Academic orientation and cannabis use-findings from a population-based study of Swedish adolescents in upper secondary school.

AIM: To examine the association between academic orientation and frequent cannabis use among Swedish adolescents in upper secondary school and include pupils from introductory programs (IPs), a large group of adolescents previously overlooked in research on adolescent cannabis use. METHODS: We used cross-sectional data from two anonymous school surveys carried out in upper secondary school in 2021. The samples consisted of pupils from all academic orientations, and the analysis included 3151 pupils in higher education preparatory programs (HEPs), 1010 pupils in vocational programs (VPs), and 819 pupils in IPs. The association between the exposure academic orientation and the outcome frequent (21+ times) cannabis was analyzed using multi-level mixed-effects Poisson regression. RESULTS: Estimates from the first model showed a significant (P < 0.05) 2.45 times higher risk of frequent cannabis use among pupils in IPs compared with in HEPs [incidence rate ratio (IRR) 2.45, 95% confidence interval (CI) 1.28-4.66] and 82% higher in VPs (IRR 1.82, 95% CI 1.09-3.04) compared with in HEPs. However, the associations between academic orientation and frequent (21+ times) cannabis use were attenuated and no longer significant when socioeconomic status, truancy, school dissatisfaction, and early onset of substance use were adjusted for. CONCLUSIONS: There was a higher risk of frequent (21+ times) cannabis use among pupils in IPs, and this differential was explained by higher exposure to risk factors in this group. This result is important from a policy perspective as it provides knowledge of a previously neglected risk group for frequent cannabis use.

Further Insight into Extractable (Organo)fluorine Mass Balance Analysis of Tap Water from Shanghai, China.

The ubiquitous occurrence of per- and polyfluoroalkyl substances (PFAS) and the detection of unexplained extractable organofluorine (EOF) in drinking water have raised growing concerns. A recent study reported the detection of inorganic fluorinated anions in German river systems, and therefore, in some samples, EOF may include some inorganic fluorinated anions. Thus, it might be more appropriate to use the term "extractable fluorine (EF) analysis" instead of the term EOF analysis. In this study, tap water samples (n = 39) from Shanghai were collected to assess the levels of EF/EOF, 35 target PFAS, two inorganic fluorinated anions (tetrafluoroborate (BF4-) and hexafluorophosphate (PF6-)), and novel PFAS through suspect screening and potential oxidizable precursors through oxidative conversion. The results showed that ultra-short PFAS were the largest contributors to target PFAS, accounting for up to 97% of ΣPFAS. To the best of our knowledge, this was the first time that bis(trifluoromethanesulfonyl)imide (NTf2) was reported in drinking water from China, and p-perfluorous nonenoxybenzenesulfonate (OBS) was also identified through suspect screening. Small amounts of precursors that can be oxidatively converted to PFCAs were noted after oxidative conversion. EF mass balance analysis revealed that target PFAS could only explain less than 36% of EF. However, the amounts of unexplained extractable fluorine were greatly reduced when BF4- and PF6- were included. These compounds further explained more than 44% of the EF, indicating the role of inorganic fluorinated anions in the mass balance analysis.

Exploring the Link between ADHD and Cannabis Use in Swedish Ninth Graders: The Role of Conduct Problems and Sensation-Seeking.

Background: Attention deficit hyperactivity disorder (ADHD) has in several studies been linked to substance use, including cannabis use. However, crucial gaps remain regarding how to understand this association. Analyzing the association between ADHD and substance use is complicated because of a pronounced overlap between ADHD, conduct problems, and traits such as sensation-seeking. Objectives: Using data from a large and nationally representative study among Swedish adolescents, this study explored the role of conduct problems, but also of sensation-seeking, in accounting for the association between ADHD and cannabis use. Results: There was a notable association between ADHD and cannabis use that was attenuated when conduct problems were controlled for. The association between cannabis use and conduct problems, in turn, was attenuated when sensation-seeking was controlled for. Individuals with both ADHD and conduct problems were more likely to have used cannabis than individuals with ADHD only, but not compared with individuals with conduct problems only. Conclusions: Whereas conduct problems largely explain the link between ADHD and cannabis use, sensation-seeking seems to account for the association between conduct problems and cannabis use.

Stability and Change in Substance Use Among Swedish Adolescents: A Latent Transition Analysis.

Background: Research is needed on how substance use patterns develop over time in the general adolescent population. This knowledge is crucial in calibrating prevention and other interventions. Method: The study concerns use of cigarettes, alcohol, and cannabis in a nationally representative cohort of Swedish adolescents (n = 3999). Two waves (9th and 11th school grade) from the Futura01 study were analyzed using latent transition analysis (LTA) and multinomial regression analysis. Results: Four substance use patterns, were identified, ranging from Non-user, Alcohol experienced, Alcohol User to Co-user of cigarettes, alcohol, and cannabis. Statuses thus conveyed a continuum from no use to more advanced use. Half of the individuals remained in their original status between time-points, and half transitioned, most often one step on the continuum. Alcohol user was the most stable status over time (0.78), and the Non-user status the least (0.36). The probability of remaining in the Alcohol experienced status was 0.57, and 0.45 for the Co-user status. There was a low probability of transitioning from alcohol to cannabis use. Females were more likely to belong to Alcohol experienced and males to Co-user statuses, but these associations weakened over time. Conclusions: The study identified transitions across substance use statuses between time-points. These usually concerned different levels of alcohol use, and not into more advanced substance use that included the illegal substance cannabis. The study corroborates that young Swedes belong to a "sober" generation and usually do not transition from legal into illegal substance use during late adolescence, though with some gender differences.

Self-interpellation in narratives about craving: Multiple and unitary selves.

The concept of addiction seeks to explain why people act contrary to their own best interest. At the centre stage of addiction discourse is craving, conceptualised as a strong urge to use substances. This article analyses how talk therapies such as relapse prevention and self-help groups shape identity constructions and understandings of craving among clients. Drawing upon interviews with individuals who have engaged in talk therapies in Sweden, we analyse how craving is made up through 'self-interpellation', that is, personal narratives about past, present or future thoughts, feelings and actions. The main 'self-interpellation' included multiple selves, where craving was elided by the true self and only felt by the inauthentic self. Less dominant were narratives which drew on a unitary self that remained stable over time and had to fight craving. The notion of multiple selves appeared as a master narrative that the participants were positioned by in their identity constructions. We conclude that this multiplicity seems ontologically demanding for people who try to recover from substance use problems. A demystification of craving, in which neither substance effects nor malfunctioning brains are blamed for seemingly irrational thoughts and actions, may reduce the stigmatisation of those who have developed habitual substance use.

Reasons Not to Drink Alcohol among 9th Graders in Sweden.

AIM: Alcohol is one of the leading contributors to the disease burden among young people. Drinking motives are one of the strongest factors influencing drinking behaviors among youth, yet we know little about reasons for why young people do not drink. The aim of the present study is to examine reasons for not drinking in a nationally representative sample of Swedish youth. DATA AND METHODS: Data from a survey of a nationally representative sample of students in year 9 (15-16 years old) was used. Data was collected in 2017 and the total sample comprise 5549 respondents. Ten items measured reasons not to drink alcohol. Comparisons were made between drinkers and nondrinkers in endorsement of the reasons for not drinking. A multivariable logistic regression model was fitted to examine the relative importance of the different reasons. RESULTS: That alcohol is bad for health and parents disapproval of drinking was the most commonly endorsed reasons both among drinkers and nondrinkers. The multivariable analysis showed that the strongest association with being a nondrinker was found for "Alcohol tastes horrible" (OR 2.995), "I have religious reasons for not drinking" (OR 2.775), "People who drink lose control in an unpleasant way" (OR 2.460) and "Drinking is too likely to lead to serious accidents" (OR 2.458). DISCUSSION AND CONCLUSIONS: Harm avoidance and religious reasons are the most important reasons not to drink among Swedish youth. Future research should examine how different reasons predict abstinence.

An Explainable Machine Learning Model for Material Backorder Prediction in Inventory Management.

