Differential effect of short-term popular diets on TMAO and other cardio-metabolic risk markers.

BACKGROUND: Dietary nutrient intake and its metabolism by the gut microbiome have recently been implicated in cardiovascular disease (CVD) risk. In particular, trimethylamine N-oxide (TMAO), a metabolite of the gut microbiota, has been shown to be a predictor of incident CVD events. Elevated levels of branched-chain amino acids (BCAA) have also been associated with an increased propensity for insulin resistance. METHODS: To study the association of dietary intake with systemic TMAO, its nutrient precursors, and BCAA levels on fasting plasma levels of TMAO and its nutrient precursors and BCAA, we conducted an exploratory post-hoc analysis of 3 popular diets - high fat (Atkins), Mediterranean (South Beach), and very low fat (Ornish) - using plasma samples from a prior randomized, crossover study, with each isocaloric dietary phase lasting 4 weeks. Metabolites were quantified using stable isotope dilution HPLC with on-line tandem mass spectrometry. RESULTS: Compared to the low fat Ornish phase, the high fat Atkins dietary phase was characterized by increased levels of TMAO (3.3 vs. 1.8 µM, p = 0.01), and the BCAA valine (272.8 vs. 235.8 µM, p = 0.005) and leucine (105.9 vs. 96.4 µM, p = 0.01). The high fat Atkins dietary phase was also associated with higher levels of TMAO (3.3 vs 1.6 µM, p = 0.04), valine (272.8 vs. 240.7 µM, p = 0.004), and leucine (105.9 vs. 96.4 µM, p = 0.01) compared to baseline. CONCLUSIONS: These data suggest that over a 4-week interval, a saturated fat diet that is predominantly animal-based, compared to an isocaloric, low fat, predominantly plant-based diet, is associated with heightened risk for cardiometabolic derangements, as monitored by a higher plasma levels of both TMAO and BCAA.

Origin of surface canting within Fe3O4 nanoparticles.

The nature of near-surface spin canting within Fe3O4 nanoparticles is highly debated. Here we develop a neutron scattering asymmetry analysis which quantifies the canting angle to between 23° and 42° at 1.2 T. Simultaneously, an energy-balance model is presented which reproduces the experimentally observed evolution of shell thickness and canting angle between 10 and 300 K. The model is based on the concept of Td site reorientation and indicates that surface canting involves competition between magnetocrystalline, dipolar, exchange, and Zeeman energies.

Fatal Apophysomyces elegans infection transmitted by deceased donor renal allografts.

Two patients developed renal mucormycosis following transplantation of kidneys from the same donor, a near-drowning victim in a motor vehicle crash. Genotypically, indistinguishable strains of Apophysomyces elegans were recovered from both recipients. We investigated the source of the infection including review of medical records, environmental sampling at possible locations of contamination and query for additional cases at other centers. Histopathology of the explanted kidneys revealed extensive vascular invasion by aseptate, fungal hyphae with relative sparing of the renal capsules suggesting a vascular route of contamination. Disseminated infection in the donor could not be definitively established. A. elegans was not recovered from the same lots of reagents used for organ recovery or environmental samples and no other organ transplant-related cases were identified. This investigation suggests either isolated contamination of the organs during recovery or undiagnosed disseminated donor infection following a near-drowning event. Although no changes to current organ recovery or transplant procedures are recommended, public health officials and transplant physicians should consider the possibility of mucormycosis transmitted via organs in the future, particularly for near-drowning events. Attention to aseptic technique during organ recovery and processing is re-emphasized.

Core-shell magnetic morphology of structurally uniform magnetite nanoparticles.

A new development in small-angle neutron scattering with polarization analysis allows us to directly extract the average spatial distributions of magnetic moments and their correlations with three-dimensional directional sensitivity in any magnetic field. Applied to a collection of spherical magnetite nanoparticles 9.0 nm in diameter, this enhanced method reveals uniformly canted, magnetically active shells in a nominally saturating field of 1.2 T. The shell thickness depends on temperature, and it disappears altogether when the external field is removed, confirming that these canted nanoparticle shells are magnetic, rather than structural, in origin.

Tricritical point and the doping dependence of the order of the ferromagnetic phase transition of La1-xCaxMnO3.

We report on the doping dependence of the order of the ferromagnetic metal to paramagnetic insulator phase transition in La1-xCaxMnO3. At x=0.33, magnetization and specific heat data show a first order transition, with an entropy change (2.3 J/mol K) accounted for by both volume expansion and the discontinuity of M approximately 1.7mu(B) via the Clausius-Clapeyron equation. At x=0.4, the data show a continuous transition with tricritical point exponents alpha=0.48+/-0.06, beta=0.25+/-0.03, gamma=1.03+/-0.05, and delta=5.0+/-0.8. This tricritical point separates first- (x<0.4) from second-order (x>0.4) transitions.

