BackgroundArachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date.ResultsIn this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10-48) and lower DGLA levels (p = 9.80 × 10-11) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10-16 in African Americans, 2.68 × 10-23 in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups.ConclusionsWe conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.

Spatial QRS/T angle and spatial T-wave axis were shown to be strong independent predictors of incident coronary heart disease (CHD) and total mortality, but they are not routinely available. We evaluated whether frontal plane QRS/T angle, easily obtained as the difference between frontal plane axes of QRS and T, provides a suitable substitute for spatial QRS/T angle as a risk predictor. Our study consisted of 13,973 participants from the ARIC Study. Outcome variables were incident CHD and total mortality during a median follow-up of 14 years. Electrocardiographic variables were categorized as abnormal (>/=95th percentile), borderline (>/=75th and <95th percentile), and normal (<75th percentile) separately for men and women. Cox regression was used to assess the effect of electrocardiographic variables on risk of each outcome. The normal category was considered the reference cell. With adjustment for demographic and clinical characteristics, both QRS/T angles were approximately equally strong predictors of total mortality with >50% increased risk. Spatial QRS/T angle was a stronger predictor of incident CHD in women, with a 114% increased risk, but it was not significantly associated with risk of incident CHD in men. Similarly, frontal plane QRS/T angle was statistically significant for only women with a 74% increased risk of incident CHD. In conclusion, frontal plane QRS/T angle as an easily derived risk measure is a suitable clinical substitute for spatial QRS/T angle for risk prediction.

The amount of root substance removed by scaling and root planing is largely unknown. The present study evaluated in vitro the root substance loss caused by a defined number of working strokes at known forces. Forty extracted teeth with loss of connective tissue attachment into the middle third of the roots were washed and embedded in plaster, leaving one entire corono-apical tooth aspect exposed. The teeth were reproducibly repositioned in a bench-vise, where a profilometer repeatedly measured root surface levels at the same location. In a standard area of the roots a total of 40 working strokes were applied. Low forces were used in 30 teeth and high forces in 10 teeth. The forces were recorded using a piezo-electric receiver built into the upper shank of the curet. Root substance loss was measured after 5, 10, 20, and 40 working strokes. The results showed that the mean low force used per working stroke across all 40 strokes was 3.04 Newtons for the low forces, and 8.48 Newtons for the high forces. Mean cumulative loss of root substance across 40 strokes was 148.7 microns at low forces, and 343.3 microns at high forces. The mean force per stroke increased slightly across the 40 strokes, while substance removal per stroke decreased. Substance removal per stroke during strokes 1 to 5 was 6.8 microns using low forces and 20.6 microns using high forces. During strokes 21 to 40 mean removal per stroke was 2.3 microns at low forces, and 5.6 microns at high forces. These results suggest that high forces remove more root substance, and loss per stroke becomes less with increasing numbers of strokes.

Rationale: Survivorship from critical illness has improved; however, factors mediating the functional recovery of persons experiencing a critical illness remain incompletely understood. Objectives: To identify groups of acute respiratory failure (ARF) survivors with similar patterns of physical function recovery after discharge and to determine the characteristics associated with group membership in each physical function trajectory group. Methods: We performed a secondary analysis of a randomized controlled trial, using group-based trajectory modeling to identify distinct subgroups of patients with similar physical function recovery patterns after ARF. Chi-square tests and one-way analysis of variance were used to determine which variables were associated with trajectory membership. A multinomial logistic regression analysis was performed to identify variables jointly associated with trajectory group membership. Results: A total of 260 patients enrolled in a trial evaluating standardized rehabilitation therapy in patients with ARF and discharged alive (NCT00976833) were included in this analysis. Physical function was quantified using the Short Physical Performance Battery at hospital discharge and 2, 4, and 6 months after enrollment. Latent class analysis of the Short Physical Performance Battery scores identified four trajectory groups. These groups differ in both the degree and rate of physical function recovery. A multinomial logistic regression analysis was performed using covariates that have been previously identified in the literature as influencing recovery after critical illness. By multinomial logistic regression, age (P , 0.001), female sex (P = 0.001), intensive care unit (ICU) length of stay (LOS) (P = 0.003), and continuous intravenous sedation days (P = 0.004) were the variables that jointly influenced trajectory group membership. Participants in the trajectory demonstrating most rapid and complete functional recovery consisted of younger females with fewer continuous sedation days and a shorter LOS. The participant trajectory that failed to functionally recover consisted of older patients with greater sedation time and the longest LOS. Conclusions: We identified distinct trajectories of physical function recovery after critical illness. Age, sex, continuous sedation time, and ICU length of stay impact the trajectory of functional recovery after critical illness. Further examination of these groups may assist in clinical trial design to tailor interventions to specific subgroups.

