Inhalation exposure to nanosized and fine TiO2 particles inhibits features of allergic asthma in a murine model

<p>Abstract</p> <p>Background</p> <p>Nanotechnology and engineered nanomaterials (ENM) are here to stay. Recent evidence suggests that exposure to environmental particulate matter exacerbates symptoms of asthma. In the present study we investigated the modulatory effects of titanium dioxide particle exposure in an experimental allergic asthma.</p> <p>Methods</p> <p>Nonallergic (healthy) and ovalbumin-sensitized (asthmatic) mice were exposed via inhalation to two different sizes of titanium dioxide particles, nanosized (nTiO₂) and fine (fTiO₂), for 2 hours a day, three days a week, for four weeks at a concentration of 10 mg/m³. Different endpoints were analysed to evaluate the immunological status of the mice.</p> <p>Results</p> <p>Healthy mice elicited pulmonary neutrophilia accompanied by significantly increased chemokine CXCL5 expression when exposed to nTiO₂. Surprisingly, allergic pulmonary inflammation was dramatically suppressed in asthmatic mice which were exposed to nTiO₂or fTiO₂particles - i.e. the levels of leucocytes, cytokines, chemokines and antibodies characteristic to allergic asthma were substantially decreased.</p> <p>Conclusions</p> <p>Our results suggest that repeated airway exposure to TiO₂particles modulates the airway inflammation depending on the immunological status of the exposed mice.</p

A test of the effort equalization hypothesis in children with cerebral palsy who have an asymmetric gait

Healthy people can walk nearly effortlessly thanks to their instinctively adaptive gait patterns that tend to minimize metabolic energy consumption. However, the economy of gait is severely impaired in many neurological disorders such as stroke or cerebral palsy (CP). Moreover, self-selected asymmetry of impaired gait does not seem to unequivocally coincide with the minimal energy cost, suggesting the presence of other adaptive origins. Here, we used hemiparetic CP gait as a model to test the hypothesis that pathological asymmetric gait patterns are chosen to equalize the relative muscle efforts between the affected and unaffected limbs. We determined the relative muscle efforts for the ankle and knee extensors by relating extensor joint moments during gait to maximum moments obtained from all-out hopping reference test. During asymmetric CP gait, the unaffected limb generated greater ankle (1.36 +/- 0.15 vs 1.17 +/- 0.16 Nm/kg, p = 0.002) and knee (0.74 +/- 0.33 vs 0.44 +/- 0.19 Nm/kg, p = 0.007) extensor moments compared with the affected limb. Similarly, the maximum moment generation capacity was greater in the unaffected limb versus the affected limb (ankle extensors: 1.81 +/- 0.39 Nm/kg vs 1.51 +/- 0.34 Nm/kg, p = 0.033; knee extensors: 1.83 +/- 0.37 Nm/kg vs 1.34 +/- 0.38 Nm/kg, p = 0.021) in our force reference test. As a consequence, no differences were found in the relative efforts between unaffected and affected limb ankle extensors (77 +/- 12% vs 80 +/- 16%, p = 0.69) and knee extensors (41 +/- 17% vs 38 +/- 23%, p = 0.54). In conclusion, asymmetric CP gait resulted in similar relative muscle efforts between affected and unaffected limbs. The tendency for effort equalization may thus be an important driver of self-selected gait asymmetry patterns, and consequently advantageous for preventing fatigue of the weaker affected side musculature.Peer reviewe

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P= 3.96 x 10(-14)). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P= 3.96 x 10(-14)). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality

A deep dive into the birth process of linking 6G and the UN SDGs

Abstract United Nations Sustainable Development Goals (UN SDGs) are becoming an increasingly important theme for researchers in multiple fields to investigate. In this paper, we look at how a group of 40 experts from academia and the mobile communications industry identified ways in which future 6th generation (6G) mobile communications is linked with the UN SDGs while writing a white paper on the topic. In this paper, building on the methodology of critical participatory action research, we look into the detailed operations of the expert group, offer a new way to look at the 6G development process guided by the UN SDGs and describe the linking process for the UN SDGs and 6G in a way that may guide other researchers in similar endeavors. We also present initial outcomes of the linking process that led to the white paper published in 2020 (Matinmikko-Blue et al., 2020). The aim of this research is to identify and formulate a process to recognise the connection between UN SDGs and 6G

Modes of Collaboration in Digital Transformation of Municipal Wastewater Management

Abstract Digital transformation introduces new opportunities for public services, such as wastewater management. The opportunities include better interoperability and data availability, leading to such benefits as predictive maintenance and efficient allocation of resources. To reach the envisioned benefits, inter-organisational collaboration is essential. However, municipal water utilities have varying objectives, expectations, and challenges related to collaboration. This paper reports a field study on the digitalisation opportunities of municipal water services in Finland. We report the observed collaboration forms, rationale, expected benefits, and recognised challenges (i.e., the modes of inter-organizational collaboration) for deploying digitalised operations. This study provides insight into inter-organisational collaboration on the digital transformation of municipal water management. On a theoretical level, the study supports and complements the previously theorised collaboration modes of autonomous development, standardisation, and central service organization. The results also describe why and how limited company mode emerges in the sector, corresponding to the previously described consortium mode