Electronic cigarette use in 12 European countries. Results from the TackSHS survey.

BACKGROUND: Limited data on electronic cigarette prevalence, patterns and settings of use are available from several European countries. METHODS: Within the TackSHS project, a face-to-face survey was conducted in 2017-2018 in 12 European countries (Bulgaria, England, France, Germany, Greece, Ireland, Italy, Latvia, Poland, Portugal, Romania and Spain). Overall, 11,876 participants, representative of the population aged ≥15 years in each country, provided information on electronic cigarette. RESULTS: 2.4% (95% confidence interval, CI: 2.2-2.7) of the subjects (2.5% among men and 2.4% among women; 0.4% among never, 4.4% among current- and 6.5% among ex-smokers) reported current use of electronic cigarette, ranging from 0.6% in Spain to 7.2% in England. Of the 272 electronic cigarette users, 52.6% were dual users (i.e., users of both electronic and conventional cigarettes) and 58.8% used liquids with nicotine. In all, 65.1% reported using electronic cigarette in at least one indoor setting where smoking is forbidden, in particular in workplaces (34.9%), and bars and restaurants (41.5%). Multivariable logistic regression analysis showed that electronic cigarette use was lower among older individuals (p for trend <0.001) and higher among individuals with high level of education (p for trend 0.040). Participants from countries with higher tobacco cigarette prices more frequently reported electronic cigarette use (odds ratio 3.62; 95% CI: 1.80-7.30). CONCLUSIONS: Considering the whole adult population of these 12 European countries, more than 8.3 million people use electronic cigarettes. The majority of users also smoked conventional cigarettes, used electronic cigarettes with nicotine and consumed electronic cigarettes in smoke-free indoor areas

Optimized low-dose combinatorial drug treatment boosts selectivity and efficacy of colorectal carcinoma treatment.

The current standard of care for colorectal cancer (CRC) is a combination of chemotherapeutics, often supplemented with targeted biological drugs. An urgent need exists for improved drug efficacy and minimized side effects, especially at late-stage disease. We employed the phenotypically driven therapeutically guided multidrug optimization (TGMO) technology to identify optimized drug combinations (ODCs) in CRC. We identified low-dose synergistic and selective ODCs for a panel of six human CRC cell lines also active in heterotypic 3D co-culture models. Transcriptome sequencing and phosphoproteome analyses showed that the mechanisms of action of these ODCs converged toward MAP kinase signaling and cell cycle inhibition. Two cell-specific ODCs were translated to in vivo mouse models. The ODCs reduced tumor growth by ~80%, outperforming standard chemotherapy (FOLFOX). No toxicity was observed for the ODCs, while significant side effects were induced in the group treated with FOLFOX therapy. Identified ODCs demonstrated significantly enhanced bioavailability of the individual components. Finally, ODCs were also active in primary cells from CRC patient tumor tissues. Taken together, we show that the TGMO technology efficiently identifies selective and potent low-dose drug combinations, optimized regardless of tumor mutation status, outperforming conventional chemotherapy

A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models

BACKGROUND: This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model. METHODS: Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT. RESULTS: At 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15-20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25-40%) and plate porosity was strongly increased (25-85%) at all time points studied. CONCLUSION: These findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process

The changing form of Antarctic biodiversity

Antarctic biodiversity is much more extensive, ecologically diverse and biogeographically structured than previously thought. Understanding of how this diversity is distributed in marine and terrestrial systems, the mechanisms underlying its spatial variation, and the significance of the microbiota is growing rapidly. Broadly recognizable drivers of diversity variation include energy availability and historical refugia. The impacts of local human activities and global environmental change nonetheless pose challenges to the current and future understanding of Antarctic biodiversity. Life in the Antarctic and the Southern Ocean is surprisingly rich, and as much at risk from environmental change as it is elsewher

Functional Foveal Splitting: Evidence from Neuropsychological and Multimodal MRI Investigations in a Chinese Patient with a Splenium Lesion

It remains controversial and hotly debated whether foveal information is double-projected to both hemispheres or split at the midline between the two hemispheres. We investigated this issue in a unique patient with lesions in the splenium of the corpus callosum and the left medial occipitotemporal region, through a series of neuropsychological tests and multimodal MRI scans. Behavioral experiments showed that (1) the patient had difficulties in reading simple and compound Chinese characters when they were presented in the foveal but left to the fixation, (2) he failed to recognize the left component of compound characters when the compound characters were presented in the central foveal field, (3) his judgments of the gender of centrally presented chimeric faces were exclusively based on the left half-face and he was unaware that the faces were chimeric. Functional MRI data showed that Chinese characters, only when presented in the right foveal field but not in the left foveal field, activated a region in the left occipitotemporal sulcus in the mid-fusiform, which is recognized as visual word form area. Together with existing evidence in the literature, results of the current study suggest that the representation of foveal stimuli is functionally split at object processing levels

Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases

Age-associated neurodegenerative disorders such as Alzheimer’s disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential

Queen mandibular pheromone: questions that remain to be resolved

The discovery of ‘queen substance’, and the subsequent identification and synthesis of keycomponents of queen mandibular pheromone, has been of significant importance to beekeepers and to thebeekeeping industry. Fifty years on, there is greater appreciation of the importance and complexity of queenpheromones, but many mysteries remain about the mechanisms through which pheromones operate. Thediscovery of sex pheromone communication in moths occurred within the same time period, but in this case,intense pressure to find better means of pest management resulted in a remarkable focusing of research activityon understanding pheromone detection mechanisms and the central processing of pheromone signals in themoth. We can benefit from this work and here, studies on moths are used to highlight some of the gaps in ourknowledge of pheromone communication in bees. A better understanding of pheromone communication inhoney bees promises improved strategies for the successful management of these extraordinary animals

Neuroimaging in anxiety disorders

Neuroimaging studies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, “normal anxiety” does not equal “pathological anxiety” although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors