Amanda Wendt

INTERACTION OF CALPASTATIN WITH CALPAIN: A REVIEW

Abstract Calpastatin is a multiheaded inhibitor capable of inhibiting more than one calpain molecule. Each inhibitory domain of calpastatin has three subdomains, A, B, and C; A binds to domain IV and C binds to domain VI of the calpains. Crystallographic evidence shows that binding of C to domain VI involves hydrophobic interactions at a site near the first EF-hand in domain VI. Sequence homology suggests that binding of A to calpain domain IV also involves hydrophobic interactions near the EF1- hand of domain IV. Neither subdomain A nor C have inhibitory activity without subdomain B, but both increase the inhibitory activity of B. Subdomain B peptides have no inhibitory activity unless they contain at least 13 amino acids, and inhibitory activity increases with the number of amino acid residues, suggesting that inhibition requires interaction over a large area of the calpain molecule. Although subdomain B inhibition kinetically is competitive in nature, subdomain B does not seem to interact with the active site of the calpains directly, but may bind to domain III of the calpains and act to block access to the active site. It is possible that subdomain B binds to calpain only after it has been activated by Ca[2+].

Impact of Increasing Inter‐pregnancy Interval on Maternal and Infant Health

Short inter-pregnancy intervals (IPIs) have been associated with adverse maternal and infant health outcomes in the literature. However, many studies in this area have been lacking in quality and appropriate control for confounders known to be associated with both short IPIs and poor outcomes. The objective of this systematic review was to assess this relationship using more rigorous criteria, based on GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. We found too few higher-quality studies of the impact of IPIs (measured as the time between the birth of a previous child and conception of the next child) on maternal health to reach conclusions about maternal nutrition, morbidity or mortality. However, the evidence for infant effects justified meta-analyses. We found significant impacts of short IPIs for extreme preterm birth [<6 m adjusted odds ratio (aOR): 1.58 [95% confidence interval (CI) 1.40, 1.78], 6-11 m aOR: 1.23 [1.03, 1.46]], moderate preterm birth (<6 m aOR: 1.41 [1.20, 1.65], 6-11 m aOR: 1.09 [1.01, 1.18]), low birthweight (<6 m aOR: 1.44 [1.30, 1.61], 6-11 m aOR: 1.12 [1.08, 1.17]), stillbirth (aOR: 1.35 [1.07, 1.71] and early neonatal death (aOR: 1.29 [1.02, 1.64]) outcomes largely in high- and moderate-income countries. It is likely these effects would be greater in settings with poorer maternal health and nutrition. Future research in these settings is recommended. This is particularly important in developing countries, where often the pattern is to start childbearing at a young age, have all desired children quickly and then control fertility through permanent contraception, thereby contracting womens fertile years and potentially increasing their exposure to the ill effects of very short IPIs.

Individual and Facility-Level Determinants of Iron and Folic Acid Receipt and Adequate Consumption among Pregnant Women in Rural Bihar, India

Background In Bihar, India, high maternal anemia prevalence and low iron and folic acid supplement (IFA) receipt and consumption have continued over time despite universal IFA distribution and counseling during pregnancy. Purpose To examine individual and facility-level determinants of IFA receipt and consumption among pregnant women in rural Bihar, India. Methods Using District Level Household Survey (2007–08) data, multilevel modeling was conducted to examine the determinants of two outcomes: IFA receipt (any IFA receipt vs. none) and IFA consumption (≥90 days vs. <90 days). Individual-level and facility-level factors were included. Factor analysis was utilized to construct antenatal care (ANC) quality and health sub-center (HSC) capacity variables. Results Overall, 37% of women received any IFA during their last pregnancy. Of those, 24% consumed IFA for 90 or more days. Women were more likely to receive any IFA when they received additional ANC services and counseling, and attended ANC earlier and more frequently. Significant interactions were found between ANC quality factors (odds ratio (OR): 0.37, 95% confidence interval (CI): 0.25, 0.56) and between ANC services and ANC timing and frequency (OR: 0.68, 95% CI: 0.56, 0.82). No HSC factors were significantly associated with IFA receipt. Women were more likely to consume IFA for ≥90 days if they attended at least 4 ANC check-ups and received more ANC services. IFA supply at the HSC (OR: 1.37, 95% CI: 1.04, 1.82) was also significantly associated with IFA consumption. Conclusions Our findings indicate that individual and ANC factors (timing, frequency, and quality) play a key role in facilitating IFA receipt and consumption. Although HSC capacity factors were not found to influence our outcomes, significant variation at the facility level indicates unmeasured factors that could be important to address in future interventions.

Obese women less likely to have low serum ferritin, Nicaragua

OBJECTIVE To examine the association between overweight and obesity and serum ferritin among women of reproductive age (15-49 years) in Nicaragua, considering the effect of α1-acid glycoprotein (AGP), a marker of inflammation. DESIGN We analysed data from the 2004-05 Nicaraguan Integrated Surveillance System for Nutrition Interventions. Three logistic regression models were analysed with low serum ferritin (<15 μg/l) as the dependent variable: (i) overweight or obese status and covariates; (ii) model 1 plus AGP; and (iii) model 1 restricted to only women with normal AGP levels (≤1.0 g/l). SETTING Nicaragua. SUBJECTS Included in this analysis were 832 non-pregnant mother/caregivers (15-49 years) surveyed in 2004-2005. RESULTS In the sample, prevalence of overweight and obesity was 31.8 % and 19.2 %, respectively, and 27.6 % had low serum ferritin. In model 1, the adjusted OR of low serum ferritin was 0.74 (95 % CI 0.52, 1.05) for overweight women and 0.42 (95 % CI 0.26, 0.65) for obese women. In model 2, AGP was significantly independently associated with low serum ferritin (adjusted OR=0.56, 95 % CI 0.34, 0.92) while the adjusted OR for overweight and obesity were largely unchanged. Excluding women with elevated AGP did not appreciably affect the relationship between overweight or obesity and low serum ferritin (model 3). CONCLUSIONS Overall, in this population of reproductive-age women, obese women were less likely to have low serum ferritin levels, and this was independent of inflammation as measured by AGP.

Identifying bottlenecks in the iron and folic acid supply chain in Bihar, India: a mixed-methods study

BackgroundMaternal anaemia prevalence in Bihar, India remains high despite government mandated iron supplementation targeting pregnant women. Inadequate supply has been identified as a potential barrier to iron and folic acid (IFA) receipt. Our study objective was to examine the government health system’s IFA supply and distribution system and identify bottlenecks contributing to insufficient IFA supply.MethodsPrimary data collection was conducted in November 2011 and July 2012 across 8 districts in Bihar, India. A cross-sectional, observational, mixed methods approach was utilized. Auxiliary Nurse Midwives were surveyed on current IFA supply and practices. In-depth interviews (n = 59) were conducted with health workers at state, district, block, health sub-centre, and village levels.ResultsOverall, 44% of Auxiliary Nurse Midwives were out of IFA stock. Stock levels and supply chain practices varied greatly across districts. Qualitative data revealed specific bottlenecks impacting IFA forecasting, procurement, storage, disposal, lack of personnel, and few training opportunities for key players in the supply chain.ConclusionsInadequate IFA supply is a major constraint to the IFA supplementation program, the extent of which varies widely across districts. Improvements at all levels of infrastructure, practices, and effective monitoring will be critical to strengthen the IFA supply chain in Bihar.