Key FeaturesThe Vukuzazi programme was established to address public health responses and scientific priorities in light of the convergence of the HIV, tuberculosis and non-communicable disease epidemics in South Africa.The programme is a nested closed cohort of the Population Intervention Programme and performed community-based health phenotyping in the uMkhanyakude district of rural KwaZulu-Natal, South Africa, while simultaneously creating a data, image and bio-sample repository.Baseline data collection began in May 2018 and was completed in March 2020, having enrolled 50% of the eligible population aged 15 years and over [18 041: 12 230 female (68%) female and 5811 male (32%)].The community-based phenotyping consisted of: a nurse-administered health questionnaire on personal history of HIV, tuberculosis, diabetes, hypertension, cancer, tobacco and alcohol use; quality of life; anthropometric measurements and blood pressure readings; venous blood sample for clinical testing and bio-banking; digital chest radiograph, sputum collection and sputum mycobacterial tests; as well as rectal swab collection for biobanking.https://data.ahri.org].Data for secondary analysis, access to the biological samples and imaging data are available through request on this link: , in which they express their interest and outline the intended use of the data or biological samples. The Vukuzazi Scientific Steering Committee will review requests on an ongoing basis and invite proposals for collaboration. Vukuzazi data are accessible through the AHRI Data Repository after approval and completion of a data use agreement. Data documentation including questionnaires used for data collection and a full data dictionary are available on the AHRI Data Repository.Researchers who would like to use the data for secondary analyses, or use the biological samples or imaging data, must complete a letter of intent accessible on this link: [IJE onlineThis research was funded in part, by the Wellcome Strategic Core award: 201433/Z/16/A, in part by the Bill and Melinda Gates Foundation (OPP175182) and in part by the Africa Health Research Institute. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.dyab229_Supplementary_DataClick here for additional data file.


Objective: This study aimed to review and provide an informative synthesis of the findings from longitudinal studies that describe the relationship between sedentary behavior and various health outcomes among young adults. Methods: A literature search was conducted in Web of Science, PubMed, APA PsycInfo, MEDLINE, Embase, and the Cochrane Library for articles that examined the association between sedentary behavior and health outcomes among young adults aged 18–34 years. Two reviewers independently examined the articles and performed data extraction and quality assessment. The level of evidence was determined using the best-evidence synthesis. Results: A total of 34 studies were included in the analysis, 18 of which were high-quality studies. On the basis of inconsistency in the findings among studies, insufficient evidence was concluded for sedentary behavior and adiposity indicators, physical fitness, metabolic syndrome/cardiovascular disease risk factors, cognitive function, and mood disorders. Based on one high-quality study, moderate evidence for a negative relationship between sedentary behavior and physical fitness was observed. Conclusions: Given the trend toward increased time in sedentary behaviors and the inconsistent current findings, additional longitudinal studies of high methodologic quality are recommended to clarify the relationships between sedentary behavior and health outcomes among young adults. Sedentary behavior, an important area of study in health research, is defined as activities that involve energy expenditure ≤1.5 metabolic equivalent units such as sleeping, sitting, lying down, watching TV, and other forms of screen-based entertainment ,3. By usTo strengthen the evidence based on sedentary behavior as an adult health risk, a large number of longitudinal studies have been conducted to investigate the association between sedentary behavior and health outcomes among adults, but the findings have been mixed ,11,12,13To date, two systematic reviews have focused on the longitudinal studies that examined the relationship between sedentary behavior and health outcomes among adults range = 18–90 years) ,15. Neve–90 yearsA systematic search of the relevant studies in Web of Science, PubMed, APA PsycInfo, MEDLINE, Embase, and the Cochrane Library was conducted from the inception of the databases up to May 2022. The search strategy included a combination of three main areas: (1) sedentary behavior: sedentary behavior OR physical inactivity OR sedentary OR sedentary lifestyle OR sitting OR television OR computer OR TV OR screen time OR video game OR social media OR internet; (2) health outcomes: adiposity indicators (overweight OR obesity OR body mass index OR waist circumference OR skinfolds), physical fitness , metabolic syndrome/cardiovascular disease risk factors (metabolic syndrome OR hypertension OR diabete* OR cardiovascular disease*), cognitive function (attention OR memor*), and emotional disorder (depress* OR anxiety OR stress); and (3) young adult: young adult* or adult* or college student or postgraduate*. The complete search terms and search strategies used in each database are shown in the The inclusion and exclusion criteria for this review were as follows. (1) Peer-reviewed journals with full-text studies published in the English language until May 2022 were included. Unpublished articles, conference papers, doctoral dissertations, monographs, and literature reviews were excluded. (2) Studies that presented longitudinal data on the relationship between sedentary behavior and health outcomes among young adults were included. Cross-sectional and intervention research  were excluded. Longitudinal studies vary enormously in the duration of follow-up (from a few days or weeks to over decades) . No limiTwo researchers independently performed the data extraction and quality assessment of all of the included articles and discussed the inconsistent results until an agreement was reached . Data inThe quality of the included articles was evaluated using criteria adapted from the Quality of Reporting of Observational Longitudinal Research and the Evaluation of the Quality of Prognosis Studies in Systematic Reviews ,24. The After summarizing the included studies, the results showed that studies were heterogeneous in terms of statistical analyses, type and measurement of sedentary behavior, and health outcome. A formal meta-analysis is thought to be inappropriate. Therefore, the best-evidence synthesis was applied to synthesize the methodological quality of the studies and provide conclusions on the association between sedentary behavior and health outcomes ,26. ThisThe search resulted in 15,386 studies . After removing duplicate publications, 8058 publications remained. After screening the titles and abstracts, 3130 studies were identified as potentially relevant, and full-texts were then obtained. Afterward, 28 studies met the inclusion and exclusion criteria. The search of reference lists from relevant papers and reviews yielded six more publications. Therefore, 34 studies were included in this review . The intA total of five, 17, and 12 studies reported follow-up periods of <1, 1–5, >5 years, respectively. Most studies (23 studies) used subjective methods to assess sedentary behavior , and the 11 remaining studies used objective methods . A total of 19 studies compositely measured the effect of all sedentary behaviors on health outcomes, and 15 studies examined the influences of specific types of sedentary behavior  on the health outcomes. Most studies (20 studies) controlled the influence of age, gender, race, and education level on the results, and a few studies (14 studies) controlled the effect of physical activity and sleep. A total of 33 studies used multivariate analysis methods  to examine the relationship between sedentary behavior and health outcomes. Only one article used univariate analysis methods .The initial agreement in the methodological quality assessment was 82.2% between the two reviewers. Out of the 34 studies included in this review, three studies reported two different categories of health outcomes ,13,53. TTwelve studies examined the relationship between sedentary behavior and adiposity indicators . Five studies examined the sedentary time in relation to body fat mass such as waist circumference, body fat percentage, or skinfold thickness. Of these five studies, two studies found that the sedentary time was associated with body fat percentage and waist and hip circumference gain ,54, wherTwo studies examined the relationship between sedentary behavior and physical fitness  and indicated a negative association between sedentary behavior and cardiorespiratory fitness ,53. In aEleven studies investigated the relationship between sedentary behavior and metabolic syndrome/cardiovascular disease risk factors . Two studies showed that sedentary behavior was positively associated with triglycerides and negatively associated with HDL cholesterol ,29. HancTwo studies investigated the correlation between sedentary behavior and cognitive function. Hoang et al., 2016 found that compared with adults with low sedentary behavior time, those with high sedentary behavior time had low levels of processing speed and executive function . HoweverTen studies examined the relationship between sedentary behavior and emotional disorders . Two studies found a positive association between sedentary behavior and depression ,56. DeMeThe present review aimed to systematically summarize the literature with regard to the longitudinal relationship between sedentary behavior and health outcomes among young adults, taking into account the methodological quality of the studies. Despite the start date of the literature being 1998, the majority (25 of 34 studies) of the studies included were published after 2010. This indicates that over recent years, the topic of sedentary behavior as an independent predictor for health outcomes has gained much attention in the literature. Based on the studies identified, moderate evidence for the negative relationship between sedentary behavior and physical fitness was found. Furthermore, insufficient evidence was found for the relationship between sedentary behavior and adiposity indicators, metabolic syndrome/cardiovascular disease risk factors, cognitive function, and emotional disorder.The insufficient evidence for the longitudinal relationship between sedentary behavior and adiposity indicators supports the earlier systematic review of Proper et al., 2011 . This reTwo studies found a significant negative association between sedentary behavior and physical fitness. The moderate evidence for the association was obtained since only one high-quality study was available. Long-term sedentary behavior could cause venous blood pooling in the lower limbs, which could decrease muscle blood flow and inadequate muscle contraction . More tiThere have been inconsistences in the studies on sedentary behavior and metabolic syndrome/cardiovascular disease risk factors (45.4%), leading to insufficient evidence. The result was consistent with previous reviews ,15. Two The limited number of studies (two studies) that have investigated the relationship between sedentary behavior and cognitive function precluded a consistent conclusion from being drawn. Furthermore, the relationship between sedentary behaviors and prospective changes in cognitive function may be influenced by the type of sedentary behavior. Previous longitudinal study has shown that when adults operate the mouse or locate icons on a computer screen, they can exercise basic psychomotor and sensory skills; when they figure out how to utilize computer processes to perform tasks, their learning, memory, and executive function can be improved  Hence, tIn addition, the insufficient evidence for the relationship between sedentary behavior and emotional disorder may also be related to the type of sedentary behavior. When spending time using smartphones and tablets, adults are in a passive mental state that could disturb normal neurocognitive development processes, which could be linked to stress and depression . In contThere are several strengths and limitations of this review. The strengths include the systematic approach in the extensive literature search and in the assessment of the methodological quality of each study, and the use of the best evidence systems to draw conclusions. Moreover, this review only included longitudinal studies, thus providing insights into the changes over time in the impact of sedentary behavior on the health outcomes of young adults. However, this review still had some limitations. First, although a comprehensive search of the published literature was conducted, literature using other keywords may not have been included. Second, only the published literature in English was included, certain studies that could have added relevant information to this field may have been discarded.We systematically collated the relevant literature on the relationship between sedentary behavior and health outcomes among young adults. The review showed moderate strength evidence of the negative relationship between sedentary behavior and physical fitness. In the future, more research is needed to objectively measure the pattern  and type  of sedentary behavior in combination with robust and standardized measures of health indicators to gain an explicit understanding of the impact of sedentary behavior on health indicators. Moreover, evidence from experimental studies and intervention trials will help inform policy decisions and provide guidelines of the dose–response between sedentary behavior and health indicators.