Younger women with breast cancer consistently show greater psychological distress than older women. This study examined a range of factors that might explain these age differences. A total of 653 women within 8 months of a first-time breast cancer diagnosis provided data on patient characteristics, symptoms, and psychosocial variables. Chart reviews provided cancer and treatment-related data. The primary outcome was depressive symptomatology assessed by the Beck Depression Inventory. A succession of models that built hierarchically upon each other was used to determine which variables could account for age group differences in depression. Model 1 contained age group only. Models 2–5 successively added patient characteristics, cancer-related variables, symptoms, and psychosocial variables. As expected, in the unadjusted analysis (Model 1) younger women were significantly more likely to report depressive symptomatology than older women (p < 0.0001). Age remained significantly related to depression until Model 4 which added bodily pain and vasomotor symptoms (p = 0.24; R = 0.27). The addition of psychosocial variables in Model 5 also resulted in a model in which age was nonsignificant (p = 0.49; R2 = 0.49). Secondary analyses showed that illness intrusiveness (the degree that illness intrudes on specific areas of life such as work, sex life, recreation, etc.) was the only variable which, considered individually with age, made the age group-depression association nonsignificant. Age differences in risk of depression following a breast cancer diagnosis can be explained by the impact of cancer and its treatment on specific areas of a woman’s life.

The inferior control rate for stage T2b lesions has implications for treatment. Our study supports the conclusions of reports in the literature showing that low fraction size negatively influences outcome in patients with early glottic cancer.

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Background. This review was done to assess the outcomes and patterns of recurrence in a group of patients with Stage III endometrial carcinoma that might help guide adjuvant therapy. Methods. A retrospective review was performed of 105 patients treated from 1970–1990 at three institutions. All patients underwent abdominal hysterectomy, with 60 having pathologic node assessment and 45 having cytologic examination of peritoneal washings. A single extrauterine site was involved in 75% of patients; 20% and 5% had two and three sites involved, respectively. All patients received postoperative external beam irradiation to the pelvis or pelvis and paraaortic regions for pathologically positive paraaortic nodes. Actuarial techniques were used to estimate the survival and recurrence rates. Results. The 5‐year disease‐free survival rate for all patients was 64%. Univariate analysis revealed that the depth of myometrial penetration, the clear cell or papillary serous pathologic type, the histologic grade, and the number of extrauterine sites predicted disease‐free survival. Cox regression revealed the grade and pathologic findings to be independent predictors of disease‐free survival. The overall 5‐year pelvic recurrence rate was 21%, with multivariate analysis revealing the grade to be the strongest prognostic factor. Pathologic findings and the number of involved extrauterine sites were the most important prognostic factors for abdominal recurrence and other sites of distant relapse. Conclusions. The subgroup of patients with low‐grade endometrial tumors or superficial myometrial penetration has a low distant relapse rate. Local control remains the goal of therapy in these patients. Patients with high‐grade tumors, deep myometrial penetration, clear cell or papillary serous histologic types, or two or more involved extrauterine sites are at high risk for distant recurrence that may include the abdomen. Investigative strategies delivering aggressive adjuvant therapy are appropriate.