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Oncolytic virus (OV) is increasingly being recognized as a novel vector in cancer immunotherapy. Increasing evidence suggests that OV has the ability to change the immune status of tumor microenvironment, so called transformation of 'cold' tumors into 'hot' tumors. The improved anti-tumor immunity can be induced by OV and further enhanced through the combination of various immunomodulators. The Neo-2/15 is a newly de novo synthesized cytokine that functions as both IL-2 and IL-15. However, it specifically lacks the binding site of IL-2 receptor α subunit (CD25), therefore unable to induce the Treg proliferation. In present study, a recombinant vesicular stomatitis virus expressing the Neo-2/15 (VSVM51R-Neo-2/15) was generated. Intratumoral delivery of VSVM51R-Neo-2/15 efficiently inhibited tumor growth in mice without causing the IL-2-related toxicity previously observed in clinic. Moreover, treatment with VSVM51R-Neo-2/15 increased the number of activated CD8+ T cells but not Treg cells in tumors. More tumor-bearing mice were survival with VSVM51R-Neo-2/15 treatment, and the surviving mice displayed enhanced protection against tumor cell rechallenge due to the induced anti-tumor immunity. In addition, combination therapy of OV and anti-PD-L1 immune checkpoint inhibitors further enhanced the anti-tumor immune response. These findings suggest that our novel VSVM51R-Neo-2/15 can effectively inhibit the tumor growth and enhance the sensitivity to immune checkpoint inhibitors, providing promising attempts for further clinical trials.
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Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by multi-organ involvement and the presence of autoantibodies, pathogenic factors that can serve as diagnostic biomarkers. The current research has been focusing on exploring specific autoantigens with clinical relevance for SLE subtypes. In line with this objective, this study investigated potential antigenic targets associated with specific phenotypes in SLE by leveraging an omics-based approach combined with immunoassay techniques. Methods: A transcriptomic analysis was conducted in a cohort of 70 SLE patients to identify genes significantly correlated to the relevant phenotype. Epitope mapping and sequence analysis techniques were used to predict autoantigens, and the corresponding antibodies were subsequently quantified by enzyme-linked immunosorbent assay (ELISA) and validated by Western blot. Results: Transcriptomic data analysis revealed a group of hub genes exhibiting a significant correlation with the neuropsychiatric phenotype and a positive relationship with platelets. Subsequent epitope prediction for the corresponding proteins highlighted vasodilator-stimulated phosphoprotein (VASP) as a potential autoantigen. Moreover, ELISA and immunoblotting confirmed that the anti-VASP antibody present in the serum was significantly elevated in SLE patients with neuropsychiatric involvement and positively associated with demyelination. Conclusion: VASP harbors autoantigenic epitopes associated with neuropsychiatric phenotype, especially the demyelination symptom in SLE, and its antibodies may serve as promising biomarkers in this disease.
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BACKGROUND: X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation of a neo-TAD that drives pituitary GPR101 misexpression and gigantism. As X-LAG is fully penetrant and heritable, duplications involving GPR101 identified on prenatal screening studies, like amniocentesis, can pose an interpretation challenge for medical geneticists and raise important concerns for patients and families. Therefore, providing robust information on the functional genomic impact of such duplications has important research and clinical value with respect to gene regulation and triplosensitivity traits. METHODS: We employed 4C/HiC-seq as a clinical tool to determine the functional impact of incidentally discovered GPR101 duplications on TAD integrity in three families. After defining duplications and breakpoints around GPR101 by clinical-grade and high-density aCGH, we constructed 4C/HiC chromatin contact maps for our study population and compared them with normal and active (X-LAG) controls. RESULTS: We showed that duplications involving GPR101 that preserved the centromeric invariant TAD boundary did not generate a pathogenic neo-TAD and that ectopic enhancers were not adopted. This allowed us to discount presumptive/suspected X-LAG diagnoses and GPR101 misexpression, obviating the need for intensive clinical follow-up. CONCLUSIONS: This study highlights the importance of TAD boundaries and chromatin interactions in determining the functional impact of copy number variants and provides proof-of-concept for using 4C/HiC-seq as a clinical tool to acquire crucial information for genetic counseling and to support clinical decision-making in cases of suspected TADopathies.
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Cromatina , Receptores Acoplados a Proteínas G , Humanos , Receptores Acoplados a Proteínas G/genética , Cromatina/genética , Cromatina/metabolismo , Femenino , Masculino , Duplicación de Gen , Duplicación Cromosómica , Cromosomas Humanos X/genética , LinajeRESUMEN
BACKGROUND: The Lao People's Democratic Republic (Lao PDR), a lower-middle income country, has a higher malnutrition rate than other Southeast Asian countries. The decentralization of healthcare is a determinant of the effectiveness of programs to reduce malnutrition, but no study has focused on this factor in this country. This organizational study explores the state of decentralization of the healthcare system in Lao PDR that underlies the nutrition programs in the country. METHODS: A qualitative study, which is based on a neo-institutional theory conceptual framework, explored factors related to dominant structure (laws, regulations, resources) and interpretative schemes (dominant ideas and beliefs) that characterize the nutrition services provided in the Lao healthcare system. Twenty-four semistructured interviews were performed with representatives of healthcare institutions involved in nutrition programs at different government levels, external donors and civil society organizations. The interviews were completed with relevant documents. The analysis focused on the convergence of interpretative schemes of the organizations concerned and the coherence between the structure underpinning the nutrition programs and the interpretative schemes. RESULTS: Services deployed to reduce malnutrition in the Lao PDR remain largely centralized, despite factors specific to the country that led it to promote decentralization of its services. The convergence of interpretive schemes and the coherence between the observed structure and the interpretative schemes of actors at all governance levels ensure the stability of this state of decentralization, which has persisted for almost 50 years. CONCLUSION: Nutrition programs in the Laos PDR are largely under the responsibility of the central government. The transformations in the healthcare system, notably with the use of new information technologies and the fact that the provinces are populated by a growing number of professionals trained in nutrition in addition to factors that push the system to be decentralized, such as ethnic diversity, the increasing availability of human resources in provinces, and the use of communication technologies, are not strong enough to change the balance of power between governance levels. The deconcentration that characterizes decentralization is therefore likely to continue for the foreseeable future.
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Atención a la Salud , Entrevistas como Asunto , Política , Humanos , Atención a la Salud/organización & administración , Laos , Desnutrición/prevención & control , Investigación CualitativaRESUMEN
BACKGROUND: Previous studies found that in patients with profound hearing loss the NEO- personality factor Openness-to-experience is lowered. OBJECTIVE: Assuming that lowered Openness-to-experience may be due to limited access to sounds, we hypothesized that levels of Openness-to-experience would increase in these patients after cochlear implantation. MATERIAL AND METHODS: Twenty adults (mean age: 61 years; active CI users) with bilateral profound hearing loss were assessed with the NEO-Five-Factor-Inventory before cochlear implantation (pre) and five years later (post). RESULTS: No significant pre-post changes in personality were seen. Both before and five years after cochlear implantation, the sample had normal age- and gender-specific mean values on the factors Extraversion, Neuroticism, Agreeableness, and Conscientiousness (T ≈ 50), but significantly lowered mean values on Openness-to-experience (T ≈ 42, p < 0.001). CONCLUSIONS AND SIGNIFICANCE: Cochlear implantation apparently has no (or at best very little) effect on Openness-to-experience in profoundly hearing impaired patients. While this study demonstrates once again, that high-grade hearing loss may be associated with less openness to new experiences, the reason for this association remains unclear.
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Do all birds' sex chromosomes follow the same canonical one-way direction of evolution? We combined cytogenetic and genomic approaches to analyze the process of the W chromosomal differentiation in two selected Passeriform species, named the Pale-breasted Thrush Turdus leucomelas and the Rufous-bellied thrush T. rufiventris. We characterized the full catalog of satellite DNAs (satellitome) of T. leucomelas, and the 10 TleSatDNA classes obtained together with 16 microsatellite motifs were in situ mapped in both species. Additionally, using Comparative Genomic Hybridization (CGH) assays, we investigated their intragenomic variations. The W chromosomes of both species did not accumulate higher amounts of both heterochromatin and repetitive sequences. However, while T. leucomelas showed a heterochromatin-poor W chromosome with a very complex evolutionary history, T. rufiventris showed a small and partially heterochromatic W chromosome that represents a differentiated version of its original autosomal complement (Z chromosome). The combined approach of CGH and sequential satDNA mapping suggest the occurrence of a former W-autosomal translocation event in T. leucomelas, which had an impact on the W chromosome in terms of sequence gains and losses. At the same time, an autosome, which is present in both males and females in a polymorphic state, lost sequences and integrated previously W-specific ones. This putative W-autosomal translocation, however, did not result in the emergence of a multiple-sex chromosome system. Instead, the generation of a neo-W chromosome suggests an unexpected evolutionary trajectory that deviates from the standard canonical model of sex chromosome evolution.
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ADN Satélite , Evolución Molecular , Heterocromatina , Cromosomas Sexuales , Animales , ADN Satélite/genética , Cromosomas Sexuales/genética , Femenino , Masculino , Heterocromatina/genética , Hibridación Genómica Comparativa , Repeticiones de Microsatélite/genética , Passeriformes/genética , Hibridación Fluorescente in SituRESUMEN
The rapid expansion of multi-omics data has transformed biological research, offering unprecedented opportunities to explore complex genomic relationships across diverse organisms. However, the vast volume and heterogeneity of these datasets presents significant challenges for analyses. Here we introduce SocialGene, a comprehensive software suite designed to collect, analyze, and organize multi-omics data into structured knowledge graphs, with the ability to handle small projects to repository-scale analyses. Originally developed to enhance genome mining for natural product drug discovery, SocialGene has been effective across various applications, including functional genomics, evolutionary studies, and systems biology. SocialGene's concerted Python and Nextflow libraries streamline data ingestion, manipulation, aggregation, and analysis, culminating in a custom Neo4j database. The software not only facilitates the exploration of genomic synteny but also provides a foundational knowledge graph supporting the integration of additional diverse datasets and the development of advanced search engines and analyses. This manuscript introduces some of SocialGene's capabilities through brief case studies including targeted genome mining for drug discovery, accelerated searches for similar and distantly related biosynthetic gene clusters in biobank-available organisms, integration of chemical and analytical data, and more. SocialGene is free, open-source, MIT-licensed, designed for adaptability and extension, and available from github.com/socialgene.
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Flavonoid natural products are emerging as a promising approach for treating Ulcerative Colitis (UC) due to their natural origin and minimal toxicity. This study investigates the effects of Neohesperidin (NEO), a natural flavonoid, on Dextran Sodium Sulfate (DSS)-induced UC in mice, focusing on the underlying molecular mechanisms. Early intervention with NEO (25 and 50 mg/kg) mitigated colon shortening, restored damaged barrier proteins, and significantly reduced the inflammatory cytokine levels. Moreover, NEO inhibited the MAPK/NF-κB signaling pathway and enhanced the levels of intestinal barrier proteins (Claudin-3 and ZO-1). Additionally, NEO increased beneficial intestinal probiotics (S24-7 and Lactobacillaceae) while reducing harmful bacteria (Erysipelotrichi, Enterobacteriaceae). Fecal microbial transplantation (FMT) results demonstrated that NEO (50 mg/kg) markedly improved UC symptoms. In conclusion, early NEO intervention may alleviate DSS-induced UC by inhibiting inflammatory responses, preserving intestinal barrier integrity and modulating gut microbiota.
