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Digestate is a rich source of nutrients that can be applied in agricultural fields as fertilizer or irrigation water. However, most of the research about application of digestate have focused on its agronomic properties and neglected the potential harm of the presence of contaminants of emerging concern (CECs). Aadvanced oxidation processes (AOPs) have proved to be effective for removing these compounds from drinking water, yet there are some constrains to treat wastewater and digestate mainly due to their complex matrix. In this study, the feasibility to remove different CECs from digestate using O 3 and O 3 /H 2 O 2 was assessed, and the general effect of the matrix in the oxidation was explained. While the lab-scale ozonation provided an ozone dose of 1.49 mg O 3 /mg DOC in 5 h treatment, almost all the compounds were removed at a lower ozone dose of maximum 0.48 mg O 3 /mg DOC; only ibuprofen required a higher dose of 1.1 mg O 3 /mg DOC to be oxidized. The digestate matrix slowed down the kinetic ozonation rate to approximately 1% compared to the removal rate in demineralized water. The combined treatment (O 3 /H 2 O 2 ) showed the additional contribution of H 2 O 2 by decreasing the ozone demand by 59-75% for all the compounds. The acute toxicity of the digestate, measured by the inhibition of Vibrio fisheries luminescence, decreased by 18.1% during 5 h ozonation, and by 34% during 5 h O 3 /H 2 O 2 treatment. Despite the high ozone consumption, the ozone dose (mg O 3 /mg DOC) required to remove all CECs from digestate supernatant was in the range or lower than what has been reported for other (waste-)water matrix, implying that ozonation can be considered as a post-AD treatment to produce cleaner stream for agricultural purposes., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The objectives of this study are to describe the characteristics of living systematic reviews (LSRs) and to understand their life cycles., Study Design and Setting: We conducted a comprehensive search up to April 2021 then selected articles and abstracted data in duplicate and independently. We undertook descriptive analyses and calculated delay in version update and delay since the last published version., Results: We included 76 eligible LSRs with a total of 279 eligible versions. The majority of LSRs was from the clinical field (70%), was COVID-19 related (63%), and had a funding source specified (62%). The median number of versions per LSR was 2 (interquartile range (IQR) 1-4; range 1-19). The median and IQR for the ratio of the actual period of update to the planned period of update was 1.12 (0.81; 1.71). Out of all reviews with a 'planned period of update' and at least one update (N = 19), eight LSRs (42%) had a period since last published version greater than 3 times the planned period of update. No LSR included a 'retirement notice' in their latest published version., Conclusion: While most LSR complied with the planned period of producing updates, a substantive proportion lagged since their last update., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives: To evaluate reporting of minimal important difference (MID) estimates using anchor-based methods for patient-reported outcome measures (PROMs), and the association with reporting deficiencies on their credibility., Methods: Systematic survey of primary studies empirically estimating MIDs. We searched Medline, EMBASE, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database until October 2018. We evaluated study reporting, focusing on participants' demographics, intervention(s), characteristics of PROMs and anchors, and MID estimation method(s). We assessed the impact of reporting issues on credibility of MID estimates., Results: In 585 studies reporting on 5,324 MID estimates for 526 distinct PROMs, authors frequently failed to adequately report key characteristics of PROMs and MIDs, including minimum and maximum values of PROM scale, measure of variability accompanying the MID estimate and number of participants included in the MID calculation. Across MID estimates (n = 5,324), the most serious reporting issues impacting credibility included infrequent reporting of the correlation between the anchor and PROM (66%), inadequate details to judge precision of MID point estimate (13%), and insufficient information about the threshold used to ascertain MIDs (16%)., Conclusion: Serious issues of incomplete reporting in the MID literature threaten the optimal use of MID estimates to inform the magnitude of effects of interventions on PROMs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: We conceptualize patient values and preferences as the relative importance of health outcomes (RIO) which are often obtained through utility elicitation research. A transparent and structured approach to present synthesized RIO evidence and the certainty of this evidence is needed. This study aims to adapt the summary of findings (SoF) table to describe the RIO., Study Design and Setting: We performed three interactive workshops with a protype version of the SoF table for RIO, evidence adapted from the SoF table for intervention effects. We then tested the new format through semi-structured interviews with professionals who interpret RIO evidence (e.g., systematic review authors and guideline developers)., Results: We adapted the SoF table for the presentation of RIO evidence. This SoF table may be easy to use, but bears one risk: some participants misunderstood the utility information and the variability around the RIO. We added a visual analogue scale to clarify the concept of utilities., Conclusion: Through a multi-stage process including brainstorming sessions and interviews, we adapted the SoF table to present RIO evidence. This table may enhance understanding of evidence synthesis of values and preferences, facilitating the incorporation of this type of evidence in decision-making., (Copyright © 2022. Published by Elsevier Inc.)

