Up-regulation of Tissue Factor in Human Pulmonary Artery Endothelial Cells after Ultrafine Particle Exposure

BACKGROUND: Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity, but the mechanisms remain unknown. OBJECTIVES: We tested the hypothesis that the ultrafine fraction of ambient pollutant particles would cause endothelial cell dysfunction. METHODS: We profiled gene expression of human pulmonary artery endothelial cells (HPAEC) exposed to ultrafine particles (UFPs; 100 μg/mL) from Chapel Hill, North Carolina, or vehicle for 4 hr with Affymetrix HG U133 Plus 2.0 chips (n = 4 each). RESULTS: We found 320 up-regulated genes and 106 down-regulated genes (p < 0.01, 5% false discovery rate). We noted up-regulation of genes related to coagulation [tissue factor (F3) and coagulation factor II receptor-like 2 (F2RL2)] and differential regulation of genes related to F3 signaling (FOS, JUN, and NFKBIA). Results of quantitative polymerase chain reaction show a significant up-regulation of F3 after 10 and 100 μg/mL UFP exposures. Additionally, the water-soluble fractions of UFPs were sufficient to induce the expression of F3, F2RL2, and heme oxygenase 1 (HMOX1). Treatment of HPAEC with UFPs for 16 hr increased the release of interleukin (IL)-6 and IL-8. Pretreatment of HPAEC with a blocking antibody against F3 attenuated IL-6 and IL-8 release by 30 and 70%, respectively. CONCLUSIONS: Using gene profiling, we discovered that UFPs may induce vascular endothelial cells to express genes related to clotting. These results indicate that PM may cause adverse cardiovascular health effects by activating coagulation-inflammation circuitry

Systematic review of dietary salt reduction policies: Evidence for an effectiveness hierarchy?

Background: Non-communicable disease (NCD) prevention strategies now prioritise four major risk factors: food, tobacco, alcohol and physical activity. Dietary salt intake remains much higher than recommended, increasing blood pressure, cardiovascular disease and stomach cancer. Substantial reductions in salt intake are therefore urgently needed. However, the debate continues about the most effective approaches. To inform future prevention programmes, we systematically reviewed the evidence on the effectiveness of possible salt reduction interventions. We further compared “downstream, agentic” approaches targeting individuals with “upstream, structural” policy-based population strategies. Methods: We searched six electronic databases (CDSR, CRD, MEDLINE, SCI, SCOPUS and the Campbell Library) using a pre-piloted search strategy focussing on the effectiveness of population interventions to reduce salt intake. Retrieved papers were independently screened, appraised and graded for quality by two researchers. To facilitate comparisons between the interventions, the extracted data were categorised using nine stages along the agentic/structural continuum, from “downstream”: dietary counselling (for individuals, worksites or communities), through media campaigns, nutrition labelling, voluntary and mandatory reformulation, to the most “upstream” regulatory and fiscal interventions, and comprehensive strategies involving multiple components. Results: After screening 2,526 candidate papers, 70 were included in this systematic review (49 empirical studies and 21 modelling studies). Some papers described several interventions. Quality was variable. Multi-component strategies involving both upstream and downstream interventions, generally achieved the biggest reductions in salt consumption across an entire population, most notably 4g/day in Finland and Japan, 3g/day in Turkey and 1.3g/day recently in the UK. Mandatory reformulation alone could achieve a reduction of approximately 1.45g/day (three separate studies), followed by voluntary reformulation (-0.8g/day), school interventions (-0.7g/day), short term dietary advice (-0.6g/day) and nutrition labelling (-0.4g/day), but each with a wide range. Tax and community based counselling could, each typically reduce salt intake by 0.3g/day, whilst even smaller population benefits were derived from health education media campaigns (-0.1g/day). Worksite interventions achieved an increase in intake (+0.5g/day), however, with a very wide range. Long term dietary advice could achieve a -2g/day reduction under optimal research trial conditions; however, smaller reductions might be anticipated in unselected individuals. Conclusions: Comprehensive strategies involving multiple components (reformulation, food labelling and media campaigns) and “upstream” population-wide policies such as mandatory reformulation generally appear to achieve larger reductions in population-wide salt consumption than “downstream”, individually focussed interventions. This ‘effectiveness hierarchy’ might deserve greater emphasis in future NCD prevention strategies

Unexpected detection of SARS-CoV-2 antibodies in the prepandemic period in Italy

There are no robust data on the real onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and spread in the prepandemic period worldwide. We investigated the presence of SARS-CoV-2 receptor-binding domain (RBD)–specific antibodies in blood samples of 959 asymptomatic individuals enrolled in a prospective lung cancer screening trial between September 2019 and March 2020 to track the date of onset, frequency, and temporal and geographic variations across the Italian regions. SARS-CoV-2 RBD-specific antibodies were detected in 111 of 959 (11.6%) individuals, starting from September 2019 (14%), with a cluster of positive cases (&gt;30%) in the second week of February 2020 and the highest number (53.2%) in Lombardy. This study shows an unexpected very early circulation of SARS-CoV-2 among asymptomatic individuals in Italy several months before the first patient was identified, and clarifies the onset and spread of the coronavirus disease 2019 (COVID-19) pandemic. Finding SARS-CoV-2 antibodies in asymptomatic people before the COVID-19 outbreak in Italy may reshape the history of pandemic

A Preliminary DTI Tractography Study of Developmental Neuroplasticity 5-15 Years After Early Childhood Traumatic Brain Injury

Plasticity is often implicated as a reparative mechanism when addressing structural and functional brain development in young children following traumatic brain injury (TBI); however, conventional imaging methods may not capture the complexities of post-trauma development. The present study examined the cingulum bundles and perforant pathways using diffusion tensor imaging (DTI) in 21 children and adolescents (ages 10-18 years) 5-15 years after sustaining early childhood TBI in comparison with 19 demographically-matched typically-developing children. Verbal memory and executive functioning were also evaluated and analyzed in relation to DTI metrics. Beyond the expected direction of quantitative DTI metrics in the TBI group, we also found qualitative differences in the streamline density of both pathways generated from DTI tractography in over half of those with early TBI. These children exhibited hypertrophic cingulum bundles relative to the comparison group, and the number of tract streamlines negatively correlated with age at injury, particularly in the late-developing anterior regions of the cingulum; however, streamline density did not relate to executive functioning. Although streamline density of the perforant pathway was not related to age at injury, streamline density of the left perforant pathway was significantly and positively related to verbal memory scores in those with TBI, and a moderate effect size was found in the right hemisphere. DTI tractography may provide insight into developmental plasticity in children post-injury. While traditional DTI metrics demonstrate expected relations to cognitive performance in group-based analyses, altered growth is reflected in the white matter structures themselves in some children several years post-injury. Whether this plasticity is adaptive or maladaptive, and whether the alterations are structure-specific, warrants further investigation

An unusual location of retroperitoneal epidermoid cyst in a child: case report and a review of the literature

We report the case of a 4-year-old girl presenting with the retroperitoneal epidermoid cyst. The lesion presented as an intra-abdominal cyst on physical examination and was followed up with more specific investigations by ultrasound and computed tomographic scanning. The final diagnosis was obtained only after laparotomy where the cystic mass was completely excised and pathological examination was done. The patient is well at 3-year follow-up. epidermoid cyst of the reteroperitoneal space, although rare, should be considered in the differential diagnosis of incidentally discovered intra-abdominal cysts during investigation of irrelevant illnesses or during routine abdominal ultrasound scan

Comparison of real-world treatment outcomes of systemic immunomodulating therapy in atopic dermatitis patients with dark and light skin types

Background Few data exist on differences in treatment effectiveness and safety in atopic dermatitis patients of different skin types. Objective To investigate treatment outcomes of dupilumab, methotrexate, and ciclosporin, and morphological phenotypes in atopic dermatitis patients, stratified by Fitzpatrick skin type. Methods In an observational prospective cohort study, pooling data from the Dutch TREAT (TREatment of ATopic eczema) NL (treatregister.nl) and UK-Irish A-STAR (Atopic eczema Systemic TherApy Register; astar-register.org) registries, data on morphological phenotypes and treatment outcomes were investigated. Results A total of 235 patients were included (light skin types [LST]: Fitzpatrick skin type 1-3, n = 156 [Ethnicity, White: 94.2%]; dark skin types [DST]: skin type 4-6, n = 68 [Black African/Afro-Caribbean: 25%, South-Asian: 26.5%, and Hispanics: 0%]). DST were younger (19.5 vs 29.0 years; P .05). Limitations Unblinded, non-randomized. Conclusion Atopic dermatitis differs in several characteristics between LST and DST. Skin type may influence treatment effectiveness of dupilumab

A peptide derived from TIMP-3 inhibits multiple angiogenic growth factor receptors and tumour growth and inflammatory arthritis in mice

The binding of vascular endothelial growth factor (VEGF) to VEGF receptor-2 (VEGFR-2) on the surface of vascular endothelial cells stimulates many steps in the angiogenic pathway. Inhibition of this interaction is proving of value in moderating the neovascularization accompanying age-related macular degeneration and in the treatment of cancer. Tissue inhibitor of metalloproteinases-3 (TIMP-3) has been shown to be a natural VEGFR-2 specific antagonist—an activity that is independent of its ability to inhibit metalloproteinases. In this investigation we localize this activity to the C-terminal domain of the TIMP-3 molecule and characterize a short peptide, corresponding to part of this domain, that not only inhibits all three VEGF-family receptors, but also fibroblast growth factor and platelet-derived growth factor receptors. This multiple-receptor inhibition may explain why the peptide was also seen to be a powerful inhibitor of tumour growth and also a partial inhibitor of arthritic joint inflammation in vivo

Phylogeography and Population Structure of Glossina fuscipes fuscipes in Uganda: Implications for Control of Tsetse

Glossina fuscipes fuscipes is the most common species of tsetse in Uganda, where it transmits human sleeping sickness and nagana, a related disease of cattle. A consortium of African countries dedicated to controlling these diseases is poised to begin area wide control of tsetse, but a critical question remains: What is the most appropriate geographical scale for these activities? To address this question, we used population genetics to determine the extent of linkage between populations of tsetse confined to discrete patches of riverine habitat. Our results suggest that Uganda was colonized by two distinct lineages of G. f. fuscipes, which now co-occur only in a narrow band across central Uganda. Evidence for interbreeding at the zone of contact and movement of genes from the south to the north suggest that this historical genetic structure may dissolve in the future. At smaller scales, we have demonstrated that exchange of genes among neighboring populations via dispersal is at equilibrium with the differentiating force of genetic drift. Our results highlight the need for investment in vector control programs that account for the linkage observed among tsetse populations. Given its genetic isolation and its location at the far edge of G. fuscipes' range, the Lake Victoria region appears to be an appropriate target for area wide control