Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders

The Organ-on-a-Chip (OoC) technology shows great potential to revolutionize the drugs development pipeline by mimicking the physiological environment and functions of human organs. The translational value of OoC is further enhanced when combined with patient-specific induced pluripotent stem cells (iPSCs) to develop more realistic disease models, paving the way for the development of a new generation of patient-on-a-chip devices. iPSCs differentiation capacity leads to invaluable improvements in personalized medicine. Moreover, the connection of single-OoC into multi-OoC or body-on-a-chip allows to investigate drug pharmacodynamic and pharmacokinetics through the study of multi-organs cross-talks. The need of a breakthrough thanks to this technology is particularly relevant within the field of neurodegenerative diseases, where the number of patients is increasing and the successful rate in drug discovery is worryingly low. In this review we discuss current iPSC-based OoC as drug screening models and their implication in development of new therapies for neurodegenerative disorders

Multi- and Transgenerational Outcomes of an Exposure to a Mixture of Endocrine-Disrupting Chemicals (EDCs) on Puberty and Maternal Behavior in the Female Rat.

peer reviewedBACKGROUND: The effects of endocrine-disrupting chemicals (EDCs) on fertility and reproductive development represent a rising concern in modern societies. Although the neuroendocrine control of sexual maturation is a major target of EDCs, little is known about the potential role of the hypothalamus in puberty and ovulation disruption transmitted across generations. OBJECTIVES: We hypothesized that developmental exposure to an environmentally relevant dose of EDC mixture could induce multi- and/or transgenerational alterations of sexual maturation and maternal care in female rats through epigenetic reprograming of the hypothalamus. We investigated the transmission of a disrupted reproductive phenotype via the maternal germline or via nongenomic mechanisms involving maternal care. METHODS: Adult female Wistar rats were exposed prior to and during gestation and until the end of lactation to a mixture of the following 13 EDCs: di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), bisphenol A (BPA), vinclozolin, prochloraz, procymidone, linuron, epoxynaxole, dichlorodiphenyldichloroethylene, octyl methoxynimmate, 4-methylbenzylidene camphor (4-MBC), butylparaben, and acetaminophen. Perinatally exposed offspring (F1) were mated with unexposed males to generate germ cell (F2) and transgenerationally exposed (F3 and F4) females. Sexual maturation, maternal behavior, and hypothalamic targets of exposure were studied across generations. RESULTS: Germ cell (F2) and transgenerationally (F3) EDC-exposed females, but not F1, displayed delayed pubertal onset and altered folliculogenesis. We reported a transgenerational alteration of key hypothalamic genes controlling puberty and ovulation (Kiss1, Esr1, and Oxt), and we identified the hypothalamic polycomb group of epigenetic repressors as actors of this mechanism. Furthermore, we found a multigenerational reduction of maternal behavior (F1-F3) induced by a loss in hypothalamic dopaminergic signaling. Using a cross-fostering paradigm, we identified that the reduction in maternal phenotype was normalized in EDC-exposed pups raised by unexposed dams, but no reversal of the pubertal phenotype was achieved. DISCUSSION: Rats developmentally exposed to an EDC mixture exhibited multi- and transgenerational disruption of sexual maturation and maternal care via hypothalamic epigenetic reprogramming. These results raise concerns about the impact of EDC mixtures on future generations. https://doi.org/10.1289/EHP8795

Effects of dietary supplementation with polyphenols on meat quality in Saanen goat kids

