Proximate and Phytochemical composition and antioxidant properties of indigenous landraces of omani fenugreek seeds.

Background: Fenugreek (Trigonella foenum graecum L) is receiving global attention as a functional food due to its unique nutritional and medicinal properties as anti-diabetic, hypocholesterolemic, antipyretic, anti-carcinogenic and seasoning and flavoring agent.Materials and Methods: Seeds of indigenous fenugreek accessions were collected from three different ecological regions (Al-Dakhaliyah, Al- Dhahirah, and Al-Batinah) of Sultanate of Oman. The samples were analyzed for proximate chemical composition, phytochemical contents and antioxidant properties.Results: Only significant (P<0.05) differences were observed in the crude fiber and gross energy values of fenugreek seeds collected from different regions of Oman. The highest crude fiber content (8.6 %) was observed in samples collected from Al-Dhahirah region whereas the lowest value (7.1%) was found in samples collected from Al-Dakhaliyah region. No significant (P<0.05) differences were however observed in the moisture, crude protein, crude fat, and ash contents of samples collected from the three regions of Oman. The regional variability significantly (P<0.05) affected the phytochemicals composition and the highest amount of total phenolics (139.2 mg GAE/100g) were recorded in samples collected from Al-Batinah, followed by Al-Dhakhliyah (130.0 mg GAE/100g) and Al-Dhahirah (127.8 mg GAE/100g) regions, respectively. A significant correlation was also observed between the total phenolic contents and the antioxidant properties of fenugreek seeds as determined by reducing power potential  (FRAP).Conclusion: Indigenous landraces of Omani fenugreek seeds are a rich source of protein, dietary fiber, and many important bioactive components, which were found to be significantly correlatedwith its antioxidant properties.Keywords: Omani fenugreek, landraces, phytochemical composition, antioxidant properties

The relationship of renal function to outcome: A post hoc analysis from the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) study.

The ENSURE-AF study (NCT 02072434) of anticoagulation for electrical cardioversion in nonvalvular atrial fibrillation (NVAF) showed comparable low rates of bleeding and thromboembolism between the edoxaban and the enoxaparin-warfarin treatment arms. This post hoc analysis investigated the relationship between renal function and clinical outcomes. METHODS: ENSURE-AF was a multicenter, PROBE evaluation trial of edoxaban 60 mg, or dose reduced to 30 mg/d for weight≤60 kg, creatinine clearance (CrCl; Cockcroft-Gault) ≤50 mL/min, or concomitant P-glycoprotein inhibitors compared with therapeutically monitored enoxaparin-warfarin in 2,199 NVAF patients undergoing electrical cardioversion. Efficacy and safety outcomes and time in therapeutic range in the warfarin arm were analyzed in relation to CrCl in prespecified ranges ≥15 and ≤30, >30 and ≤50, >50 and 30 to ≤50 compared with 71.8% in those with CrCl ≥80. The odds ratios for the primary efficacy and safety end points were comparable for the different predefined renal function strata; given the small numbers, the 95% CI included 1.0. In the subset of those with CrCl ≥95, the odds ratios showed consistency with the other CrCl strata. When CrCl was assessed as a continuous variable, there was a nonsignificant trend toward higher major or clinically relevant nonmajor bleeding with reducing CrCl levels, with no significant differences between the 2 treatment arms. When we assessed CrCl at baseline compared with end of treatment, there were no significant differences in CrCl change between the edoxaban and enoxaparin-warfarin arms. The proportions with worsening of renal function (defined as a decrease of >20% from baseline) were similar in the 2 treatment arms. CONCLUSION: Given the small number of events in ENSURE-AF, no effect of renal (dys)function was demonstrated in comparing edoxaban to enoxaparin-warfarin for cardioversion; efficacy and safety of edoxaban remained consistent even in patients with normal or supranormal renal function

Anticoagulation Control in Warfarin-Treated Patients Undergoing Cardioversion of Atrial Fibrillation (from the Edoxaban Versus Enoxaparin-Warfarin in Patients Undergoing Cardioversion of Atrial Fibrillation Trial).

