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BackgroundElderly breast cancer patients are frequently affected by significant comorbidities that make sophisticated radiotherapy treatments particularly challenging.AimsWe dosimetrically analyzed two different simple free-breathing external beam radiotherapy (EBRT) techniques for the hypofractionated treatment of the left breast in elderly patients with a low compliance, to compare target coverage, and heart and left anterior descending coronary artery (LADCA) sparing.MethodsWe developed radiation plans for 24 elderly patients using 3D conformal (3DCRT) field-in-field tangential technique and intensity-modulated (IMRT) tangential beam technique. Dose-Volume-Histograms (DVHs) were used to provide a quantitative comparison between plans.ResultsThe median breast volume was 645 cm3. IMRT and 3DCRT plans comparison demonstrated no significant differences in terms of organ sparing for the heart. Regarding LADCA, mean dose (10.3 ± 9.5 Gy vs 11.9 ± 9.6 Gy, p = 0.0003), maximum dose (26.1 ± 16.1 Gy vs 29.1 ± 16.1 Gy, p = 0.004) and V17 Gy (21.5% ± 26.9% vs 25.0% ± 27.2%, p = 0.002) significantly decreased using IMRT compared with 3DCRT. IMRT plans showed a better target coverage compared with 3DCRT (0.91 ± 0.05 vs 0.93 ± 0.04, p = 0.05).DiscussionComparing the two different EBRT techniques, we demonstrated few, although substantial, dosimetric differences in terms of doses to the organs at risk characterized by a statistically significant dose reduction of LADCA in the IMRT plans.ConclusionsElderly patients with a low compliance to treatment might benefit from 3DCRT with field-in-field tangential arrangement or from a simple IMRT approach. IMRT should be preferred.

Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes and extra-pineal cells, plays an important role in timing circadian rhythms (24-h internal clock) and regulating the sleep/wake cycle in humans. However, in recent years melatonin has gained much attention mainly because of its demonstrated powerful lipophilic antioxidant and free radical scavenging action. Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant. Melatonin-induced signal transduction through melatonin receptors promotes the expression of antioxidant enzymes as well as inflammation-related genes. Melatonin also exerts an immunomodulatory action through the stimulation of high-affinity receptors expressed in immunocompetent cells. Here, we reviewed the efficacy, safety and side effects of melatonin supplementation in treating oxidative stress- and/or inflammation-related disorders, such as obesity, cardiovascular diseases, immune disorders, infectious diseases, cancer, neurodegenerative diseases, as well as osteoporosis and infertility.

We investigate a Dicke quantum battery in the dispersive regime, where the photons trapped in a resonant cavity are much more energetic with respect to the two-level systems embedded into it. Under such off-resonant conditions, even an empty cavity can lead to the charging of the quantum battery through a proper modulation of the matter–radiation coupling. This counterintuitive behaviour has its roots in the effective interaction between two-level systems mediated by virtual photons emerging from the fluctuations of the quantum electromagnetic field. In order to properly characterize it, we address relevant figures of merit such as the stored energy, the time required to reach the maximum charging, and the averaged charging power. Moreover, the possibility of efficiently extracting energy in various ranges of parameters is discussed. The scaling of stored energy and power as a function of the number N of two-level systems and for different values of the matter–radiation coupling is also discussed, showing, in the strong coupling regime, performances in line with what is reported for the Dicke quantum battery in the resonant regime.

The increasing prevalence of metabolic dysfunction-associated fatty liver disease (MASLD) in children requires robust, non-invasive biomarkers to enable accurate disease staging and risk stratification. Elevated serum levels of homocysteine (Hcy) have emerged as potential risk factors for cardiometabolic disease in adults, including MASLD. In this observational retrospective study, we investigated the role of serum Hcy levels as a potential biomarker for disease severity and liver fibrosis in a pediatric cohort of 182 children with MASLD. In 89 patients, liver biopsy allowed the classification into metabolic dysfunction-associated steatohepatitis (MASH). Associations between Hcy, metabolic parameters, fibrosis scores, and histological features were examined, and the diagnostic performance of Hcy for liver fibrosis was evaluated using ROC analysis. Multivariate analyses identified elevated Hcy levels as independently associated with HOMA-IR (β = 0.55; p = 0.049), TG/HDL ratio (β = 3.23; p = 0.002), and liver fibrosis (β = 2.59; p = 0.04). Hcy showed a predictive accuracy of 81% for fibrosis. However, the combined diagnostic models of Hcy with non-invasive fibrotic scores (i.e., APRI and FIB-4) or TG/HDL ratio showed only a modest accuracy (AUC = 0.62–0.69). In conclusion, our data suggest that Hcy is associated with fibrosis and cardiometabolic risk. However, these results should be interpreted as exploratory and do not establish homocysteine as a diagnostic biomarker.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic progressive hepatopathy in children, and the identification of non-invasive biomarkers is urgently needed. Growth differentiation factor 15 (GDF15) was associated with MASLD in adults. In this study, we investigated the circulating and hepatic levels of GDF15 and their association with liver damage in pediatric MASLD and in a murine model. This observational study included 158 children with biopsy-proven MASLD. Patients with MASLD were categorized into two groups based on steatohepatitis (MASH) presence and evaluated for GDF15 circulating levels, while GDF15 hepatic levels were assessed only in a subset of patients. Children with MASLD exhibited higher levels of circulating GDF15 compared to the controls. Moreover, the MASH subgroup had significantly higher values of GDF15 compared to the Not-MASH subgroup. The GDF15 levels in the MASH subgroup showed a positive correlation with fibrosis. Finally, the hepatic expression of the GDF15 gene correlated with GDF15 circulating levels and with the hepatic expression of the COL1A1 and COL3A1 genes in 15 children with MASLD. In conclusion, our study demonstrated that GDF15 levels are associated with liver damage, reinforcing the potential role of GDF15 as a biomarker for MASLD-related fibrosis in children.

Background/Objectives: Echocardiography is the reference standard for grading aortic stenosis (AS); however, it yields discordant severity estimates in up to 40% of patients. Multidetector computed tomography (MDCT)-derived methods for calculating aortic valve area (AVA) may improve diagnostic concordance, but their diagnostic performance, validation against invasive hemodynamics, and the influence of left ventricular outflow tract (LVOT) morphology on severity grading remain insufficiently investigated. Methods: We retrospectively analyzed 307 patients with normal-flow, high-gradient calcific AS who underwent echocardiography, MDCT, and cardiac catheterization. AVA was calculated using (1) echocardiographic LVOT diameter, (2) hybrid Doppler–MDCT planimetric LVOT area, and (3) corrected echocardiographic LVOT diameter (×1.13). Agreement, correlation, and diagnostic performance were assessed using Bland–Altman analysis, Pearson correlation, ROC analysis, and McNemar’s test. Subgroups defined by diagnostic concordance and MDCT-derived LVOT size were compared using ANOVA. Results: Hybrid AVA showed a strong correlation with echocardiographic AVA (r = 0.749, p < 0.001), with a mean difference of +0.11 ± 0.15 cm2. Both methods demonstrated similar relationships with invasive and non-invasive hemodynamic markers of AS severity. When combined with echocardiography, the hybrid method increased concordant classification of severe AS by 8%. In contrast, corrected AVA performed significantly worse, leading to more discordant classifications. LVOT size was significantly associated with variability in AVA and Doppler velocity index, independent of flow status. Conclusions: Hybrid MDCT-derived AVA provides diagnostic performance equivalent to echocardiography and improves concordance in selected patients. LVOT size influences key echocardiographic parameters and may warrant tailored diagnostic thresholds.

During pregnancy, fetal cells can migrate to the mother blood circulation. A percentage of these cells survive in maternal tissues for decades generating a population of fetal microchimeric cells (fMCs), whose biological role is unclear. The aim of this study was to investigate the association between the sex of offspring, an indirect marker of fMCs, and magnetic resonance imaging (MRI) features in women with multiple sclerosis (MS). We recruited 26 nulliparous MS patients (NPp), 20 patients with at least one male son (XYp), and 8 patients with only daughters (XXp). Each patient underwent brain MR scan to acquire 3D-T2w FLAIR FatSat and 3D-T1w FSPGR/TFE. Lesion Segmentation Tool (LST) and FreeSurfer were used to obtain quantitative data from MRI. Additional data were collected using medical records. Multiple regression models were applied to evaluate the association between sex of offspring and MS data. Comparing NPp and XXp, we found that NPp had larger 4th ventricle volume (2.02 ± 0.59 vs. 1.70 ± 0.41; = 0.022), smaller left entorhinal volume (0.55 ± 0.17 vs. 0.68 ± 0.25; = 0.028), and lower thickness in the following cortical areas: left paracentral (2.34 ± 0.16 vs. 2.39 ± 0.17; = 0.043), left precuneus (2.27 ± 0.11 vs. 2.34 ± 0.16; = 0.046), right lateral occipital (2.14 ± 0.11 vs. 2.25 ± 0.08; = 0.006). NPp also had lower thickness in left paracentral cortex (2.34 ± 0.16 vs. 2.46 ± 0.17; = 0.004), left precalcarine cortex (1.64 ± 0.14 vs. 1.72 ± 0.12; = 0.041), and right paracentral cortex (2.34 ± 0.17 vs. 2.42 ± 0.14; = 0.015) when compared to XYp. Comparing XYp and XXp, we found that XYp had higher thickness in left cuneus (1.80 ± 0.14 vs. 1.93 ± 0.10; = 0.042) and left pericalcarine areas (1.59 ± 0.19 vs. 1.72 ± 0.12; = 0.032) and lower thickness in right lateral occipital cortex (2.25 ± 0.08 vs. 2.18 ± 0.13; = 0.027). Our findings suggested an association between the sex of offspring and brain atrophy. Considering the sex of offspring as an indirect marker of fMCs, we speculated that fMCs could accumulate in different brain areas modulating MS neuropathological processes.

