Storage Conditions Influence the Quality of Ginger - A Stability Study Inspired by Clinical Trials.

Ginger has traditionally been used to treat and prevent nausea and vomiting; however, the results of clinical trials are ambiguous. The efficacy of ginger is attributed to gingerols and their metabolites, shogaols. Since these compounds have different pharmacological profiles, the clinical efficacy of ginger products is largely dependent on their chemical composition. The goal of our study was to examine the stability of ginger, determining the 6-gingerol contents in order to assess the effects of different storage conditions. We have performed a 6-month stability test with dry ginger rhizome samples stored in a constant climate chamber in three different storage containers (uncovered glass container, glass container sealed with rubber stopper, and plastic container). The 6-gingerol contents were measured by HPLC method. The concentration of 6-gingerol decreased in all samples. In the sealed glass container, the decrease in 6-gingerol content was significantly lower than in the unsealed glass container and in the plastic container. These results demonstrate that storage conditions have a significant impact on the quality of ginger, which may also affect efficacy.

Oxidized Juncuenin B Analogues with Increased Antiproliferative Activity on Human Adherent Cell Lines: Semisynthesis and Biological Evaluation.

Phenanthrenes have become the subject of intensive research during the past decades because of their structural diversity and wide range of pharmacological activities. Earlier studies demonstrated that semisynthetic derivatization of these natural compounds could result in more active agents, and oxidative transformations are particularly promising in this regard. In our work, a natural phenanthrene, juncuenin B, was transformed by hypervalent iodine(III) reagents using a diversity-oriented approach. Eleven racemic semisynthetic compounds were produced, the majority containing an alkyl substituted p-quinol ring. Purification of the compounds was carried out by chromatographic techniques, and their structures were elucidated by 1D and 2D NMR spectroscopic methods. Stereoisomers of the bioactive derivatives were separated by chiral-phase HPLC and the absolute configurations of the active compounds, 2,6-dioxo-1,8a-dimethoxy-1,7-dimethyl-8-vinyl-9,10-dihydrophenanthrenes (1a-d), and 8a-ethoxy-1,7-dimethyl-6-oxo-8-vinyl-9,10-dihydrophenanthrene-2-ols (7a,b) were determined by ECD measurements and TDDFT-ECD calculations. The antiproliferative activities of the compounds were tested on different (MCF-7, T47D, HeLa, SiHa, C33A, A2780) human gynecological cancer cell lines. Compounds 1a-d, 4a, 6a, and 7a possessed higher activity than juncuenin B on several tumor cell lines. The structure-activity relationship studies suggested that the p-quinol (2,5-cyclohexadien-4-hydroxy-1-one) moiety has a considerable effect on the antiproliferative properties, and substantial differences could be identified in the activities of the stereoisomers.

The Effects of a Fixed Combination of Berberis aristata and Silybum marianum on Dyslipidaemia - A Meta-analysis and Systematic Review.

A fixed combination of Berberis aristata and Silybum marianum (Berberol) has been used by patients with dyslipidaemia. The aim of the present meta-analysis was to systematically evaluate the efficacy and safety of a fixed combination of B. aristata and S. marianum (Berberol) on serum lipid levels compared to placebo in a meta-analysis based on randomised, controlled trials. The meta-analysis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using the PICO (patients, intervention, comparison, outcome) format, and it was registered in the International Prospective Register of Systematic Reviews. The Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science databases were searched for relevant studies. Placebo-controlled clinical studies involving adult patients with a condition of dyslipidaemia and receiving a fixed combination of B. aristata and S. marianum were included. Four randomised trials, including a total of 491 patients, were pooled in statistical analysis. According to the present meta-analysis, Berberol significantly lowered the low-density lipoprotein level, total cholesterol, fasting plasma glucose levels, and the Homeostatic Model Assessment index compared to placebo; however, its effects on the high-density lipoprotein level, triglyceride level, and body mass index were not statistically significant by the end of a 3-month treatment period. Berberol appeared to be safe, and it did not increase the levels of alanine transaminase, aspartate transaminase, and creatine kinase enzymes. Berberol is an effective and presumably safe complementary therapy for the treatment of dyslipidaemia; however, the evidence supporting its use is very limited. The optimum dose and duration of treatment are unclear. A comprehensive evaluation of efficacy and safety is required in further high-quality clinical studies involving larger patient populations.

The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis.

Herbal products, especially Hypericum perforatum extracts, have been widely used as first-line treatments for mild to moderate depression. Recently, several randomized, controlled clinical trials have been conducted to evaluate the efficacy of another plant, saffron (Crocus sativus), in mild to moderate depression. We have carried out a literature review of currently available published randomized, controlled clinical trials to give an up-to-date evaluation of the efficacy of saffron in mild to moderate depression, compared to placebo or routinely used antidepressants. The meta-analysis is reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using the PICO (patients, intervention, comparison, outcome) format and was conducted using the statistical programs Comprehensive Meta-analysis and RevMan. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for relevant studies. Only placebo or active controlled, randomized clinical studies involving patients suffering from mild to moderate depression and using pharmacological doses of saffron per os were included. Hedges' g was used to calculate effect sizes. Risk of bias was assessed using the Cochrane Collaboration tool, and heterogeneity was tested by both performing the Cochran's Q test and calculating Higgins' I2 indicator. Eleven randomized trials were included in the qualitative analysis, and nine were pooled for statistical analysis. According to the present meta-analysis, saffron has a significant effect on the severity of depression. Available data from randomized, controlled clinical trials support that saffron is significantly more effective than placebo (g = 0.891; 95% CI: 0.369 - 1.412, p = 0.001), and non-inferior to tested antidepressant drugs (g = - 0.246; 95% CI: - 0.495 - 0.004, p = 0.053).

Phenanthrenes: A Promising Group of Plant Secondary Metabolites.

Although phenanthrenes are considered to constitute a relatively small group of natural products, discovering new phenanthrene derivatives and evaluating their prospective biological activities have become of great interest to many research groups worldwide. Based on 160 references, this review covers the phytochemistry and pharmacology of 213 naturally occurring phenanthrenes that have been isolated between 2008 and 2016. More than 40% of the 450 currently known naturally occurring phenanthrenes were identified during this period. The family Orchidaceae is the most abundant source of these compounds, although several new plant families and genera have been involved in the search for phenanthrenes. The presence of certain substituent patterns may be restricted to specific families; vinyl-substituted phenanthrenes were reported only from Juncaceae plants, and prenylated derivatives occur mainly in Euphorbiaceae species. Therefore, these compounds also can serve as chemotaxonomic markers. Almost all of the newly isolated compounds have been studied for their biological activities (e.g., potential cytotoxic, antimicrobial, anti-inflammatory, and antioxidant effects), and many of them showed multiple activities. According to the accumulated data, denbinobin, with a novel mechanism of action, has great potential as a lead compound for the development of a new anticancer agent.

Phenanthrenes from Juncus inflexus with Antimicrobial Activity against Methicillin-Resistant Staphylococcus aureus.

The present study has focused on an investigation of the antibacterial effects of Juncus inflexus and the isolation and identification of its active compounds. Eleven phenanthrenes were isolated from a methanolic extract of the roots. Four compounds (jinflexins A-D, 1-4) are new natural products, while seven phenanthrenes [juncuenins A (5), B (6), and D (8), juncusol (7), dehydrojuncuenins A (9) and B (11), and dehydrojuncusol (10)] were isolated for the first time from the plant. Jinflexin D (4) is a dimer with an unprecedented heptacyclic ring system. The absolute configurations of the new compounds were determined by TDDFT-ECD calculations, and their enantiomeric purity was checked by chiral HPLC analysis. Extracts of different polarity (n-hexane, dichloromethane, and ethyl acetate) were evaluated for their antimicrobial effects against methicillin-resistant Staphylococcus aureus, extended-spectrum ß-lactamase (ESBL)-producing Citrobacter freundii, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, multiresistant Acinetobacter baumannii, and Pseudomonas aeruginosa. The MIC values of the isolated compounds were determined by a microdilution method. Jinflexin B (2), juncusol (7), juncuenin D (8), and dehydrojuncuenin B (11) showed significant activity (MIC value range 12.5-100 µg/mL) against MRSA strains.

Health outcomes associated with smoke exposure in Albuquerque, New Mexico, during the 2011 Wallow fire.

OBJECTIVE: This study examined the association between PM2.5 levels and emergency department (ED) visits for selected health outcomes in Albuquerque, New Mexico, during the Wallow fire of 2011. DESIGN: Measurements of 24-hour average concentrations of PM2.5 obtained from the City of Albuquerque were used to calculate wildfire smoke exposure in Albuquerque. Daily ED visits were collected by the New Mexico Department of Health from individual nonfederal licensed facilities in the Albuquerque area. Poisson regression was used to assess the relationship between ED visits for selected respiratory and cardiovascular conditions and varying levels of PM2.5 exposure. SETTING: Albuquerque, New Mexico. PARTICIPANTS: Patients visiting an ED for select conditions before, during, and after the wildfire. MAIN OUTCOME MEASURE: Relative increase in ED visits for selected conditions during the wildfire period. RESULTS: Analysis of PM2.5 exposure data and ED visits in Albuquerque before and during the Wallow fire indicated that compared with the period prior to the fire, there was an increased risk of ED visits for some respiratory and cardiovascular conditions during heavy smoke conditions, and risk varied by age and sex. The population of 65+ years was especially at risk for increased ED visits. There was a significantly increased risk of ED visits among the 65+ population for asthma (RR [relative rate] = 1.73, 95% confidence interval [CI] = 1.03-2.93) and for diseases of the veins, lymphatic and circulatory system (RR = 1.56, 95% CI = 1.00-2.43). For the age group of 20 to 64 years, there was a statistically significant increase in ED visits for diseases of pulmonary circulation (RR = 2.64, 95% CI = 1.42-4.9) and for cerebrovascular disease (RR = 1.69, 95% CI = 1.03-2.77). CONCLUSIONS: High levels of PM2.5 exposure due to the Wallow fire were associated with increased ED visits for respiratory and cardiovascular conditions in Albuquerque. More effective and targeted preventive measures are necessary to reduce morbidity rates associated with wildfire smoke exposure among vulnerable populations.

Not first-line antihypertensive agents, but still effective-The efficacy and safety of imidazoline receptor agonists: A network meta-analysis.

Cardiovascular disorders are the leading cause of death in the world. Many organ diseases (kidney, heart, and brain) are substantially more prone to develop in people with hypertension. In the treatment of hypertension, first-line medications are recommended, while imidazoline receptor agonists are not first-line antihypertensives. Our goal was to conduct a network meta-analysis to assess the efficacy and safety of imidazoline receptor agonists. The meta-analysis was performed following the PRISMA guidelines using the PICOS format, considering the CONSORT recommendations. Studies were collected from four databases: PubMed, Cochrane Library, Web of Science, and Embase. A total of 5960 articles were found. After filtering, 27 studies remained eligible for network meta-analysis. Moxonidine reduced blood pressure in sitting position statistically significantly after 8 weeks of treatment (SBP MD: 23.80; 95% CI: 17.45-30.15; DBP MD: 10.90; 95% CI: 8.45-13.35) compared to placebo. Moreover, moxonidine reduced blood pressure more effectively than enalapril; however, this difference was not significant (SBP MD: 3.10; 95% CI: -2.60-8.80; DBP MD: 1.30; 95% CI: -1.25-3.85). Dry mouth was experienced as a side effect in the case of all imidazoline receptor agonists. After 8 weeks of treatment, the appearance of dry mouth was highest with clonidine (OR: 9.27 95% CI: 4.70-18.29) and lowest with rilmenidine (OR: 6.46 95% CI: 0.85-49.13) compared to placebo. Somnolence was less frequent with moxonidine compared to rilmenidine (OR: 0.63 95% CI: 0.17-2.31). Imidazoline receptor agonists were nearly as effective as the first-line drugs in the examined studies. However, their utility as antihypertensives is limited due to their side effects. As a result, they are not first-line antihypertensives and should not be used in monotherapy. However, in the case of resistant hypertension, they are a viable option. According to our findings, from the point of view of safety and efficacy, moxonidine appears to be the best choice among imidazoline receptor agonists.

