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Abstract Objective Epileptic seizures occurring in late adulthood often remain of unknown origin. Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by intracerebral hemorrhage, microhemorrhage and superficial siderosis, occurring mostly in elderly. This observational case–control study aimed to assess the occurrence of CAA in patients experiencing their first seizure in late adulthood. Methods We enrolled consecutive patients aged ≥55 years presenting with late‐onset seizures (LOS) to the emergency departments or outpatient clinics of two Italian centers, from April 2021 to October 2022. Two age‐matched control subjects with neurological symptoms other than epileptic seizure were recruited for each enrolled case. All participants underwent brain MRI (1.5 Tesla) including blood‐sensitive sequences and were assessed for probable CAA diagnosis according to Boston criteria 2.0. Chi‐squared test was performed to evaluate group differences. Univariate logistic regression analysis tested the association between clinical variables and CAA. Results We included 65 patients with LOS (27 females; mean age 72.2 ± 8.9 years) and 130 controls (49 females; mean age 70.3 ± 8.9 years). Diagnosis of probable CAA was achieved in 10.8% (7/65) of LOS patients and 2.3% (3/130) controls, with a statistically significant difference (p = 0.011). The OR for CAA in the LOS group was 5.2 as compared to the control group (95% CI = 1.3–20.6, p = 0.02). Significance The frequency of CAA is significatively higher in patients with LOS as compared to other neurological diseases, suggesting that a portion of LOS of unknown or vascular origin are associated with CAA. Plain Language Summary Late‐onset seizures (LOS) are very frequent in the elderly and often have no clear cause. Cerebral amyloid angiopathy (CAA) is a condition where amyloid proteins build up in the blood vessels of the brain, causing them to become weak and prone to bleeding. In this study, we explored the occurrence of CAA in people with LOS. We found that people with LOS were more likely to have a diagnosis of CAA than controls (i.e., people with other neurological diseases).

Abstract Aims We report the results of a real‐world study based on heart failure (HF) patients' continuous remote monitoring strategy using the CardioMEMS system to assess the impact of this device on healthcare outcomes, costs, and patients' management and quality of life. Methods and results We enrolled seven patients (69.00 ± 4.88 years; 71.43% men) with HF, implanted with CardioMEMS, and daily remote monitored to optimize both tailored adjustments of home therapy and/or hospital infusions of levosimendan. We recorded clinical, pharmacological, biochemical, and echocardiographic parameters and data on hospitalizations, emergency room access, visits, and costs. Following the implantation of CardioMEMS, we observed a 50% reduction in the total number of hospitalizations and a 68.7% reduction in the number of days in the hospital. Accordingly, improved patient quality of life was recorded with EQ‐5D (pre 58.57 ± 10.29 vs. 1 year post 84.29 ± 19.02, P = 0.008). Echocardiographic data show a statistically significant improvement in both systolic pulmonary artery pressure (47.86 ± 8.67 vs. 35.14 ± 9.34, P = 0.022) and E/e′ (19.33 ± 5.04 vs. 12.58 ± 3.53, P = 0.023). The Quantikine® HS High‐Sensitivity Kit determined elevated interleukin‐6 values at enrolment in all patients, with a statistically significant reduction after 6 months (P = 0.0211). From an economic point of view, the net savings, including the cost of CardioMEMS, were on average €1580 per patient during the entire period of observation, while the analysis performed 12 months after the implant vs. 12 months before showed a net saving of €860 per patient. The ad hoc analysis performed on the levosimendan infusions resulted in 315 days of hospital avoidance and a saving of €205 158 for the seven patients enrolled during the observation period. Conclusions This innovative strategy prevents unplanned access to the hospital and contributes to the efficient use of healthcare facilities, human resources, and costs.

Anthemis L. 1753 is a species-rich genus of Asteraceae. It includes species of economic value as ornamental, edible and medicinal plants. We report here the complete chloroplast genome of Anthemis cretica subsp. calabrica (Arcang.) R. Fern. 1975, the first chloroplast genome of any Anthemis species. For the scope, we have used long reads obtained with Oxford Nanopore technology. The assembled plastome is 149,509 bp long and is subdivided in a large single-copy region (LSC, 82,317 bp), a small single-copy region (SSC, 18,212 bp) and two inverted repeat regions (IR: 24,490 bp). It comprehends 136 predicted genes, of which 92 protein-coding genes, 35 tRNAs, and 8 rRNAs. The overall GC content is 37.54%. The position of A. cretica subsp. calabrica in the phylogenetic tree is congruent with those of previous analyses based on a few chloroplast or nuclear regions.