The Program for Resistance, Immunology, Surveillance, and Modeling of Malaria (PRISM) has been conducting malaria research in Uganda since 2010 to improve the understanding of the disease and measure the impact of population-level control interventions in the country. Here, we will summarize key research findings from a series of studies addressing routine health facility-based surveillance, comprehensive cohort studies, studies of the molecular epidemiology, and transmission of malaria, evaluation of antimalarial drug efficacy, and resistance across the country, and assessments of insecticide resistance. Among our key findings are the following. First, we found that in historically high transmission areas of Uganda, a combination of universal distribution of long-lasting insecticidal-treated nets (LLINs) and sustained indoor residual spraying (IRS) of insecticides lowered the malaria burden greatly, but marked resurgences occurred if IRS was discontinued. Second, submicroscopic infections are common and key drivers of malaria transmission, especially in school-age children (5–15 years). Third, markers of drug resistance have changed over time, with new concerning emergence of markers predicting resistance to artemisinin antimalarials. Fourth, insecticide resistance monitoring has demonstrated high levels of resistance to pyrethroids, appreciable impact of the synergist piperonyl butoxide to pyrethroid susceptibility, emerging resistance to carbamates, and complete susceptibility of malaria vectors to organophosphates, which could have important implications for vector control interventions. Overall, PRISM has yielded a wealth of information informing researchers and policy-makers on the malaria burden and opportunities for improved malaria control and eventual elimination in Uganda. Continued studies concerning all the types of surveillance discussed above are ongoing. Malaria is endemic in over 95% of the country and in the remaining highland areas, transmission is unstable and epidemic-prone.The Program for Resistance, Immunology, Surveillance, and Modeling of Malaria in Uganda (PRISM) was established in 2010 and represents the East African region of the International Center of Excellence for Malaria Research (ICEMR) network with a focus on Uganda. Uganda is emblematic of the challenges faced by high-burden countries, where routine surveillance systems have limited ability to assess trends in the burden of malaria or to monitor the impact of control interventions. Through PRISM, researchers have implemented a comprehensive malaria surveillance program including enhanced health facility-based surveillance and detailed longitudinal cohort studies in areas with differing transmission intensities. Complementary laboratory-based studies have included surveillance for markers of antimalarial drug and insecticide resistance, serologic measures of malaria exposure, highly sensitive molecular assays for the detection of asexual- and sexual-stage parasites, and membrane feeding assays to assess human to mosquito transmission. These studies have greatly improved our understanding of the epidemiology of malaria in Uganda and of the impact of control interventions. In recent years, the program has expanded its malaria surveillance work and the scope of longitudinal studies to address more fundamental questions about interactions among the parasite, mosquito vector, and human host. Here, we report a summary of key research findings from our PRISM projects and some related studies from our group, which together offer a comprehensive understanding of malaria in Uganda, one of the highest malaria burden countries in the world.Malaria surveillance, which encompasses monitoring and evaluation of malaria control efforts, is essential to guide program planning and management. Malaria surveillance in Uganda is mainly dependent on passive case detection at health facilities as part of a country’s routine health management information system (HMIS). There are several strengths in conducting surveillance at health facilities: available data provide direct measures of morbidity, are collected continuously over time, and cover a wide geographic area.In 2006, the Uganda Malaria Surveillance Program (UMSP) was established to collect high-quality malaria surveillance data at six health facilities, known as Malaria Reference Centers (MRCs), in collaboration with the Uganda National Malaria Control Division (NMCD).In 2020, we used data from this enhanced malaria surveillance system to assess the impact of starting and stopping IRS of insecticide on malaria burden in Northern and Eastern Uganda.® LLINs containing deltamethrin and piperonyl butoxide (PBO) or Royal Guard® LLINs containing alpha-cypermethrin and pyriproxyfen. LLINs were distributed during Uganda’s 2020–2021 universal coverage campaign. By using malaria incidence measured within the target areas as the primary outcome for this trial, we will monitor temporal trends in malaria morbidity, and compare absolute disease burden in each trial arm.Since 2018, emphasis has been placed on collecting data on village of residence for all patients presenting to the MRCs. These data—along with the identification of target areas around the MRCs and enumeration surveys to estimate the populations of these target areas—have allowed for the estimation of malaria incidence within these target areas. Currently, data from our enhanced malaria surveillance network are being used as a platform for a cluster randomized trial evaluating the effect of two different types of newer generation LLINs on malaria incidence. A total of 64 clusters (MRC target areas) covering 32 high-burden districts have been randomized in a 1:1 ratio in blocks of two by district to receive one of each LLIN type: Permanet 3.0In summary, data from our enhanced malaria surveillance provides an efficient means to quantify the impact of malaria control interventions at the population-level using observational study designs  or cluster randomized trials through coordination with implementing partners. This approach is more cost-effective and timely compared with the Demographic and Health Surveys that are conducted every 5 years and yet provides more comprehensive information beyond what is provided by the routine HMIS.,Comprehensive cohort studies, including clinical and entomological assessments, provide a powerful design for generating longitudinal data on measures of malaria transmission, infection, and disease. We have conducted comprehensive malaria surveillance in cohorts from Tororo District, Uganda, an area with historically high transmission intensity that saw a dramatic decline in the burden of malaria following the implementation of intensive malaria control interventions (EIR = 562 infective bites/person/year in 2006 and 310 infective bites/person/year in 2011).,Anopheles and the detection of sporozoites using ELISA.Two consecutive cohort studies (referred to as the “PRISM” cohorts) were conducted in randomly selected households from Nagongera subcounty, Tororo District.Following the implementation of IRS, measures of transmission, infection, and disease reduced dramatically . Pre-IRSIn summary, our comprehensive cohort studies quantified dramatic reductions in malaria and nonmalaria indicators in an historically high-burden setting following the implementation of sustained malaria control interventions including access to prompt and effective antimalarial therapy, universal LLIN distribution, and IRS. However, despite these reductions, a substantial reservoir of asymptomatic infections remained, primarily among school-aged children and adults.varATS qPCR (limit of detection 0.03–0.15 parasites/µL) can be used to detect these infections through active surveillance.,Conventional point-of-care malaria diagnostics, such as microscopy and rapid diagnostic tests (RDTs), do not have the sensitivity required to detect low-density infections, often referred to as submicroscopic or subpatent infections. More sensitive molecular techniques, such as LAMP (limit of detection 1–5 parasites/µL) or ultrasensitive ,,,,,In PRISM 1 prior to IRS, measured parasite prevalence was approximately twice as high in children and 8-fold higher in adults with results based on LAMP compared with microscopy alone,Our experience with the use of highly sensitive molecular diagnostics shows that these techniques are critical to fully characterize the parasite reservoir, given that microscopic infections represent only the “tip of the iceberg,” and that the relative proportion of submicroscopic infections increases with decreasing transmission intensity. Furthermore, these techniques can be used to identify asymptomatic individuals who provide persistent reservoirs of transmission in lower transmission settings, to identify infected populations who, although asymptomatic, may benefit clinically from treatment, and to evaluate the results of interventions.,Plasmodium falciparum infections and to investigate whether there were sex-based differences in clearance of these infections, given that we observed higher prevalence of asymptomatic infection in males compared with females. Analyzing the data by clone, where each unique clone was counted as an infection and each clone’s disappearance as a clearance event, we found that females cleared their asymptomatic infections nearly twice as quickly as males, even after adjusting for age, baseline infection status, and parasite density .In addition to characterizing the parasite reservoir, highly sensitive molecular diagnostics can provide insight into longitudinal dynamics of infections. In PRISM 1 and 2, some individuals had low-density infections detected sequentially over numerous months. To further characterize the dynamics of these chronic infections, it is necessary to genotype parasite DNA to distinguish among individual clones (strains) as individuals in high-transmission settings are often coinfected with overlapping infections of multiple clones. Using genetic data, it is possible to follow distinct clones over time, which allows for assessment of the molecular force of infection (mFOI), or the incidence of genetically distinct parasite clones acquired over time, and estimation of the duration of infections.As described previously, amplicon deep-sequencing provides information vital to understanding the host response to malaria infection and better characterizes the dynamics of polyclonal asymptomatic infections compared with molecular methods that cannot differentiate among parasite clones. Because amplicon sequencing data can be used to estimate the mFOI, it can also be used to better understand changes in transmission in the setting of malaria control interventions. We plan to use amplicon deep-sequencing to assess changes in the mFOI and clinical antimalarial immunity in the setting of repeated rounds of IRS during longitudinal evaluation of the PRISM 1 and 2 cohorts.An. gambiae s.s. mosquitoes.Understanding who in the human population sustains transmission to mosquitoes is of great relevance for malaria control and elimination efforts.P = 0.033); this result suggests that in a cohort that is treated promptly whenever symptomatic malaria is diagnosed, most transmission will be from asymptomatic individuals. Mosquito feeding assays were successfully performed on both symptomatic and asymptomatic parasite carriers. At least one infected mosquito was observed in 7.2% of feeding experiments, with 1.2% of all examined mosquitoes becoming infected. The likelihood that a mosquito became infected rose rapidly when gametocyte densities exceeded 10 gametocytes/µL (assessed by molecular methods), corroborating findings from other African settings  has been common in Uganda for many years, and first-line therapy changed to the ACT AL in 2004. Sulfadoxine-pyrimethamine remains the standard-of-care for intermittent preventive treatment of malaria in pregnancy.The treatment of malaria is challenged by resistance of We have systematically studied antimalarial drug efficacy and resistance in Uganda for the last two decades, with therapeutic efficacy studies, characterization of genetic markers of resistance, and measurement of ex vivo drug susceptibilities of cultured isolates. Our results have demonstrated changing susceptibilities to key treatment regimens over time.,–Evaluation of the therapeutic efficacy of chloroquine in 1998–1999 suggested poor efficacy,,,–,,––,,Trials of ACTs showed excellent antimalarial efficacies for artesunate-SP,pfcrt 76T and pfmdr1 86Y.