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Inflammation is regarded as an important mechanism behind mortality and morbidity experienced by cardiorespiratory patients exposed to urban air particulate matter (PM). Small-scale biomass combustion is an important source of particulate air pollution. In this study, we investigated association between inflammatory responses and chemical composition of PM(1) emissions from seven different small-scale wood combustion appliances representing old and modern technologies. Healthy C57Bl/6J mice were exposed by intratracheal aspiration to single dose (10 mg/kg) of particulate samples. At 4 and 18 h after the exposure, bronchoalveolar lavage fluid (BALF) as well as serum was collected for subsequent analyses of inflammatory indicators (interleukin (IL)-6, IL-1β, IL-12, and IL-10; tumor necrosis factor-α (TNF-α); keratinocyte-derived chemoattractant (KC), and interferon-γ (IFN-γ)) in multiplexing assay. When the responses to the PM(1) samples were compared on an equal mass basis, the PM from modern technology appliances increased IL-6, KC, and IL-1β levels significantly in BALF at 4 and 18 h after the exposure. In contrast, these responses were seen only at 4 h time point in serum. Increased cytokine concentrations correlated with metal-rich ash related compounds which were more predominant in the modern technology furnaces emissions. These particles induced both local and systemic inflammation. Instead, polycyclic hydrocarbon (PAH) rich PM(1) samples from old technology (OT) evoked only minor inflammatory responses. In conclusion, the combustion technology largely affects the toxicological and chemical characteristics of the emissions. The large mass emissions of old combustion technology should be considered, when evaluating the overall harmfulness between the appliances. However, even the small emissions from modern technologies may pose significant toxic risks.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide. The only possibly curative therapeutic option is surgical resection. Due to impaired liver function and/or anatomical reasons only a low percentage of patients can be treated surgically. For the remainder, several non-surgical treatment approaches have been developed. In addition to percutaneous ethanol injection, transarterial interventions, and several medical interventions, radiofrequency thermal ablation has been investigated in coagulating HCC lesions.To evaluate the effects of radiofrequency thermal ablation in HCC patients with respect to clinically relevant outcomes (mortality, rate of recurrences, adverse events, quality of life, and duration of hospital stay).We searched The Cochrane Hepato-Biliary Group Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library, MEDLINE, Current Contents, EMBASE, and CancerLit until June 2001 and further handsearch was conducted. Reference lists of the identified articles were checked for further trials.All randomised or quasi-randomised clinical trials investigating radiofrequency thermal ablation versus placebo, no intervention, or any other therapeutic approach were considered for inclusion, regardless of blinding, language, and publication status.Trial inclusion, quality assessment, and data extraction were performed independently by two reviewers. Principal investigators were contacted for further information.One randomised trial which is still ongoing and only published as an interim analysis was identified. This trial compared radiofrequency thermal ablation versus percutaneous ethanol injection in 102 patients with small HCC. With respect to mortality the trial showed no significant difference between the two treatments (relative risk = 0.19, 95% confidence interval 0.02 to 1.59). Concerning the recurrence free survival the trial demonstrated no significant superiority of radiofrequency thermal ablation versus percutaneous ethanol injection (relative risk = 0.70, 95% confidence interval 0.46 -1.04).At present, radiofrequency thermal ablation is an insufficiently studied intervention for HCC.

ABSTRACTBackground  Ethyl sulphate (EtS), a direct ethanol metabolite, appears to offer potential as a biomarker for recent alcohol consumption. Although its window of assessment is similar to that of ethyl glucuronide (EtG), there are differences between the two markers in their pathways for formation and degradation.Aims  (a) To assess the excretion of EtS compared to EtG and ethanol in drinking experiments with healthy volunteers, and (b) to elucidate the possibility of using the two metabolites for monitoring abstinence in substance use disorder patients during rehabilitation treatment.Design, setting, participants  (a) Nine drinking experiments were performed by six healthy volunteers (two females, four males), with a mean age of 34.1 years (20–62), average oral intake of 0.2 g/kg ethanol (0.1–0.61), and having 74 spot urine samples. (b) Thirty‐six substance abuse patients (mean age 41.9 years, 20–59; 22 males, 14 females) in a rehabilitation programme after withdrawal, producing 98 urine samples. Ethyl glucuronide and ethyl sulphate were measured using liquid chromatography tandem mass spectrometry (LC‐MS/MS) using d5‐EtG and d5‐EtS, respectively, as an internal standard.Findings  (a) Volunteers: EtG and EtS were detectable for up to 36 hours and reached the limits of determination in urine at 20.6 hours and 21.2 hours (median), respectively, after ethanol intake. EtG‐100 (standardized to a creatinine of 100 mg/dl) reached its maximum level at 2.8 hours and EtS‐100 at 2.1 hours (median) after the beginning of the experiment. Of the ethanol ingested, 0.022% was excreted as EtS in one volunteer. Eight samples were positive for EtS only and six for EtG only. Spearman's rank correlation coefficients of 0.84 (P < 0.0001) between EtG and EtS and 0.87 (P < 0.0001) between EtG‐100 and EtS‐100 were found. (b) Patients: of the 98 urine samples evaluated, 27 were positive for EtS and of these only 20 were also positive for EtG. Spearman's rank correlation coefficients of 0.84 (P < 0.0001) between EtG and EtS and 0.82 (P < 0.0001) between EtG‐100 and EtS‐100 were found.Conclusions  The data from patients and volunteers suggest that the direct ethanol metabolite ethyl sulphate has the potential to serve as a biomarker of recent ethanol intake. Because EtG and EtS are formed via different pathways they might be used conjointly, thereby increasing sensitivity.

