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)

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

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

Comparing inequalities in the labour market from a segmentation perspective

Production of INCASI Project H2020-MSCA-RISE-2015 GA 691004The purpose of this chapter is to carry out a comparative analysis of labour markets in Europe and Latin America from the perspective of segmentation in order to explain the processes of social inequality that arise in the workplace, in light of recent trends in global socio-economic changes. The chapter proposes two main objectives. The first is to perform a comparative descriptive analysis of the main features of labour markets among 60 European and Latin American countries. The second objective is to propose a model of comparative analysis of labour inequality from the theoretical perspective of the segmentation of the labour market and structural heterogeneity. We will focus our analysis by selecting two countries, Spain and Argentina, which both underwent a late development of capitalism. The following general hypothesis is formulated: Spain and Argentina, having clearly differentiated features in economic structure, level of development, institutional frameworks and socio-historical processes, show common dynamics in the structuring of the capitalist labour market between a primary and secondary segment. Using equivalent databases on the workforce a typology of segmentation of employment is constructed that show, in addition to the specificities of each country, the similarities in the structuring of the labour market

Rate , correlates and outcomes of repeat pregnancy in HIV-infected women

Objectives: The aim of the study was to assess the rate, determinants, and outcomes of repeat pregnancies in women with HIV infection. Methods: Data from a national study of pregnant women with HIV infection were used. Main outcomes were preterm delivery, low birth weight, CD4 cell count and HIV plasma viral load. Results: The rate of repeat pregnancy among 3007 women was 16.2%. Women with a repeat pregnancy were on average younger than those with a single pregnancy (median age 30 vs. 33 years, respectively), more recently diagnosed with HIV infection (median time since diagnosis 25 vs. 51 months, respectively), and more frequently of foreign origin [odds ratio (OR) 1.36; 95% confidence interval (CI) 1.10–1.68], diagnosed with HIV infection in the current pregnancy (OR: 1.69; 95% CI: 1.35–2.11), and at their first pregnancy (OR: 1.33; 95% CI: 1.06–1.66). In women with sequential pregnancies, compared with the first pregnancy, several outcomes showed a significant improvement in the second pregnancy, with a higher rate of antiretroviral treatment at conception (39.0 vs. 65.4%, respectively), better median maternal weight at the start of pregnancy (60 vs. 61 kg, respectively), a higher rate of end-of-pregnancy undetectable HIV RNA (60.7 vs. 71.6%, respectively), a higher median birth weight (2815 vs. 2885 g, respectively), lower rates of preterm delivery (23.0 vs. 17.7%, respectively) and of low birth weight (23.4 vs. 15.4%, respectively), and a higher median CD4 cell count (+47 cells/μL), with almost no clinical progression to Centers for Disease Control and Prevention stage C (CDC-C) HIV disease (0.3%). The second pregnancy was significantly more likely to end in voluntary termination than the first pregnancy (11.4 vs. 6.1%, respectively). Conclusions: Younger and foreign women were more likely to have a repeat pregnancy; in women with sequential pregnancies, the second pregnancy was characterized by a significant improvement in several outcomes, suggesting that women with HIV infection who desire multiple children may proceed safely and confidently with subsequent pregnancies

Pregnancy outcomes and cytomegalovirus DNAaemia in HIV infected pregnant women with CMV

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Risk Factors Associated with Adverse Fetal Outcomes in Pregnancies Affected by Coronavirus Disease 2019 (COVID-19): A Secondary Analysis of the WAPM study on COVID-19

To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Mean gestational age at diagnosis was 30.6\ub19.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible