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Delusions are commonly conceived as false beliefs that are held with certainty and which cannot be corrected. This conception of delusion has been influential throughout the history of psychiatry and continues to inform how delusions are approached in clinical practice and in contemporary schizophrenia research. It is reflected in the full psychosis continuum model, guides psychological and neurocognitive accounts of the formation and maintenance of delusions, and it substantially determines how delusions are approached in cognitive-behavioural treatment. In this Review, we draw on a clinical-phenomenological framework to offer an alternative account of delusion that incorporates the experiential dimension of delusion, emphasising how specific alterations to self-consciousness and reality experience underlie delusions that are considered characteristic of schizophrenia. Against that backdrop, we critically reconsider the current research areas, highlighting empirical and conceptual issues in contemporary delusion research, which appear to largely derive from an insufficient consideration of the experiential dimension of delusions. Finally, we suggest how the alternative phenomenological approach towards delusion could offer new ways to advance current research and clinical practice.As a setting where children and adolescents live and learn, linked to the family and embedded within the wider community, schools have an important influence on every student's health. Many health interventions have used schools as a platform, often for standalone programmatic initiatives to reduce health risks, and sometimes for more comprehensive approaches, but the interventions, uptake, and sustainability are generally disappointing. Evidence shows that, to improve health and to reduce inequality, all students must attend school from a young age and for as long as possible, and their educational success therein must be maximised. Thus, beyond educational benefits, schools are also important for health. Coherence between each school's policies, structures and systems, human resources, and practices is required to advance both academic and health outcomes. Beyond simply implementing ready-made programmes into schools, health professionals can position themselves as catalysts for structural change as they have many opportunities to advocate for, and participate in, the intersectoral implementation of reforms and innovations in school systems to promote the health of all students.Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC50 (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.MF59, an oil-in-water nanoemulsion, has been used in licensed seasonal influenza vaccines for many years. Administration of such vaccines by injection is associated with pain and safety issues. Here, we evaluated the potential of administering MF59 via a transcutaneous route with antigen loading (either encapsulated into or mixed with MF59) to intact or microneedle-pretreated skin. In addition to commercial MF59, we also prepared a nanoemulsion to encapsulate hydrophilic antigens by mimicking the formulation and preparation technique of MF59. The nanoemulsion was prepared using a water-in-oil-in-water emulsion method, and was similar to MF59 in composition, particle size, and morphology. Compared with the intact skin group, the microneedle-pretreated group showed significant enhanced antigen penetration. In vivo transcutaneous immunization analysis showed that the MF59-adjuvant influenza vaccine elicited approximately 3-5 times higher hemagglutination inhibition titers than the influenza solution alone in BALB/c mice after microneedle pretreatment. The intact skin group showed negative immune results at the same dose, suggesting that microneedle pretreatment was critical for efficient delivery of antigens, to obtain strong immune responses. Furthermore, the loading method (encapsulation or mixing with the vehicle) did not affect the dermal penetration or transcutaneous immunization of antigens on microneedle-pretreated skin. Moreover, in vitro cellular assays showed that MF59 facilitated the maturation of dendritic cells and enhanced antigen uptake by antigen-presenting cells. In conclusion, the combination of microneedle pretreatment and mixing of MF59 with antigen provides a simple approach to enhance transcutaneous immunization.A layered double hydroxide (LDH) incorporated with Ocimum basilicum essential oil (OB) was prepared and its acaricide efficacy against Rhipicephalus annulatus tick was investigated. The OB essential oil was extracted from plants farmed in the study area. Selleckchem EGFR inhibitor Zn-Al LDH/Gallate was prepared by co-precipitation method then OB oil was added to obtain OB/LDH nano-composite. The obtained product was characterized by X-Ray Diffraction (XRD), Fourier-transform infrared (FT-IR) and scanning electron microscopy (SEM). The acaricidal activity of different concentrations of the obtained OB/LDH nanocomposite (6.25, 12.5, 25, 50, 100, 200 and 300 l/mL) was evaluated via the adult immersion test (AIT), egg hatchability test (EHT), larval packet test (LPT) and repellency test. OB oil and OB/LDH nano-composite showed 100% adult mortality and prevent