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This study investigates the presence of new psychoactive substances (NPS) and their metabolites in two wastewater treatment plants (WWTPs) situated in South Wales, UK (WWTP-1 and WWTP-2). Analysis was conducted for 35 NPS and metabolites, along with the inclusion of benzoylecgonine (main cocaine metabolite) and cannabis, the most detected illicit substances. Benzoylecgonine was identified as the predominant substance in both WWTPs. Epidemiological calculations revealed the average population consumption of cocaine to be 3.88 mg/d/1000 inhabitants around WWTP-1 and 1.97 mg/d/1000 inhabitants for WWTP-2. The removal efficiency of benzoylecgonine across both WWTPs was observed at an average of 73%. Subsequent qualitative analyses on randomly selected wastewater samples detected medicinal compounds including buprenorphine, methadone, and codeine in both WWTPs. An additional experiment employing enzymatic hydrolysis revealed the presence of morphine, an increased presence of codeine, and 11-Nor-9-Carboxy-THC (THC-COOH) post-hydrolysis. These findings underscore the significant presence of illicit substances and medicinal compounds in wastewater systems with the absence of NPS within the South Wales area, highlighting the necessity for enhanced monitoring and treatment strategies to address public health and environmental concerns.
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Cocaína , Psicotrópicos , Águas Residuárias , Poluentes Químicos da Água , Águas Residuárias/química , Cocaína/análise , Cocaína/análogos & derivados , Poluentes Químicos da Água/análise , Psicotrópicos/análise , Cannabis/química , Humanos , Drogas Ilícitas/análise , País de Gales , Purificação da Água/métodosRESUMO
Those involved in drug testing continue to grapple with the dynamic nature of emerging psychoactive substances (NPS) and their rapid infiltration into society. The challenge extends beyond merely detecting and measuring NPS using analytical tools; it also encompasses the complexities arising from the formation and presence of metabolites and degradation products. This study utilises liquid chromatography time-of-flight mass spectrometry to investigate the stability of new psychoactive substances in wastewater. Seven NPS compounds including 25C-NBOMe, 5F-APINACA 4-hydroxyphenyl, AB-PINACA, APINACA 4-hydroxyphenyl, fentanyl, norfentanyl and MDPV, along with their corresponding internal standard, were examined. Reference material for each NPS compound was introduced into a wastewater sample from a Wessex water treatment plant. The sample was then exposed to four different environments: room temperature, refrigerator temperature, acidification to pH 2, and the introduction of sodium metabisulfite. The findings highlight the critical dependence of storage conditions on target analytes, emphasizing the paramount importance of the time elapsed between collection and analysis for NPS wastewater analysis. Notably, synthetic cannabinoids exhibit limited stability in wastewater whereas cathinone-like substances demonstrate greater stability. Furthermore, metabolites prove to be more stable in wastewater than the parent drug, suggesting that focusing on metabolite detection may be more favourable for future analysis.
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Globally, glaciers and icefields contribute significantly to sea level rise. Here we show that ice loss from Juneau Icefield, a plateau icefield in Alaska, accelerated after 2005 AD. Rates of area shrinkage were 5 times faster from 2015-2019 than from 1979-1990. Glacier volume loss remained fairly consistent (0.65-1.01 km3 a-1) from 1770-1979 AD, rising to 3.08-3.72 km3 a-1 from 1979-2010, and then doubling after 2010 AD, reaching 5.91 ± 0.80 km3 a-1 (2010-2020). Thinning has become pervasive across the icefield plateau since 2005, accompanied by glacier recession and fragmentation. Rising equilibrium line altitudes and increasing ablation across the plateau has driven a series of hypsometrically controlled melt-accelerating feedbacks and resulted in the observed acceleration in mass loss. As glacier thinning on the plateau continues, a mass balance-elevation feedback is likely to inhibit future glacier regrowth, potentially pushing glaciers beyond a dynamic tipping point.
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BACKGROUND: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA). METHODS AND FINDINGS: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies. CONCLUSIONS: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management. PROSPERO NUMBER: CRD42022348045.
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Úlcera , Descarga Vaginal , Humanos , África Subsaariana/epidemiologia , Feminino , Descarga Vaginal/epidemiologia , Descarga Vaginal/etiologia , Úlcera/epidemiologia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/diagnóstico , Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/diagnóstico , Vaginose Bacteriana/complicações , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/complicações , Infecções por Chlamydia/diagnóstico , Doenças Uretrais/epidemiologia , Doenças Uretrais/etiologia , Doenças dos Genitais Femininos/epidemiologiaRESUMO
Background: There is an increasing body of evidence associating short-term ambient nitrogen dioxide (NO2) exposure with asthma-related hospital admissions in children. However, most studies have relied on temporally resolved exposure information, potentially ignoring the spatial variability of NO2. We aimed to investigate how daily NO2 estimates from a highly resolved spatio-temporal model are associated with the risk of emergency hospital admission for asthma in children in England. Methods: We conducted a time-stratified case-crossover study including 111,766 emergency hospital admissions for asthma in children (aged 0-14 years) between 1st January 2011 and 31st December 2015 in England. Daily NO2 levels were predicted at the patients' place of residence using spatio-temporal models by combining land use data and chemical transport model estimates. Conditional logistic regression models were used to obtain the odds ratios (OR) and confidence intervals (CI) after adjusting for temperature, relative humidity, bank holidays, and influenza rates. The effect modifications by age, sex, season, area-level income deprivation, and region were explored in stratified analyses. Results: For each 10 µg/m³ increase in NO2 exposure, we observed an 8% increase in asthma-related emergency admissions using a five-day moving NO2 average (mean lag 0-4) (OR 1.08, 95% CI 1.06-1.10). In the stratified analysis, we found larger effect sizes for male (OR 1.10, 95% CI 1.07-1.12) and during the cold season (OR 1.10, 95% CI 1.08-1.12). The effect estimates varied slightly by age group, area-level income deprivation, and region. Significance: Short-term exposure to NO2 was significantly associated with an increased risk of asthma emergency admissions among children in England. Future guidance and policies need to consider reflecting certain proven modifications, such as using season-specific countermeasures for air pollution control, to protect the at-risk population.
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[This corrects the article DOI: 10.1021/acscatal.3c03951.].
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New psychoactive substances are produced and marketed to mimic the effects of their illicit counterparts and to attempt to evade drug tests and prosecution. Here, we present the optimisation, validation and application of an analytical method using liquid chromatography-time-of-flight mass spectrometry to detect and quantify 37 new psychoactive substances and illicit substances in wastewater from South Wales, UK, using a targeted analysis method. Sample preparation was performed using solid-phase extraction with Oasis HLB cartridges. The LC separation was performed using a YMC-Triart Phenyl 450 bar column (12 nm, 5 µm, 100 × 3 mm) which provided good separation and resolution for all targeted analytes with a run time of 9 min. The method was validated using the following parameters: sensitivity, selectivity, linearity, accuracy, precision, recovery and matrix effects. The method was then applied to influent wastewater samples collected from two wastewater treatment plants in Wales, UK.
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BACKGROUND: Studies have linked daily pollen counts to respiratory allergic health outcomes, but few have considered allergen levels. OBJECTIVE: We sought to assess associations of grass pollen counts and grass allergen levels (Phl p 5) with respiratory allergic health symptoms in a panel of 93 adults with moderate-severe allergic rhinitis and daily asthma hospital admissions in London, United Kingdom. METHODS: Daily symptom and medication scores were collected from adult participants in an allergy clinical trial. Daily counts of asthma hospital admissions in the London general population were obtained from Hospital Episode Statistics data. Daily grass pollen counts were measured using a volumetric air sampler, and novel Phl p 5 levels were measured using a ChemVol High Volume Cascade Impactor and ELISA analyses (May through August). Associations between the 2 pollen variables and daily health scores (dichotomized based on within-person 75th percentiles) were assessed using generalized estimating equation logistic models and with asthma hospital admissions using Poisson regression models. RESULTS: Daily pollen counts and Phl p 5 levels were each positively associated with reporting a high combined symptom and medication health score in separate models. However, in mutually adjusted models including terms for both pollen counts and Phl p 5 levels, associations remained for Phl p 5 levels (odds ratio [95% CI]: 1.18 [1.12, 1.24]), but were heavily attenuated for pollen counts (odds ratio [95% CI]: 1.00 [0.93, 1.07]). Similar trends were not observed for asthma hospital admissions in London. CONCLUSIONS: Grass allergen (Phl p 5) levels are more consistently associated with allergic respiratory symptoms than grass pollen counts.
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Asma , Rinite Alérgica Sazonal , Rinite Alérgica , Adulto , Humanos , Rinite Alérgica Sazonal/epidemiologia , Pólen , Alérgenos , Poaceae , Asma/epidemiologia , Proteínas de Plantas/análiseRESUMO
BACKGROUND: Cancers are the leading cause of death in England. We aimed to estimate trends in mortality from leading cancers from 2002 to 2019 for the 314 districts in England. METHODS: We did a high-resolution spatiotemporal analysis of vital registration data from the UK Office for National Statistics using data on all deaths from the ten leading cancers in England from 2002 to 2019. We used a Bayesian hierarchical model to obtain robust estimates of age-specific and cause-specific death rates. We used life table methods to calculate the primary outcome, the unconditional probability of dying between birth and age 80 years by sex, cancer cause of death, local district, and year. We reported Spearman rank correlations between the probability of dying from a cancer and district-level poverty in 2019. FINDINGS: In 2019, the probability of dying from a cancer before age 80 years ranged from 0·10 (95% credible interval [CrI] 0·10-0·11) to 0·17 (0·16-0·18) for women and from 0·12 (0·12-0·13) to 0·22 (0·21-0·23) for men. Variation in the probability of dying was largest for lung cancer among women, being 3·7 times (95% CrI 3·2-4·4) higher in the district with the highest probability than in the district with the lowest probability; and for stomach cancer for men, being 3·2 times (2·6-4·1) higher in the district with the highest probability than in the one with the lowest probability. The variation in the probability of dying was smallest across districts for lymphoma and multiple myeloma (95% CrI 1·2 times [1·1-1·4] higher in the district with the highest probability than the lowest probability for women and 1·2 times [1·0-1·4] for men), and leukaemia (1·1 times [1·0-1·4] for women and 1·2 times [1·0-1·5] for men). The Spearman rank correlation between probability of dying from a cancer and district poverty was 0·74 (95% CrI 0·72-0·76) for women and 0·79 (0·78-0·81) for men. From 2002 to 2019, the overall probability of dying from a cancer declined in all districts: the reductions ranged from 6·6% (95% CrI 0·3-13·1) to 30·1% (25·6-34·5) for women and from 12·8% (7·1-18·8) to 36·7% (32·2-41·2) for men. However, there were increases in mortality for liver cancer among men, lung cancer and corpus uteri cancer among women, and pancreatic cancer in both sexes in some or all districts with posterior probability greater than 0·80. INTERPRETATION: Cancers with modifiable risk factors and potential for screening for precancerous lesions had heterogeneous trends and the greatest geographical inequality. To reduce these inequalities, factors affecting both incidence and survival need to be addressed at the local level. FUNDING: Wellcome Trust, Imperial College London, UK Medical Research Council, and the National Institute of Health Research.
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Neoplasias Hepáticas , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Idoso de 80 Anos ou mais , Lactente , Causas de Morte , Teorema de Bayes , Fatores de Risco , MortalidadeRESUMO
The rapid uptake of lithium ion batteries (LIBs) for large scale electric vehicle and energy storage applications requires a deeper understanding of the degradation mechanisms. Capacity fade is due to the complex interplay between phase transitions, electrolyte decomposition and transition metal dissolution; many of these poorly understood parasitic reactions evolve gases as a side product. Here we present an on-chip electrochemistry mass spectrometry method that enables ultra-sensitive, fully quantified and time resolved detection of volatile species evolving from an operating LIB. The technique's electrochemical performance and mass transport is described by a finite element model and then experimentally used to demonstrate the variety of new insights into LIB performance. We show the versatility of the technique, including (a) observation of oxygen evolving from a LiNiMnCoO2 cathode and (b) the solid electrolyte interphase formation reaction on graphite in a variety of electrolytes, enabling the deconvolution of lithium inventory loss (c) the first direct evidence, by virtue of the improved time resolution of our technique, that carbon dioxide reduction to ethylene takes place in a lithium ion battery. The emerging insight will guide and validate battery lifetime models, as well as inform the design of longer lasting batteries.
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Li-mediated ammonia synthesis is, thus far, the only electrochemical method for heterogeneous decentralized ammonia production. The unique selectivity of the solid electrode provides an alternative to one of the largest heterogeneous thermal catalytic processes. However, it is burdened with intrinsic energy losses, operating at a Li plating potential. In this work, we survey the periodic table to understand the fundamental features that make Li stand out. Through density functional theory calculations and experimentation on chemistries analogous to lithium (e.g., Na, Mg, Ca), we find that lithium is unique in several ways. It combines a stable nitride that readily decomposes to ammonia with an ideal solid electrolyte interphase, balancing reagents at the reactive interface. We propose descriptors based on simulated formation and binding energies of key intermediates and further on hard and soft acids and bases (HSAB principle) to generalize such features. The survey will help the community toward electrochemical systems beyond Li for nitrogen fixation.
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The COVID-19 pandemic is having a lasting impact on health and well-being. We compare current self-reported health, quality of life and symptom profiles for people with ongoing symptoms following COVID-19 to those who have never tested positive for SARS-CoV-2 infection and those who have recovered from COVID-19. Overall, 276,840/800,000 (34·6%) of invited participants took part. Mental health and health-related quality of life were worse among participants with ongoing persistent symptoms post-COVID compared with those who had never had COVID-19 or had recovered. In this study, median duration of COVID-related symptoms (N = 130,251) was 1·3 weeks (inter-quartile range 6 days to 2 weeks), with 7·5% and 5·2% reporting ongoing symptoms ≥12 weeks and ≥52 weeks respectively. Female sex, ≥1 comorbidity and being infected when Wild-type variant was dominant were associated with higher probability of symptoms lasting ≥12 weeks and longer recovery time in those with persistent symptoms. Although COVID-19 is usually of short duration, some adults experience persistent and burdensome illness.
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COVID-19 , Humanos , Adulto , Feminino , COVID-19/epidemiologia , Pandemias , Qualidade de Vida , SARS-CoV-2 , Inglaterra/epidemiologiaRESUMO
The global drug market has been significantly impacted by the emergence of new psychoactive substances, leading to challenges in creating effective legislative controls and their use within recreational drug consumption. This research explores the prevalence of new psychoactive substances and non-medicinal and medicinal compounds within a prison facility in Northern Ireland. Wastewater samples collected from seven different manholes within the prison were analysed for 37 target compounds including the two most found illicit substances: benzoylecgonine (primary metabolite of cocaine) and cannabis. Using solid phase extraction with Oasis HLB and liquid-chromatography-time-of-flight-mass spectrometry across a gradient of 9 min, our analysis revealed that benzoylecgonine was the sole compound consistently present in all collected samples. Following this finding, our target compound selection was broadened to encompass medicinal compounds and employing qualitative analysis we re-evaluated the samples and discovered the presence of buprenorphine, benzodiazepines, methadone, morphine, and codeine. Finally, the study explored the application of enzymatic beta-glucuronidase hydrolysis to the samples. This final phase yielded significant findings, indicating the presence of codeine and nordiazepam at higher peak intensities, thereby shedding light on the potential implications of this enzymatic process.
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Cannabis , Cocaína , Alucinógenos , Poluentes Químicos da Água , Águas Residuárias , Irlanda do Norte/epidemiologia , Prisões , Fármacos do Sistema Nervoso Central , Codeína , Poluentes Químicos da Água/análise , Detecção do Abuso de Substâncias/métodosRESUMO
Data System. The UK Department of Health and Social Care funded the REal-time Assessment of Community Transmission-2 (REACT-2) study to estimate community prevalence of SARS-CoV-2 IgG (immunoglobulin G) antibodies in England. Data Collection/Processing. We obtained random cross-sectional samples of adults from the National Health Service (NHS) patient list (near-universal coverage). We sent participants a lateral flow immunoassay (LFIA) self-test, and they reported the result online. Overall, 905 991 tests were performed (28.9% response) over 6 rounds of data collection (June 2020-May 2021). Data Analysis/Dissemination. We produced weighted estimates of LFIA test positivity (validated against neutralizing antibodies), adjusted for test performance, at local, regional, and national levels and by age, sex, and ethnic group and area-level deprivation score. In each round, fieldwork occurred over 2 weeks, with results reported to policymakers the following week. We disseminated results as preprints and peer-reviewed journal publications. Public Health Implications. REACT-2 estimated the scale and variation in antibody prevalence over time. Community self-testing and -reporting produced rapid insights into the changing course of the pandemic and the impact of vaccine rollout, with implications for future surveillance. (Am J Public Health. 2023;113(11):1201-1209. https://doi.org/10.2105/AJPH.2023.307381).
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COVID-19 , Adulto , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Prevalência , Estudos Transversais , Medicina Estatal , Anticorpos Antivirais , Imunoglobulina G , Inglaterra/epidemiologiaRESUMO
The value of SARS-CoV-2 lateral flow immunoassay (LFIA) tests for estimating individual disease risk is unclear. The REACT-2 study in England, UK, obtained self-administered SARS-CoV-2 LFIA test results from 361,801 adults in January-May 2021. Here, we link to routine data on subsequent hospitalisation (to September 2021), and death (to December 2021). Among those who had received one or more vaccines, a negative LFIA is associated with increased risk of hospitalisation with COVID-19 (HR: 2.73 [95% confidence interval: 1.15,6.48]), death (all-cause) (HR: 1.59, 95% CI:1.07, 2.37), and death with COVID-19 as underlying cause (20.6 [1.83,232]). For people designated at high risk from COVID-19, who had received one or more vaccines, there is an additional risk of all-cause mortality of 1.9 per 1000 for those testing antibody negative compared to positive. However, the LFIA does not provide substantial predictive information over and above that which is available from detailed sociodemographic and health-related variables. Nonetheless, this simple test provides a marker which could be a valuable addition to understanding population and individual-level risk.
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COVID-19 , Adulto , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Anticorpos Antivirais , Inglaterra/epidemiologia , Hospitalização , Teste para COVID-19RESUMO
BACKGROUND: Brownfield land is vacant or derelict land that was previously used for industrial or commercial purposes. Brownfield land is increasingly being targeted for housing development, however, depending on the previous use and remediation activity, it might pose potential risks to the health of residents on or in the vicinity of redeveloped sites. This systematic review of the literature synthesises the empirical evidence on the associations between brownfield land and health. METHODS: We systematically searched EMBASE, MEDLINE, Global Health, Web of Science, Scopus and GreenFile using a study protocol registered on PROSPERO (CRD42022286826). The search strategy combined the keywords "brownfield" and its interchangeable terms such as "previously developed land", and any health outcomes such as "respiratory diseases" and "mortality". Publications identified from the search were screened for eligibility by two authors, and data were extracted from the selected articles. Study quality was assessed based on the Newcastle-Ottawa Scale. RESULTS: Of the 1,987 records retrieved, 6 studies met the inclusion criteria; 3 ecological studies, 2 cross-sectional studies, and 1 longitudinal study. There was considerable heterogeneity in the exposure metrics and health outcomes assessed. All studies found significant positive associations between brownfield land proximity or density with at least one health relevant outcome, including poorer self-reported general health, increased mortality rates, increased birth defects, increased serum metal levels, and accelerated immune ageing. CONCLUSIONS: Brownfield land may negatively affect the health of nearby residents. The epidemiological evidence on health effects associated with brownfield land in local communities, however, remains inconclusive and limited. Further studies are required to build the evidence base to inform future housing policies and urban planning.
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Habitação , Indústrias , Humanos , Estudos Longitudinais , Estudos TransversaisRESUMO
Quantification of in vitro osteoclast cultures (e.g. cell number) often relies on manual counting methods. These approaches are labour intensive, time consuming and result in substantial inter- and intra-user variability. This study aimed to develop and validate an automated workflow to robustly quantify in vitro osteoclast cultures. Using ilastik, a machine learning-based image analysis software, images of tartrate resistant acid phosphatase-stained mouse osteoclasts cultured on dentine discs were used to train the ilastik-based algorithm. Assessment of algorithm training showed that osteoclast numbers strongly correlated between manual- and automatically quantified values (r = 0.87). Osteoclasts were consistently faithfully segmented by the model when visually compared to the original reflective light images. The ability of this method to detect changes in osteoclast number in response to different treatments was validated using zoledronate, ticagrelor, and co-culture with MCF7 breast cancer cells. Manual and automated counting methods detected a 70% reduction (p < 0.05) in osteoclast number, when cultured with 10 nM zoledronate and a dose-dependent decrease with 1-10 µM ticagrelor (p < 0.05). Co-culture with MCF7 cells increased osteoclast number by ≥ 50% irrespective of quantification method. Overall, an automated image segmentation and analysis workflow, which consistently and sensitively identified in vitro osteoclasts, was developed. Advantages of this workflow are (1) significantly reduction in user variability of endpoint measurements (93%) and analysis time (80%); (2) detection of osteoclasts cultured on different substrates from different species; and (3) easy to use and freely available to use along with tutorial resources.
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Reabsorção Óssea , Osteoclastos , Camundongos , Animais , Ácido Zoledrônico , Ticagrelor , Técnicas de Cocultura , Células Cultivadas , Fosfatase Ácida/análise , Fosfatase Ácida Resistente a Tartarato , Diferenciação CelularRESUMO
Extracellular pyrophosphate (PPi) is well known for its fundamental role as a physiochemical mineralisation inhibitor. However, information about its direct actions on bone cells remains limited. This study shows that PPi decreased osteoclast formation and resorptive activity by ≤50 %. These inhibitory actions were associated with reduced expression of genes involved in osteoclastogenesis (Tnfrsf11a, Dcstamp) and bone resorption (Ctsk, Car2, Acp5). In osteoblasts, PPi present for the entire (0-21 days) or latter stages of culture (7-21/14-21 days) decreased bone mineralisation by ≤95 %. However, PPi present for the differentiation phase only (0-7/0-14 days) increased bone formation (≤70 %). Prolonged treatment with PPi resulted in earlier matrix deposition and increased soluble collagen levels (≤2.3-fold). Expression of osteoblast (RUNX2, Bglap) and early osteocyte (E11, Dmp1) genes along with mineralisation inhibitors (Spp1, Mgp) was increased by PPi (≤3-fold). PPi levels are regulated by tissue non-specific alkaline phosphatase (TNAP) and ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). PPi reduced NPP1 expression in both cell types whereas TNAP expression (≤2.5-fold) and activity (≤35 %) were increased in osteoblasts. Breakdown of extracellular ATP by NPP1 represents a key source of PPi. ATP release from osteoclasts and osteoblasts was decreased ≤60 % by PPi and by a selective TNAP inhibitor (CAS496014-12-2). Pertussis toxin, which prevents Gαi subunit activation, was used to investigate whether G-protein coupled receptor (GPCR) signalling mediates the effects of PPi. The actions of PPi on bone mineralisation, collagen production, ATP release, gene/protein expression and osteoclast formation were abolished or attenuated by pertussis toxin. Together these findings show that PPi, modulates differentiation, function and gene expression in osteoblasts and osteoclasts. The ability of PPi to alter ATP release and NPP1/TNAP expression and activity indicates that cells can detect PPi levels and respond accordingly. Our data also raise the possibility that some actions of PPi on bone cells could be mediated by a Gαi-linked GPCR.
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Difosfatos , Osteoclastos , Osteoclastos/metabolismo , Difosfatos/farmacologia , Toxina Pertussis/metabolismo , Toxina Pertussis/farmacologia , Osteoblastos/metabolismo , Colágeno/metabolismo , Trifosfato de Adenosina/metabolismo , Fosfatase Alcalina/metabolismoRESUMO
Low emission zones (LEZs) and congestion charging zones (CCZs) have been implemented in several cities globally. We systematically reviewed the evidence on the effects of these air pollution and congestion reduction schemes on a range of physical health outcomes. We searched MEDLINE, Embase, Web of Science, IDEAS, Greenfile, and Transport Research International Documentation databases from database inception to Jan 4, 2023. We included studies that evaluated the effect of implementation of a LEZ or CCZ on air pollution-related health outcomes (cardiovascular and respiratory diseases, birth outcomes, dementia, lung cancer, diabetes, and all-cause) or road traffic injuries (RTIs) using longitudinal study designs and empirical health data. Two authors independently assessed papers for inclusion. Results were narratively synthesised and visualised using harvest plots. Risk of bias was assessed using the Graphic Appraisal Tool for Epidemiological studies. The protocol was registered with PROSPERO (CRD42022311453). Of 2279 studies screened, 16 were included, of which eight assessed LEZs and eight assessed CCZs. Several LEZ studies identified positive effects on air pollution-related outcomes, with reductions in some cardiovascular disease subcategories found in five of six studies investigating this outcome, although results for other health outcomes were less consistent. Six of seven studies on the London CCZ reported reductions in total or car RTIs, although one study reported an increase in cyclist and motorcyclist injuries and one reported an increase in serious or fatal injuries. Current evidence suggests LEZs can reduce air pollution-related health outcomes, with the most consistent effect on cardiovascular disease. Evidence on CCZs is mainly limited to London but suggests that they reduce overall RTIs. Ongoing evaluation of these interventions is necessary to understand longer term health effects.