Nutrient intakes in women and risks of anophthalmia and microphthalmia in their offspring

BACKGROUND: There is a paucity of information about risk factors for the human eye anomalies anophthalmia and microphthalmia. In this population-based case-control study we investigated whether periconceptional intakes of supplemental folic acid, dietary folate, vitamin A, and several other nutrients were associated with these eye defects. METHODS: This study included data on deliveries that had estimated due dates from 1997-2002 and were part of the National Birth Defects Prevention Study (the National Birth Defects Prevention Study is a population-based case-control study of a wide spectrum of birth defects, incorporating data from 10 birth defects surveillance systems in the United States [Arkansas, California, Georgia/Centers for Disease Control and Prevention, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah]). Cases were those infants or fetuses born with either anophthalmia or microphthalmia. Liveborn infants without major malformations were eligible as controls. Maternal interviews were conducted, primarily by telephone, in English or Spanish. Participation in the interview was 71% among case mothers and 68% among control mothers. Interviews were completed with 89 case mothers and 4,143 control mothers. A shortened version of the food frequency questionnaire from the Nurse's Health Study was used to assess frequency of intake of 58 food items during the year before pregnancy. RESULTS: Our results did not indicate reduced risks for these eye malformations associated with maternal intake of vitamin supplements containing folic acid. The data did not show an association between malformation risk and higher or lower intakes of vitamin A. We also did not observe strong evidence that an abundance or a lack of dietary intake of any other nutrient was associated with increased risk of the studied eye malformations. CONCLUSIONS: Our observations contribute to a limited body of findings on these rare eye defects.     

Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis is associated with level and avidity of anti-cyclic citrullinated protein autoantibodies: a case study

In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity.     

Age-dependent genetic structure of arctic foxes in Svalbard

Arctic foxes are highly mobile arctic predators with a very weak population genetic structure over large parts of their range. Less is, however, known about the more local genetic structure within regions. Here, we analyze genotypes at 12 microsatellite loci for 561 arctic foxes trapped in the high-arctic archipelago Svalbard and investigate the genetic structure in three different age classes. Significant linkage disequilibrium, deficit of heterozygotes, genetic differentiation, and a decrease in relatedness with distance among animals trapped in their first winter suggested that some litter mates remain in proximity of each other during the first winter. This pattern was stronger for females than for males, indicating male-biased juvenile dispersal, and weaker for older animals. There was no genetic differentiation among adult foxes harvested in different hunting areas. The foxes from the protected area around Hornsund were however more differentiated than expected based on geographic distance alone, suggesting a possible disrupting effect of harvest on the spatial genetic structure in the rest of Svalbard. Our results also indicated a possible kin structure among adult females, suggesting natal philopatry, but further investigations will be needed to reach firm conclusions concerning kin structure in arctic foxes.     

An NMR investigation of putative interresidue H-bonding in methyl α-cellobioside in solution

Methyl α-cellobioside (methyl β-d-glucopyranosyl-(1→4)-α-d-glucopyranoside) was labeled with ¹³C at C4′ for use in NMR studies in DMSO-d₆ solvent to attempt the detection of a trans-H-bond J-coupling (^3hJ_CCOH) between C4′ and OH3. Analysis of the OH3 signal at 600 MHz revealed only the presence of two homonuclear J-couplings: ³J_H3,OH3 and a smaller, longer range J_HH. No evidence for ^3hJ_C4′,OH3 was found. The longer range J_HH was traced to ⁴J_H4,OH3 based on 2D ¹H–¹H COSY data and inspection of the H2 and H4 signal lineshapes. A limited set of DFT calculations was performed on a methyl cellobioside mimic to evaluate the structural dependencies of ⁴J_H2,O3H and ⁴J_H4,O3H on the H3–C3–O3–H torsion angle. Computed couplings range from about −0.7 to about +1.1 Hz, with maximal values observed when the C–H and O–H bonds are roughly diaxial.     

Functional genomics of the yeast DNA-damage response

High-throughput approaches are beginning to have an impact on many areas of yeast biology. Two recent studies, using different experimental platforms, provide insight into new pathways involved in the response of yeast to DNA damage.     

Women with large breasts are at an increased risk of advanced breast cancer

Background

The risk of nodal metastasis is higher in women with bigger breast. It is not clear if this increase is due to the size of the breast (largely related to obesity) or is the result of larger tumour size at presentation (due to delayed diagnosis). It is hypothesised that women with large breasts are more likely to have node positive disease mainly attributable to their breast size.

Patients and methods

One hundred and twenty consecutive patients who underwent mastectomy during the year 2004 and 2005 for primary breast cancers in a large Teaching Hospital were included in the study. Patient's variable and tumour variable were collected and analysed by SPSS^® computer programme.

Results

It was found that big breasted women (those patients with mastectomy weight greater than 800 g) had a significantly greater tumour size than those with smaller breasts (p = 0.019, Mann-Whitney test) but there was no significant difference in grade (Kendall's tau-b = 0.055, p = 0.57) or lymph node positivity (Kendall's tau-b = 0.011, p = 0.93) between the two groups. Although, the tumour size was significantly greater in those with lymph node metastases (p < 0.001) but mastectomy weight was not found to be significantly greater in those with lymph node metastases (p = 0.11). For patients with similar tumour sizes mastectomy weight was not significantly greater in those patients with lymph node metastases (p = 0.28).

Conclusion

It is concluded that increased incidence of lymph node positivity at presentation big-breasted women is because of larger size of the primary tumour and not due to the size of the breast alone.