Global competition among businesses imposes a more effective and low-cost supply chain allowing firms to provide products at a desired quality, quantity, and time, with lower production costs. The latter include holding cost, ordering cost, and backorder cost. Backorder occurs when a product is temporarily unavailable or out of stock and the customer places an order for future production and shipment. Therefore, stock unavailability and prolonged delays in product delivery will lead to additional production costs and unsatisfied customers, respectively. Thus, it is of high importance to develop models that will effectively predict the backorder rate in an inventory system with the aim of improving the effectiveness of the supply chain and, consequentially, the performance of the company. However, traditional approaches in the literature are based on stochastic approximation, without incorporating information from historical data. To this end, machine learning models should be employed for extracting knowledge of large historical data to develop predictive models. Therefore, to cover this need, in this study, the backorder prediction problem was addressed. Specifically, various machine learning models were compared for solving the binary classification problem of backorder prediction, followed by model calibration and a post-hoc explainability based on the SHAP model to identify and interpret the most important features that contribute to material backorder. The results showed that the RF, XGB, LGBM, and BB models reached an AUC score of 0.95, while the best-performing model was the LGBM model after calibration with the Isotonic Regression method. The explainability analysis showed that the inventory stock of a product, the volume of products that can be delivered, the imminent demand (sales), and the accurate prediction of the future demand can significantly contribute to the correct prediction of backorders.

Electrochemical degradation of per- and poly-fluoroalkyl substances using boron-doped diamond electrodes.

Electrochemical degradation using boron-doped diamond (BDD) electrodes has been proven to be a promising technique for the treatment of water contaminated with per- and poly-fluoroalkyl substances (PFAS). Various studies have demonstrated that the extent of PFAS degradation is influenced by the composition of samples and electrochemical conditions. This study evaluated the significance of several factors, such as the current density, initial concentration of PFAS, concentration of electrolyte, treatment time, and their interactions on the degradation of PFAS. A 24 factorial design was applied to determine the effects of the investigated factors on the degradation of perfluorooctanoic acid (PFOA) and generation of fluoride in spiked water. The best-performing conditions were then applied to the degradation of PFAS in wastewater samples. The results revealed that current density and time were the most important factors for PFOA degradation. In contrast, a high initial concentration of electrolyte had no significant impact on the degradation of PFOA, whereas it decreased the generation of F-. The experimental design model indicated that the treatment of spiked water under a current density higher than 14 mA cm-2 for 3-4 h could degrade PFOA with an efficiency of up to 100% and generate an F- fraction of approximately 40-50%. The observed high PFOA degradation and a low concentration of PFAS degradation products indicated that the mineralization of PFOA was effective. Under the obtained best conditions, the degradation of PFOA in wastewater samples was 44-70%. The degradation efficiency for other PFAS in these samples was 65-80% for perfluorooctane sulfonic acid (PFOS) and 42-52% for 6-2 fluorotelomer sulfonate (6-2 FTSA). The presence of high total organic carbon (TOC) and chloride contents was found to be an important factor affecting the efficiency of PFAS electrochemical degradation in wastewater samples. The current study indicates that the tested method can effectively degrade PFAS in both water and wastewater and suggests that increasing the treatment time is needed to account for the presence of other oxidizable matrices.

The CanMoRe trial - evaluating the effects of an exercise intervention after robotic-assisted radical cystectomy for urinary bladder cancer: the study protocol of a randomised controlled trial.

BACKGROUND: Patients who have undergone radical cystectomy for urinary bladder cancer are not sufficiently physically active and therefore may suffer complications leading to readmissions. A physical rehabilitation programme early postoperatively might prevent or at least alleviate these potential complications and improve physical function. The main aim of the CanMoRe trial is to evaluate the impact of a standardised and individually adapted exercise intervention in primary health care to improve physical function (primary outcome) and habitual physical activity, health-related quality of life, fatigue, psychological wellbeing and readmissions due to complications in patients undergoing robotic-assisted radical cystectomy for urinary bladder cancer. METHODS: In total, 120 patients will be included and assigned to either intervention or control arm of the study. All patients will receive preoperative information on the importance of early mobilisation and during the hospital stay they will follow a standard protocol for enhanced mobilisation. The intervention group will be given a referral to a physiotherapist in primary health care close to their home. Within the third week after discharge, the intervention group will begin 12 weeks of biweekly exercise. The exercise programme includes aerobic and strengthening exercises. The control group will receive oral and written information about a home-based exercise programme. Physical function will serve as the primary outcome and will be measured using the Six-minute walk test. Secondary outcomes are gait speed, handgrip strength, leg strength, habitual physical activity, health-related quality of life, fatigue, psychological wellbeing and readmissions due to complications. The measurements will be conducted at discharge (i.e. baseline), post-intervention and 1 year after surgery. To evaluate the effects of the intervention mixed or linear regression models according to the intention to treat procedure will be used. DISCUSSION: This proposed randomised controlled trial has the potential to provide new knowledge within rehabilitation after radical cystectomy for urinary bladder cancer. The programme should be easy to apply to other patient groups undergoing abdominal surgery for cancer and has the potential to change the health care chain for these patients. TRIAL REGISTRATION: ClinicalTrials.gov. Clinical trial registration number NCT03998579 . First posted June 26, 2019.

