DiscoveryBioMed (United States)

This study aims to describe students' collaboration skillsin science learning based on Project Based Learning(PjBL) integrated with STEAM with ecoprinttechniques. The research method used is descriptivequantitative with a population of 6th grade students ofCipocok Jaya 1 Elementary School. Data were obtainedthrough observations of 12 indicators of collaborationskills covering aspects of participation, communication, teamwork, and problem solving, then analyzeddescriptively. The results showed that students' overallcollaboration skills were in the very high category withan average score of 83.3% and 81% of students were in the very good category. This indicates that theimplementation of the PjBL STEAM ecoprint model successfully empowered students' collaboration skills in completing projects involving effective interaction andtask division. The responsibility aspect showed thehighest score (85.88%). This study makes an importantcontribution to the development of 21st century learning that emphasizes collaboration as a corecompetency.

To evaluate the toxic effects of the agent Relatox on mature outbred rats and mice in an acute experiment in comparison with the registered analogue Dysport. Based on the aim of experiment, the acute toxic effects of Relatox and Dysport were assessed on two animal species: rats and mice at intraperitoneal and intramuscular administration at dose levels that made it possible to calculate the toxicological parameter values (initially 10-150 U/kg with subsequent usage of additional doses 20 U/kg to 300 U/kg depending on the agent and route of administration). The LD50 values and other acute toxic parameters were calculated using probit analysis. The manifested intoxication picture was observed following administration of both agents, in which neurological symptoms specific to botulinum toxin came to the fore: muscle paresis and local paralysis, which were the result of the mode of therapeutic action of the toxin. The observed picture of intoxication, monitoring of the dynamics of body weight gains, as well as data of macroscopic analysis of organs and tissues indicate a complete analogy of animal responses to both agents administration. However, the mortality rates of animals differed when administered at different doses as well as the established LD50 values of Relatox and Dysport. Both agents were more toxic when administered intraperitoneally than intramuscularly. Species or gender sensitivities were no detected for both agents. LD50 values of Relatox and Dysport established based on the results of an acute experiment, should be considered taking into account the differences (approximately 2.5-3-folds) in the specific activity of these agents.

2044 Background: γδ T cells, MHC unrestricted immune cells, target NKG2D ligands differentially expressed on tumor cells. DeltEx drug resistant immunotherapy (DRI), a novel ex vivo expanded, activated γδ T cell expresses MGMT, conveying TMZ resistance. NCT04165941 , a phase 1 trial assessing the safety of single and multiple infusions of autologous DeltEx DRI cells presents updated safety and efficacy data. Methods: Adult newly diagnosed GBM patients with adequate organ function and KPS≥70% are enrolled. Cells engineered from apheresis after tumor resection were infused through a Rickham catheter placed during surgery. Cohort (C) 1, 2 and 3 receive 1, 3 and 6 doses of cells respectively on day (D) 1 of each 28-day maintenance cycle. Patients receive 1 x 107 γδ T cells intratumorally on D1 with 150 mg/m2 of TMZ intravenously with the Stupp regimen. Primary endpoint is safety; secondary endpoints include progression free and overall survival. Immunologic and genomic correlative analyses are being conducted. Dose limiting toxicities (DLTs) are defined as treatment related ≥ grade 3 cardiopulmonary or hepatic toxicity, grade 4 toxicity exceeding 72 hours or neurologic deterioration that exceeds 2 weeks. Results: 12 patients (58% male; median age 66.5 (range: 21-76); 66.7% IDH-WT, 66.7% MGMT unmethylated) were enrolled with 6 dosed (3 in C1, 3 in C2). No patients had DLTs, cytokine release syndrome (CRS), or neurotoxicity. The most common adverse events (AEs) were Grade 1/2 events including fever, leukopenia, nausea, and vomiting attributable to TMZ or radiotherapy. One subject had Grade 3 treatment related AEs of UTI, dehydration, and thrombocytopenia. Three evaluable C1 patients have PFS of 8.3, 11.9, 7.4 months and OS of 15.6, 17.7 and 9.6 months respectively. In C2, three patients have been dosed, with one patient with stable disease at 8.2 months after receiving all three doses and no DLTs. Patient recruitment continues with anticipated completion in 2022. Conclusions: Data demonstrates that single, repeat doses of DRI T cells have manageable toxicity with encouraging trend in PFS.

