A novel 3D imaging approach for quantification of GLUT4 levels across the intact myocardium.

Cellular heterogeneity is a well-accepted feature of tissues, and both transcriptional and metabolic diversity have been revealed by numerous approaches, including optical imaging. However, the high magnification objective lenses needed for high-resolution imaging provides information from only small layers of tissue, which can result in poor cell statistics. There is therefore an unmet need for an imaging modality that can provide detailed molecular and cellular insight within intact tissue samples in 3D. Using GFP-tagged GLUT4 as proof of concept, we present here a novel optical mesoscopy approach that allows precise measurement of the spatial location of GLUT4 within specific anatomical structures across the myocardium in ultrathick sections (5 mm x 5 mm x 3 mm) of intact mouse heart. We reveal distinct GLUT4 distribution patterns across cardiac walls and highlight specific changes in GLUT4 expression levels in response to high fat diet-feeding, and we identify sex-dependent differences in expression patterns. This method is applicable to any target that can be labelled for light microscopy, and to other complex tissues when organ structure needs to be considered simultaneously with cellular detail.

Characterizing defective lipid metabolism in the lateral septum of mice treated with olanzapine: implications for its side effects.

Schizophrenia significantly impacts cognitive and behavioral functions and is primarily treated with second-generation antipsychotics (SGAs) such as olanzapine. Despite their efficacy, these drugs are linked to serious metabolic side effects which can diminish patient compliance, worsen psychiatric symptoms and increase cardiovascular disease risk. This study explores the hypothesis that SGAs affect the molecular determinants of synaptic plasticity and brain activity, particularly focusing on the lateral septum (LS) and its interactions within hypothalamic circuits that regulate feeding and energy expenditure. Utilizing functional ultrasound imaging, RNA sequencing, and weighted gene co-expression network analysis, we identified significant alterations in the functional connection between the hypothalamus and LS, along with changes in gene expression in the LS of mice following prolonged olanzapine exposure. Our analysis revealed a module closely linked to increases in body weight and adiposity, featuring genes primarily involved in lipid metabolism pathways, notably Apoa1, Apoc3, and Apoh. These findings suggest that olanzapine may influence body weight and adiposity through its impact on lipid metabolism-related genes in the LS. Therefore, the neural circuits connecting the LS and LH, along with the accompanying alterations in lipid metabolism, are likely crucial factors contributing to the weight gain and metabolic side effects associated with olanzapine treatment.

Calcified amorphous tumor attached to the membranous septum: a rare clinical entity.

We report a rare case of a pedunculated calcified amorphous tumor (CAT) of the left ventricle attached by a stalk to the membranous septum in a 74-year-old woman who presented with a cerebrovascular accident. We believe this is the first report of a CAT attached to the membranous septum.

Cellular and circuit architecture of the lateral septum for reward processing.

The lateral septum (LS) is composed of heterogeneous cell types that are important for various motivated behaviors. However, the transcriptional profiles, spatial arrangement, function, and connectivity of these cell types have not been systematically studied. Using single-nucleus RNA sequencing, we delineated diverse genetically defined cell types in the LS that play distinct roles in reward processing. Notably, we found that estrogen receptor 1 (Esr1)-expressing neurons in the ventral LS (LSEsr1) are key drivers of reward seeking via projections to the ventral tegmental area, and these neurons play an essential role in methamphetamine (METH) reward and METH-seeking behavior. Extended exposure to METH increases the excitability of LSEsr1 neurons by upregulating hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, thereby contributing to METH-induced locomotor sensitization. These insights not only elucidate the intricate molecular, circuit, and functional architecture of the septal region in reward processing but also reveal a neural pathway critical for METH reward and behavioral sensitization.

Pulmonary Atresia with Intact Ventricular Septum, a National Comparison Between Interventional and Surgical Approach, in Combination with a Systemic Literature Review.

This study aimed to compare long-term morbidity in patients with pulmonary atresia with intact ventricular septum (PA-IVS) treated with catheter-based intervention (group A) versus those undergoing heart surgery (group B) as initial intervention. Additionally, we conducted a systematic literature review on PA-IVS treatment. All neonates born in Sweden with PA-IVS between 2007 and 2019 were screened for inclusion. The inclusion criterion was decompression of the right ventricle for initial intervention. Medical records were reviewed, as well as the initial preoperative angiogram, and the diagnostic echocardiogram. Comparisons between groups were performed with Mann-Whitney U-test and Fisher´s exact test. A systematic literature review of original studies regarding treatment of PA-IVS (2002 and onward) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, to assess the outcomes of patients with PA-IVS. 34 (11 females) patients were included, 18 in group A and 16 in group B. There was no mortality in either group. Follow-up time ranged from 2 to 15 years (median 9). All attempted perforations in group A were successful, and 16 out of 18 patients reached biventricular circulation. In the surgical group 15 out of 16 patients reached biventricular circulation. The literature review presented heterogeneity in standards for treatment. This retrospective population-based multicenter study demonstrates that both catheter-based intervention and heart surgery are safe procedures. Our results are comparable to, or exceed, those in the systematic literature review. The systematic literature review displays a great heterogeneity in study design, with no definitive golden standard treatment.

Frequency-dependent seizure-suppressing effects of optogenetic activation of septal inhibitory cells in mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) is characterized by recurring focal seizures that arise from limbic areas and are often refractory to pharmacological interventions. We have reported that optogenetic stimulation of PV-positive cells in the medial septum at 0.5 Hz exerts seizure-suppressive effects. Therefore, we compared here these results with those obtained by optogenetic stimulation of medial septum PV-positive neurons at 8 Hz in male PV-ChR2 mice (P60-P100) undergoing an initial, pilocarpine-induced status epilepticus (SE). Optogenetic stimulation (5 min ON, 10 min OFF) was performed from day 8 to day 12 after SE at a frequency of 8 Hz (n = 6 animals) or 0.5 Hz (n = 8 animals). Surprisingly, in both groups, no effects were observed on the occurrence of interictal spikes and interictal high frequency oscillations (HFOs). However, 0.5 Hz stimulation induced a significant decrease of seizure occurrence (p < 0.05). Such anti-ictogenic effect was not observed in the 8 Hz protocol that instead triggered seizures (p < 0.05); these seizures were significantly longer under optogenetic stimulation compared to when optogenetic stimulation was not implemented (p < 0.05). Analysis of ictal HFOs revealed that in the 0.5 Hz group, but not in the 8 Hz group, seizures occurring under optogenetic stimulation were associated with significantly lower rates of fast ripples compared to when optogenetic stimulation was not performed (p < 0.05). Our results indicate that activation of GABAergic PV-positive neurons in the medial septum exerts seizure-suppressing effects that are frequency-dependent and associated with low rates of fast ripples. Optogenetic activation of medial septum PV-positive neurons at 0.5 Hz is efficient in blocking seizures in the pilocarpine model of MTLE, an effect that did not occur with 8 Hz stimulation.

The Effects of Nasal Septal Deviation on Anterior Skull Base Parameters.

Introduction Functional endoscopic sinus surgery and endoscopic skull base surgery are frequently performed surgeries today. Nasal septal deviation is a common finding and can affect the surgical area. Therefore, it is important to examine the effect of this deviation on other anatomical structures. Objective The aim of the present study was to determine whether there is a relationship between the degree of nasal septal deviation and anterior skull base structures using computed tomography (CT). Methods A total of 312 patients (aged 18 to 65 years old) whose paranasal sinus CT images were available were included in the study. Measurements were obtained on images retrieved from Picture Archiving and Communication System (PACS) and Horos image archive systems in the bone window in the coronal and axial plane. Results The mean age of 312 patients was 33.00 years old (standard deviation [SD] 11.22 years). The presence of septal deviation was not associated with changes in olfactory fossa (OF) depths, Keros degrees, and the angle between the lateral lamella and the cribriform lamella. However, OF depths and Keros degrees on the deviated side of the septum were found to change at a significant level ( p < 0.05). No significant association was observed between the degree of septal deviation and cribriform lamella-lateral lamella angle. Conclusion The study showed significantly increased OF depth and Keros degree on the deviated side of the nasal septum. Performing CT scans before endoscopic sinus surgery and endoscopic skull base surgery is important to increase the chances of a successful surgical outcome and to reduce complications.

