Integrative mechanisms of oriented neuronal migration in the developing brain.

The emergence of functional neuronal connectivity in the developing cerebral cortex depends on neuronal migration. This process enables appropriate positioning of neurons and the emergence of neuronal identity so that the correct patterns of functional synaptic connectivity between the right types and numbers of neurons can emerge. Delineating the complexities of neuronal migration is critical to our understanding of normal cerebral cortical formation and neurodevelopmental disorders resulting from neuronal migration defects. For the most part, the integrated cell biological basis of the complex behavior of oriented neuronal migration within the developing mammalian cerebral cortex remains an enigma. This review aims to analyze the integrative mechanisms that enable neurons to sense environmental guidance cues and translate them into oriented patterns of migration toward defined areas of the cerebral cortex. We discuss how signals emanating from different domains of neurons get integrated to control distinct aspects of migratory behavior and how different types of cortical neurons coordinate their migratory activities within the developing cerebral cortex to produce functionally critical laminar organization.

APC sets the Wnt tone necessary for cerebral cortical progenitor development.

Adenomatous polyposis coli (APC) regulates the activity of ß-catenin, an integral component of Wnt signaling. However, the selective role of the APC-ß-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated ß-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-ß-catenin pathway indicates that the maintenance of appropriate ß-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates ß-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. ß-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of ß-catenin or inhibition of ß-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated ß-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development.

The effect of substituent position and solvent on thermal Z‒E isomerization of dihydroquinolylazotetrazole dyes: kinetic, thermodynamic, and spectral approaches.

Kinetic and thermodynamic parameters have been investigated for the thermal Z‒E isomerization of dihydroquinolylazotetrazole dyes with alkyl substituents (Me, t-Bu, and Adm) at positions 1 (dyes 2) and 2 (dyes 3) of the tetrazole moiety in two solvents of different polarity, acetonitrile (MeCN) and toluene. The experimental results show crucial dependence of these parameters on a substituent position in the tetrazole moiety and on a solvent. For dyes 2, Eact and ΔH‡ are lower in MeCN than in toluene that results in a high increase in the lifetimes of the Z isomers: from milliseconds in MeCN to minutes in toluene. For dyes 3, the difference in Eact and ΔH‡ in the two solvents is opposite: Eact and ΔH‡ are by more than 20 kJ mol-1 higher in MeCN, nevertheless, the rate constants for 3 in toluene are comparable with those in MeCN at the ambient temperature and the difference in the behavior is determined by the value of negative entropy of activation. Quantum-chemical calculations of the thermal Z‒E isomerization show the possibility of the process to occur via crossing from the S0 to the thermally induced T1 state. The contribution of this path is highest for 3 in toluene. The analysis of the absorption spectra demonstrates that for the E isomers, the n‒π* and π‒π* transitions are within the long-wavelength absorption band and their positions relative each other are opposite in the solvents: the n‒π* transition is blue-shifted relative to the π‒π* transition in MeCN and is red-shifted in toluene.

Smoking Cessation Support in Social and Community Service Organizations: Potential Activities, Barriers, and Facilitators.

INTRODUCTION: Social and Community Service Organizations (SCSOs) are a potential setting to reach and support people with a low socioeconomic position who smoke, yet smoking cessation is not widely supported by SCSO professionals. AIMS AND METHODS: This study aims to identify SCSO professionals' (1) potential activities to support smoking cessation and (2) barriers and facilitators in undertaking these activities. Between July and November 2022, semi-structured interviews were conducted with 21 professionals recruited through SCSOs in Amsterdam North, including participation workers, welfare workers, parent and child counselors, budget coach, debt counselor, welfare work, community sports, and community center coordinators. Data were analyzed using a thematic approach. RESULTS: Eight activities were identified that could support the client either directly (ie, recognizing smoking clients, discussing smoking and smoking cessation, referring clients, providing smoking cessation counseling, offering help around services) or indirectly (ie, collaboration with relevant network partners, implementing smoke-free environments, enhancing professional skills). Various barriers and facilitators were identified related to the (1) client and their environment (ie, clients' readiness and social environment), (2) interaction between professional and client (ie, topic sensitivity), (3) professional (ie, professional is non-smoker, knowledge, and self-efficacy), (4) professionals' work environment (ie, necessity, responsibility, priority, and time), and (5) smoking cessation services (ie, availability of appropriate services and referral process). CONCLUSIONS: There is potential for SCSO professionals to support smoking cessation, but several barriers hinder their efforts. To address these barriers, it is essential to take into account the factors that SCSO professionals believe facilitate the provision of smoking cessation support. IMPLICATIONS: This study provides insight into how the potential of SCSOs in Amsterdam North to support smoking cessation efforts among people with a low socioeconomic position can be harnessed. Barriers were found at multiple levels (client, professional, client-professional interaction, and organizational) and these findings imply that stakeholders across these levels will need to prioritize smoking cessation to facilitate and stimulate SCSO professionals in supporting smoking cessation. A concrete action would be to offer SCSO professionals additional training in conversational skills to discuss smoking. As a prerequisite, easily accessible and suitable smoking cessation services should be available in the neighborhood.

