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The predictions of two mathematical models describing the transmission dynamics of schistosome infection and the impact of mass drug administration are compared. The models differ in their description of the dynamics of the parasites within the host population and in their representation of the stages of the parasite lifecycle outside of the host. Key parameters are estimated from data collected in northern Mozambique from 2011 to 2015. This type of data set is valuable for model validation as treatment prior to the study was minimal. Predictions from both models are compared with each other and with epidemiological observations. Both models have difficulty matching both the intensity and prevalence of disease in the datasets and are only partially successful at predicting the impact of treatment. The models also differ from each other in their predictions, both quantitatively and qualitatively, of the long-term impact of 10 years’ school-based mass drug administration. We trace the dynamical differences back to basic assumptions about worm aggregation, force of infection and the dynamics of the parasite in the snail population in the two models and suggest data which could discriminate between them. We also discuss limitations with the datasets used and ways in which data collection could be improved.

While youth and young adult e-cigarette use has risen in the U.S., few studies have explored e-cigarette cessation behavior. This study estimates quit attempts and intentions among young people (aged 15–36) since the rise of high-nicotine products, and examines factors associated with e-cigarette quit attempts and intentions. Current e-cigarette users (past 30-day use, not already quit) were drawn from a national probability-based cohort sample. Data were collected from September to December 2019 (n = 1158). Weighted proportions of past-year quit attempts, intentions to quit in next 30 days, and general intentions to quit (at some point) were calculated. Models estimated cessation outcomes with respect to harm perceptions, friend use, dependence, use frequency, combustible use and demographic factors. Among current e-cigarette users, 54.2% reported general intentions to quit, 15.3% reported intention to quit within 30 days, and 33.3% reported a past-year quit attempt. Past-year quit attempts were associated with higher levels of harm perceptions (adjusted odds ratio (aOR) = 2.08, 95% confidence interval (CI): 1.49–2.92), dependence (aOR = 1.92, 95% CI: 1.44–2.56) and daily use (28 + days) compared to infrequent use (1–5 days) (aOR = 0.23, 95% CI: 0.12–0.43). General intentions to quit were positively associated with harm perceptions (aOR = 1.77, 95% CI: 1.23–2.56) and dependence (aOR = 1.89, 95% CI: 1.41–2.52), and negatively associated with daily use compared to infrequent use (aOR = 0.35, 95% CI: 0.19–0.65). Findings indicate that over half of young e-cigarette users want to quit, highlighting a critical need for policies and resources to promote and sustain e-cigarette cessation among young people.

To effectively evaluate the performance of capacitive deionization (CDI), an electrochemical ion separation technology, it is necessary to accurately estimate the number of ions removed (effluent concentration) according to energy consumption. Herein, we propose and evaluate a deep learning model for predicting the effluent concentration of a CDI process. The developed deep learning model exhibited excellent prediction accuracy for both constant current and constant voltage modes (R 2 ≥ 0.968), and the accuracy increased with the data size. This model was based on the open-source language, Python, and the code has since been distributed with proper instructions for general use. Owing to the nature of the data-oriented deep learning model, the findings of this study are not only applicable to conventional CDI but also to various types of CDI (membrane CDI, flow CDI, faradaic CDI, etc.). Therefore, by referring to the examples shown in this study, we hope that this open-source deep learning code will be widely used in CDI research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Iron excess is a risk factor for cardiovascular diseases and it is important to understand the effect of iron on vascular permeability, particularly for the transport of large metabolic hormones such as adiponectin., Methods: We used 2-dimensional monolayers of cultured human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells (HUVEC) as well as 3-dimensional microvascular networks to measure transendothelial flux., Results: Iron supplementation reduced transendothelial electric resistance (TEER). Flux analysis indicated that under control conditions permeability of 70 kDa dextran and oligomeric forms of adiponectin were restricted in comparison with a 3 kDa dextran, however upon iron treatment permeability of the larger molecules was increased. The increased permeability and size-dependent trans-endothelial movement in response to iron was also observed in 3-dimensional microvascular networks. Mechanistically, the alteration in barrier functionality was associated with increased oxidative stress in response to iron since alterations in TEER and permeability were rescued when reactive oxygen species production was attenuated by pre-treatment with the antioxidant N-acetyl cysteine.]., Conclusions: Iron supplementation induced ROS production resulting in increased transendothelial permeability., General Significance: Altogether, this suggests that the oxidative stress associated with iron excess could play an important role in the regulation of endothelial functionality, controlling hormone action in peripheral tissues by regulating the first rate-limiting step controlling hormone access to target tissues., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Momordica charantia (bitter melon) is widely used for its glucose-lowering effects. This study was conducted to assess the efficacy and safety of M. charantia as an adjuvant treatment in patients with type 2 diabetes., Methods: We performed a randomized, placebo-controlled study. Blood glucose levels, lipid profile, and adverse events were investigated after 12 weeks of treatment. Ninety subjects were included in the final analysis for glucose lowering efficacy of bitter melon., Results: There were no differences in age, sex, or glycated hemoglobin (HbA1c) levels between the bitter melon extract and placebo groups. After treatment with bitter melon extract for 12 weeks, the HbA1c levels of the bitter melon and placebo groups remained unchanged; however, the average fasting glucose level of the bitter melon group decreased (p = 0.014). No serious adverse events were reported during the treatment period., Conclusions: Our data showed that bitter melon has effects of glucose lowering in patients with type 2 diabetes., (Copyright © 2020. Published by Elsevier Ltd.)

Despite being a major breakthrough in multiple myeloma therapy, carfilzomib (CFZ, a second-generation proteasome inhibitor drug) has been largely ineffective against solid cancer, possibly due to its pharmacokinetic drawbacks including metabolic instability. Recently, quinic acid (QA, a low-affinity ligand of selectins upregulated in peritumoral vasculature) was successfully utilized as a surface modifier for nanoparticles containing paclitaxel. Here, we designed QA-conjugated nanoparticles containing CFZ (CFZ@QANP; the surface of poly(lactic-co-glycolic acid) nanoparticles modified by conjugation with a QA derivative). Compared to the clinically used cyclodextrin-based formulation (CFZ-CD), CFZ@QANP enhanced the metabolic stability and in vivo exposure of CFZ in mice. CFZ@QANP, however, showed little improvement in suppressing tumor growth over CFZ-CD against the murine 4T1 orthotopic breast cancer model. CFZ@QANP yielded no enhancement in proteasomal inhibition in excised tumors despite having a higher level of remaining CFZ than CFZ-CD. These results likely arise from delayed, incomplete CFZ release from CFZ@QANP as observed using biorelevant media in vitro. These results suggest that the applicability of QANP may not be predicted by physicochemical parameters commonly used for formulation design. Our current results highlight the importance of considering drug release kinetics in designing effective CFZ formulations for solid cancer therapy., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Mesenchymal stromal cells (MSCs) promote wound healing, including after radiotherapy (RT) and surgery. The use of MSCs in regenerative medicine in the context of malignancy, such as to enhance wound healing post-RT/surgery in patients with soft tissue sarcomas (STSs), requires safety validation. The aim of this study was to determine the effects of human MSCs on STS growth in vitro and local recurrence and metastasis in vivo., Methods: Human primary STS and HT-1080 fibrosarcoma lines were transduced to express luciferase/eGFP (enhanced green fluorescent protein). Sarcoma cells were co-cultured or co-injected with bone marrow-derived MSCs for growth studies. Xenograft tumor models were established with STS lines in NOD/SCID/γ c null mice. To emulate a clinical scenario, subcutaneous tumors were treated with RT/surgery prior to MSC injection into the tumor bed. Local and distant tumor recurrence was studied using histology and bioluminescence imaging., Results: MSCs did not promote STS proliferation upon co-culture in vitro, which was consistent among MSCs from different donors. Co-injection of MSCs with sarcoma cells in mice exhibited no significant tumor-stimulating effect, compared with control mice injected with sarcoma cells alone. MSC administration after RT/surgery had no effect on local recurrence or metastasis of STS., Discussion: These studies are important for the establishment of a safety profile for MSC administration in patients with STS. Our data suggest that MSCs are safe in STS management after standard of care RT/surgery, which can be further investigated in early-phase clinical trials to also determine the efficacy of MSCs in reducing morbidity and to mitigate wound complications in these patients., (Copyright © 2018. Published by Elsevier Inc.)

