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1.
Acad Radiol ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38969575

ABSTRACT

RATIONALE AND OBJECTIVES: To assess image quality and radiation dose of ultra-high-pitch CT pulmonary angiography (CTPA) with free-breathing technique for diagnosis of pulmonary embolism using a photon-counting detector (PCD) CT compared to matched energy-integrating detector (EID)-based single-energy CTPA. MATERIALS AND METHODS: Fifty-one PCD-CTPAs were prospectively compared to 51 CTPAs on a third-generation dual-source EID-CT. CTPAs were acquired with an ultra-high-pitch protocol with free-breathing technique (40 mL contrast medium, pitch 3.2) at 140 kV (PCD) and 70-100 kV (EID). Iodine maps were reconstructed from spectral PCD-CTPAs. Image quality of CTPAs and iodine maps was assessed independently by three radiologists. Additionally, CT attenuation numbers within pulmonary arteries as well as signal-to-noise and contrast-to-noise ratios (SNR, CNR) were compared. Administered radiation dose was compared. RESULTS: CT attenuation was higher in the PCD-group (all P < 0.05). CNR and SNR were higher in lobar pulmonary arteries in PCD-CTPAs (P < 0.05), whereas no difference was ascertained within the pulmonary trunk (P > 0.05). Image quality of PCD-CTPA was rated best by all readers (excellent/good image quality in 96.1% of PCD-CTPAs vs. 50.9% of EID-CTPAs). PCD-CT produced no non-diagnostic scans vs. three non-diagnostic (5.9%) EID-CTPAs. Radiation dose was lower with PCD-CT than with EID-CT (effective dose 1.33 ± 0.47 vs. 1.80 ± 0.82 mSv; all P < 0.05). CONCLUSION: Ultra-high-pitch CTPA with free-breathing technique with PCD-CT allows for superior image quality with significantly reduced radiation dose and full spectral information. With the ultra-high pitch, only PCD-CTPA enables reconstruction of iodine maps containing additional functional information.

2.
Acad Radiol ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38955591

ABSTRACT

RATIONALE AND OBJECTIVES: To compare a conventional T1 volumetric interpolated breath-hold examination (VIBE) with SPectral Attenuated Inversion Recovery (SPAIR) fat saturation and a deep learning (DL)-reconstructed accelerated VIBE sequence with SPAIR fat saturation achieving a 50 % reduction in breath-hold duration (hereafter, VIBE-SPAIRDL) in terms of image quality and diagnostic confidence. MATERIALS AND METHODS: This prospective study enrolled consecutive patients referred for upper abdominal MRI from November 2023 to December 2023 at a single tertiary center. Patients underwent upper abdominal MRI with acquisition of non-contrast and gadobutrol-enhanced conventional VIBE-SPAIR (fourfold acceleration, acquisition time 16 s) and VIBE-SPAIRDL (sixfold acceleration, acquisition time 8 s) on a 1.5 T scanner. Image analysis was performed by four readers, evaluating homogeneity of fat suppression, perceived signal-to-noise ratio (SNR), edge sharpness, artifact level, lesion detectability and diagnostic confidence. A statistical power analysis for patient sample size estimation was performed. Image quality parameters were compared by a repeated measures analysis of variance, and interreader agreement was assessed using Fleiss' κ. RESULTS: Among 450 consecutive patients, 45 patients were evaluated (mean age, 60 years ± 15 [SD]; 27 men, 18 women). VIBE-SPAIRDL acquisition demonstrated superior SNR (P < 0.001), edge sharpness (P < 0.001), and reduced artifacts (P < 0.001) with substantial to almost perfect interreader agreement for non-contrast (κ: 0.70-0.91) and gadobutrol-enhanced MRI (κ: 0.68-0.87). No evidence of a difference was found between conventional VIBE-SPAIR and VIBE-SPAIRDL regarding homogeneity of fat suppression, lesion detectability, or diagnostic confidence (all P > 0.05). CONCLUSION: Deep learning reconstruction of VIBE-SPAIR facilitated a reduction of breath-hold duration by half, while reducing artifacts and improving image quality. SUMMARY: Deep learning reconstruction of prospectively accelerated T1 volumetric interpolated breath-hold examination for upper abdominal MRI enabled a 50 % reduction in breath-hold time with superior image quality. KEY RESULTS: 1) In a prospective analysis of 45 patients referred for upper abdominal MRI, accelerated deep learning (DL)-reconstructed VIBE images with spectral fat saturation (SPAIR) showed better overall image quality, with better perceived signal-to-noise ratio and less artifacts (all P < 0.001), despite a 50 % reduction in acquisition time compared to conventional VIBE. 2) No evidence of a difference was found between conventional VIBE-SPAIR and accelerated VIBE-SPAIRDL regarding lesion detectability or diagnostic confidence.

