The ability of CD8
T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8
T cells marked ...by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39
CD8
T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8
T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39
CD8
T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39
CD8
T cells inhibited IFNγ production by responder CD8
T cells. In specimens from breast cancer and melanoma patients, CD39
CD8
T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhibited an exhausted phenotype with impaired production of IFNγ, TNF, IL2, and high expression of coinhibitory receptors. Although T-cell receptor engagement was sufficient to induce CD39 on human CD8
T cells, exposure to IL6 and IL27 promoted CD39 expression on stimulated CD8
T cells from human or murine sources. Our findings show how the tumor microenvironment drives the acquisition of CD39 as an immune regulatory molecule on CD8
T cells, with implications for defining a biomarker of T-cell dysfunction and a target for immunotherapeutic intervention.
The tumor microenvironment elicits a subset of functionally exhausted CD8
T cells by creating conditions that induce cell surface expression of CD39, an immunosuppressive molecule that can be therapeutically targeted to restore effector T-cell function.
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The generation of hydroxyl radicals (•OH) during the chlorination of air saturated solutions of different hydroxyphenols (hydroquinone, resorcinol, catechol, gallic and tannic acids) at pH 7 has been ...determined by the formation of phenol (in presence of benzene in excess) or 2-hydroxyterephthalic acid (in presence of terephthalic acid). Formation of •OH was only detected during the chlorination of o- or p-hydroxyphenols, compounds that react with chlorine by electron transfer forming the corresponding semiquinones/quinones. In aerated solutions, oxygen is reduced by the semiquinone to the superoxide radical, O2•−, which reacts with HOCl to •OH. Compared to the studied o-hydroxyphenols, the lower reactivity of hydroquinone towards chlorine favours the reaction between chlorine and O2•−, and its •OH formation potential is ∼50 times higher. The extent of •OH generated increased with the concentration of the hydroxyphenol and chlorine, but the •OH yield (moles formed per mole of hydroxyphenol eliminated), decreased due to the formation of the quinone, that acts as O2•− scavenger. The yield was almost not affected by the pH (6 ≤ pH ≤ 7.5), whereas a strong impact of dissolved O2 was observed. The •OH production was null in absence of O2 and 2.5–3 times higher at oxygen saturated conditions compared to air-saturated. Contrary to chlorination, during bromination of hydroquinone •OH was not formed, which can be attributable to a much faster consumption of the oxidant, with no chance for O2•− to react with bromine.
Formation of •OH during the chlorination of different NOM extracts (SRHA, SRFA, PLFA and Nordic Lake NOM) and water from Lake Greifensee (Switzerland) was also studied using terephthalic acid as •OH scavenger. For SRHA, SRFA and Nordic Lake NOM (all of allochthonous origin and presenting high electron-donating capacity, EDC), •OH yields expressed as moles formed per mole of DOC0 (%), were between 1.1 and 2.0, similar to that of hydroquinone (∼1.5). For PLFA and Lake Greifensee water (autochthonous, lower EDC) much lower •OH yields were observed (0.1–0.3). Both chlorination rate and EDC, the later favouring the formation/stabilization of O2•−, seem to be key factors involved in •OH generation during the chlorination of NOM. A mechanism for these findings is proposed based on kinetic simulations of hydroquinone chlorination at pH 7.
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•Chlorination of o- and p-hydroxyphenols leads to the formation of •OH.••OH formation potential of p-hydroxyphenols is ∼50 times higher.•Oxygen is a prerequisite for •OH formation.•Superoxide, formed from semiquinone/O2 reaction, reacts with chlorine to yield •OH.••OH formation from SRHA, SRFA and NL-NOM is comparable to p-hydroxyphenols.
Members of the IL-17 cytokine family play an important role in protection against pathogens through the induction of different effector mechanisms. We determined that IL-17A, IL-17E and IL-17F are ...produced during the acute phase of T. cruzi infection. Using IL-17RA knockout (KO) mice, we demonstrate that IL-17RA, the common receptor subunit for many IL-17 family members, is required for host resistance during T. cruzi infection. Furthermore, infected IL-17RA KO mice that lack of response to several IL-17 cytokines showed amplified inflammatory responses with exuberant IFN-γ and TNF production that promoted hepatic damage and mortality. Absence of IL-17RA during T. cruzi infection resulted in reduced CXCL1 and CXCL2 expression in spleen and liver and limited neutrophil recruitment. T. cruzi-stimulated neutrophils secreted IL-10 and showed an IL-10-dependent suppressive phenotype in vitro inhibiting T-cell proliferation and IFN-γ production. Specific depletion of Ly-6G+ neutrophils in vivo during T. cruzi infection raised parasitemia and serum IFN-γ concentration and resulted in increased liver pathology in WT mice and overwhelming wasting disease in IL-17RA KO mice. Adoptively transferred neutrophils were unable to migrate to tissues and to restore resistant phenotype in infected IL-17RA KO mice but migrated to spleen and liver of infected WT mice and downregulated IFN-γ production and increased survival in an IL-10 dependent manner. Our results underscore the role of IL-17RA in the modulation of IFN-γ-mediated inflammatory responses during infections and uncover a previously unrecognized regulatory mechanism that involves the IL-17RA-mediated recruitment of suppressive IL-10-producing neutrophils.
Recent advances in hardware and information technology have accelerated the proliferation of smart and interconnected devices facilitating the rapid development of the Internet of Things (IoT). IoT ...applications and services are widely adopted in environments such as smart cities, smart industry, autonomous vehicles, and eHealth. As such, IoT devices are ubiquitously connected, transferring sensitive and personal data without requiring human interaction. Consequently, it is crucial to preserve data privacy. This paper presents a comprehensive survey of recent Machine Learning (ML)- and Deep Learning (DL)-based solutions for privacy in IoT. First, we present an in depth analysis of current privacy threats and attacks. Then, for each ML architecture proposed, we present the implementations, details, and the published results. Finally, we identify the most effective solutions for the different threats and attacks.
Aims and Objectives
This study examined the predictors of caregiver burden based on patient and caregiver characteristics in a sample of Spanish caregivers looking after adult patients with chronic ...disease. The effect of task type and patient–caregiver interaction is also analysed.
Background
Specific predictors of caregiver burden have been widely examined in the literature. Few studies, however, jointly analyse a wide range of factors, including the effect of task type and patient–caregiver interaction.
Design
Correlational study.
Methods
One hundred and thirty five informal caregivers for 148 care recipients were recruited from primary health care centres. The caregivers responded to the short version of the Zarit Burden Interview (ZBI), the DEPendency index‐6 Dimensions (DEP‐6D), and reported how long they spent on caregiving on a daily basis. Sociodemographic and health characteristics were also recorded. Linear and logistic regression models were used to evaluate factors associated with ZBI scores and the likelihood of being severely burdened, respectively. This research complies with STROBE guidelines for observational studies.
Results
Severe burden was present in 62% of the caregivers. Regression analysis shows that burden severity increases significantly with the level of dependence when the latter is measured either by DEP‐6D or by time spent on basic activities. Care related to incontinence and mobility has the greatest effect on burden, which is aggravated when the patient has behavioural problems. Poor caregiver health or not being retired also contributes to burden levels.
Conclusions
These results establish that caregiver burden is related to characteristics of both the caregiver and the care recipient as well as to their interaction.
Relevance to clinical practice
The findings indicate that the socio‐sanitary attention focused on reducing caregiver burden must address the caregiver and patient as a dyad. Identifying the dependence level and the patient's aggressive behaviour can be a good predictor of caregiver burden.
•Regardless of pH, initial DOC is transformed by PCOz due to bulk HO• and O3.•At pH < pHpzc, h+ is the main responsible for DOC mineralization by PCOz.•Higher pH and alkalinity strongly inhibit ...organics adsorption. Low DOC removal.•Clear synergy between O3/UVA and TiO2/UVA only when treating a secondary effluent.•No direct interaction between O3/UVA and TiO2/UVA systems is deduced.
Numerous studies report on the synergy between ozonation and photocatalytic oxidation (TiO2/UVA), which could open the way to the application of photocatalytic ozonation (PCOz) in water treatment. With the aim of establishing the existence of this synergy and its origin, in this work, using TiO2 P25, 365 nm UVA LEDs and ozone transferred doses up to 5 mg (mg DOC0)−1 (DOC0 7 – 10 mg L−1), a systematic study has been carried out featuring the effect of pH, alkalinity and water matrix in each of the systems involved in PCOz, with special attention to the role of organics adsorption onto TiO2. In ultrapure water, an increase in pH and carbonates content exerted a slight negative effect on the photocatalytic degradation of primidone (low adsorption onto TiO2 and mainly abated by free HO•), this effect being higher on its mineralization. The negative effect of pH and alkalinity was much stronger for oxalic acid (high tendency to adsorb and mainly oxidized by positive holes). Accordingly, the results obtained at pH < pHpzc (point of zero charge of the catalyst) in ultrapure water cannot at all be extrapolated to secondary effluents, since their composition negatively affects the photocatalytic performance. At the experimental conditions applied, only for the secondary effluent a synergy between O3/UVA and TiO2/UVA systems was observed. This synergy would be related, on the one hand, to the generation, from the matrix itself, of reactive entities or intermediates that promote the decomposition of ozone into HO•; and, on the other hand, to an increase in catalyst activity as the matrix UVA absorption decreases, rather than from direct interactions between both systems. Despite de above, ozone requirement to achieve a significant reduction of DOC is high and would only be an interesting strategy for the elimination of ozone-refractory micropollutants.
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•Taphonomic conditions partly influence quality and quantity of DNA from remains.•Intrinsic (bone features) and extrinsic (environmental) factors must be considered.•Interaction between different ...factors is key in the DNA preservation and recovery.
The identification of skeletal human remains, severely compromised by putrefaction, or highly deteriorated, is important for legal and humanitarian reasons. There are different tools that can help in the identification process such as anthropological and genetic studies. The success observed during the last decade in genetic analysis of skeletal remains has been possible especially due to the refinements of DNA extraction and posterior analysis techniques. However, despite these progresses, many challenges keep influencing the results of such analysis, mainly the limited amount and the degradation of the DNA recovered from badly preserved samples. By now, there is still no wide-range knowledge about post-mortem kinetics of DNA degradation. Therefore, taphonomy studies can play a key role in the reconstruction of post-mortem transformations that skeletal remains, and consequently DNA, have undergone. Thus, the goal of the present review focuses on the assessment of the literature regarding the possible effect of intrinsic (characteristics of the bone) and extrinsic (environmental) factors on the state of preservation of skeletal remains recovered in a terrestrial environment and their genetic material. The establishment of useful indicators describing the state of the remains is a key factor in order to determine their suitability for posterior biomolecular analysis.
The food industry seeks alternatives to satisfy consumer demands of safe foods with a long shelf-life able to maintain the nutritional and organoleptic quality. The application of antimicrobial ...compounds-producing protective cultures may provide an additional parameter of processing in order to improve the safety and ensure food quality, keeping or enhancing its sensorial characteristics. In addition, strong evidences suggest that certain probiotic strains can confer resistance against infection with enteric pathogens. Several mechanisms have been proposed to support this phenomenon, including antimicrobial compounds secreted by the probiotics, competitive exclusion, or stimulation of the immune system. Recent research has increasingly demonstrated the role of antimicrobial compounds as protective mechanism against intestinal pathogens and therefore certain strains could have an effect on both the food and the gut. In this aspect, the effects of the combination of different strains keep unknown. The development of multistrain probiotic dairy products with good technological properties and with improved characteristics to those shown by the individual strains, able to act not only as protective cultures in foods, but also as probiotics able to exert a protective action against infections, has gained increased interest.
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