Deceptively Simple NMR Spectra of Contiguously 13C-enriched Compounds

Contiguously 13C-enriched compounds are widely used in biosynthetic studies, since they effectively label a bonded pair of carbon atoms, rather than an individual atom. Such compounds are referred to as »bond labeled« compounds. With such substrates, the course of biosynthesis can be followed using 13C-NMR spectroscopy. When the enriched carbon atoms are chemically but not magnetically equivalent, the 13C-NMR spectra are unusual, and such spectra have been labeled "deceptively simple«. Furthermore, the use of standard NMR experiments such as DEPT (Distortionless Enhancement by Polarization Transfer) is complicated by the presence of homonuclear coupling between 13C nuclei. At natural abundance, the 13C nucleus is magnetically dilute and shows no homonuclear coupling. This paper analyzes the 13C-NMR spectra of a series of molecules derived from fully 13C-enriched acetylene, and explores some of the complications that arise in applying pulse NMR methods

An economic appraisal of lower extremity bypass graft maintenance

AbstractObjective: Infrainguinal graft surveillance leads to intervention on the basis of duplex-identified stenoses. We have become increasingly concerned about the high frequency with which such revisions are required to maximize graft patency and limb salvage rates. The economic implications of these procedures have not been carefully analyzed or justified. Methods: We retrospectively reviewed 155 consecutive autogenous infrainguinal bypass grafts performed for chronic leg ischemia in 141 patients. All patients were enrolled in a prospective surveillance program using color flow duplex imaging. Full economic appraisal (cost analysis, cost-effect analysis, and cost-benefit analysis) was performed for all graft surveillance and limb salvage–related interventions through use of standard accounting and valuation techniques. Results: Mean follow-up was 27 months. Five-year assisted primary patency (72%) and limb salvage rates (91%) were calculated by means of life table analysis. A total of 61 grafts required 86 revisions. Within 1 year of implantation, 36% of the grafts required revision. During this first year, the mean cost per graft enrolled was $9417. Time intervals after the initial year demonstrated a reduced annual revision rate (6$1725 per graft). The mean 5-year cost of graft maintenance ($16,318) approached that of the initial bypass graft ($19,331). The sum of the initial cost of bypass graft and 5-year graft maintenance cost ($35,649) was similar to the cost of amputation ($36,273). Grafts revised for duplex-detected stenoses (n = 46), in comparison with those revised after thrombosis (n = 15), had an improved 1-year patency (93% vs 57%; P <.01), required fewer amputations (2% vs 33%; P <.01), less frequently required multiple graft revisions (P =.06), and generated fewer expenses (at 12 months after revision, $17,688 vs$45,252, P <.01). Conclusion: The cost associated with graft maintenance is significant, particularly within the first year, and demands consideration. Revision of a duplex-identified stenosis was significantly less costly than revision after graft thrombosis. Compared with the cost of limb amputation, limb salvage–related expenses appear to be justified. (J Vasc Surg 2000;32:1-12.

High-resolution temporal profiling of transcripts during Arabidopsis leaf senescence reveals a distinct chronology of processes and regulation

Leaf senescence is an essential developmental process that impacts dramatically on crop yields and involves altered regulation of thousands of genes and many metabolic and signaling pathways, resulting in major changes in the leaf. The regulation of senescence is complex, and although senescence regulatory genes have been characterized, there is little information on how these function in the global control of the process. We used microarray analysis to obtain a highresolution time-course profile of gene expression during development of a single leaf over a 3-week period to senescence. A complex experimental design approach and a combination of methods were used to extract high-quality replicated data and to identify differentially expressed genes. The multiple time points enable the use of highly informative clustering to reveal distinct time points at which signaling and metabolic pathways change. Analysis of motif enrichment, as well as comparison of transcription factor (TF) families showing altered expression over the time course, identify clear groups of TFs active at different stages of leaf development and senescence. These data enable connection of metabolic processes, signaling pathways, and specific TF activity, which will underpin the development of network models to elucidate the process of senescence

The correlation of early flow disturbances with the development of infrainguinal graft stenosis: A 10-year study of 341 autogenous vein grafts