Aromatase Inhibitors and Plasma Lipid Changes in Postmenopausal Women with Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid profiles. Aromatase inhibitors (AI) are used to prevent the progression of cancer; however, a further reduction in estrogen levels may have detrimental effects on lipid levels, which was our working hypothesis. Methods: Our meta-analysis was conducted on the lipid profiles of postmenopausal breast cancer patients at baseline and at different treatment time points. Results: We identified 15 studies, including 1708 patients. Studies using anastrozole (ANA), exemestane (EXE), letrozole (LET), and tamoxifen (TMX) were involved. Subgroup analyses revealed that 3- and 12-month administrations of LET and EXE lead to negative changes in lipid profiles that tend to alter the lipid profile undesirably, unlike ANA and TMX. Conclusions: Our results suggest that, despite statistically significant results, EXE and LET may not be sufficient to cause severe dyslipidemia in patients without cardiovascular comorbidities according to the AHA/ACC Guideline on the Management of Blood Cholesterol. However, the results may raise the question of monitoring the effects of AIs in patients, especially those with pre-existing cardiovascular risk factors such as dyslipidemia.

Epidemiology and patients' self-reported knowledge of implantable medical devices: Results of a cross-sectional survey in Hungary.

BACKGROUND: Implantable medical devices (IMDs) are medical instruments embedded inside the body. Well-informed and empowered patients living with IMDs are key players of improving IMD-related patient safety and health outcomes. However, little is known about IMD patients' epidemiology, characteristics, and current awareness levels. Our primary aim was to investigate the point and lifetime prevalence of patients living with IMDs. Patients' IMD-related knowledge and determinants of IMDs' impact on their life were also explored. METHODS: An online cross-sectional survey was conducted. Respondents' IMD history, whether they received instructions for use and IMD's overall impact on life were recorded by self-reports. Patients' knowledge about living with IMDs was assessed on visual analogue scales (VAS, 0-10). Shared decision-making was analyzed by the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Descriptive statistics and subgroup comparisons between IMD wearers were performed for statistical differences. Significant determinants of IMD's overall impact on life were examined in linear regression analysis. RESULTS: In the total sample (N = 1400, mean age 58.1 ±11.1; female 53.7%), nearly one third of respondents were living with IMD (30.9%; 433/1400). Among them, the most frequent IMDs were tooth implants (30.9%) and intraocular lens (26.8%). Mean knowledge VAS scores were similar (range: 5.5 ±3.8-6.5 ±3.2) but differences by IMD types were observed. Patients who received instructions for use or reported better impact on life indicated higher self-reported knowledge. Regression confirmed that patients' knowledge was significant predictor of IMD's impact on life, but this effect was overwritten by the SDM-Q-9. CONCLUSIONS: This first comprehensive epidemiological study on IMDs provides basic data for public health strategy planning alongside the implementation of MDR. Improved self-perceived outcomes were associated with higher knowledge hence education of patients receiving IMD deserves consideration. We suggest to investigate further the role of shared decision-making on IMD's overall impact on patients' life in future prospective studies.