–,,,,pfcrt and plasmepsin gene amplification) or lumefantrine (pfmdr1 amplification) have shown very low prevalence in Uganda.,P. falciparum parasites now circulating in Uganda appear to be sensitive to available aminoquinolines and lumefantrine.Considering molecular markers of resistance , serial ,pfdhfr 164L, and pfdhps 581G, were very low through ∼2012, but have since increased, especially in Western Uganda, with prevalences near or exceeding 40% at multiple sites in 2018–2019.,Considering SP, five mutations that mediate increasing levels of resistance showed > 90% prevalence in parasites collected across Uganda as early as 2002.,–,–Of recent concern is potential emergence of resistance to ACTs in Africa.50s < 100 nM, consistent with chloroquine sensitivity, although a minority had high IC50s.,,,,,Ex vivo analyses of cultured parasites have shown results consistent with molecular studies of resistance markers. Isolates collected in Kampala in 2006–2008 demonstrated chloroquine susceptibilities suggesting high-level resistance.In summary, surveillance over the last two decades has demonstrated remarkable changes in drug resistance profiles of Ugandan malaria parasites. Recent results suggest a return to chloroquine sensitivity for most, but not all circulating parasites; major limitations in the antimalarial chemopreventive activity of SP; and worrisome emergence of artemisinin resistance in Northern Uganda. There is an urgent need for continued surveillance and clinical trials to determine whether current regimens for the treatment and prevention of malaria in Uganda will need to be replaced.,The dramatic scale-up of malaria vector control interventions across Africa, including LLINs and IRS, has been associated with an estimated 40% decrease in the incidence of disease between 2000 and 2015.Anopheles mosquitoes.An. gambiae s.s. and An. funestus populations was observed following universal distribution of LLINs plus multiple rounds of IRS, with the more behaviorally resilient An. arabiensis becoming the predominant vector species.An. gambiae s.s and An. arabiensis,In our PRISM projects, we have conducted entomologic surveillance, monitored for insecticide resistance, and assessed the impact of vector control interventions on An. gambiae genome;An. gambiae genome has enabled exploration of gene targets with putative association with insecticide resistance. The PRISM projects used this platform to aid the discovery of two novel variants (Cyp4j5 and Coeaeld),Through our PRISM projects, we have established foundations and collaborations that have been leveraged to conduct additional research on insecticide resistance,Utilizing comprehensive malaria surveillance studies, we demonstrated reductions in measures of transmission, infection, and disease following roll out of effective malaria control interventions. Similar trends were seen and conclusions drawn from data collected from both enhanced health facility-based surveillance and comprehensive cohort studies, highlighting our understanding that both surveillance methods are effective tools for quantifying the impacts of population-level malaria control inventions. We also demonstrated that although younger children are at greatest risk of malaria, school-aged children are the main reservoir of infection and drivers of transmission. This finding is particularly true in settings, where recent malaria control efforts have been successful. Thus, with the goal of reducing human to mosquito transmission, school-aged children may be an ideal group to target for control interventions. We have shown that surveillance of drug and insecticide resistance is critical for informing policy, as evidenced by recent emergence of markers predicting resistance to artemisinin antimalarials and expanding vector resistance to multiple classes of commonly used insecticides. With a recent emphasis on the high burden to high impact approach in countries such as Uganda, our ICEMR program is committed to providing valuable data to support an evidence-based approach to reducing the burden of malaria, eventually moving toward elimination.


Each year the GSA publications team sponsors a symposium to assist authors who wish to publish in GSA’s high impact and influential journals. The first part of the session will include five brief presentations from the editors of The Gerontologist, Innovation in Aging, and the Journals of Gerontology Series A and B plus journal managing editors. We will integrate practical tips with principles of publication ethics and scholarly integrity. The topics will be as follows: (1) Preparing your manuscript: strong and ethical scholarly writing for multidisciplinary audiences, (2) common problems that affect peer review, (3) addressing translational significance and fit to journal expectations, (4) transparency, documentation, and Open Science; and (5) working with Scholar One. Following these presentations, we will hold round table discussions with editors from the GSA journals portfolio. At these round tables, editors will answer questions related to the podium presentations and other questions specific to each journal. Intended audiences include emerging and international scholars, and authors interested in learning more about best practices and tips for getting their scholarly work published.


Top choices by autistic adults, carers or professionals for services best suiting their current needs were: residential services: “help in own home” , “fulltime residential facility” (carers of low independent adults); employment services: “job mentors” , “Sheltered employment” (carers of low independent adults); education services: “support in regular education setting” ; financial services: financial support in lieu of employment  or to supplement employment earnings for carers of high independent adults and professionals; social services: “behavior training” (adults) and “life skills training” . Waiting times for specific services were generally < 1 month or 1–3 months, except for residential services which could be up to 6 months; most professionals were uninformed of waiting times (>50% responded “don’t know”). Five of seven residential services features recommended for autistic adults were experienced by <50% of adults. The knowledge of good local services models that work well for autistic adults was generally low across all services areas. The variation in services experiences and perceptions reported by autistic adults, carers, or professionals underscore the need to query all groups for a complete picture of community services availability and needs. The results showed areas for potential improvement in autistic adult services delivery in the EU to achieve recommended standards.There is very little knowledge regarding autistic adult services, practices, and delivery. The study objective was to improve understanding of current services and practices for autistic adults and opportunities for improvement as part of the Autism Spectrum Disorder in the European Union (ASDEU) project. Separate survey versions were created for autistic adults, carers of autistic adults, and professionals in adult services. 2,009 persons responded to the survey and 1,085 (54%) of them completed at least one of the services sections: 469 autistic adults (65% female; 55%  Autism is characterized by deficits in social communication and interaction, and restricted/repetitive repertoires of behaviors, interests, and activities  and usuIn adulthood, autistic persons often face challenges around services, such as lack of autism training of service providers and chaotic services management or, alternatively, having to pay for private services. Consequently, autistic adults or carers of autistic adults tend to express dissatisfaction with post-diagnostic support, interventions, and management of medical and psychiatric co-occurring conditions –15. A reThe overall objective of the present study was to improve understanding of current services experienced by autistic adults and opportunities for improvement as part of the Autism Spectrum Disorder in the European Union (ASDEU) project. Specific study objectives were to examine perceptions and experiences of autistic adults, carers, and professionals on a variety of features of the overall services infrastructure  for autistic adults including: availability of public (versus private) services; whether the service they received was designed for autism specifically; what services were received versus what is perceived as most needed now; indicators of limited services availability ; level of autism expertise in offices where services were applied for; alignment of user experiences of residential services with published guidelines for residential services; and users’ awareness of good services models across all services types.The ASDEU project conducted a survey on services based, in part, on a variety of published guidelines and recommendations regarding services for autistic adults , mo, mo41)],The National Institute for Health and Care Excellence autism guidelines , thus tThe ASDEU survey sheds light on the state of different types of autistic adult services in 11 countries of the European Union from the perspective of autistic adults, carers and professionals. The results underscore the highly diverse needs and preferences of the autistic community such that the different residential, employment, educational, financial, and social