Social Inequalities in Harmful Drinking and Alcohol-Related Problems Among Swedish Adolescents.

AIMS: The study aims to examine how socio-economic status (SES) among youth is related to binge-drinking and alcohol-related problems using three SES indicators: (i) SES of origin (parental education level), (ii) SES of the school environment (average parental education level at student's school) and (iii) SES of destination (academic orientation). METHODS: Cross-sectional data on upper secondary students (n= 4448) in Sweden. Multilevel logistic and negative binomial regression were used to estimate the relationship between each SES indicator and binge-drinking and alcohol-related problems, respectively. RESULTS: Only SES of destination was significantly associated with binge-drinking, with higher odds for students in vocational programmes (OR= 1.42, 95% CI= 1.13-1.80). For the second outcome, SES of destination (rr=1.25; 95%CI=1.08-1.45) and SES of the school environment (rr=1.19, 95% CI=1.02-1.39) indicated more alcohol-related problems in vocational programmes and in schools with lower-educated parents. After adjustment for drinking patterns, the relationship remained for SES of the school environment, but became non-significant for SES of destination. CONCLUSION: Our results suggest that the SES gradient among youth is stronger for alcohol-related problems than for harmful drinking. By only focusing on SES differences in harmful alcohol use, researchers may underestimate the social inequalities in adverse alcohol-related outcomes among young people. Our findings also support the notion that the environment young people find themselves in matters for social inequalities in alcohol-related harm.

The Arabidopsis thylakoid transporter PHT4;1 influences phosphate availability for ATP synthesis and plant growth.

The Arabidopsis phosphate transporter PHT4;1 was previously localized to the chloroplast thylakoid membrane. Here we investigated the physiological consequences of the absence of PHT4;1 for photosynthesis and plant growth. In standard growth conditions, two independent Arabidopsis knockout mutant lines displayed significantly reduced leaf size and biomass but normal phosphorus content. When mutants were grown in high-phosphate conditions, the leaf phosphorus levels increased and the growth phenotype was suppressed. Photosynthetic measurements indicated that in the absence of PHT4;1 stromal phosphate was reduced to levels that limited ATP synthase activity. This resulted in reduced CO2 fixation and accumulation of soluble sugars, limiting plant growth. The mutants also displayed faster induction of non-photochemical quenching than the wild type, in line with the increased contribution of ΔpH to the proton-motive force across thylakoids. Small-angle neutron scattering showed a smaller lamellar repeat distance, whereas circular dichroism spectroscopy indicated a perturbed long-range order of photosystem II (PSII) complexes in the mutant thylakoids. The absence of PHT4;1 did not alter the PSII repair cycle, as indicated by wild-type levels of phosphorylation of PSII proteins, inactivation and D1 protein degradation. Interestingly, the expression of genes for several thylakoid proteins was downregulated in the mutants, but the relative levels of the corresponding proteins were either not affected or could not be discerned. Based on these data, we propose that PHT4;1 plays an important role in chloroplast phosphate compartmentation and ATP synthesis, which affect plant growth. It also maintains the ionic environment of thylakoids, which affects the macro-organization of complexes and induction of photoprotective mechanisms.

Psychosocial correlates of drinking transitions: A longitudinal study among adolescents in Sweden.