The metabolic effect of Momordica charantia cannot be determined based on the available clinical evidence: a systematic review and meta-analysis of randomized clinical trials.

Several studies have shown that Momordica charantia L. (Cucurbitaceae, bitter melon) has beneficial effects on metabolic syndrome (MetS) parameters and exerts antidiabetic, anti-hyperlipidemic, and anti-obesity activities. Since the findings of these studies are contradictory, the goal of this systematic review and meta-analysis was to assess the efficacy of bitter melon in the treatment of metabolic syndrome, with special emphasis on the anti-diabetic effect. Embase, Cochrane, PubMed, and Web of Science databases were searched for randomized controlled human trials (RCTs). The meta-analysis was reported according to the PRISMA statement. The primary outcomes of the review are body weight, BMI, fasting blood glucose, glycated hemoglobin A1c, systolic blood pressure, diastolic blood pressure, serum triglyceride, HDL, LDL, and total cholesterol levels. Nine studies were included in the meta-analysis with 414 patients in total and 4-16 weeks of follow-up. In case of the meta-analysis of change scores, no significant effect could be observed for bitter melon treatment over placebo on fasting blood glucose level (MD = -0.03; 95% CI: -0.38 to 0.31; I2 = 34%), HbA1c level (MD = -0.12; 95% CI: -0.35 to 0.11; I2 = 56%), HDL (MD = -0.04; 95% CI: -0.17 to 0.09; I2 = 66%), LDL (MD = -0.10; 95% CI: -0.28 to 0.08; I2 = 37%), total cholesterol (MD = -0.04; 95% CI: -0.17 to 0.09; I2 = 66%,), body weight (MD = -1.00; 95% CI: -2.59-0.59; I2 = 97%), BMI (MD = -0.42; 95% CI: -0.99-0.14; I2 = 95%), systolic blood pressure (MD = 1.01; 95% CI: -1.07-3.09; I2 = 0%) and diastolic blood pressure levels (MD = 0.24; 95% CI: -1.04-1.53; I2 = 0%). Momordica treatment was not associated with a notable change in ALT, AST, and creatinine levels compared to the placebo, which supports the safety of this plant. However, the power was overall low and the meta-analyzed studies were also too short to reliably detect long-term metabolic effects. This highlights the need for additional research into this plant in carefully planned clinical trials of longer duration.

Results of a systematic review and meta-analysis of early studies on ivermectin in SARS-CoV-2 infection.

Ivermectin, an antiparasitic drug, has been repurposed for COVID-19 treatment during the SARS-CoV-2 pandemic. Although its antiviral efficacy was confirmed early in vitro and in preclinical studies, its clinical efficacy remained ambiguous. Our purpose was to assess the efficacy of ivermectin in terms of time to viral clearance based on the meta-analysis of available clinical trials at the closing date of the data search period, one year after the start of the pandemic. This meta-analysis was reported by following the PRISMA guidelines and by using the PICO format for formulating the question. The study protocol was registered on PROSPERO. Embase, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), bioRvix, and medRvix were searched for human studies of patients receiving ivermectin therapy with control groups. No language or publication status restrictions were applied. The search ended on 1/31/2021 exactly one year after WHO declared the public health emergency on novel coronavirus. The meta-analysis of three trials involving 382 patients revealed that the mean time to viral clearance was 5.74 days shorter in case of ivermectin treatment compared to the control groups [WMD = -5.74, 95% CI (-11.1, -0.39), p = 0.036]. Ivermectin has significantly reduced the time to viral clearance in mild to moderate COVID-19 diseases compared to control groups. However, more eligible studies are needed for analysis to increase the quality of evidence of ivermectin use in COVID-19.

The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis.