Ultrasound and radiofrequency renal denervation (RDN) have been shown to safely lower blood pressure (BP) in hypertension.The TARGET BP OFF-MED trial investigated the efficacy and safety of alcohol-mediated renal denervation (RDN) in the absence of antihypertensive medications.This randomised, blinded, sham-controlled trial was conducted in 25 centres in Europe and the USA. Patients with a 24-hour systolic BP of 135-170 mmHg, an office systolic BP 140-180 mmHg and diastolic BP ≥90 mmHg on 0-2 antihypertensive medications were enrolled. The primary efficacy endpoint was the change in mean 24-hour systolic BP at 8 weeks. Safety endpoints included major adverse events up to 30 days.A total of 106 patients were randomised; the baseline mean office BP following medication washout was 159.4/100.4±10.9/7.0 mmHg (RDN) and 160.1/98.3±11.0/6.1 mmHg (sham), respectively. At 8 weeks post-procedure, the mean (±standard deviation) 24-hour systolic BP change was â2.9±7.4 mmHg (p=0.009) versus â1.4±8.6 mmHg (p=0.25) in the RDN and sham groups, respectively (mean between-group difference: 1.5 mmHg; p=0.27). There were no differences in safety events between groups. After 12 months of blinded follow-up, with medication escalation, patients achieved similar office systolic BP (RDN: 147.9±18.5 mmHg; sham: 147.8±15.1 mmHg; p=0.68) with a significantly lower medication burden in the RDN group (mean daily defined dose: 1.5±1.5 vs 2.3±1.7; p=0.017).In this trial, alcohol-mediated RDN was delivered safely but was not associated with significant BP differences between groups. Medication burden was lower in the RDN group up to 12 months.

Periodontitis is one of the most prevalent diseases worldwide. The degree of radiographic bone loss can be used to assess the course of therapy or the severity of the disease. Since automated bone loss detection has many benefits, our goal was to develop a multi-object detection algorithm based on artificial intelligence that would be able to detect and quantify radiographic bone loss using standard two-dimensional radiographic images in the maxillary posterior region. This study was conducted by combining three recent online databases and validating the results using an external validation dataset from our organization. There were 1414 images for training and testing and 341 for external validation in the final dataset. We applied a Keypoint RCNN with a ResNet-50-FPN backbone network for both boundary box and keypoint detection. The intersection over union (IoU) and the object keypoint similarity (OKS) were used for model evaluation. The evaluation of the boundary box metrics showed a moderate overlapping with the ground truth, revealing an average precision of up to 0.758. The average precision and recall over all five folds were 0.694 and 0.611, respectively. Mean average precision and recall for the keypoint detection were 0.632 and 0.579, respectively. Despite only using a small and heterogeneous set of images for training, our results indicate that the algorithm is able to learn the objects of interest, although without sufficient accuracy due to the limited number of images and a large amount of information available in panoramic radiographs. Considering the widespread availability of panoramic radiographs as well as the increasing use of online databases, the presented model can be further improved in the future to facilitate its implementation in clinics.

