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Despite copious data linking brain function with changes to social behavior and mental health, little is known about how puberty relates to brain functioning. We investigated the specificity of brain network connectivity associations with pubertal indices and age to inform neurodevelopmental models of adolescence. We examined how brain network connectivity during a peer evaluation fMRI task related to pubertal hormones (dehydroepiandrosterone and testosterone), pubertal timing and status, and age. Participants were 99 adolescents assigned female at birth aged 9-15 (M = 12.38, SD = 1.81) enriched for the presence of internalizing symptoms. Multivariate analysis revealed that within Salience, between Frontoparietal - Reward and Cinguloopercular - Reward network connectivity were associated with all measures of pubertal development and age. Specifically, Salience connectivity linked with age, pubertal hormones, and status, but not timing. In contrast, Frontoparietal - Reward connectivity was only associated with hormones. Finally, Cinguloopercular - Reward connectivity related to age and pubertal status, but not hormones or timing. These results provide evidence that the salience processing underlying peer evaluation is jointly influenced by various indices of puberty and age, while coordination between cognitive control and reward circuitry is related to pubertal hormones, pubertal status, and age in unique ways.

Abstract Background Patients with cancer (PwC) who undergo specific treatments reported greater fatigue and reduced functional capacity as predominant outcomes, compromising their QoL during and following the treatment. Prehabilitation intervention, provided after diagnosis and before treatments, is to optimize the physiological reserve and address modifiable risk factors before surgery or chemotherapy to improve post-treatment results. The primary aim of this study is to obtain a common line of efficacy compared with prehabilitation treatment; the secondary endpoint is to assess the methodological quality of the studies eligible in the review. Methods The systematic review was conducted from September to February 2024, in accordance with PRISMA guidelines. Databases consulted were MEDLINE, Scopus, Web of science and CINAHL, RCTs related to Prehabilitation intervention on PwC were included. The methodological quality of the included studies was assessed through the RoB2 Cochrane tool and the PEDro scale. Meta-analysis was performed to estimate relative treatment effects among evaluated outcomes. Results Forty-two studies were included in the systematic review, 13 were included in the quantitative analysis. The results of the studies reporting reduced postoperative hospital stay, improved endurance, muscle strength, respiratory function, quality of life, and urinary incontinence. Critical analysis of the articles using the PEDro scale revealed 28 RCTs with a good rating, 9 with a fair rating, and 5 with a poor rating; in contrast, the Cochrane RoB2 tool revealed that all articles were at high risk of bias. Meta-analysis showed statistically significant values for 6MWT (38.53, 95%CI 33.03 - 44.04); HADS-depression (-0.71, 95%CI -0.93 -0.49) and HADS-anxiety (-0.49, 95%CI -0.76 -0.23). Conclusions Prehabilitation represents a specific intervention that aims to improve postoperative outcomes in fragile patients undergoing surgery, increasing their preoperative physiological reserve in anticipation of the stress they will face and facilitating the postoperative recovery of functional capacity. Prehabilitation is a good intervention to use, especially in terms of functional capacity and mental health, the latter being very impactful in terms of reduced levels of anxiety and depression. These data make it possible to justify supportive intervention by physical therapists aimed at improving and restoring health-related QoL especially in the short term.

Abstract Molecular dynamics (MD) simulation of the green ionic liquid [C₄mim][PF₆] mixed with polar benzonitrile (BNZ) solvent provides detailed insights into their structural and dynamic properties, essential for electrochemistry and materials science applications. The simulations we carried out at varying mole fractions (X BZN) reveal the mixtures’ physical, structural, and dynamic properties, with radial, spatial, and combined distribution functions, highlighting the effective interaction through H-bonding involved. The simulation indicates that BZN stacks on the cation butyl tail, providing a significant explanation for the unique experimental observations (following). Adding BZN causes the mixture’s liquid dynamics to increase linearly at low X BZN and exponentially at high X BZN, with a notable singular transition at 0.5X BZN. Comprehensive efforts were made to verify and support experimental sum frequency generation (SFG) spectroscopy by simulating the surface structure of the mixtures. Consequently, the simulated BZN stacking structure explains (1) the absence of the C≡N vibrational mode in the SFG spectrum for X BZN < 0.8, and (2) the gradual diminishing of the CH3 SFG signal, which disappears as X BZN approaches 0.5. Finally, this research removes a persistent ambiguity, proving that only the molecular moieties on the surface generate the SFG vibrational signal, while those in the subsurface do not.

Water-in-water (w/w) emulsions, comprising aqueous droplets within another continuous aqueous phase, rely on a low interfacial tension for stability. Thus far, it has been challenging to control their size and stability without the use of stabilizers. In this study, we introduce a microfluidic technique that addresses these challenges, producing stable w/w emulsions with precisely controlled size and uniformity. Results shows that using an acoustically actuated microfluidic mixer, PEG, Dextran, and alginate solutions (84.66 mPa.s viscosity difference) were homogenized rapidly, forming uniformly distributed w/w emulsions stabilized in alginate gels.The emulsion size, uniformity, and shear sensitivity can be tuned by modifying the alginate concentration. Biocompatibility was evaluated by monitoring the viability of kidney cells in the presence of emulsions and gels. In conclusion, this study not only showed emulsion formation with a high mixing efficiency exceeding 90 % for all viscosities, actuated at an optimized frequency of 1.064 MHz, but also demonstrated that an aqueous, solvent, and emulsifier-free composition exhibited remarkable biocompatibility, holding promise for precise drug delivery, cosmetics, and food applications.

