Transport of Aflatoxin M1 in Human Intestinal Caco-2/TC7 Cells

Aflatoxin M1 (AFM1) is a hydroxylated metabolite of aflatoxin B1 (AFB1). After it is formed, it is secreted in the milk of mammals. Despite the potential risk of human exposure to AFM1, data reported in literature on the metabolism, toxicity, and bioavailability of this molecule are limited and out of date. The aim of the present research was to study the absorption profile of AFM1 and possible damage to tight junctions (TJ) of the intestinal Caco-2/TC7 clone grown on microporous filter supports. These inserts allowed for the separation of the apical and basolateral compartments which correspond to the in vivo lumen and the interstitial space/vascular systems of intestinal mucosa respectively. In this study, the Caco-2/TC7 cells were treated with different AFM1 concentrations (10–10,000 ng/kg) for short (40 min) and long periods of time (48 h). The AFM1 influx/efflux transport and effects on TJ were evaluated by measuring trans-epithelial electrical resistance and observing TJ protein (Zonula occludens-1 and occludin) localization. The results showed that: (i) when introduced to the apical and basolateral compartments, AFM1 was poorly absorbed by the Caco-2/TC7 cells but its transport across the cell monolayer occurred very quickly (Papp value of 105.10 ± 7.98 cm/s × 10−6). (ii) The integrity of TJ was not permanently compromised after exposure to the mycotoxin. Viability impairment or barrier damage did not occur either. The present results contribute to the evaluation of human risk exposure to AFM1, although the AFM1 transport mechanism need to be clarified

Fisheye Photogrammetry to Survey Narrow Spaces in Architecture and a Hypogea Environment

Nowadays, the increasing computation power of commercial grade processors has actively led to a vast spreading of image-based reconstruction software as well as its application in different disciplines. As a result, new frontiers regarding the use of photogrammetry in a vast range of investigation activities are being explored. This paper investigates the implementation of fisheye lenses in non-classical survey activities along with the related problematics. Fisheye lenses are outstanding because of their large field of view. This characteristic alone can be a game changer in reducing the amount of data required, thus speeding up the photogrammetric process when needed. Although they come at a cost, field of view (FOV), speed and manoeuvrability are key to the success of those optics as shown by two of the presented case studies: the survey of a very narrow spiral staircase located in the Duomo di Milano and the survey of a very narrow hypogea structure in Rome. A third case study, which deals with low-cost sensors, shows the metric evaluation of a commercial spherical camera equipped with fisheye lenses

An Animal-Assisted Education Intervention with Dogs to Promote Emotion Comprehension in Primary School Children—The Federico II Model of Healthcare Zooanthropology

Emotion comprehension (EC) is a crucial competence for children, as it determines the quality of peer interactions. This study assessed the efficacy of an animal-assisted education (AAE) intervention with dogs based on the Federico II Model of Healthcare Zooanthropology (FMHZ) to promote EC in a group of primary school children. One hundred and four children (48 females) aged 6–7 years took part in the study, of whom 63 participated in the AAE intervention (i.e., experimental group) and 41 did not (i.e., control group). The intervention was deployed in a school setting through a group format and consisted of five bimonthly sessions. EC was assessed pre- and post-intervention, and at a 3-month follow-up. Student’s t-test and mixed-model ANOVA were performed to analyze the effect of the intervention on EC. EC significantly improved in children of the experimental group compared to the control group. Significant time effects from pre- to post-intervention, post-intervention to follow-up, and pre-intervention to follow-up assessment were found in the experimental group only. AAE based on FMHZ was effective in improving EC in children

SPLICS: a split green fluorescent protein-based contact site sensor for narrow and wide heterotypic organelle juxtaposition

Contact sites are discrete areas of organelle proximity that coordinate essential physiological processes across membranes, including Ca2+ signaling, lipid biosynthesis, apoptosis, and autophagy. However, tools to easily image inter-organelle proximity over a range of distances in living cells and in vivo are lacking. Here we report a split-GFP-based contact site sensor (SPLICS) engineered to fluoresce when organelles are in proximity. Two SPLICS versions efficiently measured narrow (8\u201310 nm) and wide (40\u201350 nm) juxtapositions between endoplasmic reticulum and mitochondria, documenting the existence of at least two types of contact sites in human cells. Narrow and wide ER\u2013mitochondria contact sites responded differently to starvation, ER stress, mitochondrial shape modifications, and changes in the levels of modulators of ER\u2013mitochondria juxtaposition. SPLICS detected contact sites in soma and axons of D. rerio Rohon Beard (RB) sensory neurons in vivo, extending its use to analyses of organelle juxtaposition in the whole anim

life expectancy in italian patients with hereditary angioedema due to c1 inhibitor deficiency

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Pregnancy in epileptic patients: comparison between well-established therapeutic strategies and opportunities coming from new drugs

Treating women affected by epilepsy during pregnancy is challenging.  Clinicians have to consider both the teratogenic effects of Antiepileptic Drugs (AEDs) and the risk of seizure recurrence. Pharmacokinetic changes during pregnancy are rapid and conspicuous so that the serum concentration of drugs can be modified and the effectiveness of AEDs cannot be guaranteed. The aim of this study is to evaluate the risk of Major Congenital Malformation (MCM) associated with AEDs treatment during the first trimester of pregnancy. We collected data from 338 patients who contacted the Teratology Information Services of XXX University Hospital and we found that only the variable monotherapy vs politherapy had statistical significance for MCM. More studies are needed to assess the efficacy and safety of newer AEDs