In the Edoxaban Versus Enoxaparin-Warfarin in Patients Undergoing Cardioversion of Atrial Fibrillation (ENSURE-AF) study (NCT 02072434), edoxaban was compared with enoxaparin-warfarin in 2,199 patients undergoing electrical cardioversion of nonvalvular atrial fibrillation (AF). In this multicenter prospective randomized open blinded end-point trial, we analyzed patients randomized to enoxaparin-warfarin. We determined time to achieve therapeutic range (TtTR); time in therapeutic range (TiTR); their clinical determinants; relation to sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT2R2) score; and impact on primary end points (composite of stroke, systemic embolic event[SEE], myocardial infarction [MI], and cardiovascular death [CVD] and composite of major + clinically relevant nonmajor bleeding). Among 1,104 patients randomized to enoxaparin-warfarin, 27% were naïve to oral anticoagulants. Mean age was 64.2 ± 11 years and mean congestive heart failure, hypertension, age ≥75 (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65-74, female (CHA2DS2-VASc) score was 2.6. Mean TtTR was 7.7 days (median 7 days) and mean TiTR after reaching an international normalized ratio of 2.0 to 3.0 was 71%. In 695 patients who had an INR 2. On multivariate regression, an independent predictor of extended TtTR was creatinine clearance (p = 0.02). TtTR was marginally related to stroke/SEE/MI/CVD (p = 0.06; odds ratio  0.23, 95% confidence interval 0.02 to 1.17) but not to any bleeding. Independent predictors of TiTR were previous vitamin K antagonist experience (p65, concomitant drugs or alcohol (HAS-BLED) score (p = 0.02). TiTR was related to any bleeding (p = 0.02; odds ratio  0.39, 95% confidence interval 0.16 to 0.88), but not stroke/SEE/MI/CVD. In this cohort of warfarin users with a high TiTR no difference was seen between TtTR and TiTR in relation to SAMe-TT2R2 score. In conclusion, even in this short-term study, TiTR was significantly related to bleeding events

Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study.

We designed a placebo controlled, double-blind, randomized, dose-finding phase II study on OMT-28 in the maintenance of sinus rhythm after electrical cardioversion (DCC) in patients with persistent atrial fibrillation (PROMISE-AF). OMT-28 is a first-in-class, synthetic analog of 17,18-epoxyeicosatetetraenoic acid, a bioactive lipid mediator generated by cytochrome P450 enzymes from the omega-3 fatty acid eicosapentaenoic acid. OMT-28 improves Ca2+-handling and mitochondrial function in cardiomyocytes and reduces pro-inflammatory signaling. This unique mode of action may provide a novel approach to target key mechanism contributing to AF pathophysiology. In a recent phase I study, OMT-28 was safe and well tolerated and showed favorable pharmacokinetics. The PROMISE-AF study (NCT03906799) is designed to assess the efficacy (primary objective), safety, and population pharmacokinetics (secondary objectives) of three different doses of OMT-28, administered once daily, versus placebo until the end of the follow-up period. Recruitment started in March 2019 and the study will include a total of 120 patients. The primary efficacy endpoint is the AF burden (% time with any AF), evaluated over a 13-week treatment period after DCC. AF burden is calculated based on continuous ECG monitoring using an insertable cardiac monitor (ICM). The primary efficacy analysis will be conducted on the modified intention-to-treat (mITT) population, whereas the safety analysis will be done on the safety population. Although ICMs have been used in other interventional studies to assess arrhythmia, PROMISE-AF will be the first study to assess antiarrhythmic efficacy and safety of a novel rhythm-stabilizing drug after DCC by using ICMs

Segmentation of intrinsically very low contrast magnetic resonance brain images using tensor-based DTI registration

Background: In patients with hypomyelinating leukodystrophies, contrast of T1-weighted brain MRI is very low due to the lack of myelin, preventing a reliable segmentation. In diffusion tensor images the contrast is higher, thanks to anisotropy and orientation of white matter (WM) tracts. We aimed to develop and assess a tensor-guided atlas-based segmentation method suitable for segmentation of very low contrast images. Methods: 17 control subjects (mean age 8.0 yrs (SD 8.0)) and 27 subjects with hypomyelinating leukodystrophies (mean age 10.7 yrs (SD 10.2)) were included. DTI and 3D T1 images were segmented using a DTI-TK tensor-guided IIT-atlas-based segmentation method. For the control subjects, these segmentations were compared with a conventional segmentation of their 3D T1-weighted images. A qualitative visual assessment and a quantitative assessment using DTI metrics was performed to assess the patient segmentations. Results: In control subjects, the tensor-based method performed as can be expected for atlas-based segmentation methods, with Dice coefficients of 0.65, 0.72, 0.81 and 0.86 for cortical grey matter (GM), WM, deep grey matter (DGM), and thalamus, respectively. In patients with hypomyelination the visual assessment showed anatomically adequate segmentations. All tissue-specific DTI metrics differed between patients and controls. Patients with hypomyelination had reduced FA and increased mean, axial and radial diffusivities, not only in total WM, but also in the corticospinal tracts, optic radiations and thalamus. Conclusion: Even in the absence of normal myelin, the presence and direction of axons allowed tensor-based registration and thereby atlas-based segmentation. We showed the applicability of the segmentation method in the context of quantitative MRI, allowing for whole-brain or regional tissue-specific and tract-specific analyses of very low contrast images