Thermally induced behavior of the K-exchanged erionite. A further step in understanding the structural modifications of the erionite group upon heating

Fibrous erionite is a naturally occurring zeolite considered to be highly carcinogenic upon inhalation, even more than crocidolite. Since no iron is typically present in erionite, its toxicity has been attributed to ion-exchanged Fe participating in Fenton chemistry. Recently, a study aimed at investigating possible fiber inactivation routes surprisingly showed that, despite having completely occluded all available pores with K ions, the erionite-Na sample preserved the property to upload Fe (II) within the structure. In this work, the thermal behavior of the K-exchanged erionite-Na was investigated by TG/ DSC and in situ XRPD analyses in order to provide relevant information for modeling the thermally induced behavior of the erionite group. Rietveld refinement results evidenced a general trend of cell parameters and volume with temperature similar to that observed for erionite-K from Rome (Oregon, USA). However, the dependence of Tdehydrand Tbreakfrom Si/Si+Al ratio observed in zeolites (high Si content favours a lower Tdehydrand a higher Tbreak) is not observed, possibly due to the effect of the relevant amount of large K ions dispersed within the erionite cage, acting as reinforcing blocks for the framework. Heating produces a progressive emptying of the Ca sites, common effect previously observed in erionite samples showing different chemistry. In addition, K1 s.s. remains unchanged evidencing the absence of any “internal ion exchange” process, whereas s.s. at K2 increases in the range 438-573 K and then slowly decreases in the range 700-1218 K. Both Rietveld and DSC data suggest the motion of K ions from OW sites toward the walls of the erionite cavity during dehydration

Surface and Bulk Modifications of Fibrous Erionite in Mimicked Gamble's Solution at Acidic pH

This study aimed at investigating both the surface and bulk modifications occurring on fibrous erionite during leaching in a mimicked Gamble's solution (MGS) at pH of 4.5 and T = 37 degrees C, up to one month of incubation. Samples were characterized by a multi-analytical approach: field-emission scanning electron microscopy (FE-SEM) was employed to investigate the morphological changes of both pristine and reacted fibres, inductively coupled plasma optical emission spectrometry (ICP-OES) was used to measure the concentration of the released cations; X-ray photoelectron spectroscopy (XPS) was exploited for highlighting possible modifications of surface chemistry; X-ray powder diffraction (XRPD) and high-resolution transmission electron microscopy (HR-TEM) were applied aiming to get information on the structural state of the fibres following the incubation. ICP results integrated with those obtained by both bulk- and surface-chemical characterization highlighted that erionite binds Na especially in the first 24 h of sample incubation in the MGS, following ion exchange with the extra framework cations, in particular Ca. Moreover, our new results show that the Na binding process caused structural modifications with the migration of Na toward the Ca2 site and redistribution of the cations within the erionite cage. TEM investigation pointed out that the interaction between erionite and MGS results in the formation of a new surface amorphous layer with an irregular lobate pattern on an earlier surface weathered layer. However, the silicate framework is not weakened by incubation in the MGS at acidic pH. In addition, on the basis of the Si release normalized to the mineral surface area, fibrous erionite resulted significantly more biodurable than amphibole asbestos. Notably, considering the primary role played by biodurability in inducing pathogenicity, this result certainly supports in vivo observations showing that erionite is much more tumorigenic than asbestos. Moreover, the ions released by erionite when immersed in MGS may trigger biological effects, such as those on lipid packing and membrane permeability. On this basis, we expect a regulatory definition that would provide protection from this carcinogenic fibre

Surface and bulk modifications of amphibole asbestos in mimicked gamble's solution at acidic PH

This study aimed at investigating the surface modifications occurring on amphibole asbestos (crocidolite and tremolite) during leaching in a mimicked Gamble’s solution at pH of 4.5 and T = 37 °C, from 1 h up to 720 h. Results showed that the fibre dissolution starts with the release of cations prevalently allocated at the various M- and (eventually) A-sites of the amphibole structure (incongruent dissolution). The amount of released silicon, normalized to fibre surface area, highlighted a leaching faster for the crocidolite sample, about twenty times higher than that of tremolite. Besides, the fast alteration of crocidolite promotes the occurrence of Fe centres in proximity of the fibre surface, or possibly even exposed, particularly in the form of Fe(II), of which the bulk is enriched with respect to the oxidized surface. Conversely, for tremolite fibres the very slow fibre dissolution prevents the underlying cations of the bulk to be exposed on the mineral surface, and the iron oxidation, faster than the leaching process, significantly depletes the surface Fe(II) centres initially present. Results of this work may contribute to unravel possible correlations between surface properties of amphibole asbestos and its long-term toxicity

Action minimizing orbits in the n-body problem with simple choreography constraint

In 1999 Chenciner and Montgomery found a remarkably simple choreographic motion for the planar 3-body problem (see \cite{CM}). In this solution 3 equal masses travel on a eight shaped planar curve; this orbit is obtained minimizing the action integral on the set of simple planar choreographies with some special symmetry constraints. In this work our aim is to study the problem of $n$ masses moving in \RR^d under an attractive force generated by a potential of the kind $1/r^\alpha$, $\alpha >0$, with the only constraint to be a simple choreography: if $q_1(t),...,q_n(t)$ are the $n$ orbits then we impose the existence of x \in H^1_{2 \pi}(\RR,\RR^d) such that q_i(t)=x(t+(i-1) \tau), i=1,...,n, t \in \RR, where $\tau = 2\pi / n$. In this setting, we first prove that for every d,n \in \NN and $\alpha>0$, the lagrangian action attains its absolute minimum on the planar circle. Next we deal with the problem in a rotating frame and we show a reacher phenomenology: indeed while for some values of the angular velocity minimizers are still circles, for others the minima of the action are not anymore rigid motions.Comment: 24 pages; 4 figures; submitted to Nonlinearit

Reduction in regulatory T cells in preterm newborns is associated with necrotizing enterocolitis

BackgroundDespite multifactorial pathogenesis, dysregulation of inflammatory immune response may play a crucial role in necrotizing enterocolitis (NEC). Regulatory T cells (Tregs) are involved in immune tolerance early in life. We aimed to investigate the predicting role of Tregs in developing NEC in neonates at high risk.MethodsWe studied six newborns with a diagnosis of NEC (cases) in comparison with 52 controls (without NEC). We further classified controls as neonates with feeding intolerance (FI) and neonates without it (FeedTol). The rate of female and male neonates (sex defined as a biological attribute) was similar. We analyzed the blood frequency of Tregs (not overall numbers) at three time points: 0-3 (T0), 7-10 (T1), and 27-30 (T2) days after birth by flow cytometry. Neonates' sex was defined based on the inspection of external genitalia at birth.ResultsWe observed, at T0, a significantly lower frequency of Tregs in NEC cases (p < 0.001) compared with both FI (p < 0.01) and FeedTol controls (p < 0.01). Multivariate analysis reported that the occurrence of NEC was independently influenced by Treg frequency at birth (ss 2.98; p = 0.039).ConclusionTregs frequency and features in the peripheral blood of preterm neonates, early in life, may contribute to identifying neonates at high risk of developing NEC.ImpactRegulatory T cells may play a pivotal role in regulating the immune response in early life. Reduction of Tregs in early life could predispose preterm newborns to necrotizing enterocolitis.Early markers of necrotizing enterocolitis are still lacking. We demonstrated a predicting role of assessment of regulatory T cells in the diagnosis of this gastrointestinal emergency.Early identification of newborns at high risk of necrotizing enterocolitis through measurement of regulatory T cells may guide clinicians in the management of preterm newborns in order to reduce the development of this severe condition

ISG15 protects human Tregs from interferon alpha-induced contraction in a cell-intrinsic fashion

Objectives: Type I interferons (IFNs) inhibit regulatory T-cell (Treg) expansion and activation, making them beneficial in antiviral responses, but detrimental in autoimmune diseases. Herein, we investigate the role of ISG15 in human Tregs in the context of refractoriness to type I IFN stimulation. Methods: ISG15 expression and Treg dynamics were analysed in vitro and ex vivo from patients with chronic hepatitis C, with lupus and ISG15 deficiency. Results: ISG15 is expressed at high levels in human Tregs, renders them refractory to the IFN-STAT1 signal, and protects them from IFN-driven contraction. In vitro, Tregs from healthy controls upregulate ISG15 upon activation to higher levels than conventional CD4 T cells, and ISG15-silenced Tregs are more susceptible to IFNα-induced contraction. In human ISG15 deficiency, patient Tregs display an elevated IFN signature relative to Tregs from healthy control. In vivo, in patients with chronic hepatitis C, 2 days after starting pegIFN/ribavirin therapy, a stronger ISG15 inducibility correlates with a milder Treg depletion. Ex vivo, in systemic lupus erythematosus patients, higher levels of ISG15 are associated to reduced STAT1 phosphorylation in response to IFNα, and also to increased frequencies of Tregs, characterising active disease. Conclusion: Our results reveal a Treg-intrinsic role of ISG15 in dictating their refractoriness to the IFN signal, thus preserving the Treg population under inflammatory conditions

Regulatory T cells with multiple suppressive and potentially pro-tumor activities accumulate in human colorectal cancer

Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor. Ex vivo, those Tregs suppressed the proliferation of tumor-infiltrating CD8(+) and CD4(+) T cells. A differential compartmentalization was detected between Helioshigh and Helios(low) Treg subsets (thymus-derived versus peripherally induced): while Helios(low) Tregs were enriched in both sites, only Helios(high) Tregs accumulated significantly and specifically in tumors, displayed a highly demethylated TSDR region and contained high proportions of cells expressing CD39 and OX40, markers of activation and suppression. Besides the suppression of T cells, Tregs may contribute to CRC progression also through releasing IL-17, or differentiating into Tfr cells that potentially antagonize a protective Tfh response, events that were both detected in tumor-associated Tregs. Overall, our data indicate that Treg accumulation may contribute through multiple mechanisms to CRC establishment and progression

Estimating the changing burden of disease attributable to unsafe water and lack of sanitation and hygiene in South Africa for 2000, 2006 and 2012

Background. The incidence of diarrhoeal disease is closely linked to socioeconomic and environmental factors, household practices and access to health services. South African (SA) district health information and national survey data report wide variation in the incidence and prevalence of diarrhoeal episodes in children under 5 years of age. These differentials indicate potential for reducing the disease burden through improvements in provision of water and sanitation services and changes in hygiene behaviour. Objectives. To estimate the burden of disease attributed to unsafe water, sanitation and hygiene (WASH) by province, sex and age group for SA in 2000, 2006 and 2012. Methods. Comparative risk assessment methodology was used to estimate the disease burden attributable to an exposure by comparing the observed risk factor distribution with a theoretical lowest possible population distribution. The study adapts the original World Health Organization scenario-based approach for estimating diarrhoeal disease burden from unsafe WASH, by assigning different standards of household water and sanitation-specific geographical classification to capture SA living conditions in rural, urban and informal settlements. Results. SA experienced an improvement in water and sanitation supply in eight of the nine provinces between 2001 and 2011, with the exception of Northern Cape Province. In 2011, 41% of South Africans lived with poor water and sanitation conditions; however, wide provincial inequalities exist. In 2012, it was estimated that 84.1% of all deaths due to diarrhoeal disease were attributable to unsafe WASH; this equates to 13 757 deaths (95% uncertainty interval (UI) 13 015 - 14 300). Of these diarrhoeal disease deaths, 48.2% occurred in children under 5 years of age, accounting for 13.9% of all deaths in this age group (95% UI 13.1 - 14.4). Between 2000 and 2012, the proportion of deaths attributable to diarrhoea reduced from 3.6% to 2.6%. Gauteng and Western Cape provinces experienced much lower WASHattributable death rates than the more rural, poorer provinces. Conclusion. Unsafe WASH remains an important risk factor for disease in SA, especially in children. High priority needs to be given to the provision of safe and sustainable sanitation and water facilities and promoting safe hygiene behaviours. The COVID-19 pandemic has reinforced the critical importance of clean water for preventing and containing disease

Estimating the changing burden of disease attributable to low levels of physical activity in South Africa for 2000, 2006 and 2012

Background. Physical activity is associated with a lower risk of cardiovascular outcomes, certain cancers and diabetes. The previous South African Comparative Risk Assessment (SACRA1) study assessed the attributable burden of low physical activity for 2000, but updated estimates are required, as well as an assessment of trends over time. Objective. To estimate the national prevalence of physical activity by age, year and sex and to quantify the burden of disease attributable to low physical activity in South Africa (SA) for 2000, 2006 and 2012. Methods. Comparative risk assessment methodology was used. Physical activity was treated as a categorical variable with four categories, i.e. inactive, active, very active and highly active. Prevalence estimates of physical activity levels, representing the three different years, were derived from two national surveys. Physical activity estimates together with the relative risks from the Global Burden of Disease, Injuries, and Risk Factors (GBD) 2016 study were used to calculate population attributable fractions due to inactive, active and very active levels of physical activity relative to highly active levels considered to be the theoretical minimum risk exposure (>8 000 metabolic equivalent of time (MET)-min/wk), in accordance with the GBD 2016 study. These were applied to relevant disease outcomes sourced from the Second National Burden of Disease Study to calculate attributable deaths, years of life lost, years lived with disability and disability adjusted life years (DALYs). Uncertainty analysis was performed using Monte Carlo simulation. Results. The prevalence of physical inactivity (<600 METS) decreased by 16% and 8% between 2000 and 2012 for females and males, respectively. Attributable DALYs due to low physical activity increased between 2000 (n=194 284) and 2006 (n=238 475), but decreased thereafter in 2012 (n=219 851). The attributable death age-standardised rates (ASRs) declined between 2000 and 2012 from 60/100 000 population in 2000 to 54/100 000 population in 2012. Diabetes mellitus type 2 displaced ischaemic heart disease as the largest contributor to attributable deaths, increasing from 31% in 2000 to 42% in 2012. Conclusions. Low physical activity is responsible for a large portion of disease burden in SA. While the decreased attributable death ASR due to low physical activity is encouraging, this burden may be lowered further with an additional reduction in the overall prevalence of physical inactivity, in particular. It is concerning that the attributable burden for diabetes mellitus is growing, which suggests that existing non-communicable disease policies need better implementation, with ongoing surveillance of physical activity, and population- and community-based interventions are required in order to reach set targets