After myocardial infarction (MI), adult mammals exhibit scar formation, adverse left ventricular (LV) remodeling, LV stiffening, and impaired contractility, ultimately resulting in heart failure. Neonatal mammals, however, are capable of natural heart regeneration after MI. We hypothesized that neonatal cardiac regeneration conserves native biaxial LV mechanics after MI. Wistar rat neonates (1 day old, n = 46) and adults (8-10 weeks old, n = 20) underwent sham surgery or permanent left anterior descending coronary artery ligation. At 6 weeks after neonatal MI, Masson's trichrome staining revealed negligible fibrosis. Echocardiography for the neonatal MI (n = 15) and sham rats (n = 14) revealed no differences in LV wall thickness or chamber diameter, and both groups had normal ejection fraction (72.7% vs 77.5%, respectively, p = 0.1946). Biaxial tensile testing revealed similar stress-strain curves along both the circumferential and longitudinal axes across a full range of physiologic stresses and strains. The circumferential modulus (267.9 kPa vs 274.2 kPa, p = 0.7847), longitudinal modulus (269.3 kPa vs 277.1 kPa, p = 0.7435), and maximum shear stress (3.30 kPa vs 3.95 kPa, p = 0.5418) did not differ significantly between the neonatal MI and sham groups, respectively. In contrast, transmural scars were observed at 4 weeks after adult MI. Adult MI hearts (n = 7) exhibited profound LV wall thinning (p < 0.0001), chamber dilation (p = 0.0246), and LV dysfunction (ejection fraction 45.4% vs 79.7%, p < 0.0001) compared to adult sham hearts (n = 7). Adult MI hearts were significantly stiffer than adult sham hearts in both the circumferential (321.5 kPa vs 180.0 kPa, p = 0.0111) and longitudinal axes (315.4 kPa vs 172.3 kPa, p = 0.0173), and also exhibited greater maximum shear stress (14.87 kPa vs 3.23 kPa, p = 0.0162). Our study is the first to show that native biaxial LV mechanics are conserved after neonatal heart regeneration following MI, thus adding biomechanical support for the therapeutic potential of cardiac regeneration in the treatment of ischemic heart disease., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China in December 2019. On February 11, the World Health Organization (WHO) announced the name for the new illness caused by SARS-CoV-2: COVID-19. By March 11, the outbreak of COVID-19 was declared a pandemic by the WHO. This virus has extensively altered daily life for many across the globe, while claiming hundreds of thousands of lives. While fundamentally a respiratory illness, many infected individuals experience symptoms that involve the central nervous system (CNS). It is likely that many of these symptoms are the result of the virus residing outside of the CNS. However, the current evidence does indicate that the SARS-CoV-2 virus can use olfactory neurons (or other nerve tracts) to travel from the periphery into the CNS, and that the virus may also enter the brain through the blood-brain barrier (BBB). We discuss how the virus may use established infection mechanisms (ACE2, NRP1, TMPRSS2, furin and Cathepsin L), as well mechanisms still under consideration (BASIGIN) to infect and spread throughout the CNS. Confirming the impact of the virus on the CNS will be crucial in dealing with the long-term consequences of the epidemic., (Published by Elsevier Inc.)

