Exploring the Relationship between Maternal Meal Location and Infant Weight Gain

Exploring the Relationship between Maternal Meal Location and Infant Weight Gain. Background: For the first time in history, the current generation of children is projected to have a shorter life expectancy than their parents primarily because of children’s overweight status. Many factors place young children at risk for becoming overweight. The risk factors include: a family history of obesity, family lifestyle, diet sedentary living environments, and a lack of exercise. Purpose: To examine the relationship(s) between a mother’s mealtime habits, maternal BMI, the location of maternal meals, and infant weight gain at two months of age and at six months of life. Subjects: Mother and infant dyads (N=160) from three different pediatric clinics participated in the study. Racial and financial considerations were considered in clinic selection. Exclusion criteria required that the infant was: not born younger than 36 weeks, not hospitalized, not diagnosed with a genetic syndrome, and not diagnosed with a gastrointestinal disease or a metabolic disorder. Almost 60% of the mothers of the sample are African American, 34% are white, and 2.5% are Hispanic. The age of the mothers was positively skewed, and ranged from 15 years of age to 42 years of age, with a mean age of 24. Methods: Questionnaires were administered to each maternal participant at the 2 month and 6 month well-child visit. A series of closed-ended questions assessing maternal eating habits were included. It is hypothesized that mothers who eat their main meal at the kitchen or dining room table will have infants at average weight at 6 months of age and mothers who eat their main meal elsewhere would have heavier infants at 6 months of age. Descriptive statistics including frequencies, means and standard deviations as well as Pearson correlations will be conducted. Independent t-tests or chi-square tests will be conducted to compare differences between the mother groups, using p<.05. Plan: In order to analyze the data, we ran descriptive statistics to describe the sample including frequency, means, and standard deviations. To analyze the specific questions we used SPSS to run Pearson’s correlations with two tailed significance with a p value = .05 to examine the difference between the locations of mothers’ meal consumption with dependent variables of baby weight gain, and mothers’ BMI. We also ran a 3 way ANOVA to examine… Results: We found no statistically significant correlations between the mother’s BMI at 6 months and her meal score at 6 months. There was no statistically significant correlation between maternal meal scores at baseline or 6 months of age and infant’s weight gain by 6 months. However, we did find a weak positive correlation between the occurrence of adults in the household skipping meals or reducing meal size due to the lack of money and the mother’s BMI (Pearsons’s correlation = .178 where p<.05). Additionally, there was a weak negative correlation between infant weight gain from birth to 6 months and mother’s BMI (Pearson’s correlation = -.172 where p<.05). Conclusion: No significant correlations were found in response to the research questions, suggesting that the location of meals does not influence infant weight. However, other significant results that we were found may demonstrate the influence of eating habits and BMI.No embarg

Amide conjugates of the DO3A-N-(alpha-amino)propionate ligand: leads for stable, high relaxivity contrast agents for MRI?

A novel synthetic methodology for preparing amide conjugates of the DO3A-N-(alfa-amino)propionate chelator is described, using the synthesis of the DO3A-N-(alfa-benzoylamido)propionate chelator as an illustrative example. The model Gd(DO3A-N-(alfa-benzoylamido)propionate) chelate displays accelerated water exchange, stability in a wide pH range and inertness towards transmetallation by Zn2+. The Gd(DO3A-N-(alafa-benzoylamido)propionate) complex is mainly excreted via the kidneys, producing a significant increase of the kidney medulla/cortex enhancement ratio in MR images of Wistar rats, reflecting probably its increased hydrophobicity compared to Gd(DTPA). The results presented suggest that Gd(DO3A-N-(alfa-amido)propionate) chelates can be valuable leads for preparing potentially safe high relaxivity MRI contrast agents.This work was financially supported by Fundação para a Ciência e a Tecnologia, Portugal: project PTDC/QUI/70063/2006, including a grant to C.I.O.M., grant SFRH/BD/63994/2009 to M.F.F. and grant SFRH/BD/46370/2008 to A.F.M. and Rede Nacional de RMN (REDE/1517/RMN/2005) for the acquisition of the Varian VNMRS 600 NMR spectrometer in Coimbra. T.B.R. was supported by a Marie Curie Fellowship (FP/-PEOPLE-2009-IEF 254380) and an EMBO Fellowship (ALTF 1145-2009). Financial support from La Ligue Contre le Cancer, France (E. T.), and from Ministerio de Ciencia e Innovación, Spain: projects SAF2011-23622 (S.C.) and CTQ2010-20960-C02-02 (P.L.-L.), and Comunidad de Madrid, Spain, project S2010/BMD-2349 (S.C. and P.L.-L). This work was carried out in the frame of the COST D38 Action “Metal Based Systems for Molecular Imaging” and COST TD1004