Disruption of hospital care during the first year of the COVID-19 pandemic impacted socioeconomic groups differently: population based study using routine registration data.

BACKGROUND: During the COVID-19 pandemic, provision of non-COVID healthcare was recurrently severely disrupted. The objective was to determine whether disruption of non-COVID hospital use, either due to cancelled, postponed, or forgone care, during the first pandemic year of COVID-19 impacted socioeconomic groups differently compared with pre-pandemic use. METHODS: National population registry data, individually linked with data of non-COVID hospital use in the Netherlands (2017-2020). in non-institutionalised population of 25-79 years, in standardised household income deciles (1 = low, 10 = high) as proxy for socioeconomic status. Generic outcome measures included patients who received hospital care (dichotomous): outpatient contact, day treatment, inpatient clinic, and surgery. Specific procedures were included as examples of frequently performed elective and acute procedures, e.g.: elective knee/hip replacement and cataract surgery, and acute percutaneous coronary interventions (PCI). Relative risks (RR) for hospital use were reported as outcomes from generalised linear regression models (binomial) with log-link. An interaction term was included to assess whether income differences in hospital use during the pandemic deviated from pre-pandemic use. RESULTS: Hospital use rates declined in 2020 across all income groups. With baseline (2019) higher hospital use rates among lower than higher income groups, relatively stronger declines were found for lower income groups. The lowest income groups experienced a 10% larger decline in surgery received than the highest income group (RR 0.90, 95% CI 0.87 - 0.93). Patterns were similar for inpatient clinic, elective knee/hip replacement and cataract surgery. We found small or no significant income differences for outpatient clinic, day treatment, and acute PCI. CONCLUSIONS: Disruption of non-COVID hospital use in 2020 was substantial across all income groups during the acute phases of the pandemic, but relatively stronger for lower income groups than could be expected compared with pre-pandemic hospital use. Although the pandemic's impact on the health system was unprecedented, healthcare service shortages are here to stay. It is therefore pivotal to realise that lower income groups may be at risk for underuse in times of scarcity.

The contribution of Dutch municipalities to stimulate smoke-free outdoor sports clubs: a qualitative study.

Local governments may play a key role in making outdoor sports clubs smoke free. This study aims to assess the activities, motives, challenges and strategies of Dutch municipalities regarding stimulating outdoor sports clubs to become smoke free. Semi-structured interviews were conducted with 19 policy officers of different municipalities in the Netherlands. The included municipalities varied in terms of region, population size and degree of urbanization. Data were analyzed using content analysis. Municipalities stimulated sports clubs to become smoke free by providing information and support and, to a lesser extent, by using financial incentives. Motives of municipalities varied from facilitating a healthy living environment for youth, responding to denormalization of smoking and aligning with goals formulated in national prevention policy. Policy officers faced several challenges, including limited capacity and funds, a reluctance to interfere with sports clubs and little support within the municipal organization. These challenges were addressed by employing various strategies such as embedding smoke-free sports in a broader preventive policy, setting a good example by creating outdoor smoke-free areas around municipal buildings, and collaborating with stakeholders in the municipality to join forces in realizing smoke-free sports clubs. Municipalities demonstrated evident motivation to contribute to a smoke-free sports environment. Currently, most municipalities fulfil an informative and supportive role, while some municipalities still explore their role and position in relation to supporting sports clubs to become smoke free. Other municipalities have established, according to them, effective strategies.

Cooperative lipolytic control of neuronal triacylglycerol by spastic paraplegia-associated enzyme DDHD2 and ATGL.

Intracellular lipolysis-the enzymatic breakdown of lipid droplet-associated triacylglycerol (TAG)-depends on the cooperative action of several hydrolytic enzymes and regulatory proteins, together designated as lipolysome. Adipose triglyceride lipase (ATGL) acts as a major cellular TAG hydrolase and core effector of the lipolysome in many peripheral tissues. Neurons initiate lipolysis independently of ATGL via DDHD domain-containing 2 (DDHD2), a multifunctional lipid hydrolase whose dysfunction causes neuronal TAG deposition and hereditary spastic paraplegia. Whether and how DDHD2 cooperates with other lipolytic enzymes is currently unknown. In this study, we further investigated the enzymatic properties and functions of DDHD2 in neuroblastoma cells and primary neurons. We found that DDHD2 hydrolyzes multiple acylglycerols in vitro and substantially contributes to neutral lipid hydrolase activities of neuroblastoma cells and brain tissue. Substrate promiscuity of DDHD2 allowed its engagement at different steps of the lipolytic cascade: In neuroblastoma cells, DDHD2 functioned exclusively downstream of ATGL in the hydrolysis of sn-1,3-diacylglycerol (DAG) isomers but was dispensable for TAG hydrolysis and lipid droplet homeostasis. In primary cortical neurons, DDHD2 exhibited lipolytic control over both, DAG and TAG, and complemented ATGL-dependent TAG hydrolysis. We conclude that neuronal cells use noncanonical configurations of the lipolysome and engage DDHD2 as dual TAG/DAG hydrolase in cooperation with ATGL.

Time to match; when do homologous chromosomes become closer?

In most eukaryotes, pairing of homologous chromosomes is an essential feature of meiosis that ensures homologous recombination and segregation. However, when the pairing process begins, it is still under investigation. Contrasting data exists in Mus musculus, since both leptotene DSB-dependent and preleptotene DSB-independent mechanisms have been described. To unravel this contention, we examined homologous pairing in pre-meiotic and meiotic Mus musculus cells using a three-dimensional fluorescence in situ hybridization-based protocol, which enables the analysis of the entire karyotype using DNA painting probes. Our data establishes in an unambiguously manner that 73.83% of homologous chromosomes are already paired at premeiotic stages (spermatogonia-early preleptotene spermatocytes). The percentage of paired homologous chromosomes increases to 84.60% at mid-preleptotene-zygotene stage, reaching 100% at pachytene stage. Importantly, our results demonstrate a high percentage of homologous pairing observed before the onset of meiosis; this pairing does not occur randomly, as the percentage was higher than that observed in somatic cells (19.47%) and between nonhomologous chromosomes (41.1%). Finally, we have also observed that premeiotic homologous pairing is asynchronous and independent of the chromosome size, GC content, or presence of NOR regions.

A Novel Methodological Approach to Measure Linear Trends in Health Inequalities: Proof of Concept With Adolescent Smoking in Europe.

We describe a new method for presenting and interpreting linear trends in health inequalities, and present a proof-of-concept analysis of inequalities in smoking among adolescents in Europe. We estimated the regression line of the assumed linear relationship between smoking prevalence in low- and high-socioeconomic status (SES) youth over time. Using simulation, we constructed a 95% confidence interval (CI) for the smoking prevalence in low-SES youth for when this would be 0% in high-SES youth, and we calculated the likelihood of eradicating smoking inequality (<5% for both low and high SES). This method was applied to data on adolescents aged 15-16 years (n = 250,326) from 23 European countries, derived from the 2003-2015 European Survey Project on Alcohol and Other Drugs. Smoking prevalence decreased more slowly among low- than among high-SES adolescents. The estimated smoking prevalence was 9.4% (95% CI: 6.1, 12.7) for boys and 5.4% (95% CI: 1.4, 9.2) for girls with low SES when 0% with high SES. The likelihood of eradicating smoking inequality was <1% for boys and 37% for girls. We conclude that this novel methodological approach to trends in health inequalities is feasible in practice. Applying it to trends in smoking inequalities among adolescents in Europe, we found that Europe is currently not on track to eradicate youth smoking across SES groups.

