Smart polyaniline nanoparticles with thermal and photothermal sensitivity.

Conductive polyaniline nanoparticles (PANI NPs) are synthesized by oxidation of aniline with persulfate in acid media, in the presence of polymeric stabilizers: polyvinilpyrrolidone (PVP), poly(N-isopropylacrylamide) (PNIPAM), and hydroxylpropylcellulose (HPC). It is observed that the size of the nanoparticles obtained depends on the polymeric stabilizer used, suggesting a mechanism where the aggregation of polyaniline molecules is arrested by adsorption of the polymeric stabilizer. Indeed, polymerization in the presence of a mixture of two polymers having different stabilizing capacity (PVP and PNIPAM) allows tuning of the size of the nanoparticles. Stabilization with biocompatible PVP, HPC and PNIPAM allows use of the nanoparticle dispersions in biological applications. The nanoparticles stabilized by thermosensitive polymers (PNIPAM and HPC) aggregate when the temperature exceeds the phase transition (coil to globule) temperature of each stabilizer (Tpt = 32 °C for PNIPAM or Tpt = 42 °C for HPC). This result suggests that an extended coil form of the polymeric stabilizer is necessary to avoid aggregation. The dispersions are reversibly restored when the temperature is lowered below Tpt. In that way, the effect could be used to separate the nanoparticles from soluble contaminants. On the other hand, the PANI NPs stabilized with PVP are unaffected by the temperature change. UV-visible spectroscopy measurements show that the nanoparticle dispersion changes their spectra with the pH of the external solution, suggesting that small molecules can easily penetrate the stabilizer shell. Near infrared radiation is absorbed by PANI NPs causing an increase of their temperature which induces the collapse of the thermosensitive polymer shell and aggregation of the NPs. The effect reveals that it is possible to locally heat the nanoparticles, a phenomenon that can be used to destroy tumor cells in cancer therapy or to dissolve protein aggregates of neurodegenerative diseases (e.g. Alzheimer). Moreover, the long range control of aggregation can be used to modulate the nanoparticle residence inside biological tissues.

Liquid Biopsies for Monitoring Medulloblastoma: Circulating Tumor DNA as a Biomarker for Disease Progression and Treatment Response.

Pediatric brain tumors, including medulloblastoma (MB), represent a significant challenge in clinical oncology. Early diagnosis, accurate monitoring of therapeutic response, and the detection of minimal residual disease (MRD) are crucial for improving outcomes in these patients. This review aims to explore recent advancements in liquid biopsy techniques for monitoring pediatric brain tumors, with a specific focus on medulloblastoma. The primary research question is how liquid biopsy techniques can be effectively utilized for these purposes. Liquid biopsies, particularly the analysis of circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF), are investigated as promising noninvasive tools. This comprehensive review examines the components of liquid biopsies, including ctDNA, cell-free DNA (cfDNA), and microRNA (miRNA). Their applications in diagnosis, prognosis, and MRD assessment are critically assessed. The review also discusses the role of liquid biopsies in categorizing medulloblastoma subgroups, risk stratification, and the identification of therapeutic targets. Liquid biopsies have shown promising applications in the pediatric brain tumor field, particularly in medulloblastoma. They offer noninvasive means of diagnosis, monitoring treatment response, and detecting MRD. These biopsies have played a pivotal role in subgroup classification and risk stratification of medulloblastoma patients, aiding in the identification of therapeutic targets. However, challenges related to sensitivity and specificity are noted. In conclusion, this review highlights the growing importance of liquid biopsies, specifically ctDNA analysis in CSF, in pediatric brain tumor management, with a primary focus on medulloblastoma. Liquid biopsies have the potential to revolutionize patient care by enabling early diagnosis, accurate monitoring, and MRD detection. Nevertheless, further research is essential to validate their clinical utility fully. The evolving landscape of liquid biopsy applications underscores their promise in improving outcomes for pediatric brain tumor patients.

Rasch development and validation of the "Medellín Dry Eye Inventory" (ME·Dry), an instrument to measure multidimensional quality of life compromise in patients with dry eye disease.

