Changing climate both increases and decreases European river floods.

Climate change has led to concerns about increasing river floods resulting from the greater water-holding capacity of a warmer atmosphere1. These concerns are reinforced by evidence of increasing economic losses associated with flooding in many parts of the world, including Europe2. Any changes in river floods would have lasting implications for the design of flood protection measures and flood risk zoning. However, existing studies have been unable to identify a consistent continental-scale climatic-change signal in flood discharge observations in Europe3, because of the limited spatial coverage and number of hydrometric stations. Here we demonstrate clear regional patterns of both increases and decreases in observed river flood discharges in the past five decades in Europe, which are manifestations of a changing climate. Our results-arising from the most complete database of European flooding so far-suggest that: increasing autumn and winter rainfall has resulted in increasing floods in northwestern Europe; decreasing precipitation and increasing evaporation have led to decreasing floods in medium and large catchments in southern Europe; and decreasing snow cover and snowmelt, resulting from warmer temperatures, have led to decreasing floods in eastern Europe. Regional flood discharge trends in Europe range from an increase of about 11 per cent per decade to a decrease of 23 per cent. Notwithstanding the spatial and temporal heterogeneity of the observational record, the flood changes identified here are broadly consistent with climate model projections for the next century4,5, suggesting that climate-driven changes are already happening and supporting calls for the consideration of climate change in flood risk management.

A Comparative Pharmacokinetic Study for Cysteamine-Containing Eye Drops as an Orphan Topical Therapy in Cystinosis.

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis.

Case-crossover study for the association between increased hospital admissions for respiratory diseases and the increase in atmospheric PM2.5 and PM2.5-bound trace elements in Pretoria, South Africa.

Outdoor PM2.5 was sampled in Pretoria, 18 April 2017 to 28 February 2020. A case-crossover epidemiology study was associated for increased PM2.5 and trace elements with increased hospital admissions for respiratory disorders (J00-J99). The results included a significant increase in hospital admissions, with total PM2.5 of 2.7% (95% CI: 0.6, 4.9) per 10 µg·m-3 increase. For the trace elements, Ca of 4.0% (95% CI: 1.4%-6.8%), Cl of 0.7% (95% CI: 0.0%-1.4%), Fe of 3.3% (95% CI: 0.5%-6.1%), K of 1.8% (95% CI: 0.2-3.5) and Si of 1.3% (95% CI: 0.1%-2.5%). When controlling for PM2.5, only Ca of 3.2% (95% CI: 0.3, 6.1) and within the 0-14 age group by 5.2% (95% CI: 1.5, 9.1). Controlling for a co-pollutant that is highly correlated with PM2.5 does reduce overestimation, but further studies should include deposition rates and parallel sampling analysis.

Source apportionment of fine atmospheric particles in Bloemfontein, South Africa, using positive matrix factorization.

Air pollution is of major health and environmental concern globally and in South Africa. Studies on the sources of PM2.5 air pollution in low- and middle-income countries such as South Africa are limited. This study aimed to identify local and distant sources of PM2.5 pollution in Bloemfontein. PM2.5 samples were collected from June 16, 2020 to August 18, 2021. Trace element concentrations were determined by EDXRF spectroscopy. By use of the US EPA PMF 5.0 program, local sources were determined to be combustion/wood burning (49%), industry (22%), soil dust (10%), base metal/pyrometallurgical and traffic (9.6%) and water treatment/industry (9.4%). The HYSPLIT program was applied to determine distant PM2.5 source areas and the following clusters were identified: Mpumalanga province (52%), Northern Cape province (35%), Indian Ocean (8%) and Atlantic Ocean (6%). The majority of the air was found to come from the Mpumalanga province in the north-east, while the majority of local sources are ascribed to combustion/wood burning. Results from this study can be used to develop an Air Quality Management Plan for Bloemfontein.

Intracellular signaling pathways of muscarinic acetylcholine receptor-mediated detrusor muscle contractions.