Background: Long-haul truck drivers (LHTD) experience disproportionately greater chronic disease risk, which may be influenced by both occupational and lifestyle factors. This study aimed to explore the multilevel factors associated with LHTD's diet and physical activity (PA). Methods: Thirty in-depth interviews were conducted with LHTD in the Southern California border region. Interview questions captured occupational and lifestyle factors relating to PA and diet at multiple levels and were analyzed using thematic analysis. Results: Emergent themes relating to both diet and PA included time constraints, attitudes and perceived beliefs, and accessibility of environments to engage in PA and healthy eating. Themes specific to PA were weather conditions and flatbed job duties. Themes specific to diet included access to refrigerators/microwaves and social interactions. Conclusion: Findings from this study can inform the development of tailored, multi-level interventions to encourage PA and healthy dietary behaviors among LHTD.

Abstract The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role in shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) in CTL in the context of adoptive T cell therapy (ACT) elicits phenotypic and functional alterations, resulting in a robust antitumor immunity in preclinical models in female mice. In addition, the combination of anti-PDL1 treatment with LSD1i-based ACT eradicates the tumor and leads to long-lasting tumor-free survival in a melanoma model, complementing the limited efficacy of the immune or epigenetic therapy alone. Collectively, these results demonstrate that LSD1 modulation improves antitumoral responses generated by ACT and anti-PDL1 therapy, providing the foundation for their clinical evaluation.

Many heritage buildings from ancient Rome are being refurbished based on their original plan’s structure. One of them is the piscina mirabilis located nearby in Naples, which was a cistern used by the Romans to collect drinkable water for the navy waiting in the port of Misenum. The piscina mirabilis has similar architectural characteristics to a “cathedral”; however, its current precarious architectural state is the result of high levels of humidity that have caused the proliferation of mold on its vertical and horizontal surfaces over the centuries. Acoustic measurements were conducted inside the piscina mirabilis, highlighting an existing condition of the room being very reverberant, not suitable for occasional speech and conversations. The design proposed by the authors involves some mitigation solutions for the acoustics, mainly focused on controlling the low–medium frequencies and the realization of a restoration project consisting of a raised timber-floored walkway that runs along the perimeter walls, with the addition of water covering the existing floor as a natural element dominating the room volume, which represents the primary function of the building in antiquity. A waterfall was designed to be on the northern side wall. Acoustic studies were an important part of the refurbishment strategy, and a mitigation solution was devised to control medium–low frequencies by using inflated balloons of different sizes that were suspended from the ceiling vaults instead of widely used acoustic panels. The proposed strategy lowered the reverberation time by 3–4 s to accommodate a minimal level of conversational understanding. Such a solution is appropriate for this heritage building as well as other future conservation projects.

Objective: Suicide is the second leading cause of death among college-age students in the U.S., with disparities in suicide ideation and attempts among Latinas. The current study aims to examine if depression severity predicts suicide ideation and attempts and to examine if caregiver intergeneration acculturation conflict (IAC) moderates this link. Participants: A sample of 246 Mexican-descent female college students. Methods: Self-reported measures for depression severity, male and female caregiver IAC, and suicide ideation and attempts in the previous 12-months were ascertained. Results: In our sample, 31.1% endorsed suicide ideation and 15.9% suicide attempts. Controlling for age, both male and female caregiver IAC moderated the relationship between depression severity and suicide ideation. A similar moderation pattern emerged for the suicide attempts outcome. Conclusions: Understanding this exacerbating contextual factor can help inform prevention/intervention efforts targeting Mexican-descent college students who are experiencing depressive symptoms by focusing on decreasing IAC with both caregivers.

Abstract The worldline formalism is a useful scheme in Quantum Field Theory which has also become a powerful tool for numerical computations. It is based on the first quantisation of a point-particle whose transition amplitudes correspond to the heat-kernel of the operator of quantum fluctuations of the field theory. However, to study a quantum field theory in a bounded manifold one needs to restrict the path integration domain of the point-particle to a specific subset of worldlines enclosed by those boundaries. In the present article it is shown how to implement this restriction for the case of a spinor field in a two-dimensional curved half-plane under MIT bag boundary conditions, and compute the first few heat-kernel coefficients as a verification of the proposed construction. This construction admits several generalisations.

Abstract Mutations in CHCHD10, a mitochondrial protein with undefined functions, are associated with autosomal dominant mitochondrial diseases. Chchd10 knock-in mice harboring a heterozygous S55L mutation (equivalent to human pathogenic S59L) develop a fatal mitochondrial cardiomyopathy caused by CHCHD10 aggregation and proteotoxic mitochondrial integrated stress response (mtISR). In mutant hearts, mtISR is accompanied by a metabolic rewiring characterized by increased reliance on glycolysis rather than fatty acid oxidation. To counteract this metabolic rewiring, heterozygous S55L mice were subjected to chronic high-fat diet (HFD) to decrease insulin sensitivity and glucose uptake and enhance fatty acid utilization in the heart. HFD ameliorated the ventricular dysfunction of mutant hearts and significantly extended the survival of mutant female mice affected by severe pregnancy-induced cardiomyopathy. Gene expression profiles confirmed that HFD increased fatty acid utilization and ameliorated cardiomyopathy markers. Importantly, HFD also decreased accumulation of aggregated CHCHD10 in the S55L heart, suggesting activation of quality control mechanisms. Overall, our findings indicate that metabolic therapy can be effective in mitochondrial cardiomyopathies associated with proteotoxic stress.