Purpose: Dry eye disease (DED) is a common condition that affects the quality of life. There is a great need for better-developed scales that comply with Rasch model requirements. Methods: Prospective study including patients with DED. A series of focus groups were performed to determine the best items to be included. A Rasch modeling methodology was used to validate the Medellín Dry Eye Inventory (ME·Dry). After iterative analysis and scale modification, a final version of the scale was attained which complied with the Rasch analysis expectations. Correlation between the different subscales of the ME·Dry and the Ocular Surface Disease Index (OSDI) was evaluated through Spearman correlation. Results: A total of 166 patients with DED were included. Rasch modeling demonstrated an excellent behavior for the ME·Dry, including four subscales: Symptoms, Triggers, Activity Limitation, and Emotional Compromise. Infit and Outfit parameters were all between 0.50 and 1.50, with excellent category utilization. Person and item separation and reliability were excellent for all subscales. There was a need for a category collapsing for the Emotional Compromise subscale. There was a strong correlation between the different subscales of the ME·Dry except for the Emotional Compromise subscale, which seems to be independent. Conclusion: The ME·Dry is a reliable scale, complying with the Rasch model expectations, that allows for a reliable measurement of quality of life compromise in patients with DED. Emotional compromise secondary to DED does not seem to correlate with disease severity as assessed by the other quality-of-life subscales.

Deltamethrin-Evoked ER Stress Promotes Neuroinflammation in the Adult Mouse Hippocampus.

Endoplasmic reticulum (ER) stress and neuroinflammation are involved in the pathogenesis of many neurodegenerative disorders. Previously, we reported that exposure to pyrethroid insecticide deltamethrin causes hippocampal ER stress apoptosis, a reduction in neurogenesis, and learning deficits in adult male mice. Recently, we found that deltamethrin exposure also increases the markers of neuroinflammation in BV2 cells. Here, we investigated the potential mechanistic link between ER stress and neuroinflammation following exposure to deltamethrin. We found that repeated oral exposure to deltamethrin (3 mg/kg) for 30 days caused microglial activation and increased gene expressions and protein levels of TNF-α, IL-1ß, IL-6, gp91phox, 4HNE, and iNOS in the hippocampus. These changes were preceded by the induction of ER stress as the protein levels of CHOP, ATF-4, and GRP78 were significantly increased in the hippocampus. To determine whether induction of ER stress triggers the inflammatory response, we performed an additional experiment with mouse microglial cell (MMC) line. MMCs were treated with 0-5 µM deltamethrin for 24-48 h in the presence or absence of salubrinal, a pharmacological inhibitor of the ER stress factor eIF2α. We found that salubrinal (50 µM) prevented deltamethrin-induced ER stress, as indicated by decreased levels of CHOP and ATF-4, and attenuated the levels of GSH, 4-HNE, gp91phox, iNOS, ROS, TNF-α, IL-1ß, and IL-6 in MMCs. Together, these results demonstrate that exposure to deltamethrin leads to ER stress-mediated neuroinflammation, which may subsequently contribute to neurodegeneration and cognitive impairment in mice.

Anticoagulant therapy for venous thromboembolism in patients with inflammatory bowel disease.

BACKGROUND: There is lack of evidence to guide the type, intensity, and the duration of anticoagulation following venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Registro Informatizado Enfermedad Trombo Embólica (RIETE) is an ongoing, multicenter, observational registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We used the RIETE database to compare the rate of VTE recurrences and major bleeding during the course of anticoagulation in noncancer patients with or without IBD. RESULTS: As of October 2014, 41 927 patients without active cancer have been recruited in RIETE. Of these, 265 (0.63%) had IBD and 85 (32%) had the VTE during an acute flare. The duration of anticoagulation was similar in patients with VTE during an acute flare (8.3±8.8 months), in remission (9.4±11.5 months), or without IBD (10.0±12.8 months). The rate of VTE recurrences [7.25, 95% confidence interval (CI): 1.46-21.2; 8.84, 95% CI: 3.23-19.2; and 5.85, 95% CI: 5.46-6.26 per 100 patient-years, respectively] and major bleeding (7.25, 95% CI: 1.46-21.2; 2.95, 95% CI: 0.33-10.6; and 4.79, 95% CI: 4.44-5.15, respectively) were similar in all three subgroups. Propensity score matching analysis confirmed the absence of differences in the rate of VTE recurrences (rate ratio: 1.16, 95% CI: 0.54-2.47) or major bleeding (rate ratio: 0.84, 95% CI: 0.31-2.23) between patients with or without IBD. CONCLUSION: Therapeutic anticoagulation for patients with IBD and VTE is as safe and effective as for those with VTE without IBD.