Periprocedural Management and Multidisciplinary Care Pathways for Patients With Cardiac Implantable Electronic Devices: A Scientific Statement From the American Heart Association.

The rapid technological advancements in cardiac implantable electronic devices such as pacemakers, implantable cardioverter defibrillators, and loop recorders, coupled with a rise in the number of patients with these devices, necessitate an updated clinical framework for periprocedural management. The introduction of leadless pacemakers, subcutaneous and extravascular defibrillators, and novel device communication protocols underscores the imperative for clinical updates. This scientific statement provides an inclusive framework for the periprocedural management of patients with these devices, encompassing the planning phase, procedure, and subsequent care coordinated with the primary device managing clinic. Expert contributions from anesthesiologists, cardiac electrophysiologists, and cardiac nurses are consolidated to appraise current evidence, offer patient and health system management strategies, and highlight key areas for future research. The statement, pertinent to a wide range of health care professionals, underscores the importance of quality care pathways for patient safety, optimal device function, and minimization of hemodynamic disturbances or arrhythmias during procedures. Our primary objective is to deliver quality care to the expanding patient cohort with cardiac implanted electronic devices, offering direction in the era of evolving technologies and laying a foundation for sustained education and practice enhancement.

Rehabilitation Surgery for Peripheral Facial Nerve Injury after Facial Trauma.

Introduction Facial trauma can cause damage to the facial nerve, which can have negative effects on function, aesthetics, and quality of life if left untreated. Objective To evaluate the effectiveness of peripheral facial nerve direct end-to-end anastomosis and/or nerve grafting surgery for patients with facial nerve injury after facial trauma. Methods Fifty-nine patients with peripheral facial nerve paralysis after facial injuries underwent facial nerve rehabilitation surgery from November 2017 to December 2021 at Ho Chi Minh City National Hospital of Odontology. Results All 59 cases of facial trauma with damage to the peripheral facial nerve underwent facial nerve reconstruction surgery within 8 weeks of the injury. Of these cases, 25/59 (42.3%) had end-to-end anastomosis, 22/59 (37.3%) had nerve grafting, and 12/59 (20.4%) had a combination of nerve grafting and end-to-end anastomosis. After surgery, the rates of moderate and good recovery were 78.4% and 11.8%, respectively. All facial paralysis measurements showed statistically significant improvement after surgery, including the Facial Nerve Grading Scale 2.0 (FNGS 2.0) score, the Facial Clinimetric Evaluation (FaCE) scale, and electroneurography. The rate of synkinesis after surgery was 34%. Patient follow-up postoperatively ranged from 6 to > 36 months; 51 out of 59 patients (86.4%) were followed-up for at least 12 months or longer. Conclusion Nerve rehabilitation surgery including direct end-to-end anastomosis and nerve grafting is effective in cases of peripheral facial nerve injury following facial trauma. The surgery helps restore nerve conduction and improve facial paralysis.

Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque.

Mayaro virus (MAYV), a mosquito-borne alphavirus, is considered an emerging threat to public health with epidemic potential. Phylogenetic studies show the existence of three MAYV genotypes. In this study, we provide a preliminary analysis of the pathogenesis of all three MAYV genotypes in cynomolgus macaques (Macaca facicularis, Mauritian origin). Significant MAYV-specific RNAemia and viremia were detected during acute infection in animals challenged intravenously with the three MAYV genotypes, and strong neutralizing antibody responses were observed. MAYV RNA was detected at high levels in lymphoid tissues, joint muscle and synovia over 1 month after infection, suggesting that this model could serve as a promising tool in studying MAYV-induced chronic arthralgia, which can persist for years. Significant leucopenia was observed across all MAYV genotypes, peaking with RNAemia. Notable differences in the severity of acute RNAemia and composition of cytokine responses were observed among the three MAYV genotypes. Our model showed no outward signs of clinical disease, but several major endpoints for future MAYV pathology and intervention studies are described. Disruptions to normal blood cell counts and cytokine responses were markedly distinct from those observed in macaque models of CHIKV infection, underlining the importance of developing non-human primate models specific to MAYV infection.

Mediation Analysis of Acute Carotid Stenting in Tandem Lesions: Effect on Functional Outcome in a Multicenter Registry.

BACKGROUND AND OBJECTIVES: Current evidence suggests that acute carotid artery stenting (CAS) for cervical lesions is associated with better functional outcomes in patients with acute stroke with tandem lesions (TLs) treated with endovascular therapy (EVT). However, the underlying causal pathophysiologic mechanism of this relationship compared with a non-CAS strategy remains unclear. We aimed to determine whether, and to what degree, reperfusion mediates the relationship between acute CAS and functional outcome in patients with TLs. METHODS: This subanalysis stems from a multicenter retrospective cohort study across 16 stroke centers from January 2015 to December 2020. Patients with anterior circulation TLs who underwent EVT were included. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale ≥2B by the local team at each participating center. Mediation analysis was conducted to examine the potential causal pathway in which the relationship between acute CAS and functional outcome (90-day modified Rankin Scale) is mediated by successful reperfusion. RESULTS: A total of 570 patients were included, with a median age (interquartile range) of 68 (59-76), among whom 180 (31.6%) were female. Among these patients, 354 (62.1%) underwent acute CAS and 244 (47.4%) had a favorable functional outcome. The remaining 216 (37.9%) patients were in the non-CAS group. The CAS group had significantly higher rates of successful reperfusion (91.2% vs 85.1%; p = 0.025) and favorable functional outcomes (52% vs 29%; p = 0.003) compared with the non-CAS group. Successful reperfusion was a strong predictor of functional outcome (adjusted common odds ratio [acOR] 4.88; 95% CI 2.91-8.17; p < 0.001). Successful reperfusion partially mediated the relationship between acute CAS and functional outcome, as acute CAS remained significantly associated with functional outcome after adjustment for successful reperfusion (acOR 1.89; 95% CI 1.27-2.83; p = 0.002). Successful reperfusion explained 25% (95% CI 3%-67%) of the relationship between acute CAS and functional outcome. DISCUSSION: In patients with TL undergoing EVT, successful reperfusion predicted favorable functional outcomes when CAS was performed compared with non-CAS. A considerable proportion (25%) of the treatment effect of acute CAS on functional outcome was found to be mediated by improvement of successful reperfusion rates.

Combination of Searches for Resonant Higgs Boson Pair Production Using pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

A combination of searches for a new resonance decaying into a Higgs boson pair is presented, using up to 139 fb^{-1} of pp collision data at sqrt[s]=13 TeV recorded with the ATLAS detector at the LHC. The combination includes searches performed in three decay channels: bb[over ¯]bb[over ¯], bb[over ¯]τ^{+}τ^{-}, and bb[over ¯]γγ. No excess above the expected Standard Model background is observed and upper limits are set at the 95% confidence level on the production cross section of Higgs boson pairs originating from the decay of a narrow scalar resonance with mass in the range 251 GeV-5 TeV. The observed (expected) limits are in the range 0.96-600 fb (1.2-390 fb). The limits are interpreted in the type-I two-Higgs-doublet model and the minimal supersymmetric standard model, and constrain parameter space not previously excluded by other searches.

From bedside to bench: New insights in epilepsy-associated tumors based on recent classification updates and animal models on brain tumor networks.

Low-grade neuroepithelial tumors (LGNTs), particularly those with glioneuronal histology, are highly associated with pharmacoresistant epilepsy. Increasing research focused on these neoplastic lesions did not translate into drug discovery; and anticonvulsant or antitumor therapies are not available yet. During the last years, animal modeling has improved, thereby leading to the possibility of generating brain tumors in mice mimicking crucial genetic, molecular and immunohistological features. Among them, intraventricular in utero electroporation (IUE) has been proven to be a valuable tool for the generation of animal models for LGNTs allowing endogenous tumor growth within the mouse brain parenchyma. Epileptogenicity is mostly determined by the slow-growing patterns of these tumors, thus mirroring intrinsic interactions between tumor cells and surrounding neurons is crucial to investigate the mechanisms underlying convulsive activity. In this review, we provide an updated classification of the human LGNT and summarize the most recent data from human and animal models, with a focus on the crosstalk between brain tumors and neuronal function.

Ecology and geography of Cache Valley virus assessed using ecological niche modeling.

BACKGROUND: Cache Valley virus (CVV) is an understudied Orthobunyavirus with a high spillover transmission potential due to its wide geographical distribution and large number of associated hosts and vectors. Although CVV is known to be widely distributed throughout North America, no studies have explored its geography or employed computational methods to explore the mammal and mosquito species likely participating in the CVV sylvatic cycle. METHODS: We used a literature review and online databases to compile locality data for CVV and its potential vectors and hosts. We linked location data points with climatic data via ecological niche modeling to estimate the geographical range of CVV and hotspots of transmission risk. We used background similarity tests to identify likely CVV mosquito vectors and mammal hosts to detect ecological signals from CVV sylvatic transmission. RESULTS: CVV distribution maps revealed a widespread potential viral occurrence throughout North America. Ecological niche models identified areas with climate, vectors, and hosts suitable to maintain CVV transmission. Our background similarity tests identified Aedes vexans, Culiseta inornata, and Culex tarsalis as the most likely vectors and Odocoileus virginianus (white-tailed deer) as the most likely host sustaining sylvatic transmission. CONCLUSIONS: CVV has a continental-level, widespread transmission potential. Large areas of North America have suitable climate, vectors, and hosts for CVV emergence, establishment, and spread. We identified geographical hotspots that have no confirmed CVV reports to date and, in view of CVV misdiagnosis or underreporting, can guide future surveillance to specific localities and species.

Focused review: Clinico-neuropathological aspects of late onset epilepsies: Pathogenesis.

The aim of the present study was to review the current knowledge on the neuropathological spectrum of late onset epilepsies. Several terms including 'neuropathology*' AND 'late onset epilepsy' (LOE) combined with distinct neuropathological diagnostic terms were used to search PubMed until November 15, 2023. We report on the relevance of definitional aspects of LOE with implications for the diagnostic spectrum of epilepsies. The neuropathological spectrum in patients with LOE is described and includes vascular lesions, low-grade neuroepithelial neoplasms and focal cortical dysplasias (FCD). Among the latter, the frequency of the FCD subtypes appears to differ between LOE patients and those with seizure onset at a younger age. Neurodegenerative neuropathological changes in the seizure foci of LOE patients require careful interdisciplinary interpretation with respect to the differential diagnosis of primary neurodegenerative changes or epilepsy-related changes. Innate and adaptive neuroinflammation represents an important cause of LOE with intriguing therapeutic options.

Easy recognition and high autoimmune hepatitis specificity of smooth muscle antibodies giving an actin microfilament immunofluorescent pattern on embryonal vascular smooth muscle cells.

Smooth muscle antibodies (SMA) with anti-microfilament actin (MF-SMA) specificity are regarded as highly specific markers of type 1 autoimmune hepatitis (AIH-1) but their recognition relying on immunofluorescence of vessel, glomeruli, and tubules (SMA-VGT pattern) in rodent kidney-tissue, is restricted by operator-dependent interpretation.A gold standard method for their identification is not available. We assessed and compared the diagnostic accuracy for AIH-1 of an embryonal-aorta vascular-smooth-muscle(VSM) cell line-based assay with those of the rodent-tissue based assay for the detection of MF-SMA pattern in AIH-1 patients and controls. Sera from 138 AIH-1 patients and 295 controls (105 primary biliary cholangitis,40 primary sclerosing cholangitis,50 chronic viral hepatitis,20 alcohol-related liver disease,40 steatotic liver disease,and 40 healthy controls) were assayed for MF-SMA and for SMA-VGT using VSM-based and rodent tissue-based assays, respectively. MF-SMA and SMA-VGT were found in 96(70%) and 87(63%) AIH-1 patients, and 2 controls (p<0.0001).Compared with SMA-VGT, MF-SMA showed similar specificity (99%), higher sensitivity (70% vs 63%,p=ns) and likelihood ratio for a positive test (70 vs 65). Nine (7%) AIH-1 patients were MF-SMA positive despite being SMA-VGT negative. Overall agreement between SMA-VGT and MF-SMA was 87% (kappa coefficient 0.870,[0.789-0.952]). MF-SMA were associated with higher serum γ-globulin [26(12-55) vs 20 g/l(13-34),p<0.005] and immunoglobulin G (IgG) levels [3155(1296-7344) vs 2050 mg/dl(1377-3357), p<0.002]. The easily recognizable IFL MF-SMA pattern on VSM cells strongly correlated with SMA-VGT and has an equally high specificity for AIH-1. Confirmation of these results in other laboratories would support the clinical application of the VSM cell-based assay for reliable detection of AIH-specific SMA.

Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis.

BACKGROUND: Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear. METHODS: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24. RESULTS: A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events. CONCLUSIONS: In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).

Dupilumab Improves Health-Related Quality of Life and a Range of Symptoms in Patients With Eosinophilic Esophagitis.

INTRODUCTION: Improvements in symptomatic experience and health-related quality of life (HRQoL) are among the most important treatment benefits in patients with eosinophilic esophagitis (EoE). We assessed the impact of dupilumab treatment on HRQoL, patients' impression of dysphagia, and symptoms beyond dysphagia in adults/adolescents (≥12 years) with EoE in Parts A and B of the LIBERTY EoE TREET (NCT03633617) study. METHODS: The EoE Symptom Questionnaire (EoE-SQ; frequency and severity of non-dysphagia symptoms), EoE Impact Questionnaire (EoE-IQ; impact of EoE on HRQoL), and Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) of dysphagia were used to assess the efficacy of weekly dupilumab 300 mg vs placebo. RESULTS: At Week 24, dupilumab reduced EoE-SQ Frequency (least squares mean difference vs placebo [95% confidence interval] Part A -1.7 [-2.9, -0.5], Part B -1.4 [-2.3, -0.5]; both P<0.01) and EoE-SQ Severity (Part A -2.0 [-3.9, 0.0], P<0.05, Part B -1.5 [-3.0, 0.1], P=0.07) overall scores, and improved scores across all individual items. Improvement in the dupilumab group was clinically meaningful to patients. Dupilumab also meaningfully improved EoE-IQ average scores and improved individual item scores at Week 24, particularly emotional and sleep disturbance. More dupilumab-treated patients reported improvement in the PGIC of dysphagia vs placebo or reported having no symptoms per the PGIS of dysphagia at Week 24. DISCUSSION: Dupilumab reduced the impact of EoE on multiple aspects of HRQoL, patients' impression of dysphagia, and frequency and severity of symptoms beyond dysphagia in adults/adolescents with EoE.

Cervical Dissection in Patients With Tandem Lesions Is Associated With Distal Embolism and Lower Recanalization Success.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

Gene and protein sequence features augment HLA class I ligand predictions.

The sensitivity of malignant tissues to T cell-based immunotherapies depends on the presence of targetable human leukocyte antigen (HLA) class I ligands. Peptide-intrinsic factors, such as HLA class I affinity and proteasomal processing, have been established as determinants of HLA ligand presentation. However, the role of gene and protein sequence features as determinants of epitope presentation has not been systematically evaluated. We perform HLA ligandome mass spectrometry to evaluate the contribution of 7,135 gene and protein sequence features to HLA sampling. This analysis reveals that a number of predicted modifiers of mRNA and protein abundance and turnover, including predicted mRNA methylation and protein ubiquitination sites, inform on the presence of HLA ligands. Importantly, integration of such "hard-coded" sequence features into a machine learning approach augments HLA ligand predictions to a comparable degree as experimental measures of gene expression. Our study highlights the value of gene and protein features for HLA ligand predictions.