services options that adults or their carers tried to get and failed, or succeeded in receiving, or believed would better suit their current needs varied depending on the respondent group and the level of independence of the autistic adult in question. Although there was some concordance between professional and adult/carer responses in terms of the availability and preferences/needs of different services options, the differences are also important to note since they highlight the different perspectives of the professional providers versus the adult/carer services users. Thus, for services policy planning, it is important to consider the perspectives of all these types of respondents when assessing autistic adult services needs and gaps in the community .The results also highlight specific gaps in knowledge: lack of autism knowledge and training in services office staff, shortfalls in meeting published recommendations around residential services (which may reflect lack of knowledge about them by the service provider), professionals’ lack of awareness of services waiting times, and lack of knowledge by all respondent groups of good local services models that work well for autistic adults. Filling these knowledge gaps may be important steps toward more equitable service delivery and better support for the autistic adult community.diana.schendel@ph.au.dk and MS, marialuisa.scattoni@iss.it.The datasets presented in this article are not readily available because we can only share aggregated data , and any data based on a small sample size (<5) may not be shared as an extra data privacy precaution. Requests to access the datasets should be directed to DS, The studies involving human participants were reviewed and approved by Each ASDEU site obtained local ethical approval. The patients/participants provided their written informed consent to participate in this study.MLS, TS, MM, and DS: formal analysis. MM, MLS, and DS: writing – original draft preparation. MP: funding acquisition for the survey dissemination and data collection and analysis (DGSANCO) and principal investigator. MLS: funding acquisition for the Italian participation at the survey, data analysis and writing  and principal investigator. All authors contributed to the conceptualization, investigation, and writing – review and editing and have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Tendinopathy is highly prevalent in the general public and common in athletes. It makes up nearly 50% of all sport injuries. A number of treatment techniques with varying evidence of effectiveness are currently available. Intratissue percutaneous electrolysis (EPI) is one such modality, however little consensus exists for EPI’s efficacy or the most effective treatment parameters.To review and appraise available evidence for Intratissue Percutaneous Electrolysis (EPI) in the treatment of tendinopathy, examining the effectiveness of EPI in conjunction with other modalities and identifying the strengths and limitations of the evidence base for EPI in order to make evidence-based recommendation for future studies of EPI.PubMed, Embase and Scopus were searched with keywords related to EPI and tendinopathy. Grey literature searches were conducted with Embase, OpenGrey, and ProQuest. Extensive citation searching was undertaken. Randomised controlled trials (RCTs), uncontrolled and observational studies of the application of EPI in patients aged 18–65 years with Magnetic Resonance Imaging (MRI) or clinical Ultrasonography (US) confirmed diagnosis of tendinopathy were eligible.Eleven studies met inclusion criteria: six randomised control trials (RCTs) and five uncontrolled studies. Clinical trials of EPI as an adjunct modality with physical therapy reporting greater decreased pain and return to function than treatment with physical therapy alone. The evidence for EPI is limited and influenced by small sample sizes, varying treatment protocols, clinical heterogeneity and high risk of bias.It is currently not possible to conclude that EPI is an effective modality for the treatment of tendinopathy. RCTs with clearly described EPI treatment protocols, larger sample sizes and intervention reporting sufficient to support reproducibility are needed to determine the effectiveness of EPI for the treatment of tendinopathy. The term ‘tendinopathy’ is generally used to describe tendon disorders that include acute tendonitis, as well as chronic tendinosis.Tendinopathy is a chronic overuse injury characterised by tendon degeneration, resulting in pain and decreased activity level. Tendinopathy is highly prevalent in the general public and common in athletes, representing up to 50% of all sports injuries. Tendinitis refers to tendon inflammation and results from microtears that happen when the musculotendinous unit is acutely overloaded with a tensile force that is too heavy for it and/or applied too suddenly. Tendinitis lasts up to three weeks. Tendinosis is characterised by a chronic evolution of the degenerative process, including the formation of fibrotic tissue, degradation of myxoid substance, and decreased capillary blood flow, resulting in stagnation of the inflammatory cells (neutrophils and macrophages) required for phagocytosis. From acute tendinitis to chronic tendinosis, it is important to recognise that each stage of the tendinopathy process involves specific histological changes, and that each stage of the disease has the potential to respond differently to various treatment modalities. extracorporeal shockwave therapy, non-steroidal anti-inflammatory drugs, corticosteroids, and platelet-rich plasma injections. Despite this, up to 29% of patients with tendon injuries develop chronic tendinopathy and require surgical management. Patients with decreased functional status compared to preinjury level and increased pain before treatment may also be less likely to return to a pre-tendinopathy functional level.Many treatment techniques, with varying evidence of effectiveness, are currently used to treat tendinopathy including rest, physiotherapy, eccentric exercise, Various synonymous terms for EPI are found in the literature, including ultrasound-guided galvanic electrolysis technique (USGET), percutaneous micro electrolysis (MEPV), percutaneous needle electrolysis (PNE), and ultrasound-guided percutaneous electrolysis. Intratissue percutaneous electrolysis is an ultrasound-guided physiotherapeutic technique in which electrical stimulation is applied to the injured tendon via an acupuncture needle to produce localised inflammation at the treatment area and stimulate tendon healing . Intratissue percutaneous electrolysis utilises a combination of mechanical (needle) and electrical  stimulation to provide controlled micro-trauma and non-thermal electrochemical ablation directly to the area of the degenerated tendon. This leads to the production of sodium hydroxide molecules, altered pH and increased oxygen in the treatment site, enabling cellular phagocytosis, and activating tendon repair.,7Intratissue percutaneous electrolysis (EPI) is one modality for the treatment of chronic tendinopathy.Little consensus exists for EPI’s efficacy or the most effective treatment protocol. To the best of our knowledge, no systematic review of EPI treatment had been published at the time this systematic review was undertaken. A systematic review of EPI is needed to critically appraise the evidence for its effectiveness and provide recommendations for clinicians and future research on its use in the treatment of tendinopathy. The primary objective of this review is to examine, categorise and critically appraise available evidence for EPI in the treatment of tendinopathy to determine if EPI is a safe and effective treatment for tendinopathy, identifying the strengths and limitations of the current body of evidence and making evidence-based recommendations for future research. The review protocol was registered on PROSPERO: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018118345This systematic review was undertaken with the guidance of the Cochrane Handbook for Systematic Reviews of Interventions, the Centers for Review and Dissemination (CRD), the University of York Guide, and reported according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Keywords and medical subject headings (MeSH) related to tendinopathy, tendinosis, intratissue percutaneous electrolysis, and percutaneous electrolysis were used in searches across multiple search engines and databases. No publication date or language limits were imposed.Searches were undertaken on PubMed, Cinahl, Embase, Scopus, and the Cochrane library. The PROSPERO was searched for ongoing or recently completed systematic reviews addressing the review questions. To include EPUBS available ahead of the full publication, PubMed and Embase were searched again with the same methods, limiting results to articles added within the previous 90 days. Extensive searches in Embase, OpenGrey, Scopus, and ProQuest-Digital Dissertations were conducted for grey literature, including academic and conference papers. To ensure literature saturation, the reference lists of relevant papers were also searched, and citation searches were run on Scopus and PubMed.Randomised controlled trials, uncontrolled and observational studies of the application of EPI in patients aged 18–65 years with clinical Ultrasonography (US) or Magnetic Resonance Imaging (MRI) confirming diagnosis of tendinopathy were eligible. Patients included in these studies had to have tendinopathy symptoms present for more than three weeks, the time frame where post-inflammatory (tendinitis) degeneration is present.Single subject case studies, case series, and animal studies were excluded. Studies with patients with bilateral symptoms, or who had undergone prior surgery for tendinopathy or received corticosteroid injections or used non-steroidal anti-inflammatory drugs during treatment were excluded. Studies of EPI not used in tendons were ineligible.Search results were organised and collated into an electronic bibliographic database using RefWorks Citation Manager. Duplicate articles were identified and removed before proceeding with the screening process. Eligibility assessment was performed independently by two reviewers. Papers were initially screened against the review’s inclusion and exclusion criteria by title and abstract, then by full-text if eligible. A full-text review was also performed when eligibility was unclear by title or abstract. When necessary, study authors were contacted for additional information to resolve questions about their study’s eligibility.A custom Excel spreadsheet was developed to collect data about and summarise included articles and to quantify extracted information. Information related to study design, sample characteristics, EPI methods, and outcome measures was extracted into the spreadsheet. Simple, descriptive statistics were used to quantify the results of the literature searches, screening, and