Integrating de novo QTL-seq and linkage mapping to identify quantitative trait loci conditioning physiological resistance and avoidance to white mold disease in dry bean.

White mold (WM), caused by the ubiquitous fungus Sclerotinia sclerotiorum, is a devastating disease that limits production and quality of dry bean globally. In the present study, classic linkage mapping combined with QTL-seq were employed in two recombinant inbred line (RIL) populations, "Montrose"/I9365-25 (M25) and "Raven"/I9365-31 (R31), with the initial goal of fine-mapping QTL WM5.4 and WM7.5 that condition WM resistance. The RILs were phenotyped for WM reactions under greenhouse (straw test) and field environments. The general region of WM5.4 and WM7.5 were reconfirmed with both mapping strategies within each population. Combining the results from both mapping strategies, WM5.4 was delimited to a 22.60-36.25 Mb interval in the heterochromatic regions on Pv05, while WM7.5 was narrowed to a 0.83 Mb (3.99-4.82 Mb) region on the Pv07 chromosome. Furthermore, additional QTL WM2.2a (3.81-7.24 Mb), WM2.2b (11.18-17.37 Mb, heterochromatic region), and WM2.2c (23.33-25.94 Mb) were mapped to a narrowed genomic interval on Pv02 and WM4.2 in a 0.89 Mb physical interval at the distal end of Pv04 chromosome. Gene models encoding gibberellin 2-oxidase proteins regulating plant architecture are likely candidate genes associated with WM2.2a resistance. Nine gene models encoding a disease resistance protein (quinone reductase family protein and ATWRKY69) found within the WM5.4 QTL interval are putative candidate genes. Clusters of 13 and 5 copies of gene models encoding cysteine-rich receptor-like kinase and receptor-like protein kinase-related family proteins, respectively, are potential candidate genes associated with WM7.5 resistance and most likely trigger physiological resistance to WM. Acquired knowledge of the narrowed major QTL intervals, flanking markers, and candidate genes provides promising opportunities to develop functional molecular markers to implement marker-assisted selection for WM resistant dry bean cultivars.

Position statement from the Indian Society of Gastroenterology, Cardiological Society of India, Indian Academy of Neurology and Vascular Society of India on gastrointestinal bleeding and endoscopic procedures in patients on antiplatelet and/or anticoagulant therapy.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.

Independent Validation of the Hematoma Expansion Prediction Score: A Non-contrast Score Equivalent in Accuracy to the Spot Sign.

BACKGROUND AND PURPOSE: The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. METHODS: We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. RESULTS: A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01-1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57-0.71). Youden's method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09-3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61-5.42) were similar to HEP scores ≥ 4. CONCLUSION: The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

Cut stroke in half: Polypill for primary prevention in stroke.

This review summarizes the potential for polypill therapies for stroke prevention. While a number of studies applying different approaches regarding polypill have been performed, none of them has had a focus on stroke as the main outcome. A combination pill containing drugs such as statins, diuretics, and other antihypertensives is currently available in various formats. Estimates focusing mostly on primary prevention show that using such a combination drug a reduction in the 5-year stroke incidence by 50% can be achieved - especially in low- and middle-income countries with a high prevalence of risk factors even among people at young ages. A combination of a large supporting population-wide program with a registry-based quality control is the most likely perspective and can be achieved within a reasonable time frame and potentially have significant influence in young stroke populations.

A Cross-sectional Assessment of Risk Factors of Non-Communicable Diseases in a Sub-Himalayan Region of West Bengal, India Using who Steps Approach.

BACKGROUND: Non-communicable diseases (NCDs), principally cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes are the leading causes of death and disability globally. The basic element of NCD prevention is the identification of the common risk factors and their prevention and control. OBJECTIVE: To determine the prevalence of risk factors for non-communicable diseases, in Siliguri city of West Bengal, India using WHO Steps approach. METHODS: Between April 2012 to July 2012, 779 adults of 18-64 years from Siliguri city were chosen by 30-cluster sampling. They were interviewed and measurements and laboratory tests were done. RESULTS: The prevalence of behavioural risk factors like tobacco use, alcohol, unhealthy diet was 57.5%, 12.5%, 50.87% and 60.4%, respectively while that of biological risk factors like overweight, abdominal obesity and hypertension was 29.8%, 20.2% and 17.8%, respectively. The prevalence of biochemical risk categories like diabetes, hypercholesterolemia, hypertriglyceridaemia, low HDL-C was 9.1%, 17.8%, 16.6% and 67.5%, respectively. CONCLUSIONS: A high prevalence of risk factors for non-communicable diseases was found in Siliguri city which emphasizes the need of interventions to reduce these risk factors.

Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study.

BACKGROUND: In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion. METHODS: PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis. FINDINGS: We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22-470), and time from onset to CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5-80·9) in spot-sign-positive patients versus 10·0 mL (0·1-102·7) in spot-sign negative patients (p<0·001). Median ICH expansion was 8·6 mL (-9·3 to 121·7) for spot-sign positive patients and 0·4 mL (-11·7 to 98·3) for spot-negative patients (p<0·001). In those with haematoma expansion, the positive predictive value for the spot sign was61% (95% CI 47­73) for the positive predictive value and 78% (71­84) for the negative predictive value, with 51% (39­63) sensitivity and 85% (78­90) specificity[corrected]. Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p<0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4-4·0, p=0·002). INTERPRETATION: These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH. FUNDING: Canadian Stroke Consortium and NovoNordisk Canada.

Relative energy index of microembolic signal can predict malignant microemboli.

BACKGROUND AND PURPOSE: Microembolic signals (MES) found on transcranial Doppler range from harmless air bubbles to large, solid, particulate emboli from the heart and large vessels. The presence of MES is not always associated with poor clinical outcome. The purpose of our study was to determine whether the relative energy index of MES measured by power M-mode Doppler can distinguish malignant from benign MES and to identify patients with worse prognosis. METHODS: We prospectively collected transcranial Doppler emboli monitoring data from patients with symptomatic carotid stenosis presenting with TIA or ischemic stroke. For each patient, we calculated the relative energy index of MES and categorized those >1.0 as malignant MES. We compared the clinical characteristics, number, and volume of diffusion-weighted imaging lesions, and degree of stenosis and plaque characteristics on CT angiogram of patients with malignant and benign MES. RESULTS: We enrolled 92 patients, 29 with TIA and 63 with stroke, within 48 hours of symptom onset. Twenty-six patients had a total of 319 MES; of these, 82.4% were benign and were 17.6% malignant. Malignant MES traveled further within intracranial vessels than benign MES. The 9 patients with >1 malignant MES had significantly larger baseline diffusion-weighted imaging lesion volume, had a higher prevalence of intraluminal thrombus on CT angiogram of the neck and plaque ulceration, and were more likely to have a poor clinical outcome (modified Rankin Score > or = 2) than those with benign MES (OR, 6.5; 95% CI, 1.47-28.68). The presence of malignant MES led to the institution of more aggressive secondary prevention measures. CONCLUSIONS: Power M-mode transcranial Doppler identifies a subgroup of patients with malignant MES. These signals are more frequent in longer arterial trajectory. Patients with malignant MES have larger baseline infarcts, a higher prevalence of intraluminal thrombus or ulcerated plaque in the carotid artery, and worse clinical outcome.