an acute alcohol injection diminished homeostatic Cl− transport in VTA GABA neurons. Critically, in vivo TCB‐2 administration normalized Cl− transport in the VTA after alcohol exposure. Thus, we show a potent effect of alcohol consumption on VTA inhibitory circuitry, in the form of dysregulated Cl− homeostasis that is reversible with agonism of 5‐HT2ARs. Our results provide insight into the potential therapeutic action of 5‐HT2AR agonists for alcohol abuse.
Using volitional or experimenter‐administered alcohol (ethanol, EtOH) exposure in mice, we determined the consequences of the psychedelic‐like compound TCB‐2 on EtOH‐induced midbrain plasticity and behaviour. Electrophysiological recordings of ventral tegmental area (VTA) GABA neurons revealed chloride ion dysregulation following EtOH exposure that could be reversed with TCB‐2 intervention. In parallel, TCB‐2 reduced ongoing EtOH consumption suggesting that restoration of VTA chloride homeostasis may contribute to beneficial effects seen with other psychedelic drugs when given to humans with alcohol use disorder.
Simulation-based training often fails to meet the needs of low- and middle-income countries with limited access to high-cost models. We built on an existing surgical simulation curriculum for medical ...students in Rwanda and assessed students’ experience.
Based on a contextual simulation-based education curriculum that was piloted in 2022, our team designed and delivered an intensive week-long surgical simulation course for medical students. We increased interactive clinical scenarios using high-fidelity mannequins, improved and added benchtop models for training, and incorporated a new postcourse assessment of students’ experiences using a survey on the first Kirkpatrick level to determine sessions with the highest utility. Modules included informed consent, preoperative patient preparation, trauma simulations, and procedural skills. The final day focused on integrating and applying skills learned throughout the week in an interactive circuit.
Thirty-six students participated in the 5-d simulation course and 24 completed an end of course survey. When asked about their exposure to simulation prior to the course, 20/24 (83%) students reported “a lot” and 4/24 (17%) reported “a little”, 24/24 (100%) strongly agreed that simulation is a valuable educational tool and 23/24 (96%) felt that the week enhanced their knowledge and skills to “a great extent”. The modules with the highest self-rated level of engagement were the interactive trauma simulations, knot-tying and suturing practice and competition, and a model-based session on cutaneous lesions. The lowest ranked session was the interactive circuit on integrated skills.
Implementing a locally-informed and locally-sourced surgical simulation curriculum is feasible and effectively engages medical students in low-income settings.
The Glasgow Coma Scale (GCS) is intended to be an objective, reliable measure of a patient’s mental status. It is included as a metric for trauma registries, having implications for performance ...metrics and research. Our study compared the GCS recorded in the trauma registry (GCS-1) with that recorded in the neurosurgery consultation (GCS-2).
This retrospective review compared GCS-1 with GCS-2. The Trauma Injury Severity Score (TRISS) method was used to calculate probability of survival (POS) for patients using both GCS-1 and GCS-2.
GCS-1 score significantly differed from GCS-2 score (6.69 vs. 7.84, ± 2.553; P < 0.001). There were 172 patients (37.55%) with a GCS-1 score of 3 and 87 (19.00%) with a GCS-2 score of 3 (χ2P < 0.001). The POS calculated using TRISS methodology with GCS-1 (POS-1) was 74.7% ± 26.6% compared with GCS-2 (POS-2), which was 79.3% ± 24.4%. There was a statistically significant difference in the means of POS-2 and POS-2 (P < 0.001). The actual observed survival for the cohort was 71.0% (325/458).
The immediate GCS score recorded on patient arrival after trauma differs significantly from the GCS score recorded at later times. This finding significantly altered the probability of survival as calculated by the TRISS methodology. This situation could have profound effects on risk-adjusted benchmarking, assessments of quality of care, and injury severity stratification for research. More studies into the optimal timing of GCS score recording or changes in GCS score and their impact on survival are warranted.
