Abstract Despite recent advances in behavioral interventions for cannabis use disorders, effect sizes remain modest, and few individuals achieve long-term abstinence. One strategy to enhance outcomes ...is the addition of pharmacotherapy to complement behavioral treatment, but to date no efficacious medications targeting cannabis use disorders in adults through large, randomized controlled trials have been identified. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) is currently conducting a study to test the efficacy of N -acetylcysteine (NAC) versus placebo (PBO), added to contingency management, for cannabis cessation in adults (ages 18–50). This study was designed to replicate positive findings from a study in cannabis-dependent adolescents that found greater odds of abstinence with NAC compared to PBO. This paper describes the design and implementation of an ongoing 12-week, intent-to-treat, double-blind, randomized, placebo-controlled study with one follow-up visit four weeks post-treatment. Approximately 300 treatment-seeking cannabis-dependent adults will be randomized to NAC or PBO across six study sites in the United States. The primary objective of this 12-week study is to evaluate the efficacy of twice-daily orally-administered NAC (1200 mg) versus matched PBO, added to contingency management, on cannabis abstinence. NAC is among the first medications to demonstrate increased odds of abstinence in a randomized controlled study among cannabis users in any age group. The current study will assess the cannabis cessation efficacy of NAC combined with a behavioral intervention in adults, providing a novel and timely contribution to the evidence base for the treatment of cannabis use disorders.
Many individuals without coeliac disease or wheat allergy reduce their gluten intake because they believe that gluten causes their gastrointestinal symptoms. Symptoms could be affected by negative ...expectancy. Therefore, we aimed to investigate the effects of expectancy versus actual gluten intake on symptoms in people with non-coeliac gluten sensitivity (NCGS).
This randomised, double-blind, placebo-controlled, international, multicentre study was done at the University of Leeds (Leeds, UK), Maastricht University (Maastricht, the Netherlands), and Wageningen University and Research (Wageningen, the Netherlands). People aged 18-70 years with self-reported NCGS (ie, gastrointestinal symptoms within 8 h of gluten consumption) without coeliac disease and wheat allergy were recruited. Participants had to follow a gluten-free or gluten-restricted diet for at least 1 week before (and throughout) study participation and had to be asymptomatic or mildly symptomatic (overall gastrointestinal symptom score ≤30 mm on the Visual Analogue Scale VAS) while on the diet. Participants were randomly assigned (1:1:1:1; blocks of eight; stratified by site and gender) to one of four groups based on the expectation to consume gluten-containing (E
) or gluten-free (E
) oat bread for breakfast and lunch (two slices each) and actual intake of gluten-containing (G
) or gluten-free (G
) oat bread. Participants, investigators, and those assessing outcomes were masked to the actual gluten assignment, and participants were also masked to the expectancy part of the study. The primary outcome was overall gastrointestinal symptom score on the VAS, which was measured at and corrected for baseline (before breakfast) and hourly for 8 h, with lunch served after 4 h, and analysed per-protocol. Safety analysis included all participants incorporated in the per-protocol analysis. The study is registered at ClinicalTrials.gov, NCT05779358, and has ended.
Between Oct 19, 2018, and Feb 14, 2022, 165 people were screened and 84 were randomly assigned to E
G
(n=21), E
G
(n=21), E
G
(n=20), or E
G
(n=22). One person in the E
G
group was excluded due to not following test day instructions, leaving 83 participants in the per-protocol analysis. Median age was 27·0 years (IQR 21·0-45·0), 71 (86%) of 83 people were women, and 12 (14%) were men. Mean overall gastrointestinal symptom score was significantly higher for E
G
(16·6 mm 95% CI 13·1 to 20·0) than for E
G
(6·9 mm 3·5 to 10·4; difference 9·6 mm 95% CI 3·0 to 16·2, p=0·0010) and E
G
(7·4 mm 4·2 to 10·7; difference 9·1 mm 2·7 to 15·6, p=0·0016), but not for E
G
(11·7 mm 8·3 to 15·1; difference 4·9 mm -1·7 to 11·5, p=0·28). There was no difference between E
G
and E
G
(difference 4·7 mm -1·8 to 11·3, p=0·33), E
G
and E
G
(difference 4·2 mm -2·2 to 10·7, p=0·47), and E
G
and E
G
(difference -0·5 mm -7·0 to 5·9, p=1·0). Adverse events were reported by two participants in the E
G
group (itching jaw n=1; feeling lightheaded and stomach rumbling n=1) and one participant in the E
G
group (vomiting).
The combination of expectancy and actual gluten intake had the largest effect on gastrointestinal symptoms, reflecting a nocebo effect, although an additional effect of gluten cannot be ruled out. Our results necessitate further research into the possible involvement of the gut-brain interaction in NCGS.
Government of the Netherlands Topsector Agri & Food Top Consortium for Knowledge and Innovation, AB Mauri Global Bakery Ingredients, Baking Industry Research Trust, Borgesius-Albert Heijn, CSM Innovation Centre, the International Maize and Wheat Improvement Center (CIMMYT), DSM Food Specialties, Fazer, Healthgrain Forum, the International Association for Cereal Science and Technology, the International Wheat Gluten Association, Lantmännen, Mondelez International, Nederlands Bakkerij Centrum, Nutrition & Santé, Puratos, Rademaker, Sonneveld Group, and Zeelandia HJ Doeleman.
Nursing has been perceived as oppressed by virtue of among other things gender, occupation and class. It has been suggested that historically, nursing education perpetuated the rituals of tradition ...and was oppressive in terms of what was taught and how it was taught. Developments in nurse education have resulted in nurse educators seeking alternative means of educating, with the aim of emancipating nurses. Paulo Freire (1921–1997) promoted liberation through reflection and action, directed at transforming the conditions which lead to oppression. The fundamental basis of this approach is critical social theory, which is underpinned by the philosophy that social phenomena must be understood in terms of their context and history. From a critical social theory perspective, fruitful nursing education will only be possible if the history and structure of nursing are clearly understood by those involved in the educational process. We contend that the adoption of Freire’s theory in nursing education may contribute towards the development of nurses who will be competent to meet the demands of contemporary healthcare practice. However, the application of this theory to nursing education can be challenging because of constraints imposed by the system in which nurse education takes place. It is therefore important that the application of critical social theory in nurse education be evaluated.
To increase and sustain hospital-wide compliance with hand hygiene through a long-term ongoing multidimensional improvement program emphasizing behavioral factors.
Quasi-experimental short study ...(August 2000-November 2001) and descriptive time series (April 2003-December 2006).
A 450-bed teaching tertiary-care hospital.
An initial intervention bundle was introduced in pilot locations that addressed cognitive behavioral factors, which included access to alcohol sanitizer, education, and ongoing audit and feedback. The bundle was subsequently disseminated hospital-wide, along with a novel approach focused on behavior modification through positive reinforcement and annually changing incentives.
A total of 36,123 hand hygiene opportunities involving all categories of healthcare workers from 12 inpatient units were observed from October 2000 to October 2006. The rate of compliance with hand hygiene significantly improved after the intervention in 2 cohorts over the first year (from 40% to 64% of opportunities and from 34% to 49% of opportunities;P <.001, compared with the control group). Mean compliance rates ranged from 19% to 41% of 4174 opportunities (at baseline), increased to the highest levels of 73%-84% of 6,420 opportunities 2 years after hospital-wide dissemination, and remained improved at 59%-81% of 4,990 opportunities during year 6 of the program.
This interventional cohort study used a behavioral change approach and is one of the earliest and largest institution-wide programs promoting alcohol sanitizer from the United States that has shown significant and sustained improvements in hand hygiene compliance. This creative campaign used ongoing frequent audit and feedback with novel use of immediate positive reinforcement at an acceptable cost to the institution.
It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the ...organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CSC hierarchies and chemoresistance in an ovarian cancer model. Using a single cell-based approach to CSC discovery and validation, we report a novel, four-component CSC hierarchy based around the markers cluster of differentiation 10 (CD10) and aldehyde dehydrogenase (ALDH). In a change to our understanding of CSC biology, resistance to chemotherapy drug cisplatin was found to be the sole property of CD10
/ALDH
CSCs, while all four CSC types were sensitive to chemotherapy drug paclitaxel. Cisplatin treatment quickly altered the hierarchy, resulting in a three-component hierarchy dominated by the cisplatin-resistant CD10
/ALDH
CSC. This organisation was found to be hard-wired in a long-term cisplatin-adapted model, where again CD10
/ALDH
CSCs were the sole cisplatin-resistant component, and all CSC types remained paclitaxel-sensitive. Molecular analysis indicated that cisplatin resistance is associated with inherent- and adaptive-specific drug efflux and DNA-damage repair mechanisms. Clinically, low CD10 expression was consistent with a specific set of ovarian cancer patient samples. Collectively, these data advance our understanding of the relationship between CSC hierarchies and chemoresistance, which was shown to be CSC- and drug-type specific, and facilitated by specific and synergistic inherent and adaptive mechanisms. Furthermore, our data indicate that primary stage targeting of CD10
/ALDH
CSCs in specific ovarian cancer patients in future may facilitate targeting of recurrent disease, before it ever develops.
Biological processes are fundamentally driven by complex interactions between biomolecules. Integrated high-throughput omics studies enable multifaceted views of cells, organisms, or their ...communities. With the advent of new post-genomics technologies, omics studies are becoming increasingly prevalent; yet the full impact of these studies can only be realized through data harmonization, sharing, meta-analysis, and integrated research. These essential steps require consistent generation, capture, and distribution of metadata. To ensure transparency, facilitate data harmonization, and maximize reproducibility and usability of life sciences studies, we propose a simple common omics metadata checklist. The proposed checklist is built on the rich ontologies and standards already in use by the life sciences community. The checklist will serve as a common denominator to guide experimental design, capture important parameters, and be used as a standard format for stand-alone data publications. The omics metadata checklist and data publications will create efficient linkages between omics data and knowledge-based life sciences innovation and, importantly, allow for appropriate attribution to data generators and infrastructure science builders in the post-genomics era. We ask that the life sciences community test the proposed omics metadata checklist and data publications and provide feedback for their use and improvement.
Detecting adverse effects of drugs on cardiac contractility is becoming a priority in pre-clinical safety pharmacology. The aim of this work was to optimise conditions and explore the potential of ...using the anaesthetized guinea pig as an in vivo model.
Guinea pigs were anaesthetized with Hypnorm/Hypnovel, isoflurane, pentobarbital or fentanyl/pentobarbital. The electrocardiogram (ECG), heart rate, arterial blood pressure and indices of cardiac contractility were recorded. In further experiments in fentanyl/pentobarbital anaesthetized guinea pigs the influence of bilateral versus unilateral carotid artery occlusion on haemodynamic responses was investigated and the effects of inotropic drugs on left ventricular (LV) dP/dtmax and the QA interval were determined.
Pentobarbital, given alone or after fentanyl, provided suitable anaesthesia for these experiments. Bilateral carotid artery occlusion did not alter heart rate or arterial blood pressure responses to isoprenaline or angiotensin II. Isoprenaline and ouabain increased LVdP/dtmax and decreased the QA interval whereas verapamil had opposite effects and strong inverse correlations between LVdP/dtmax and the QA interval were found.
Conditions can be optimised to allow the pentobarbital-anaesthetized guinea pig to be used for simultaneous measurement of the effects of drugs on the ECG, haemodynamics and indices of cardiac contractility. The use of this small animal model in early pre-clinical safety pharmacology should contribute to improvements in detecting unwanted actions on the heart during the drug development process.
International ecosystem assessment Ayensu, Edward; Claasen, Daniel van R.; Collins, Mark; Dearing, Andrew; Fresco, Louise O.; Gadgil, Madhav; Gitay, Habiba; Glaser, Gisbert; Juma, Calestous; Krebs, John; Lenton, Roberto; Lubchenco, Jane; McNeely, Jeffrey A.; Mooney, Harold A.; Pinstrup-Andersen, Per; Ramos, Mario; Raven, Peter; Reid, Walter V.; Samper, Cristian K.; Sarukhán, José; Schei, Peter; Tundisi, José Galízia; Watson, Robert T.; Guanhua, Xu; Zakri, A. H
03/2012
Journal Article
This article develops the case for adopting an international system for assessing how humans have impacted the ecosystem. It explains the rationale for making such an assessment and proposes a ...methodology for developing and administering it.
A polymerase chain reaction (PCR)-based heteroduplex assay was evaluated for the detection of mandarin juice in processed orange juice. PCR amplification of a fragment of the chloroplast trnT-trnL ...intergenic spacer derived from mixtures of DNA extracted from orange and mandarin juice resulted in heteroduplex formation. The heteroduplex resulted from the co-amplification of a fragment containing an 8 base-pair indel that distinguished mixtures of orange and mandarin juice from orange juice and mandarin juice alone. The heteroduplex assay was evaluated against authentic juices obtained from different citrus species and confirmed that the marker was homogeneous within Citrus. The data obtained demonstrated maternal inheritance of chloroplast type in Citrus sp. and allowed the identification and confirmation of the maternal parentage of unknown and known citrus hybrids. Analysis of the quantitative potential of the PCR and polyacrylamide gel electrophoresis (PAGE) analysis demonstrated good repeatability with a coefficient of variation of 7.5%. Greatest sources of variance in experimental results were attributable to species and varietal differences in the levels of the PCR target. Mandarin juice contained approximately 18% (w/v) less PCR target sequence than did orange juice. The assay was tested in a blind trial using processed juices and correctly identified 20/22 samples with no false-positive results.
International Ecosystem Assessment Ayensu, Edward; Daniel van R. Claasen; Collins, Mark ...
Science (American Association for the Advancement of Science),
10/1999, Letnik:
286, Številka:
5440
Journal Article
Recenzirano
A system of international ecosystem assessment is urgently needed. A look at how this could be accomplished is presented.
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