INTRODUCTION: Non-drinkers have been shown in older studies to have poorer mental health and social life compared to their alcohol-using counterparts. Given the profound decline in adolescent drinking observed in most high-income countries, this pattern may have changed. This study explores drinking transitions and examines psychosocial factors among adolescents by longitudinal drinking status. METHODS: Data were based on two waves of a prospective longitudinal nationwide study (n = 4018). The first wave (T1) of data was collected in 2017 (age 15/16) and the second wave (T2) was in 2019 (age 17/18). Respondents were asked about their past year drinking status, general health, psychosomatic problems, psychiatric medication, school enjoyment, emotional symptoms, peer relationship problems, prosocial ability, friendships satisfaction and satisfaction with relation to mother/father. Comparisons by mean values were assessed and multinomial logistic regressions were used to examine associations. RESULTS: Abstainers and later drinkers differed significantly from early drinkers on 9/10 factors respectively at T1. Fewer psychosomatic problems, less psychiatric medication, higher school enjoyment, more emotional symptoms, higher parental relationship satisfaction, more peer problems and lower friendships satisfaction at T1 were associated with abstaining and/or later drinking. All factors were more strongly associated with abstaining. School enjoyment predicted abstaining but not later drinking. DISCUSSION AND CONCLUSIONS: Longitudinal drinking status relates to small to moderate systematic psychosocial differences. Adolescents with better mental health, more content relationships with parents and lower friendships satisfaction are more often abstainers. Those generally worse off are more likely early drinkers but they also have better friendships.

Is there a gender paradox in the association between conduct problems and cannabis use? A cohort-study among Swedish adolescents.

INTRODUCTION: Conduct problems (CP) predict cannabis use prospectively but the research is mixed as to whether this association is stronger among girls. A stronger association among girls would suggest a 'gender paradox' as both CP and cannabis use is less common in this group. This study aimed to assess whether the longitudinal association between CP and cannabis use in Swedish adolescents is stronger among girls. METHODS: Data from two waves of a nationally representative cohort study of Swedish adolescents born in 2001 were used. Baseline measurements were collected in 9th grade (at age 15-16) and follow-up measures at 11th grade (at age 17-18). RESULTS: CP at baseline were significantly associated with cannabis use at follow-up adjusted for hyperactivity problems, emotional problems, socio-demographics, parental monitoring, school grades and truancy at baseline (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.06-1.24) but not when also adjusting for substance use at baseline. Boys were more likely to have used cannabis during the past year, even when controlling for prior substance use (OR 2.29, 95% CI 1.76-2.98). The association between CP and cannabis use was significantly weaker for boys (OR 0.83, 95% CI 0.72-0.95 in the fully adjusted model). The predicted probability of cannabis use was stable at 0.13 for boys across levels of CP, but ranged from 0.05 to 0.16 for girls. DISCUSSION AND CONCLUSION: The longitudinal association between CP and cannabis use was stronger among girls. The findings are indicative of a 'gender paradox' in the association between CP and cannabis use.

Polyphonic narratives: The mixing of Alcoholics Anonymous and relapse prevention in stories about recovery and relapse.

Aim: This exploratory study analyses the interplay between the treatment philosophies of Alcoholics Anonymous (AA) and Relapse Prevention (RP) in personal stories of addiction. While the basic ideas of AA and RP are compatible in many ways, they also carry some fundamental differences. Methods: The data consisted of interviews with 12 individuals recovering from substance use problems, who had experience of both AA and RP. The analysis drew on a dialogical narrative perspective, and the concept polyphony was used to shed light on the interplay between different treatment philosophies in personal stories of relapse. Findings: Although sometimes resulting in incoherence, the treatment philosophies were combined idiosyncratically, in ways that appeared productive for the participants' self-images and recovery journeys. Conclusion: The combination of AA and RP philosophies in narratives of relapse and recovery may reflect a new treatment discourse where individualisation and responsibilisation stand in a complicated relationship with collectivism and surrendering to so-called addicting processes.

How well do DSM-5 criteria measure alcohol use disorder in the general population of older Swedish adolescents? An item response theory analysis.

