Preclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack of a suitable large animal model.
To develop and characterize a porcine model of ...pancreatic cancer. Unlike small animals, pigs have similar physiology, drug dosing, and immune response to humans. Locoregional therapy in pigs can be performed using the same size catheters and devices as in humans.
The Oncopig is a transgenic pig with Cre-inducible TP53R167H and KRASG12D mutations. In 12 Oncopigs, CT-guided core biopsy of the pancreas was performed. The core biopsy was incubated with an adenoviral vector carrying the Cre recombinase gene. The transformed core biopsy was injected back into the pancreas (head, tail, or both). The resulting tumors (n = 19) were characterized on multi-phase contrast-enhanced CT, and on pathology, including immunohistochemistry. Angiographic characterization of the tumors was performed in 3 pigs.
Pancreatic tumors developed at 19 out of 22 sites (86%) that were inoculated. Average tumor size was 3.0 cm at 1 week (range: 0.5-5.1 cm). H&E and immunohistochemical stains revealed undifferentiated carcinomas, similar to those of the pancreatobiliary system in humans. Neoplastic cells were accompanied by a major inflammatory component. 1 of 12 pigs only had inflammatory nodules without evidence of neoplasia. On multiphase CT, tumors were hypovascular compared to the normal pancreas. There was no pancreatic duct dilation. In 3 pigs, angiography was performed, and in all 3 cases, the artery supplying the pancreatic tumor could be catheterized using a 2.4 F microcatheter. Selective angiography showed the pancreatic tumor, without extra-pancreatic perfusion.
Pancreatic cancer can be induced in a transgenic pig. Intra-arterial procedures using catheters designed for human interventions were technically feasible in this large animal model.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Matricaria discoidea DC. (Asteraceae) has documented use as an insect repellent by Blackfoot Indians and other indigenous groups of North America. This investigation was conducted to evaluate this ...practice and systematically identify chemical constituents responsible for any insect repelling effect by utilizing a mosquito (Aedes aegypti (Linnaeus)) biting deterrent bioactivity-directed purification approach. Hydrodistilled oil from dried aerial parts of M. discoidea was the most bioactive crude extract generated and was as. Fractionation of this extract, followed by re-evaluation for mosquito biting deterrence using the K & D (Klun and Debboun) bioassay, produced many active fractions that were subsequently evaluated by spectroscopic techniques and the most active compounds were determined to be α-terpineol, spathulenol, and neryl isovalerate. A & K (Ali and Khan) large cage in vitro evaluation of pure compounds isolated from M. discoidea indicated α-terpineol to be the most active compound providing complete protection at 25 μg/cm2. This is the first report on the mosquito repellency of neryl isovalerate and scientific evidence reported here validates the traditional use of M. discoidea as a biting-insect deterrent.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genomic instability plays an important role in human cancers. We previously characterized genomic instability in esophageal squamous cell carcinomas (ESCC) in terms of loss of heterozygosity (LOH) ...and copy number (CN) changes in tumors using the Affymetrix GeneChip Human Mapping 500K array in 30 cases from a high-risk region of China. In the current study we focused on copy number neutral (CN = 2) LOH (CNNLOH) and its relation to gene expression in ESCC.
Overall we found that 70% of all LOH observed was CNNLOH. Ninety percent of ESCCs showed CNNLOH (median frequency in cases = 60%) and this was the most common type of LOH in two-thirds of cases. CNNLOH occurred on all 39 autosomal chromosome arms, with highest frequencies on 19p (100%), 5p (96%), 2p (95%), and 20q (95%). In contrast, LOH with CN loss represented 19% of all LOH, occurred in just half of ESCCs (median frequency in cases = 0%), and was most frequent on 3p (56%), 5q (47%), and 21q (41%). LOH with CN gain was 11% of all LOH, occurred in 93% of ESCCs (median frequency in cases = 13%), and was most common on 20p (82%), 8q (74%), and 3q (42%). To examine the effect of genomic instability on gene expression, we evaluated RNA profiles from 17 pairs of matched normal and tumor samples (a subset of the 30 ESCCs) using Affymetrix U133A 2.0 arrays. In CN neutral regions, expression of 168 genes (containing 1976 SNPs) differed significantly in tumors with LOH versus tumors without LOH, including 101 genes that were up-regulated and 67 that were down-regulated.
Our results indicate that CNNLOH has a profound impact on gene expression in ESCC, which in turn may affect tumor development.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To simulate the cost-effectiveness of Mesenchymal Stromal Cell (MSC) therapy compared to sodium/glucose co-transporter 2 inhibitors (SGLT2i) or usual care (UC) in treating patients with Diabetic ...Kidney Disease (DKD).
This Markov-chain Monte Carlo model adopted a societal perspective and simulated 10,000 patients with DKD eligible for MSC therapy alongside UC using a lifetime horizon. This cohort was compared with an SGLT2i alongside UC arm and a UC only arm. Model input data were extracted from the literature. A threshold of $47,000 per quality-adjusted life year and a discount rate of 3% were used. The primary outcome measure was incremental net monetary benefit (INMB). Sensitivity analysis was conducted to examine: parameter uncertainty; threshold effects regarding MSC effectiveness and cost; and INMB according to patient age (71 vs 40 years), sex, and jurisdiction (UK, Italy and Ireland).
While MSC was more cost-effective than UC, both the UC and MSC arms were dominated by SLGT2i. Relative to SGLT2i, the INMB's for MSC and UC were -$4,158 and -$10,085 respectively indicating that SGLT2i, MSC and UC had a 64%, 34% and 1% probability of being cost-effective at the given threshold, respectively. This pattern was consistent across most scenarios; driven by the relatively low cost of SGLT2i and demonstrated class-effect in delaying kidney failure and all-cause mortality. When examining younger patients at baseline, SGLT2i was still the most cost-effective but MSC performed better against UC given the increased lifetime benefit from delaying progression to ESRD.
The evidence base regarding the effectiveness of MSC therapy continues to evolve. The potential for these therapies to reverse kidney damage would see large improvements in their cost-effectiveness as would targeting such therapies at younger patients and/or those for whom SGLT2i is contra-indicated.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In recent years high-THC (psychoactive) and low-THC (industrial hemp) type cannabis (
L.) have gained immense attention in medical, food, and a plethora of other consumer product markets. Among the ...planting materials used for cultivation, tissue culture clones provide various advantages such as economies of scale, production of disease-free and true-to-type plants for reducing the risk of GMP-EuGMP level medical cannabis production, as well as the development and application of various technologies for genetic improvement. Various tissue culture methods have the potential application with cannabis for research, breeding, and novel trait development, as well as commercial mass propagation. Although tissue culture techniques for plant regeneration and micropropagation have been reported for different cannabis genotypes and explant sources, there are significant variations in the response of cultures and the morphogenic pathway. Methods for many high-yielding elite strains are still rudimentary, and protocols are not established. With a recent focus on sequencing and genomics in cannabis, genetic transformation systems are applied to medical cannabis and hemp for functional gene annotation via traditional and transient transformation methods to create novel phenotypes by gene expression modulation and to validate gene function. This review presents the current status of research focusing on different aspects of tissue culture, including micropropagation, transformation, and the regeneration of medicinal cannabis and industrial hemp transformants. Potential future tissue culture research strategies helping elite cannabis breeding and propagation are also presented.
Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide and in China. We know miRNAs influence gene expression in tumorigenesis, but it is unclear how miRNAs affect ...gene expression or influence survival at the genome-wide level in ESCC.
We performed miRNA and mRNA expression arrays in 113 ESCC cases with tumor/normal matched tissues to identify dysregulated miRNAs, to correlate miRNA and mRNA expressions, and to relate miRNA and mRNA expression changes to survival and clinical characteristics.
Thirty-nine miRNAs were identified whose tumor/normal tissue expression ratios showed dysregulation (28 down- and 11 up-regulated by at least two-fold with P < 1.92E-04), including several not previously reported in ESCC (miR-885-5p, miR-140-3p, miR-708, miR-639, miR-596). Expressions of 16 miRNAs were highly correlated with expressions of 195 genes (P < 8.42E-09; absolute rho values 0.51-0.64). Increased expressions of miRNA in tumor tissue for both miR-30e* and miR-124 were associated with increased survival (P < 0.05). Similarly, nine probes in eight of 818 dysregulated genes had RNA expression levels that were nominally associated with survival, including NF1, ASXL1, HSPA4, TGOLN2, BAIAP2, EZH2, CHAF1A, SUPT7L.
Our characterization and integrated analysis of genome-wide miRNA and gene expression in ESCC provides insights into the expression of miRNAs and their relation to regulation of RNA targets in ESCC tumorigenesis, and suggest opportunities for the future development of miRs and mRNAs as biomarkers for early detection, diagnosis, and prognosis in ESCC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract We retrospectively reviewed 1012 consecutive patients undergoing elective primary hip and knee arthroplasties to identify risk factors associated with postoperative complications. A total of ...70 complications (6.9%) requiring additional physician interventions occurred following surgery and 59 (84%) occurred past 24 hours postoperatively. Independent multivariate risk factors for developing late (>24 hours) complications included COPD (adjusted OR 4.16), CHF (adjusted OR 9.71), CAD (adjusted OR 2.80), and cirrhosis (adjusted OR 8.43). These results suggest that most major medical complications requiring additional physician interventions occur greater than 24 hours following primary THA/TKA. Patients with history of COPD, CHF, CAD, and cirrhosis should not undergo short stay or outpatient TJA.
Hierochloë odorata (L.) P. Beauv. (Poaceae), commonly known as sweetgrass, has documented use as an insect repellent by the Flatheads of Montana and Blackfoot of Alberta. Both the Flatheads of ...Montana and Blackfoot of Alberta would use braided plant material in a sachet in clothing or burn them from one end as incense, air/clothing freshener, and insect repellent. This study evaluated the insect-repellent properties of this plant using an in vitro mosquito Aedes aegypti feeding bioassay-directed approach to identify the compound(s) responsible for the observed activities. Evaluation of crude extracts produced from H. odorata revealed that the hydrodistillate had the highest level of mosquito biting deterrence. Fractionation of this extract, followed by re-evaluation for mosquito biting deterrence, produced many active fractions, which were evaluated by spectroscopic techniques and determined to contain phytol, coumarin, and 2-methoxy-4-vinylphenol. Phytol and coumarin were both determined to be responsible for the Ae. aegypti biting deterrency. Scientific evidence reported here validates its traditional use as a biting-insect deterrent.
In recent years, the demand for emerging electronic devices has driven efforts to develop electrochemical capacitors with high power and energy densities that can preserve capacitance under and after ...recovery from mechanical deformation. We have developed superelastic pseudocapacitors using ∼1.5 mm thick graphene-coated single-walled carbon nanotube (SWCNT) aerogels decorated with manganese oxide (MnO2) as freestanding electrodes that retain high volumetric capacitance and electrochemical stability before, under, and after recovery from 50% compression. Graphene-coated SWCNT aerogels are superelastic and fatigue-resistant with high specific surface area and electrical conductivity. Electrodeposition of MnO2 onto these aerogels does not alter their superelasticity, with full shape recovery even after 10 000 compression−release cycles to 50% strain. Total (utilized) gravimetric capacitances of these aerogels before compression are similar to those under and after recovery from 50% compression over a wide range of scan rates with capacitances reaching 98 (468), 106 (522), and 128 F/g (626 F/g) at a scan rate of 2 mV/s, respectively. These gravimetric capacitances are preserved even after 10 000 compression–release cycles to 50% strain. Further, 50% compression of these aerogels increases the volumetric capacitance from 1.5 to 3.3 F/cm3. Before compression, the lifetime performances of these aerogels remain largely stable, with capacitance degrading by only ∼14% over the first 2000 charge–discharge cycles and remains constant for further 8000 cycles. Under 50% compression, capacitance displays a similar trend over 10 000 charge–discharge cycles. After recovery from 10 000 compression–release cycles to 50% strain, the aerogels show slightly greater capacitance loss of ∼28% over the first 2000 charge–discharge cycles and an additional ∼10% loss over the subsequent 8000 charge–discharge cycles. Finally, substantially higher gravimetric capacitance is achieved through greater MnO2 deposition, facilitated by the large porosity of these aerogels, albeit at a loss of capacitance retention upon compression. These capacitors display the feasibility of coating graphene-coated SWCNT aerogels with various pseudocapacitive materials to create superelastic energy-storage devices.
Background Although teacher training institutions have introduced courses in inclusive education to equip teachers with the necessary pedagogical skills to teach in diverse classrooms, it has been ...argued that the services of special educators are essential when it comes to teaching students with disabilities in regular classrooms. Unfortunately, there is scant literature on the views of special educators regarding the enactment of inclusive education in sub-Saharan African countries, such as Ghana.Objective In an effort towards promoting inclusive education in Ghana, there has been deployment of special educators across Ghana to supervise the implementation of inclusive education in schools. The purpose of this study was to explore the intentions of special educators towards supporting teachers to teach students with disabilities in secondary schools.Method Ajzen’s theory of planned behaviour guided the development of interview guide for data collection for this qualitative study. Twelve special educators were purposively selected and interviewed from five districts in Ghana.Results The participants expressed their unpreparedness to work in secondary schools because of multiple factors, such as their job description, resistance from teachers, and inadequate teaching and learning materials.Conclusion This study concludes on the need for policymakers to reconsider the deployment of special educators to cluster of schools or geographical areas in order to supervise the education of children with disabilities.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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