BackgroundThe etiology of birth defects has been widely studied but is not yet fully clarified, previously published data had suggested that maternal age or parity maybe involved, but without consistent conclusions.MethodsA population-based, case-control study was nested in a cohort of perinatal infants born from 2010 to 2012 in Baoan District, Shenzhen. Four categories of isolated birth defects were defined as cases: congenital heart defects (CHD, n = 693), polydactyly (n = 352), cleft lip with or without palate (CL/P, n = 159) and equinovarus (n = 119). Controls were non-malformed infants (n = 11,307) randomly selected from the same area and period. Odds ratios (ORs) and the 95% confidence intervals (CIs) were computed by multivariable unconditional logistic regression analysis.ResultsYoung maternal age (<25 years old) was associated with a reduced risk of CHD (adjusted OR = 0.73, 95% CI 0.59–0.90), while with an elevated risk of polydactyly (adjusted OR = 1.42, 95% CI 1.09-1.84). Increased risk of CL/P-affected pregnancy was observed in mothers older than 35 years old (adjusted OR = 2.12, 95% CI 1.26–3.57). Compared to primipara, those having their second, and third or more delivery were less likely to have infants with equinovarus, with significant adjusted ORs of 0.59 (0.40–0.89) and 0.42 (0.19–0.93), respectively.ConclusionMaternal age was significantly associated with CHD, polydactyly and CL/P relevant pregnancy. Mothers with higher parity might have lower risk of equinovarus occurrence in offsprings.

Electronic literature searches of the PubMed, EmBase, and Medline databases were performed up to October 31, 2011. Fixed-effects or random-effects models were used to calculate the pooled odds ratios (ORs) for two genetic comparisons (heterozygous mutation vs. wild type, homozygous mutation vs. wild type). RESULTS A total of 18 studies were ultimately identified. The pooled results revealed no statistical association between infant and maternal C677T and A1298C variants and risk of cleft lip with or without palate (CL/P) or cleft palate only (CPO), except for the maternal 677TT genotype for CL/P, the OR was 1.32 (95% confidence interval [CI], 1.06-1.63) as compared to the normal 677CC genotype. In the subgroup analyses on CL/P data based on ethnicity and source of control subjects, almost all of the results were replicated as nonsignificant associations in both examined polymorphisms, whereas the pooled risk estimate calculated for maternal 677TT genotype in the white population remained statistically significant, with an OR of 1.36 (95% CI, 1.05-1.76). CONCLUSIONS This meta-analysis suggests that maternal MTHFR 677TT genotype might increase the risk of having a CL/P offspring in the white population. However, these findings remain to be confirmed by additional investigations.

Chalcones containing tertiary amine side-chains have potent activity as acetylcholinesterase (AChE) inhibitors. However, the effects of the location of the tertiary amine groups as well as of other groups on AChE and butyrylcholinesterase (BChE) activity have not been reported. Here, we report the synthesis and testing of 36 new coumarin-chalcone hybrids (5d-7j, 9d-11f, 12k-13m) against AChE and BChE. The nature and position of the chalcone substituents had major effects on inhibitory activity as well as selectivity for AChE over BChE. Compounds with para-substituted chalcone fragments in which the substituents were choline-like had potent activity against AChE and poor activity against BChE, while ortho-substituted analogs exhibited an opposite effect. Replacement of the terminal amine groups by amide, alkyl or alkenyl groups abrogated activity. Compound 5e showed potent inhibitory activity [Formula: see text]) and good selectivity for AChE over BChE (ratio 27.4), and a kinetic study showed that 5e exhibited mixed-type inhibition against AChE. Computational docking results indicate that 5e binds to Trp 279, Tyr334 and Trp 84 in AChE, but only to Trp 82 in BChE. Overall, the results show that coumarin-chalcone hybrids with choline-like side-chains have promising activity and selectivity against AChE and be promising therapeutic leads for Alzheimer's disease.

This study was aimed to evaluate the long-term effects of telbivudine (LdT) in the treatment of chronic hepatitis B (CHB) and HBV-related liver cirrhosis (LC) and to observe the changes of immunological responses during LdT treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with LdT for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen (HBeAg) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after LdT treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid (HA), human laminin (LN), human type IV collagen (IV-C) and human N-terminal procollagen III peptide (PC-III), were detected before and after LdT treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with LdT for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, LdT treatment led to the fluctuation of the circulating interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels at different time points in CHB group. It was concluded that LdT could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during LdT therapy.

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