BACKGROUND: This study assesses the psychometric properties of DSM-5 criteria of AUD in older Swedish adolescents using item response theory models, focusing specifically on the precision of the scale at the cut-offs for mild, moderate, and severe AUD. METHODS: Data from the second wave of Futura01 was used. Futura01 is a nationally representative cohort study of Swedish people born 2001 and data for the second wave was collected when participants were 17/18 years old. This study included only participants who had consumed alcohol during the past 12 months (n = 2648). AUD was measured with 11 binary items. A 2-parameter logistic item response theory model (2PL) estimated the items' difficulty and discrimination parameters. RESULTS: 31.8% of the participants met criteria for AUD. Among these, 75.6% had mild AUD, 18.3% had moderate, and 6.1% had severe AUD. A unidimensional AUD model had a good fit and 2PL models showed that the scale measured AUD over all three cut-offs for AUD severity. Although discrimination parameters ranged from moderate (1.24) to very high (2.38), the more commonly endorsed items discriminated less well than the more difficult items, as also reflected in less precision of the estimates at lower levels of AUD severity. The diagnostic uncertainty was pronounced at the cut-off for mild AUD. CONCLUSION: DSM-5 criteria measure AUD with better precision at higher levels of AUD severity than at lower levels. As most older adolescents who fulfil an AUD diagnosis are in the mild category, notable uncertainties are involved when an AUD diagnosis is set in this group.

Different measures of alcohol use as predictors of DSM-5 alcohol use disorder among adolescents - A cohort study from Sweden.

BACKGROUND AND AIMS: This study addresses a significant gap in existing research by investigating the longitudinal relationship between various measures of alcohol use and the development of alcohol use disorders (AUDs) in a cohort of Swedish adolescents. METHODS: A prospective longitudinal survey was conducted on 3999 adolescents in Sweden who were in 9th grade in 2017 and were followed up in 2019. Baseline assessments included lifetime alcohol use, recent use (past 30 days), risky drinking (AUDIT-C), and heavy episodic drinking (HED). Follow-up assessments comprised eleven items measuring DSM-5 AUD criteria. The study explores prospective associations between these diverse alcohol use measures and the occurrence of AUD, while also calculating population attributable fractions (PAF). FINDINGS: The proportion of alcohol consumers who met the criteria for AUD at follow-up was 31.8%. All baseline measures of alcohol use exhibited associations with subsequent AUD. Notably, the HED group demonstrated the highest prevalence of AUD at 51.4% (p<.001). However, when calculating PAFs, any lifetime alcohol use emerged as the most substantial contributor, accounting for 10.8% of all subsequent AUD cases. CONCLUSIONS: This study underscores that alcohol use during mid-adolescence heightens the risk of developing AUD in late adolescence. Among the various measures, heavy episodic drinking presents the highest risk for later AUD. From a public health perspective, preventing any alcohol use emerges as the most effective strategy to mitigate the population-level burden of disease of AUD.

The feasibility of an exercise intervention after robotic-assisted radical cystectomy for urinary bladder cancer, prior to the CanMoRe trial.

BACKGROUND: Complications after radical cystectomy for urinary bladder cancer are common. Physical activity after surgery is thought to reduce complications. However, patients with urinary bladder cancer have low levels of physical activity, and interventions supporting physical exercise are needed. This study aimed to evaluate the feasibility of a physical exercise intervention in primary health care. One of the aims of the larger clinical trial will be to reduce complications. METHODS: Patients with urinary bladder cancer and who were scheduled for a robotic-assisted radical cystectomy were recruited from Karolinska University Hospital, between February and May 2019. The patients had to be mobile, understand Swedish, and live in Stockholm. The exercise programme was conducted at one primary health care setting over 12 weeks. The exercise programme included supervised aerobic and strengthening exercises, which were performed twice a week, as well as daily walks. Feasibility was measured with process feasibility, including eligibility criteria, adherence, and acceptability, and scientific feasibility, including the ability of outcomes to indicate change, safety, and progression in the exercise programme. RESULTS: Ten patients with a median age of 70 years (min 53-max 86) were included. Adherence to all parts of the intervention was not feasible because of patients' postoperative complications, resulting in dropouts. For the patients who took part in the exercise programme, adherence and acceptability for the exercise period were feasible, but the 6-min walk test was not feasible at discharge from the hospital. Physiotherapists in the primary health care setting perceived the process as feasible. Moreover, the ability of outcomes to indicate change and progression in the exercise programme was feasible, meanwhile no adverse events were registered. CONCLUSIONS: The exercise intervention was feasible for the patients that took part in the exercise programme, with respect to safety and progression through the exercise programme. Furthermore, this study suggests that some improvements needed to be implemented in the process, prior to the upcoming randomised controlled trial.

