1,774 research outputs found
EVALUATION OF THE PHYSICOCHEMICAL PROPERTIES AND STABILITY OF SOLID LIPID NANOPARTICLES DESIGNED FOR THE DELIVERY OF DEXAMETHASONE TO TUMORS
Pre-clinical and clinical trials suggest that pre-treatment with dexamethasone (Dex) may facilitate enhanced uptake of subsequently administered chemotherapeutic agents. To reduce the side effects associated with systemic administration of Dex, solid lipid nanoparticles (SLNs) containing dexamethasone palmitate (Dex-P) were prepared as a means of achieving tumor-targeted drug delivery. These studies were aimed at evaluating the physicochemical properties and both the physiological and storage stability of the SLNs.
SLNs were prepared using nanotemplate engineering technology. Stearyl alcohol (SA) was used as the lipid phase with BrijÂź 78 and Polysorbate 60 as surfactants and PEG6000 monostearate as a long-chain PEGylating agent. Both formulations exhibited a small particle size, ellipsoidal shape, and low polydispersity. 1H-NMR spectroscopy confirmed that SLNs have the expected solid core and PEGylated surface. Analysis of the bulk materials indicated that a number of complex interactions are present among the SLN components, including a eutectic between SA and BrijÂź 78.
Dex-P could be incorporated in SLNs at 10-30% w/w SA with encapsulation efficiencies \u3e85%. A preferential interaction with the SA-BrijÂź 78 eutectic was identified, indicating a possible interfacial localization. For comparison, SLNs were also prepared with ascorbyl palmitate (AP) and curcumin. Higher drug loads were achieved with both palmitate-containing prodrugs than curcumin, though all appeared to align differently within the SLNs.
SLNs undergo a concentration-dependent particle size growth when incubated at physiological temperature. However, they appear to remain intact with over 85% of the added Dex-P retained at 24 h in conditions mimicking human plasma. In the presence of carboxylesterase, SLNs became turbid and showed a reduction in particle size as compared to controls. This instability was shown to be a result of the hydrolysis of PEG6000 monostearate and Polysorbate 60.
To enhance storage stability, a lyophilization protocol designed to minimize changes in the physicochemical properties of SLNs was developed. During a 3 month period, lyophilized SLNs stored at 4°C demonstrated the greatest stability, showing a consistent particle size and an encapsulation efficiency \u3e80%. Overall, these results indicate that Dex-P loaded SLNs possess the physicochemical properties and stability desirable for development as a tumor-targeted drug delivery system
Feasibility and preliminary efficacy of remotely delivering cognitive training to people with schizophrenia using tablets.
Limited access to Cognitive Training (CT) for people with schizophrenia (SZ) prevents widespread adoption of this intervention. Delivering CT remotely via tablets may increase accessibility, improve scheduling flexibility, and diminish patient burden.In this reanalysis of data from a larger trial of CT, we compared two samples of individuals with SZ who chose to complete 40Â h of CT either on desktop computers in the laboratory (NÂ =Â 33) or remotely via iPads (NÂ =Â 41). We examined attrition rates and adherence to training, and investigated whether remote iPad-based CT and in-person desktop-based CT induced significantly different improvements in cognitive and real-world functioning.The attrition rate was 36.6%. On average, participants completed 3.06Â h of CT per week. There were no significant between-group differences in attrition and adherence to CT requirements. Participants who completed iPad-based CT were significantly younger and had lower symptoms at baseline compared to participants who completed CT on the lab desktops. Controlling for age and symptom severity, rANCOVA showed that iPad-based and desktop-based CT similarly and significantly improved verbal learning and problem solving. Main effects of time, at trend level significance, were evident in global cognition, verbal memory, quality of life, and social functioning. All group by time interactions were non-significant except for verbal memory, where iPad users showed greater gains. Within-group effect sizes for changes in outcomes were in the small range.Although underpowered and not randomized, this study demonstrates that delivering CT remotely to people with SZ using tablets is feasible and results in retention rates, adherence, and cognitive and functional outcome improvements that are comparable to those observed when CT is delivered in the laboratory. This has important implications in terms of scalability and dissemination of CT. These results require confirmation in larger samples
Redeemed
The purpose for this dress came from mission trips. On these trips, I saw houses that were made from or repaired with garbage bags. There was also an area where the people lived near the garbage dump. This reminded me of populations of people that are written off as âunworthyâ or âundesirable.
