Defining the Normal Dorsal Contour of the Corpus Callosum with Time.

BACKGROUND AND PURPOSE: Morphological changes of the corpus callosum have been associated with a large number of congenital neurocognitive and psychiatric disorders. Focal defects or notches of the dorsal surface of the corpus callosum have not been well characterized. Our purpose was the following; 1) to characterize the dorsal contour of the corpus callosum during the life span, 2) to characterize the relationship of contour deviations to neighboring vessels, and 3) to determine whether contour deviations are congenital or acquired. MATERIALS AND METHODS: We retrospectively reviewed normal sagittal T1-weighted brain MR images. A "notch" was defined as a concavity in the dorsal surface at least 1 mm in depth. The corpus callosum was considered to be "undulating" if there were >2 notches, including an anterior and posterior notch. The presence of a pericallosal artery and its relationship to a notch were assessed. RESULTS: We reviewed 1639 MR imaging studies, spanning 0-89 years of age. A total of 1102 notches were identified in 823 studies; 344 (31%) were anterior, 660 (60%) were posterior, and 98 (9%), undulating. There was a positive correlation between the prevalence (P < .001) and depth (P = .028) of an anterior notch and age and a negative correlation between the prevalence of a posterior notch and age (P < .001). There was no difference between patient sex and corpus callosum notching (P = .884). Of the 823 studies with notches, 490 (60%) were associated with a pericallosal artery (P < .001). CONCLUSIONS: The prevalence and depth of notches in the anterior corpus callosum increase significantly with age; this finding suggests that most notches are acquired. There is a significant positive association between the presence of a corpus callosum notch and adjacent pericallosal arteries, suggesting that this may play a role in notch formation.

Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study.

BACKGROUND: Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF). OBJECTIVE: We compared effectiveness and safety of standard and reduced dose NOAC in AF patients. METHODS: Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula). RESULTS: Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%). CONCLUSIONS: Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.

Initiation of anticoagulation in atrial fibrillation: which factors are associated with choice of anticoagulant?

BACKGROUND: The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs). METHODS: Using Danish nationwide registry data, we identified AF patients initiating either a VKA or a NOAC from 22 August 2011 until 30 September 2016. We compared patient characteristics including age, gender, comorbidities, concomitant pharmacotherapy and CHA2 DS2 -VASc and HAS-BLED scores in patients initiated on a VKA, dabigatran, rivaroxaban or apixaban. Differences were examined using multivariable logistic regression models. RESULTS: The study population comprised 51 981 AF patients of whom 19 989 (38.5%) were initiated on a VKA, 13 242 (25.5%) on dabigatran, 8475 (16.3%) on rivaroxaban and 10 275 (19.8%) on apixaban. Those patients initiated on apixaban had higher mean ± SD CHA2 DS2 -VASc scores than those initiated on a VKA (3.1 ± 1.6 vs. 2.9 ± 1.6). Those initiated on dabigatran had lower mean CHA2 DS2 -VASc scores (2.7 ± 1.6) than all other groups. Patients with a history of a prior stroke were significantly more likely to be initiated on a NOAC compared with a VKA [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.28-1.43]. By contrast, patients with a history of myocardial infarction were less likely to be initiated on a NOAC compared with a VKA (OR 0.72, 95% CI 0.67-0.77). CONCLUSIONS: Atrial fibrillation patients who were initiated on apixaban had higher stroke risk scores than patients initiated on VKAs. Interestingly, opposite results were found for dabigatran.

Effects of farmyard manure and fertilizers on yield, fibre quality and nutrient balance of rainfed cotton (Gossypium hirsutum).

Two-year field experiments were conducted to evaluate the effect of fertilizer with or without farmyard manure (FYM) application on cotton productivity and fibre quality. A partial nutrient balance was calculated by the difference method (nutrient applied--crop removal). Seed cotton yield was improved with addition of FYM (5 Mg ha(-1)). Application of both N and P resulted in significant improvements in seed cotton yield than the control and without N plots (PK). Uniformity ratio and ginning outturn (GOT) was greater in the FYM amended plots than the plots without FYM. Nitrogen and P balance was positive in the fertilizer-N and P applied plots whereas K balance was negative in spite of the addition of fertilizer-K. Potassium balance was positive only when FYM was applied. These studies suggest that it is advantageous to apply FYM as it improves fibre yield by way of improved GOT and maintains a positive nutrient balance.

Effects of sucrose on resting metabolic rate, nitrogen balance, leucine turnover and oxidation during weight loss with low calorie diets.