The predictions of two mathematical models describing the transmission dynamics of schistosome infection and the impact of mass drug administration are compared. The models differ in their description of the dynamics of the parasites within the host population and in their representation of the stages of the parasite lifecycle outside of the host. Key parameters are estimated from data collected in northern Mozambique from 2011 to 2015. This type of data set is valuable for model validation as treatment prior to the study was minimal. Predictions from both models are compared with each other and with epidemiological observations. Both models have difficulty matching both the intensity and prevalence of disease in the datasets and are only partially successful at predicting the impact of treatment. The models also differ from each other in their predictions, both quantitatively and qualitatively, of the long-term impact of 10 years' school-based mass drug administration. We trace the dynamical differences back to basic assumptions about worm aggregation, force of infection and the dynamics of the parasite in the snail population in the two models and suggest data which could discriminate between them. We also discuss limitations with the datasets used and ways in which data collection could be improved., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background Aims: Previously, we showed that human mesenchymal stromal cells (hMSCs) were activated to express tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) upon TNF-α stimulation, induced cell death in triple-negative breast cancer (TNBC) MDA-MB-231 cells (MDA), and RNA released from apoptotic MDA further increased TRAIL expression in hMSCs. This feed-forward stimulation increased apoptosis in MDA cells. Here, we tested whether TRAIL-expressing hMSCs, in combination with a sub-toxic-dose of a chemotherapy drug doxorubicin, would overcome TRAIL resistance and create synergistic effects on targeting metastatic TNBC., Methods: To optimize conditions for the combination treatment, we (i) selected an optimal condition to activate hMSCs for TRAIL expression, (ii) selected an optimal dose of doxorubicin treatment, (iii) examined underlying mechanisms in vitro and (iv) tested the efficacy of the optimized conditions in a xenograft mouse model of human breast cancer lung metastasis., Results: The results showed that DNA fragments from apoptotic MDA triggered hMSCs to increase further TRAIL expression in an absent in melanoma 2 (AIM2)-dependent manner, and thus higher TRAIL-expressing hMSCs stimulated with synthetic DNA, poly(deoxyadenylic-deoxythymidylic) acid [poly(dA:dT)], more effectively suppressed tumor progression in vivo. Furthermore, activated hMSCs increased apoptosis in MDA cells when combined with a sub-toxic dose of doxorubicin, which was mediated by up-regulating TRAIL and Fas-related pathways. When we combined the optimized conditions, pre-activated hMSCs with poly (dA:dT) synergistically reduced tumor burden even with minimal doxorubicin treatment in a xenograft mouse model of human breast cancer lung metastasis., Conclusions: These results suggest that the treatment of hMSCs with a sub-toxic dose of doxorubicin can overcome TRAIL resistance and be a potential novel therapy for TNBC metastasis treatment., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated that computerized physician order entry (CPOE) of prescriptions reduces both turnaround time (TAT) and medication errors. However, these studies have been performed primarily in large academic centers with a relatively small number of medication orders. As such, many studies investigating the impact of CPOE on the level of pharmacist intervention have yielded conflicting results., Objective: The objective of this study was to examine the effects of CPOE on medication order TAT and the frequency of medication orders requiring pharmacist intervention in a community-based medical center., Methods: A prospective cohort study was conducted at a community-based medical center. A total of 24,767 prescriptions written for 940 patients over a six-month period were stratified into CPOE or non-CPOE (handwritten) cohorts. TAT between cohorts were tested using analysis of variance and Tukey's Honestly Significant Difference test. The number of orders requiring pharmacist intervention was compared between cohorts and tested using chi-square test or Fisher's exact test. Medication orders requiring pharmacist intervention were stratified by patient characteristics, therapeutic class, and types of medication error., Results: Medication orders not using CPOE were approximately 8 times more likely to require pharmacist intervention (2.26% versus 0.29%; P < 0.001), with the majority of pharmacist interventions performed to prevent medication errors. The overall mean TAT for medication orders was significantly shorter in the CPOE group in comparison with the non-CPOE group (22.2 ± 86.5 min versus 81 ± 256.7 min; P < 0.001). CPOE orders nearly eliminated medication errors with wrong dosage forms and formulary issues., Conclusions: Medication orders entered via CPOE are associated with a significant reduction in medication TAT and less likely to require pharmacist intervention. Use of CPOE may improve quality of patient care and efficiency of health care delivery., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Endothelin contributes to abnormalities in peripheral blood vessel function of subjects with obesity, with or without concurrent type 2 diabetes mellitus, but it is unknown if endothelin contributes specifically to obesity and diabetes-associated changes in blood pressure. We evaluated the effect of systemic endothelin antagonism on peripheral and central hemodynamics and peripheral vascular tone in lean, obese, and type 2 diabetic subjects without overt hypertension by cuff plethysmography. We measured the effects of acute systemic infusions of BQ123 (an antagonist of type A endothelin receptors) in seven lean (body mass index [BMI] 22.7 +/- 3.2 kg/m(2)), seven obese (BMI 35.8 +/- 4.6), and six diabetic subjects (BMI 38.2 +/- 5.0, glycosylated hemoglobin 8.1 +/- 2.2%). BQ123 was infused via antecubital vein sequentially at infusion rates from 0.1 to 1.0 mumol/min. Diastolic blood pressure was significantly lower than baseline across this dose range, but without a clear dose dependence and without differences in the dose response across groups. Obese and diabetic subjects exhibited progressive dilation of peripheral blood vessels (P