To assess the safety and feasibility of low-dose, novel, allogenic mesenchymal precursor cell (MPC) therapy as an adjunct to left ventricular (LV) recruitment for patients with hypoplastic left heart ...syndrome (HLHS) and borderline left ventricles. MPC injections into the hypoplastic left ventricle may stimulate neovascularization and beneficial LV remodeling and may improve the likelihood of achieving biventricular (BiV) or 1.5 ventricle (1.5V) circulation.
Children <5 years with prior single ventricle palliation undergoing LV recruitment surgery at a single center were randomized to MPC injections into the LV endocardium/papillary muscles (MPCs) or standard-of-care (controls) and followed for 24 months. The primary endpoint was safety, including (serious) adverse events (S/AEs), and panel reactive antibodies (PRAs). Secondary endpoints included BiV/1.5V conversion and LV size and function.
Nineteen subjects were enrolled, including 9 MPC recipients and 10 controls. Fourteen patients (74%) had >1 AE, and 2 patients had SAEs, both deemed unrelated to the trial product. AE severity and frequency were similar in the 2 groups. Baseline PRA levels were high, with no difference between the groups at 12 months. The overall probability of BiV/1.5V conversion was 0.16 (95% confidence interval CI, 0.05 to 0.41) at 12 months and 0.52 (95% CI, 0.31 to 0.77) at 24 months. For patients with imaging data at both time points, increases in LV volumes from baseline to 12 months were larger in the MPC group by 3-dimensional echocardiography and cardiac magnetic resonance imaging.
MPC injections were considered safe and feasible in HLHS patients. More than 50% of subjects underwent BiV/1.5V conversion within 2 years. Larger trials are needed to investigate the therapeutic potential of MPCs in this population.
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This study evaluated how surgical and anesthesiology departments adapted their resources in response to the coronavirus disease 2019 (COVID-19) pandemic.
This scoping review used the Preferred ...Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews protocol, with Covidence as a screening tool. An initial search of PubMed, Embase, Web of Science, Global Index Medicus, and Cochrane Systematic Reviews returned 6,131 results in October 2021. After exclusion of duplicates and abstract screening, 415 articles were included. After full-text screening, 108 articles remained.
Most commonly, studies were retrospective in nature (47.22 percent), with data from a single institution (60.19 percent). Nearly all studies occurred in high-income countries (HICs), 78.70 percent, with no articles from low-income countries. The reported responses to the COVID-19 pandemic involving surgical departments were grouped into seven categories, with multiple responses reported in some articles for a total of 192 responses. The most frequently reported responses were changes to surgical department staffing (29.17 percent) and task-shifting or task-sharing of personnel (25.52 percent).
Our review reflects the mechanisms by which hospital surgical systems responded to the initial stress of the COVID-19 pandemic and reinforced the many changes to hospital policy that occurred in the pandemic. Healthcare systems with robust surgical systems were better able to cope with the initial stress of the COVID-19 pandemic. The well-resourced health systems of HICs reported rapid and dynamic changes by providers to assist in and ultimately improve the care of patients during the pandemic. Surgical system strengthening will allow health systems to be more resilient and prepared for the next disaster.
Purpose: The purpose of the article is to describe a novel case of idiopathic central nervous system inflammatory disease with bilateral human leukocyte antigen (HLA)-B27-positive anterior uveitis.
...Methods/Results: A 15-year-old African American boy with bilateral HLA-B27-positive anterior uveitis controlled with topical and oral steroids for 8 months acutely developed headaches, left eyelid ptosis, and binocular diplopia. Imaging showed lesions in the right midbrain, superior colliculus, cerebellar peduncles, and cerebellar vermis and leptomeningeal enhancement along the vermian foliae. Cerebral spinal fluid tests showed mild lymphohistiocytic pleocytosis with negative cytology; inflammatory and infectious workup were negative. He received intravenous methylprednisolone without initial symptomatic improvement; repeat magnetic resonance imaging (MRI) showed reduced lesion burden. Oral steroids were continued; his symptoms resolved in 1 month. Repeat MRI 2 months after presentation showed almost complete lesion resolution.
Conclusions: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was diagnosed. HLA-B27 positivity may represent a novel association with CLIPPERS.
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