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case–control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4′-DDT and 4,4′-DDE) were measured in the serum by liquid or gas chromatography–mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants’ levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10–3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41–0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants’ mixture and TC. BRAFV600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case–control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants’ mixture, likely due to a potential reverse causality.

Background The percentage of women

In aqueous environment amphiphilic molecules organize themselves into supramolecular structures deeply affecting the chemo-physical properties. Supramolecular assemby is also crucial in the pharmaceutical development of bioactive lipophilic molecules whose attitude to self-aggregate is a recognized factor affecting the in vivo pharmacokinetic, but can also play a crucial role in the interaction with the biological targets in in vitro tests. In aqueous solution, amphiphilic drugs exist in a complex equilibrium involving free monomers, oligomers and larger supramolecular aggregates held together by noncovalent bonds. In this review we focus our attention on the dual effect of drugs self-assembly, which can both reduce the availability of active compounds and create multivalent scaffolds, potentially improving binding affinity and avidity to cellular targets. We examine the effect of aggregation on different classes of amphiphatic molecules with significant biological activities, such as immunomodulatory, anti-tumor, antiviral, and antibiotic.Our purpose is to provide a comprehensive overview of how supramolecular chemistry influences the pharmacological and biological responses of amphiphilic molecules, emphasizing the need to consider these effects in early-stage drug development and in vitro testing. By elucidating these phenomena, this review aims to offer insights into optimizing drug design and formulation to overcome challenges posed by self-aggregation.

Chloroplast genomes (plastomes) represent a very important source of valuable information for phylogenetic and biogeographic reconstructions. The use of short reads (as those produced from Illumina sequencing), along with de novo read assembly, has been considered the “gold standard” for plastome reconstruction. However, short reads often cannot reconstruct long repetitive regions in chloroplast genomes. Long Nanopore (ONT) reads can help bridging long repetitive regions but are by far more error-prone than those produced by Illumina sequencing. Verbesina is the largest genus of tribe Heliantheae (Asteraceae) and includes species of economic importance as ornamental or as invasive weeds. However, no complete chloroplast genomes have been published yet for the genus. We utilized Illumina and Nanopore sequencing data and different assembly strategies to reconstruct the plastome of Verbesina alternifolia and evaluated the usefulness of the Nanopore assemblies. The two plastome sequence assemblages, one obtained with the Nanopore sequencing and the other inferred with Illumina reads, were identical, except for missing bases in homonucleotide regions. The best-assembled plastome of V. alternifolia was 152,050 bp in length and contained 80, 29, and four unique protein-coding genes, tRNAs, and rRNAs, respectively. When used as reference for mapping Illumina reads, all plastomes performed similarly. In a phylogenetic analysis including 28 other plastomes from closely related taxa (from the Heliantheae alliance), the two Verbesina chloroplast genomes grouped together and were nested among the other members of the tribe Heliantheae s.str. Our study highlights the usefulness of the Nanopore technology for assembling rapidly and cost-effectively chloroplast genomes, especially in taxonomic groups with paucity of publicly available plastomes.

Designer fuel fraud consists in the smuggling of modified diesel blends as engine lubricant oils and their illegal trade avoiding payment of the excise duty applied to energy products. The fraudulent mixture contains regular diesel fuel plus a heavier hydrocarbon fraction, originating from waste automotive lubricant or cheap, residual base oils.Raman spectroscopy was tested as a rapid in-situ screening method to separate regular diesel fuel samples from those suspected to contain a heavier component, and thus demanding a more extensive characterization. The Raman fingerprint region from the screened sample is matched to purposely created spectral libraries of compliant and non-compliant diesel fuels using the instrumental search algorithm. Overall, 177 compliant fuel samples and 28 non-compliant samples (all designer fuels with a confirmed heavier fraction and/or anomalous distillation parameters) were measured. The designer fuels were all positively identified, with ∼18 % false positives.Subsequently, the Raman data-set was studied by Principal Component Analysis (PCA) and then classified as either compliant or non-compliant using Linear Discriminant Analysis (LDA). PCA using up to three principal components for data visualization shows only an incipient separation but still a partial overlap between compliant and non-compliant samples. LDA, on the opposite, performed superiorly in the binary classification task, with no false negatives and less than 4 % false positives.