Acetylcholine plays an essential role in the regulation of detrusor muscle contractions, and antimuscarinics are widely used in the management of overactive bladder syndrome. However, several adverse effects limit their application and patients' compliance. Thus, this study aimed to further analyze the signal transduction of M2 and M3 receptors in the murine urinary bladder to eventually find more specific therapeutic targets. Experiments were performed on adult male wild-type, M2, M3, M2/M3, or Gαq/11 knockout (KO), and pertussis toxin (PTX)-treated mice. Contraction force and RhoA activity were measured in the urinary bladder smooth muscle (UBSM). Our results indicate that carbamoylcholine (CCh)-induced contractions were associated with increased activity of RhoA and were reduced in the presence of the Rho-associated kinase (ROCK) inhibitor Y-27632 in UBSM. CCh-evoked contractile responses and RhoA activation were markedly reduced in detrusor strips lacking either M2 or M3 receptors and abolished in M2/M3 KO mice. Inhibition of Gαi-coupled signaling by PTX treatment shifted the concentration-response curve of CCh to the right and diminished RhoA activation. CCh-induced contractile responses were markedly decreased in Gαq/11 KO mice; however, RhoA activation was unaffected. In conclusion, cholinergic detrusor contraction and RhoA activation are mediated by both M2 and M3 receptors. Furthermore, whereas both Gαi and Gαq/11 proteins mediate UBSM contraction, the activation at the RhoA-ROCK pathway appears to be linked specifically to Gαi. These findings may aid the identification of more specific therapeutic targets for bladder dysfunctions.NEW & NOTEWORTHY Muscarinic acetylcholine receptors are of utmost importance in physiological regulation of micturition and also in the development of voiding disorders. We demonstrate that the RhoA-Rho-associated kinase (ROCK) pathway plays a crucial role in contractions induced by cholinergic stimulation in detrusor muscle. Activation of RhoA is mediated by both M2 and M3 receptors as well as by Gi but not Gq/11 proteins. The Gi-RhoA-ROCK pathway may provide a novel therapeutic target for overactive voiding disorders.

Local thermal adaptation and local temperature regimes drive the performance of a parasitic helminth under climate change: The case of Marshallagia marshalli from wild ungulates.

Across a species' range, populations are exposed to their local thermal environments, which on an evolutionary scale, may cause adaptative differences among populations. Helminths often have broad geographic ranges and temperature-sensitive life stages but little is known about whether and how local thermal adaptation can influence their response to climate change. We studied the thermal responses of the free-living stages of Marshallagia marshalli, a parasitic nematode of wild ungulates, along a latitudinal gradient. We first determine its distribution in wild sheep species in North America. Then we cultured M. marshalli eggs from different locations at temperatures from 5 to 38°C. We fit performance curves based on the metabolic theory of ecology to determine whether development and mortality showed evidence of local thermal adaptation. We used parameter estimates in life-cycle-based host-parasite models to understand how local thermal responses may influence parasite performance under general and location-specific climate-change projections. We found that M. marshalli has a wide latitudinal and host range, infecting wild sheep species from New Mexico to Yukon. Increases in mortality and development time at higher temperatures were most evident for isolates from northern locations. Accounting for location-specific parasite parameters primarily influenced the magnitude of climate change parasite performance, while accounting for location-specific climates primarily influenced the phenology of parasite performance. Despite differences in development and mortality among M. marshalli populations, when using site-specific climate change projections, there was a similar magnitude of impact on the relative performance of M. marshalli among populations. Climate change is predicted to decrease the expected lifetime reproductive output of M. marshalli in all populations while delaying its seasonal peak by approximately 1 month. Our research suggests that accurate projections of the impacts of climate change on broadly distributed species need to consider local adaptations of organisms together with local temperature profiles and climate projections.

Long-term exposure to traffic noise and risk of incident colon cancer: A pooled study of eleven Nordic cohorts.

Background Colon cancer incidence is rising globally, and factors pertaining to urbanization have been proposed involved in this development. Traffic noise may increase colon cancer risk by causing sleep disturbance and stress, thereby inducing known colon cancer risk-factors, e.g. obesity, diabetes, physical inactivity, and alcohol consumption, but few studies have examined this. Objectives The objective of this study was to investigate the association between traffic noise and colon cancer (all, proximal, distal) in a pooled population of 11 Nordic cohorts, totaling 155,203 persons. Methods We identified residential address history and estimated road, railway, and aircraft noise, as well as air pollution, for all addresses, using similar exposure models across cohorts. Colon cancer cases were identified through national registries. We analyzed data using Cox Proportional Hazards Models, adjusting main models for harmonized sociodemographic and lifestyle data. Results During follow-up (median 18.8 years), 2757 colon cancer cases developed. We found a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 0.99-1.10) per 10-dB higher 5-year mean time-weighted road traffic noise. In sub-type analyses, the association seemed confined to distal colon cancer: HR 1.06 (95% CI: 0.98-1.14). Railway and aircraft noise was not associated with colon cancer, albeit there was some indication in sub-type analyses that railway noise may also be associated with distal colon cancer. In interaction-analyses, the association between road traffic noise and colon cancer was strongest among obese persons and those with high NO2-exposure. Discussion A prominent study strength is the large population with harmonized data across eleven cohorts, and the complete address-history during follow-up. However, each cohort estimated noise independently, and only at the most exposed façade, which may introduce exposure misclassification. Despite this, the results of this pooled study suggest that traffic noise may be a risk factor for colon cancer, especially of distal origin.

A unifying framework for the transient parasite dynamics of migratory hosts.

Migrations allow animals to track seasonal changes in resources, find mates, and avoid harsh climates, but these regular, long-distance movements also have implications for parasite dynamics and animal health. Migratory animals have been dubbed "superspreaders" of infection, but migration can also reduce parasite burdens within host populations via migratory escape from contaminated habitats and transmission hotspots, migratory recovery due to parasite mortality, and migratory culling of infected individuals. Here, we show that a single migratory host-macroparasite model can give rise to these different phenomena under different parametrizations, providing a unifying framework for a mechanistic understanding of the parasite dynamics of migratory animals. Importantly, our model includes the impact of parasite burden on host movement capability during migration, which can lead to "parasite-induced migratory stalling" due to a positive feedback between increasing parasite burdens and reduced movement. Our results provide general insight into the conditions leading to different health outcomes in migratory wildlife. Our approach lays the foundation for tactical models that can help understand, predict, and mitigate future changes of disease risk in migratory wildlife that may arise from shifting migratory patterns, loss of migratory behavior, or climate effects on parasite development, mortality, and transmission.

Health risk assessment of PM2.5 and PM2.5-bound trace elements in Pretoria, South Africa.

Exposure to outdoor air pollutants poses a risk for both non-carcinogenic and carcinogenic respiratory disease outcomes. A standardized health risk assessment (US EPA) utilizes air quality data, body mass and breathing rates to determine potential risk. This health risk assessment study assesses the hazard quotient (HQ) for total PM2.5 and trace elemental constituents (Br, Cl, K, Ni, S, Si, Ti and U) exposure in Pretoria, South Africa. The World Health Organization (WHO) air quality guideline (5 µg m-3) and the yearly South African National Ambient Air Quality Standard (NAAQS) (20 µg m-3) were the references dosages for total PM2.5. A total of 350 days was sampled in Pretoria, South Africa. The mean total PM2.5 concentration during the 34-month study period was 23.2 µg m-3 (0.7-139 µg m-3). The HQ for total PM2.5 was 1.17, 3.47 and 3.78 for adults, children and infants. Non-carcinogenic risks for trace elements K, Cl, S and Si were above 1 for adults. Seasonally, Si was the highest during autumn for adults (1.9) and during spring for S (5.5). The HQ values for K and Cl were highest during winter. The exposure to Ni posed a risk for cancer throughout the year and for As during winters.

The effects of phylogeny, habitat and host characteristics on the thermal sensitivity of helminth development.

Helminth parasites are part of almost every ecosystem, with more than 300 000 species worldwide. Helminth infection dynamics are expected to be altered by climate change, but predicting future changes is difficult owing to lacking thermal sensitivity data for greater than 99.9% of helminth species. Here, we compiled the largest dataset to date on helminth temperature sensitivities and used the Metabolic Theory of Ecology to estimate activation energies (AEs) for parasite developmental rates. The median AE for 129 thermal performance curves was 0.67, similar to non-parasitic animals. Although exceptions existed, related species tended to have similar thermal sensitivities, suggesting some helminth taxa are inherently more affected by rising temperatures than others. Developmental rates were more temperature-sensitive for species from colder habitats than those from warmer habitats, and more temperature sensitive for species in terrestrial than aquatic habitats. AEs did not depend on whether helminth life stages were free-living or within hosts, whether the species infected plants or animals, or whether the species had an endotherm host in its life cycle. The phylogenetic conservatism of AE may facilitate predicting how temperature change affects the development of helminth species for which empirical data are lacking or difficult to obtain.

Human disturbance and shifts in vertebrate community composition in a biodiversity hotspot.

Understanding how human modification of the landscape shapes vertebrate community composition is vital to understanding the current status and future trajectory of wildlife. Using a participatory approach, we deployed the largest camera-trap network in Mesoamerica to date to investigate how anthropogenic disturbance shapes the occupancy and co-occurrence of terrestrial vertebrate species in a tropical biodiversity hotspot: the Osa Peninsula, Costa Rica. We estimated species richness in different categories of land protection with rarefaction analysis and estimated the expected occupancy with a joint species distribution model that included covariates for anthropogenic disturbance, land protection, habitat quality, and habitat availability. Areas with the most stringent land-use protections (e.g., Corcovado National Park, 24 species [95% CI 23-25]) harbored significantly more species than unprotected areas (20 species [19.7-20.3]), mainly due to a reduced presence of large-bodied species of conservation concern in unprotected areas (e.g., jaguar Panthera onca and white-lipped peccary Tayassu pecari). Small-bodied generalist species, such as opossums (Didelphidae) and armadillos (Dasypus novemcinctus), in contrast, were more common at disturbed sites, resulting in a significant difference in vertebrate community composition between sites with low and high disturbance. Co-occurrence of species was also mainly associated with response to disturbance. Similar responses to disturbance create two groups of species, those whose site-level occupancy usually increased as anthropogenic disturbance increased and those whose estimated occupancy decreased. The absence of large-bodied species entails an important loss of ecological function in disturbed areas and can hinder forest development and maintenance. Efforts to protect and restore forested landscapes are likely having a positive effect on the abundance of some threatened species. These efforts, however, must be sustained and expanded to increase connectivity and ensure the long-term viability of the wildlife community.

