Brazilian smokers are ready for the ban on flavour additives in tobacco to be implemented

Brazil became the first country to approve a national policy to ban all flavour additives in all tobacco leaf products in 2012. However, as of February 2022, the policy remained to be implemented. Cross-sectional data come from the International Tobacco Control (ITC) Brazil Wave 3 Survey among adult smokers (N = 1216) in 2016–2017. The majority of smokers supported a ban on menthol (56.0%; 95%CI: 51.7–60.2%) and a ban on all additives (61.7%; 57.5–65.8%), with no significant differences across sociodemographic groups in adjusted logistic regression models. More than half of menthol smokers reported they would either quit or reduce the amount they smoked if menthol cigarettes were banned. Findings suggest that there is support for Brazil's ban on flavour additives, which is a determinant of successful policy implemented. Continued delays will postpone an important measure with demonstrated public health gains

Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain

<p>Abstract</p> <p>Background</p> <p>The water channel protein aquaporin-4 (AQP4) is reported to be of possible major importance for accessory cerebrospinal fluid (CSF) circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus.</p> <p>Methods</p> <p>Hydrocephalus was induced in adult rats (~8 weeks) by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI) we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4.</p> <p>Results</p> <p>Lateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC) value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP) in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells.</p> <p>Conclusions</p> <p>AQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF disorders.</p

Aquaporin water channels in the nervous system.

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage

Widespread Contribution of Gdf7 Lineage to Cerebellar Cell Types and Implications for Hedgehog-Driven Medulloblastoma Formation

The roof plate is a specialized embryonic midline tissue of the central nervous system that functions as a signaling center regulating dorsal neural patterning. In the developing hindbrain, roof plate cells express Gdf7 and previous genetic fate mapping studies showed that these cells contribute mostly to non-neural choroid plexus epithelium. We demonstrate here that constitutive activation of the Sonic hedgehog signaling pathway in the Gdf7 lineage invariably leads to medulloblastoma. Lineage tracing analysis reveals that Gdf7-lineage cells not only are a source of choroid plexus epithelial cells, but are also present in the cerebellar rhombic lip and contribute to a subset of cerebellar granule neuron precursors, the presumed cell-of-origin for Sonic hedgehog-driven medulloblastoma. We further show that Gdf7-lineage cells also contribute to multiple neuronal and glial cell types in the cerebellum, including glutamatergic granule neurons, unipolar brush cells, Purkinje neurons, GABAergic interneurons, Bergmann glial cells, and white matter astrocytes. These findings establish hindbrain roof plate as a novel source of diverse neural cell types in the cerebellum that is also susceptible to oncogenic transformation by deregulated Sonic hedgehog signaling

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Smoke-free legislation and neonatal and infant mortality in Brazil: a longitudinal quasi-experimental study

Objective To examine the associations of partial and comprehensive smoke-free legislation with neonatal and infant mortality in Brazil using a quasi-experimental study design. Design Monthly longitudinal (panel) ecological study from January 2000 to December 2016. Setting All Brazilian municipalities (n=5565). Participants Infant populations. Intervention Smoke-free legislation in effect in each municipality and month. Legislation was encoded as basic (allowing smoking areas), partial (segregated smoking rooms) or comprehensive (no smoking in public buildings). Associations were quantified by immediate step and longer term slope/trend changes in outcomes. Statistical analyses Municipal-level linear fixed-effects regression models. Main outcomes measures Infant and neonatal mortality. Results Implementation of partial smoke-free legislation was associated with a −3.3 % (95% CI −6.2% to −0.4%) step reduction in the municipal infant mortality rate, but no step change in neonatal mortality. Comprehensive smoke-free legislation implementation was associated with −5.2 % (95% CI −8.3% to −2.1%) and −3.4 % (95% CI −6.7% to −0.1%) step reductions in infant and neonatal mortality, respectively, and a −0.36 (95% CI −0.66 to−0.06) annual decline in the infant mortality rate. We estimated that had all smoke-free legislation introduced since 2004 been comprehensive, an additional 10 091 infant deaths (95% CI 1196 to 21 761) could have been averted. Conclusions Strengthening smoke-free legislation in Brazil is associated with improvements in infant health outcomes—particularly under comprehensive legislation. Governments should accelerate implementation of comprehensive smoke-free legislation to protect infant health and achieve the United Nation’s Sustainable Development Goal three