Tip Surgery in Dorsal Preservation Rhinoplasty: The Effect of Modified Low Septal Strip Septoplasty on Tip Plasty.

BACKGROUND: The aim in tip surgery is to provide rotation, derotation, projection and deprojection. In this study, we aimed to show the effects of modified low septal strip septoplasty, septal extension graft, TIG technique and additional maneuvers on tip shape in dorsal preservation rhinoplasty (DPR) and to discuss our clinical results. PATIENTS AND METHODS: One hundred eighty-nine patients who underwent DPR with modified low septal strip septoplasty between November 2021 and August 2023 were included in the study. Demographic data, complications, revision surgeries and follow-up periods of the patients were analyzed retrospectively. RESULTS: The mean age of the patients is 29.58±9.04 (17-65). The mean follow-up period was 14, 50±2,98 months. Complications were observed in 1.1% of the patients (n=2/189). Revision surgery was performed in all these patients. Residual hump in 2 were observed and dorsum rasping was performed under local anesthesia. No tip revision was performed on any patient. CONCLUSIONS: A strong tip fixation is achieved with the modified low septal septoplasty technique described in this publication, and when combined with septal extension graft, tongue in groove technique and other suture techniques, an effective and permanent tip plasty can be performed in DPR. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Circularly Polarized Vivaldi Antennas Integrated with Septum-like Polarizer.

In this paper, two orthogonally placed Vivaldi antennas with a septum-like polarizer to generate circular polarized (CP) waves are presented. Septum polarizers have garnered attention due to their simple structure and high quality of CP waves. While a typical septum polarizer has been applied to various types of waveguides, its applicability to the substrate integrated Vivaldi antenna is demonstrated here for the first time. A pulse train-shaped polarizer is used, which is placed on one of the two Vivaldi antennas. The contours of the polarizer are optimized using a genetic algorithm to provide an equal amplitude and 90° phase difference between the two orthogonal electric fields. In contrast to typical feed networks with a 90° phase shifter, any unwanted loss caused by an electronic circuit can be greatly mitigated. The antenna prototype was fabricated, and its radiation pattern and impedance matching were measured and compared to the simulated results.

Transposition of the Great Arteries With Ventricular Septal Defect in a One-Month-Old Infant.

Transposition of the great arteries (TGA), also termed complete transposition, is a congenital cardiac defect, and it is subjected to the concordance of the atrioventricular system discordance of the ventriculoarterial (VA) system. Male babies have slightly more preponderance than female babies. In almost half of the cases reported, the discordance in the VA system is the sole finding. In 10% of cases, TGA is often caused by other cardiac deformities, which incorporate defects in the septum of the ventricular chamber and stenosis in the left ventricular outlet. Eventually, these recite the progression, prognosis, and clinical presentation. In most cases, the onset is as soon as the birth. However, it may vary and depend on the difference in the anatomical and functional types, which determine the level of amalgamation between the oxygenated and deoxygenated blood. The etiology of the following condition is still unknown, but this defect is known to have a genetic preponderance. The definitive management of this condition is surgery, but medical management is optional and is prescribed according to the clinical evaluation and includes furosemide. Surgical correction can be performed in the later course of time, ensuring the fitness of the child. The procedure of choice is the arterial switch operation. This case report emphasizes the vital function of extensive critical care of newborns and prompt antenatal screening of high-risk pregnancies. It also highlights the importance of quick healthcare practices for newborns with congenital disabilities.

