Animals produce diverse motor actions that enable expression of context-appropriate behaviors. Neuromodulators facilitate behavioral flexibility by altering the output of neural circuits. Discrete populations of serotonergic (5-HT) neurons target circuits in the brainstem and spinal cord, but their roles in motor behavior are unclear. Here, we define the pre- and post-synaptic organization of spinal-projecting serotonergic neurons in mice and identify a role in locomotor control. While forebrain-targeting 5-HT neurons decrease their activity during locomotion, spinal-projecting neurons increase their activity in a context-dependent manner. Optogenetic activation of ventrally projecting 5-HT neurons does not initiate movement, but rather enhances the speed and duration of ongoing locomotion. Serotonergic neurons can influence motor output beyond periods of increased activity, indicating that neuromodulators can act over extended timescales. These findings indicate that the descending serotonergic system potentiates locomotor output and demonstrate a role for serotonergic neurons in modulating the temporal dynamics of motor circuits.
Publications by Year: 2026
2026
BACKGROUND: Rises in the prevalence of multi-drug-resistant organisms threaten patient safety globally. Vancomycin-resistant enterococci (VREs) and carbapenem-resistant Enterobacterales (CRE) are linked with prolonged hospitalisation, treatment failure, and increased mortality. Decolonisation strategies could reduce transmission and improve outcomes, but their efficacy and safety remain uncertain. This study systematically evaluates decolonisation protocols for VRE and CRE through a meta-analysis.
METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review and meta-analysis were performed on studies using PubMed, ScienceDirect, Web of Science, and Scopus. Studies evaluating decolonisation protocols for VRE and CRE were included. Papers were assessed for risk of bias using the Risk of Bias 2 tool and Newcastle-Ottawa Scale. Meta-analyses were performed using RevMan, Cochrane, London, United Kingdom.
RESULTS: Sixteen studies with a total of 872 participants were included for meta-analysis. Faecal microbiota transplantation (FMT) significantly improved clearance of CRE (risk ratio [RR]: 2.01; 95% confidence interval [CI]: 1.27-3.18) and VRE (RR: 2.96, 95% CI: 1.60-5.47) compared with controls, with low to moderate heterogeneity. Selective digestive decontamination (SDD) significantly increased clearance of CRE (RR: 2.47, 95% CI: 1.32-4.63), but not VRE (RR: 1.52, 95% CI: 0.70-3.30). Adverse events were generally mild, but SDD was associated with increased antimicrobial resistance in several studies.
CONCLUSIONS: FMT and SDD are promising interventions for CRE decolonisation, with FMT also showing benefit in VRE. The durability of SDD effects appears limited, with significant risk of promoting resistance. Future studies should standardise endpoints, evaluate combination approaches, and explore bacteriophage therapy. We suggest implementing uniform terminology with 'provisional clearance' as a descriptor for eradication at 1 month post intervention and 'enduring clearance' following continuous eradication for 6 months.
INTRODUCTION: Treatment-refractory obsessive-compulsive disorder (trOCD) is a complex network disorder that may require personalized treatment strategies due to disease heterogeneity. A multi-site, multi-stage, double-blinded, randomized crossover clinical trial is underway, using stereo-electroencephalography (sEEG) to guide selection of multi-nodal targets for deep brain stimulation (DBS) for trOCD.
OBJECTIVES: To describe the clinical trial design, emphasizing personalized surgical targeting strategies that ensure the feasibility and precision of sEEG electrode placement, and enable adequate sampling of relevant targets in trOCD for network evaluation and modulation.
METHODS: Adults with severe trOCD (Yale-Brown Obsessive Compulsive Scale ≥28) who meet eligibility criteria are enrolled in this three-stage clinical trial (NCT05623306). Stage 1 involves sEEG electrode implantation in trOCD implicated regions and inpatient evaluation. Individualized probabilistic tractography-guided target refinement is performed for surgical planning. Multimodal recordings are taken while participants stay in the psychiatric monitoring unit for 12 days. In stage 2, up to four permanent DBS electrodes are implanted followed by stimulation optimization. Stage 3 is the randomized, double-blinded crossover phase.
EXPECTED OUTCOMES: Safety, feasibility and preliminary efficacy will be assessed in this ongoing study. We anticipate that the use of sEEG to guide selection of multi-nodal targets for DBS will be safe, feasible and result in clinically meaningful improvements in symptom severity and functional impairment in trOCD.
DISCUSSION: We present the clinical protocol of sEEG-guided investigation of brain networks involved in trOCD and describe our tractography-guided surgical targeting strategy designed to optimize individualized network engagement and neuromodulation.
BACKGROUND: Spironolactone and oral minoxidil are effective female alopecia monotherapies. Combination therapy is commonly used, though safety and tolerability data are limited.
OBJECTIVE: To assess safety and tolerability by adverse effect incidence.
METHODS: Retrospective cohort study conducted in females aged ≥18 taking combination therapy for hair loss.
