De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

Modelling India’s coal production with a negatively skewed curve-fitting model

India’s coal demand is forecast to increase at a rapid pace in the future due to the country’s economic and population growth. Analyzing the scope for future production of India’s domestic coal resources, therefore, plays a vital role in the country’s development of sound energy policies. This paper presents a quantitative scenario analysis of India’s potential future coal production by using a negatively skewed curve-fitting model and a range of estimates of the country’s ultimately recoverable resources (URR) of coal. The results show that the resource base is sufficient for India’s coal production to keep increasing over the next few decades, to reach between 2400 and 3200 Mt/y at 2050, depending on the assumed value of URR. A further analysis shows that the high end of this range, which corresponds to our ‘GSI’ scenario, can be considered as the probable upper-bound to India’s domestic coal production. Comparison of production based on the ‘GSI’ scenario with India’s predicted demand shows that the domestic production of coal will be insufficient to meet the country’s rising coal demand, with the gap between demand and production increasing from its current value of about 268 Mt/y to reach 300 Mt/y in 2035, and 700 Mt/y by 2050. This increasing gap will be challenging for the energy security of India

In situ observation of oscillatory redox dynamics of copper

How a catalyst behaves microscopically under reaction conditions, and what kinds of active sites transiently exist on its surface, is still very much a mystery to the scientific community. Here we present an in situ study on the red-ox behaviour of copper in the model reaction of hydrogen oxidation. Direct imaging combined with on-line mass spectroscopy shows that activity emerges near a phase boundary, where complex spatio-temporal dynamics are induced by the competing action of simultaneously present oxidizing and reducing agents. Using a combination of in situ imaging with in situ X-ray absorption spectroscopy and scanning photoemission microscopy, we reveal the relation between chemical and morphological dynamics and demonstrate that a static picture of active sites is insufficient to describe catalytic function of redox-active metal catalysts. The observed oscillatory redox dynamics provide a unique insight on phase-cooperation and a convenient and general mechanism for constant re-generation of transient active sites

Exercise-induced left bundle branch block accompanied by chest pain - Correlation with coronary artery disease

A case of a 25-year-old woman with familiar hypercholesterolemia, who was admitted complaining for chest pain on exertion, is presented. She underwent a treadmill stress test and during the exercise left bundle branch block with concomitant chest pain in low heart rate (105/min) was demonstrated. After these findings TL-201 scintigraphy with dipyridamole infusion was performed: Chest pain and left bundle branch block appeared again during the test, and the stress TL-201 tomographic images showed reversible defect in the anterior wall. Finally, the young woman underwent coronary arteriography, which showed normal coronary vessels. The ergonovine test for coronary spasm was negative

EXERCISE-INDUCED QRS DURATION CHANGES IN PATIENTS WITH CORONARY-ARTERY DISEASE-APPEARING WALKTHROUGH ANGINA

Two patients with coronary artery disease appearing as ‘’walkthrough” angina underwent a treadmill exercise test. During the exercise, the patients appeared to have anginal pain associated with ST-segment depression and increased QRS duration. As the patients continued walking, anginal pain disappeared and a concomitant lessening in ST-segment depression and QRS prolongation was observed. Thus, the fact that the onset of angina was associated with ST-segment depression and prolonged QRS duration, while the disappearance of angina was associated with a decrease in ST-segment depression and QRS prolongation, is indicative of the effect of exercise-induced myocardial ischemia on QRS duration

Antianginal efficacy of the combination of trimetazidine-propranolol compared with isosorbide dinitrate-propranolol in patients with stable angina

Trimetazidine is a new anti-ischaemic drug that exerts cytoprotective effects without modifying coronary blood flow or systemic haemodynamics. We tested the antianginal efficacy of trimetazidine in combination with propranolol, using a double-blind isosorbide dinitrate-controlled design. Male patients (n = 53) with stable, effort-induced angina not sufficiently controlled with propranolol 40mg 3 times daily received at random either trimetazidine 20mg 3 times daily (n = 27) or isosorbide dinitrate 10mg 3 times daily (n = 26) for 2 months. From day 0 to day 60, in both groups, there was a decrease in the average number of anginal attacks per week (p < 0.01) and in the weekly consumption of nitroglycerin (p < 0.01), the latter being more decreased in the trimetazidine group (p < 0.05). On exercise testing, both exercise duration and rime to I mm ST depression were improved in the trimetazidine group at day 60 compared with day 0 values (p < 0.001), while no significant changes were observed in the isosorbide dinitrate group. The total workload increased significantly more in the trimetrtzidine group than in the isosorbide dinitrate group for patients performing the exercise test on a bicycle (n = 31, p < 0.001), but not on a treadmill (n = 22, p = not significant). We concluded that in patients with stable induced angina not sufficiently controlled with propranolol, a better antianginal efficacy was observed with the addition of trimetazidine than with the addition of isosorbide dinitrate, and this confirmed the clinical interest in the new anti-ischaemic drug

INDEPENDENCE OF BLOOD-PRESSURE RESPONSE TO EXERCISE AND AMBULATORY BLOOD-PRESSURE VALUES IN ESSENTIAL-HYPERTENSION

Ambulatory blood pressure (ABP) recordings over 24 h are used in the diagnosis and evaluation of arterial hypertension severity, while blood pressure response to exercise may unmask hypertensive patients. To evaluate the relationship of the two methods, 40 medication-free patients with mild and moderate essential hypertension underwent symptom-limited treadmill stress test (TST) within 48 h of ABP. TST time, blood pressure increase, decrease, mode of increase and decrease, were independent of ABP systolic (SBP) and diastolic blood pressure (DBP) over 24 h, daytime and nighttime (p = NS). SBP fall immediately postexercise were independent of ABP data. TST-achieved heart rate was related to both 24-hour SBP (r = -0.65, p = 0.00005) and DBP (r = -0.57, p = 0.0002) in both day (r = -0.65, p = 0.00001 and r = -0.57, p 0.0002) and night (r = -0.56, p = 0.0002 and r = -0.47, p = 0.003) time periods. Thus, patients with achieved heart rate <100% (n = 15) had higher 24-hour SBP (144 vs. 130 mm Hg, p = 0.0007) and DBP (93 vs. 86 mm Hg, p 0.007), day and night. It is concluded that there is no overlap of diagnostic information using blood pressure values in TST or ABP, although achieved heart rate in exercise is inversely related to hypertension severity