3.
Hellenic J Cardiol ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38977061

ABSTRACT

BACKGROUND: Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling, studied in chronic RV pressure overload syndromes. However, its prognostic utility in patients with acute myocardial infarction (AMI) that may cause acute RV pressure overload remains unexplored. OBJECTIVES: To determine predictors of RV-PA uncoupling in patients with first AMI and examine whether it could improve risk stratification for cardiovascular in-hospital mortality after revascularization. METHODS: Three-hundred consecutive patients with first AMI were prospectively studied (age 61.2±11.8, 24% females). An echocardiogram was performed 24 hours after successful revascularization and TAPSE/PASP was evaluated. Cardiovascular in-hospital mortality was recorded. RESULTS: The optimal cutoff value of TAPSE/PASP to determine cardiovascular in-hospital mortality was 0.49 mm/mmHg. RV-PA uncoupling was considered for patients with TAPSE/PASP ≤0.49 mm/mmHg. Left ventricular ejection fraction (LVEF) was independently associated with RV-PA uncoupling. A total of 23 (7.7%) patients died in-hospital despite successful revascularization. TAPSE/PASP was independently associated with in-hospital mortality, after adjustment for Global Registry of Cardiovascular Events (GRACE) risk score and LVEF (Odds Ratio 0.14, 95% Confidence Intervals [0.03-0.56], P-value 0.007). The prognostic value of a baseline model including GRACE risk score and NT-pro-BNP (χ2 26.55) was significantly improved by adding LVEF ≤40 % (χ2 44.71, P-value <0.001), TAPSE ≤17 mm (χ2 75.42, P-value <0.001) and TAPSE/PASP ≤0.49 mm/mmHg (χ2 101.74, P-value <0.001) for predicting cardiovascular in-hospital mortality. CONCLUSIONS: RV-PA uncoupling, assessed by echocardiographic TAPSE/PASP ≤0.49 mm/mmHg 24 hours after revascularization, may improve risk stratification for cardiovascular in-hospital mortality post first AMI.

4.
J Proteome Res ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008891

ABSTRACT

Lipidomics emerges as a promising research field with the potential to help in personalized risk stratification and improve our understanding on the functional role of individual lipid species in the metabolic perturbations occurring in coronary artery disease (CAD). This study aimed to utilize a machine learning approach to provide a lipid panel able to identify patients with obstructive CAD. In this posthoc analysis of the prospective CorLipid trial, we investigated the lipid profiles of 146 patients with suspected CAD, divided into two categories based on the existence of obstructive CAD. In total, 517 lipid species were identified, from which 288 lipid species were finally quantified, including glycerophospholipids, glycerolipids, and sphingolipids. Univariate and multivariate statistical analyses have shown significant discrimination between the serum lipidomes of patients with obstructive CAD. Finally, the XGBoost algorithm identified a panel of 17 serum biomarkers (5 sphingolipids, 7 glycerophospholipids, a triacylglycerol, galectin-3, glucose, LDL, and LDH) as totally sensitive (100% sensitivity, 62.1% specificity, 100% negative predictive value) for the prediction of obstructive CAD. Our findings shed light on dysregulated lipid metabolism's role in CAD, validating existing evidence and suggesting promise for novel therapies and improved risk stratification.