High-pressure processing (HPP) has been employed in the food and pharmaceutical industries for multiple applications, such as microbial inactivation, shelf life extension, homogenizing/stabilizing emulsions, suspensions, gels, and other colloidal systems, cold extraction of meat in crustaceans, the opening of mollusks, etc. However, high pressure is known to affect the stability and the quality of barosensitive (i.e., sensitivity because of the level of pressure) components of the bioproducts, such as proteins. In general, Le Chatelier's principle dictates the fate of high molecular weight polymeric compounds like proteins under high pressure, suggesting a tendency to degrade into simpler monomers. From a structural analysis point of view, this generally results in increased tendencies for the protein to denature from its native state and possibly affect its ability to renature. Protein crystallization is also affected favorably or unfavorably by pressure, depending on the effect of pressure on nucleation and crystal growth steps for the particular type of protein. Protein refolding is another effect whose kinetics can be optimized by pressure. This work discusses the mechanisms of the impact of pressure on protein structure, crystallization refolding, and unfolding, with examples of the application of these processes in recent literature.

We prove an existence result for a p-Laplacian problem set in the whole Euclidean space and exhibiting a critical term perturbed by a singular, convective reaction. The approach used combines variational methods, truncation techniques, and concentration compactness arguments, together with set-valued analysis and fixed point theory. De Giorgi’s technique, a priori gradient estimates, and nonlinear regularity theory are employed to obtain local C1,α{C}^{1,\alpha } regularity of solutions, as well as their pointwise decay at infinity. The result is new even in the non-singular case, also for the Laplacian.

Abstract Background Tumor heterogeneity is a main contributor of resistance to anti-cancer targeted agents though it has proven difficult to study. Unfortunately, model systems to functionally characterize and mechanistically study dynamic responses to treatment across coexisting subpopulations of cancer cells remain a missing need in oncology. Methods Using single cell cloning and expansion techniques, we established monoclonal cell subpopulations (MCPs) from a commercially available epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer cell line. We then used this model sensitivity to the EGFR inhibitor osimertinib across coexisting cell populations within the same tumor. Pathway-centered signaling dynamics associated with response to treatment and morphological characteristics of the MCPs were assessed using Reverse Phase Protein Microarray. Signaling nodes differentially activated in MCPs less sensitive to treatment were then pharmacologically inhibited to identify target signaling proteins putatively implicated in promoting drug resistance. Results MCPs demonstrated highly heterogeneous sensitivities to osimertinib. Cell viability after treatment increased > 20% compared to the parental line in selected MCPs, whereas viability decreased by 75% in other MCPs. Reduced treatment response was detected in MCPs with higher proliferation rates, EGFR L858R expression, activation of EGFR binding partners and downstream signaling molecules, and expression of epithelial-to-mesenchymal transition markers. Levels of activation of EGFR binding partners and MCPs’ proliferation rates were also associated with response to c-MET and IGFR inhibitors. Conclusions MCPs represent a suitable model system to characterize heterogeneous biomolecular behaviors in preclinical studies and identify and functionally test biological mechanisms associated with resistance to targeted therapeutics.

Abstract Background Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting. Patients and methods Retrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated. Results Two hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0–7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RRadjusted 1.59 (95%CI:1.09–2.31), 1.46 (95%CI:1.03–2.07) and 1.73 (95%CI:1.27–2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44–0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39–0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css. Conclusions We provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs. Key points Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs.

The motivation to socially connect with peers increases during adolescence in parallel with changes in neurodevelopment. These changes in social motivation create opportunities for experiences that can impact risk for psychopathology, but the specific motivational presentations that confer greater psychopathology risk are not fully understood. To address this issue, we used a latent profile analysis to identify the multidimensional presentations of self-reported social goals in a sample of 220 girls (9-15 years old, M = 11.81, SD = 1.81) that was enriched for internalizing symptoms, and tested the association between social goal profiles and psychopathology. Associations between social goals and brain network connectivity were also examined in a subsample of 138 youth. Preregistered analyses revealed four unique profiles of social goal presentations in these girls. Greater psychopathology was associated with heightened social goals such that higher clinical symptoms were related to a greater desire to attain social competence, avoid negative feedback and gain positive feedback from peers. The profiles endorsing these excessive social goals were characterized by denser connections among social-affective and cognitive control brain regions. These findings thus provide preliminary support for adolescent-onset changes in motivating factors supporting social engagement that may contribute to risk for psychopathology in vulnerable girls.

Abstract Background Listeria monocytogenes is a foodborne pathogen, which can cause a severe illness, especially in people with a weakened immune system or comorbidities. The interactions between host and pathogens and between pathogens and tumor cells have been debated in recent years. However, it is still unclear how bacteria can interact with tumor cells, and if this interaction can affect tumor progression and therapy. Methods In this study, we evaluated the involvement of L. monocytogenes in pre-neoplastic and colorectal cancer cell proliferation and tumorigenic potential. Results Our findings showed that the interaction between heat-killed L. monocytogenes and pre-neoplastic or colorectal cancer cells led to a proliferative induction; furthermore, by using a three-dimensional cell culture model, the obtained data indicated that L. monocytogenes was able to increase the tumorigenic potential of both pre-neoplastic and colorectal cancer cells. The observed effects were then confirmed as L. monocytogenes-specific, using Listeria innocua as negative control. Lastly, data suggested the Insulin Growth Factor 1 Receptor (IGF1R) cascade as one of the possible mechanisms involved in the effects induced by L. monocytogenes in the human colorectal adenocarcinoma cell line. Conclusions These findings, although preliminary, suggest that the presence of pathogenic bacterial cells in the tumor niches may directly induce, increase, and stimulate tumor progression.