Outdoor smoke-free policies at sports clubs across Europe: Current status, recent evidence, and future challenges.

OBJECTIVE: This commentary emphasizes the importance of implementing outdoor smoke-free policies at sports clubs, particularly highlighting their limited adoption across Europe. The primary aim was to assess the progress made in the Netherlands, explore the strategies employed, and outline future challenges. METHODS: Our methodology involved an examination of national regulations and the voluntary adoption of smoke-free policies at sports clubs throughout Europe. We also assessed the adoption and implementation of these policies using recent evidence, leading to the identification of impending challenges in their implementation across Europe. RESULTS: While only a few European countries currently have national legislation prohibiting outdoor smoking at sports clubs, voluntary initiatives promoting such policies have emerged in various nations. Experiences from the Netherlands have demonstrated the feasibility of implementing outdoor smoke-free policies at sports clubs. To expand these policies across Europe, five key challenges need to be addressed: 1) encouraging smoke-free policies at sports clubs that are less inclined to adopt them, 2) ensuring consistent compliance and enforcement of outdoor smoke-free policies, 3) preventing smoking just outside the sports club, 4) garnering support from various stakeholders to ensure widespread adoption of smoke-free sports clubs, and 5) establishing monitoring and evaluation mechanisms for policy implementation. CONCLUSION: The Dutch experiences serve as a testimony to the feasibility of outdoor smoke-free policies at sports clubs. By addressing the remaining challenges, we can create healthier sports environments for children and take substantial steps towards realizing a smoke-free Europe.

Conjugates of nucleobases with triazole-hydroxamic acids for the reactivation of acetylcholinesterase and treatment of delayed neurodegeneration induced by organophosphate poisoning.

A series of new uncharged conjugates of adenine, 3,6-dimetyl-, 1,6-dimethyl- and 6-methyluracil with 1,2,4-triazole-3-hydroxamic and 1,2,3-triazole-4-hydroxamic acid moieties were synthesized and studied as reactivators of organophosphate-inhibited cholinesterase. It is shown that triazole-hydroxamic acids can reactivate acetylcholinesterase (AChE) inhibited by paraoxon (POX) in vitro, offering reactivation constants comparable to those of pralidoxime (2-PAM). However, in contrast to 2-PAM, triazole-hydroxamic acids demonstrated the ability to reactivate AChE in the brain of rats poisoned with POX. At a dose of 200 mg/kg (i.v.), the lead compound 3e reactivated 22.6 ± 7.3% of brain AChE in rats poisoned with POX. In a rat model of POX-induced delayed neurodegeneration, compound 3e reduced the neuronal injury labeled with FJB upon double administration 1 and 3 h after poisoning. Compound 3e was also shown to prevent memory impairment of POX-poisoned rats as tested in a Morris water maze.

Wearable Nanocomposite Sensor System for Motion Phenotyping Chronic Low Back Pain: A BACPAC Technology Research Site.

Chronic low back pain (cLBP) is a prevalent and multifactorial ailment. No single treatment has been shown to dramatically improve outcomes for all cLBP patients, and current techniques of linking a patient with their most effective treatment lack validation. It has long been recognized that spinal pathology alters motion. Therefore, one potential method to identify optimal treatments is to evaluate patient movement patterns (ie, motion-based phenotypes). Biomechanists, physical therapists, and surgeons each utilize a variety of tools and techniques to qualitatively assess movement as a critical element in their treatment paradigms. However, objectively characterizing and communicating this information is challenging due to the lack of economical, objective, and accurate clinical tools. In response to that need, we have developed a wearable array of nanocomposite stretch sensors that accurately capture the lumbar spinal kinematics, the SPINE Sense System. Data collected from this device are used to identify movement-based phenotypes and analyze correlations between spinal kinematics and patient-reported outcomes. The purpose of this paper is twofold: first, to describe the design and validity of the SPINE Sense System; and second, to describe the protocol and data analysis toward the application of this equipment to enhance understanding of the relationship between spinal movement patterns and patient metrics, which will facilitate the identification of optimal treatment paradigms for cLBP.