Synephrine has been used to promote weight loss; however, its safety and efficacy have not been fully established. The goals of our study were to give an overview of the safety and efficacy of p-synephrine, to systematically evaluate its efficacy regarding weight loss and to assess its safety, focusing on its cardiovascular side effects in a meta-analysis. PubMed, the Cochrane Library, Web of Science and Embase were searched for relevant studies. Only placebo-controlled, human clinical trials with synephrine intervention were included in the meta-analysis. The meta-analysis was reported according to the PRISMA guidelines using the PICOS format and taking into account the CONSORT recommendations. Altogether, 18 articles were included in the meta-analysis. Both systolic and diastolic blood pressure (DBP) increased significantly after prolonged use (6.37 mmHg, 95% CI: 1.02-11.72, p = 0.02 and 4.33 mmHg, 95% CI: 0.48-8.18, p = 0.03, respectively). The weight loss in the synephrine group was non-significant after prolonged treatment, and it did not influence body composition parameters. Based on the analyzed clinical studies, synephrine tends to raise blood pressure and heart rate, and there is no evidence that synephrine can facilitate weight loss. Further studies are needed to confirm evidence of its safety and efficacy.

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials.

Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64-31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92-152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33-68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19-9.78), dizziness (OR: 4.60 95% CI: 2.39-8.83) and headache (OR: 2.90; 95% CI: 1.07-7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds.

Bearberry in the treatment of acute uncomplicated cystitis (BRUMI): protocol of a multicentre, randomised double-blind clinical trial.

BACKGROUND: Bearberry (Arctostaphylos uva-ursi) leaf is available as a treatment of uncomplicated cystitis in several European countries. The antimicrobial activity of its extracts and some of its individual constituents has been observed in vitro; however, the efficacy of bearberry compared with standard antimicrobial therapy has not been assessed yet. OBJECTIVE: The objective of the study is to assess the safety and non-inferiority of bearberry as an alternative therapy in the treatment of acute uncomplicated cystitis in comparison with standard antibiotic therapy (fosfomycin). METHODS AND ANALYSIS: This is a randomised controlled double-blinded multicentre trial. Eligible patients will be premenopausal women with a sum score of ≥6 for the typical acute uncomplicated cystitis symptoms (frequency, urgency, painful urination, incomplete emptying, suprapubic pain and visible haematuria) reported on the Acute Cystitis Symptom Score (ACSS) typical domain and pyuria. Patients will be randomly assigned to receive 3 g single dose of fosfomycin powder and two placebo tablets three times a day for 7 days or B a single dose of placebo powder and two tablets containing a dry extract of Uvae ursi folium. At least 504 patients (allocated as 1:1) will need to be enrolled to access non-inferiority with a non-inferiority limit of 14% for the primary endpoint.Improvement of symptoms of uncomplicated cystitis (based on the ACSS score) at day 7 is defined as the primary endpoint, whereas several secondary endpoints such as the number and ratio of patients with bacteriuria at day 7, frequency and severity of side effects; recurrence of urinary tract infection, concurrent use of other over the counter (OTC) medications and food supplements will be determined to elucidate more detailed differences between the groups. The number of recurrences and medications taken for treatment will be monitored for a follow-up period of 90 days (80-100 days). ETHICS AND DISSEMINATION: This study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/4225-1/2021/EKU). The results will be disseminated by publication of peer-reviewed manuscripts. TRIAL REGISTRATION NUMBER: NCT05055544.

CBD, a precursor of THC in e-cigarettes.

The use of cannabidiol (CBD) in electronic cigarettes is widespread. Previously, it was reported that CBD is partly transformed to THC in case smoking as a cigarette, however, the pyrolysis of this compound has not been assessed extensively. The aim of our study was to investigate the effect of temperature on the composition of pyrolysis products of CBD. The experiments were performed in the typical operating temperature range of e-cigarettes (250-400 °C) and at 500 °C under both inert and oxidative conditions, and the pyrolysis products were identified and quantified by GC-MS. Depending on the temperature and atmosphere, 25-52% of CBD was transformed into other chemical substances: Δ9-THC, Δ8-THC, cannabinol and cannabichromene were the predominant pyrolysates in both conditions, all formed by cyclization reaction. THC was the main pyrolysis product at all temperatures under both oxidative and inert conditions. Our results point out that CBD in e-cigarettes can be considered as a precursor of THC, thus it bears all the dangers related to this psychoactive compound. Our findings are fundamental contributions to the safety profile of CBD-based e-cigarettes.