Objectives: The objective of the study was to develop an inventory summarizing all anchor-based minimal important difference (MID) estimates for patient-reported outcome measures (PROMs) available in the medical literature., Study Design and Setting: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database internal library (January 1989-October 2018). We included primary studies empirically calculating an anchor-based MID estimate for any PROM in adults and adolescents. Pairs of reviewers independently screened and selected studies, extracted data, and evaluated the credibility of the MIDs., Results: We identified 585 eligible studies, the majority conducted in Europe (n = 211) and North America (n = 179), reporting 5,324 MID estimates for 526 distinct PROMs. Investigators conducted their studies in the context of patients receiving surgical (n = 105, 18%), pharmacological (n = 85, 15%), rehabilitation (n = 65, 11%), or a combination of interventions (n = 194, 33%). Of all MID estimates, 59% (n = 3,131) used a global rating of change anchor. Major credibility limitations included weak correlation (n = 1,246, 23%) or no information regarding the correlation (n = 3,498, 66%) between the PROM and anchor and imprecision in the MID estimate (n = 2,513, 47%)., Conclusion: A large number of MIDs for assisting in the interpretation of PROMs exist. The MID inventory will facilitate the use of MID estimates to inform the interpretation of the magnitude of treatment effects in clinical research and guideline development., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields., Study Design and Setting: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group., Results: A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan., Conclusion: An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: RENASCENT is a prospective, multi-center first-in-human clinical study to evaluate the clinical performance of the novel sirolimus-eluting 150-μm strut thickness FORTITUDE® BRS for percutaneous coronary intervention of single de novo coronary lesions., Methods: FORTITUDE® BRS was tested in a prospective study in Italy and Colombia. Study objectives were in-scaffold angiographic late lumen loss (LLL) measured by quantitative coronary angiography and target vessel failure (TVF) defined as the composite rate of cardiac death, target vessel myocardial infarction or ischemia driven target lesion revascularization (TLR) at 9- and 24-months with clinical results up to 36-months., Results: A total of 63 patients were enrolled. All patients underwent lesion pre-dilatation and 22 patients (34.9%) underwent post-dilatation. Clinical device and procedural success was 98.4% (62/63 patients) and 96.8% (61/63 patients) respectively. At 9-months, TVF occurred in 3/61 (4.9%) of the patients including 2 peri-procedural MI and one ischemia-driven TLR. Between 9- to 24-months, ischemia-driven TLR occurred in 3 additional patients (4.9%) including 1 patient who presented with very late ST after stopping all medications. There were no further TVF between 24- and 36-months., Conclusions: In this multi-center prospective study, the FORTITUDE® BRS was shown to be safe and effective in the treatment of single coronary lesions with low levels of TVF and LLL at 9- and 24-months. It was shown to be clinically safe upto 36-months follow-up., Competing Interests: Declaration of Competing Interest Alaide Chieffo, MD: Proctorship fees from Amaranth Medical Inc. Juan F. Granada, MD: Scientific advisor and equity shareholder Amaranth Medical Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Objective: The objective of the study is to develop a pragmatic tool to prioritize clinical guideline (CG) questions for updating, the UpPriority tool., Study Design and Setting: The development of this tool consisted of the following: (1) establishment of the working group, (2) generation of the initial version, (3) optimization of the tool (including an initial feasibility test, semistructured interviews, Delphi consensus survey, second feasibility test, external review, and pilot test), and (4) approval of the final version., Results: A total of 87 participants including methodologists, clinicians, and other relevant stakeholders contributed to the development of the UpPriority tool. The tool consists of six items: (1) impact of outdated recommendations on safety, (2) availability of new relevant evidence, (3) context relevance of the clinical question, (4) methodological applicability of the clinical question, (5) user's interest, and (6) impact on access to health care. The UpPriority tool includes detailed guidance for using the tool and rating each item (using a 7-point Likert scale), for calculating and ranking the questions, and for summarizing results., Conclusion: The UpPriority tool could be useful for standardizing prioritization processes when updating CGs and for fostering more efficient use of resources in the CG field., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this research was to generate and validate a questionnaire that identifies determinants of guideline use from the clinician perspective., Study Design and Setting: From January 2017 to March 2018, a seven-member six-country multidisciplinary team used a five-step multimethod design to search for and compile determinant frameworks, map items to determinants (content validity), select the best items for each determinant (content validity), refine wording of determinants and items (face validity), merge or separate items (construct validity), and review the final questionnaire., Results: The Clinician Guideline Determinants Questionnaire includes four sections: clinician demographic information (including two determinants: attitudes about/experience with guidelines), 26 close-ended items reflecting clinician- and guideline-specific determinants, four open-ended items reflecting enablers and barriers perceived as most important, and three items on learning style (preferred sources of guideline information)., Conclusion: The Clinician Guideline Determinants Questionnaire is a comprehensive, validated instrument that addresses multiple potential determinants specific to guideline use from a clinician perspective. The Questionnaire can be used at multiple time points in the guideline development cycle to assess determinants of the use of new, updated, or adapted guidelines and before and after interventions to assess their impact on the determinants of guideline use. In future research, we will establish psychometric properties of the new questionnaire., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (n = 45) underwent sham surgery (n = 15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n = 15) or ESA (6 μg/kg, n = 15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68 ± 0.05 mm vs 1.42 ± 0.08 mm, p = 0.008), smaller end-diastolic LV internal dimension (6.88 ± 0.29 mm vs 7.69 ± 0.22 mm, p = 0.044), and improved ejection fraction (62.8 ± 3.0% vs 49.4 ± 4.5%, p = 0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4 ± 2.9% vs 41.6 ± 3.1%, p = 0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5 ± 6.9 kPa vs 264.3 ± 12.5 kPa, p = 0.001) and longitudinal axes (194.5 ± 6.5 kPa vs 258.1 ± 14.4 kPa, p < 0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To provide Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidance for assessing inconsistency, imprecision, and other domains for the certainty of evidence about the relative importance of outcomes., Study Design and Setting: We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance, and consulted GRADE members and other stakeholders for feedback., Results: We describe the rationale for considering the remaining GRADE domains when rating the certainty in a body of evidence for the relative importance of outcomes. As meta-analyses are not common in this context, inconsistency and imprecision assessments are challenging. Furthermore, confusion exists about inconsistency, imprecision, and true variability in the relative importance of outcomes. To clarify this issue, we suggest that the true variability is neither equivalent to inconsistency nor imprecision. Specifically, inconsistency arises from population, intervention, comparison and outcome and methodological elements that should be explored and, if possible, explained. The width of the confidence interval and sample size inform judgments about imprecision. We also provide suggestions on how to detect publication bias and discuss the domains to rate up the certainty., Conclusion: We provide guidance and examples for rating inconsistency, imprecision, and other domains for a body of evidence describing the relative importance of outcomes., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group defines patient values and preferences as the relative importance patients place on the main health outcomes. We provide GRADE guidance for assessing the risk of bias and indirectness domains for certainty of evidence about the relative importance of outcomes., Study Design and Setting: We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance and consulted GRADE members and other stakeholders for feedback., Results: This is the first of two articles. A body of evidence addressing the importance of outcomes starts at "high certainty"; concerns with risk of bias, indirectness, inconsistency, imprecision, and publication bias lead to downgrading to moderate, low, or very low certainty. We propose subdomains of risk of bias as selection of the study population, missing data, the type of measurement instrument, and confounding; we have developed items for each subdomain. The population, intervention, comparison, and outcome elements associated with the evidence determine the degree of indirectness., Conclusion: This article provides guidance and examples for rating the risk of bias and indirectness for a body of evidence summarizing the importance of outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To identify, describe, and map contemporary nutrition guidelines (NGs) from reviews that used the Appraisal of Guidelines, Research and Evaluation (AGREE) tool., Study Design and Setting: We performed an overview of reviews that systematically assessed the quality of NGs using the AGREE tool. We searched MEDLINE and EMBASE from inception to February 2018. Two authors independently selected and assessed reviews and extracted data., Results: We included nine evaluations with a total of 67 NGs. The higher median AGREE scores were for the domains "scope and purpose" (80%, Q1-Q3: 59-89%) and "clarity and presentation" (69%, Q1-Q3: 53-89%), while the lower were for "rigor of