Perturbaciones Humanas y Cambios en la Composición de la Comunidad de Vertebrados en un Punto Caliente de Biodiversidad Resumen El entendimiento de cómo las modificaciones humanas del paisaje conforman la composición de las comunidades de vertebrados es vital para entender el estado actual y la trayectoria futura de la fauna. Mediante una estrategia participativa, desplegamos la mayor red de cámaras trampa en Mesoamérica hasta la fecha para investigar cómo la perturbación antropogénica determina la ocupación y coocurrencia de las especies terrestres de vertebrados en un punto caliente de biodiversidad tropical: la Península de Osa, Costa Rica. Estimamos la riqueza de especies en diferentes categorías de protección de suelo con un análisis de rarefacción y estimamos la ocupación esperada con un modelo de distribución conjunta de especies que incluyó covariables para la perturbación antropogénica, la protección del suelo, la calidad del hábitat y la disponibilidad del hábitat. Las áreas con la protección más estricta de uso de suelo (p. ej.: Parque Nacional Corcovado, 24 especies [95% CI 23-25]) albergaron significativamente a más especies que las áreas desprotegidas (20 especies [19.7-20.3]), principalmente debido a la presencia reducida de especies de talla grande de interés para la conservación en las áreas desprotegidas (p. ej.: el jaguar Panthera onca, el pecarí de labios blancos, Tayassu pecari). Al contrario, las especies generalistas de talla pequeña, como las zarigüeyas (Didelphidae) y el armadillo (Dasypus novemcinctus) fueron más comunes en los sitios perturbados, lo que resulta en una diferencia significativa en la composición de las comunidades de vertebrados entre los sitios con una perturbación baja y alta. La coocurrencia de especies también estuvo asociada principalmente con la respuesta a la perturbación. Las respuestas similares a la perturbación crean dos grupos de especies: aquellas cuya ocupación a nivel de sitio generalmente incrementó conforme incrementó la perturbación antropogénica y aquellas cuya ocupación estimada disminuyó. La ausencia de especies de talla grande conlleva una pérdida importante de la función ecológica en las áreas perturbadas y puede dificultar el desarrollo y mantenimiento del bosque. Los esfuerzos para proteger y restaurar los paisajes forestales probablemente estén teniendo un efecto positivo sobre la abundancia de algunas especies amenazadas. Estos esfuerzos, sin embargo, deben ser sostenidos y expandidos para incrementar la conectividad y asegurar la viabilidad a largo plazo de la comunidad faunística.

Occupational noise exposure and risk of incident stroke: a pooled study of five Scandinavian cohorts.

OBJECTIVES: To investigate the association between occupational noise exposure and stroke incidence in a pooled study of five Scandinavian cohorts (NordSOUND). METHODS: We pooled and harmonised data from five Scandinavian cohorts resulting in 78 389 participants. We obtained job data from national registries or questionnaires and recoded these to match a job-exposure matrix developed in Sweden, which specified the annual average daily noise exposure in five exposure classes (LAeq8h): <70, 70-74, 75-79, 80-84, ≥85 dB(A). We identified residential address history and estimated 1-year average road traffic noise at baseline. Using national patient and mortality registers, we identified 7777 stroke cases with a median follow-up of 20.2 years. Analyses were conducted using Cox proportional hazards models adjusting for individual and area-level potential confounders. RESULTS: Exposure to occupational noise at baseline was not associated with overall stroke in the fully adjusted models. For ischaemic stroke, occupational noise was associated with HRs (95% CI) of 1.08 (0.98 to 1.20), 1.09 (0.97 to 1.24) and 1.06 (0.92 to 1.21) in the 75-79, 80-84 and ≥85 dB(A) exposure groups, compared with <70 dB(A), respectively. In subanalyses using time-varying occupational noise exposure, we observed an indication of higher stroke risk among the most exposed (≥85 dB(A)), particularly when restricting analyses to people exposed to occupational noise within the last year (HR: 1.27; 95% CI: 0.99 to 1.63). CONCLUSIONS: We found no association between occupational noise and risk of overall stroke after adjustment for confounders. However, the non-significantly increased risk of ischaemic stroke warrants further investigation.

PDGF-BB-mediated activation of CREB in vascular smooth muscle cells alters cell cycling via Rb, FoxO1 and p27kip1.

INTRODUCTION & AIM: The vascular response to injury leads to the secretion of several factors, including platelet-derived growth factor (PDGF-BB). PDGF-BB stimulates smooth muscle cell (SMC) conversion to the synthetic phenotype, thereby enhancing proliferation and migration, and contributing to neointimal hyperplasia. Likewise, the cAMP response element binding protein (CREB) transcription factor has been shown to mediate SMC proliferation in response to various mitogens. We therefore investigated the contribution of CREB to PDGF-BB-dependent proliferation of SMCs with the intention of identifying signaling pathways involved both up and downstream of CREB activation. METHODS & RESULTS: Treatments were performed on vascular SMCs from a porcine coronary artery explant model. The role of CREB was examined via adenoviral expression of a dominant-negative CREB mutant (kCREB) as well as inhibition of CREB binding protein (CBP). Involvement of the p27kip1 pathway was determined using a constitutively expressing p27kip1 adenoviral vector. PDGF-BB stimulated transient CREB phosphorylation on Ser-133 via ERK1/2-, PI3-kinase- and Src-dependent pathways. Expression of kCREB decreased PDGF-BB-dependent cell proliferation. PCNA expression and Rb phosphorylation were also inhibited by kCREB. These cell cycle proteins are controlled via p27kip1 expression in response to CREB-dependent post-translational modification of FoxO1. kCREB had no effect on Cyclin D1 expression, but did prevent PDGF-BB-induced Cyclin D1 nuclear translocation. An interaction inhibitor of CBP confirmed that Cyclin D1 is downstream of PDGF-BB and CREB. CONCLUSION: CREB phosphorylation is required for SMC proliferation in response to PDGF-BB. This phenotypic change requires CBP and is mediated by Cyclin D1 and p27kip as a result of changes in FoxO1 activity.

Incident cardiovascular disease and long-term exposure to source-specific air pollutants in a Swedish cohort.

BACKGROUND: Air pollution is associated with cardiovascular morbidity and mortality, but its role in the development of congestive heart failure (CHF) and the role of different pollution sources in cardiovascular disease remain uncertain. METHODS: Participants were enrolled in the Malmö Diet and Cancer cohort in 1991-1996 with information on lifestyle and clinical indicators of cardiovascular disease. The cohort participants were followed through registers until 2016. Annual total and local source-specific concentrations of particulate matter less than 10 µm and 2.5 µm (PM10 and PM2.5), black carbon (BC), and nitrogen oxides (NOx) from traffic, residential heating, and industry were assigned to each participant's address throughout the study period. Cox proportional hazards models adjusted for possible confounders was used to estimate associations between air pollution 1-5 years prior to outcomes of incident CHF, fatal myocardial infarction (MI), major adverse coronary events (MACE), and ischemic stroke. RESULTS: Air pollution exposure levels (mean annual exposures to PM2.5 of 11 µg/m3 and NOx of 26 µg/m3) within the cohort were moderate in terms of environmental standards. After adjusting for confounders, we observed statistically significant associations between NOx and CHF (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.01-1.22) and NOx and fatal MI (HR 1.10, 95%CI 1.01-1.20) per interquartile range (IQR) of 9.6 µg/m3. In fully adjusted models, the estimates were similar, but the precision worse. In stratified analyses, the associations were stronger in males, ever-smokers, older participants, and those with baseline carotid artery plaques. Locally emitted and traffic-related air pollutants generally showed positive associations with CHF and fatal MI. There were no associations between air pollution and MACE or stroke. DISCUSSION/CONCLUSION: In an area with low to moderate air pollution exposure, we observed significant associations of long-term residential NOx with increased risk of incident CHF and fatal MI, but not with coronary events and stroke.

Long-term exposure to air pollution, coronary artery calcification, and carotid artery plaques in the population-based Swedish SCAPIS Gothenburg cohort.

