Cytokine profile in peripheral blood mononuclear cells differs between embryo donor and potential recipient sows

IntroductionPregnancy success relies on the establishment of a delicate immune balance that requires the early activation of a series of local and systemic immune mechanisms. The changes in the immunological profile that are normally occurring in the pregnant uterus does not take place in cyclic (non-pregnant) uterus, a fact that has been widely explored in pigs at the tissue local level. Such differences would be especially important in the context of embryo transfer (ET), where a growing body of literature indicates that immunological differences at the uterine level between donors and recipients may significantly impact embryonic mortality. However, whether components of peripheral immunity also play a role in this context remains unknown. Accordingly, our hypothesis is that the immune status of donor sows differs from potential recipients, not only at the tissue local level but also at the systemic level. These differences could contribute to the high embryonic mortality rates occurring in ET programs.MethodsIn this study differences in systemic immunity, based on cytokine gene expression profile in peripheral blood mononuclear cells (PBMCs), between embryo-bearing donor (DO group; N = 10) and potential recipient sows (RE group; N = 10) at Day 6 after the onset of the estrus were explored. Gene expression analysis was conducted for 6 proinflammatory (IL-1α, IL-1β, IL-2, GM-CSF, IFN-γ, and TNF-α) and 6 anti-inflammatory (IL-4, IL-6, IL-10, IL-13, TGF-β1, and LIF) cytokines.Results and discussionAll cytokines were overexpressed in the DO group except for IL-4, suggesting that stimuli derived from the insemination and/or the resultant embryos modify the systemic immune profile in DO sows compared to RE (lacking these stimuli). Our results also suggest that certain cytokines (e.g., IL-1α and IL-1β) might have a predictive value for the pregnancy status

Magnesium in Kidney Function and Disease—Implications for Aging and Sex—A Narrative Review

Magnesium (Mg) has a vital role in the human body, and the kidney is a key organ in the metabolism and excretion of this cation. The objective of this work is to compile the available evidence regarding the role that Mg plays in health and disease, with a special focus on the elderly population with chronic kidney disease (CKD) and the eventual sex differences. A narrative review was carried out by executing an exhaustive search in the PubMed, Scopus, and Cochrane databases. Ten studies were found in which the role of Mg and sex was evaluated in elderly patients with CKD in the last 10 years (2012–2022). The progression of CKD leads to alterations in mineral metabolism, which worsen as the disease progresses. Mg can be used as a coadjuvant in the treatment of CKD patients to improve glomerular filtration, but its use in clinical applications needs to be further characterized. In conclusion, there’s a need for well-designed prospective clinical trials to advise and standardize Mg supplementation in daily clinical practice, taking age and sex into consideration

Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations

Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized

Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability. © 2021, The Author(s)

Ongoing flyby in the young multiple system UX Tauri

We present observations of the young multiple system UX Tauri to look for circumstellar disks and for signs of dynamical interactions. We obtained SPHERE/IRDIS deep differential polarization images in the J and H bands. We also used ALMA archival CO data. Large extended spirals are well detected in scattered light coming out of the disk of UX Tau A. The southern spiral forms a bridge between UX Tau A and C. These spirals, including the bridge connecting the two stars, all have a CO (3-2) counterpart seen by ALMA. The disk of UX Tau C is detected in scattered light. It is much smaller than the disk of UX Tau A and has a major axis along a different position angle, suggesting a misalignment. We performed PHANTOM SPH hydrodynamical models to interpret the data. The scattered light spirals, CO emission spirals and velocity patterns of the rotating disks, and the compactness of the disk of UX Tau C all point to a scenario in which UX Tau A has been perturbed very recently (∼1000 years) by the close passage of UX Tau C. Movies associated to Fig. 3 are available at http://https://www.aanda.orgPeer reviewe

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Time trends in socioeconomic differences in incidence rates of cancers of gastro-intestinal tract in Finland

BACKGROUND: The magnitude of socioeconomic differences in health varies between societies, and over time within a given society. We studied the association between social class and incidence of cancers of the gastro-intestinal tract over time in a large cohort in Finland. METHODS: We studied social class variation among 45–69 year-old Finns during 1971–95 in incidence of cancers of the gastro-intestinal tract by means of a computerized record linkage of the Finnish Cancer Registry and the 1970 Population Census, which included social class data. RESULTS: There were 2.3 million individuals in the cohort under follow-up, with 1622 cases of cancer of the esophagus, 8069 stomach (non-cardia), 1116 cardia, 408 small intestine, 6361 colon, 5274 rectum, 1616 liver, 1756 gallbladder, and 5084 pancreas during 1971–1995. Cancers of the esophagus, stomach, cardia, gallbladder and pancreas were most common among persons belonging to a low social class. Cancers of the small intestine in males only, colon in both genders, and rectum in females were most common in the higher social classes. Incidence of stomach cancer decreased and incidence of colon cancer increased over time in both genders in all social classes, and the large differences between social classes remained unchanged over time. Incidence rates of cardia cancer did not change substantially over time. CONCLUSION: There is a large variation in incidence of cancer of the gastrointestinal tract by social class in Finland. Although much of the observed social class differences probably could be explained by known etiological factors such as diet, physical exercise, alcohol consumption, smoking and exogenous hormone use, part of the variation is apparently attributable to largely unknown factors

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified