A new predictive technology for perinatal stem cell isolation suited for cell therapy approaches

The use of stem cells for regenerative applications and immunomodulatory effect is in-creasing. Amniotic epithelial cells (AECs) possess embryonic‐like proliferation ability and multipo-tent differentiation potential. Despite the simple isolation procedure, inter‐individual variability and different isolation steps can cause differences in isolation yield and cell proliferation ability, compromising reproducibility observations among centers and further applications. We investi-gated the use of a new technology as a diagnostic tool for quality control on stem cell isolation. The instrument label‐free separates cells based on their physical characteristics and, thanks to a micro-camera, generates a live fractogram, the fingerprint of the sample. Eight amniotic membranes were processed by trypsin enzymatic treatment and immediately analysed. Two types of profile were generated: a monomodal and a bimodal curve. The first one represented the unsuccessful isolation with all recovered cell not attaching to the plate; while for the second type, the isolation process was successful, but we discovered that only cells in the second peak were alive and resulted adherent. We optimized a Quality Control (QC) method to define the success of AEC isolation using the frac-togram generated. This predictive outcome is an interesting tool for laboratories and cell banks that isolate and cryopreserve fetal annex stem cells for research and future clinical applications

Neurodevelopmental outcomes of very preterm infants born following early foetal growth restriction with absent end-diastolic umbilical flow

This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes and on preterm infants' clinical and neurodevelopmental outcomes up to 2 years corrected age. This is a retrospective, cohort study led at a level IV Obstetric and Neonatal Unit in Bologna, Italy. Pregnant women were eligible if having singleton pregnancies, with no major foetal anomaly detected, and diagnosed with early FGR + AEDF (defined as FGR + AEDF detected before 32 weeks gestation). Early FGR + AEDF was further classified according to time of onset and specific features into very early and persistent (VEP, FGR + AEDF first detected at 20-24 weeks gestation and persistent at the following scans), very early but transient (VET, FGR + AEDF detected at 20-24 weeks gestation and progressively improving at the following scans) and later (LA, FGR + AEDF detected between 25 and 32 weeks gestation). Pregnancy and neonatal outcomes and infant follow-up data were collected and compared among groups. Neurodevelopment was assessed using the revised Griffiths Mental Developmental Scales (GMDS-R) 0-2 years. A regression analysis was performed to identify early predictors of preterm infants' neurodevelopmental impairment. Fifty-two pregnant women with an antenatal diagnosis of early FGR + AEDF were included in the study (16 VEP, 14 VET, 22 LA). Four intrauterine foetal deaths occurred, all in the VEP group (p = 0.010). Compared to LA infants, VEP infants were born with lower gestational age and lower birth weight, had lower arterial cord blood pH and were at higher risk for intraventricular haemorrhage and periventricular leukomalacia (p < 0.05 for all comparisons). At 12 months, VEP infants had worse GMDS-R scores, both in the general quotient (mean [SD] 91.8 [12.4] vs 104.6 [8.7] in LA) and in the performance domain (mean [SD] 93.3 [15.4] vs 108.8 [8.8] in LA). This latter difference persisted at 24 months (mean [SD] 68.3 [17.0] vs 92.9 [17.7] in LA). In multivariate analysis, at 12 months corrected age, PVL was found to be an independent predictor of impaired general quotient, while the features and timing of antenatal Doppler alterations predicted worse scores in the performance domain.Conclusion: Timing of onset and features of early FGR + AEDF might impact differently on neonatal clinical and neurodevelopmental outcomes. Shared awareness of the importance of FGR + AEDF features between obstetricians and neonatologists may offer valuable tools for antenatal counselling and for tailoring pregnancy management and neonatal follow-up in light of specific antenatal and neonatal risk factors

Histone deacetylase 4 protects from denervation and skeletal muscle atrophy in a murine model of amyotrophic lateral sclerosis

Background: Histone deacetylase 4 (HDAC4) has been proposed as a target for Amyotrophic Lateral Sclerosis (ALS) because it mediates nerve-skeletal muscle interaction and since its expression in skeletal muscle correlates with the severity of the disease. However, our recent studies on the skeletal muscle response upon long-term denervation highlighted the importance of HDAC4 in maintaining muscle integrity. Methods: To fully identify the yet uncharacterized HDAC4 functions in ALS, we genetically deleted HDAC4 in skeletal muscles of a mouse model of ALS. Body weight, skeletal muscle, innervation and spinal cord were analyzed over time by morphological and molecular analyses. Transcriptome analysis was also performed to delineate the signaling modulated by HDAC4 in skeletal muscle of a mouse model of ALS. Findings: HDAC4 deletion in skeletal muscle caused earlier ALS onset, characterized by body weight loss, muscle denervation and atrophy, and compromised muscle performance, although the main catabolic pathways were not activated. Transcriptome analysis identified the gene networks modulated by HDAC4 in ALS, revealing UCP1 as a top regulator that may be implicated in worsening ALS features. Interpretation: HDAC4 plays an important role in preserving innervations and skeletal muscle in ALS, likely by modulating the UCP1 gene network. Our study highlights a possible risk in considering HDAC inhibitors for the treatment of ALS. Fund: This work was supported by FIRB grant (RBFR12BUMH) from Ministry of Education, Universities and Research, by Fondazione Veronesi, by Sapienza research project 2017 (RM11715C78539BD8) and Polish National Science Center grant (UMO-2016/21/B/NZ3/03638)

Pregnancy Loss in Women with HIV is not Associated with HIV Markers: Data from a National Study in Italy, 2001-2018.

BACKGROUND: There is limited information on pregnancy loss in women with HIV, and it is still debated whether HIV-related markers may play a role.Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. METHODS: Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (<22 weeks) and stillbirth ( 6522 weeks). Possible associations of pregnancy loss were evaluated in univariate and multivariate analyses. RESULTS: Among 2696 eligible pregnancies reported between 2001 and 2018, 226 (8.4%) ended in pregnancy loss (miscarriage 198, 7.3%; stillbirth 28, 1.0%). In multivariate analyses, only older age (adjusted odds ratio [AOR] per additional year of age: 1.079, 95% confidence interval [CI] 1.046-1.113), HIV diagnosis before pregnancy (AOR: 2.533, 95%CI 1.407-4.561) and history of pregnancy loss (AOR: 1.625, 95%CI 1.178-2.243) were significantly associated with pregnancy loss. No significant association with pregnancy loss was found for parity, coinfections, sexually transmitted diseases, hypertension, smoking, alcohol and substance use, CD4 cell count, HIV-RNA viral load, and CDC HIV stage. CONCLUSIONS: Older women and those with a previous history of pregnancy loss should be considered at higher risk of pregnancy loss. The severity of HIV disease and potentially modifiable risk factors did not increase the risk of pregnancy loss

The business of care: Private placement agencies and female migrant workers in London

This article presents the results of a qualitative research project on private domestic and care placement agencies in London. Although there is a paucity of empirical studies on these private actors, they have become increasingly important in the domestic and care sector in the UK. In a context of growing commodification and marketization, the article shows how domestic and care services constitute an extremely profitable ‘industry’ in which large companies are increasingly investing. Drawing on content analysis of agencies' websites and in‐depth interviews with agencies' managers/owners, migrant workers and key informants, the article sheds light on these intermediary figures' marketing and business strategies as well as on the ways they contribute to establish the language and practice of domestic and care work as a business. Furthermore, it highlights the employment conditions and selection criteria established by these private agencies for female migrant workers, particularly in a context in which commodification/marketization is expected to foster more professionalization. The article thus fills a significant gap in the literature on domestic and care work, gender and migration by analysing the ways in which for‐profit recruitment agencies have become important players in the care industry

Notulae to the Italian alien vascular flora: 15

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, exclusions for Italy or for Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrections are provided as Suppl. material 1

Information and communication technologies for informal carers and paid assistants:Benefits from micro-, meso-, and macro-levels

The aim of this study was to explore the benefits of information and communication technologies (ICT)-based services for informal carers and paid assistants of older people living in the community. We cross-case analysed the effects of twelve initiatives in the EU, the USA and Canada, based on their individual analysis documented through interviews with promoters and a literature review. We carried out the cross-case analysis following a variables-oriented strategy on seven dimensions of impact at micro-, meso- and macro-levels: the quality of life of informal carers and paid assistants, quality of life of care recipients, quality of care, care efficiency and sustainability, acceptability, and infrastructure and accessibility. ICT-based services for informal carers and paid assistants improve the quality of life of older people and their carers and access to qualified care. They also generate savings which contribute to the sustainability of the care systems. These findings constitute a first look at the benefits of the use of ICT-based services for informal carers and paid assistants. Nevertheless, more research using experimental methods is needed to demonstrate the impact of these ICT-based services at meso- and macro-levels. This would help to support policy-makers to deploy these technologies for long-term care delivery.JRC.J.3-Information Societ

Atazanavir and darunavir in pregnant women with HIV: Evaluation of laboratory and clinical outcomes from an observational national study

Background: Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparativedata in pregnant women are limited.We assessed the safety and activity profile of these two drugs in pregnancyusing data from a national observational study.Methods: Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measuresand main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatalgestational age-adjusted birthweight Z-score).Results: Final analysis included 500 pregnancies with either atazanavir (n"409) or darunavir (n"91) exposure.No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA,haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the twogroups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides(median 235.5 versus 179 mg/dL; P"0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03versus 3.27; P"0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54versus 0.32 mg/dL; P<0.001).Conclusions: In this observational study, the two main HIV PIs currently recommended by perinatal guidelinesshowed similar safety and activity in pregnancy, with no evidence of differences between the two drugs in termsof main pregnancy outcomes. Based on the minor differences observed in laboratory measures, prescribingphysicians might prefer either drug in some particular situations where the different impacts of treatment onlipid profile and bilirubin may have clinical relevance