Iveyknapp9485
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has demonstrated notable clinical activity in cancer immunotherapy, but it is limited by systemic toxicities, poor bioavailability, rapid clearance, and instability in vivo. Nanoparticles (NPs) may overcome these limitations and provide a mechanism for passive targeting of tumors. This study aimed to develop GM-CSF-loaded PLGA/PLGA-PEG NPs and evaluate them in vitro as a potential candidate for in vivo administration. NPs were created by a phase-separation technique that did not require toxic/protein-denaturing solvents or harsh agitation techniques and encapsulated GM-CSF in a more stable precipitated form. NP sizes were within 200 nm for enhanced permeability and retention (EPR) effect with negative zeta potentials, spherical morphology, and high entrapment efficiencies. The optimal formulation was identified by sustained release of approximately 70% of loaded GM-CSF over 24 h, alongside an average size of 143 ± 35 nm and entrapment efficiency of 84 ± 5%. These NPs were successfully freeze-dried in 5% (w/v) hydroxypropyl-β-cyclodextrin for long-term storage and further characterized. Bioactivity of released GM-CSF was determined by observing GM-CSF receptor activation on murine monocytes and remained fully intact. NPs were not cytotoxic to murine bone marrow-derived macrophages (BMDMs) at concentrations up to 1 mg/mL as determined by MTT and trypan blue exclusion assays. Lastly, NP components generated no significant transcription of inflammation-regulating genes from BMDMs compared to IFNγ+LPS "M1" controls. This report lays the preliminary groundwork to validate in vivo studies with GM-CSF-loaded PLGA/PEG-PLGA NPs for tumor immunomodulation. Overall, these data suggest that in vivo delivery will be well tolerated.Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. A recently described nuclear-grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The present study was undertaken to validate this grading system in epithelioid malignant peritoneal mesothelioma (EMPM) and to compare to combined grade, including nuclear atypia, mitotic count, and tumor necrosis. Cases of EMPM, from 1995 to 2018, were analyzed from 7 French institutions from RENAPE network. Solid growth, tumor necrosis, nuclear atypia, and mitotic count were evaluated by at least 3 pathologists from the RENAPATH group. The predictions in terms of OS and PFS of nuclear grade and combined grade were analyzed. Nuclear grade was computed combining nuclear atypia score and mitotic count into a grade of I-III. Another system combining nuclear atypia score, mitotic score, and tumor necrosis was evaluated and defined as a combined grade I-III. A total of 138 cases were identified. The median follow-up was 38.9 months (range 1.1-196.6). Nuclear and combined grades III were independently associated with a shorter OS (p less then 0.05), and a shorter PFS (p less then 0.05). Patients with combined grade I tumors had the best overall and progression-free survivals, in comparison to nuclear grade I. In this large multicentric study, combined grade and nuclear grade were the best independent predictors of OS and PFS in EMPM. These systems should be easily described by pathologists involved into the management of malignant peritoneal mesothelioma, because of their potential therapeutic implications.Pakistan has 35 goat breeds. Moreover, the province of Punjab has highest goat population constituting 37% of country's total population with seven goat breeds including Beetal, Daira Deen Panah, Nachi, Barbari, Teddi, Pahari, and Pothwari. The diversity study of breeds warrants the documentation of breeds particularly using genome wide panel of markers, i.e., SNP chip. The objective of the current study was to fill this gap of information. Therefore, in current study we collected total of 879 unrelated goat blood samples along with data on body weight measurements; genomic DNA was extracted, and genotyping was carried out using 50 K SNP bead chip. Quality control measures were performed in Plink 1.07. Genetic diversity was observed among studied populations using heterozygosity and pairwise FST estimates, principal component analysis, admixture analysis in Plink software with visualization in Clumpak, and constructing phylogenetic tree in Mega 7 software. Moderate to high level of heterozygosity was observedal breeding schemes.
In the rapidly-progressing healthcare environment, it is essential to improve treatment quality through continuous clarification of the needs and concerns of esophageal cancer patients and their families. Effective collaboration between information providers and academic associations could help make such clarified information available.
We analyzed esophageal cancer patients' views and preferences (PVPs) using data that were previously obtained from medical staff in Japan. Based on these PVPs, we created a question and answer (Q&A) resource through collaboration with the Cancer Information Service in Japan (CISJ) and the Japan Esophageal Society (JES).
Regarding esophageal cancer, "diet and eating behavior" was the most frequent PVP mentioned by patients and their families, followed by "treatment-related symptoms and adverse effects" and "daily life, recuperation, and survivorship." These PVPs were noted by a wide variety of medical specialties. By analyzing the PVPs, the CISJ developed 11 proposed questions and sent them to the JES, which then created answers based on evidence and clinical-practice-associated consensus. The resultant Q&A resource was uploaded to the CISJ website with mutual linkage to the JES website.
This study showed the usefulness of collecting esophageal-cancer-related PVPs from medical staff and fostering successful collaboration between a cancer-information provider and an academic association. This arrangement may represent a model case for developing a sustainable system that can satisfactorily respond to PVPs regarding other cancers and/or issues.
This study showed the usefulness of collecting esophageal-cancer-related PVPs from medical staff and fostering successful collaboration between a cancer-information provider and an academic association. This arrangement may represent a model case for developing a sustainable system that can satisfactorily respond to PVPs regarding other cancers and/or issues.
In this retrospective study, we compared inhaled sedation with isoflurane to intravenous propofol in invasively ventilated COVID-19 patients with ARDS (Acute Respiratory Distress Syndrome).
Charts of all 20 patients with COVID-19 ARDS admitted to the ICU of a German University Hospital during the first wave of the pandemic between 22/03/2020 and 21/04/2020 were reviewed. Among screened 333days, isoflurane was used in 97days, while in 187days, propofol was used for 12 h or more. The effect and dose of these two sedatives were compared. Mixed sedation days were excluded.
Patients' age (median [interquartile range]) was 64 (60-68) years. They were invasively ventilated for 36 [21-50] days. End-tidal isoflurane concentrations were high (0.96 ± 0.41 Vol %); multiple linear regression yielded the ratio (isoflurane infusion rate)/(minute ventilation) as the single best predictor. TBOPP Infusion rates were decreased under ECMO (3.5 ± 1.4 versus 7.1 ± 3.2ml∙h
; p < 0.001). In five patients, the maximum recommended dose of propofol of 4mg∙hour
∙kg
ABW was exceeded on several days. On isoflurane compared to propofol days, neuro-muscular blocking agents (NMBAs) were used less frequently (11% versus 21%; p < 0.05), as were co-sedatives (7% versus 31%, p < 0.001); daily opioid doses were lower (720 [720-960] versus 1080 [720-1620] mg morphine equivalents, p < 0.001); and RASS scores indicated deeper levels of sedation (-4.0 [-4.0 to -3.0] versus -3.0 [-3.6 to -2.5]; p < 0.01).
Isoflurane provided sufficient sedation with less NMBAs, less polypharmacy and lower opioid doses compared to propofol. High doses of both drugs were needed in severely ill COVID-19 patients.
Isoflurane provided sufficient sedation with less NMBAs, less polypharmacy and lower opioid doses compared to propofol. High doses of both drugs were needed in severely ill COVID-19 patients.The usefulness and safety of continuous glucose monitoring (CGM) systems in adult patients with severe coronavirus disease (COVID-19) have been reported. Using CGM might reduce the exposure patients and healthcare workers to COVID-19 and limit the use of personal protective equipment during the pandemic. CGM devices measure glucose in the subcutaneous interstitial fluid, but the accuracy of this technique has not been established in critically ill patients. The artificial pancreas, STG-55 (Nikkiso, Tokyo), is a closed-loop device that conducts continuous blood glucose monitoring using a peripheral vein. We used the STG-55 for glucose control in a 60-year-old woman with severe COVID-19 admitted to the intensive care unit. Due to severe respiratory failure, the patient was intubated, and extracorporeal membrane oxygenation was introduced. Because she had hyperglycemia despite high-dose intravenous insulin therapy, we decided to use STG-55 for glucose control. The STG-55 safely titrated the insulin infusion and monitored glucose levels. Fifty-six hours after adopting the STG-55, it was removed because the blood sampling failed. No episodes of hypoglycemia were observed despite deep sedation during this period. In conclusion, this case demonstrates the potential utility of an artificial pancreas in patients with severe COVID-19.Global climate change has drastically affected natural ecosystems and crop productivity. Among several factors of global climate change, CO2 is considered to be the dynamic parameter that will regulate the responses of all biological system on earth in the coming decade. A number of experimental studies in the past have demonstrated the positive effects of elevated CO2 on photosynthesis, growth and biomass, biochemical and physiological processes such as increased CN ratio, secondary metabolite production, as well as phytohormone concentrations. On the other hand, elevated CO2 imparts an adverse effect on the nutritional quality of crop plants and seed quality. Investigations have also revealed effects of elevated CO2 both at cellular and molecular level altering expression of various genes involved in various metabolic processes and stress signaling pathways. Elevated CO2 is known to have mitigating effect on plants in presence of abiotic stresses such as drought, salinity, temperature etc., while contrasting effects in the presence of different biotic agents i.e. phytopathogens, insects and herbivores. However, a well-defined crosstalk is incited by elevated CO2 both under abiotic and biotic stresses in terms of phytohormones concentration and secondary metabolites production. With this background, the present review attempts to shed light on the major effects of elevated CO2 on plant growth, physiological and molecular responses and will highlight the interactive effects of elevated CO2 with other abiotic and biotic factors. The article will also provide deep insights into the phytohormones modulation under elevated CO2.