Coordinate-Independent 3-D Ultrasound Principal Stretch and Direction Imaging.

OBJECTIVE: In clinical ultrasound, current 2-D strain imaging faces challenges in quantifying three orthogonal normal strain components. This requires separate image acquisitions based on the pixel-dependent cardiac coordinate system, leading to additional computations and estimation discrepancies due to probe orientation. Most systems lack shear strain information, as displaying all components is challenging to interpret. METHODS: This paper presents a 3-D high-spatial-resolution, coordinate-independent strain imaging approach based on principal stretch and axis estimation. All strain components are transformed into three principal stretches along three normal principal axes, enabling direct visualization of the primary deformation. We devised an efficient 3-D speckle tracking method with tilt filtering, incorporating randomized searching in a two-pass tracking framework and rotating the phase of the 3-D correlation function for robust filtering. The proposed speckle tracking approach significantly improves estimates of displacement gradients related to the axial displacement component. Non-axial displacement gradient estimates are enhanced using a correlation-weighted least-squares method constrained by tissue incompressibility. RESULTS: Simulated and in vivo canine cardiac datasets were evaluated to estimate Lagrangian strains from end-diastole to end-systole. The proposed speckle tracking method improves displacement estimation by a factor of 4.3 to 10.5 over conventional 1-pass processing. Maximum principal axis/direction imaging enables better detection of local disease regions than conventional strain imaging. CONCLUSION: Coordinate-independent tracking can identify myocardial abnormalities with high accuracy. SIGNIFICANCE: This study offers enhanced accuracy and robustness in strain imaging compared to current methods.

Long-term evaluation of anterior thalamic deep brain stimulation for epilepsy in the European MORE registry.

OBJECTIVE: Short-term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) were reported for people with drug-resistant focal epilepsy (PwE). Because long-term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT-DBS. METHODS: In this multicenter registry, PwE with ANT-DBS were followed up for safety, efficacy, and battery longevity. Follow-up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%. RESULTS: Of 170 eligible PwE, 104, 62, and 49 completed the 3-, 4-, and 5-year follow-up, respectively. Most discontinuations (68%) were due to planned study closure as follow-up beyond 2 years was optional. The 5-year follow-up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5-year follow-up (p < .001), with most-pronounced effects on focal-to-bilateral tonic-clonic seizures (n = 15, 77% reduction, p = .008). At last follow-up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy (p = .035) and a negative history of epilepsy surgery (p = .002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS-related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT-DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months. SIGNIFICANCE: MORE provides further evidence for the long-term application of ANT-DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management.

Azimuthal Angle Correlations of Muons Produced via Heavy-Flavor Decays in 5.02 TeV Pb+Pb and pp Collisions with the ATLAS Detector.

Angular correlations between heavy quarks provide a unique probe of the quark-gluon plasma created in ultrarelativistic heavy-ion collisions. Results are presented of a measurement of the azimuthal angle correlations between muons originating from semileptonic decays of heavy quarks produced in 5.02 TeV Pb+Pb and pp collisions at the LHC. The muons are measured with transverse momenta and pseudorapidities satisfying p_{T}^{µ}>4 GeV and |η^{µ}|<2.4, respectively. The distributions of azimuthal angle separation Δϕ for muon pairs having pseudorapidity separation |Δη|>0.8, are measured in different Pb+Pb centrality intervals and compared to the same distribution measured in pp collisions at the same center-of-mass energy. Results are presented separately for muon pairs with opposite-sign charges, same-sign charges, and all pairs. A clear peak is observed in all Δϕ distributions at Δϕ∼π, consistent with the parent heavy-quark pairs being produced via hard-scattering processes. The widths of that peak, characterized using Cauchy-Lorentz fits to the Δϕ distributions, are found to not vary significantly as a function of Pb+Pb collision centrality and are similar for pp and Pb+Pb collisions. This observation will provide important constraints on theoretical descriptions of heavy-quark interactions with the quark-gluon plasma.

What makes a habitat a home? Habitat associations of juvenile European sea bass, Dicentrarchus labrax, in estuarine nurseries.