Septo-optic dysplasia plus syndrome in a 2-year-old child: A case report.

Septo-optic dysplasia (SOD) is a rare congenital condition characterized by a triad of septum pellucidum dysgenesis, optic nerve hypoplasia, and hypothalamic-hypophyseal dysfunction. In some cases, additional brain anomalies such as schizencephaly can occur, leading to a more complex presentation known as septo-optic dysplasia plus (SOD+). This case report describes a 2-year-old boy presenting with delayed psychomotor development and visual impairment, ultimately diagnosed with SOD+.

Interventricular septum involvement is related to right ventricular dysfunction in anterior STEMI patients without right ventricular infarction: a cardiovascular magnetic resonance study.

The value of cardiovascular magnetic resonance (CMR) in assessing and predicting acute right ventricular (RV) dysfunction in patients with anterior ST-segment elevation myocardial infarction (STEMI) remains ascertained. Eighty eight patients with anterior STEMI were prospectively recruited and underwent CMR examinations within one week following the coronary intervention. Patients with RV ejection fraction (RVEF) less than 2 standard deviations below the average at the center (RVEF ≤ 45.0%) were defined as having RV dysfunction. The size of infarction, segmental wall motion, and T1 and T2 mapping values of global myocardium and the interventricular septum (IVS) were measured. Predictive performance was calculated using receiver-operating characteristic curve analysis and logistic regression test. Twenty two patients presented with RV dysfunction. The RV dysfunction group had a larger IVS infarct extent (54.28 ± 10.35 vs 33.95 ± 15.09%, P < 0.001) and lower left ventricle stroke volume index (33.93 ± 7.96 vs 42.46 ± 8.14 ml/m2, P < 0.001) compared to the non-RV dysfunction group. IVS infarct extent at 48.8% best predicted the presence of RV dysfunction with an area under the curve of 0.864. Left ventricular stroke volume index (LVSVI) and IVS infarct extent were selected by stepwise multivariable logistic regression analysis. Lower LVSVI (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.79 to 0.99; P = 0.044) and higher IVS infarct extent (OR 1.16; 95% CI 1.05 to 1.33; P = 0.01) were found to be independent predictors for RV dysfunction. In patients with anterior STEMI, those with larger IVS infarct extent and worse LV function are more likely to be associated with RV dysfunction.

Increased Diastolic Energy Loss Associated with Cardiac Events in Adults with Pulmonary Atresia Suffering from Intact Ventricular Septum.

PURPOSE: To assess right heart diastolic energy loss (EL) as a cardiac workload and evaluate its association with major cardiac events (MACE) in adult patients with pulmonary atresia with an intact ventricular septum (PAIVS). METHODS: We retrospectively enrolled and compared 30 consecutive adult patients (18 with PAIVS and 12 with pulmonary stenosis [PS] as controls) who underwent right ventricular (RV) outflow tract reconstruction and 4D flow MRI. EL, conventional parameters on MRI, and the severity of tricuspid regurgitation (TR) on echocardiography were assessed. We also evaluated the association between MACE including arrhythmias, heart failure, surgical intervention, and imaging parameters in adults with PAIVS. RESULTS: Patients with PAIVS were younger, had a higher diastolic EL/cardiac output (CO) ratio, and had a more significant TR than those with PS (controls). However, RV volume, ejection fraction (EF), and pulmonary regurgitation (PR) severity did not differ between the two groups. Higher RV end-diastolic pressure (EDP) and lower cardiac index (CI) correlated with the diastolic EL/CO in patients with PAIVS. Univariate logistic analysis demonstrated that older age and a higher diastolic EL/CO ratio were important factors for MACE in adults with PAIVS (P = 0.048, 0.049). CONCLUSION: A higher diastolic EL/CO ratio was associated with a higher RV EDP and lower CI. A high diastolic EL/CO ratio is also associated with MACE in adults with PAIVS. Even in adults with normal RV volume and EF, the right heart EL was elevated, suggesting an excessive right-sided cardiac workload that integrated both afterload and preload beyond the RV size in adult patients with PAIVS.