Biomechanical Phenotyping of Chronic Low Back Pain: Protocol for BACPAC.

OBJECTIVE: Biomechanics represents the common final output through which all biopsychosocial constructs of back pain must pass, making it a rich target for phenotyping. To exploit this feature, several sites within the NIH Back Pain Consortium (BACPAC) have developed biomechanics measurement and phenotyping tools. The overall aims of this article were to: 1) provide a narrative review of biomechanics as a phenotyping tool; 2) describe the diverse array of tools and outcome measures that exist within BACPAC; and 3) highlight how leveraging these technologies with the other data collected within BACPAC could elucidate the relationship between biomechanics and other metrics used to characterize low back pain (LBP). METHODS: The narrative review highlights how biomechanical outcomes can discriminate between those with and without LBP, as well as among levels of severity of LBP. It also addresses how biomechanical outcomes track with functional improvements in LBP. Additionally, we present the clinical use case for biomechanical outcome measures that can be met via emerging technologies. RESULTS: To answer the need for measuring biomechanical performance, our "Results" section describes the spectrum of technologies that have been developed and are being used within BACPAC. CONCLUSION AND FUTURE DIRECTIONS: The outcome measures collected by these technologies will be an integral part of longitudinal and cross-sectional studies conducted in BACPAC. Linking these measures with other biopsychosocial data collected within BACPAC increases our potential to use biomechanics as a tool for understanding the mechanisms of LBP, phenotyping unique LBP subgroups, and matching these individuals with an appropriate treatment paradigm.

The Back Pain Consortium (BACPAC) Research Program Data Harmonization: Rationale for Data Elements and Standards.

OBJECTIVE: One aim of the Back Pain Consortium (BACPAC) Research Program is to develop an integrated model of chronic low back pain that is informed by combined data from translational research and clinical trials. We describe efforts to maximize data harmonization and accessibility to facilitate Consortium-wide analyses. METHODS: Consortium-wide working groups established harmonized data elements to be collected in all studies and developed standards for tabular and nontabular data (eg, imaging and omics). The BACPAC Data Portal was developed to facilitate research collaboration across the Consortium. RESULTS: Clinical experts developed the BACPAC Minimum Dataset with required domains and outcome measures to be collected by use of questionnaires across projects. Other nonrequired domain-specific measures are collected by multiple studies. To optimize cross-study analyses, a modified data standard was developed on the basis of the Clinical Data Interchange Standards Consortium Study Data Tabulation Model to harmonize data structures and facilitate integration of baseline characteristics, participant-reported outcomes, chronic low back pain treatments, clinical exam, functional performance, psychosocial characteristics, quantitative sensory testing, imaging, and biomechanical data. Standards to accommodate the unique features of chronic low back pain data were adopted. Research units submit standardized study data to the BACPAC Data Portal, developed as a secure cloud-based central data repository and computing infrastructure for researchers to access and conduct analyses on data collected by or acquired for BACPAC. CONCLUSIONS: BACPAC harmonization efforts and data standards serve as an innovative model for data integration that could be used as a framework for other consortia with multiple, decentralized research programs.

The Back Pain Consortium (BACPAC) Research Program: Structure, Research Priorities, and Methods.

In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it is often attributed to complex, multifaceted issues involving biological, psychological, and social components. Due to the difficulty in treating the true cause of chronic low back pain (cLBP), an over-reliance on opioid pain medications among cLBP patients has developed, which is associated with increased prevalence of opioid use disorder and increased risk of death. To combat the rise of opioid-related deaths, the National Institutes of Health (NIH) initiated the Helping to End Addiction Long-TermSM (HEAL) initiative, whose goal is to address the causes and treatment of opioid use disorder while also seeking to better understand, diagnose, and treat chronic pain. The NIH Back Pain Consortium (BACPAC) Research Program, a network of 14 funded entities, was launched as a part of the HEAL initiative to help address limitations surrounding the diagnosis and treatment of cLBP. This paper provides an overview of the BACPAC research program's goals and overall structure, and describes the harmonization efforts across the consortium, define its research agenda, and develop a collaborative project which utilizes the strengths of the network. The purpose of this paper is to serve as a blueprint for other consortia tasked with the advancement of pain related science.

Diffusion of smoke-free policies at outdoor sports clubs in the Netherlands.

BACKGROUND: Although outdoor smoke-free policies (SFPs) at sports clubs represent an important new area of tobacco control, the majority of sports clubs are not smoke free. This study aims to assess diffusion patterns of outdoor SFPs at sports clubs in the Netherlands. METHODS: Using a retrospective, registry-based design, an inventory was made of football, field hockey, tennis and korfball clubs that became smoke free between 2016 and 2020. We determined the type of sports, number of members and proportion of youth members. The degree of urbanisation and density of smoke-free sports clubs were measured at the municipality level. The association between sports clubs' characteristics, degree of urbanisation and SFP adoption was analysed using multilevel regression analysis. Horizontal diffusion was tested by analysing the association between the density and annual incidence of smoke-free sports clubs. RESULTS: Since 2016, the number of sports clubs with an outdoor SFP increased from 0.3% to 26.4%. Field hockey and korfball clubs and clubs with many (youth) members were more likely to be smoke-free. SFPs spread from the most urbanised to less urbanised municipalities, which could mostly be attributed to sports clubs' characteristics. A higher density of smoke-free sports clubs within municipalities was associated with an increased incidence of new SFPs in the following year. CONCLUSION: Outdoor SFPs at sports clubs in the Netherlands diffused across horizontal and hierarchical lines. National strategies for smoke-free sports should monitor clubs that are more likely to stay behind, such as football and tennis clubs, smaller clubs and clubs in less urbanised areas.

Ex ante evaluation of the impact of tobacco control policy measures aimed at the point of sale in the Netherlands.

INTRODUCTION: The Netherlands aims to implement stricter tobacco control policies targeting the retail environment. This paper is an ex ante policy evaluation of the potential impact of the current tobacco display and advertising ban as well as future tobacco sales bans on tobacco outlet visibility and availability. METHODS: Between September 2019 and June 2020, all potential tobacco retailers in four Dutch cities (Amsterdam, Eindhoven, Haarlem and Zwolle) were visited and mapped using Global Positioning System. For each retailer selling tobacco, we completed a checklist on the visibility of tobacco products and advertising. Expected reductions in tobacco outlet visibility and availability were calculated per policy measure in absolute numbers (percentage or percentage point decrease) as well as density and proximity. RESULTS: Out of 870 tobacco outlets, 690 were identified with visible tobacco products/advertising. The display ban in supermarkets and small outlets (respectively) is expected to decrease the number (-15; -42 percentage points), outlet density per 10 000 capita (-0.9; -2.6) and proximity in metres (+27 m; +400 m) of outlets with visible products/advertising. The upcoming bans on vending machines and sales in supermarkets are expected to decrease the number (-12%; -31%), density (-0.7; -1.9) and proximity (+12 m; +68 m) of tobacco outlets. Further changes in the number, density and proximity (respectively) of tobacco outlets may be achieved with future sales bans in petrol stations (-7%; -0.4; +60 m) and particularly with a ban on sales in small outlets (-43%; -2.7; +970 m). CONCLUSION: A display ban and a sales ban in small outlets will contribute most to reducing tobacco outlet visibility and availability, assuming that no market shift towards other tobacco outlets will take place.

Bans on tobacco display, advertising and vending machines in the Netherlands: impact on visibility of tobacco and compliance of retailers.

