Cost–Effective Prediction of Gender-Labeling Errors and Estimation of Gender-Labeling Error Rates in Candidate-Gene Association Studies

We describe a statistical approach to predict gender-labeling errors in candidate-gene association studies, when Y-chromosome markers have not been included in the genotyping set. The approach adds value to methods that consider only the heterozygosity of X-chromosome SNPs, by incorporating available information about the intensity of X-chromosome SNPs in candidate genes relative to autosomal SNPs from the same individual. To our knowledge, no published methods formalize a framework in which heterozygosity and relative intensity are simultaneously taken into account. Our method offers the advantage that, in the genotyping set, no additional space is required beyond that already assigned to X-chromosome SNPs in the candidate genes. We also show how the predictions can be used in a two-phase sampling design to estimate the gender-labeling error rates for an entire study, at a fraction of the cost of a conventional design

Low expression of estrogen receptor β in T lymphocytes and high serum levels of anti-estrogen receptor α antibodies impact disease activity in female patients with systemic lupus erythematosus

BACKGROUND: Current evidence indicates that estrogens, in particular 17β-estradiol (E2), play a crucial role in the gender bias of autoimmune diseases although the underlying molecular mechanisms have not yet been fully elucidated. Immune cells have estrogen receptors (ERs), i.e., ERα and ERβ, that play pro- and anti-inflammatory functions, respectively, and the presence of one estrogen receptor (ER) subtype over the other might change estrogen effects, promoting or dampening inflammation. In this study, we contributed to define the influences of E2 on T cells from female patients with systemic lupus erythematosus (SLE), a representative autoimmune disease characterized by a higher prevalence in women than in men (female/male ratio 9:1). Particularly, our aim was to evaluate whether alterations of ERα and ERβ expression in T cells from female SLE patients may impact lymphocyte sensitivity to E2 and anti-ERα antibody (anti-ERα Ab) stimulation interfering with cell signaling and display a direct clinical effect. METHODS: Sixty-one premenopausal female patients with SLE and 40 age-matched healthy donors were recruited. Patients were divided into two groups based on the SLE Disease Activity Index 2000 (SLEDAI-2K) (i.e., <6 and ≥6). ER expression was evaluated in T lymphocytes by flow cytometry, immunofluorescence, and Western blot analyses. Serum anti-ERα Ab levels were analyzed by enzyme-linked immunosorbent assay (ELISA). ER-dependent signaling pathways were measured by a phosphoprotein detection kit. RESULTS: Intracellular ERβ expression was significantly lower in T cells from patients with SLEDAI-2K ≥6 as compared with healthy donors and patients with SLEDAI-2K <6 and negatively correlated with disease activity. The expression of intracellular and membrane-associated-ERα was similar in SLE and control T cells. ER-dependent signaling pathways were activated in T cells from SLE patients with SLEDAI-2K ≥6, but not with SLEDAI-2K <6, when both membrane and intracellular ERs were stimulated by co-treatment with E2 and anti-ERα Abs. CONCLUSIONS: Our results demonstrate an altered ER profile in SLE patients, possibly contributing to SLE pathogenesis and interfering with clinical activity, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of disease activity

Prevalence of breastfeeding in Italy: a population based follow-up study

Abstract Introduction Breastfeeding is widely recommended. Updated data are needed to assess its prevalence and the effectiveness of interventions. Breastfeeding practices in Italy need to be promoted and monitored with updated and standard data The objective of this study is to provide estimates of the prevalence of breastfeeding and exclusively breastfeeding and to identify factors that may be modified to improve them. Materials and methods Two population-based follow-up surveys were conducted to evaluate the quality of maternal care in 25 Local Health Units in Italy during 2008-2011. Women were interviewed soon after giving birth and after 3, 6 and 12 months. Breastfeeding prevalences were estimated. A logistic regression model was used to investigate factors associated with exclusive breastfeeding at 3 months. Results Breastfeeding and exclusively breastfeeding prevalences were 91.6% and 57.2% at discharge, 71.6% and 48.6% at 3 months, 57.7% and 5.5% at 6 months. At 12 months, 32.5% were still breastfeeding. Women who are more likely to exclusively breastfeed at 3 months are multiparous, more educated, resident in the north/center, have attended antenatal classes and groups of breastfeeding support, have practiced the skin-to-skin contact in hospital and have initiated breastfeeding early. Conclusion In Italy many mothers do not comply with breastfeeding recommendations. The promotion and support of breastfeeding is still necessary in Italy and still needs to be monitored with representative data. Actions should aim at empowering women, reducing social inequalities and improving practices in hospitals and maternal care services which encourage breastfeeding

Targeting CDK6 and BCL2 Exploits the MYB Addiction of Ph+ Acute Lymphoblastic Leukemia

Philadelphia chromosome–positive acute lymphoblastic leukemia (Phþ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Phþ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Phþ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced Phþ ALL cells rescues their impaired proliferation and survival. Levels of MYB and CDK6 were highly correlated in adult Phþ ALL (P ¼ 0.00008). Moreover, Phþ ALL cells exhibited a specific requirement for CDK6 but not CDK4 expression, most likely because, in these cells, CDK6 was predominantly localized in the nucleus, whereas CDK4 was almost exclusively cytoplasmic. Consistent with their essential role in Phþ ALL, pharmacologic inhibition of CDK6 and BCL2 markedly suppressed proliferation, colony formation, and survival of Phþ ALL cells ex vivo and in mice. In summary, these findings provide a proof-of-principle, rational strategy to target the MYB addiction of Phþ ALL. © 2017 American Association for Cancer Research

Hospitalisation among immigrants in Italy

BACKGROUND: Immigration is increasing in Italy. In 2003, 2.6 million foreign citizens lived in the country; 52% were men and the majority were young adults who migrated for work. The purpose of this study was to investigate differences in hospitalisation between immigrants and the resident population during the year 2000 in the Lazio region. METHODS: Hospital admissions of immigrants from Less Developed Countries were compared to those of residents. We measured differences in hospitalisation rates and proportions admitted. RESULTS: Adult immigrants have lower hospitalisation rates than residents (134.6 vs. 160.5 per thousand population for acute care; 26.4 vs. 38.3 for day care). However, hospitalisation rates for some specific causes (injuries, particularly for men, infectious diseases, deliveries and induced abortions, ill-defined conditions) were higher for immigrants than for residents. Immigrants under 18 years seem to be generally healthy; causes of admission in this group are similar to those of residents of the same age (respiratory diseases, injuries and poisoning). The only important differences are for infectious and parasitic diseases, with a higher proportion among immigrant youths. CONCLUSION: The low hospitalisation rates for foreigners may suggest that they are a population with good health status. However, critical areas, related to poor living and working conditions and to social vulnerability, have been identified. Under-utilisation of services and low day care rates may be partially due to administrative, linguistic, and cultural barriers. As the presence of foreigners becomes an established phenomenon, it is important to evaluate their epidemiological profile, develop instruments to monitor and fulfil their specific health needs and plan health services for a multi-ethnic population

Antioxidant Properties of Pulp, Peel and Seeds of Phlegrean Mandarin (Citrus reticulata Blanco) at Different Stages of Fruit Ripening

In this work, we assess the potential of waste products of Phlegrean mandarin (Citrus reticulata Blanco), namely seeds and peel, to be reutilized as a source of bioactive compounds beneficial for the human diet. Starting from the evidence that the by-products of this specific cultivar are the most powerful sources of antioxidants compared to pulp, we have investigated if and how the bioactive compounds in peel and seeds may be affected by fruit ripening. Three stages of fruit ripening have been considered in our study: unripe fruits = UF, semi-ripe fruits = SRF, ripe fruits = RF. The overall results indicated that RF showed the highest concentration of antioxidants. Among fruit components, peel was the richest in total antioxidant capacity, total polyphenol content, total flavonoids, total chlorophylls and carotenoids, while seeds exhibited the highest concentration of total condensed tannins and ascorbic acid. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay indicates the occurrence, in peel extracts, of 28 phenolic compounds, mainly flavonoids (FLs); in seeds, 34 derivatives were present in the first stage (UF), which diminish to 24 during the ripening process. Our data indicated that the content of phytochemicals in citrus strongly varies among the fruit components and depends on the ripening stage. The higher antioxidant activity of peel and seeds, especially in RF, encourage a potential use of by-products of this specific citrus cultivar for industrial or pharmacological applications. However, to maximize the occurrence of desired bioactive compounds, it is important also to consider the ripening stage at which fruits must be collected

VRAC Channels and the Cellular Redox Balance

Volume-regulated anion channels (VRAC) are mainly involved in the regulated transport of osmolytes such as ions or small organic compounds across the plasma membrane during anisosmotic cell swelling. However, they also play additional roles in various pathophysiological processes, such as the transport of metabolites and drugs, extracellular signal transduction and anti-cancer drug resistance. These channels are formed by heteromers of LRRC8 proteins, of which LRRC8A is the essential subunit that combines with its paralogs LRRC8B–E to form hexameric complexes. Despite the extensive research devoted to the understanding of VRACs functions, different aspects of these channels are still to be characterized in depth. In this chapter, recent findings concerning the involvement of VRAC channels in the cellular redox balance will be summarized. Also, their relevance as potential targets of antioxidant therapies will be discussed