Case Report: Persistent residual shunt after a first percutaneous PFO closure followed by minimally invasive surgical failure: third time is a charm.

Background: Even though the optimal management of a moderate or large residual shunt following patent foramen ovale (PFO) closure is open to question, recent data confirmed that it is associated with an increased risk of stroke recurrence. Case summary: A 48-year-old woman, a migraineur with visual aura, was diagnosed with a PFO associated with a huge multifenestrated atrial septal aneurysm (mfASA) and a moderate right-to-left shunt, detectable only after a Valsalva maneuver on contrast-transthoracic echocardiography. Brain magnetic resonance imaging showed a 1-mm silent white matter lesion in the right frontal lobe. Although the indication was not supported by guidelines, a transcatheter PFO closure was performed at another center with implantation of a large, equally sized, double-disc device (Figulla UNI 33/33 mm). At 6-month follow-up, a 2D/3D transesophageal echocardiography (TEE) color Doppler showed incorrect orientation of the device, which was not parallel to the interatrial septum, with two discs failing to capture the aortic muscular rim and partially protruding in the right atrium; furthermore, a 4 mm × 7 mm ASA fenestration was documented with a residual bidirectional shunt. Thereafter, the same team performed a minimally invasive cardiac surgery under femoro-femoral cardiopulmonary bypass; however, the procedure proved ineffective and was complicated by postoperative pericarditis with pericardial effusion, requiring further rehospitalization 1 month later due to persistent pericarditis, bilateral pleuritis, phrenic nerve palsy, and atrial flutter, which was treated with amiodarone. The patient asked for a second opinion, and our multidisciplinary heart team decided to offer a percutaneous redo intervention. An uneventful implantation of a regular PFO occluder (Figulla Flex II 16/18 mm) across the septal defect was performed successfully. Twelve-month follow-up with 2D TTE color Doppler and contrast transcranial Doppler showed correct position and good interaction between the two devices, with no residual shunt. Discussion: In addition to the incorrect indication for PFO closure and the failure of minimally invasive surgery, the procedural mishap in this case could have been due to the inappropriate implantation of the first large device within the tunnel. It would have been better to deploy the same large device in the most central fenestration, covering the PFO and a greater part of the remaining mfASA at the same time.

Evaluation of a safety-engineered peripherally inserted intravenous catheter with multiple access blood control: clinician acceptability and ease of use.

AIM: Acceptability of a new safety-engineered peripherally inserted intravenous catheter (PIVC) with multiple access blood control (MBC) was evaluated in this observational study by experienced volunteer clinicians on healthy volunteers. METHODS: Clinicians and healthy volunteers were recruited for this study. Observers documented study procedures, including if there was any blood leakage from the catheter hub at various times during hub connections and disconnections and how many attempts it took a clinician to get a successful stick. Clinicians responded to yes-or-no and Likert-scale questionnaires describing their experiences with PIVC with MBC after each procedure. Questionnaire data were summarized by frequency and percent of responses; analyses were conducted using binomial statistics. RESULTS: Overall, clinicians considered PIVC with MBC to be acceptable (93.6% agreement). Clinicians were able to easily remove the catheter protective cap, insert the catheter, visualize primary and secondary flashbacks, easily remove the needle from the catheter hub and determine if the safety clip was activated after withdrawing the needle. In addition, they were able to connect or disconnect and flush extension sets. Clinicians did not have to change their insertion technique, found the catheter easy to insert, and believed the catheter would protect them from blood exposure during insertion of the catheter and subsequent hub accesses (agreement ranged from 82.3% to 98.9%). CONCLUSIONS: No blood leakage was observed from the catheter hub at any time during the procedures. Overall, clinicians found the new PIVC with MBC to be acceptable, easy to use, and functioned properly. HIGHLIGHTS: Acceptability, usability, and ease of use of a new safety-engineered PIVC with MBC was evaluated. PIVC with MBC was >93% acceptable: prevented blood exposure after multiple insertions/removals. Most clinicians (96%) achieved first stick success when using their product. PIVC with MBC was easy to use, worked properly and allowed clinicians to keep their PIVC technique.

