Therapeutic strategies for achieving sustained virologic remission are being explored in human immunodeficiency virus (HIV)-infected individuals who began antiretroviral therapy (ART) during the ...early phase of infection. In the evaluation of such therapies, clinical protocols should include analytical treatment interruption (ATI); however, the immunologic and virologic impact of ATI in individuals who initiated ART early has not been fully delineated. We demonstrate that ATI causes neither expansion of HIV reservoirs nor immunologic abnormalities following reinitiation of ART. Our findings support the use of ATI to determine whether sustained virologic remission has been achieved in clinical trials of individuals who initiated ART early during HIV infection.
Four non-conventional oleaginous and pigmented yeast strains of
,
,
, and
were used in this study. Complex yeast extracts were prepared and tested for biological activity, safety, and effect on human ...health. In this paper, we measured the antioxidant activity and antimicrobial effect of yeast biomass as a whole and their extracts to compare the influence of carotenoids and other bioactive substances in the studied biomass. All yeast extracts exhibited a significant dose-dependent antimicrobial effect against both G+ and G- bacteria and had a strong antioxidant effect. No cytotoxicity in the mouse melanoma B16F1 cell line was found in concentrations up to 20% of rehydrated biomass in cell medium. All of the extracts were cytotoxic at a concentration of 5 mg of extract/g of dry biomass. All the pigmented yeast extracts showed some positive results for apoptosis of murine melanoma cell lines and are therefore strong candidates positively effect human health. Red yeast cell biomass is a prospective material with many attractive biological functions and can be used in the food industry, as a pharmaceutical material, or in the feed industry.
Compendia of large-scale datasets available in public repositories provide an opportunity to identify and fill current gaps in biomedical knowledge. But first, these data need to be readily ...accessible to research investigators for interpretation. Here, we make available a collection of transcriptome datasets relevant to HIV infection. A total of 2717 unique transcriptional profiles distributed among 34 datasets were identified, retrieved from the NCBI Gene Expression Omnibus (GEO), and loaded in a custom web application, the Gene Expression Browser (GXB), designed for interactive query and visualization of integrated large-scale data. Multiple sample groupings and rank lists were created to facilitate dataset query and interpretation via this interface. Web links to customized graphical views can be generated by users and subsequently inserted in manuscripts reporting novel findings, such as discovery notes. The tool also enables browsing of a single gene across projects, which can provide new perspectives on the role of a given molecule across biological systems. This curated dataset collection is available at:
http://hiv.gxbsidra.org/dm3/geneBrowser/list.
Activation, infection, and eventual depletion of human immunodeficiency virus (HIV)-specific cluster of differentiation 4 (CD4) T cells are the crucial pathogenetic events in acquired ...immunodeficiency syndrome (AIDS). We developed a cell and gene therapy to reconstitute HIV-specific CD4 T cells and prevent their destruction by HIV. Antigen-specific CD4 T cells will provide helper functions to support antiviral cytotoxic T lymphocyte (CTL) function and the production of virus-specific antibodies. However, ex vivo expansion of HIV-specific CD4 T cells is poor and previous gene therapies focused on bulk CD4 T cells without enriching for an antigen-specific subset. We developed a method for manufacturing autologous CD4+ T cell products highly enriched with Gag-specific T cells. Rare Gag-specific CD4 T cells in peripheral blood mononuclear cells (PBMCs) were increased nearly 1,000-fold by stimulating PBMC with Gag peptides, followed by depleting nontarget cells and transducing with lentivirus vector AGT103 to protect against HIV-mediated depletion and inhibit HIV release from latently infected cells. The average percentage of HIV-specific CD4 cells in the final products was 15.13%, and the average yield was 7 × 108 cells. The protocol for clinical-scale manufacturing of HIV-specific and HIV-resistant CD4 T cells is an important step toward effective immunotherapy for HIV disease.
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Cell and gene therapy can reconstitute HIV-specific CD4 T cells and correct the key defect in HIV disease. A new process enriches for Gag-specific CD4+ T cells from HIV-infected individuals to an average of 15% with yields nearing 109-specific cells per product and may improve antiviral immunity. Keywords: HIV; AIDS; functional cure; immunotherapy; lentivirus vector; autologous; CD4 T cell; gene therapy; NCT03215004
The paper investigates the impact of the implementation of Directive 2014/95/EU nonfinancial reporting into Czech accounting regulations by evaluating the level and quality of non-financial reporting ...by banking institutions, including their foreign branches based in the Czech Republic. Information from the area Environment, Social and Governance are considered globally topical and relevant. They contribute to increasing competitiveness and responsible building of the future. The verification of level and quality of non-financial reporting was based on the comparison of the years 2016 and 2021, i.e., periods before and after the implementation of the directive. For the purpose of comparison, banking institutions were divided into three groups: banks with an obligation to report non-financial information, banks that are large accounting entities, and other banks. Key indicators of five basic areas of non-financial reporting were identified and the level of their reporting by banks was subsequently examined. The quality of the reported information was assessed using a point scale. The level of non-financial reporting in the sector of financial institutions in the Czech Republic was compared with the level of reporting in the Visegrad countries, Germany and France. By means of correlation and regression analysis, factors that influence the quality and level of non-financial reporting were identified, the most significant being net assets, gross loans to customers and Tier 1. it was also found that non-financial reporting is unsystematic due to the absence of a comprehensive methodology, mainly in the group of banks 11 and HI. At the same time, the V4 countries report less non-financial information compared to Germany and France. A positive finding is the fact that there has been an increasing tendency in non-financial reporting in all monitored countries.
Background
Childhood thalamopeduncular gliomas arise at the interface of the thalamus and cerebral peduncle. The optimal treatment is total resection but not at the cost of neurological function. ...We present long-term clinical and oncological outcomes of maximal safe resection.