Binary Central Stars of Planetary Nebulae Discovered Through Photometric Variability III: The Central Star of Abell 65
A growing number of close binary stars are being discovered among central
stars of planetary nebulae. Recent and ongoing surveys are finding new systems
and contributing to our knowledge of the evolution of close binary systems. The
push to find more systems was largely based on early discoveries which
suggested that 10 to 15% of all central stars are close binaries. One goal of
this series of papers is confirmation and classification of these systems as
close binaries and determination of binary system parameters. Here we provide
time-resolved multi-wavelength photometry of the central star of Abell 65 as
well as further analysis of the nebula and discussion of possible
binary--nebula connections. Our results for Abell 65 confirm recent work
showing that it has a close, cool binary companion, though several of our model
parameters disagree with the recently published values. With our longer time
baseline of photometric observations from 1989--2009 we also provide a more
precise orbital period of 1.0037577 days.Comment: Accepted for publication in the Astronomical Journa
Student and Instructor Perceptions of Online Teaching Related to COVID-19: The Need for Reflective Practices
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Although online learning has been in existence for over 20 years, not all instructors have been trained to teach online or had the desire to teach online. The recent COVID-19 pandemic quickly changed typical face-to-face instruction and disrupted the current educational system by requiring all college courses be delivered online, either asynchronous or synchronous using various software platforms. This paper investigated both instructorsâ and studentsâ perceptions of faculty online teaching preparedness as well as their thoughts related to various technological resources and issues that arose during this time period. Results indicated fairly high satisfaction rates of facultyâs thoughts on preparedness and access to technological resources and tools. Students were fairly satisfied with the transition to online teaching and learning using quantitative measures; however, qualitative comments indicated otherwise. The need to use more reflective and metacognitive strategies to better online pedagogy as well as communicate more with students through a virtual environment was discovered
Germline and Somatic DNA Damage Repair Gene Mutations and Overall Survival in Metastatic Pancreatic Adenocarcinoma Patients Treated with FOLFIRINOX
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with lack of predictive biomarkers. We conducted a study to assess DNA damage repair (DDR) gene mutations as a predictive biomarker in PDAC patients treated with FOLFIRINOX.
Experimental Design: Indiana University Simon Cancer Center pancreatic cancer database was used to identify patients with metastatic PDAC, treated with FOLFIRINOX and had tissue available for DNA sequencing. Baseline demographic, clinical, and pathologic information was gathered. DNA isolation and targeted sequencing was performed using the Ion AmpliSeq protocol. Overall survival (OS) analysis was conducted using KaplanâMeier, logistic regression and Cox proportional hazard methods. Multivariate models were adjusted for age, gender, margin status, CA 19-9, adjuvant chemotherapy, tumor and nodal stage.
Results: Overall, 36 patients were sequenced. DDR gene mutations were found in 12 patients. Mutations were seen in BRCA1 (N = 7), BRCA2 (N = 5), PALB2 (N = 3), MSH2 (N = 1), and FANCF (N = 1) of all the DDR genes sequenced. Median age was 65.5 years, 58% were male, 97.2% were Caucasian and 51.4% had any family history of cancer. The median OS was near significantly superior in those with DDR gene mutations present vs. absent [14 vs. 5 months; HR, 0.58; 95% confidence interval (CI), 0.29â1.14; log-rank P = 0.08]. Multivariate logistic (OR, 1.47; 95% CI, 1.04â2.06; P = 0.04) and Cox regression (HR, 0.37; 95% CI, 0.15â0.94; P = 0.04) showed presence of DDR gene mutations was associated with improved OS.