Pulmonary Atresia with Intact Ventricular Septum: Correlation of Preoperative Computed Tomography-Derived Parameters with Echocardiographic Tricuspid Valve Z-Score and Surgical Outcomes.

The role of preoperative cardiac computed tomography (CT) in neonates with pulmonary atresia and intact ventricular septum (PA-IVS) remains unclear. This study was aimed to elaborate the role of preoperative CT-derived anatomical and functional findings in planning treatment strategies in neonates with PA-IVS. The presence of ventriculocoronary arterial connections was evaluated by CT. CT-derived ventricular volumetric parameters were compared and correlated with echocardiographic tricuspid valve (TV) z-score in 12 neonates with PA-IVS. Cardiac CT and echocardiographic findings were compared between definite surgical types (median follow-up, 4 years). Ventriculocoronary arterial connections were identified with CT in 58.3% of cases (7/12) and associated with higher incidence of Fontan procedure (42.9%, 3/7) and high mortality (28.6%, 2/7). The CT-derived and echocardiographic TV z-scores exhibited a high correlation (R = 0.924, p < 0.001). The CT-derived right ventricle (RV) volume and RV-left ventricle volume ratio also displayed high correlations (R = 0.875 and 0.867, respectively; p < 0.001) with echocardiographic TV z-score. More positive echocardiographic TV z-score, high CT-derived RV end-diastolic volume and RV-left ventricle volume ratio, and low CT-derived left ventricular end-diastolic volume were observed in biventricular surgery group (N = 2), compared to Fontan operation (N = 3) and 1.5 ventricular surgery (N = 3) groups, and mortality cases (N = 3). Preoperative CT-derived coronary artery anatomy and ventricular volumetric parameters may supplement treatment planning in neonates with PA-IVS especially when multifactorial decision including echocardiographic TV z-score is in a gray zone.W.

Disengagement of somatostatin neurons from lateral septum circuitry by oxytocin and vasopressin restores social-fear extinction and suppresses aggression outbursts in Prader-Willi syndrome model.

Background: Responding to social signals by expressing the correct behavior is not only challenged in autism, but also in diseases with high prevalence of autism, like Prader-Willi Syndrome (PWS). Clinical evidence suggests aberrant pro-social behavior in patients can be regulated by intranasal oxytocin (OXT) or vasopressin (AVP). However, what neuronal mechanisms underlie impaired behavioral responses in a socially-aversive context, and how can they be corrected, remains largely unknown. Methods: Using the Magel2 knocked-out (KO) mouse model of PWS (crossed with CRE-dependent transgenic lines), we devised optogenetic, physiological and pharmacological strategies in a social-fear-conditioning paradigm. Pathway specific roles of OXT and AVP signaling were investigated converging on the lateral septum (LS), a region which receives dense hypothalamic inputs. Results: OXT and AVP signaling promoted inhibitory synaptic transmission in the LS, which failure in Magel2KO mice disinhibited somatostatin (SST) neurons and disrupted social-fear extinction. The source of OXT and AVP deficits mapped specifically in the supraoptic nucleus→LS pathway of Magel2KO mice disrupting social-fear extinction, which could be corrected by optogenetic or pharmacological inhibition of SST-neurons in the LS. Interestingly, LS SST-neurons also gated the expression of aggressive behavior, possibly as part of functional units operating beyond local septal circuits. Conclusions: SST cells in the LS play a crucial role in integration and expression of disrupted neuropeptide signals in autism, thereby altering the balance in expression of safety versus fear. Our results uncover novel mechanisms underlying dysfunction in a socially-aversive context, and provides a new framework for future treatments in autism-spectrum disorders.