Methods
Retrospective review of prospectively collected data: demography, symptomatology, imaging, extent of resection, surgical complications, histology, functional and oncological outcome.
Results
During 16-year period (2005–2020), 21 patients were treated at our institution. These were 13 girls and 8 boys (mean age 7.6 years). Presentation included progressive hemiparesis in 9 patients, raised intracranial pressure in 9 patients and cerebellar symptomatology in 3 patients. The tumour was confined to the thalamus in 6 cases. Extent of resection was judged on postoperative imaging as total (6), near-total (6) and less extensive (9). Surgical complications included progression of baseline neurological status in 6 patients, and 5 of these gradually improved to preoperative status. All tumours were classified as low-grade gliomas. Disease progression was observed in 9 patients (median progression-free survival 7.3 years). At last follow-up (median 6.1 years), all patients were alive, median Lansky score of 90. Seven patients were without evidence of disease, 6 had stable disease, 7 stable following progression and 1 had progressive disease managed expectantly.
Conclusion
Paediatric patients with low-grade thalamopeduncular gliomas have excellent long-term functional and oncological outcomes when gross total resection is not achievable. Surgery should aim at total resection; however, neurological function should not be endangered due to excellent chance for long-term survival.
Abstract
BACKGROUND: Childhood thalamopeduncular gliomas arise at the interface of thalamus and cerebral peduncle. The optimal treatment is total resection but not at the cost of neurological ...function. We present long-term clinical and oncological outcomes of maximal safe resection. METHODS: Retrospective review of prospectively collected data: demography, symptomatology, imaging, extent of resection, surgical complications, histology, functional and oncological outcome. RESULTS: During 16-year period (2005-20) 21 patients were treated at our institution. These were 13 girls and 8 boys (mean age 7.6 years). Presentation included progressive hemiparesis in 9 patients, raised intracranial pressure in 9 patients and cerebellar symptomatology in 3 patients. The tumor was confined to the thalamus in 6 cases. Extent of resection was judged on postoperative imaging as total (6), near-total (6) and less extensive (9). Surgical complications included progression of baseline neurological status in 6 patients, 5 of these gradually improved to preoperative status. All tumors were classified as low-grade gliomas. Disease progression was observed in 9 patients (median progression free survival 7.3 years). At last follow-up (median 6.1 years) all patients were alive; median Lansky score of 90. Seven patients were without evidence of disease, 6 had stable disease, 7 stable following progression and 1 had progressive disease managed expectantly. CONCLUSION: Pediatric patients with low grade thalamopeduncular gliomas have excellent long-term functional and oncological outcomes even when gross total resection is not achievable. Surgery should aim at total resection; however neurological function should not be endangered due to excellent chance for long-term survival.
An effective chemotherapy for neoplastic diseases requires the use of drugs that can reach the site of action at a therapeutically efficacious concentration and maintain it at a constant level over a ...sufficient period of time with minimal side effects. Currently, conjugates of high-molecular-weight hydrophilic polymers or biocompatible nanoparticles with stimuli-releasable anticancer drugs are considered to be some of the most promising systems capable of fulfilling these criteria. In this work, conjugates of thermoresponsive diblock copolymers with the covalently bound cancerostatic drug pirarubicin (PIR) were synthesized as a reversible micelle-forming drug delivery system combining the benefits of the above-mentioned carriers. The diblock copolymer carriers were composed of hydrophilic polyN-(2-hydroxypropyl)methacrylamide-based block containing a small amount (∼5 mol %) of comonomer units with reactive hydrazide groups and a thermoresponsive poly2-(2-methoxyethoxy)ethyl methacrylate block. PIR was attached to the hydrophilic block of the copolymer through the pH-sensitive hydrazone bond designed to be stable in the bloodstream at pH 7.4 but to be degraded in an intratumoral/intracellular environment at pH 5–6. The temperature-induced conformation change of the thermoresponsive block (coil–globule transition), followed by self-assembly of the copolymer into a micellar structure, was controlled by the thermoresponsive block length and PIR content. The cytotoxicity and intracellular transport of the conjugates as well as the release of PIR from the conjugates inside the cells, followed by its accumulation in the cell nuclei, were evaluated in vitro using human colon adenocarcinoma (DLD-1) cell lines. It was demonstrated that the studied conjugates have a great potential to become efficacious in vivo pharmaceuticals.
Purpose
Literature dedicated to growth patterns and growth rate influencing factors of radiation-induced meningiomas (RIMs) is limited. To deliver new insights into the topic, a volumetric growth ...analysis of RIMs was performed.
Methods
This single-center, retrospective cohort study included patients diagnosed with intracranial meningioma who received radiation treatment at least > 5 years before the RIM diagnosis. Volumetric analysis of individual RIMs was performed using 3D volumetry at the time of RIM diagnosis and during follow-up. RIM growth was determined by calculating absolute (AGR), and relative (RGR) growth rates. Prognostic factors associated with RIM growth were evaluated.
Results
A total of 26 patients with 33 meningiomas were enrolled in the study and radiologically/clinically followed up during a median duration of 5.6 years (IQR 3.9–8.8 years). Median AGR was 0.19 cm
3
per year and the median RGR was 34.5% per year. Surgically managed RIMs were more likely fast-growing compared to observed ones based on the AGR (p < 0.002). The recurrence rate after total resection was 14.3%. Younger age at RIM diagnosis was associated with higher tumor growth (RGR ≥ 30%, p = 0.040). A significant correlation was found between the length of latency period and the RGR (p = 0.005).
Conclusion
To diagnose RIM as early as possible comprehensive MRI surveillance is required. Younger patients with shorter latency periods may profit from shortened MRI intervals, with further management being dependent on the growth rate and eventual symptomatology.
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