Affiliative Bonds and Cruel Behavior in Childhood Interspecific Relationships: A Conceptual Framework on the Psychodynamics of Affect Regulation

Background: Childhood interspecific relationships can be viewed as a mirror of the person’s capacity to interact with other living beings. The interspecific relationship can involve different attachment styles, affect regulation skills, transitional object dynamics, and self-awareness and mentalization processes. Yet interspecific relationships can also be disrupted, since they can be associated with cruel behavior toward animals, which is in turn related to possible psychopathology. Method: We provided a conceptual framework based on the literature addressing the interspecific relationship in both its adaptive and positive features as well as in its disrupted aspects. Discussion: Pets have often been regarded as attachment figures that can aid children in socialization and growth processes. They have been deemed to represent “social catalysts” that tend to facilitate human relationships, thus increasing prosocial behaviors. On the dark side of the pet-child interaction, childhood abuse of animals tends to be associated with behavioral and emotional problems that have been thought of as underlying psychopathology (e.g., conduct disorder and antisocial personality traits). Childhood cruelty to animals seems to accompany emotion dysregulation, poor social information processing, and low empathy. Conclusions: Since the child-pet relationship has substantial implications for the individual’s mental health and for the potential development of psychopathology, addressing children’s attitudes toward animals can aid in understanding the affective and emotional dimensions of their interpersonal experience

HER2-Displaying M13 Bacteriophages induce Therapeutic Immunity against Breast Cancer

The advent of trastuzumab has significantly improved the prognosis of HER2-positive (HER2+) breast cancer patients; nevertheless, drug resistance limits its clinical benefit. Anti-HER2 active immunotherapy represents an attractive alternative strategy, but effective immunization needs to overcome the patient's immune tolerance against the self-HER2. Phage display technology, taking advantage of phage intrinsic immunogenicity, permits one to generate effective cancer vaccines able to break immune tolerance to self-antigens. In this study, we demonstrate that both preventive and therapeutic vaccination with M13 bacteriophages, displaying the extracellular (EC) and transmembrane (TM) domains of human HER2 or its Δ16HER2 splice variant on their surface (ECTM and Δ16ECTM phages), delayed mammary tumor onset and reduced tumor growth rate and multiplicity in ∆16HER2 transgenic mice, which are tolerant to human ∆16HER2. This antitumor protection correlated with anti-HER2 antibody production. The molecular mechanisms underlying the anticancer effect of vaccine-elicited anti-HER2 antibodies were analyzed in vitro against BT-474 human breast cancer cells, sensitive or resistant to trastuzumab. Immunoglobulins (IgG) purified from immune sera reduced cell viability mainly by impairing ERK phosphorylation and reactivating retinoblastoma protein function in both trastuzumab-sensitive and -resistant BT-474 cells. In conclusion, we demonstrated that phage-based HER2 vaccines impair mammary cancer onset and progression, opening new perspectives for HER2+ breast cancer treatment

miR-181a/b downregulation exerts a protective action on mitochondrial disease models.

Mitochondrial diseases (MDs) are a heterogeneous group of devastating and often fatal disorders due to defective oxidative phosphorylation. Despite the recent advances in mitochondrial medicine, effective therapies are still not available for these conditions. Here, we demonstrate that the microRNAs miR-181a and miR-181b (miR-181a/b) regulate key genes involved in mitochondrial biogenesis and function and that downregulation of these miRNAs enhances mitochondrial turnover in the retina through the coordinated activation of mitochondrial biogenesis and mitophagy. We thus tested the effect of miR-181a/b inactivation in different animal models of MDs, such as microphthalmia with linear skin lesions and Leber\u27s hereditary optic neuropathy. We found that miR-181a/b downregulation strongly protects retinal neurons from cell death and significantly ameliorates the disease phenotype in all tested models. Altogether, our results demonstrate that miR-181a/b regulate mitochondrial homeostasis and that these miRNAs may be effective gene-independent therapeutic targets for MDs characterized by neuronal degeneration

Safety and efficacy of a feed additive consisting of endo‐1,4‐β‐d‐mannanase produced by Thermothelomyces thermophilus DSM 33149 (Natupulse® TS/TS L) for chickens and turkeys for fattening, minor poultry species for fattening and ornamental birds (BASF SE)

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9972018/Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of endo-1,4-β-d-mannanase produced by Thermothelomyces thermophilus DSM 33149 (Natupulse® TS/TS L) as a zootechnical feed additive for chickens and turkeys for fattening, minor poultry species for fattening and ornamental birds. The additive under assessment, Natupulse® TS/TS L, does not pose any safety concern regarding the production strain. The FEEDAP Panel concluded that the additive is tolerated by chickens for fattening, and this conclusion can be extrapolated to all poultry for fattening. Due to the lack of reliable data regarding the potential of the additive to induce chromosomal damage, the FEEDAP Panel cannot conclude on the safety of the additive for the target species and on the safety for consumer. The use of the additive in animal nutrition is considered safe for the environment. The additive is considered not to be irritant to the skin and eyes but is considered a respiratory sensitiser, although exposure by inhalation is unlikely. The Panel could not conclude on the potential of the additive to be a skin sensitiser. Due to the lack of reliable data, the FEEDAP Panel considered that a potential of the additive to induce chromosomal damage in exposed unprotected users cannot be excluded. Consequently, exposure of users should be minimised. The Panel concluded that the additive Natupulse® TS/TS L has the potential to be efficacious in chickens for fattening at the proposed conditions of use and this conclusion can be extrapolated to turkeys for fattening, minor poultry species for fattening and ornamental birds.info:eu-repo/semantics/publishedVersio