AbstractPurpose: Although duplex surveillance of infrainguinal bypass grafts is widely accepted, the optimal frequency and intensity of graft surveillance remains controversial. Earlier reports have suggested that grafts can be stratified into high-risk and low-risk groups based on the presence or absence of early graft flow disturbances. The purpose of this study was to provide long-term data in determining whether early graft flow disturbances detected by means of duplex scanning can predict the development of intrinsic vein graft stenosis. Methods: We reviewed a series of patients undergoing prospective duplex graft surveillance after autogenous infrainguinal bypass grafting procedures from 1987 to 1997. Patients included in the study underwent at least one duplex scan within 3 months of graft implantation and were observed for a minimum of 6 months. Grafts were categorized as abnormal when a focal flow disturbance with a peak systolic velocity greater than 150 cm/s was identified within 3 months of graft implantation. Results: Of 341 vein grafts in 296 patients who met inclusion criteria, 89 grafts (26%) required revision for intrinsic stenosis; the mean follow-up period was 35 months (range, 6 months to 10 years). Early flow disturbances were detected in 84 (25%) grafts. Grafts with early flow disturbances were more likely to ultimately require revision (43% vs 21%; P = .0001) and required initial revision earlier (8 months vs 16 months; P = .019). Eighty-two percent of initial graft revisions occurred in the first 2 postoperative years; 69% occurred in the first year. However, an annual 2% to 4% incidence of late-appearing graft stenosis persisted during long-term follow-up. An additional 24 patients (7% of grafts) required an inflow or outflow reconstruction. Conclusion: Grafts with early postoperative flow disturbances detected by means of duplex scanning have nearly three times the incidence of graft-threatening stenosis and an earlier requirement for revision, when compared with normal grafts. This suggests that the biology and etiology of these lesions may differ. These data support not only aggressive efforts to detect early graft lesions to stratify grafts at highest risk, but also continued lifelong graft surveillance to detect late-appearing lesions, inflow and outflow disease progression, and maximize graft patency. (J Vasc Surg 1999;30:8-15.

Acute hypoalgesic, neurophysiological and perceptual responses to low-load blood flow restriction exercise and high-load resistance exercise.

This study compared the acute hypoalgesic and neurophysiological responses to low-load resistance exercise with and without blood flow restriction (BFR), and free-flow, high-load exercise. Participants performed four experimental conditions where they completed baseline measures of pain pressure threshold (PPT), maximum voluntary force (MVF) with peripheral nerve stimulation to determine central and peripheral fatigue. Corticospinal excitability (CSE), corticospinal inhibition and short interval intracortical inhibition (SICI) were estimated with transcranial magnetic stimulation. Participants then performed low-load leg press exercise at 30% of one-repetition maximum (LL); low-load leg press with BFR at 40% (BFR40) or 80% (BFR80) of limb occlusion pressure; or high-load leg press of four sets of 10 repetitions at 70% one-repetition maximum (HL). Measurements were repeated at 5, 45 min and 24 h post-exercise. There were no differences in CSE or SICI between conditions (all P > 0.05); however, corticospinal inhibition was reduced to a greater extent (11%-14%) in all low-load conditions compared to HL (P 40, BFR80 and HL compared to LL (P ≤ 0.016). Neuromuscular fatigue displayed no clear difference in the magnitude or time course between conditions (all P > 0.05). In summary, low-load BFR resistance exercise does not induce different acute neurophysiological responses to low-load, free-flow exercise but it does promote a greater degree of hypoalgesia and reduces corticospinal inhibition more than high-load exercise, making it a useful rehabilitation tool. The changes in neurophysiology following exercise were not related to changes in PPT

Feeding styles and child weight status among recent immigrant mother-child dyads

Background: Research has shown that parental feeding styles may influence children’s food consumption, energy intake, and ultimately, weight status. We examine this relationship, among recent immigrants to the US. Given that immigrant parents and children are at greater risk for becoming overweight/obese with increased time in the US, identification of risk factors for weight gain is critical. Methods: Baseline data was collected on 383 mother-child dyads enrolled in Live Well, a community-based, participatory, randomized controlled lifestyle intervention to prevent weight gain in recent immigrant mothers. Socio-demographic information together with heights and weights were collected for both mother and child. Acculturation, behavioral data, and responses to the Caregiver’s Feeding Styles Questionnaire (CFSQ) were also obtained from the mother. Results: The children’s average age was 6.2 ± 2.7 years, 58% male. Mothers had been in the country for an average of 6.0 ± 3.3 years, and are Brazilian (36%), Haitian (34%) and Latino (30%). Seventy-two percent of the mothers were overweight/obese, while 43% of the children were overweight/obese. Fifteen percent of mothers reported their feeding style as being high demanding/high responsive; 32% as being high demanding/low responsive; 34% as being low demanding/high responsive and 18% as being low demanding/low responsive. In bivariate analyses, feeding styles significantly differed by child BMIz-score, ethnic group, and mother’s perceived stress. In multiple linear regression, a low demanding/high responsive feeding style was found to be positively associated (ß = 0.56) with a higher child weight as compared to high demanding/high responsive, controlling for known covariates (p = 0.01). Conclusions: Most mothers report having a low demanding/high responsive feeding style, which is associated with higher child weight status in this diverse immigrant population. This finding adds to the growing literature that suggests this type of feeding style may be a risk factor for childhood obesity. Further research is needed to help understand the larger socio-cultural context and its influence on feeding dynamics among immigrant families and families of lower incomes. How parents establish a certain feeding style in their home country compared to when they move to the US “obesogenic” environment, should also be explored

Feeding styles and evening family meals among recent immigrants

The protective effect of family meals on unhealthy weight gain and diet has been shown across multiple age groups; however, it is unknown whether a similar effect is present among diverse immigrant populations. In addition, little research has focused on factors associated with the frequency of evening family meals, such as feeding styles (how parents interact with their child around feeding). Therefore the goals of this paper are to explore the 1) association between the frequency of evening family meals and child weight status among new immigrant families, and 2) influence of immigrant mothers’ feeding styles on the frequency of evening family meals. Baseline self-reported socio-demographic information and measured heights and weights were collected for both mother and child (age range: 3–12 years) among 387 mother-child dyads enrolled in Live Well, a community-based, participatory-research, randomized controlled lifestyle intervention to prevent excessive weight gain in recent (U.S.) immigrant mothers and children. For children, height and weight measurements were transformed into BMI z-scores using age-and sex-specific CDC standards and categorized as overweight (85th–94th percentile) and obese (≥95th percentile); mothers’ BMI was calculated. Frequency of evening family meals, eating dinner in front of the TV, acculturation and responses to the Caregiver’s Feeding Styles Questionnaire (CFSQ) were also obtained from the mother. Children were categorized as “eating evening family meals regularly” if they had an evening family meal ≥5 times per week. Overall, 20% of children were overweight and 25% were obese. Less than half (40.9%) of families had regular evening family meals. In multivariate analyses, adjusting for covariates, children who were overweight/obese were significantly less likely to have ≥5 evening family meals/week compared with normal weight children (OR = 0.51, 95% CI 0.32-0.82) . Mothers who had a low demanding/high responsive or a low demanding/low responsive feeding style, were less likely to have ≥5 evening family meals/week compared to mothers with a high demanding/high responsive feeding style (OR = 0.41, 95% CI 0.18-0.0.96, OR = 0.33, 95% CI 0.13-0.87, respectively). Future interventions and programs that seek to help parents establish healthy household routines, such as family meals, may consider tailoring to specific maternal feeding styles

Literature review of visual representation of the results of benefit–risk assessments of medicinal products

Background The PROTECT Benefit–Risk group is dedicated to research in methods for continuous benefit–risk monitoring of medicines, including the presentation of the results, with a particular emphasis on graphical methods. Methods A comprehensive review was performed to identify visuals used for medical risk and benefit–risk communication. The identified visual displays were grouped into visual types, and each visual type was appraised based on five criteria: intended audience, intended message, knowledge required to understand the visual, unintentional messages that may be derived from the visual and missing information that may be needed to understand the visual. Results Sixty-six examples of visual formats were identified from the literature and classified into 14 visual types. We found that there is not one single visual format that is consistently superior to others for the communication of benefit–risk information. In addition, we found that most of the drawbacks found in the visual formats could be considered general to visual communication, although some appear more relevant to specific formats and should be considered when creating visuals for different audiences depending on the exact message to be communicated. Conclusion We have arrived at recommendations for the use of visual displays for benefit–risk communication. The recommendation refers to the creation of visuals. We outline four criteria to determine audience–visual compatibility and consider these to be a key task in creating any visual. Next we propose specific visual formats of interest, to be explored further for their ability to address nine different types of benefit–risk analysis information