Orally Administered Probiotics Decrease Aggregatibacter actinomycetemcomitans but Not Other Periodontal Pathogenic Bacteria Counts in the Oral Cavity: A Systematic Review and Meta-Analysis.

Introduction: At the initial part of the gastrointestinal tract, multiple tissues serve the normal function of food delivery. Periodontal structures are integral elements of these. When they deteriorate, it is extremely challenging to regenerate and reconstruct them. The conventional intervention for periodontal disease is scaling and root planning with the aim of reducing pathogenic bacteria. However, periodontal pathogens can rapidly recolonize treated areas. Probiotics have been proposed as novel tools for managing oral health by suppressing pathogenic bacteria through their anti-inflammatory effect, but the available data are controversial. Aim: Therefore, we performed a meta-analysis to study the effect of probiotics on periodontal pathogenic bacteria. Methods: The study was registered in PROSPERO under registration number CRD42018094903. A comprehensive literature search from four electronic databases (PubMed, Cochrane CENTRAL, Embase, and Web of Science) yielded nine eligible records for statistical analysis. Studies measuring bacterial counts in saliva and supra- and subgingival plaque were included. Bacterial counts were analyzed using standard mean difference (SMD) and by a random effects model with the DerSimonian-Laird estimation. Results: The results showed a significant decrease in the overall count of Aggregatibacter actinomycetemcomitans in the probiotic-treated group compared to the control at 4 weeks (SMD: -0.28; 95% CI: -0.56--0.01; p = 0.045) but not later. Analyzing the bacterial counts in subgroups, namely, in saliva and supra- and subgingival plaque, separately, yielded no significant difference. Probiotics had no significant effect on the overall count of Porphyromonas gingivalis at 4 weeks (SMD: -0.02; 95% CI: -0.35-0.31; p = 0.914) or later. Subgroup analysis also revealed no significant difference between treatment and control groups nor did probiotics significantly decrease the overall and subgroup bacterial counts of Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Conclusion: Our data support the beneficial effect of probiotics in reducing A. actinomycetemcomitans counts, but not of other key periodontal pathogenic bacteria in periodontal disease patients. However, due to the complex mechanism associated with periodontal disease and the limitations of the available studies, there is a further need for well-designed randomized clinical trials to assess the efficacy of probiotics.

A Systematic Review of the European Rapid Alert System for Food and Feed: Tendencies in Illegal Food Supplements for Weight Loss.

Background: Slimming products represent a dynamically growing group of food supplements worldwide. The efficacy of safely usable natural ingredients is usually below consumers' expectations. Certain manufacturers add unauthorized or prohibited ingredients to weight loss supplements in order to increase their efficacy. Hence, many of these products are adulterated and may pose a risk to the consumers' health. Aims: The aim of our work was to give an overview on natural ingredients used in slimming products, to summarize the frequently used synthetic adulterants and also to assess the trends of adulterated and illegal food supplements in the European Union based on the warnings of the Rapid Alert System for Food and Feed (RASFF) in the time period of 1988-2019. Methods: Reports between 1988-2019 were extracted from the RASFF portal on January 1, 2020. Each entry was individually reviewed. Results: 2,559 records of food supplements with quality problems were identified in the RASFF, several of which [319 (12,5%)] were marketed to facilitate weight loss. 202 (63,3%) contained unapproved, synthetic drug ingredients. The major adulterant (113 of 319, 35.4%) was DNP (2,4-dinitrophenol), whereas sibutramine was the second most frequent adulterant agent (69 products, 21,6%) between 1988 and 2019. Conclusion: The number of approved medicines for the indication of weight loss is relatively low and their efficacy (and also that of the natural ingredients) is limited. Therefore, a significant number of weight loss supplements is adulterated to satisfy patients' expectations. Hence, these products may cause serious adverse effects in sensitive patients.

Comprehensive chemotaxonomic analysis of saffron crocus tepal and stamen samples, as raw materials with potential antidepressant activity.

Saffron crocus (Crocus sativus L.) has been widely grown in Iran. Its stigma is considered as the most valuable spice for which several pharmacological activities have been reported in preclinical and clinical studies, the antidepressant effect being the most thoroughly studied and confirmed. This plant part contains several characteristic secondary metabolites, including the carotenoids crocetin and crocin, and the monoterpenoid glucoside picrocrocin, and safranal. Since only the stigma is utilized industrially, huge amount of saffron crocus by-product remains unused. Recently, the number of papers dealing with the chemical and pharmacological analysis of saffron is increasing; however, there are no systematic studies on the chemical variability of the major by-products. In the present study, we harvested saffron crocus flowers from 40 different locations of Iran. The tepals and stamens were separated and subjected to qualitative and quantitative analysis by HPLC-DAD. The presence and amount of seven marker compounds, including crocin, crocetin, picrocrocin, safranal, kaempferol-3-O-sophoroside, kaempferol-3-O-glucoside, and quercetin-3-O-sophoroside were determined. The analytical method was validated for filter compatibility, stability, suitability, accuracy, precision, intermediate precision, and repeatability. Tepal and stamen samples contained three flavonol glycosides. The main constituent of the tepals was kaempferol-3-O-sophoroside (62.19-99.48 mg/g). In the stamen, the amount of flavonoids was lower than in the tepal. The amount of kaempferol-3-O-glucoside, as the most abundant compound, ranged between 1.72-7.44 mg/g. Crocin, crocetin, picrocrocin, and safranal were not detected in any of the analysed samples. Our results point out that saffron crocus by-products, particularly tepals might be considered as rich sources of flavonol glucosides. The data presented here can be useful in setting quality standards for plant parts of C. sativus that are currently considered as by-products of saffron production.

Effects of Chlorine Dioxide on Oral Hygiene - A Systematic Review and Meta-analysis.

BACKGROUND: Effective and selective oral rinses are required in the daily medical and dental practice. Currently mouthwashes used have substantial side effects. OBJECTIVES: Our aim was to evaluate the efficacy of chlorine dioxide-containing mouthwashes in comparison with other previously established mouth rinses in healthy adults using oral hygiene indices. METHODS: This work was registered in PROSPERO (CRD42018099059) and carried out using multiple databases and reported according to the PRISMA statement. The search terms used were "chlorine dioxide" AND "oral", and only randomised controlled trials (RCTs) were included. The primary outcome was the alteration of the plaque index (PI), while the secondary outcomes were the gingival index (GI) and bacterial counts. For the risk of bias assessment, the Cochrane Risk of Bias Tool was used. Statistical analysis for data heterogeneity was performed by Q-value and I2-tests. RESULTS: 364 articles were found in the databases. After the selection process, only five RCTs were eligible for meta-analysis. Data heterogeneity was low. There were no statistical differences in effectiveness between chlorine dioxide and other effective mouth rinses in PI (0.720±0.119 vs 0.745±0.131; 95%; confidence intervals (CIs): 0.487-0.952 vs 0.489-1.001, respectively) and GI (0.712±0.130 vs 0.745±0.131; 95% CIs: 0.457-0.967 vs 0.489- 1.001, respectively) and also in bacterial counts. CONCLUSION: Chlorine dioxide reduces both plaque and gingival indices and bacterial counts in the oral cavity similar to other routinely used oral rinses, however, the evidence supporting this outcome is very limited. Therefore, further large scale RCTs are needed to decrease the risk of bias.