Cathepsin B cysteine protease gene is upregulated during leaf senescence and exhibits differential expression behavior in response to phytohormones in Picrorhiza kurrooa Royle ex Benth.

AbstractMedicinal importance of Picrorhiza (Picrorhiza kurrooa Royle ex Benth — an herb of western Himalayan region) and its endangered status in Red Data Book presses an urgent need for intensive R&D interventions towards ensuring its availability for the medicinal use, its sustainability and improvement. The present study was conducted on cathepsin B cysteine protease in Picrorhiza. Cathepsin B cysteine protease has been reported to function in diverse processes such as senescence, abscission, programmed cell death, fruit ripening and in response to pathogen and pest attacks. A full-length cDNA-Pk-cbcp encoding cathepsin B-like cysteine protease was cloned from Picrorhiza. The full length Pk-cbcp cDNA consisted of 1369bp with an open reading frame of 1080bp, 80bp 5′ untranslated region and 209bp 3′ untranslated region. The deduced Pk-cbcp protein contained 359 amino acids with a molecular weight of 39.981kDa and an isoelectric point of 5.75. Secondary structure analysis revealed that Pk-cbcp had 28.97% α-helices, 14.48% β-turns, 19.50% extended strands and 37.05% random coils. Semi-quantitative PCR analysis revealed 157% higher expression of Pk-cbcp during senescence compared to that of pre-senescence. Further, application of phytohormones abscisic acid, jasmonic acid and cytokinin influenced the temporal expression status of Pk-cbcp. Abscisic acid and jasmonic acid increased the expression level whereas cytokinin reduced the expression. The findings suggest the role of Pk-cbcp in leaf senescence in Picrorhiza which may be differentially mediated through phytohormones

Diabetes education program for people with type 2 diabetes: An international perspective

© 2016 Elsevier Ltd. Background: In the Palestinian community, lifestyle changes, rapid urbanization and socioeconomic development, stress, smoking, and changes in food habits has increased the risk of non-communicable diseases especially diabetes mellitus. Diabetes complications can be prevented if the glycemic status of patients with diabetes is maintained within a nearly normal range. Therefore, patient education is critical in controlling blood glucose levels within the normal range. Objective: This study aimed at measuring the effect of diabetes educational intervention program for patients suffering from type 2 diabetes attending the Diabetes Clinic in Tulkarim Directorate of Health. Methods: A short duration observational study involving pre- and post-test educational intervention program was carried out on a relatively small number of type 2 diabetes patients at the Diabetes Clinic in Tulkarim Directorate of Health. In total, 215 patients attended a group-based 4 h educational intervention session about diabetes. The program included explaining diabetes mellitus-symptoms, risk factors, types, treatment and complications and main aspects of self-care of the disease (foot care, eye care, and blood glucose monitoring), main aspects of dietary management, weight reduction, blood pressure, smoking cessation, periodic investigations, home monitoring and importance of physical activity. Knowledge evaluation questionnaire were evaluated pre- and post-study. Anthropometric measurements such as body weight (WT), body mass index (BMI) and laboratory tests such as fasting blood glucose (FBG), hemoglobin A1C (HbA1c), cholesterol (Chol), and triglycerides (TG) were measured both at the beginning and at the end of the study. Significance of the results was assessed by paired t-test at 95% confidence interval. Results: The participant\u27s mean age was 51.07 that ranged between 31 and 70 years. For a total of 215 participants, 41.4% were males and 58.6% were females. The mean weight before educational intervention was 80.81 ± 14.95 kg (82.6 kg for males and 79.5 kg for females) that decreased to 78.9 ± 14.33 kg (81.1 kg for males and 77.3 kg for females) after educational intervention program. The BMI also decreased significantly after educational intervention. The mean fasting blood sugar was 188.65 ± 71.45 mg/dL before educational intervention that decreased to 177.7 ± 66.11 mg/dL after the educational intervention (p = 0.049). The mean glycosylated hemoglobin was 8.57 ± 1.21 before educational intervention that decreased to 7.95 ± 1.42 after educational intervention. The mean value of cholesterol before educational intervention was 183.27 ± 37.74 mg/dL that decreased to 169.57 ± 34.23 mg/dL after educational intervention. The mean triglycerides value decreased after educational intervention from 209.85 ± 171.04 mg/dL to 183.28 ± 152.4 mg/dL (p = 0.025). The mean score of knowledge questionnaire before educational intervention was 60.6 ± 20.65 that increased to 78.1 ± 13.4 after conducting educational intervention. Conclusions: Diabetes education was found to be effective on BMI, FBG, HbA1c, Chol, TG, and knowledge. Recommendations: Diabetes education is a cornerstone in the management and care of diabetes and should be an integral part of health planning involving patient\u27s family, diabetes care team, community, and decision makers in the education process

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362