Selection of nursery habitats by marine fish, such as European sea bass (Dicentrarchus labrax), is poorly understood. Identifying and protecting the full range of juvenile nursery habitats is vital to supporting resilient fish populations and economically important fisheries. We examined how the condition, stomach fullness, and diet of juvenile European sea bass, along with their abundance, differ at high or low tide between the following estuarine habitats: saltmarsh, oyster reefs, shingle, sand, and mud edge habitats. Using a combination of fyke and seine netting we found no difference in sea bass abundance or condition across high-tide habitats, suggesting that rather than differentially selecting between them, juvenile sea bass use all available shallow habitats at high tide. Stomach fullness was significantly higher on saltmarsh and sand compared to mud, and thus these habitats may support better foraging. Dietary DNA metabarcoding revealed that sand and saltmarsh diets mostly comprised Hediste polychaetes, whereas zooplanktonic taxa dominated diets over mud. At low tide, sea bass abundance was highest in shingle and oyster reefs, where stomach fullness and condition were lowest. This may indicate a potential trade-off between using habitats for foraging and refuge. Although sea bass abundance alone does not capture productivity, the high abundance across all estuarine habitats at high tide suggests that it is important to consider the protection of a mosaic of interconnected habitats to support nursery functions rather than focus on individual habitat types.

Evaluating functional connectivity differences between DBS ON/OFF states in essential tremor.

Deep brain stimulation (DBS) targeting the ventral intermediate (Vim) nucleus of the thalamus is an effective treatment for essential tremor (ET). We studied 15 â€‹ET patients undergoing DBS to a major input/output tract of the Vim, the dentato-rubro-thalamic tract (DRTt), using resting state functional MRI (rsfMRI) to evaluate connectivity differences between DBS ON and OFF and elucidate significant regions most influential in impacting tremor control and/or concomitant gait ataxia. Anatomical/functional 1.5T MRIs were acquired and replicated for each DBS state. Tremor severity and gait ataxia severity were scored with DBS ON at optimal stimulation parameters and immediately upon DBS OFF. Whole brain analysis was performed using dual regression analysis followed by randomized permutation testing for multiple correction comparison. Regions of interest (ROI) analysis was also performed. All 15 patients had tremor improvement between DBS ON/OFF (p â€‹< â€‹0.001). Whole brain analysis revealed significant connectivity changes between states in the left pre-central gyrus and left supplemental motor area. Group analysis of ROIs revealed that, with threshold p â€‹< â€‹0.05, in DBS ON vs. OFF both tremor duration and tremor improvement were significantly correlated to changes in connectivity. A sub-group analysis of patients with greater ataxia had significantly decreased functional connectivity between multiple ROIs in the cortex and cerebellum when DBS was ON compared to OFF. Stimulation of the DRTt and concordant improvement of tremor resulted in connectivity changes seen in multiple regions outside the motor network; when combined with both structural and electrophysiologic connectivity, this may help to serve as a biomarker to improve DBS targeting and possibly predict outcome.

Intrinsic Gata4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model.

Loeys-Dietz syndrome (LDS) is an aneurysm disorder caused by mutations that decrease transforming growth factor-ß (TGF-ß) signaling. Although aneurysms develop throughout the arterial tree, the aortic root is a site of heightened risk. To identify molecular determinants of this vulnerability, we investigated the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1 M318R/+ LDS mice by single cell and spatial transcriptomics. Reduced expression of components of the extracellular matrix-receptor apparatus and upregulation of stress and inflammatory pathways were observed in all LDS VSMCs. However, regardless of genotype, a subset of Gata4-expressing VSMCs predominantly located in the aortic root intrinsically displayed a less differentiated, proinflammatory profile. A similar population was also identified among aortic VSMCs in a human scRNAseq dataset. Postnatal VSMC-specific Gata4 deletion reduced aortic root dilation in LDS mice, suggesting that this factor sensitizes the aortic root to the effects of impaired TGF-ß signaling.