systematic reviews. If two or more domains were scored as high, the study was rated as having a high risk of bias. Studies that were in between were scored as having a moderate risk of bias. For assessments using the Cochrane Collaboration tool, a study was assessed with a low risk of bias when all items were assessed as low. When at least one item was assessed as moderate, the article received a score with a moderate risk of bias. A high risk of bias was rated when at least one item was assessed as high. The checklists were assessed and cross-checked by two researchers (DA and AP). If a difference of opinion arose concerning the scoring of an item, a consensus was reached.To assess the methodological quality of the included articles, two different checklists were used. For the articles related to descriptive epidemiology and aetiology, the Quality in Prognosis Studies (QUIPS) tool was used . The Coc was used for randomised controlled trials. The ROB is widely available, and its reliability and validity have been shown previously. The Cochrane ROB was chosen based on the authors’ experience and prior training with the ROB and following the recommendations of the Cochrane Collaboration Guide to Systematic Reviews. The ROB focuses on different aspects of trial design, conduct, and reporting across seven domains of bias  tool of bias . A serieThe framework for assessing the internal validity of prognostic studies developed by Altman , posing Fifty-five papers were found: 48 in pre-specified search engines and seven from citation and bibliographic searching . After d,11 the Numerical Rating Scale (NRS), the Visual Analogue Scale (VAS),,9 and the Shoulder Pain and Disability Index (SPADI). Each of these scales is used to rate pain from zero (no pain) to 10 (worst pain).A variety of outcome measures for patient-reported pain levels were used across eligible studies, including the Numerical Pain Rating Scale (NPRS),,16,17 and one each for the knee, ankle, and thigh tendons. Primary outcome measures used by two shoulder tendon studies was the VAS,,17 the third used the DASH questionnaire. The knee tendon study utilised the VISA-P scale, the ankle study the VISA-A scale, and the thigh study the VAS as primary outcome measures. Three of the RCTs used a treatment intensity between two and six milliampere (mA) with a maximum of five seconds active EPI up to three times per session;,15,17 however, Abat et al. applied EPI to the area until complete debridement without time specification. The three remaining RCTs used intensities between 100 and 450 microamperes (μA) with a treatment duration up to 90 seconds.,10,16 The characteristics of each study, as well as primary outcome measures, are listed in Of the six eligible RCTs, three investigated EPI treatment of shoulder tendons,,18,19,20 Three investigated EPI treatment in patellar tendon tendinopathy using the VISA-P scale as the primary outcome measure.,18,19 One study had a 10-year follow up (88% completion rate), one a two year follow up and one a six week follow up (both 100% completion rate). Two studies investigated lateral epicondylitis of the elbow and used the VAS and the DASH questionnaire as primary outcome measures,,20 with 6 week follow-up periods (100% completion rate). All uncontrolled studies utilized a treatment intensity of three to six milli ampere, three studies utilized a duration of three to five seconds performed three times,,18,20 while two studies applied EPI until the area was debrided.,19 The Characteristics of each study as well as primary outcome measures are listed in Five prospective, uncontrolled studies were eligible for inclusion.) resulted in a high risk of bias in all of the RCTs and uncontrolled studies eligible for inclusion in this systematic review. The greatest risk of bias among RCTs was found in the blinding of outcome assessment and selective reporting. Among uncontrolled studies, risk of bias was found in all studies, ranging low to high risk.,18,19,20Quality assessment of RCTs with the Cochrane ROB  and otheTable 1Intratissue percutaneous electrolysis (EPI) is an innovative treatment technique for a musculoskeletal condition affecting a large portion of the general population. Results from this systematic review indicate that EPI shows promise as an adjunct modality in the treatment of tendinopathy when combined with exercise or manual therapy, but insufficient quality evidence is currently available to determine whether EPI is an effective treatment for tendinopathy. Relatively small sample sizes, heterogenic EPI treatment parameters and comparator interventions, and a high risk of bias found across available studies makes it difficult to reach definitive conclusions about EPI’s effectiveness. The demonstration of a treatment’s efficacy requires a comparison of the response in the treated group with that of a control group receiving a placebo or another active treatment. Patients reported a return to function and reduced pain in four uncontrolled studies of EPI together with eccentric exercises, though it is impossible to attribute this to EPI in these studies as there were no comparison groups.,9,17,18 There were no adverse events reported with EPI treatment in the five uncontrolled studies during treatment or at follow-up; however, indicating that EPI may be a safe procedure in the treatment of tendinopathy.The scope and quality of evidence for EPI are limited. No RCTs were found investigating EPI in comparison to a placebo adjunct modality or placebo intervention. Thus it is not currently possible to differentiate between the placebo benefit of a modality added to other interventions, such as exercise or manual therapy, and the true effects of EPI. Additionally, almost half (five of 11) of eligible studies were uncontrolled clinical trials, which can offer preliminary evidence of safety and indicate if there may be a clinical effect worth investigating further but cannot offer evidence of efficacy.,18,20 Treatment duration lasting between four and 90 seconds in two studies,,16 and three other studies describe treatment until the area was “fully debrided,” but how that was characterised or measured was not specified.,7,19The high risk of bias found across all eligible studies may have been influenced by heterogenic treatment dosages, participant characteristics and outcome measures, and incomplete reporting of intervention details. A variety of treatment dosages were identified in the review, with EPI treatment intensity variously reported in milliamperes (mA) and microamperes (μA). The most consistent EPI treatment dosage reported was four-six mA for three sets of three seconds, though other dosages included 350 μA or two mA.,10 active physical therapy, manual therapy, electrophysiotherapeutic treatment, and general exercises, though these were often not reported sufficiently for reproducibility. Control interventions, or cointerventions within the EPI group, were not well described across eligible studies. Cointerventions in both the EPI and control groups may have influenced treatment outcomes separately from EPI tendon treatment. For example, Moreno investigated stand-alone EPI treatment of adductor tendons in a study of four groups of 10 patients each but does not report if any other treatment was received in addition to EPI, and the treatment protocol was not described in detail. Greater decreased pain was reported by the EPI group than the control groups in both the tendon and a muscular trigger point, though the study investigated the effect of EPI on tendinopathy, rather than trigger points.Intratissue percutaneous electrolysis treatment was investigated as an added modality with various interventions among eligible studies, ranging from EPI and eccentric exercise,,17 One RCT presented results based on VISA-P scores categorically as greater or lesser than 90 at follow-up, greatly reducing reported details of EPI treatment effects. One RCT utilised a goniometric range of motion values at the shoulder as outcome measures without describing the measuring procedure, its validation, or reliability, raising the risk bias in the study, and only three studies assessed EPI in the same joint, further limiting the generalisability of the available evidence.,16,17 An uncontrolled study comparing EPI to surgery focused outcomes on estimated cost, making direct comparison of treatment effects among both interventions difficult. Notably, none of the current studies investigated EPI for the treatment of tendonitis in the elbow, despite its high prevalence in the general population.Differences in the reporting of results and outcome measures used also make an assessment of EPI effectiveness difficult. Three RCTs presented results supported only by p-values, without reporting confidence intervals. while some studies only reported improved outcomes in the EPI groups.,12,15,17 One study found small improvements in pain but not in function for the EPI group, and one study found no differences between the groups.All of these factors may also have influenced the inconsistent findings reported among eligible studies. One RCT found improved outcomes in both the EPI and control groups, which is an established framework for guiding evidence-gathering in complex, practitioner-based interventions like EPI. The IDEAL framework prioritises transparent reporting of intervention details and delivery, consideration of pratitioner learning curves or skill with the intervention, standardisation of patient outcomes, and the selection of appropriate study designs for the level of development of innovative complex interventions like EPI.EPI is a complex intervention, with a number of independent and interdependent factors potentially influencing the effects of EPI treatment. These may include not only EPI dosage but also interventionist experience or a learning curve with EPI, patient and practitioners’ perception of equipoise and characteristics. Differences in practitioners’ skill with EPI and their inter- and intrapractitioner reliability, may also influence the outcome of EPI treatment and need to be established and further explored in future research. Future studies of EPI may benefit from the guidance of frameworks such as IDEAL-Physio or IDEAL,Clinical trials investigating EPI as an adjunct modality with physical therapy report greater decreased pain and return to function than treatment with physical therapy alone, but the evidence for EPI treatment is limited and influenced by clinical heterogeneity, high risk of bias and small sample sizes. Therefore, it is not possible to definitely conclude that EPI is an effective modality for the treatment of tendinopathy. Randomised controlled studies with clearly defined and described protocols for EPI treatment, larger sample sizes, better defined control interventions, and reporting sufficient to support reproducibility are needed to determine the effectiveness of EPI as an adjunct modality in the treatment of tendinopathy.