Long-term exposure to air pollution is associated with cardiovascular events. A main suggested mechanism is that air pollution accelerates the progression of atherosclerosis, yet current evidence is inconsistent regarding the association between air pollution and coronary artery and carotid artery atherosclerosis, which are well-established causes of myocardial infarction and stroke. We studied associations between low levels of long-term air pollution, coronary artery calcium (CAC) score, and the prevalence and area of carotid artery plaques, in a middle-aged population-based cohort. The Swedish CArdioPulmonary bioImage Study (SCAPIS) Gothenburg cohort was recruited during 2013-2017 and thoroughly examined for cardiovascular risk factors, including computed tomography of the heart and ultrasonography of the carotid arteries. In 5070 participants (age 50-64 years), yearly residential exposures to air pollution (PM2.5, PM10, PMcoarse, NOx, and exhaust-specific PM2.5 1990-2015) were estimated using high-resolution dispersion models. We used Poisson regression to examine associations between long-term (26 years' mean) exposure to air pollutants and CAC score, and prevalence of carotid artery plaques, adjusted for potential confounders. Among participants with carotid artery plaques, we also examined the association with plaque area using linear regression. Mean exposure to PM2.5 was low by international standards (8.5 µg/m3). There were no consistent associations between long-term total PM2.5 exposure and CAC score or presence of carotid artery plaques, but an association between total PM2.5 and larger plaque area in participants with carotid plaques. Associations with traffic-related air pollutants were consistently positive for both a high CAC score and bilateral carotid artery plaques. These associations were independent of road traffic noise. We found stronger associations among men and participants with cardiovascular risk factors. The results lend some support to atherosclerosis as a main modifiable pathway between low levels of traffic-related ambient air pollution and cardiovascular disease, especially in vulnerable individuals.

Air pollution and biomarkers of cardiovascular disease and inflammation in the Malmö Diet and Cancer cohort.

INTRODUCTION: Air pollution is associated with increased risk of cardiovascular disease, possibly through chronic systemic inflammation that promotes the progression of atherosclerosis and the risk of cardiovascular events. This study aimed to investigate the associations between air pollution and established biomarkers of inflammation and cardiovascular disease. METHODS: The Cardiovascular Subcohort of the Malmö Diet and Cancer cohort includes 6103 participants from the general population of Malmö, Sweden. The participants were recruited 1991-1994. Annual mean residential exposure to particulate matter < 2.5 and < 10 µm (PM2.5 and PM10), and nitrogen oxides (NOx) at year of recruitment were assigned from dispersion models. Blood samples collected at recruitment, including blood cell counts, and biomarkers (lymphocyte- and neutrophil counts, C-reactive protein (CRP), soluble urokinase-type plasminogen activator receptor (suPAR), lipoprotein-associated phospholipase A2 (Lp-PLA2), ceruloplasmin, orosomucoid, haptoglobin, complement-C3, and alpha-1-antitrypsin) were analyzed. Multiple linear regression models were used to investigate the cross-sectional associations between air pollutants and biomarkers. RESULTS: The mean annual exposure levels in the cohort were only slightly or moderately above the new WHO guidelines of 5 µg/m3 PM2.5 (10.5 µg/m3 PM2.5). Residential PM2.5 exposure was associated with increased levels of ceruloplasmin, orosomucoid, C3, alpha-1-antitrypsin, haptoglobin, Lp-PLA2 and the neutrophil-lymphocyte ratio. Ceruloplasmin, orosomucoid, C3 and alpha-1-antitrypsin were also positively associated with PM10. There were no associations between air pollutants and suPAR, leukocyte counts or CRP. The associations between particles and biomarkers were still significant after removing outliers and adjustment for CRP levels. The associations were more prominent in smokers. CONCLUSION: Long-term residential exposure to moderate levels of particulate air pollution was associated with several biomarkers of inflammation and cardiovascular disease. This supports inflammation as a mechanism behind the association between air pollution and cardiovascular disease.

Particulate Matter (PM2.5) Characterization, Air Quality Level and Origin of Air Masses in an Urban Background in Pretoria.

Several sources have been identified as contributing to the concentration of ambient fine particulate matter, which has been associated to a variety of health issues. The chemical characteristics and sources of trace elements in PM2.5, as well as the air quality index, were investigated in this study. Twenty four-hour fine aerosol particles were collected in an urban area in Pretoria, South Africa, from April 2017 to April 2018. Eighteen trace elements were determined using an XEPOS 5 energy-dispersive X-ray fluorescence (EDXRF) spectrometer, while black and organic carbon were estimated using an optical transmissometer from the samples collected. The HYPLIT model (version 4.9) was used to estimate air mass trajectories. Health risk was calculated by comparing it to the World Health Organization's air quality index (AQI). The overall mean PM2.5 concentration of the collected sample equals 21 µg/m3. Majority of PM2.5 exceedances were reported during mid-autumn and winter seasons, as compared to daily WHO guidelines and South African standards. S had the highest concentrations, greater than 1 µg/m3. Ni, Se, Br and Sb showed they were extremely enriched, (EF > 10) and suggestive of anthropogenic or non crustal origin The 24-h PM, soot, BC and OC were significantly different by the geographical origin of air masses (p < 0.05). The AQI showed that 70% of the samples showed levels above the AQI range of good and healthy air. The findings include details on the concentration, composition, and potential sources of fine PM2.5, which is essential for policy formulation and mitigation strategies in South Africa's fight against air pollution.

Comparison of the short-term complications of TTA-rapid and modified cTTA procedures.

The objective of this retrospective study was to determine the complications of the first 30 tibial tuberosity advancement rapid (TTA-rapid) and 30 modified circular tibial tuberosity advancement (mcTTA) procedures performed by our team, and to compare the results with the findings reported in the literature. Our research was based on 30 procedures in each group. All dogs were client-owned. Data were collected only for the study of cases that had a minimum follow-up period of 3 months. Intraoperative (IO) and postoperative (PO) complications were assessed, with the latter divided into two subgroups: major and minor. Results obtained for the TTA-rapid group: IO complications 23.3% (7/30), major PO complications 13.3% (4/30), minor PO complications 16.7% (5/30). Results of the mcTTA group: IO complications 0% (0/30), major PO complications 3.3% (1/30), minor PO complications 20% (6/30). Comparing the complication rates, we found that there was a significant difference between the two groups in the occurrence of IO complications (P = 0.01054); however, there was no significant difference in the incidence of major (P = 0.3533) and minor (P > 0.9999) PO complications between groups. Our results are consistent with the findings reported in the literature and suggest that both techniques are efficient and carry a relatively low complication rate.

Biomechanical testing of canine tibiae: Changes resulting from different tibial tuberosity advancement techniques - Pilot study.

The objective of the present pilot study was to determine the force required to break (a) intact canine tibiae, (b) tibiae following the osteotomy of the tibial tuberosity and (c) tibiae following Tibial Tuberosity Advancement- (TTA-) rapid surgery. Six pairs of tibiae of dogs between 15 and 35 kg body weight were used in a cadaver study. Three groups were created with four tibiae in each group; intact (Group 1), osteotomy of the tibial tuberosity and tibial crest (Group 2) and TTA-rapid (Group 3). The tibiae were put under static axial compressive load, applied until failure. The force required to break the tibiae was termed maximal force (F max). The mean of F max was 8193.25 ± 2082.84 N in Group 1, 6868.58 ± 1950.44 N in Group 2 and 7169.71 ± 4450.39 N in Group 3. The sample size was small for a statistical analysis but as a preliminary result, we have determined the force (F max) required to break canine tibiae. Furthermore, we hypothesise that osteotomies result in weakening of the tibial structure.

Connectedness of energy markets around the world during the COVID-19 pandemic.

This paper studies the connectedness among energy equity indices of oil-exporting and oil-importing countries around the world. For each country, we construct time-varying measures of how much shocks this country transmits to other countries and how much shocks this country receives from other countries. We analyze the network of countries and find that, on average, oil-exporting countries are mainly transmitting shocks, and oil-importing countries are mainly receiving shocks. Furthermore, we use panel data regressions to evaluate whether the connectedness among countries is influenced by economic sentiment, uncertainty, and the global COVID-19 pandemic. We find that the connectedness among countries increases significantly in periods of uncertainty, low economic sentiment, and COVID-19 problems. This implies that diversification benefits across countries are severely reduced exactly during crises, that is, during the times when diversification benefits are most important.