INTRODUCTION: Visibility of tobacco products at retail tobacco outlets is associated with smoking initiation. To address this, across 2020-2022 the Netherlands banned tobacco product displays, advertisements and vending machines in the retail environment. Tobacco/vape specialist shops were exempted. This study assessed the impact of these policies on tobacco visibility in the retail environment and retailer compliance. METHODS: We conducted observational audits of all tobacco outlets in four Dutch cities (Amsterdam, Haarlem, Eindhoven and Zwolle) between 2019 and 2022 (before and after policy implementation), assessing visibility of tobacco products and advertisements, compliance and remaining sources of tobacco visibility (after implementation). We described results by location and outlet type. RESULTS: The number of tobacco outlets with any tobacco advertising or product visibility declined from 530 to 267 (-50%). Among outlets not exempt from the ban, the number with visibility declined from 449 to 172 (-62%), with lower postban visibility in petrol stations (12%) and supermarkets (6%) than small shops (47%). Visibility among tobacco/vape shops increased by 17%. Tobacco product displays remained the main source of visibility. 93% of tobacco vending machines were removed. Maps showed that non-compliance is concentrated in Amsterdam's city centre and more evenly distributed in other cities. CONCLUSION: The bans on tobacco display and tobacco advertising halved the visibility of tobacco in the retail environment, and the vending machine ban practically eradicated vending machines. To further reduce tobacco visibility, violations in small shops should be addressed and tobacco visibility should be regulated in currently exempt tobacco specialist shops.

The emergence of socioeconomic inequalities in smoking during adolescence and early adulthood.

BACKGROUND: While it is known that educational inequalities in smoking start during early and middle adolescence, it is unknown how they further develop until adulthood. The aim of this article is to map, in the Portuguese context, how educational inequalities in smoking emerge from pre-adolescence until young adulthood. METHODS: This study used longitudinal data from the EPITeen Cohort, which recruited adolescents enrolled in schools in Porto, Portugal. We included the 1,038 participants followed at ages 13 (2003/2004), 17, 21, and 24 years. We computed the odds ratio (OR) for the prevalence of smoking states (never smoking, experimenter, less-than-daily, daily and former smoker) and the incidence of transitions between these states, as function of age and education, stratified by sex. We also added interaction terms between age and education. RESULTS: Educational inequalities in daily smoking prevalence, with higher prevalence among those with lower educational level, emerged at 17 years old and persisted until higher ages. They were formed in a cumulative way by the increased risk of experimenting between 13 and 17 years, and increased risk of becoming daily smoker between 17 and 21 years. The incidence of smoking cessation was higher among the higher educated. Inequalities were formed similarly for women and men, but with lower level and showed no significance among women. CONCLUSIONS: These results highlight that actions to prevent smoking should also take in account the potential impact in smoking inequalities, and should focus not only on middle adolescence but also on late adolescence and early adulthood.

Socioeconomic differences in tobacco outlet presence, density, and proximity in four cities in the Netherlands.

BACKGROUND: Previous studies found that tobacco outlets were unevenly distributed by area socioeconomic status (SES). However, evidence from continental Europe is limited. This study aims to assess differences in tobacco outlet presence, density and proximity by area SES in the Netherlands. METHODS: All tobacco outlets in four Dutch cities (Amsterdam, and medium-sized cities Eindhoven, Haarlem, and Zwolle) were mapped between September 2019 and June 2020. We estimated associations between average property value of neighbourhoods (as an indicator of SES, grouped into quintiles) and (1) tobacco outlet presence in the neighbourhood (yes/no), (2) density (per km2), and (3) proximity to the closest outlet (in meters), using logistic and linear regression models. RESULTS: 46% of neighbourhoods contained at least one tobacco outlet. Tobacco outlets were mostly situated in city centres, but the distribution of tobacco outlets varied per city due to differences in urban structures and functions. In the medium-sized cities, each quintile higher neighbourhood-SES was associated with lower tobacco outlet presence (OR:0.71, 95%CI:0.59;0.85), lower density (B:-1.20 outlets/km2, 95%CI:-2.20;-0.20) and less proximity (B:40.2 m, 95%CI 36.58;43.83). Associations were the other way around for Amsterdam (OR:1.22, 95%CI:1.05;1.40, B:3.50, 95%CI:0.81;6.20, and B:-18.45, 95%CI:-20.41;-16.49, respectively). Results were similar for most types of tobacco outlets. CONCLUSION: In medium-sized cities in the Netherlands, tobacco outlets were more often located in low-SES neighbourhoods than high-SES. Amsterdam presented a reverse pattern, possibly due to its unique urban structure. We discuss how licensing might contribute to reducing tobacco outlets in low-SES neighbourhoods.