Regulatory initiatives in the European Union (EU) have led to proposed carcinogenicity classifications for poorly soluble low toxicity particles (PSLTs). Although PSLTs lack a widely accepted definition, commonly cited examples include carbon black, titanium dioxide and iron oxide, among others. In light of the demanding time challenges in proper review and regulation of substances used in commerce, it can be appealing to consider classes of compounds to facilitate regulatory applications. In a similar vein, the German MAK Commission has proposed workplace exposure limits for poorly soluble low toxicity particles. To foster an update on the science regarding PSLTs, and potential regulatory applications, the Particles and Health 2021 conference was designed to update the interdisciplinary science of PSLTs related to toxicology, epidemiology, occupational, and pulmonary medicine and exposure assessment, among others. This special issue focusing on “Particles and Health” includes peer reviewed papers on the topics of human health, the role of rat inhalation studies and inflammatory responses in addressing health risks, followed by papers on non-pulmonary effects of PSLTs and papers related to the regulatory impact of scientific studies related to PSLTs.Regulatory initiatives in the European Union (EU) have led to proposed carcinogenicity classifications for poorly soluble low toxicity particles (PSLTs). Although PSLTs lack a widely accepted definition, commonly cited examples include carbon black, titanium dioxide and iron oxide, among others. In light of the demanding time challenges in proper review and regulation of substances used in commerce, it can be appealing to consider classes of compounds to facilitate regulatory applications. In a similar vein, the German MAK Commission has also proposed workplace exposure limits for poorly soluble low toxicity particles.www.particlesandhealth.org for more detail). Occupational exposure to PSLTs can occur in many industrial sectors, including mineral mining and milling; welding and asphalt use; and in the manufacture of textiles, glassware, roofing, pulp, and paper products. Nanomaterial manufacturing and use  presents other challenges. PSLT exposures may impact millions of workers globally.To foster an update on the science regarding PSLTs, and its potential regulatory application, the Particles and Health 2021 conference was designed to update the interdisciplinary science of PSLTs in toxicology, epidemiology, occupational and pulmonary medicine, and exposure assessment, among others  Uncertainties of defining poorly soluble low toxicity particles (PSLTs); (2) Whether PSLTs should be considered separate entities or broadly defined; and (3) Appropriate regulatory applications of the health related science of PSLTs.The conference was divided into four major sections held over a two period in which 30 formal presentations were made, including:The role of human studies, including epidemiology, in assessing health risk.in vitro studies in assessing inflammation as a key adverse outcome pathway in particle induced effects.The role of animal and The role of nanoparticle toxicology and potential impact of PSLTs on non-pulmonary adverse effects.The critical aspect of appropriate regulatory application of science.What follows are highlights of the key sections led by the respective moderators of the session.Role of human studies in assessing health risk.Seaton et al.).The Health section was introduced by a discussion of the history of The Institute of Occupational Medicine (IOM) from its inceptions in the 1960s when it played a major investigative role in understanding coal workers pneumonoconiosis to today's challenges in addressing the potential impact of nanomaterials  No 1272/2008 , complementing the European REACH Regulation (EC No 1907/2006), “Where evidence is available from both humans and animals and there is a conflict between the findings, the quality, and reliability of the evidence from both sources shall be evaluated to resolve the question of classification. Generally, adequate, reliable, and representative data on humans  shall have precedence over other data.”In the regulatory application of scientific studies regarding health implications of the production and use of certain materials, including PSLTs, human studies led by Mundt et al. reported on several chronic inhalation studies of PSLTs  in rats that demonstrated risk of lung cancer, but only at “lung particle overload” doses in rats.The US Centers for Disease Control has also noted that Epidemiology is the preferred basis of Risk Evaluation. Epidemiology, often described as the basic science of public health, can demonstrate human health risks of PSLTs under the “natural” circumstances of use and exposure. In a presentation regarding the “Role of epidemiology in human risk assessment,” Mundt et al.).Similar findings were not observed in mice, hamsters, and guinea pigs. In contrast, epidemiological studies of talc, carbon black, and titanium dioxide workers have not shown statistically significant associations between PSLT particles and risk of lung cancer , coal is a complex mixture of >50 elements and their oxides. Coal dust is composed of numerous substances, including Human Carcinogens, such as crystalline silica, beryllium and cadmium. Moreover, coal mining activities often occur in the context of exposure to machinery that emits diesel exhaust particles—an IARC Type I carcinogen. In contrast to coal, Carbon Black (CAS No. 1333-86-4)—a manufactured product considered a PSLT- is virtually pure elemental carbon (upwards of 98–99%) produced by incomplete combustion of gaseous or liquid hydrocarbons under controlled conditions. Its physical appearance is that of a black, finely divided pellet or powder.Risk of lung cancer among coal miners has been investigated in cohort mortality studies conducted over nearly 50 years. Over 120,000 coal miners have been part of studies in UK, Germany, Netherlands, USA, Poland, Japan, Czech Republic, and Australia. The weight of epidemiological evidence suggests no increase in risk of lung cancer among coal miners. Slight elevations in SMR cannot lead to a reliable conclusion about an increased risk due to limitations in exposure assessment, and inherent biases in case-control studies, most notably confounding and recall bias.Despite the lack of scientific appropriateness of using coal as a surrogate for PSLTs in evaluating the significance of rat inhalation studies, the preponderance of epidemiological results of cohort mortality studies of coal-mine workers do not indicate a consistent increase in lung cancer risk.Harber summarized the application of causal inference analysis to questions concerning the health effects of such particles. Relationships with malignancies remain uncertain. Inflammation has been postulated as a key intermediary step in the pathogenesis. Observational predictive epidemiologic studies have limited ability to address poorly observable mechanistic steps. Causal inference analysis, such as the use of Directed Acyclic Graphs (DAG), can create a useful analytic framework to allow integration of data from epidemiologic, clinical, and experimental studies to address mechanistic questions. In addition, these methods are useful to clarify potential bona fide and artifactual observed relationships.Since poorly soluble low toxicity particles such as carbon black or titanium dioxide have raised concern about potential malignant or non-malignant adverse effects such as lung cancer or chronic airflow obstruction, As a means of detecting early signs of pulmonary inflammation that may presage malignant and non-malignant lung disease, Professor Chris Fanta summarized the potential utility of measurement of exhaled nitric oxide. Exhaled nitric oxide assessment is a non-invasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma . This paConsiderable overlap in results may be present, however, between normal and disease and may be Influenced by age, atopy, sinus disease, and cigarette smoking, among others. Dramatic suppression by inhaled corticosteroids, for example, can occur and lead to results in a “gray zone” (20–40 ppb).Yong et al. describe their evaluation of the effect of cumulative exposure to respirable synthetic amorphous silica (SAS) dust on respiratory morbidity, as assessed by spirometry. Multiple exposure assessments were conducted in a cross sectional analysis of 462 exposed male workers. An averaged cumulative respirable SAS dust concentration of 6.44 mg/m3 years was estimated. Internal regression models suggested a reduction of 8.11 ml (95% CI: 0.49–15.73) in forced vital capacity (FVC) per 1 mg/m3 year increase of exposure. No effect on forced expiratory volume in 1 s (FEV1) or the FEV1/FVC ratio was observed in association with exposure to the respirable fraction of SAS. No adverse effects on the occurrence of respiratory diseases were observed. The authors concluded that there was no clear evidence of adverse pulmonary effects from occupational exposure to respirable SAS.Borm et al. focused on inflammation as a key adverse outcome pathway in particle induced adverse health effects. Dominique Lisone presented a study related to the role of pulmonary macrophages in inflammation and the development of lung cancer. Driscoll then presented paper on particle induced inflammation and lung cancer based on the outcome of an Edinburgh workshop. Roger Duffin then presented an overview of inflammatory pathways in humans followed by a discussion by Jack Harkema, a pathologist who discussed pulmonary cell proliferation, the missing link in particle induced lung cancer. The session concluded with a group discussion related to the Global Harmonization System (GHS) based target organ toxicity design and interpretation of existing studies.In a luncheon address, Dr. Paul Brandt-Rauf, the editor of the Journal of Occupational and Environmental Medicine, described some of the vagaries of journal publications. He described the role of the impact factor in raising a journal's reputation and reviewed some of methods employed by editors to raise a journal's impact factor, most notably by publishing major review articles, which customarily receive more citations than individual articles. The afternoon session, moderated by Nanoparticles can be defined as particulate materials having at least one external dimension smaller than 100 nm. Airborne nanoparticles can occur naturally ; be anthropogenic, arising as by-products of human activity, e.g., fossil fuel combustion; or can be materials purposely engineered to be of nanometer size and possessing unique properties.Scarcello et al.)  , 11. TheDrs. Oberdörster, Creutzenberg, and Graham discussed dosimetric and biokinetic considerations of nanoparticles. Important factors differentiating nano from larger micron sized inhaled particles include: the larger number and surface area per unit mass (or volume) of nanoparticles and consequently the potential for greater reactivity; the role of diffusion mechanisms in the deposition of nanosized materials resulting in deposition patterns in the respiratory tract which differ from larger size particles for which inertial mechanism are more important; and the nanosize potentially enabling translocation into cells and along axons and dendrites.Creutzenberg et al. summarized studies in rats with inhaled and/or intratracheally instilled titanium dioxide, zinc oxide, silica, and carbon black which demonstrated that shortly after exposure deposited nanoparticles were found as aggregates localized in macrophages. Tissue analysis after days or weeks demonstrated retention in lung macrophages, pneumocytes, and translocation to the lung associated lymph nodes. These studies supported the major clearance pathway was via the gastrointestinal track with no significant translocation to remote organs.Regarding translocation of nanoparticles, Creutzenberg et al. and that observed in humans in extra-pulmonary particle translocation may reflect the sensitivity of the detection methodologies used.Dr. Graham described studies conducted studies on human autopsy tissues using high resolution transmission electron microscopy combined with elemental mapping which demonstrated the present of nanosized particles in the olfactory bulbs. The particle composition  indicated an exogenous origin, hypothesized to be due to inhaled air pollution particles depositing in the nasal passages and translocating to the brain. In support of this hypothesis, studies in rats have demonstrated nanoparticle depositing on the nasal mucosa can translocate to the brain . The silThe potential for nanoparticles to elicit effects on DNA and in non-pulmonary tissues was addressed in presentations by Drs. Moller, Schins, Hougaard, and McCunney.In vitro, MWCNT-7 nanotubes produce DNA damage, albeit only at extremely high doses. These findings on material dependent differences in inflammatory and DNA damaging effects are consistent with other studies demonstrating differences in bioactivity of various MWCNT  reporting MWCNT-7  elicits inflammation and production of reactive oxygen species when injected into peritoneal cavities of rats; however, no DNA damage was detected. Comparable results were observed with NM-401, another long, thin nanotube, however, intraperitoneal injection of shorter nanotubes did not produce inflammatory effects. us MWCNT  and supp2, CeO2) did not increase brain plaque formation in 5 × FAD mice and were without effect in a mouse model of atherosclerosis. Studies on oral exposure of mice to titanium or silver nanoparticles had no effect on markers of neuroinflammation with some behavioral changes observed in female mice as well as biochemical changes in cortical tyrosine kinase activity. Overall, the neurotoxicity research summarized supports that inhaled or ingested nanoparticles may have effects distance from the lungs or GI tract with the effects being material dependent.Regarding the potential for neurotoxic effects, Dr. Schins reported inhalation of diesel exhaust increases b amyloid protein accumulation in the brains of 5 × FAD mice, a model of Alzheimer's Disease amyloid protein accumulation. These findings suggest inhaled diesel exhaust can have neurological effects distance from the respiratory tract. Additional studies on inhaled engineered nanoparticles . The studies supported exposure-associated changes on the central nervous system, immune system, and male fertility. The mechanisms underlying the changes reported by Drs. Schins and Hougaard were not defined and will require further investigation. The association of occupational carbon black exposure with cardiovascular disease was discussed by  unclear , 9, 14. McCunney et al. reviewed the three major occupational epidemiology studies on carbon black investigating populations in the United States, Great Britain, and Germany which collectively have includes over 9,300 workers. After accounting for cigarette smoking, none of these studies have demonstrated an increased risk of mortality or cardiovascular disease. A meta-analysis of these studies confirmed an absence of an association between occupational carbon black exposure and heart disease, ischemic heart disease, or acute myocardial infarction. The negative studies on carbon black considered alongside the evidence on air pollution and cardiovascular disease suggest the complex chemical properties of air pollution are a critical factor in the elevated cardiovascular disease risk vs. a specific effect of poorly soluble nanosized particles  but more recently, by the EU European Chemical Agency's (ECHA's) Risk Assessment Committee (RAC) .The first-scene setting presentation addressed the regulatory application of science and stakeholder engagement in the setting of EU occupational exposure limits (OELs) by Alick Morris from the EU Health and Safety at Work Unit, DG Employment, Social Affairs and Inclusion, European Commission, Luxembourg. His presentation described how this activity takes place at the EU level when setting limit values (OELs) to protect the health of workers from risks due to occupational exposure to chemicals. Alick Morris described the EU Pillar of Social Rights Action Plan, the EU Occupational Safety and Health strategic framework and how the key steps in setting OELs and Biological Limit Values (BLVs) as well as their benefits. He noted how the social partners  participate in regulatory decision-making through the EU Advisory Committee on Safety and Health (ACSH) which also adopts new lists of priorities for future limit values. He also described some current initiatives driven by the Occupational Safety and Health Directive and the Carcinogens and Mutagens Directive which included recent work on asbestos, lead and diisocyanates. He pointed out how this work was assisted Schulte et al. from the US National Institute for Safety and Health (NIOSH) described the application of translational science approaches to protect workers exposed to nanomaterials. In his presentation he noted that nanotechnology, like translational science, is a relatively new and transdisciplinary field. Translational science in occupational safety and health (OSH) focuses on the process of taking scientific knowledge for the protection of workers from the laboratory to the workplace and back again. Translational science has been conceptualized as having number of multiple phases of research along a continuum, from scientific discovery (T0) to efficacy (T1), to effectiveness (T2), to dissemination and implementation (D&I) (T3), to outcomes and effectiveness research in populations (T4). The translational research process applied to occupational exposure to nanomaterials might well-involve similar phases. This includes basic research (T1) in the areas of toxicology, epidemiology, industrial hygiene, medicine, and engineering. He described iterative interrelationship of these four phases in some detail, including potential barriers to the implementation of solutions. Of critical importance, and in accord with the first presentation by Alick Morris, he emphasized that stakeholder participation and engagement was critical to all four phases of the translational continuum.in vitro test methods are urgently needed to compare different materials, including SAS, and to test their toxicological properties for oral and inhalative exposure.The next series of presentations dealt with one particulate nanomaterial; synthetic amorphous silica (SAS) to illustrate a number of scientific, ethical, and regulatory issues. In the case of many PSLTs and nanomaterials, including nanostructured SAS, the most important exposure pathway for such materials is inhalation; depending on the possible applications of the substance in foodstuffs, cosmetics, among others that dermal and oral exposure must also be taken into account. Additionally, to reduce the need for animal experiments, in vitro screening of nanomaterials with an advanced in vitro intestine model.In the first of these illustrative presentations on SAS, Peter Wick described an oral in vivo like setting. The exposition of the advanced coculture model with six different SASs selected due to the different production routes, specific surface areas and different silanol content led to no differences in the viability, barrier integrity, microvilli function, and lipid uptake. Nevertheless, the treatment had shown that the mucus production increases after the treatment with SAS materials that present certain aggregate sizes and a high silanol content. A co-effect has been found for the investigation of the iron uptake. Precipitated SAS with a small specific surface area decreased the iron uptake in the advanced co-culture only in iron uptake but not in the also on the gene level. The results show that the use of this advanced in vitro model could lead to an improved prediction on potential adverse outcomes of food components on the intestine. Mucus seems to be a very important protective barrier in the interaction of food components with the intestinal epithelium and should be studied in more detail. The advanced co-culture model established in this work can be used for an initial estimate of the interactions of food components with intestinal epithelium and ideally, a further reduction of animal experiments in the future. Overall, this in vitro test model for oral intake showed that no adverse effects were observed with SAS. Further information on this alternative screening method for oral exposure is provided by Hempt et al. . Five non-treated and nine surface-treated SAS  were included in the in vitro study with alveolar macrophages. Dispersion of the hydrophobic SAS (8/14) required pre-wetting with ethanol and extensive ultrasonic treatment in the presence of 0.05% BSA (Protocol 1). Hydrophilic SAS were suspended by moderate ultrasonic treatment (Protocol 2) and with Protocol 1.t system , 20. Sern et al. . He presin vitro studies correlate very well with the results of subchronic in vivo studies (90-day study) with hydrophobic surface-treated SAS  and concentrations up to 5,000 mg/m3 or the maximum technical feasible concentration. This technical feasible concentration, however, and more importantly, its measurement, is not defined. The challenge of creating particulate aerosols for acute toxicity testing using a systematic approach was presented. The aim is to examine optimized aerosol generation and its monitoring, including detailed characterization of the exposure atmospheres in the test equipment  from the point of generation to the point of release out of the system prior to performing OECD animal inhalation studies . It was the intention to perform rat studies with the highest technically feasible concentration without significant aerosol altering. Studies of aerosol generation on this scale and detail with several different particular substances, e.g., silica, organic pigments, aluminum oxide, sugar, flour dust, and calcium carbonate have not previously been carried out in any acute animal inhalation studies. A key conclusion was that a detailed evaluation of the aerosol generation can help predict the outcome of rat inhalation studies with particles and therefore, reduce the number of animals required in future acute inhalation tests.The results above raise the question that if hydrophobic surface-treated SAS materials show reduced bioactivity Krueger et al. presented a study on hydrophobic surface treated SAS: “Non-specific particle effects now trigger classification?.” The aim of the study was to understand the mechanism of lethality associated with high dose inhalation of hydrophobic surface treated SAS observed in some acute inhalation studies. It was demonstrated that physical obstruction of the upper respiratory tract  caused effects observed when hydrophobic surface-treated SAS was inhaled  by six Wistar rats  in an acute toxicity study at a concentration of ~500 mg/m3 for 4 h . Under the conditions of the test set-up, the concentration applied was found to be the highest that can be delivered to the test animal port without significant alteration of the aerosol size distribution over time. None of the test-material-exposed animals survived the observation period. Histopathology and energy dispersive X-ray (EDX) analysis demonstrated that test material particles agglomerated and formed a gel-like substrate that blocked the upper respiratory airways, which is fatal for the rat as an obligatory nose breather. This observation is in line with the findings reported by Hofmann et al. , most notably carbon black, titanium dioxide and talc. From this conference, 20 peer reviewed scientific papers were published in this special issue. The role of epidemiology and toxicology in assessing potential human health risks of regulatory impact was emphasized. Clearly, as regulatory challenges persist in establishing appropriate classification schemes and exposure limits for PSLTs, the role of scientific investigations will play a major role.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Cellular homeostasis is tightly connected to the broad variety of mitochondrial functions. To stay healthy, cells need a constant supply of nutrients, energy production and antioxidants defenses, undergoing programmed death when a serious, irreversible damage occurs. The key element of a functional integration of all these processes is the correct crosstalk between cell signaling and mitochondrial activities. Once this crosstalk is interrupted, the cell is not able to communicate its needs to mitochondria, resulting in oxidative stress and development of pathological conditions. Conversely, dysfunctional mitochondria may affect cell viability, even in the presence of nutrients supply and energy production, indicating the existence of feed-back control mechanisms between mitochondria and other cellular compartments. The ubiquitin proteasome system (UPS) is a multi-step biochemical pathway that, through the conjugation of ubiquitin moieties to specific protein substrates, controls cellular proteostasis and signaling, removing damaged or aged proteins that might otherwise accumulate and affect cell viability. In response to specific needs or changed extracellular microenvironment, the UPS modulates the turnover of mitochondrial proteins, thus influencing the organelle shape, dynamics and function. Alterations of the dynamic and reciprocal regulation between mitochondria and UPS underpin genetic and proliferative disorders. This review focuses on the mitochondrial metabolism and activities supervised by UPS and examines how deregulation of this control mechanism results in proliferative disorders and cancer. They are primary involved in ATP production, ion storage and metabolic intermediates production, and represent the principal source of reactive oxygen species (ROS). All these roles place mitochondria at the center stage of cellular health, making them essential for cell differentiation, growth and survival. Mitochondrial fusion and fission, mitochondrial unfolded protein response  and the mitochondrial health ,6. UbiquMitochondria abundance and activity are fundamental elements underlying the dynamic adaptation of cells to stress conditions. The shape and number of mitochondria are tightly controlled by key biological processes, such as fusion and fission  and mitophagy that operate in an interconnected and dynamic way to sustain cellular health and metabolic needs.Mitochondrial fusion and fission are reversible rearrangements of mitochondrial structure. Mitochondria can fuse or divide their inner and outer membranes, assuming an elongated shape or punctiform pattern and promoting the cellular adaptation to changes in nutrients and oxygen availability, to cope cellular stress conditions. Mitochondria fusion relies on the concerted action of two distinct GTPase family proteins, mitofusins (MFN1/2) and optic atrophy 1 (OPA1). MFN1/2 are two GTPases that mediate the OMM fusion, whereas the fusion of inner mitochondrial membranes is mediated by cristae remodeling protein OPA-1 . On the The number of mitochondria is tightly regulated through two different processes that promote the formation (biogenesis) or the elimination (mitophagy) of mitochondria. The mitochondrial biogenesis is an evolutionary conserved mechanism of self-replication through which cells enhance the number of mitochondria in response to cellular stresses, such as oxidative stress, or as consequence of extracellular stimulation by hormones, growth factors or endurance training . A coordMitophagy is a conserved cellular mechanism that eliminates damaged or unneeded mitochondria through the autophagy pathway, avoiding the accumulation of dysfunctional organelles . It is wMitochondria are the powerhouse of the cell and through the tricarboxylic acid cycle (TCA), also known as Krebs cycle and the oxidative phosphorylation chain produce metabolites and ATP required for cell differentiation, growth and survival. The enzymes of TCA cycle and of the respiratory chain are located within mitochondrial matrix and in the inner mitochondrial membrane (IM), respectively. In the past years, the ubiquitination of inner mitochondrial proteins seemed to be extremely unlikely, due to their spatial separation from the cytoplasm. Nevertheless, recently, the ubiquitination of inner mitochondrial proteins has been experimentally proved ,47. InteThe impact of the ubiquitin system in the regulation of mitochondrial activities has been thoroughly explored in mammalian cells where mitochondrial glutamine metabolism is essential to furnish important intermediates to the TCA cycle and metabolites for the fatty acid synthesis ,49. GlutThe C-terminal to LisH (CTLH) complex, also called the glucose-induced degradation deficient (GID) complex, is an E3 ligase complex composed of 7 subunits that is activated by high glucose levels. In yeast, it has been linked to the ubiquitination of gluconeogenic enzymes, such as fructose 1,6 bisphosphate . Cryo-elThe reciprocal regulation between UPS and mitochondrial homeostasis has been elegantly demonstrated over the past years ,61,62,63Mitochondrial uncoupling proteins (UCP) are integral inner mitochondrial membrane proteins that dissipate the energy generated by the electron transport chain . The eneMitochondria modify their morphology and biochemical functions in response to metabolic needs, cellular damage or changes in nutrients and oxygen availability. Mitochondria can be considered as sentinel organelles that drive the cellular homeostasis by integrating different signaling input and supplying energy and metabolites under healthy conditions. Due to their role in cellular metabolism, mitochondria coordinate different molecular pathways involved in cell proliferation and survival . In the The integrated stress response (ISR) is an alternative p53-independent pathway induced by nutrients (glucose or amino acid) depletion, hypoxia, genotoxic damage and the ER stress/UPR, that increases NOXA transcription. Activation of ISR by a combined treatment of cancer cells with Navitoclax, that acts through B cell lymphoma extra-large (BCLXL) blockade, and protein kinase inhibitors induces MARCH5-mediated ubiquitination and proteolysis of the BCL2 family apoptosis regulator (MCL1). Downregulation of MCL1 markedly enhances apoptotic cancer cell death .Overexpression of MARCH5 has been also linked to TGFβ-induced autophagy and promotion of growth and motility of several cancer cell types ,78. In pThe phosphatidylinositol 3 kinase-AKT pathway is one of the most frequently deregulated signaling pathways in human cancer. This signaling cascade can be activated by a broad variety of extracellular stimuli, such as growth factors, hormones and cytokines and regulates multiple downstream targets resulting in increased growth, survival and proliferation ,80. The Cancer cells are strictly dependent on energy and metabolites production for growth and survival ,89,90. IMitochondria are the principal providers of energy and metabolites for all cellular activities. These organelles represent the place where signaling networks and metabolic pathways converge and integrate to support differentiation, cell growth and survival. Environmental stress conditions, poisoning or genetic mutations that affect mitochondrial activities play a pathogenic role in a wide variety of human diseases. In the last years, an important influence of the ubiquitin proteasome system in the control of mitochondrial activities emerged. The fine regulation of localization, activity and turnover of mitochondrial proteins by the UPS is a key element in the maintenance of the mitochondrial homeostasis, promoting the elimination of damaged proteins and, in some instances, priming dysfunctional mitochondria to autophagic elimination . Alterat


Sustainable pork production must evolve from a linear supply chain towards a circular system that integrates and optimizes multiple environmental, human and animal health, societal, and economic factors.Improving carbon, nitrogen, and phosphorus utilization efficiency of pork production requires new approaches for sourcing feed ingredients, formulating diets, precision feeding, and upcycling nutrients from food waste streams.One Health, circular, and sustainable swine feeding strategies can provide complementary or synergistic benefits for optimizing nutrition-health-environment interactions but widespread implementation is needed.Interdisciplinary and transdisciplinary research and education is needed to develop and implement meaningful sustainability action plans in the global agriculture and food industry.Global agriculture and human food system is at a critical point for achieving future food security and sustainability because of destruction of soil, loss of biodiversity, degradation and pollution of water and land resources, and inefficient use, recovery, and recycling of nitrogen (N) and phosphorus (P) which have exceeded Earth’s planetary boundaries . Many inThe current food and agriculture supply chains are inefficient because they function as linear models comprised of independent actors attempting to achieve the greatest economic benefits in an extraction–production–consumption–discard manner at significant environmental costs . TherefoPork production is the largest contributor to global meat production, and future consumer demand for pork is expected to increase . AlthougOne Health goals must also be achieved in sustainable pork production systems and have been used to evaluate and compare positive and negative impacts of future scenarios of improved pig production . One HeaThe introduction of a foreign animal disease, such as African Swine Fever virus (ASFV), to a major pork producing country  can have numerous detrimental effects on sustainability including huge economic losses , inabiliBecause of the perceived risk of ASFV and other foreign virus transmission through feed, demand for using rendered animal by-products and various sources of food waste in swine diets to reduce feed costs, improve nitrogen and phosphorus recovery, and reduce the environmental footprint has been diminished . FurtherDisruptions in “just-in-time” delivery of feed ingredients in global supply chains in recent years have led feed manufacturers to attempt to develop shorter supply chains that often include a desire to use more locally produced grains and oilseed meals compared with imported ingredients to provide a more reliable supply. Depending on the environmental impacts associated with using local feed ingredients, there may also be opportunities to feed diets with a lower environmental footprint to reduce overall environmental impacts of pig production , while ahttps://tools.blonkconsultants.nl/tool/16/) has developed a large feed ingredient database consisting of 18 Life Cycle Assessment (LCA) environmental impact variables . The risk of abrupt environmental changes on Earth has increased because of human activity causing disruption of N and P flows from excessive waste  compared with methane (16%) and carbon dioxide (76%) but its global warming potential is nearly 10 times greater than methane and nearly 300 times greater than carbon dioxide , with the poultry and pork supply chains contributing 29% of the total from food animals, and 68% of these N emissions are associated with feed production . NitrousPhosphorus is also a finite nutrient that has also exceeded planetary boundaries, caused by human activities that have disrupted biogeochemical flows , and losSeveral researchers have modeled dietary N utilization efficiency in swine by estimating the amount of N retained in the body, N excretion in feces and urine, and N emissions from manure as a percentage of total dietary N . ResultsStrategies to improve dietary N utilization efficiency include 1) the use of precision diet formulation to avoiding overfeeding protein above the pig’s requirements , 2) precBacteroides and Clostridium species in the hindgut, thereby reducing the incidence of postweaning diarrhea and improving gut health in weaned pigs  concentrations can be reduced by up to 4 percentage units when supplementing diets with L-lysine, DL-methionine, L-threonine, and L-tryptophan without compromising growth performance of pigs . In genened pigs .Like dietary N utilization, pigs also have low (34%) dietary P utilization efficiency . To optiAn LCA study was conducted to determine environmental impacts of three swine diet formulation scenarios including standard base diets without or with supplemental crystalline amino acids, and the same base diets supplemented with synthetic amino acids and phytase for commercial pork production systems in Europe, North America, and South America of live pigs at the farm gate  is lost or wasted and not consumed globally , upcycliNew biotic processing methods  are emerging to upcycle nutrients from waste streams in animal production, food processing, and postconsumer food waste into higher value nutrient sources as animal feeds. For example, low value agri-food waste streams such as animal manure and postconsumer food waste are being used as substrates to produce insects which are more concentrated and highly palatable protein and energy sources for use in animal feeds . SelecteSustainable pork production requires increased attention to sourcing of feed ingredients, use of LCA and antinutritional factor constraints for feed ingredients in multi-objective feed formulation and precision nutrition practices, and further development and implementation of strategies to upcycle nutrients from nutritionally inferior by-products and food waste streams into swine feed ingredients to improve carbon, nitrogen, and phosphorus utilization efficiency and reduce the environmental footprint of pork production. Many of these strategies are complementary to achieving One Health and circular agriculture and food system goals but continued use of pharmacological dietary levels of Cu and Zn in weaned pig diets are not. Future swine feeding programs must be designed to not only be economical and optimize swine health and productivity, but they must also minimize risk of transmission of pathogens, avoid contributing to antimicrobial resistance, and reduce the environmental footprint of pork production.Conflict of interest statement. None declared.