An Effective and Safe Enkephalin Analog for Antinociception.
Ontology highlight
ABSTRACT:
SUBMITTER: Viswanadham KKD
PROVIDER: S-EPMC8308721 | biostudies-literature |
REPOSITORIES: biostudies-literature
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2023-07-07 | GSE236502 | GEO
Project description:Introduction:Percutaneous nephrolithotomy (PCNL) is traditionally performed with the patient in the prone position for large renal calculi. However, anesthetic limitations exist with the prone position. Similarly, the supine position is associated with poorer ergonomics due to the awkward downward position of the renal tract, a smaller window for percutaneous puncture, and a higher risk of anterior calyx puncture. This study aimed to demonstrate the feasibility and safety of lateral-PCNL in managing large renal calculi without the disadvantages of prone and supine positions. Methods:Retrospectively, 347 lateral-PCNL cases performed from July 2001 to July 2015 were examined. the patient's thorax, abdomen, and pelvis were positioned over a bridge perpendicular to a "broken" table, creating an extended lumbodorsal space. The procedure was evaluated in terms of stone clearance at 3 months' postprocedure, operative time, and complications. Results:Primary stone clearance was achieved in 82.7% of patients. The mean operating time was 97 min. The average time taken to establish the tract and mean radiation time were 4.5 min and 6.93 min, respectively. In total, 2.3% of patients required postoperative transfusion, and 13.5% of patients had postoperative fever. There was one case of hydrothorax, but no bowel perforation. Conclusions:Our lateral-PCNL technique allows for effective stone clearance due to good stone ergonomics and it should be considered as a safe alternative even in the most routine procedures.
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Project description:ObjectivesThe global spread of SARS-CoV-2 is a serious public health issue. Large-scale surveillance screenings are crucial but can exceed test capacities. We (A) optimized test conditions and (B) implemented pool testing of respiratory swabs into SARS-CoV-2 diagnostics.Study design(A) We determined the optimal pooling strategy and pool size. In addition, we measured the impact of vortexing prior to sample processing, compared a pipette-pooling method (by combining transport medium of several specimens) and a swab-pooling method (by combining several swabs into a test tube filled with PBS) as well as determined the sensitivities of three PCR assays. (B) Finally, we applied high-throughput pool testing for diagnostics.Results(A) In a low prevalence setting, we defined a preferable pool size of ten in a two-stage hierarchical pool testing strategy. Vortexing of swabs (n = 33) increased cellular yield by a factor of 2.34. By comparing Ct-values of 16 pools generated with two different pooling strategies, pipette-pooling was more efficient compared to swab-pooling. Measuring dilution series of 20 SARS-CoV-2 positive samples in three PCR assays simultaneously revealed detection rates of 85% (assay I), 50% (assay II), and 95% (assay III) at a 1:100 dilution. (B) We systematically pooled 55,690 samples in a period of 44 weeks resulting in a reduction of 47,369 PCR reactions.ConclusionsFor implementing pooling strategies into high-throughput diagnostics, we recommend utilizing a pipette-pooling method, performing sensitivity validation of the PCR assays used, and vortexing swabs prior to analyses. Pool testing for SARS-CoV-2 detection is feasible and effective in a low prevalence setting.
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Project description:Recent efforts to develop tumor-targeted photodynamic therapy (PDT) photosensitizers (PSs) have greatly advanced the potential of PDT in cancer therapy, although complete eradication of tumor cells by PDT alone remains challenging. As a way to improve PDT efficacy, we report a new combinatory PDT therapy technique that specifically targets multilayers of cells. Simply mixing different PDT PSs, even those that target distinct receptors (this may still lead to similar cell-killing pathways), may not achieve ideal therapeutic outcomes. Instead, significantly improved outcomes likely require synergistic therapies that target various cellular pathways. In this study, we target two proteins upregulated in cancers: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the CB2R-targeted PS, IR700DX-mbc94, triggered necrotic cell death upon light irradiation, whereas PDT with the TSPO-targeted IR700DX-6T agent led to apoptotic cell death. Both PSs significantly inhibited tumor growth in vivo in a target-specific manner. As expected, the combined CB2R- and TSPO-PDT resulted in enhanced cell killing efficacy and tumor inhibition with lower drug dose. The median survival time of animals with multilayer PDT treatment was extended by as much as 2.8-fold over single PDT treatment. Overall, multilayer PDT provides new opportunities to treat cancers with high efficacy and low side effects.Statement of significancePhotodynamic therapy (PDT) is increasingly used as a minimally invasive, controllable and effective therapeutic procedure for cancer treatment. However, complete eradication of tumor cells by PDT alone remains challenging. In this study, we investigate the potential of multilayer PDT in cancer treatment with high efficacy and low side effects. Through PDT targeting two cancer biomarkers located at distinct subcellular localizations, remarkable synergistic effects in cancer cell killing and tumor inhibition were observed in both in vitro and in vivo experiments. This strategy may be widely applied to treat various cancer types by using strategically designed PDT photosensitizers that target corresponding upregulated receptors at tactical subcellular localization.
