Cannabidiol (CBD) is a highly touted product for many different disorders among the lay press. Numerous CBD products are available, ranging from a US Food and Drug Administration (FDA)‐approved ...product called Epidiolex to products created for medical marijuana dispensaries and products sold in smoke shops, convenience stores, and over the Internet. The legal status of the non–FDA‐approved products differs depending on the source of the CBD and the state, while the consistency and quality of the non–FDA‐approved products vary markedly. Without independent laboratory verification, it is impossible to know whether the labeled CBD dosage in non–FDA‐approved CBD products is correct, that the delta‐9‐tetrahydrocannabinol content is <0.3%, and that it is free of adulteration and contamination. On the Internet, CBD has been touted for many ailments for which it has not been studied, and in those diseases with evaluable human data, it generally has weak or very weak evidence. The control of refractory seizures is a clear exception, with strong evidence of CBD's benefit. Acute CBD dosing before anxiety‐provoking events like public speaking and the chronic use of CBD in schizophrenia are promising but not proven. CBD is not risk free, with adverse events (primarily somnolence and gastrointestinal in nature) and drug interactions. CBD has been shown to increase liver function tests and needs further study to assess its impact on suicidal ideation.
Despite their popularity, quantitative instruments like Likert scales struggle with a practical issue for research projects – how many participants have to fill out the instrument? This study started ...with the data for 31,271 articles downloaded from Scopus and, after exclusions, reviewed the sample size used in 21,506 studies. Scimago highest quartile data was brought in for 1999–2021 and linked to the exported articles. Anthropic's Claude and Claude-Instant AI tools were used to analyze the journal article abstracts and extract the sample size information. Frequency distribution of sample size used are presented. Descriptive statistics such as maximum, average and trimmed averaged sample size values are presented by quartile of the journal where the article was published, range of years when the article was published, 3 common analyses which tend to increase sample size, and two population groups which have been shown to impact sample size. The study concludes with ranges for commonly used sample sizes based on a number of criteria. This is one of the first studies to use AI tools to assist in the analysis for a systematic review study.
Due to the range of conflicting criteria regarding minimum sample size needed for a scale/questionnaire validation study, the objective of this review is to analyze sample sizes used in published ...journal articles to contribute a pragmatic perspective to the discussion on sample sizes.
A sample of 1999 articles published in a Scopus-indexed journal about the validation of a scale or questionnaire during 2021 were analyzed for this study. Abstracts from these articles were tabulated by two data entry professionals and any discrepancies were reviewed by the author. The sample size data was grouped by highest quartile of the journal publishing the article and further sub-categorized based on the inclusion of medical patients or students in each study's population.
From the total sample, 1750 articles provided sufficient information in their summary to determine the sample size used. Of these, the majority were published in quartile 1 (784) and quartile 2 (620) journals. Mean values by quartile ranged from 389 (quartile 3) to 2032 (quartile 1), but extreme outliers limited the usefulness of the simple mean. Thus, outlier-removed means were calculated, and in most cases, these sample size values were higher for studies involving students and lower for studies involving patients.
This study is limited by its focus on a single database and by including all phases of validation from initial quantitative instrument design studies (which tend to have the lowest sample sizes) up to international macro-studies (which can have hundreds of thousands of participants.) Nevertheless, the results of this study provide an additional practical perspective for the academic discussion regarding minimum sample size based on accepted practice.
Sample size; Instrument validation; Systematic review
PURPOSE.This article reviews the pharmacology, clinical utility, adverse effects, and abuse potential of kratom.
SUMMARY.The leaves of Mitragyna speciosa contain the biologically active alkaloids of ...kratom. Kratom exerts opioid and α-2 receptor agonistic effects as well as antiinflammatory and parasympathetic-impeding effects. There are no published human pharmacologic, pharmacokinetic, or drug interaction studies on kratom or mitragynine, making it virtually impossible to fully understand kratomʼs therapeutic potential and risks and the populations most likely to benefit or experience harm from its use. Kratom has been used to ameliorate opioid withdrawal symptoms but also induces withdrawal. Human pharmacologic, pharmacokinetic, and clinical data are of low quality, precluding any firm conclusions regarding safety and efficacy. Respiratory depression has not been commonly reported, but kratom does cause a host of adverse effects without clear guidance for how they should be treated. There are numerous assessments where people have been unable to stop using kratom therapy, and withdrawal signs and symptoms are problematic. Kratom does not appear in normal drug screens and, when taken with other substances of abuse, may not be recognized. Thirty-six deaths have been attributed to kratom, and the Food and Drug Administration issued a public health warning about the substance in November 2017.
CONCLUSION.Kratom exerts opioid and α-2 receptor agonistic effects as well as antiinflammatory and parasympathetic-impeding effects. Human pharmacologic, pharmacokinetic, and clinical data are of low quality, precluding any firm conclusions regarding safety and efficacy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
5.
Measurement of single-cell dynamics White, Michael R. H; Spiller, David G; Wood, Christopher D ...
Nature (London),
06/2010, Letnik:
465, Številka:
7299
Journal Article
Recenzirano
Populations of cells are almost always heterogeneous in function and fate. To understand the plasticity of cells, it is vital to measure quantitatively and dynamically the molecular processes that ...underlie cell-fate decisions in single cells. Early events in cell signalling often occur within seconds of the stimulus, whereas intracellular signalling processes and transcriptional changes can take minutes or hours. By contrast, cell-fate decisions, such as whether a cell divides, differentiates or dies, can take many hours or days. Multiparameter experimental and computational methods that integrate quantitative measurement and mathematical simulation of these noisy and complex processes are required to understand the highly dynamic mechanisms that control cell plasticity and fate.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this Perspective, we review recent studies of size-selected cluster deposition for catalysis applications performed at the U.S. DOE National Laboratories, with emphasis on work at Argonne National ...Laboratory (ANL) and Brookhaven National Laboratory (BNL). The focus is on the preparation of model supported catalysts in which the number of atoms in the deposited clusters is precisely controlled using a combination of gas-phase cluster ion sources, mass spectrometry, and soft-landing techniques. This approach is particularly effective for investigations of small nanoclusters, 0.5–2 nm (<200 atoms), where the rapid evolution of the atomic and electronic structure makes it essential to have precise control over cluster size. Cluster deposition allows for independent control of cluster size, coverage, and stoichiometry (e.g., the metal-to-oxygen ratio in an oxide cluster) and can be used to deposit on any substrate without constraints of nucleation and growth. Examples are presented for metal, metal oxide, and metal sulfide cluster deposition on a variety of supports (metals, oxides, carbon/diamond) where the reactivity, cluster–support electronic interactions, and cluster stability and morphology are investigated. Both UHV and in situ/operando studies are presented that also make use of surface-sensitive X-ray characterization tools from synchrotron radiation facilities. Novel applications of cluster deposition to electrochemistry and batteries are also presented. This review also highlights the application of modern ab initio electronic structure calculations (density functional theory), which can essentially model the exact experimental system used in the laboratory (i.e., cluster and support) to provide insight on atomic and electronic structure, reaction energetics, and mechanisms. As amply demonstrated in this review, the powerful combination of atomically precise cluster deposition and theory is able to address fundamental aspects of size-effects, cluster–support interactions, and reaction mechanisms of cluster materials that are central to how catalysts function. The insight gained from such studies can be used to further the development of novel nanostructured catalysts with high activity and selectivity.
IMPORTANCE: Combined use of inhaled corticosteroids and long-acting β-agonists (LABAs) as the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) is a ...potential therapeutic regimen for the management of persistent asthma. OBJECTIVE: To conduct a systematic review and meta-analysis of the effects of SMART in patients with persistent asthma. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE via OVID, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched from database inception through August 2016 and updated through November 28, 2017. Two reviewers selected randomized clinical trials or observational studies evaluating SMART vs inhaled corticosteroids with or without a LABA used as the controller therapy and short-acting β-agonists as the relief therapy for patients aged 5 years or older with persistent asthma and reporting on an outcome of interest. DATA EXTRACTION AND SYNTHESIS: Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs), risk differences (RDs), and mean differences with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength of evidence grading were completed by 2 independent reviewers. MAIN OUTCOMES AND MEASURES: Asthma exacerbations. RESULTS: The analyses included 16 randomized clinical trials (N = 22 748 patients), 15 of which evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Among patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634 65% were female), SMART was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.68 95% CI, 0.58 to 0.80; RD, −6.4% 95% CI, −10.2% to −2.6%) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.77 95% CI, 0.60 to 0.98; RD, −2.8% 95% CI, −5.2% to −0.3%). Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy. Among patients aged 4 to 11 years (n = 341; median age, 8 range, 4-11 years; 69 31% were female), SMART was associated with a reduced risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids as the controller therapy (RR, 0.55 95% CI, 0.32 to 0.94; RD, −12.0% 95% CI, −22.5% to −1.5%) or the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.38 95% CI, 0.23 to 0.63; RD, −23.2% 95% CI, −33.6% to −12.1%). CONCLUSIONS AND RELEVANCE: In this meta-analysis of patients with persistent asthma, the use of single maintenance and reliever therapy compared with inhaled corticosteroids as the controller therapy (with or without a long-acting β-agonist) and short-acting β-agonists as the relief therapy was associated with a lower risk of asthma exacerbations. Evidence for patients aged 4 to 11 years was limited.
In individual mammalian cells the expression of some genes such as prolactin is highly variable over time and has been suggested to occur in stochastic pulses. To investigate the origins of this ...behavior and to understand its functional relevance, we quantitatively analyzed this variability using new mathematical tools that allowed us to reconstruct dynamic transcription rates of different reporter genes controlled by identical promoters in the same living cell. Quantitative microscopic analysis of two reporter genes, firefly luciferase and destabilized EGFP, was used to analyze the dynamics of prolactin promoter-directed gene expression in living individual clonal and primary pituitary cells over periods of up to 25 h. We quantified the time-dependence and cyclicity of the transcription pulses and estimated the length and variation of active and inactive transcription phases. We showed an average cycle period of approximately 11 h and demonstrated that while the measured time distribution of active phases agreed with commonly accepted models of transcription, the inactive phases were differently distributed and showed strong memory, with a refractory period of transcriptional inactivation close to 3 h. Cycles in transcription occurred at two distinct prolactin-promoter controlled reporter genes in the same individual clonal or primary cells. However, the timing of the cycles was independent and out-of-phase. For the first time, we have analyzed transcription dynamics from two equivalent loci in real-time in single cells. In unstimulated conditions, cells showed independent transcription dynamics at each locus. A key result from these analyses was the evidence for a minimum refractory period in the inactive-phase of transcription. The response to acute signals and the result of manipulation of histone acetylation was consistent with the hypothesis that this refractory period corresponded to a phase of chromatin remodeling which significantly increased the cyclicity. Stochastically timed bursts of transcription in an apparently random subset of cells in a tissue may thus produce an overall coordinated but heterogeneous phenotype capable of acute responses to stimuli.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
From 1987 to 1995, Bristol, England's Sarah Records was a modest underground success and, for the most part, a critical laughingstock in its native country-sneeringly dismissed as the sad, final ...repository for a fringe style of music (variously referred to as "indie-pop,a ? "C86,a ? "cutiea ? and "tweea ?) whose moment had passed. Yet now, more than 20 years after its founders symbolically "destroyeda ? it, Sarah is among the most passionately fetishized record labels of all time. Its rare releases command hundreds of dollars, devotees around the world hungrily seek out any information they can find about its poorly documented history, and young musicians-some of them not yet born when Sarah shut down-claim its bands (such as Blueboy, the Field Mice, Heavenly, and the Wake) as major influences.Featuring dozens of exclusive interviews with the music-makers, producers, writers and assorted eyewitnesses who played a part in Sarah's eight-year odyssey, Popkiss: The Life and Afterlife of Sarah Records is the first authorised biography of an unlikely cult legend.
The interest in graphene and its translation into commercial products has been expanding at a high pace. Based on previously described pulmonary safety concerns for carbon nanomaterials, there is a ...great need to define parameters guiding interactions between graphene-based materials and the pulmonary system. The aim of the present study was to determine the importance of two critical parameters: lateral dimensions of the material and coating with proteins in relation to each other and their pulmonary impact. Endotoxin-free materials with distinct lateral dimensions, s-GO (50–200 nm) and l-GO (5–15 μm), were produced and thoroughly characterized. Exploiting intrinsic fluorescence of graphene oxide (GO) and using confocal live-cell imaging, the behavior of the cells in response to the material was visualized in real time. Although BEAS-2B cells internalized GO efficiently, l-GO was linked to higher plasma membrane interactions correlated with elevated reactive oxygen species (ROS) levels, pro-inflammatory response, and greater cytotoxicity, in agreement with the oxidative stress paradigm. For both GO types, the presence of serum alleviated lipid peroxidation of plasma membrane and decreased intracellular ROS levels. However, protein coating was not enough to entirely mitigate toxicity and inflammatory response induced by l-GO. In vitro results were validated in vivo, as l-GO was more prone to induce pulmonary granulomatous response in mice compared to s-GO. In conclusion, the lateral dimension of GO played a more important role than serum protein coating in determining biological responses to the material. It was also demonstrated that time-lapse imaging of live cells interacting with label-free GO sheets can be used as a tool to assess GO-induced cytotoxicity.
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