A novel TC deletion resulting in Pro(260)-->Stop in the human LCAT gene is associated with a dominant effect on HDL-cholesterol.

Human lecithin:cholesterol acyltransferase (LCAT) plays a key role in the biogenesis of circulating high-density lipoprotein-cholesterol (HDL-C) and reverse cholesterol efflux. We investigated the molecular defect in the LCAT gene in a family with low levels of HDL-C. The proband, a 53-year-old woman from Oklahoma City, had a HDL-C level of 0.21 mmol/l. The LCAT activity in the proband was 5 nmol/ml/h and cholesterol esterification rate was 54.2 nmol/ml/h, consistent with LCAT deficiency. Analysis of polymerase chain reaction (PCR) amplified subgenomic fragments of LCAT DNA on polyacrylamide gels revealed heteroduplex bands in the proband and three other affected individuals in exon 6. DNA sequence analyses of the proband's LCAT gene identified a 2 base pair deletion (TC) (base pairs 4544-4545, corresponding to amino acid 255) in the heteroduplex allele, thereby converting Pro(260) to a premature stop codon and a predicted truncated protein of 260 amino acids. This is approximately 60% of the length of the normal translated protein. The heterozygous individuals also revealed significant reduction in apolipoprotein A-1 levels compared with the unaffected family members (n=4). The marked reduction in HDL-C in the proband and sibling suggests a dominant effect of this mutation on HDL-C levels. Furthermore, because the deletion results in a heterozygous allele that can be detected by a simple PCR reaction and polyacrylamide gel-size fractionation, it may be possible to rapidly screen susceptible individuals for the presence of this mutation.

Prevalence of the APOC3 promoter polymorphisms T-455C and C-482T in Asian-Indians.

Potential mechanisms accounting for the high cardiovascular death rates observed in Asian-Indians are dyslipidemia and insulin resistance. Polymorphisms in the APOC3 promoter (-455 T/C and -482 C/T) were frequently encountered in young Asian-Indians and they correlated with reduced concentrations of apolipoprotein A-I.

Minocycline and ethylenediaminetetraacetate for the prevention of recurrent vascular catheter infections.

Three patients with recurrent vascular catheter-related bacteremia were successfully treated by allowing a solution of minocycline and ethylenediaminetetraacetate (EDTA) to dwell in the lumen of the indwelling catheter or by coating polyurethane catheters with minocycline/EDTA and flushing the lumen daily with the same solution. In vitro and in vivo experiments showed that minocycline/EDTA may have broad-spectrum antimicrobial activity, may have optimal anticoagulant activity, and may be highly efficacious in preventing catheter colonization.

Characterization of the human interleukin 1 receptor on human polymorphonuclear leukocytes.

Interleukin 1 (IL-1) is a mediator of inflammation with multiple proinflammatory and immunologic enhancing activities. Human polymorphonuclear leukocytes (PMN) also play a major role in the inflammatory response. We have found that PMN possess a single type of high affinity receptor for human recombinant (r) IL-1 alpha with an apparent dissociation constant of 0.28 nM. Approximately 700 receptors are present per cell. Binding is rapid with 50% of maximal binding occurring within 20 min at 4 degrees C. Internalization of the receptor occurs within 25 min after shifting the cells to 37 degrees C. The receptor exhibits an apparent molecular weight of approximately 60-70 kDa. Electron microscopic autoradiography studies reveal that the 125I-rIL-1 alpha localized in the nucleus within 180 min after shifting cells to 37 degrees C. The accumulation of relatively high levels of 125I-rIL-1 alpha in the nucleus is consistent with earlier observations on the nuclear localization of IL-1 in T lymphocytes. The possibility that IL-1 may exert a direct action in the nucleus remains to be determined.

Sign language and autism.

Research findings and issues in teaching sign language to nonspeaking autistic children are reviewed. Data on over 100 children indicate that nearly all autistic children learn receptive and expressive signs, and many learn to combine signs. These children also exhibit marked improvement in adaptive behaviors. Speech skills are acquired by fewer children and may be developed through simultaneous speech and sign training. Possible explanations for these results are given, together with suggestions for future research and data collection. Recommended innovations include exposure to fluent signers and training in discourse and code-switching. Different sign language teaching methods need to be investigated more fully, including emphasis on training sign language within the children's total environment and with greater staff and parental participation.