development" (58%, Q1-Q3: 31-84%), "editorial independence" (53%, Q1-Q3: 19-79%), "stakeholder involvement" (50%, Q1-Q3: 28-72%), and "applicability" (22%, Q1-Q3: 11-50%). The median AGREE overall rating was 5 (Q1-Q3: 4-6), and most were recommended for use (75%; 30/40). Twenty-nine NGs (43.3%; 29/67) scored ≥60% in three or more domains, including "rigor of development" domain. The methodological quality of NGs did not improve over time., Conclusion: The methodological quality of NGs varies widely, but there is general need for improvement in most AGREE domains. NG developers could incorporate available tools to ensure the development of high-quality NGs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The Gulf of Mexico is considered one of the world's major marine ecosystems, supporting important fisheries and habitats such as barrier islands, mangrove forests, seagrass beds, coral reefs etc. It also hosts a range of complex offshore petroleum exploration, extraction, and refining industries, which may have chronic or acute impacts on ecosystem functioning. Previous work on the marine effects of this activity is geographically incomplete, and has tended to focus on direct hydrocarbon impacts, while impacts from other related contaminants (e.g. heavy metals, salt-rich drilling muds) which may be discharged from oil facilities have not been widely assessed. Here, we examine historical trace element accumulation in marine sediments collected from four sites in the Tamaulipas shelf, Gulf of Mexico, in the area of the Arenque oil field. Dated sediment cores were used to examine the sources, and historical and contemporary inputs, of trace metals (including those typically present in oil industry discharges) and their potential biological impact in the Tamaulipas aquatic environment over the last 100years. CaO (i.e. biogenic component) normalized data showed increasing V, Cr, Zn, Cu, Pb, Zr and Ba towards the sediment surface in three of the four cores, with Ba and V (based on an adverse effect index) possibly associated with adverse effects on organisms. Dated Ba/CaO profiles show an increase of 30-137% after opening of oil installations in the study area, and can be broadly correlated with increasing oil industry activities across the wider Gulf of Mexico. Data do not record however a clear enhancement of Ba concentration in sediment cores collected near to oil platforms over more distal cores, indicating that any Ba released from drilling platforms is incorporated quickly into the sediments around the drilling sites, and once this element has been deposited its rate of resuspension and mobility is low., Capsule Abstract: Sediment core data from the Tamaulipas shelf show the influence of oil industry activities on selected trace element concentrations, with Ba/CaO broadly correlating with increasing oil industry activities across the wider Gulf of Mexico., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In a recent article from the Center for Disease Control, the authors addressed the current opioid epidemic in America and emphasized the importance of utilizing non-opioid analgesic alternatives to opioid medication for treating chronic pain. In cases where non-opioid analgesic drugs alone have failed to produce adequate pain relief, these authors suggested that non-pharmacologic therapies should also be considered. This Case Series describes a pilot study designed to evaluate a novel non-pharmacologic approach to treating long-standing (>1year) opioid dependency. The therapy involved the use of a high intensity cold laser device to treat three patients who had become addicted to prescription opioid-containing analgesic medication for treating chronic (residual) pain after a major operation. After receiving a series of 8-12 treatment sessions lasting 20-40min to the painful surgical area over a 3-4week period of time with the high intensity (42W) Phoenix Thera-lase laser device, an FDA-approved Class IV cold laser, these patients were able to discontinue their use of all oral opioid-containing analgesic medications and resume their normal activities of daily living. At a follow-up evaluation 1-2months after their last laser treatment, these patients reported that they have been able to control their pain with over-the-counter non-opioid analgesics and they have remained largely opioid-free. Further larger-scale studies are needed to verify these preliminary findings with this powerful cold laser in treating opioid-dependent patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The aim of the study was to identify and describe strategies to prioritize the updating of systematic reviews (SRs), health technology assessments (HTAs), or clinical guidelines (CGs)., Study Design and Setting: We conducted an SR of studies describing one or more methods to prioritize SRs, HTAs, or CGs for updating. We searched MEDLINE (PubMed, from 1966 to August 2016) and The Cochrane Methodology Register (The Cochrane Library, Issue 8 2016). We hand searched abstract books, reviewed reference lists, and contacted experts. Two reviewers independently screened the references and extracted data., Results: We included 14 studies. Six studies were classified as descriptive (6 of 14, 42.9%) and eight as implementation studies (8 of 14, 57.1%). Six studies reported an updating strategy (6 of 14, 42.9%), six a prioritization process (6 of 14, 42.9%), and two a prioritization criterion (2 of 14, 14.2%). Eight studies focused on SRs (8 of 14, 57.1%), six studies focused on CGs (6 of 14, 42.9%), and none were about HTAs. We identified 76 prioritization criteria that can be applied when prioritizing documents for updating. The most frequently cited criteria were as follows: available evidence (19 of 76, 25.0%), clinical relevance (10 of 76; 13.2%), and users' interest (10 of 76; 13.2%)., Conclusion: There is wide variability and suboptimal reporting of the methods used to develop and implement processes to prioritize updating of SRs, HTAs, and CGs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Silver nanoparticles (AgNPs) have been widely used because of their antimicrobial properties. However, several reports suggest that AgNPs exposure promote cardiac effects that involve nitric oxide (NO) and oxidative stress (OS). Nevertheless, there are no studies related to AgNPs-induced effects in cardiac physiology. The aim of this study was to evaluate the AgNPs direct actions on coronary vascular tone and cardiac contractility using Langendorff rat heart preparation. Low concentrations of AgNPs (0.1 and 1 μg/mL) increased NO derived from inducible NO-synthase (iNOS), without modifying cardiac parameters. Meanwhile, high concentrations (10 and 100 μg/mL) promoted a sustained vasoconstriction and increased cardiac contractility related to OS, leading to rhabdomyolysis. Furthermore, AgNPs were internalized in the cardiac muscle, hindering classic actions induced by phenylephrine (Phe) and acetylcholine (ACh). These data suggest that AgNPs affect cardiac physiology in function of the concentration and in part of the NO generation, NOS expression and OS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question., Study Design and Setting: We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data., Results: We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1-13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision)., Conclusion: About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Previous studies have shown inhibition of cervical cancer cell growth by treatment with high concentrations of IL-2. In the present study, we evaluated the in vitro and in vivo effects of recombinant human IL-2 on HPV-associated tumor cells (3T3-16). Treatment of 3T3-16 cells with rhIL-2 for 72 h inhibited cell growth in a dose-dependent manner and this effect was evidenced at nanomolar concentrations. These tumor cells expressed mRNA for beta and gamma subunits of the IL-2 receptor, which are required for signal transduction. In experiments to explore the effect of IL-2 on the growth of the HPV-associated tumor, mice received rhIL-2 through different routes: (i) intraperitoneal; (ii) subcutaneous, at the tumor inoculation site; or (iii) subcutaneous, distant from the tumor inoculation site. An effective antitumor response was observed only in those animals that received IL-2 at the tumor site (P<0.01). These results indicate the potential adequacy of therapeutic strategies based on local administration of rhIL-2 for cervical carcinoma, not only based on the ability of this cytokine to stimulate cellular-mediated immunity but also because of its direct effects on tumor cells.

Assimilatory NADH:nitrate reductase (EC 1.6.6.1), a complex Mo-pterin-, cytochrome b(557)-, and FAD-containing protein, catalyzes the regulated and rate-limiting step in the utilization of inorganic nitrogen by higher plants. A codon-optimized gene has been synthesized for expression of the central cytochrome b(557)-containing fragment, corresponding to residues A542-E658, of spinach assimilatory nitrate reductase. While expression of the full-length synthetic gene in Escherichia coli did not result in significant heme domain production, expression of a Y647* truncated form resulted in substantial heme domain production as evidenced by the generation of "pink" cells. The histidine-tagged heme domain was purified to homogeneity using a combination of NTA-agarose and size-exclusion FPLC, resulting in a single protein band following SDS-PAGE analysis with a molecular mass of approximately 13 kDa. MALDI-TOF mass spectrometry yielded an m/z ratio of 12,435 and confirmed the presence of the heme prosthetic group (m/z=622) while cofactor analysis indicated a 1:1 heme to protein stoichiometry. The oxidized heme domain exhibited spectroscopic properties typical of a b-type cytochrome with a visible Soret maximum at 413 nm together with epr g-values of 2.98, 2.26, and 1.49, consistent with low-spin bis-histidyl coordination. Oxidation-reduction titrations of the heme domain indicated a standard midpoint potential (E(o)') of -118 mV. The isolated heme domain formed a 1:1 complex with cytochrome c with a K(A) of 7 microM (micro=0.007) and reconstituted NADH:cytochrome c reductase activity in the presence of a recombinant form of the spinach nitrate reductase flavin domain, yielding a k(cat) of 1.4 s(-1) and a K(m app) for cytochrome c of 9 microM. These results indicate the efficient expression of a recombinant form of the heme domain of spinach nitrate reductase that retained the spectroscopic and thermodynamic properties characteristic of the corresponding domain in the native spinach enzyme.