RESULTS: A total of 432 patients were included. Average spironolactone and low-dose oral minoxidil doses at time of adverse drug effects were 87.6 ± 51.4 mg and 1.8 ± 1.1 mg, respectively. Adverse effect incidence was 37.7% (n = 163). Hypertrichosis was most common (n = 53, 12.3%) followed by dizziness/lightheadedness/orthostasis (n = 52, 12.0%). Simultaneous initiation was observed to reduce hypertrichosis risk by 64.8% (odds ratio: 0.35; 95% confidence interval 0.13-0.94; P = .037). Concurrent use of ≥1 additional blood pressure-altering medications increased orthostatic effects risk (odds ratio: 3.29; 95% confidence interval: 1.65-6.58; P = .001). Dosage and treatment initiation pattern did not significantly increase risk of blood pressure effects. In 46.0% of cases, the therapeutic regimen was unmodified. When adjustments were made, they largely occurred in the outpatient setting (94.3%).
LIMITATIONS: Retrospective descriptive study lacking a control group.
CONCLUSION: Adverse effects from combination therapy are generally mild and managed outpatient. Concomitant use of ≥1 blood pressure-altering drugs increases risk of hypotension-related symptoms. Simultaneous initiation may reduce risk of hypertrichosis without increasing risk of hypotension-related effects.
OBJECTIVE: Both standard and low-profile endografts have been used for physician-modified endografts (PMEGs) to treat complex aortic aneurysms; however, recent data from a 2025 multi-institutional analysis suggest that low-profile devices are associated with type IIIc endoleak rates as high as 15% at the 20-month follow-up. Early demonstrations of PMEG modifications, including fenestration reinforcement with polytetrafluoroethylene (PTFE) cuffs, have proposed a possible remedy to these elevated endoleak rates. This analysis evaluates a single center's experience with PTFE cuff reinforcement for PMEG fenestrations.
METHODS: All PMEGs performed at our institution between 2016 and 2025 were retrospectively reviewed. Each PMEG included fenestrations that were individually reinforced with a PTFE cuff and an embolization coil, secured with a running locking Ethibond suture. Primary outcomes included target vessel-related (type Ic and IIIc) endoleaks and endoleak-related reintervention. Outcomes were analyzed on both per-patient and per-fenestration bases. Bridging stent type (iCAST vs VBX) was also evaluated as a potential modifier of outcomes, with secondary outcomes including stent patency and target vessel instability. Rates of endoleak at 1 month and beyond were reported using Kaplan-Meier estimates.
RESULTS: Overall, 229 PMEGs (100% low profile; 861 PTFE cuffs) were included in our analysis with a median follow-up of 1.3 years. The median age was 76 years and patients were primarily White (89%) and male (72%). The majority of cases were done electively (82%) for juxtarenal aneurysms (65%). The median aneurysm diameter at time of repair was 62 mm, and 80% included four or more target vessel fenestrations. Through 2 years, 26% (n = 42) of patients underwent an aneurysm- or PMEG-associated reintervention; of these, nearly one-half (n = 21 [15% of all patients]) were endoleak related. The most common indication for endoleak-related reintervention was sac expansion from type II endoleaks (8.9%). Type Ic and IIIc endoleaks occurred in 2.2% and 1.1% of patients, respectively. Bridging stents included 358 iCAST and 489 VBX. Stent distribution differed significantly by vessel, yet no significant differences were observed in 2-year patency (98% vs 99%), stent-related stenosis/occlusion (2.1% vs 2.0%), or reintervention rates (1.0% vs 1.3%) (all P > .05). On a per-fenestration basis, type Ic and IIIc endoleaks occurred in 0.6% and 0.1% of fenestrations, respectively, with no difference based on stent type (iCAST, 0.7% vs VBX, 0.8%; P = .23). Overall, freedom from target vessel instability at 2 years was >98% across all groups and vessels, without any difference in bridging stent type (98.3% vs 98.6%; P = .82).
CONCLUSIONS: PMEG modification with individual fenestration reinforcement using a PTFE cuff and an embolization coil demonstrates effective fenestration sealing with notably low rates of target vessel-related endoleaks. Bridging stent choice does not appear to be a primary determinant of target vessel instability, endoleaks, or reinterventions, potentially underscoring the importance of fenestration modifications over stent platform differences. These findings suggest the value of using this technique for PMEG customization in low-profile devices.
Patients often need to interrupt anticoagulation for invasive procedures or surgery. Periprocedural bleeding can contribute to substantial morbidity and mortality. Procedural bleed risk stratification informs whether anticoagulation needs to be interrupted, for how long, and when to restart anticoagulation after procedure. Guidance on procedure-specific bleeding risk varies and contributes to discordant perioperative anticoagulation management. To address this important knowledge gap, the Perioperative and Critical Care Thrombosis and Hemostasis Subcommittee of the International Society on Thrombosis and Haemostasis undertook a review of contemporary procedural bleeding risk stratification schemas and developed a practical bleeding risk stratification approach for use in anticoagulated adult patients having a planned elective surgery or procedures.
