Central adiposity and other anthropometric factors in relation to risk of macrosomia in an african american population

Objective:

Previous studies have consistently identified maternal obesity and gestational weight gain (GWG) as risk factors for macrosomia, but little is known about the effects of central adiposity and body fat distribution. Using self‐reported data from the Black Women's Health Study (BWHS), a large follow‐up study of US black women, we examined the risk of macrosomia in relation to prepregnancy waist circumference, prepregnancy waist‐to‐hip ratio (WHR), prepregnancy BMI, and GWG.

Design and Methods:

During 1995–2003, BWHS participants ages 21–44 years delivered 6,687 full‐term singleton births (gestational age >37 weeks). We compared mothers of 691 infants weighing ≥4,000 g with mothers of 5,996 infants weighing <4,000 g. Generalized estimating equation models (GEE) that accounted for more than one birth per mother were used to estimate multivariable odds ratios (OR) and 95% confidence intervals (CI).

Results:

Independent of prepregnancy BMI, prepregnancy waist circumference was positively associated with risk of macrosomia (OR = 1.58, 95% CI: 1.07–2.32, for ≥35.0 vs. <27.0 inches (≥88.9 vs. <68.6 cm); P trend = 0.04). As expected, prepregnancy BMI was also positively associated with macrosomia (OR = 1.74, 95% CI: 1.25–2.41 for BMI ≥35.0 vs. 18.5–24.9 kg m^?2). GWG above the amount recommended by the 2009 Institute of Medicine report was associated with an increased risk of macrosomia and the association was present in each category of prepregnancy BMI (18.5–24.9, 25.0–29.9, and ≥30.0 kg m^?2; P trend <0.001).

Conclusions:

Our data suggest that overall obesity, high GWG, and high waist circumference are independent risk factors for macrosomia among US black women.

     

Identification of Small Molecule Inhibitors of Jumonji AT-rich Interactive Domain 1B (JARID1B) Histone Demethylase by a Sensitive High Throughput Screen

JARID1B (also known as KDM5B or PLU1) is a member of the JARID1 family of histone lysine demethylases responsible for the demethylation of trimethylated lysine 27 in histone H3 (H3K4me3), a mark for actively transcribed genes. JARID1B is overexpressed in several cancers, including breast cancer, prostate cancer, and lung cancer. In addition, JARID1B is required for mammary tumor formation in syngeneic or xenograft mouse models. JARID1B-expressing melanoma cells are associated with increased self-renewal character. Therefore, JARID1B represents an attractive target for cancer therapy. Here we characterized JARID1B using a homogeneous luminescence-based demethylase assay. We then conducted a high throughput screen of over 15,000 small molecules to identify inhibitors of JARID1B. From this screen, we identified several known JmjC histone demethylase inhibitors, including 2,4-pyridinedicarboxylic acid and catechols. More importantly, we identified several novel inhibitors, including 2-4(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one (PBIT), which inhibits JARID1B with an IC₅₀ of about 3 μm in vitro. Consistent with this, PBIT treatment inhibited removal of H3K4me3 by JARID1B in cells. Furthermore, this compound inhibited proliferation of cells expressing higher levels of JARID1B. These results suggest that this novel small molecule inhibitor is a lead compound that can be further optimized for cancer therapy.     

The FTO A/T Polymorphism and Elite Athletic Performance: A Study Involving Three Groups of European Athletes

Objective

The FTO A/T polymorphism (rs9939609) is a strong candidate to influence obesity-related traits. Elite athletes from many different sporting disciplines are characterized by low body fat. Therefore, the aim of this study was to assess whether athletic status is associated with the FTO A/T polymorphism.

Subjects and Methods

A large cohort of European Caucasians from Poland, Russia and Spain were tested to examine the association between FTO A/T polymorphism (rs9939609) and athletic status. A total of 551 athletes were divided by type of sport (endurance athletes, n = 266 vs. sprint/power athletes, n = 285) as well as by level of competition (elite-level vs. national-level). The control group consisted of 1,416 ethnically-matched, non-athletic participants, all Europeans. Multinomial logistic regression analyses were conducted to assess the association between FTO A/T genotypes and athletic status/competition level.