Background:Serotonin and γ–aminobutyric acid (GABA) transmission is crucial in coping strategies.Methods:Here, using mice from 2 inbred strains widely exploited in behavioral neurochemistry, we investigated whether serotonin transmission in medial prefrontal cortex and GABA in basolateral amygdala determine strain-dependent liability to stress response and differences in coping.Results:C57BL/6J mice displayed greater immobility in the forced swimming test, higher serotonin outflow in medial prefrontal cortex, higher GABA outflow in basolateral amygdala induced by stress, and higher serotonin 1A receptor levels in medial prefrontal cortex accompanied by lower GABAb receptor levels in basolateral amygdala than DBA/2J mice. In assessing whether serotonin in medial prefrontal cortex determines GABA functioning in response to stress and passive coping behavior in C57BL/6J and DBA/2J mice, we observed that selective prefrontal serotonin depletion in C57BL/6J and DBA/2J reduced stress-induced GABA outflow in basolateral amygdala and immobility in the forced swimming test.Conclusions:These results show that strain-dependent prefrontal corticolimbic serotonin/GABA regulation determines the strain differences in stress-coping behavior in the forced swimming test and point to a role of a specific neuronal system in genetic susceptibility to stress that opens up new prospects for innovative therapies for stress disorders.

Despite the wide knowledge about prevalent effects of ocean acidification on single species, the consequences on species interactions that may promote or prevent habitat shifts are still poorly understood. Using natural CO 2 vents, we investigated changes in a key tri-trophic chain embedded within all its natural complexity in seagrass systems. We found that seagrass habitats remain stable at vents despite the changes in their tri-trophic components. Under high p CO 2 , the feeding of a key herbivore (sea urchin) on a less palatable seagrass and its associated epiphytes decreased, whereas the feeding on higher-palatable green algae increased. We also observed a doubled density of a predatory wrasse under acidified conditions. Bottom-up CO 2 effects interact with top-down control by predators to maintain the abundance of sea urchin populations under ambient and acidified conditions. The weakened urchin herbivory on a seagrass that was subjected to an intense fish herbivory at vents compensates the overall herbivory pressure on the habitat-forming seagrass. Overall plasticity of the studied system components may contribute to prevent habitat loss and to stabilize the system under acidified conditions. Thus, preserving the network of species interactions in seagrass ecosystems may help to minimize the impacts of ocean acidification in near-future oceans.

In the “Sicilian study on juvenile myocardial infarction,” we had evaluated plasma viscosity (PV) and neutrophil/lymphocyte ratio (NLR) in patients with acute myocardial infarction (AMI) at the age of ⩽45 years. Now, we examined the relationship between these 2 parameters in 120 subjects (109 men and 11 women) aged ⩽45 years with recent AMI. The patients were classified according to the number of cardiovascular risk factors, the electrocardiographic criteria (ST-segment elevation myocardial infarction [STEMI] or non-ST-segment elevation myocardial infarction [NSTEMI]), and the extent of coronary stenosis, evaluated with coronary angiography. On fasting venous blood, we measured PV at the shear rate of 450 s−1 and NLR. The control group included 50 healthy subjects (mean age = 35.1 ± 7.8 years). At the initial stage, PV and NLR were significantly increased in comparison with controls. Subdividing AMI patients according to the median value of NLR, in the group with high NLR PV was significantly higher, whereas subdividing the patients according to the PV median value, NLR was not different between the 2 groups; 3 and 12 months after AMI, we observed only a significant decrease in NLR. Only PV was discriminant regarding the cardiovascular complications registered during an 18-month follow-up. The evaluation of PV may be of prognostic value in juvenile AMI.