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Colitis Ulcerosa , Sulfato de Dextran , Microbioma Gastrointestinal , Hesperidina , Mucosa Intestinal , Ratones Endogámicos C57BL , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/inmunología , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Sulfato de Dextran/efectos adversos , Masculino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Hesperidina/farmacología , Hesperidina/administración & dosificación , Hesperidina/análogos & derivados , Humanos , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/genética , FN-kappa B/metabolismo , FN-kappa B/genética , Colon/microbiología , Colon/efectos de los fármacos , Colon/inmunología , Colon/metabolismo , Colon/patología , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológicoRESUMEN
OBJECTIVE: Findings concerning the effects of hormone therapy (HT) on cognition and dementia are mixed, with some trials suggesting increased harm at older ages. Personality, like cognition, changes with dementia, but no clinical trials to date have examined the effects of HT on personality traits. This study aimed to determine the effects of HT on personality traits in older men and women. METHOD: Secondary data analysis was performed from randomized, double-blind, placebo-controlled cross-over studies of menopausal HT in women and testosterone therapy (TT) in men. Participants were community-dwelling cognitively normal adults (mean age = 75.2 years), including 29 men and 22 women. Three months of hormone intervention (for women, 0.625 mg/day conjugated equine estrogen with or without 2.5 mg/day medroxyprogesterone acetate; for men, 200 mg intramuscular testosterone enanthate every 2 weeks) were crossed over with 3 months of identical placebo with a 3-month washout between intervention phases. The main outcome measure was neuroticism and conscientiousness personality domains and facets assessed with the Revised NEO Personality Inventory (NEO-PI-R) after the active and placebo intervention phases. RESULTS: In linear mixed-effect models, HT in women decreased conscientiousness (p < 0.01) and the conscientiousness facet of achievement striving (p < 0.01), and increased vulnerability, a facet of neuroticism (p < 0.05). Testosterone in men decreased conscientiousness (p < 0.05) and the conscientiousness facet of dutifulness (p < 0.05), and increased vulnerability (p < 0.05). CONCLUSION: In a preliminary study of healthy older adults, HT and TT formulations produced adverse changes in vulnerability and conscientiousness facets that parallel personality changes in dementia.
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The aim of this work was to identify the underlying genetic cause in a four-generation family segregating an unusual phenotype comprising a severe form of skeletal Class II malocclusion with gingival hyperplasia. SNP-array identified a copy number gain on chr1, however this chromosomal region did not segregate correctly in the extended family. Exome sequencing also failed to identify a candidate causative variant, but highlighted co-segregating genetic markers on chr17 and chr19. Short- and long-read genome sequencing allowed us to pinpoint and characterize at nucleotide-level resolution a chromothripsis-like complex rearrangement (CR) inserted into the chr17 co-segregating region at the KCNJ2-SOX9 locus. The CR involved the gain of five different regions from chr1 that are shuffled, chained and inserted as a single block (â¼828 kb) at chr17q24.3. The inserted sequences contain craniofacial enhancers that are predicted to interact with KCNJ2/KCNJ16 through neo-topologically associating domain (TAD) formation to induce ectopic activation. Our findings suggest that the CR inserted at chr17q24.3 is the cause of the severe skeletal Class II malocclusion with gingival hyperplasia in this family and expands the panoply of phenotypes linked to variation at the KCNJ2-SOX9 locus. In addition, we highlight a previously overlooked potential role for misregulation of the KCNJ2/KCNJ16 genes in the pathomechanism of gingival hyperplasia associated with deletions and other rearrangements of the 17q24.2-q24.3 region (MIM 135400).
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Ganoderma, a traditional medicine in Asian countries, has been used to prevent and treat various ailments for centuries. Ganoderma neo-japonicum (synonym Ganoderma bambusicola), also known as purple Lingzhi, is a species that is currently underutilised when compared to Ganoderma lucidum (Lingzhi). However, in recent decades, this mushroom has garnered significant attention due to its ethnomedicinal uses, especially in Southeast Asia regions like Malaysia. The taxonomy and nomenclature of this mushroom have been extensively studied. Numerous publications have reported that G. neo-japonicum displays a variety of medicinal properties, including antioxidation, anticancer, anti-hyperglycaemic, genoprotective, hepatoprotective, neuritogenic, and antidiabetic effects, both in vitro and in vivo. With the surge of research findings on this mushroom, this review aims to provide a systematic bibliometric analysis of G. neo-japonicum, published between 1991 to 2021. Additionally, the taxonomic description of this mushroom is discussed in detail. Our review reveals that G. neo-japonicum contains polysaccharides (α/ß-D-glucans), triterpenoids, and sterols/ergosterol. However, the existing literature suggests that these active compounds have not yet been explored to their full potential as drug candidates. Moreover, most of the studies are preclinical and have several drawbacks. In conclusion, G. neo-japonicum possesses valuable pharmacological activities that merit further exploration.
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Primary sternal tumours are rare. Most of them are malignant in nature. When localized, cure can be achieved by radical resection. However, it leaves a large bony defect in front of the heart that makes reconstruction a challenge. In this report, we describe our experience of sternal reconstruction using a custom-made 3D-printed titanium neo-sternum after en-bloc resection of sternal body and anterior ends of bilateral second to fifth ribs for chondrosarcoma.
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BACKGROUND: Research suggests that participating in a stuttering simulation-based learning (SBL) program could help speech-language pathology (SLP) students feel more at ease, less nervous and more capable while interacting with people who stutter. Personality traits may influence SLP students' self-efficacy beliefs as well as their level of interest in working with clients who stutter. In particular, we suggest that the combination of low neuroticism and high extraversion, previously linked with a more outgoing, emotionally stable and social personality, may enhance self-efficacy. AIMS: To examine the impact of participating in a stuttering SBL program on clinical self-efficacy (CSE) in managing stuttering therapy among SLP students, as well as its influence on their interest in working with fluency disorders and their associations with personality dimensions. The study also evaluated satisfaction with the SBL experience. METHODS & PROCEDURES: SLP students (n = 49) underwent a fluency disorders academic course, self-reported on CSE, and had an interest in working in the field of stuttering and NEO-Five-Factor Inventory (NEO-FFI). Post-stuttering SBL program participation, CSE and level of interest in practice of stuttering were reassessed. Satisfaction with the simulation was also gauged. OUTCOMES & RESULTS: Students interested in working with fluency disorders scored lower in neuroticism and higher in extraversion than their uninterested counterparts. Before the SBL activity, interest ratings were negatively correlated with neuroticism and positively correlated with extraversion. Pre-SBL neuroticism was negatively correlated with CSE. Following the SBL activity, increased CSE and interest in working with fluency disorders were evident, indicating robust and medium effects of the simulation on those indices, respectively. Post-SBL neuroticism was also negatively correlated with CSE. Overall, participants reported high satisfaction with the SBL experience. CONCLUSIONS & IMPLICATIONS: The study suggests SBL is an effective tool for enhancing motivation to work with fluency disorders. Consideration of personality traits and professional interests in designing educational interventions for SLP students, along with tailoring approaches to individual differences, may enhance learning outcomes. The study also highlights the need to differentiate between CSE and objectively assessed clinical competence and the fact that professional development is influenced by various factors. Nonetheless, the positive correlations between personality traits, CSE and satisfaction emphasize the potential of SBL programs in shaping not only clinical skills but also the attitudes and preferences of future SLPs. WHAT THIS PAPER ADDS: What is already known on this subject SLPs in the field of stuttering therapy reportedly experience low levels of comfort and professional confidence, possibly due to insufficient clinical experience. According to earlier research, taking part in SBL programs may elevate the CSE of SLP students and help them feel more confident about treating people with stuttering. What this study adds to the existing knowledge In addition to showing the beneficial effects of an SBL activity on SLP students' self-efficacy and interest in working in stuttering therapy, our research shows a significant relationship between personality traits and CSE. Specifically, the combination of high extraversion and low neuroticism was found to be associated with higher CSE and higher levels of satisfaction from the SBL. What are the potential or actual clinical implications of this work? The study shows that SBL is an effective tool for enhancing motivation to work with fluency disorders. Overall, students who exhibit high extraversion and low neuroticism show higher levels of CSE, greater motivation in stuttering treatment, and higher levels of SBL stratification. Development of future SBL activities and other educational interventions should take into consideration such personality traits, to enhance learning outcomes.
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The influenza pandemic of 1781-1782 was remarkably well-documented, with investigations and treatment records produced in Britain, France, Germany, Italy, and Russia. Everyone agreed that outbreak began in St. Petersburg in December 1781 and then spread across northern Europe, but the medical communities' consensus did not solve all issues. Two questions would inspire years of debate. The first concerned the transmission vector of the pandemic: was it the result of neo-Hippocratic, miasmatic, or contagionist exposure? This was perhaps the greatest concern of the late-eighteenth century, and multiple physicians hoped the latest influenza pandemic could provide an answer. The second was no less difficult - where did the disease originate? This was not only because geography affected both prophylactic measures and treatment options but also produced diplomatic and commercial consequences. Was a quarantine necessary, preventing commercial exchanges? Did the risk of infection result in peace negotiations being delayed, potentially extending the American Revolution and the ongoing naval conflict in the Atlantic? Even if a consensus could be reached that this was a "Russian" catarrh, this would not resolve the method of disease transmission. The pandemic of 1781-1782 was not a turning point in the arguments among neo-Hippocratic, miasmatic, and contagionist physicians, but rather reveals all three positions could be held simultaneously.
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To investigate the value of prognostic nutrition index (PNI) and systemic immunoinflammatory index (SII) for predicting pathological responses of patients with advanced gastric cancer (GC) after neo-adjuvant chemotherapy (NACT). The clinicopathological data of 326 patients with advanced GC who received NACT in Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) from January 2017 to December 2021 were retrospectively collected. The SII and PNI of patients were calculated. The receiver operating characteristics (ROC) curve was leveraged for getting the optimal cutoff values of SII and PNI. The pathological response of patients after NACT, as obtained from their postoperative pathological examinations, was evaluated based on the tumor regression grade (TRG) criteria. Multivariate regression analysis was employed for identifying factors that led to various pathological responses after NACT in advanced GC patients. The log-rank test was utilized for between-group comparison of patients' survival curves. The SII and PNI were 507.45 and 48.48 respectively, and their levels were divided into high and low groups. Pathological response (TRG 0-1) was observed in 66 cases (20.25%), while non-pathological response (TRG 2-3) was observed in 260 cases (79.75%). The results of multivariate logistic regression analysis showed that tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX (capecitabine combined with oxaliplatin), SII < 507.45 (P=0.002), PNI > 48.48 were all independent factors affecting the pathological responses of advanced GC patients after NACT (all P < 0.05). With SII and PNI being included, the AUC was 0.821 (95% CI: 0.765-0.876), and the specificity was 87.90% and the sensitivity was 64.20%. The Kaplan-Meier survival curve analysis showed that NACT patients with tumor diameter < 5 cm, ypT T0-T2, ypN N0, XELOX chemotherapy regimen, SII < 507.45 and SII ≥ 507.45 had a higher survival rate. (P < 0.001). Before treatment, tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX, SII < 507.45, PNI > 48.48 were all independent factors affecting the pathological response of advanced GC patients after NACT. Moreover, the inclusion of SII and PNI increased the accuracy of predicting the pathological response of patients after NACT.
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Few predictive biomarkers exist for identifying patients who may benefit from neoadjuvant therapy (NAT). The intratumoral microbial composition is comprehensively profiled to predict the efficacy and prognosis of patients with esophageal squamous cell carcinoma (ESCC) who underwent NAT and curative esophagectomy. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis is conducted to screen for the most closely related microbiota and develop a microbiota-based risk prediction (MRP) model on the genera of TM7x, Sphingobacterium, and Prevotella. The predictive accuracy and prognostic value of the MRP model across multiple centers are validated. The MRP model demonstrates good predictive accuracy for therapeutic responses in the training, validation, and independent validation sets. The MRP model also predicts disease-free survival (p = 0.00074 in the internal validation set and p = 0.0017 in the independent validation set) and overall survival (p = 0.00023 in the internal validation set and p = 0.11 in the independent validation set) of patients. The MRP-plus model basing on MRP, tumor stage, and tumor size can also predict the patients who can benefit from NAT. In conclusion, the developed MRP and MRP-plus models may function as promising biomarkers and prognostic indicators accessible at the time of diagnosis.