Results

There were no significantly greater/lesser odds of harbouring any type of genotype when comparing across athletic status (endurance athletes, sprint/power athletes or control participants). These effects were observed after controlling for sex and nationality. Furthermore, no significantly greater/lesser odds ratios were observed for any of the genotypes in respect to the level of competition (elite-level vs. national-level).

Conclusion

The FTO A/T polymorphism is not associated with elite athletic status in the largest group of elite athletes studied to date. Large collaborations and data sharing between researchers, as presented here, are strongly recommended to enhance the research in the field of exercise genomics.     

The Economic Burden Attributable to a Child’s Inpatient Admission for Diarrheal Disease in Rwanda

Background

Diarrhea is one of the leading causes of childhood morbidity and mortality. Hospitalization for diarrhea can pose a significant burden to health systems and households. The objective of this study was to estimate the economic burden attributable to hospitalization for diarrhea among children less than five years old in Rwanda. These data can be used by decision-makers to assess the impact of interventions that reduce diarrhea morbidity, including rotavirus vaccine introduction.

Methods

This was a prospective costing study where medical records and hospital bills for children admitted with diarrhea at three hospitals were collected to estimate resource use and costs. Hospital length of stay was calculated from medical records. Costs incurred during the hospitalization were abstracted from the hospital bills. Interviews with the child’s caregivers provided data to estimate household costs which included transport costs and lost income. The portion of medical costs borne by insurance and household were reported separately. Annual economic burden before and after rotavirus vaccine introduction was estimated by multiplying the reported number of diarrhea hospitalizations in public health centers and district hospitals by the estimated economic burden per hospitalization. All costs are presented in 2014 US$.

Results

Costs for 203 children were analyzed. Approximately 93% of the children had health insurance coverage. Average hospital length of stay was 5.3 ± 3.9 days. Average medical costs for each child for the illness resulting in a hospitalization were $44.22 ± $23.74 and the total economic burden was $101, of which 65% was borne by the household. For households in the lowest income quintile, the household costs were 110% of their monthly income. The annual economic burden to Rwanda attributable to diarrhea hospitalizations ranged from $1.3 million to $1.7 million before rotavirus vaccine introduction.

Conclusion

Households often bear the largest share of the economic burden attributable to diarrhea hospitalization and the burden can be substantial, especially for households in the lowest income quintile.     

CD44 and annexin A2 mediate the C5a chemotactic cofactor function of the vitamin D binding protein

The vitamin D binding protein (DBP) is a plasma protein that significantly enhances the chemotactic activity of C5a and C5a(desArg) (cochemotactic activity). The objective of this study was to investigate how DBP mediates this process using neutrophils and U937 cells transfected with the C5a receptor (U937-C5aR cells) and comparing chemotaxis to C-activated serum (DBP dependent) vs purified C5a (DBP independent). Binding to the cell surface is essential for this protein to function as a chemotactic cofactor, and DBP binds to a chondroitin sulfate proteoglycan (CSPG) on neutrophil plasma membrane preparations. To determine whether a CSPG also functions to mediate cochemotactic activity, U937-C5aR cells were grown in chlorate to inhibit CSPG sulfation or treated with chondroitinase AC. Either treatment significantly inhibited chemotaxis only to C-activated serum. CD44 is a major cell surface CSPG on leukocytes, and functions to facilitate chemotaxis. Treatment of cells with anti-CD44 blocks chemotaxis of neutrophils and U937-C5aR cells to C-activated serum but not purified C5a. DBP binds to CD44 on the cell surface as evidenced by coimmunoprecipitation, confocal microscopy, and cell binding studies. Annexin A2 associates with CD44 in lipid rafts; therefore, its potential role in mediating cochemotactic activity was investigated. Results demonstrate that anti-A2 inhibits neutrophil and U937-C5aR chemotaxis specifically to C-activated serum, blocks DBP binding to cells, and colocalizes with anti-DBP on the cell surface. These results provide clear evidence that CD44 and annexin A2 mediate the C5a chemotactic cofactor function of DBP.     

Immediate early gene activity in song control nuclei and brain areas regulating motivation relates positively to singing behavior during, but not outside of, a breeding context

In some species, such as songbirds, much is known about how the brain regulates vocal learning, production, and perception. What remains a mystery is what regulates the motivation to communicate. European starlings (Sturnus vulgaris) sing throughout most of the year, but the social and environmental factors that motivate singing behavior differ seasonally. Male song is highly sexually motivated during, but not outside of, the breeding season. Brain areas outside the song control system, such as the medial preoptic nucleus (POM) and ventral tegmental area (VTA), have been implicated in regulating sexually motivated behaviors in birds, including song. The present study was designed to explore whether these regions, as well as three song control nuclei [area X, the high vocal center (HVC), and the robust nucleus of the arcopallium (RA)], might be involved differentially in song produced within compared to outside of a breeding context. We recorded the behavioral responses of breeding and nonbreeding condition male starlings to the introduction of a female conspecific. Males did not show context-dependent differences in the overall amount of song sung. However, immunocytochemistry for the protein product of the immediate early gene cFOS revealed a positive linear relationship between the total amount of songs sung and number of cFOS-labeled cells in POM, VTA, HVC, and RA for birds singing during, but not outside of, a breeding context. These results suggest that these regions differentially regulate male song production depending on reproductive context. Overall the data support the hypothesis that the POM and VTA interact with the song control system, specifically HVC and RA, to regulate sexually motivated vocal communication in songbirds.     

Comparison of transient protein expression in tobacco leaves and plant suspension culture

Transient gene expression is being developed to provide a more rapid means of assessing plant tissues as a protein production platform without the labor-intensive and time-consuming process of generating stably transformed transgenic plants. Transient expression of the gus-intron reporter gene was facilitated in three different tobacco species. Two different approaches to T-DNA delivery were compared: (1) infiltration of a prototrophic strain of Agrobacterium into leaves and (2) coculture of plant cell suspension cultures with an Agrobacterium auxotroph. Wounding of plant tissues with a wire brush prior to infiltration had a large positive impact on Nicotianabenthamiana leaves but not for Nicotiana tabacum or Nicotiana glutinosa. The best expression level achieved by leaf infiltration was in N. benthamiana (0.025% total soluble protein). A cell suspension culture line of N. glutinosa achieved an expression level greater than 0.04% TSP. The tissue culture-based technique therefore provides improved levels of transient expression under aseptic conditions to facilitate improvements in expression by control of the plant cell culture and Agrobacterium coculture environments.     

Mitochondrial DNA mutations activate programmed cell survival in the mouse heart

Increased frequencies of mitochondrial DNA (mtDNA) mutations characterize the aging heart and are also found in idiopathic dilated cardiomyopathy and end-stage heart failure. The pathogenic potential of such mutations is unclear. Transgenic mice showing accelerated accumulation of mtDNA mutations and dilated cardiomyopathy due to expression of an error-prone mtDNA polymerase specifically in the heart were characterized by Western blot analysis and immunohistochemistry for the levels of pro- and antiapoptotic proteins. By 8 wk of age, when frequencies of mtDNA mutations were approximately 0.01% and all transgenic mice showed four-chamber cardiac dilation, a vigorous prosurvival response was evident. Upregulated were Bcl-2, Bcl-xl, Bfl1, heat shock protein 27, and X-linked inhibitor of apoptosis protein, all of which function to inhibit apoptosis. Although translocation of Bax to mitochondria was also seen, it was not integrated into the mitochondrial membrane. Treatment of transgenic mice with doxorubicin failed to induce apoptosis, in contrast to controls, showing that the prosurvival response protected cardiomyocytes from a death stimulus. Increased apoptosis and release of cytochrome c appeared to precede the establishment of the prosurvival state suggesting that it may reflect a response to activation of programmed cell death pathways. It has been proposed that a programmed cell survival response is activated in the failing and aging heart. We show that elevated frequencies of mtDNA mutations may serve as one trigger for the activation of such a response.     

African Indigenous Vegetable Seed Systems in Western Kenya

Economic Botany - African indigenous vegetable (AIV) production systems are often constrained by the availability of high-quality seed. Concerted efforts to improve the informal seed sector could...