Our research has shown that 800 kcal/day sucrose diets, unlike pure protein diets, maintained resting metabolic rate (RMR) and triiodothyronine (T3) levels. Concern that thermogenesis from sucrose might reflect protein catabolism led to this study, in which 23 obese women were studied as inpatients for 2 weeks on diets (kcal = 50 percent of RMR) containing either 93 percent sucrose (S, n = 7), sucrose plus protein (75 percent/20 percent, SP, n = 9), or fat plus protein (75 percent/20 percent, FP, n = 7). RMR, leucine kinetics (1-14C)leucine method) and nitrogen balance were measured. RMR fell (P less than 0.03) with SP and FP (-8.4 +/- 2.5 percent, -7.5 +/- 2.5 percent), but was maintained by S (+ 0.3 +/- 2.4 percent, P = 0.05 vs. SP and FP). Plasma leucine decreased (P less than 0.01) with S and SP by 36.6 +/- 4.0 percent and 17.0 +/- 4.7 percent, but increased by +52.8 +/- 9.0 percent (P less than 0.01) with FP (P = 0.0001 vs. S or SP). Leucine turnover, oxidation, and nonoxidative disposal all decreased (P = 0.0001) with S and with SP, in contrast to FP, in which these parameters were unchanged (all P = 0.0001 vs. S or SP). Cumulative (2 week) nitrogen loss was least (P = 0.001) in SP (-2.56 +/- 0.41 mol) compared with S (-4.37 +/- 0.19 mol) and FP (-4.76 +/- 0.12 mol), which did not differ. Since inclusion of sucrose in hypocaloric diets maintained RMR while decreasing leucine turnover, oxidation, and nitrogen loss, we conclude that the thermogenic effects of sucrose do not depend on protein catabolism.

Very-low-calorie diets with high and low protein content: impact on triiodothyronine, energy expenditure, and nitrogen balance.

Optimal composition of reducing diets remains controversial. Seventeen obese inpatients received 440 kcal/d, either 41% protein plus 55% carbohydrate (CD) or 95% protein (PP), for 3 wk. There were no significant diet effects (all data CD vs PP) in weight loss (8.88 +/- 1.01 vs 8.74 +/- 0.79 kg), loss of lean mass (2.10 +/- 0.35 vs 1.61 +/- 0.39 kg), metabolic rate reduction (15.3 +/- 2.8 vs 13.0 +/- 5.2%), or meal-stimulated thermogenesis (26.6-37.9 vs 29.0-26.1 net kcal/3 h [time NS also]). Triiodothyronine (T3) responses differed (2.35 +/- 0.11 to 1.57 +/- 0.14 vs 2.43 +/- 0.11 to 1.47 +/- 0.12 nmol/L, p less than 0.01) as did free T3 (3.4 +/- 0.2 to 2.6 +/- 0.2 vs 3.2 +/- 0.2 to 2.0 +/- 0.2 pmol/L, (p less than 0.01]; thyroxine declined similarly in both groups. Subjects fed CD gained no advantage over subjects fed PP. Regression analyses revealed no relationship between thyroid hormones, energy deficit, or lean mass with nitrogen losses, suggesting that other or more complex processes govern endogenous protein metabolism during weight loss.

Catabolic effects of thyroid hormone excess: the contribution of adrenergic activity to hypermetabolism and protein breakdown.

Although patients with thyrotoxicosis improve clinically after treatment with beta-adrenergic blocking drugs, it has never been established whether the hypermetabolism and body protein wasting caused by thyroid hormone excess are actually mediated by adrenergic mechanisms. To evaluate this issue, we measured basal energy expenditure, epinephrine-stimulated calorigenesis, and leucine kinetics (an index of body protein catabolism) in six normal volunteers before and after triiodothyronine (T3) administration (150 micrograms/d for 1 week). Serum T3 rose nearly threefold (P less than 0.001) during T3 administration, producing significant increases in basal metabolic rate (21%, P less than 0.001), nitrogen excretion (45%, P less than 0.001), and leucine flux (45%, P less than 0.01). In response to epinephrine infusion, the absolute rise in metabolic rate above basal was 57% greater in the thyrotoxic condition (P less than 0.02). Although beta-adrenergic blockade with intravenous propranolol totally abolished the calorigenic response to epinephrine, it had no detectable effect on either the accelerated basal metabolic rate or the augmented body protein catabolism caused by thyroid horomone excess. Our data suggest that in the basal, resting state, the increased metabolic rate and accelerated protein breakdown caused by thyroid hormone are not adrenergically mediated. However, under nonbasal conditions (when sympathetic activity is stimulated), enhanced responsiveness to catecholamine calorigenesis may exaggerate the hypermetabolic state and thereby contribute to weight loss and other clinical manifestations of thyrotoxicosis. This mechanism may explain the clinical efficacy of beta-adrenergic blocking agents in the treatment of thyrotoxicosis.