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Burow's solution is a 13% aluminum acetate solution used for treating chronic suppurative otitis media. However, multiple formulations for Burow's and neo-Burow's solutions are used as in-hospital preparations. Each formulation uses different types and amounts of reagents, and takes a different time to prepare. Thus, the ions, including aluminum ion (Al3+), and other molecules in the prepared Burow's and neo-Burow's solutions are not identical, and the pH also differs. Furthermore, details about the antibacterial activity of these preparations are unknown. This study evaluated the stability and antibacterial activity of four Burow's and two neo-Burow's solutions prepared using different methods. Preparation times ranged from 20 min to 3 d, and the pH ranged from 2.2 to 4, meaning some solutions were more acidic or more basic than the pH 3 devised by Burow. In addition, the Al3+ concentrations ranged from 0.05 to 1.51 mol/L, meaning some solutions were more concentrated or diluted than 13% aluminum acetate (0.64 mol/L). One of the Burow's solutions we prepared produced a white residue after 14 d, making it difficult to ensure stability. In addition, confirming the antibacterial activity of another Burow's solution against the test bacteria was problematic. Despite the differences in pH and Al3+ concentrations between the various Burow's and neo-Burow's solutions, the antibacterial activity was equivalent. It was considered necessary to use the basic data obtained in this study to select a formulation for each hospital. Evaluation of the antibacterial activity of each formulation in clinical settings will be a subject for future study.
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Antibacterianos , Estabilidad de Medicamentos , Antibacterianos/farmacología , Concentración de Iones de Hidrógeno , Otitis Media Supurativa/tratamiento farmacológico , Aluminio , Factores de Tiempo , Acetatos , Soluciones Farmacéuticas , Composición de Medicamentos/métodosRESUMEN
BACKGROUND: Mouse brains can contain specific polyglucosan aggregates known as Periodic Acid-Schiff (PAS)-granules. Generated in astrocytes, these granules increase with age and exhibit neo-epitopes of carbohydrate nature that are recognized by natural IgM antibodies (IgMs). The existence of neoepitopes on PAS granules suggests the presence of neoepitopes in other brain structures, and this is investigated here. To this end, brain sections from SAMP8 and ICR-CD1 mice were examined at different ages. RESULTS: We have identified two novel structures that, apart from PAS granules, are recognized by natural IgMs. On one side, IgM reactive (IgM+) granular structures which are placed in the longitudinal fissure, the quadrigeminal cistern, and a region that extends from the quadrigeminal cistern to the interpeduncular cistern. This last region, located between the telencephalon and both the mesencephalon and diencephalon, is designated henceforth as the fissura magna, as it is indeed a fissure and the largest in the brain. As all these regions are extraparenchymal (EP), the IgM+ granules found in these zones have been named EP granules. These EP granules are mainly associated with fibroblasts and are not stained with PAS. On the other side, some IgM+ astrocytes have been found in the glia limitans, near the above-mentioned fissures. Remarkably, EP granules are more prevalent at younger ages, while the number of IgM+ astrocytes increases with age, similarly to the already described evolution of PAS granules. CONCLUSIONS: The present work reports the presence of two brain-related structures that, apart from PAS granules, contain neo-epitopes of carbohydrate nature, namely EP granules and IgM+ astrocytes. We suggest that EP granules, associated to fibroblasts, may be part of a physiological function in brain clearance or brain-CSF immune surveillance, while both PAS granules and IgM+ astrocytes may be related to the increasing accumulation of harmful materials that occurs with age and linked to brain protective mechanisms. Moreover, the specific localisation of these EP granules and IgM+ astrocytes suggest the importance of the fissura magna in these brain-related cleaning and immune functions. The overall results reinforce the possible link between the fissura magna and the functioning of the glymphatic system.
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Gardenia fruit is a popular functional food and raw material for natural pigments. It comes from a wide range of sources, and different products sharing the same name are very common. Volatile organic compounds (VOCs) are important factors that affect the flavor and quality of gardenia fruit. This study used the Heracles NEO ultra-fast gas phase electronic nose with advanced odor analysis performance and high sensitivity to analyze six batches of gardenia fruit from different sources. This study analyzed the VOCs to find a way to quickly identify gardenia fruit. The results show that this method can accurately distinguish the odor characteristics of various gardenia fruit samples. The VOCs in gardenia fruit are mainly organic acid esters, ketones, and aldehyde compounds. By combining principal component analysis (PCA) and discriminant factor analysis (DFA), this study found that the hexanal content varied the most in different gardenia fruit samples. The VOCs allowed for the fruit samples to be grouped into two main categories. One fruit sample was quite different from the fruits of other origins. The results provide theoretical support for feasibility of rapid identification and quality control of gardenia fruit and related products in the future.