Atlantic salmon aquaculture is expanding, and with it, the need to find suitable replacements for conventional protein sources used in formulated feeds. Torula yeast (Cyberlindnera jadinii), has been identified as a promising alternative protein for feed and can be sustainably cultivated on lignocellulosic biomasses. The present study investigated the impact of torula yeast on the growth performance and gut microbiome of freshwater Atlantic salmon. A marine protein base diet and a mixed marine and plant protein base diet were tested, where conventional proteins were replaced with increasing inclusion levels of torula yeast, (0%, 10%, 20%). This study demonstrated that 20% torula yeast can replace fish meal without alteration to growth performance while leading to potential benefits for the gut microbiome by increasing the presence of bacteria positively associated with the host. However, when torula yeast replaced plant meal in a mixed protein diet, results suggested that 10% inclusion of yeast produced the best growth performance results but at the 20% inclusion level of yeast, potentially negative changes were observed in the gut microbial community, such as a decrease in lactic acid bacteria. This study supports the continued investigation of torula yeast for Atlantic salmon as a partial replacement for conventional proteins.

Certain aminoglycosides are capable of inducing "translational readthrough" of premature termination codons (PTCs). However, toxicity and relative lack of efficacy deter treatment with clinically available aminoglycosides for genetic diseases caused by PTCs, including cystic fibrosis (CF). Using a structure-based approach, the novel aminoglycoside NB54 was developed that exhibits reduced toxicity and enhanced suppression of PTCs in cell-based reporter assays relative to gentamicin. We examined whether NB54 administration rescued CFTR protein and function in clinically relevant CF models. In a fluorescence-based halide efflux assay, NB54 partially restored halide efflux in a CF bronchial epithelial cell line (CFTR genotype W1282X/F508del), but not in a CF epithelial cell line lacking a PTC (F508del/F508del). In polarized airway epithelial cells expressing either a CFTR-W1282X or -G542X cDNA, treatment with NB54 increased stimulated short-circuit current (I (SC)) with greater efficiency than gentamicin. NB54 and gentamicin induced comparable increases in forskolin-stimulated I (SC) in primary airway epithelial cells derived from a G542X/F508del CF donor. Systemic administration of NB54 to Cftr-/- mice expressing a human CFTR-G542X transgene restored 15-17% of the average stimulated transepithelial chloride currents observed in wild-type (Cftr+/+) mice, comparable to gentamicin. NB54 exhibited reduced cellular toxicity in vitro and was tolerated at higher concentrations than gentamicin in vivo. These results provide evidence that synthetic aminoglycosides are capable of PTC suppression in relevant human CF cells and a CF animal model and support further development of these compounds as a treatment modality for genetic diseases caused by PTCs.

We correlated the mean transcranial Doppler blood flow velocity (FVm) during carotid endarterectomy with the functional collateral pathway(s) documented by angiography. Three patient groups were established: group 1 was dependent on the anterior communicating artery, group 2 on the anterior communicating artery and ipsilateral posterior communicating artery, and group 3 on the ipsilateral posterior communicating artery. Continuous middle cerebral artery FVm and electroencephalographic monitoring were performed in 45 patients during carotid endarterectomy. Clamped FVm was lowest in group 3 at 17+/-9 cm/s versus 36+/-16 and 33+/-11 cm/s for groups 1 and 2 (P<0.01). FVm values in groups 1 and 2 were similar. There was significant cerebral arterial vasodilation in group 3 patients on the basis of a pulsatility index of 0.38+/-0.15. The maximum FVm after clamp release was similar among the 3 groups. Normalized blood flow velocity 1 minute before release of the clamp was increased from the minimum flow velocity after clamping only in group 1 and 2 patients. The ipsilateral posterior communicating artery is a minor collateral pathway during acute carotid occlusion that contributes little to the collateral flow if there is a functional anterior communicating artery. Collateral flow through the middle cerebral artery is not recruited during occlusion in group 3 patients. The reperfusion FVm transient is independent of the primary collateral pathway. Documentation of functional collateral pathways on the basis of Doppler or angiographic examination may be advantageous in future studies since it can provide the basis for comparison among studies.