Diet supplementation with polyphenols is a novel strategy to improve meat quality in livestock, by preventing oxidative deterioration of lipids and protein. Polyphenols have beneficial effects on both human and animal health and can be obtained from several sources, such as olive mill wastewaters (OMWW). These are severe environmental pollutants and therefore may be recycled and utilized in other sectors. The aim of this study was to evaluate growth performance, meat characteristics, fatty acid composition, antioxidant status, different forms of myoglobin and malondialdehyde formation in kids who received a diet supplemented with polyphenols obtained from OMWW. Weaned goat kids (n = 18) were divided into two homogenous groups: control (C) group (n = 9) received a fattening standard diet while the other group (n = 9) received the same diet, supplemented with 3.2 mg/day of polyphenols powder extract (PE group). Average daily gain (ADG) was calculated 10 days apart throughout the study. After 78 days, the kids were slaughtered and pH and carcass yield were evaluated. Longissimus thoracis et lumborum muscle was collected and utilized for chemical analysis, meat quality evaluation and oxidative stability

Human gut epithelium features recapitulated in MINERVA 2.0 millifluidic organ-on-a-chip device

We developed an innovative millifluidic organ-on-a-chip device, named MINERVA 2.0, that is optically accessible and suitable to serial connection. In the present work, we evaluated MINERVA 2.0 as millifluidic gut epithelium-on-a-chip by using computational modeling and biological assessment. We also tested MINERVA 2.0 in a serially connected configuration prodromal to address the complexity of multiorgan interaction. Once cultured under perfusion in our device, human gut immortalized Caco-2 epithelial cells were able to survive at least up to 7 days and form a three-dimensional layer with detectable tight junctions (occludin and zonulin-1 positive). Functional layer development was supported by measurable trans-epithelial resistance and FITC-dextran permeability regulation, together with mucin-2 expression. The dynamic culturing led to a specific transcriptomic profile, assessed by RNASeq, with a total of 524 dysregulated transcripts (191 upregulated and 333 downregulated) between static and dynamic condition. Overall, the collected results suggest that our gut-on-a-chip millifluidic model displays key gut epithelium features and, thanks to its modular design, may be the basis to build a customizable multiorgan-on-a-chip platform

Impact of the COVID-19 Pandemic on Child and Adolescent Psychiatric Emergencies

By forcing closure of schools, curtailing outpatient services, and imposing strict social distancing, the COVID-19 pandemic has abruptly affected the daily life of millions worldwide, with still unclear consequences for mental health. This study aimed to evaluate if and how child and adolescent psychiatric visits to hospital emergency departments (EDs) changed during the pandemic lockdown, which started in Italy on February 24, 2020

Dyslexic Art Week, La fortuna di essere dislessici

Un viaggio dentro la realtà concreta delle persone con DSA e il loro linguaggio aristico. Questo libro grazie alle testimonianze e le opere creative riflette sulla vita, arte e la peculiarità dell'arte dei giovani (le studentesse e gli studenti del liceo artistico di via Ripetta e l'accademia di Belle Arti di Roma) riconosciuti dislessici

Impact of asthma and comorbid allergic rhinitis on quality of life and control in patients of italian general practitioners

Objective. Asthma is a disease with elevated prevalence within the general population. Although general practitioners (GPs) are among the first health-care professionals to whom patients refer for their symptoms, there are few evaluations of this disease based on data provided by the GPs. The aim of this observational study is to assess the impact of asthma and comorbid allergic rhinitis on individual/social burden, quality of life, and disease control in asthmatic patients of Italian GPs. Methods. Throughout Italy, 107 GPs enrolled 995 patients diagnosed with asthma and using anti-asthmatic drug prescriptions, or with asthma-like symptoms during the previous 12 months. Data were collected through questionnaires filled out by GPs and patients. Results. Of the 995 asthmatic patients, 60.6 had concomitant allergic rhinitis (RA), 39.4 had asthma alone. The latter, compared to those with RA, showed significantly lower prevalence of intermittent asthma (37.5 vs. 55.6) and higher prevalence of mild, moderate, and severe persistent asthma (28.4 vs. 23.2, 28.7 vs. 18.8, and 5.4 vs 2.4, respectively). Individual/social burden due to asthma was frequent and increased with disease severity: 87.5 of severe persistent asthma patients reported at least one medical consultation in the last 12 months, 37.5 emergency department visits, 26.7 hospitalization, and 62.5 limitations in daily activities. Control and quality of life were inversely associated with disease severity and were worse in patients with RA than in those with asthma alone. Conclusions. This study showed the negative impact of high severity levels and comorbid allergic rhinitis on quality of life of asthmatic patients and on individual/social burden due to asthma in an Italian GPs setting. \uc2\ua9 2012 Informa Healthcare USA, Inc

