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3 months. After adjustment for age, sex, and comorbidities, RM was associated with a lower risk of death (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.36-0.52; P < 0.001) and CV hospitalization (HR 0.76, 95% CI 0.64-0.91; P= 0.002). In the economic model, cost savings were observed over 5 years with an estimated savings of $12,195 per person (95% CI-$21,818 to-$4,790). The model estimated a cost-savings associated with RM strategy in 99% of simulations.
These population data support more widespread implementation of RM technology to facilitate better patient outcomes and improve health system efficiency.
These population data support more widespread implementation of RM technology to facilitate better patient outcomes and improve health system efficiency.
Abdominal aortic aneurysm (AAA) shrinkage after endovascular aortic aneurysm repair (EVAR) is a surrogate marker for successful exclusion. Our study characterized aneurysm sac remodeling after EVAR to identify a pattern that may be associated with benign AAA behavior and would safely allow a less rigorous follow-up regimen after EVAR.
Elective infrarenal EVARs performed between 2008 and 2011 at our institution were retrospectively reviewed. AAA sac diameters using the minor axis measurement from ultrasound imaging or computer tomography angiogram imaging were compared with the baseline diameter from the 1-month postoperative computer tomography angiogram. The primary outcome was a composite of freedom from postoperative reintervention or rupture. We compared those with AAA sacs who regressed to predefined minimum diameter thresholds with those who did not. Outcomes were plotted with Kaplan-Meier curves and compared using log-rank testing and Fine-Gray regression using death as a competing risk, clustered but two occurred at least 3years after initially regressing to ≤40mm.
In long-term follow-up, patients whose minimum AAA sac diameter regressed ≤40mm after EVAR experienced a very low rate of reintervention, rupture, or sac re-expansion. Most sac re-expansion occurred at least 3years after reaching this threshold and did not result in clinical events. Increasing follow-up frequency up to 3-year intervals once the AAA sac regresses to 40mm would carry minimal risk of aneurysm-related morbidity.
In long-term follow-up, patients whose minimum AAA sac diameter regressed ≤40 mm after EVAR experienced a very low rate of reintervention, rupture, or sac re-expansion. Most sac re-expansion occurred at least 3 years after reaching this threshold and did not result in clinical events. Increasing follow-up frequency up to 3-year intervals once the AAA sac regresses to 40 mm would carry minimal risk of aneurysm-related morbidity.Bioelution tests measure in vitro the release of metal ion in surrogate physiological conditions (termed "bioaccessibility") and estimate the potential bioavailability relative to that of a known reference metal substance. Bioaccessibility of cobalt ion from twelve cobalt substances was tested in three artificial lung fluids (interstitial, alveolar and lysosomal) to gather information about the substances' fate and potential bioavailability in the respiratory tract after inhalation. The results can be used as one line of evidence to support grouping and read-across for substances lacking in vivo data, and where in vivo testing is not readily justifiable. Strong differences were observed in the dissolution behaviour of the substances in the different fluids, with the cobalt substances generally being less soluble in neutral pH fluids and more soluble in the acidic pH fluid. The resulting database, presented with its strengths and limitations, was used to support the formulation of an initial grouping of these cobalt substances into three categories.An in vitro release test based on pulsatile microdialysis (PMD) is presented for the purpose of measuring the release of cyclosporine from ophthalmic emulsions, along with a method to determine the drug distribution within the oil-rich globule, surfactant-rich micelle and aqueous phases of the emulsion formulation. Compositionally equivalent formulations containing 0.05% cyclosporine were prepared with similar physical parameters (globule size, viscosity, surface tension zeta potential, osmolality, pH) but made with different manufacturing conditions. Emulsions were made by ultrasonication, using different ultrasonication times (22-49 min) and temperatures (50-82 °C). Formulations were stored at room temperature (20 °C) and PMD was performed under two conditions, one in which the receiving medium temperature was 20 °C, and another in which the receiving medium temperature was 35 °C to mimic the temperature change expected when a drop of formulation is administered to the eye. The PMD release data were taken at release times of 20, 40, 60, 90, 120, 180, 300 and 600 s. All experiments showed a qualitatively similar release pattern, with a rapid initial rate of drug release (Release-1) for the first few minutes, followed by a much slower release (Release-2). In addition, imposing a sudden temperature change on the formulation was observed to affect the release, with some formulations releasing faster into receiver media at 35 °C than at 20 °C, while others released faster into 20 °C than 35 °C receiver media. The drug distribution was also calculated from PMD release data into 20 °C receiver media using a novel release kinetics model. The drug distribution varied among the formulations, with 54-77% of the cyclosporine in the oil phase of the emulsions. PMD is a promising method to evaluate how manufacturing-induced differences affect the distribution and release kinetics of cyclosporine within the emulsion formulation.Using nanocrystals (NCs) technology may be a promising drug delivery strategy for oral administration of multicomponent anticancer drugs. However, the intestinal epithelium and the mucus layer on the intestine extremely limited drug transport and absorption by orally. In this study, we selected multicomponent inartificial compound Bufadienolides (BU) with broad spectrum antitumor activity as the model drug to prepare BU NCs with different stabilizers by wet grinding, and explored the efficiency of penetrating through the mucus layer and transporting intestinal epithelial cells in vitro and ex vivo. Results revealed that BU NCs can dramatically improve dissolution behavior synergistically and the efficiency of mucus permeation. Besides, we found that BU NCs with different stabilizers enhanced cellular uptake, which was mainly attributed to increasing or changing the endocytosis pathway and plasma membrane/Endoplasmic reticulum (ER) pathway involved in the transmembrane transport of NCs. Furthermore, BU NCs could definitely improve intestinal absorption efficiency and change the absorption site of BU ex vivo. This multi-angle exploration will provide reference for the development of BU oral delivery formulations.Cell-penetrating peptides such as oligoarginines are one of promising tools that improve mucosal absorption of poorly membrane-permeable biologics. We have already demonstrated that conjugation of L-octaarginine to hyaluronic acid via a tetraglycine spacer resulted in a 3-fold enhancement of nasal absorption of somatropin (Mw ca. 22.1 kDa) in mice when compared with the unmodified peptide. Here, we evaluated absorption-enhancing abilities and safety profiles of oligopeptides with short chain arginine residues conjugated to hyaluronic acid. Somatropin absorption was hardly ever enhanced by diglycine-L-tetraarginine. Kinase Inhibitor Library The peptide acquired the absorption-enhancing ability through the conjugation; however, it disappeared when arginine residues were halved. In vivo data were consistent to in vitro cellular uptake of somatropin. When somatropin was substituted with exendin-4 (Mw ca. 4.2 kDa), cellular uptake was significantly enhanced by diglycine-L-diarginine conjugated to hyaluronic acid under comparison with the unmodified peptide. The conjugate also exhibited the enhancement ability in mice, as observed for hyaluronic acid derivatives with four and more arginine residues. Another cell studies revealed that oligoarginine-linked hyaluronic acid tended to be less toxic as arginine residues were reduced. Results indicated that diglycine-L-tetraarginine-linked hyaluronic acid was the most suitable candidate as an absorption enhancer whose Mw-independent enhancement ability and safety were well-balanced.Teenagers are a major group likely to love junk foods, such as potato chips and bread items, which contain high levels of acrylamide (AA). The increasing evidence suggests that AA exposure may be associated with decreased reproductive capacity in humans and animals. However, the reproductive toxicity of AA in pubertal males has not been fully elucidated. In this study, we evaluated the effects of pubertal AA exposure on adult spermatogenesis in male mice. Mice were exposed to AA at 0, 5, 10, 20, and 40 mg/kg/day by gavage from postnatal day 28 (PND28) to PND56. Our results showed that pubertal AA exposure increased apoptosis of germ cells in seminiferous tubules, decreased sperm concentration, and caused defects in sperm of adult mice. To explore the possible mechanisms of AA on spermatogenesis, the meiotic process was analyzed. The ratio of leptotene and zygotene spermatocytes increased, while the pachytene and diplotene spermatocytes decreased in AA-treated mice. Further analysis revealed that AA exposure disrupted the pattern of H2AX phosphorylation expansion, synapsis, and the crossover formation during meiotic prophase I (MPI). Taken together, these results indicate that pubertal AA exposure affects the spermatogenesis may be by disrupting the MPI progression of male mice.People of low socioeconomic status (SES) have disproportionately poorer dietary health despite efforts to improve access and highlight the health benefits of nutritious foods. While health-focused labels and advertisements make healthier options easier to recognize, they can prime a number of negative associations about healthy foods (e.g., taste, satiety, cost), which may be particularly aversive for low SES groups. This within-subjects study recruited people of low and high SES (those without and with a college degree) and compared their product expectations, experiences, satiety, and choice when consuming a bottled fruit and vegetable smoothie promoted as pleasurable ("Crave") or as healthy ("Nutralean"). Relative to Nutralean, Crave improved product expectations and behavioral measures of satiety across all participants. However, Crave enhanced expectations, experiences, and product choice more for low SES than high SES participants. Importantly, improvements were achieved without deception of nutritional facts and without decreasing perceived healthiness or increasing perceived cost. These findings identify SES as an important moderator in health-focused promotion and suggest how the rapidly growing healthy food industry can more effectively appeal to low SES groups, contexts which the majority of Americans navigate.
Painong San is a prescription composed of traditional Chinese medicine, which has been used to treat colitis. The Painong San's usage recorded in "Jingui Yaolve" by Zhongjing Zhang in the Later Han Dynasty is powder. However, the decoction is often used in reality. It's unclear which dosage form of Painong San is more suitable for colitis treatment and why?
This study aims to evaluate the different therapeutic effects of Painong San (a powder of Painong San) and Painong Decoction (a decoction of Painong San) on a dextran sulfate sodium salt-induced colitis model and the possible reasons of these different effects.
The contents of paeoniflorin, naringin, heperidin and neohesperidin in Painong San and Painong decoction were determined by an ultra-performance liquid chromatography system. The therapeutic effect on colitis was evaluated by intragastric administration of Painong San or Painong Decoction in dextran sulfate sodium salt-induced mouse model. The accumulated release rate of Painong San in vitro was analyzed with artificial gastric juice, artificial intestinal juice, and artificial colon juice.