egg deposition at a dose of 300 l/mL. Also, eggs hatching was fully inhibited at 300 l/mL while at the concentration of 200 l/mL the inhibition rate was 95%. In LPT, OB/LDH showed a high toxicological effect which leading to 100% and 43% larval mortality at doses of 200 μ l/mL and 100 μl/mL, respectively. Meanwhile OB alone showed 100% and 45% larval mortality at doses of 300 μl/mL and 200 μl/mL, respectively. The LC50, LC90 and LC99 values of OB/LDH and OB were found to be 107.46 versus 209.908 μl/mL, 171.22 versus 282.63 μl/mL and 196.15 versus 298.26 μl/mL, respectively. The repellence activity was lasted for 3 h after application against larvae. OB/LDH was found to be more repellent than OB as evidenced by the RC50 values after 2 h and 3 h (48.82 vs. 79.99 μl/mL and 89.47 vs. 185.32μ l/mL, respectively). Overall, our results proved that LDH enhanced the larvaicidal and repellent efficacy of OB against R. annulatus tick larvae.Diabetes mellitus (DM) has become an epidemic disorder that is an escalating public health risk. Currently, DM treatment is highly challenging due to temporary medical relief rather than a permanent cure. This article reports a ligand-anchored mixed micellar system formed by phospholipids and N -oleoyl-D-galactosamine aiming to enhance the oral bioavailability and hypoglycemic effects of berberine, an antidiabetic agent with poor absorption. Berberine-loaded mixed micelles (BBMMs) were prepared through a solvent diffusion technique. The resulting BB-MMs were characterized by particle size, potential, morphology, entrapment efficiency (EE) and in vitro release. The oral pharmacokinetics and hypoglycemic efficacy of BB-MMs were evaluated in rats and compared with a berberine suspension. As a result, BB-MMs prepared with the preferable formulation had a particle size of approximately 100 nm with an EE of over 85%. BB-MMs exhibited sustained drug release owing to the entrapment in the micelles. After oral administration, BB-MMs ameliorated the pharmacokinetic profile of berberine and significantly enhanced its oral bioavailability (317.17% relative to the suspension). The pharmacological effect (PE) of BB-MMs was approximately 3.44 times greater than that of the suspension. In addition, in situ single-pass intestinal perfusion and cellular testing results illustrated that BB-MMs had good intestinal permeability and cellular uptake. Our findings demonstrate that the oral bioavailability and hypoglycemic effects of berberine could be largely enhanced by encapsulation into mixed micelles with a galactose moiety. Thus, galactosylated micelles may be promising for developing berberine nanomedicines to fight DM.During the process of wound healing, avoiding the formation of aligned collagen fibrils and subsequent scarring has become the focus of numerous research efforts. However, the goal of regeneration of native or scar-free skin remains a challenge. The complex and equivocal connection between inflammation and regeneration within the process of healing contributes to unsatisfactory treatment outcomes. Inspired by the scarless repair observed in fetal wound healing, we create a two-stage treatment combining the hydrocolloid dressing to attenuate the immune response in the initial three days, and the biomimetic cell-laden hydrogel to improve skin regeneration, which meet the specific needs of each stage in the healing process. To further accelerate the skin regeneration, the patterned cell-laden hydrogels were fabricated by photo-mask based photolithography technique. The efficacy and possible mechanisms of skin regeneration using this patterned cell-laden hydrogel therapy was investigated. Results show that these two-stage patterned cell-laden treatments were able to promote vascular network formation, accelerate wound closure, decrease scar formation, increase tissue regeneration and restore structure and mechanical properties of the skin in a full-thickness murine wound model. These data suggest that our patterned cell-based two-stage treatments can be used as a promising therapeutic option for wound healing by accelerating skin tissue regeneration.Malignant ascites indicate the presence of malignant cells in the peritoneal cavity that lower patient survival and reduce quality of life. Current chemotherapy regimens suffer from the dilution of ascites and rapid metabolism limiting their therapeutic efficacy. The storage and sustained release of drugs at the tumor site represents a promising strategy to improve drug efficacy. The aim of this study was to develop injectable hyaluronic acid hydrogel containing polymeric gemcitabine nanoparticles and cisplatin for the local treatment of malignant ascites through a dual sustained drug release pattern. Cell uptake assays showed that the drug-loaded nanoparticles readily entered tumor cells. Apoptosis and cell cycle analysis showed that the hydrogel system could enhance tumor cell apoptosis and arrest more cells in the G1 phase. In vivo experiments indicated that mice treated with the drug-loaded hydrogels manifested the most significant efficacy in ascites volume, tumor nodules, body weight, abdominal circumference, and survival.
My Website: https://www.selleckchem.com/EGFR(HER).html
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