Birth weight,weight over the adult life course and risk of breast cancer

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four-time points over 25 years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n = 70,397) aged 50–79 years without breast cancer at enrollment (1993–1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self-reported. Breast cancer cases were centrally adjudicated. Compared to women with birth weight of 6–8 pounds, women with birth weight of <6 pounds had lower risk of breast cancer (HR = 0.88 95% CI: 0.79–0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer.     

DNA Methylation Variants at HIF3A Locus,B-Vitamin Intake,and Long-term Weight Change: Gene-Diet Interactions in Two U.S. Cohorts

The first epigenome-wide association study of BMI identified DNA methylation at an HIF3A locus associated with BMI. We tested the hypothesis that DNA methylation variants are associated with BMI according to intake of B vitamins. In two large cohorts, we found significant interactions between the DNA methylation–associated HIF3A single nucleotide polymorphism (SNP) rs3826795 and intake of B vitamins on 10-year changes in BMI. The association between rs3826795 and BMI changes consistently increased across the tertiles of total vitamin B₂ and B₁₂ intake (all P for interaction <0.01). The differences in the BMI changes per increment of minor allele were −0.10 (SE 0.06), −0.01 (SE 0.06), and 0.12 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B₂ intake and −0.10 (SE 0.06), −0.01 (SE 0.06), and 0.10 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B₁₂ intake. In two independent cohorts, a DNA methylation variant in HIF3A was associated with BMI changes through interactions with total or supplemental vitamin B₂, vitamin B₁₂, and folate. These findings suggest a potential causal relation between DNA methylation and adiposity.     

Amino acid utilization by Fusobacterium nucleatum grown in a chemically defined medium

The present investigation evaluated amino acid utilization by 120 strains of Fusobacterium nucleatum in a chemically defined medium and attempted to relate the patterns to 3 proposed subspecies of F. nucleatum. Strains were inoculated into a chemically defined medium, with and without 2 g/l glucose, consisting of 14 inorganic salts, 21 amino acids, 23 vitamins and cofactors, and 7 purines and pyrimidines. After 7 days of anaerobic incubation, the spent culture medium, as well as the uninoculated control medium, were analyzed for amino acid content by ion chromatography. Amino acid utilization was determined by the differences in concentrations of amino acids found in inoculated and uninoculated samples. If greater than 34% of the amino acid was removed from the medium, the amino acid was considered to be utilized. Of the 21 amino acids present in the chemically defined medium, 8 amino acids, lysine, glutamine, asparagine, histidine, threonine, serine, glutamate and cysteine were consistently utilized. Four amino acids, tyrosine, tryptophan, methionine and aspartate were utilized by some strains but not others. Nine amino acids, alanine, leucine, isoleucine, glycine, valine, phenylalanine, proline, ornithine, and arginine were not utilized by any of the strains. The utilization patterns did not relate to subspecies formed on the basis of SDS-PAGE and DNA hybridization.     

Correlates of Positive Parenting Behaviors

The present study examined the influence of maternal and child characteristics on parenting behaviors in a genetically informative study. The participants were 976 twins and their mothers from the Colorado Longitudinal Twin Study and the Twin Infant Project. Indicators of positive parenting were coded during parent–child interactions when twins were 7–36 months old. Child cognitive abilities and affection were independent correlates of positive parenting. There were significant gender differences in the magnitude of genetic and environmental influences on positive parenting, with shared environmental influences on parenting of girls and additive genetic influences on parenting of boys. Girls received significantly more positive parenting than boys. Differences in etiology of positive parenting may be explained by developmental gender differences in child cognitive abilities and affection, such that girls may have more rewarding interactions with parents, evoking more positive parenting.     

Clinical and Research Considerations for Patients With Hypertensive Acute Heart Failure: A Consensus Statement from the Society for Academic Emergency Medicine and the Heart Failure Society of America Acute Heart Failure Working Group

Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H‐AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease that is based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H‐AHF.     

Patient-centered outcomes after laparoscopic cholecystectomy

Background

Laparoscopic cholecystectomy (LC) is the second most common general surgical operation performed in the United States, yet little has been reported on patient-centered outcomes.

Methods

We prospectively followed 100 patients for 2 years as part of an institutional review board–approved study. The Surgical Outcomes Measurement System (SOMS) was used to quantify quality-of-life (QoL) values at various time points postoperatively.

Results

Maximum pain was reported at 24 h (5.5 ± 2.2), and decreased to preoperative levels at 7 days (1.2 ± 2.3 vs. 2.0 ± 1.6, P = 0.096). Bowel function improved from before the operation to 3 weeks after surgery (10.7 ± 3.8 vs. 12.0 ± 3.2, P < 0.05), but then regressed to preoperative levels. Physical function worsened from before surgery (31.7 ± 6.2) to 1 week (27.5 ± 5.9, P < 0.0001), but surpassed preoperative levels at 3 weeks (33.5 ± 3.4, P < 0.01). Return to the activities of daily living occurred at 6.3 ± 4.7 days and work at 11.1 ± 9.0 days. Fatigue increased from before surgery (15.8 ± 6.2) to week 1 (20.7 ± 6.6, P < 0.0001) before improving at week 3 (14.0 ± 5.8, P < 0.01). Forty-four patients contacted the health care team 61 times before their 3 weeks appointment, most commonly for wound issues (26.2 %), pain (24.6 %), and gastrointestinal issues (24.6 %). Seventy-two percent reported that the procedure had no negative effect on cosmesis at 6 months. Satisfaction with the procedure was high, averaging 9.52 out of 11.

Conclusions

QoL is significantly affected in the 24 h after LC but returns to baseline at week 3. Cosmesis and overall satisfaction are high, and QoL improvements are maintained in the long term except for bowel function, which regresses to preoperative levels of impairment. Analysis of patient-initiated contacts after LC may provide feedback on discharge counseling to increase patient satisfaction.     

The self-efficacy of family caregivers for helping cancer patients manage pain at end-of-life

This preliminary study examined the self-efficacy of family caregivers with regard to helping cancer patients manage pain at end of life. A sample of 63 family caregivers of hospice-eligible cancer patients with pain provided ratings of their self-efficacy in assisting the patient in pain management and rated their own mood and level of caregiver strain. Patients completed measures of pain and quality of life. Data analyses revealed that caregivers who rated their self-efficacy as high reported much lower levels of caregiver strain as well as decreased negative mood and increased positive mood. Caregiver self-efficacy in managing the patient's pain was related to the patient's physical well-being. In dyads where the caregiver reported high self-efficacy, the patient reported having more energy, feeling less ill, and spending less time in bed. Considered overall, the results of this study suggest that caregiver self-efficacy in pain management is important in understanding how caregivers adjust to the demands of caring for cancer patients who have pain at the end of life.     

Role of the AcrAB-TolC efflux pump in determining susceptibility of Haemophilus influenzae to the novel peptide deformylase inhibitor LBM415

Haemophilus influenzae isolates vary widely in their susceptibilities to the peptide deformylase inhibitor LBM415 (MIC range, 0.06 to 32 microg/ml); however, on average, they are less susceptible than gram-positive organisms, such as Staphylococcus aureus and Streptococcus pneumoniae. Insertional inactivation of the H. influenzae acrB or tolC gene in strain NB65044 (Rd strain KW20) increased susceptibility to LBM415, confirming a role for the AcrAB-TolC pump in determining resistance. Consistent with this, sequencing of a PCR fragment generated with primers flanking the acrRA region from an LBM415-hypersusceptible H. influenzae clinical isolate revealed a genetic deletion of acrA. Inactivation of acrB or tolC in several clinical isolates with atypically reduced susceptibility to LBM415 (MIC of 16 microg/ml or greater) significantly increased susceptibility, confirming that the pump is also a determinant of decreased susceptibility in these clinical isolates. Examination of acrR, encoding the putative repressor of pump gene expression, from several of these strains revealed mutations introducing frameshifts, stop codons, and amino acid changes relative to the published sequence, suggesting that loss of pump repression leads to decreased susceptibility. Supporting this, NB65044 acrR mutants selected by exposure to LBM415 at 8 microg/ml had susceptibilities to LBM415 and other pump substrates comparable to the least sensitive clinical isolates and showed increased expression of pump genes.