The Nrf2 inhibitor brusatol is a potent antitumour agent in an orthotopic mouse model of colorectal cancer

© Evans et al. Nrf2 is a transcription factor that regulates cellular stress response and irinotecan-metabolising pathways. Its aberrant activity has been reported in a number of cancers, although relatively few studies have explored a role for Nrf2 in colorectal cancer (CRC). This study assessed the expression of Nrf2 in patient CRC tissues and explored the effect of Nrf2 modulation alone, or in combination with irinotecan, in human (HCT116) and murine (CT26) cell lines in vitro and in an orthotopic syngeneic mouse model utilising bioluminescent imaging. Using a tissue microarray, Nrf2 was found to be overexpressed (p < 0.01) in primary CRC and metastatic tissue relative to normal colon, with a positive correlation between Nrf2 expression in matched primary and metastatic samples. In vitro experiments in CRC cell lines revealed that Nrf2 siRNA and brusatol, which is known to inhibit Nrf2, decreased viability and sensitised cells to irinotecan toxicity. Furthermore, brusatol effectively abrogated CRC tumour growth in subcutaneously and orthotopicallyallografted mice, resulting in an average 8-fold reduction in luminescence at the study end-point (p=0.02). Our results highlight Nrf2 as a promising drug target in the treatment of CRC

Induction of Immunological Tolerence to Kidney Allografts Following Donor-Specific Blood Transfusion: Experimental Studies in the Rat

Donor-specific blood transfusion (DSBT) prior to renal transplantation has been known to have a beneficial effect on graft survival for over twenty years. In experimental models the magnitude of this effect is markedly strain-dependent. Two principal MHC disparate rat strain combinations were used to examine possible mechanisms of DSBT induced tolerance of renal allografts in this study. The first of these was an established model where a single pretransplant blood transfusion produces tolerance (DA into PVG: fully MHC disparate). The second (R8 into RT1u: class I-disparate) involved the development of a new model where DSBT alone was ineffective but the addition of a short course of cyclosporin A (15mg/kg/day for 7 days) at the time of the first of 4 weekly blood transfusions induced tolerance. In the first model, DA into PVG, over 80% of animals showed long-term acceptance of a kidney allograft following a single I ml DSBT 7 days prior to transplant. The tolerance was not tissue-specific and was independent of the thymus gland. Graft adaptation was seen in this model as passenger leukocyte depleted grafts survived for approximately 100 days in unmodified hosts (normal rejection time 80% of animals and was independent of the thymus gland. No evidence was seen for graft adaptation. Graft acceptance following DSBT/cyclosporin A-pretreatment correlated with low levels of cytotoxic alloantibody while DSBT alone led to high alloantibody levels and graft rejection. Interestingly the production of intragraft Th2 cytokines correlated with graft rejection rather than tolerance. This observation may reflect the immunological role of alloantibody in causing graft damage in this experimental model whereas in other models alloantibody may tend to favour tolerance rather than rejection. This protocol for tolerance induction was also shown to be effective in a fully disparate strain combination (DA into Lewis) where it was found that increasing the number of transfusions improved graft survival. Both of these models suggest that DSBT-pretreatments have a potential role in clinical practice especially when cyclosporin A is likely to be used as the principle immunosuppressant. DSBT is currently used in a small number of transplant centres but a greater understanding of the underlying mechanisms and development of a more effective protocol is required if its use is to become widespread

The Lang-Trotter conjecture for Drinfeld modules

In 1986, Gupta and Murty proved the Lang-Trotter conjecture in the case of elliptic curves having complex multiplication, conditional on the generalized Riemann hypothesis. That is, given a non-torsion point P∈E(ℚ), they showed that P (mod p) generates E(p) for infinitely many primes p, conditional on the generalized Riemann hypothesis. We demonstrate that Gupta's and Murty's result can be translated into an unconditional result in the language of Drinfeld modules. We follow the example of Hsu and Yu, who proved Artin's conjecture unconditionally in the case of sign normalized rank one Drinfeld modules. Further, we will cover all necessary background information

Protein expression in colorectal cancer

Introduction: Colorectal cancer is the second most common UK cancer. Biomarkers which predict survival may be valuable for targeting adjuvant therapy and can provide insights into tumour biology. Small and early cancers are being diagnosed more commonly in the UK population due to the introduction of population-based colorectal cancer screening in 2005. Analysis of resected small (≤20mm across) tumours in Liverpool has established that flat and depressed morphology can predict advanced stage at presentation. Proteomic analysis of small cancers was conducted with the aim of generating biomarkers which correspond to morphology, stage and patient survival. Patients and Methods: Laser capture microdissection was used to procure enriched matched benign and malignant colorectal epithelial cell populations. Laser captured proteins were extracted into lysis buffer, normalised against a reference standard, separated using 2D SDS-PAGE and visualized with silver staining. Comparison was made between the tumour gels, (n=10) and matched normal colonic gels, (n=9) by two different observers and gel analysis software, Progenesis SameSpots. Differentially expressed proteins were identified using tandem mass spectrometry and included redox proteins peroxiredoxin 2, peroxiredoxin 6 and SH3 binding glutamic acid-rich protein-like 3; and cytoskeletal protein cofilin1. Also identified were the anti-apoptotic protein heat shock protein 27 and inflammatory protein S100A8, which had been previously identified in 2D gel analysis of undissected colorectal cancer in our Institution (n=12 gels) and previously validated in a small cohort of paraffin-embedded colorectal cancers (n=98). In this study, HSP27 was further evaluated in a large cohort of paraffin-embedded colorectal cancer tissue (n=404). S100A8 and related proteins S100A9 and Smad4 were similarly evaluated in a large cohort (n=313). Results: High HSP27 levels were strongly associated with poor cancer-specific survival in rectal cancer (n=205, P=0.0063) but not colon cancer; (n=199, P=0.7385). Multivariate Cox regression confirmed nodal metastases (P=0.0001) and HSP27 expression (P=0.0233) as independent markers of survival in rectal cancer. HSP27 levels remained unchanged in the majority of cases 65/80 (81%) between diagnostic biopsies and matched surgical samples, regardless of whether patients had undergone preoperative radiotherapy. S100A8 expression co-localised with a subset of S100A9-positive monocytes. S100A9 was co-expressed with CD14 in tumour-associated monocytes, but not with CD68 in tissue macrophages. Smad4 was expressed in the tumour cytoplasm of 262/304 (14%) tumours. Loss of Smad4 expression correlated with a reduction in the stromal S100A8-positive, but not S100A9-positive cell count, (P=0.034, Mann-Whitney U test) and was associated with a poorer overall survival in patients with stage I-II disease, but not stage III disease. Antibodies to cofilin1 and cofilin-phospho(ser3) were assessed in colorectal cancer cell and tissue lysate and found to be specific on 1D and 2D western blot. Conclusion: Elevated HSP27 is an independent marker of poor prognosis in rectal cancer whose expression is not altered by neo-adjuvant radiotherapy. Smad4-negative tumours are associated with fewer infiltrating S100A8 positive stromal monocytes. In node-negative tumours, loss of Smad4 expression in associated with a poorer prognosis. These findings provide a sound platform for further investigation of both S100A8 and HSP27 proteins in colorectal cancer

The Pharmacokinetics of The Biliary Excretion of Ciprofloxacin

The pharmacokinetics of ciprofloxacin excretion have been studied in 54 patients undergoing biliary and pancreatic operations with and without obstruction of the common bile duct. High concentrations were achieved in common duct bile within 20 minutes of intravenous injection and persisted for over 3 hours after 100 mg and for over 8 hours after 200 mg. The concentration of ciprofloxacin in the bile of functioning gall bladders was much greater than that in the common duct bile. Remarkably, it was identified in therapeutic concentrations in the bile of obstructed ducts. This and the rapid fall from initially high venous concentrations probably reflect diffusion from the circulation as a result of the exceptional tissue penetration. A unique feature of this study was the finding of clinically significant concentrations in the bile of obstructed ducts

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio