Knockdown of Bardet-Biedl Syndrome Gene BBS9/PTHB1 Leads to Cilia Defects

Bardet-Biedl Syndrome (BBS, MIM#209900) is a genetically heterogeneous disorder with pleiotropic phenotypes that include retinopathy, mental retardation, obesity and renal abnormalities. Of the 15 genes identified so far, seven encode core proteins that form a stable complex called BBSome, which is implicated in trafficking of proteins to cilia. Though BBS9 (also known as PTHB1) is reportedly a component of BBSome, its direct function has not yet been elucidated. Using zebrafish as a model, we show that knockdown of bbs9 with specific antisense morpholinos leads to developmental abnormalities in retina and brain including hydrocephaly that are consistent with the core phenotypes observed in syndromic ciliopathies. Knockdown of bbs9 also causes reduced number and length of cilia in Kupffer's vesicle. We also demonstrate that an orthologous human BBS9 mRNA, but not one carrying a missense mutation identified in BBS patients, can rescue the bbs9 morphant phenotype. Consistent with these findings, knockdown of Bbs9 in mouse IMCD3 cells results in the absence of cilia. Our studies suggest a key conserved role of BBS9 in biogenesis and/or function of cilia in zebrafish and mammals

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

Good prenatal detection rate of major birth defects in HIV-infected pregnant women in Italy

What's already known about this topic? Exposure to antiretroviral treatment in pregnancy does not seem to increase the risk of birth defects, but there is no information on the rate of prenatal detection of such defects. What does this study adds? We provide for the first time, in a national case series, information about prenatal detection rate in women with HIV (51.6% for any major defect, 66.7% for chromosomal abnormalities, and 85% for severe structural defect

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

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Consequences of presentation with advanced HIV disease in pregnancy : data from a national study in Italy

Among 469 women with a diagnosis of HIV in pregnancy, 74 (15.8%) presented with less than 200 CD4 cells per cubic millimeter. The only variable significantly associated with this occurrence was African origin (odds ratio: 2.22, 95% confidence intervals: 1.32 to 3.75, P = 0.003). Four women with low CD4 (5.6%), compared with none with higher CD4 counts, had severe AIDS-defining conditions (P < 0.001) during pregnancy or soon after delivery, and one transmitted HIV to the newborn. Early preterm delivery (<32 weeks) was significantly more frequent with low CD4 (6.2% vs. 1.4%, P = 0.015). An earlier access to HIV testing, particularly among immigrants of African origin, can prevent severe HIV-related morbidity

Immigrants, voter sentiment, and local public goods: The case of museums

We present a model where museum commitment to immigrant integration is conditioned by the possible negative reactions of native visitors and patrons. We then exploit the rich information provided by the 2015 Italian museum census to investigate the factors associated with a higher probability of museums developing promotion programmes targeting an immigrant audience, with a special focus on the size of immigrant communities and the importance of anti-immigrant sentiment in the local context. We proxy the latter with the municipal vote shares of parties with an anti-immigrant agenda in the 2013 national elections. Our evidence shows that the vote share of Lega Nord has a significantly negative and sizable estimated coefficient. Conversely, we find no positive association with the overall share of immigrants—only the size of specific minorities at the local level increases the likelihood that a museum engages immigrants. We control for a number of context variables and specific museum characteristics, some of which (age of establishment, type of collection) show a positive association with museum commitment to immigrant integration

Infectious diseases among foreign prisoners: results of a hospital-based management model in Palermo

Foreign prisoners have a high vulnerability in terms of morbidity and access to care in overcrowded Italian prisons. This paper presents and comments on the management model of infectious diseases in foreign prisoners at our outpatient clinic, in order to describe a model of management for these conditions. Overall, 133 subjects (mean age 35.5 years) from 29 countries were followed for a period of 15 years. The most commonly represented area of origin (54.1%) was the Maghreb region. HCV infection (40.6%), HIV (22.5%), HBV (9.8%) and co-infection (15%, HIV/HCV or HIV/HBV) were observed. Ten subjects had tuberculosis, and only 30% of them were compliant with the treatment. Only 46.3% of HCV mono-infected patients completed the entire diagnostic process and even a lower percentage (37%) of them took treatment regularly. 90% of HBV mono-infected patients and 84% of those HIV mono- and co-infected completed the diagnostic workout. 77% of patients in each group took therapy regularly. Overall, the results show limited effectiveness. Therefore, it would be necessary to improve communication between healthcare professionals and correctional systems. Moreover, it appears urgent to reduce overcrowding in prisons to limit morbidity in prisoners