Conclusions: In a single institution, retrospective study, we found that the presence of DDR gene mutations are associated with improved OS in PDAC patients treated with FOLFIRINOX
Shaping our literate lives: Examining the role of literacy experiences in shaping positive literacy identities of doctoral students
The purpose of this study was to examine the ways in which literacy histories and present literacy experiences of doctoral students shaped their literacy identities. Data were collected through surveys, interviews, and visual identity representations. This paper focuses on the literacy stories of two doctoral students with positive literacy identities. Findings suggest that participants valued literacy as a social learning experience from an early age through higher education. These social experiences with reading and writing can take many forms and can be embraced in various home and school contexts. Additionally, these findings highlight the need for schools to create and nurture such experiences across all grade levels, through multiple forums, which may lead to positive literacy identities
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Six month durability of targeted cognitive training supplemented with social cognition exercises in schizophrenia.
Background:Deficits in cognition, social cognition, and motivation are significant predictors of poor functional outcomes in schizophrenia. Evidence of durable benefit following social cognitive training is limited. We previously reported the effects of 70Â h of targeted cognitive training supplemented with social cognitive exercises (TCTÂ +Â SCT) verses targeted cognitive training alone (TCT). Here, we report the effects six months after training. Methods:111 participants with schizophrenia spectrum disorders were randomly assigned to TCTÂ +Â SCT or TCT-only. Six months after training, thirty-four subjects (18 TCTÂ +Â SCT, 16 TCT-only) were assessed on cognition, social cognition, reward processing, symptoms, and functioning. Intent to treat analyses was used to test the durability of gains, and the association of gains with improvements in functioning and reward processing were tested. Results:Both groups showed durable improvements in multiple cognitive domains, symptoms, and functional capacity. Gains in global cognition were significantly associated with gains in functional capacity. In the TCTÂ +Â SCT group, participants showed durable improvements in prosody identification and reward processing, relative to the TCT-only group. Gains in reward processing in the TCTÂ +Â SCT group were significantly associated with improvements in social functioning. Conclusions:Both TCTÂ +Â SCT and TCT-only result in durable improvements in cognition, symptoms, and functional capacity six months post-intervention. Supplementing TCT with social cognitive training offers greater and enduring benefits in prosody identification and reward processing. These results suggest that novel cognitive training approaches that integrate social cognitive exercises may lead to greater improvements in reward processing and functioning in individuals with schizophrenia
Utilization of direct smears of thyroid fineâneedle aspirates for ancillary molecular testing: A comparison of two proprietary testing platforms
Background
Ancillary molecular testing has been recommended for thyroid fineâneedle aspirates (FNA) with indeterminate cytologic diagnoses. Rosetta Genomics and Interpace Diagnostics have developed assays that can utilize direct smears as the testing substrate.
Methods
A retrospective study of indeterminate thyroid FNAs with known histologic followâup was performed. One DiffâQuikâstained smear and one Papanicolaouâstained smear with similar cellularity (at least 60â100 lesional cells) from each case were sent to Rosetta and Interpace, respectively, for analysis. The results were directly compared and correlated with the final histopathology. Neither company was aware of the followâup histologic findings in these cases.
Results
A total of 10 thyroid FNAs were identified from our 2015 files. The cytologic diagnoses included follicular lesion of undetermined significance (FLUS, nâ=â5), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN, nâ=â4), and suspicious for malignancy (SM, nâ=â1). Of the seven cases with benign histology, six smears were classified as benign by the RosettaGX microRNA classifier, and one case was designated as suspicious. Five cases were negative by both ThyGenX oncogene panel and ThyraMIR microRNA classifier. One case was negative by ThyGenX and positive on followâup ThyraMIR, and one case was positive for KRAS mutation and positive on ThyraMIR. Both the RosettaGX and ThyGenX/ThyraMIR tests demonstrated positive results for the three histologically malignant cases.
Conclusion
This study demonstrates that two molecular testing platforms performed equally well using our stained direct smears. Both molecular tests revealed a 100% negative predictive rate. RosettaGX showed a 75% positive predictive value in comparison to 60% for ThyGenX/ThyraMIR
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