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Project description:Antigen-specific immunotherapy combats autoimmunity or allergy by reinstating immunological tolerance to target antigens without compromising immune function. Optimization of dosing strategy is critical for effective modulation of pathogenic CD4(+) T-cell activity. Here we report that dose escalation is imperative for safe, subcutaneous delivery of the high self-antigen doses required for effective tolerance induction and elicits anergic, interleukin (IL)-10-secreting regulatory CD4(+) T cells. Analysis of the CD4(+) T-cell transcriptome, at consecutive stages of escalating dose immunotherapy, reveals progressive suppression of transcripts positively regulating inflammatory effector function and repression of cell cycle pathways. We identify transcription factors, c-Maf and NFIL3, and negative co-stimulatory molecules, LAG-3, TIGIT, PD-1 and TIM-3, which characterize this regulatory CD4(+) T-cell population and whose expression correlates with the immunoregulatory cytokine IL-10. These results provide a rationale for dose escalation in T-cell-directed immunotherapy and reveal novel immunological and transcriptional signatures as surrogate markers of successful immunotherapy.
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Project description:Intervention1: Irinotecan injection: ?Irinotecan injection 180 mg/m2 IV over 90 min, on Day 1, Day 15, Day 29 of each cycle.
Combination Drug:
?Leucovorin 200 mg/m2 IV over 2 hrs, on Day 1, Day 2, Day 15, Day 16, Day 29, and Day30 of each cycle.
?5-Fluoro Uracil bolus 400 mg/m2 IV bolus, on Day 1, Day 2, Day 15, Day 16, Day 29, and Day 30 of each cycle.
?5-Fluoro Uracil infusion 600 mg/m2 IV over 22 hrs, on Day1, Day 2, Day 15, Day 16, Day29, and Day 30 of each cycle.
Control Intervention1: NIL: NIL
Primary outcome(s): Overall Objective Response Rate (ORR) by RECIST criteria version 1.1Timepoint: Measured at baseline, before initiation of 3rd cycle (Day85), at the end of 6th cycle (Day240) and if required at the end of the study (1 year)
| 2572851 | ecrin-mdr-crc
Project description:OBJECTIVE:To evaluate the efficacy of a portable, wearable, wireless artificial pancreas system (the Diabetes Assistant [DiAs] running the Unified Safety System) on glucose control at home in overnight-only and 24/7 closed-loop control (CLC) modes in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS:At six clinical centers in four countries, 30 participants 18-66 years old with type 1 diabetes (43% female, 96% non-Hispanic white, median type 1 diabetes duration 19 years, median A1C 7.3%) completed the study. The protocol included a 2-week baseline sensor-augmented pump (SAP) period followed by 2 weeks of overnight-only CLC and 2 weeks of 24/7 CLC at home. Glucose control during CLC was compared with the baseline SAP. RESULTS:Glycemic control parameters for overnight-only CLC were improved during the nighttime period compared with baseline for hypoglycemia (time <70 mg/dL, primary end point median 1.1% vs. 3.0%; P < 0.001), time in target (70-180 mg/dL: 75% vs. 61%; P < 0.001), and glucose variability (coefficient of variation: 30% vs. 36%; P < 0.001). Similar improvements for day/night combined were observed with 24/7 CLC compared with baseline: 1.7% vs. 4.1%, P < 0.001; 73% vs. 65%, P < 0.001; and 34% vs. 38%, P < 0.001, respectively. CONCLUSIONS:CLC running on a smartphone (DiAs) in the home environment was safe and effective. Overnight-only CLC reduced hypoglycemia and increased time in range overnight and increased time in range during the day; 24/7 CLC reduced hypoglycemia and increased time in range both overnight and during the day. Compared with overnight-only CLC, 24/7 CLC provided additional hypoglycemia protection during the day.
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