Release from and accumulation in tissue slices of some neurotransmitters under acute ethanol in naive rats and in long‐term voluntarily ethanol drinking rats were investigated. Slices of the rat caudatoputamen were prelabeled with [3H]choline and release of [3H]acetylcholine was stimulated through either N‐methyl‐d‐aspartate (NMDA) receptors or strychnine‐sensitive glycine receptors. Ethanol in vitro at 2%, 4%, and 6% (34 mM, 68 mM, and 102 mM, respectively) concentration‐dependently depressed the maximum effect of the concentration‐response curve of NMDA in naive rats. In contrast, voluntary ethanol consumption over months led to a significantly enhanced NMDA receptor response characterized by an increase in the maximum effect of the concentration‐response curve. The glycine receptor‐mediated release of [3H]acetylcholine, which is inhibited by acute ethanol in a competitive‐like fashion, was not changed in animals that ingested ethanol over months. Electrically evoked release of [3H]noradrenaline ([3H]NA) and its presynaptic modulation by morphine through μ‐opioid receptors in neocortical slices of the rat, preloaded with [3H]NA, was nearly identical in both ethanol‐naive rats and in ethanol drinking rats. The accumulation of [3H]γ‐aminobutyric acid in rat cerebellum tissue was neither affected by acute ethanol in vitro nor after chronic ethanol consumption. In summary, long‐term voluntary ethanol intake caused a significant increase in NMDA receptor function in the rat caudatoputamen, but did not result in changes in glycine‐evoked [3H]acetylcholine release of electrically evoked [3H]NA release modulated by morphine or cerebellar [3H]γ‐aminobutyric acid accumulation.

AbstractBackground: The aim of this study was to evaluate the clinical and antibacterial properties of alcohol‐free mouthrinses, an amine fluoride/stannous fluoride mouthrinse (ASF) and two triclosan solutions in comparison with a chlorhexidine and a placebo rinse.Material and methods: In a double‐blind, randomised 5‐cell cross‐over 4‐day plaque regrowth study, 19 volunteers rinsed 2 × a day with 15 ml of each of the distributed solutions. Each test cycle was followed by a 10 days wash‐out period. On day 0 of each test week, volunteers received a dental prophylaxis. Thereafter they refrained from all mechanical oral hygiene procedures for the next four days. Plaque regrowth was assessed daily by the plaque index and on day 4 by calculating the plaque area with a computer program after disclosure and photography of the front teeth. The vitality of the plaque was examined on days 1 to 4 by the vital fluorescence technique.Results: 19 participants completed the study. Compared to the placebo the ASF solution showed 15.7% (p>0.5), 30.6% (p<0.001), 40.5% (p<0.001) and 44.7% (p<0.001) reductions on the consecutive days 1–4 in plaque index and a reduction of 61.9% in plaque area. The decrease of vitality of supragingival plaque was highly significant compared to placebo on every test day ranging between 30.9% and 36.6%. A reduction in plaque index from 19.4% (p<0.01) on day 2, 34.9% (p<0.001) on day 3 and 40.4% (p<0.001) on day 4 concommitant with a reduction in plaque area of 48.9% (p<0.001) was noted for alcohol‐free chlorhexidine. Concerning the vitality chlorhexidine reduced the percentage of vital bacteria significantly on every day (16.0% to 24.9%). The reductions in mean plaque index for the 0.15% triclosan solution during the test period were 6.3%, 22.4%, 24.6% and 36% and in plaque area 41.8%. Vitality was significantly reduced at every day compared to placebo. Plaque Index reduction with the 0.02% triclosan increased from 15.3% (day 2) to 31.0% (day 4) and a reduction of 23.6% was seen in plaque area. A significant effect concerning the vitality of the plaque was only found at the first and the last day of the test cycle.Conclusion: Alcohol‐free mouthrinse solutions were shown to be effective in reducing both plaque accumulation and plaque biofilm vitality compared to a placebo solution.

Preparation from leaves of Cordia americana have been widely used in traditional medicine in South Brazil to treat wounds and various inflammations.The objective of this work was to identify the effective compounds in the ethanolic extract prepared from the leaves of Cordia americana, which is used in traditional South Brazilian medicine as anti-inflammatory and wound healing remedy.Isolation and structure elucidation techniques were performed in order to identify the compounds of Cordia americana and HPLC analysis was used for the quantification. The major constituent and the ethanolic extract were investigated for inhibition of 5-lipoxygenase, p38alpha MAPK, TNFalpha release and NF-kappaB as well as in the fibroblast scratch assay.Rosmarinic acid (1) was identified as the major compound with an amount of 8.44% in the ethanolic extract of the leaves of Cordia americana. The ethanolic extract as well as (1) exhibited the highest inhibitory effects on 5-lipoxygenase (IC(50)=0.69 and 0.97microg/mL, resp., IC50 of BWA4C as reference: 0.3microM) and p38alpha (IC50=3.25 and 1.16microg/mL, resp., IC50 of SB203580 as reference: 0.046microM) and moderate inhibitory effects on TNFalpha release. Slight effects were observed in the fibroblast scratch assay.This study increases our knowledge on the effective compound in Cordia americana and supports its use in traditional medicine. We demonstrated for the first time pharmacological effects of Cordia americana and we provide evidences for a crucial role of rosmarinic acid as the major key player.