5.
Curr Probl Cardiol ; : 102749, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39002619

ABSTRACT

BACKGROUND: To systematically evaluate the prognostic utility of estimated plasma volume status (ePVS) on the outcomes of patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: The exposure variable of interest was the ePVS, enumerating the percentage change of the actual plasma volume from the ideal plasma volume, and being calculated on the basis of weight and hematocrit using sex-specific constants. A random-effects meta-analysis was performed after a systematic literature search in PubMed, Scopus and Web Of Science. RESULTS: The systematic literature search yielded 5 eligible observational cohort studies encompassing a total of 7,121 patients undergoing TAVI. The meta-analysis suggested that "high ePVS" status was independently associated with increased risk for 1-year all-cause mortality (pooled adjusted hazard ratio: 1.63, 95% confidence intervals: 1.36-1.95) compared to "low ePVS". Also, the pooled unadjusted odds for 1-year mortality, 30-day mortality, peri-procedural stroke, major bleeding, and acute kidney injury were significantly increased in the "high ePVS" group of patients. Conversely, the unadjusted risk of pacemaker implantation and major vascular complications did not differ significantly between the 2 groups. CONCLUSIONS: Plasma volume expansion appears to be linked with a worse peri-procedural and long-term prognostic course in TAVI. Its use in clinical practice could refine risk stratification and candidate selection practices.

7.
Eur J Radiol ; 178: 111523, 2024 May 22.
Article in English | MEDLINE | ID: mdl-39013270

ABSTRACT

BACKGROUND: Neck computed tomography (NCT) is essential for diagnosing suspected neck tumors and abscesses, but radiation exposure can be an issue. In conventional reconstruction techniques, limiting radiation dose comes at the cost of diminished diagnostic accuracy. Therefore, this study aimed to evaluate the effects of an AI-based denoising post-processing software solution in low-dose neck computer tomography. MATERIALS AND METHODS: From 01 September 2023 to 01 December 2023, we retrospectively included patients with clinically suspected neck tumors from the same single-source scanner. The scans were reconstructed using Advanced Modeled Iterative Reconstruction (Original) at 100% and simulated 50% and 25% radiation doses. Each dataset was post-processed using a novel denoising software solution (Denoising). Three radiologists with varying experience levels subjectively rated image quality, diagnostic confidence, sharpness, and contrast for all pairwise combinations of radiation dose and reconstruction mode in a randomized, blinded forced-choice setup. Objective image quality was assessed using ROI measurements of mean CT numbers, noise, and a contrast-to-noise ratio (CNR). An adequately corrected mixed-effects analysis was used to compare objective and subjective image quality. RESULTS: At each radiation dose level, pairwise comparisons showed significantly lower image noise and higher CNR for Denoising than for Original (p < 0.001). In subjective analysis, image quality, diagnostic confidence, sharpness, and contrast were significantly higher for Denoising than for Original at 100 and 50 % (p < 0.001). However, there were no significant differences in the subjective ratings between Original 100 % and Denoising 25 % (p = 0.906). CONCLUSIONS: The investigated denoising algorithm enables diagnostic-quality neck CT images with radiation doses reduced to 25% of conventional levels, significantly minimizing patient exposure.

8.
Commun Biol ; 7(1): 683, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834871

ABSTRACT

In the context of soft matter and cellular mechanics, microrheology - the use of micron-sized particles to probe the frequency-dependent viscoelastic response of materials - is widely used to shed light onto the mechanics and dynamics of molecular structures. Here we present the implementation of active microrheology in an Acoustic Force Spectroscopy setup (AFMR), which combines multiplexing with the possibility of probing a wide range of forces ( ~ pN to ~nN) and frequencies (0.01-100 Hz). To demonstrate the potential of this approach, we perform active microrheology on biological samples of increasing complexity and stiffness: collagen gels, red blood cells (RBCs), and human fibroblasts, spanning a viscoelastic modulus range of five orders of magnitude. We show that AFMR can successfully quantify viscoelastic properties by probing many beads with high single-particle precision and reproducibility. Finally, we demonstrate that AFMR to map local sample heterogeneities as well as detect cellular responses to drugs.


Subject(s)
Elasticity , Erythrocytes , Fibroblasts , Rheology , Humans , Viscosity , Fibroblasts/physiology , Rheology/methods , Collagen/chemistry , Acoustics
9.
J Phys Chem C Nanomater Interfaces ; 128(22): 9142-9153, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38864002

ABSTRACT

We present an optical study of the spontaneous emission of lead sulfide (PbS) nanocrystal quantum dots in 3D photonic band gap crystals made from silicon. The nanocrystals emit in the near-infrared range to be compatible with 3D silicon nanophotonics. The nanocrystals are covalently bound to polymer brush layers that are grafted from the Si-air interfaces inside the nanostructure by using surface-initiated atom transfer radical polymerization. The presence and position of the quantum dots were previously characterized by synchrotron X-ray fluorescence tomography. We report both continuous wave emission spectra and time-resolved, time-correlated single photon counting. In time-resolved measurements, we observe that the total emission rate greatly increases when the quantum dots are transferred from suspension to the silicon nanostructures, likely due to quenching (or increased nonradiative decay) that is tentatively attributed to the presence of Cu catalysts during the synthesis. In this regime, continuous wave emission spectra are known to be proportional to the radiative rate and thus to the local density of states. In spectra normalized to those taken on flat silicon outside the crystals, we observe a broad and deep stop band that we attribute to a 3D photonic band gap with a relative bandwidth of up to 26%. The shapes of the relative emission spectra match well with the theoretical density of states spectra calculated with plane-wave expansion. The observed inhibition is 4-30 times, similar to previously reported record inhibitions, yet for coincidental reasons. Our results are relevant to applications in photochemistry, sensing, photovoltaics, and efficient miniature light sources.

10.
J Clin Med ; 13(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38892987

ABSTRACT

Background/Objectives: Radial artery occlusion (RAO) is the most common complication of transradial coronary catheterization. In this study, we aimed to evaluate the incidence of RAO and identify the risk factors that predispose patients to it. Methods: We conducted an investigator-initiated, prospective, multicenter, open-label study involving 1357 patients who underwent cardiac catheterization via the transradial route for angiography and/or a percutaneous coronary intervention (PCI). Univariate and multivariate logistic regression analyses were performed to identify potential predictors of RAO occurrence. Additionally, a subgroup analysis only for patients undergoing PCIs was performed. Results: The incidence of RAO was 9.5% overall, 10.6% in the angiography-only group and 6.2% in the PCI group. Independent predictors of RAO were as follows: (i) the female gender (aOR = 1.72 (1.05-2.83)), (ii) access site cross-over (aOR = 4.33 (1.02-18.39)), (iii) increased total time of the sheath in the artery (aOR = 1.01 (1.00-1.02)), (iv) radial artery spasms (aOR = 2.47 (1.40-4.36)), (v) the presence of a hematoma (aOR = 2.28 (1.28-4.06)), (vi) post-catheterization dabigatran use (aOR = 5.15 (1.29-20.55)), (vii) manual hemostasis (aOR = 1.94 (1.01-3.72)) and (viii) numbness at radial artery ultrasound (aOR = 8.25 (1.70-40)). Contrariwise, two variables were independently associated with increased odds for radial artery patency (RAP): (i) PCI performance (aOR = 0.19 (0.06-0.63)), and (ii) a higher dosage of intravenous heparin per patient weight (aOR = 0.98 (0.96-0.99)), particularly, a dosage of >50 IU/kg (aOR = 0.56 (0.31-1.00)). In the PCI subgroup, independent predictors of RAO were as follows: (i) radial artery spasms (aOR = 4.48 (1.42-14.16)), (ii) the use of intra-arterial nitroglycerin as a vasodilator (aOR = 7.40 (1.67-32.79)) and (iii) the presence of symptoms at echo (aOR = 3.80 (1.46-9.87)), either pain (aOR = 2.93 (1.05-8.15)) or numbness (aOR = 4.66 (1.17-18.57)). On the other hand, the use of intra-arterial verapamil as a vasodilator (aOR = 0.17 (0.04-0.76)) was independently associated with a greater frequency of RAP. Conclusions: The incidence of RAO in an unselected, all-comers European population after transradial coronary catheterization for angiography and/or PCIs is similar to that reported in the international literature. Several RAO prognostic factors have been confirmed, and new ones are described. The female gender, radial artery trauma and manual hemostasis are the strongest predictors of RAO. Our results could help in the future identification of patients at higher risk of RAO, for whom less invasive diagnostic procedures maybe preferred, if possible.

11.
J Clin Med ; 13(11)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38893005

ABSTRACT

Background/Objectives: Contradictory results have been reported regarding the influence of obesity on the prognosis of atrial fibrillation (AF). The present study aimed to explore the potential association of body mass index (BMI) with the clinical outcomes of hospitalized patients with AF. Methods: In this retrospective, post hoc analysis of the MISOAC-AF randomized trial, 1113 AF patients were included and stratified as the following: underweight (BMI < 18 kg/m2), normal weight (BMI 18-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), and obese (BMI ≥ 30 kg/m2). The primary outcome was all-cause mortality; the secondary composite outcome was any hospitalization related to AF, heart failure (HF), or stroke. Cox regression analysis, survival analysis, and spline curve models were utilized. Results: Of the patients (median age: 76 years (IQR: 13), male: 54.6%), the majority were overweight (41.4%), followed by obese (33%), normal weight (24%), and underweight (1.6%). During a median 31-month follow-up, 436 (39.2%) patients died and 657 (59%) were hospitalized due to AF, HF, or stroke. Underweight, overweight, and obesity groups were significantly associated with an increased risk of all-cause mortality (p-values 0.02, 0.001, and <0.001, respectively), while overweight and obesity were significantly associated with the composite endpoint (p-values 0.01, <0.001, respectively) compared to normal weight. The spline curve analyses yielded that BMIs > 26.3 and > 25 were incrementally associated with all-cause mortality and the composite endpoint, respectively. A J-shaped relationship between BMI and AF prognosis was deduced. Conclusions: In conclusion, in recently hospitalized AF patients, BMI values outside the normal range were independently associated with poorer prognosis; therefore, it is essential that AF patients maintain a normal weight.

12.
Sci Adv ; 10(23): eadm7273, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848365

ABSTRACT

By analyzing 15,000 samples from 348 mammalian species, we derive DNA methylation (DNAm) predictors of maximum life span (R = 0.89), gestation time (R = 0.96), and age at sexual maturity (R = 0.85). Our maximum life-span predictor indicates a potential innate longevity advantage for females over males in 17 mammalian species including humans. The DNAm maximum life-span predictions are not affected by caloric restriction or partial reprogramming. Genetic disruptions in the somatotropic axis such as growth hormone receptors have an impact on DNAm maximum life span only in select tissues. Cancer mortality rates show no correlation with our epigenetic estimates of life-history traits. The DNAm maximum life-span predictor does not detect variation in life span between individuals of the same species, such as between the breeds of dogs. Maximum life span is determined in part by an epigenetic signature that is an intrinsic species property and is distinct from the signatures that relate to individual mortality risk.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Longevity , Mammals , Animals , Longevity/genetics , Mammals/genetics , Female , Humans , Male , Life History Traits , Species Specificity
13.
J Invasive Cardiol ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814904

ABSTRACT

A 59-year-old diabetic man with a history of numerous coronary angiographies (CAs) and peripheral artery disease underwent CA due to a non-ST elevation myocardial infarction. Femoral, radial, and ulnar arteries were unpalpable.

15.
PLoS Comput Biol ; 20(5): e1012056, 2024 May.
Article in English | MEDLINE | ID: mdl-38781156

ABSTRACT

Responses to natural stimuli in area V4-a mid-level area of the visual ventral stream-are well predicted by features from convolutional neural networks (CNNs) trained on image classification. This result has been taken as evidence for the functional role of V4 in object classification. However, we currently do not know if and to what extent V4 plays a role in solving other computational objectives. Here, we investigated normative accounts of V4 (and V1 for comparison) by predicting macaque single-neuron responses to natural images from the representations extracted by 23 CNNs trained on different computer vision tasks including semantic, geometric, 2D, and 3D types of tasks. We found that V4 was best predicted by semantic classification features and exhibited high task selectivity, while the choice of task was less consequential to V1 performance. Consistent with traditional characterizations of V4 function that show its high-dimensional tuning to various 2D and 3D stimulus directions, we found that diverse non-semantic tasks explained aspects of V4 function that are not captured by individual semantic tasks. Nevertheless, jointly considering the features of a pair of semantic classification tasks was sufficient to yield one of our top V4 models, solidifying V4's main functional role in semantic processing and suggesting that V4's selectivity to 2D or 3D stimulus properties found by electrophysiologists can result from semantic functional goals.


Subject(s)
Models, Neurological , Neural Networks, Computer , Semantics , Visual Cortex , Animals , Visual Cortex/physiology , Computational Biology , Photic Stimulation , Neurons/physiology , Macaca mulatta , Macaca
16.
Sleep Med ; 119: 467-479, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38795401

ABSTRACT

BACKGROUND: Sleep disturbances are an important symptom dimension of post-traumatic-stress-disorder (PTSD). There is no meta-analytic evidence examining the effects of all types of pharmacotherapy on sleep outcomes among patients with PTSD. METHODS: Medline/Embase/PsychInfo/CENTRAL/clinicaltrials.gov/ICTRP, reference lists of published reviews and all included studies were searched for Randomised Controlled Trials (RCTs) examining any pharmacotherapy vs. placebo or any other drug among patients with PTSD. PRIMARY OUTCOMES: total sleep time, nightmares, sleep quality. SECONDARY OUTCOMES: sleep onset latency, number of nocturnal awakenings, time spent awake following sleep onset, dropouts due to sleep-related adverse-effects, insomnia/somnolence/vivid-dreams as adverse-effects. Pairwise and network meta-analyses were performed. RESULTS: 99 RCTs with 10,481 participants were included. Prazosin may be the most effective treatment for insomnia (SMD = -0.88, 95%CI = [-1.22;-0.54], nightmares (SMD = -0.44, 95%CI = [-0.84;-0.04]) and poor sleep quality (SMD = -0.55, 95%CI = [-1.01;-0.10]). Evidence is scarce and indicates lack of efficacy for SSRIs, Mirtazapine, z-drugs and benzodiazepines, which are widely used in daily practice. Risperidone and Quetiapine carry a high risk of causing somnolence without having a clear therapeutic benefit. Hydroxyzine, Trazodone, Nabilone, Paroxetine and MDMA-assisted psychotherapy may be promising options, but more research is needed. CONCLUSIONS: Underpowered individual comparisons and very-low to moderate confidence in effect estimates hinder the generalisability of the results. More RCTs, specifically reporting on sleep-related outcomes, are urgently needed.


Subject(s)
Network Meta-Analysis , Sleep Wake Disorders , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/complications , Sleep Wake Disorders/drug therapy , Prazosin/therapeutic use , Randomized Controlled Trials as Topic , Dreams/drug effects , Sleep Initiation and Maintenance Disorders/drug therapy
17.
Nat Commun ; 15(1): 4083, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744825

ABSTRACT

Energetic stress compels cells to evolve adaptive mechanisms to adjust their metabolism. Inhibition of mTOR kinase complex 1 (mTORC1) is essential for cell survival during glucose starvation. How mTORC1 controls cell viability during glucose starvation is not well understood. Here we show that the mTORC1 effectors eukaryotic initiation factor 4E binding proteins 1/2 (4EBP1/2) confer protection to mammalian cells and budding yeast under glucose starvation. Mechanistically, 4EBP1/2 promote NADPH homeostasis by preventing NADPH-consuming fatty acid synthesis via translational repression of Acetyl-CoA Carboxylase 1 (ACC1), thereby mitigating oxidative stress. This has important relevance for cancer, as oncogene-transformed cells and glioma cells exploit the 4EBP1/2 regulation of ACC1 expression and redox balance to combat energetic stress, thereby supporting transformation and tumorigenicity in vitro and in vivo. Clinically, high EIF4EBP1 expression is associated with poor outcomes in several cancer types. Our data reveal that the mTORC1-4EBP1/2 axis provokes a metabolic switch essential for survival during glucose starvation which is exploited by transformed and tumor cells.


Subject(s)
Acetyl-CoA Carboxylase , Adaptor Proteins, Signal Transducing , Cell Cycle Proteins , Cell Survival , Fatty Acids , Glucose , Mechanistic Target of Rapamycin Complex 1 , Animals , Humans , Mice , Acetyl-CoA Carboxylase/metabolism , Acetyl-CoA Carboxylase/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Line, Tumor , Eukaryotic Initiation Factors/metabolism , Eukaryotic Initiation Factors/genetics , Fatty Acids/metabolism , Glucose/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Mechanistic Target of Rapamycin Complex 1/genetics , NADP/metabolism , Oxidative Stress , Phosphoproteins/metabolism , Phosphoproteins/genetics , Protein Biosynthesis
18.
J Clin Med ; 13(8)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38673656

ABSTRACT

Ventricular fibrillation (VF) is a common cause of sudden cardiac death in patients with channelopathies, particularly in the young population. Although pharmacological treatment, cardiac sympathectomy, and implantable cardioverter defibrillators (ICD) have been the mainstay in the management of VF in patients with channelopathies, they are associated with significant adverse effects and complications, leading to poor quality of life. Given these drawbacks, catheter ablation has been proposed as a therapeutic option for patients with channelopathies. Advances in imaging techniques and modern mapping technologies have enabled increased precision in identifying arrhythmia triggers and substrate modification. This has aided our understanding of the underlying pathophysiology of ventricular arrhythmias in channelopathies, highlighting the roles of the Purkinje network and the epicardial right ventricular outflow tract in arrhythmogenesis. This review explores the role of catheter ablation in managing the most common channelopathies (Brugada syndrome, congenital long QT syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). While the initial results for ablation in Brugada syndrome are promising, the long-term efficacy and durability of ablation in different channelopathies require further investigation. Given the genetic and phenotypic heterogeneity of channelopathies, future studies are needed to show whether catheter ablation in patients with channelopathies is associated with a reduction in VF, and psychological distress stemming from recurrent ICD shocks, particularly relative to other available therapeutic options (e.g., quinidine in high-risk Brugada patients).

19.
PLoS One ; 19(4): e0302017, 2024.
Article in English | MEDLINE | ID: mdl-38603731

ABSTRACT

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins-complete tumor removal while attempting to preserve viable tissue-remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.


Subject(s)
Neurofibroma , Neurofibromatosis 1 , Neuroma , Skin Neoplasms , Humans , Spectrum Analysis, Raman/methods , Artificial Intelligence , Neurofibroma/diagnosis , Neurofibroma/genetics , Neurofibroma/pathology , Neurofibromatosis 1/diagnosis , Neurofibromatosis 1/genetics , Neurofibromatosis 1/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Neural Networks, Computer
20.
Scand J Med Sci Sports ; 34(4): e14626, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38610121

ABSTRACT

INTRODUCTION: The potential consequences of repeated concussions in sport are well documented. However, it remains unclear whether the cumulative impact of sports-related concussions differs between different contact sports. Therefore, the aim of the current study was to investigate the cumulative effects of sports-related concussions on clinical and neurocognitive health in different contact sports. MATERIALS AND METHODS: In a prospective multicenter study, we examined 507 (74 females) active professional athletes between 18 and 40 years of age from five different contact sports (soccer, handball, American football, basketball, and ice hockey). Data collection involved concussion history, clinical symptom evaluation, neurocognitive assessment, and the collection of other sports-related information. Composite scores were built for clinical symptoms (such as neck pain and balance disturbances) and for neurocognitive symptoms (such as memory and attention impairments). RESULTS: Athletes having suffered 3+ concussions in the past showed disproportionally higher clinical symptom severity than athletes with less than three concussions across all sports. The level of clinical symptom burden in athletes with 3+ concussions indicated mild impairment. The number of past concussions did not affect neurocognitive performance. DISCUSSION: Repeated sports-related concussions appear to have a cumulative impact on clinical-but not cognitive-symptom severity. Although clinical symptom burden in athletes with 3+ concussions in the past was not alarmingly high yet in our sample, increased caution should be advised at this point. Despite few exceptions, results are similar for different contact sports, suggesting a similar multidisciplinary concussion management across all types of sport.


Subject(s)
Basketball , Brain Concussion , Soccer , Female , Humans , Prospective Studies , Athletes , Brain Concussion/complications
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