BACKGROUND & AIMS: Disruption of the intestinal barrier facilitates microbial translocation to the liver and contributes to chronic liver disease. We aimed to study the role of the fecal proteome for disease progression in patients with alcohol-associated hepatitis.
METHODS: We used fecal proteomics data from a multicenter cohort of patients with alcohol-associated hepatitis (n=80), alcohol use disorder (n=20), and controls (n=19) (InTeam), and a cathepsin B activity assay in an independent multicenter cohort of patients with alcohol-associated hepatitis (n=80), alcohol use disorder (n=20), and controls (n=18) (AlcHepNet). Mice lacking cathepsin B in myeloid cells and transgenic mice overexpressing occludin in intestinal epithelial cells, were subjected to the chronic-plus-binge ethanol feeding model (NIAAA).
RESULTS: Fecal proteomics and activity analysis revealed that the protease cathepsin B progressively increased with alcohol use disorder and alcohol-associated hepatitis compared to controls, and is associated with higher short-term mortality in patients with alcohol-associated hepatitis. Cathepsin B is predominantly expressed in intestinal macrophages and is upregulated by ethanol. Cathepsin B deficiency in myeloid cells or oral treatment with the gut-restricted cathepsin B inhibitor CA074 stabilized gut barrier by preserving the tight junction protein occludin, lowered serum LPS levels, and attenuated ethanol-induced steatohepatitis. Transgenic overexpression of occludin in intestinal epithelial cells sufficed to reduce steatohepatitis and blunted the effects of CA074 in ethanol-fed mice. Cathepsin B proteolytically cleaves occludin in enzymatic assays, and its inhibition prevented occludin degradation and barrier disruption in intestinal organoids and epithelial monolayers. Molecular modeling and peptide profiling reveal specific cathepsin B-induced cleavage sites in the extracellular region of occludin.
CONCLUSIONS: Intestinal cathepsin B is an essential mediator of gut barrier dysfunction and therapeutic target in alcohol-associated liver disease.
IMPACT AND IMPLICATIONS: Intestinal barrier disruption facilitates the microbial translocation to the liver, contributing to the progression of alcohol-associated hepatitis, however the molecular mechanisms driving barrier dysfunction remain incompletely understood. Our study identified the protease cathepsin B as a key contributor to the progression of alcohol-associated liver disease by degrading the extracellular region of tight junction protein occludin in the intestine, which in turn leads to barrier disruption. This work advances the field by addressing causality, uncovering the molecular target, and proposing cathepsin B as a promising therapeutic target in alcohol-associated hepatitis, a condition for which liver transplantation remains the only effective treatment in a limited subset of patients.
OBJECTIVE: Placenta Accreta Spectrum (PAS) occurs in approximately 0.17% pregnancies in the general obstetric population. We aimed to estimate the prevalence of PAS following myomectomy surgery and evaluate differences in the risks by myomectomy surgical approach.
DATA SOURCES: PubMed, Embase, Scopus, and Web of Science were searched on prespecified dates (inception-March 2025).
STUDY ELIGIBILITY CRITERIA: Studies were eligible if they reported pregnancy outcomes in patients with a documented history of myomectomy in which the surgical approach was specified.
STUDY APPRAISAL AND SYNTHESIS METHODS: This systematic review and meta-analysis was conducted per PRISMA guidelines and registered on PROSPERO (CRD42024513596). Pooled prevalence estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. Planned subgroup analyses were conducted for myomectomy surgical approach and PAS-accompanying morbidities of postpartum hemorrhage, placenta previa, placental abruption, and uterine rupture, and heterogeneity was assessed using I2 statistics.
RESULTS: Seventy-six studies comprising 11065 pregnancies across 24 countries were included. The pooled prevalence of PAS following myomectomy was 1% (95% CI, 1-2%). Prespecified subgroup analyses demonstrated that PAS prevalence was highest after open myomectomy (2%; 95% CI, 1-4%; 111/4474) compared to laparoscopic (1%; 95% CI, 0-3%; 36/1172), robotic (1%; 95% CI, 0-4%; 4/262), and hysteroscopic approaches (<1%; 95% CI, 0-1%; 3/271), although differences between surgical groups were not statistically significant (P = 0.67). Secondary outcomes-including postpartum hemorrhage (2%), placenta previa (1%), placental abruption (1%), and uterine rupture (<1%)-showed similar prevalence patterns across surgical approaches.
CONCLUSIONS: In this meta-analysis of over 11,000 patients, the overall prevalence of PAS following myomectomy was approximately 1-2% and did not significantly differ by surgical approach. Likewise, major obstetric complications, including postpartum hemorrhage, placenta previa, and uterine rupture, showed no significant variations among open, laparoscopic, hysteroscopic, and robotic myomectomies. Therefore, the choice of surgical approach for myomectomy can be individualized based on patient characteristics, myoma features, and surgical expertise.