The ARGA study with general practitioners: Impact of medical education on asthma/rhinitis management

Aim: To evaluate the impact of a medical education course (MEC) on the behaviour of general practitioners (GPs) to treat asthma and allergic rhinitis (AR). Methods: Data on 1820 patients (mean age 41yrs \uc2\ub1 17yrs) with asthma or AR were collected by 107 Italian GPs: 50% attended a MEC and 50% didn't (group B). The adherence for AR and asthma treatment was evaluated according to ARIA and GINA guidelines (GL). Results: AR and asthma were diagnosed in 78% and 56% of patients; 34% had concomitant AR and asthma. Regardless of the MEC, the adherence to GL was significantly higher for AR than for asthma treatment (52 versus 19%). Group B GPs were more compliant to ARIA guidelines in the treatment of mild AR, whereas group A were more compliant in the treatment of moderate-severe AR; the adherence didn't differ between the groups for AR patients with comorbid asthma. Adherence to GINA GL for asthma treatment did not differ between GPs of groups A and B, independently from concomitant AR. Though insignificantly, group A were more compliant to GINA GL in the treatment of patients with only severe persistent asthma (63 versus 46%) as group B were for patients with severe persistent asthma and concomitant AR. Conclusions: GPs often tend to treat patients independently from GL. The impact of a single MEC did not improve adherence to GL in treating less severe AR and asthma patients, while there was a trend towards the opposite attitude in more severe AR patients without concomitant asthma. \uc2\ua9 2012 Elsevier Ltd. All rights reserved

Prescriptive adherence to GINA guidelines and asthma control: An Italian cross sectional study in general practice

Background: Although general practitioners (GPs) are frequently the first healthcare professionals whom asthma patients refer to for their symptoms, few studies have explored the extent of adherence to guidelines for asthma management based on data provided directly by GPs. Aims of the present study were to assess drug prescriptions for asthma by GPs and to evaluate prescriptive adherence to GINA guidelines (GL) and its relationship with disease control in real life. Methods: 995 asthmatic patients (45% males, mean age 43.3 ± 17.7 yrs) were enrolled by 107 Italian GPs distributed throughout the country. Data on diagnosis, disease severity, prescribed anti-asthmatic drugs and control were collected through questionnaires filled out by GPs taking into consideration the 2009 GINA Guidelines. Data on drug use and chronic sinusitis, nasal polyposis, chronic bronchitis, emphysema were reported by patients through a self-administered questionnaire. Results: The large majority of patients were classified by GPs as having intermittent (48.4%) or mild persistent asthma (25.3%); 61% had co-morbid allergic rhinitis (AR). The prevalent therapeutic regimen used by patients was a combination of inhaled corticosteroids (ICS) plus long-acting β2-agonists (LABA) (54.1%), even in the intermittent/mild persistent group. ICS as mono-therapy or in combination with other drugs but LABA, was the second most frequently adopted treatment (14.4%). In general, the GPs adherence to GL treatment indications was 28.8%, with a significant association with a good asthma control (OR 1.85, 95% CI 1.18–2.92). On the other hand, comorbidity (OR 0.52, 95% CI 0.32–0.84), moderate (0.44, 0.28–0.69) and severe (0.06, 0.02–0.20) persistent asthma showed significant negative effects on asthma control. Conclusions: Our results show that over-treatment of intermittent/mild persistent asthma is frequent in the GPs setting while therapeutic regimens are more appropriately applied for moderate/severe asthma. In general, we found low adherence to GINA GL treatment recommendations even if its relevance in asthma control was confirmed