Immunotoxic, genotoxic, and endocrine disrupting impacts of polyamide microplastic particles and chemicals.

Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action. This study investigated the physicochemical properties of polyamide-12 microplastics used in AM, and assessed a number of toxicity endpoints focusing on inflammation, immunometabolism, genotoxicity, aryl hydrocarbon receptor (AhR) activation, endocrine disruption, and cell morphology. Specifically, microplastics examination by means of field emission scanning electron microscopy revealed that work flow reuse of material created a fraction of smaller particles with an average size of 1-5 µm, a size range readily available for uptake by human cells. Moreover, chemical analysis by means of gas chromatography high-resolution mass spectrometry detected several polyamide-associated chemicals including starting material, plasticizer, thermal stabilizer/antioxidant, and migrating slip additive. Even if polyamide particles and chemicals did not induce an acute inflammatory response, repeated and prolonged exposure of human primary macrophages disclosed a steady increase in the levels of proinflammatory chemokine Interleukin-8 (IL-8/CXCL-8). Moreover, targeted metabolomics disclosed that polyamide particles modulated the kynurenine pathway and some of its key metabolites. The p53-responsive luciferase reporter gene assay showed that particles per se were able to activate p53, being indicative of a genotoxic stress. Polyamide-associated chemicals triggered moderate activation of AhR and elicited anti-androgenic activity. Finally, a high-throughput and non-targeted morphological profiling by Cell Painting assay outlined major sites of bioactivity of polyamide-associated chemicals and indicated putative mechanisms of toxicity in the cells. These findings reveal that the increasing use of polyamide microplastics may pose a potential health risk for the exposed individuals, and it merits more attention.

The feasibility of using a digital tool to enhance mobilisation following abdominal cancer surgery-a non-randomised controlled trial.

BACKGROUND: Early mobilisation is strongly recommended following abdominal cancer surgery, but evidence on how to structure early mobilisation to improve outcomes and support patient adherence is lacking. Pedatim® (Phystec) is a novel digital tool designed to support mobilisation in hospital settings using prescribed activities and goals on a tablet. The aim of this study was to evaluate the feasibility of the Pedatim tablet to enhance mobilisation following abdominal cancer surgery. METHODS: In a non-randomised feasibility trial design, participants were recruited between January and May 2022 at Karolinska University Hospital, Sweden. Participants used a Pedatim tablet from postoperative day 1 (POD 1) until hospital discharge. The primary objective was to evaluate process feasibility, regarding recruitment, compliance, and acceptability. Recruitment was measured by percentage of available patients included, eligibility criteria sufficiency, and number of dropouts. Compliance was measured by number of patients using versus not using the board. Acceptability was measured using the System Usability Scale. The secondary objective was to evaluate scientific feasibility, defined as an indication of treatment effects where physical activity was assessed using an activPAL accelerometer. Unforeseen events relating to the tablet were also registered. RESULTS: Based on predetermined feasibility criteria, the overall study design was determined to be feasible regarding recruitment as 69% accepted participation (n = 20), compliance was 95%, and the acceptability mean score was high (77/100). Eligibility criteria were not feasible as 79% (n = 108) of available patients were excluded. The intervention was determined to be scientifically feasible, mean steps per day increased from 623 (SD 766) to 1823 (SD 1446), and mean sit-to-stand transitions per day increased from 11 (SD 8) to 29 (SD 12) POD 1-4. Technical issues emerged, highlighting the need for available technical support and "user champions" among healthcare professionals on the ward. CONCLUSIONS: Using the Pedatim tablet to enhance mobilisation following abdominal cancer surgery was deemed feasible, but a randomised controlled trial is needed to determine the tool's effectiveness. The study process was determined to be feasible with revisions of the eligibility criteria needed before a future trial. Involving healthcare professionals and providing available technical support are important for future implementation.

A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles.

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.