Can exercise mimetics substitute for exercise?

Exercise leads to changes in muscle phenotype with important implications for exercise performance and health. A recent paper in Cell by Narkar et al. (2008) shows that many of the adaptations in muscle phenotype elicited by exercise can be mimicked by genetic manipulation and drug treatment in mice.     

The exercise ECG: still a useful exercise?

What is wrong with traditional ST-segment criteria during the exercise ECG? As we all know from daily practice, poor sensitivity of the exercise ECG for the detection of myocardial ischaemia is a major diagnostic weakness and a critical limitation of the exercise procedure. In standard meta-analyses, 1.0 mm (0.1 mV) of horizontal or downward-sloping ST depression has a sensitivity of only 68% for the detection of coronary artery disease (CAD), and this figure is even lower for women. This might explain our increasing reliance on noninvasive imaging modalities such as nuclear imaging (SPECT), magnetic resonance imaging (MRI), and computed tomography angiography (CTA), all of which show sensitivities between 80 and 90% for detecting CAD. As a result, there is a tendency to consider the exercise ECG as a poor man’s procedure to demonstrate myocardial ischaemia due to CAD. Is this the right consideration?     

Should people with severe mental illness be prioritized for the COVID-19 vaccination?

The coronavirus disease-19 (COVID-19) has spread throughout the world, affecting many vulnerable populations including patients with severe mental illness (SMI). Recent studies have found that patients with SMI compared to the general population could have a greater risk of morbidity and mortality from COVID-19 due to cognitive impairment, poor awareness of risk, and difficulties in complying with infection control measures. Although some researchers have suggested that patients with SMI should be prioritized for COVID-19 vaccination to reduce the risk of infection, this issue remains controversial.     

Should the Arteriovenous Fistula Be Created before Starting Dialysis?: A Decision Analytic Approach

Background

An arteriovenous fistula (AVF) is considered the vascular access of choice, but uncertainty exists about the optimal time for its creation in pre-dialysis patients. The aim of this study was to determine the optimal vascular access referral strategy for stage 4 (glomerular filtration rate <30 ml/min/1.73 m²) chronic kidney disease patients using a decision analytic framework.

Methods

A Markov model was created to compare two strategies: refer all stage 4 chronic kidney disease patients for an AVF versus wait until the patient starts dialysis. Data from published observational studies were used to estimate the probabilities used in the model. A Markov cohort analysis was used to determine the optimal strategy with life expectancy and quality adjusted life expectancy as the outcomes. Sensitivity analyses, including a probabilistic sensitivity analysis, were performed using Monte Carlo simulation.

Results

The wait strategy results in a higher life expectancy (66.6 versus 65.9 months) and quality adjusted life expectancy (38.9 versus 38.5 quality adjusted life months) than immediate AVF creation. It was robust across all the parameters except at higher rates of progression and lower rates of ischemic steal syndrome.

Conclusions

Early creation of an AVF, as recommended by most guidelines, may not be the preferred strategy in all pre-dialysis patients. Further research on cost implications and patient preferences for treatment options needs to be done before recommending early AVF creation.     

Can exercise prevent osteoporosis?

Commonly used definitions of osteoporosis rely upon the measurement of bone mass or bone mineral density and regard the difference between osteopenia and osteoporosis as gradual. An alternative definition has been proposed by Harold Frost, suggesting that osteopenia is the bone's physiological response to disuse. On the contrary, true osteoporoses imply the bone's inability to adapt to the loads imposed on them by their habitual mechanical usage. As a consequence, fractures occur with no or very little trauma in osteoporotic, but not in osteopenic bones. There is now ample evidence that mechanical stimuli can increase strength. Accordingly, exercise, in particular some new forms of it that involve high strain rates, seems to be preventing bone loss and possibly also induces increases in bone mass even at older ages. Hence, exercise may ameliorate osteopenia in the sense of Frost's definition. However, exercise must be feared to facilitate rather than to ameliorate the occurrence of true osteoporoses, e.g., due to microdamage accumulation. This is in sharp contrast to the general 'understanding'.     

Does trypsin cut before proline?

Trypsin is the most commonly used enzyme in mass spectrometry for protein digestion with high substrate specificity. Many peptide identification algorithms incorporate these specificity rules as filtering criteria. A generally accepted "Keil rule" is that trypsin cleaves next to arginine or lysine, but not before proline. Since this rule was derived two decades ago based on a small number of experimentally confirmed cleavages, we decided to re-examine it using 14.5 million tandem spectra (2 orders of magnitude increase in the number of observed tryptic cleavages). Our analysis revealed a surprisingly large number of cleavages before proline. We examine several hypotheses to explain these cleavages and argue that trypsin specificity rules used in peptide identification algorithms should be modified to "legitimatize" cleavages before proline. Our approach can be applied to analyze any protease, and we further argue that specificity rules for other enzymes should also be re-evaluated based on statistical evidence derived from large MS/MS data sets.     

Should right ventricle dilatation during exercise have clinical implications in patients with chronic thromboembolic pulmonary hypertension? Case report

Background

The occurrence of pulmonary artery obstruction in the course of acute aortic dissection is an unusual complication. The mechanism implicated is the rupture of the outer layer of the aorta and the subsequent hemorrhage into the adventitia of the pulmonary artery that causes its wall thickening and, at times, produces extrinsic obstruction of the vessel. There are no reports of this complication in acute intramural hematoma.

Case presentation

An 87-year-old woman was admitted to the hospital in shock after having had severe chest pain followed by syncope. An urgent transesophageal echocardiogram revealed the presence of acute intramural hematoma, no evidence of aortic dissection, severe pericardial effusion with cardiac tamponade, and periaortic hematoma that involved the pulmonary artery generating circumferential wall thickening of its trunk and right branch with no evidence of flow obstruction. Urgent surgery was performed but the patient died in the operating room. The post mortem examination, in the operating room, confirmed that there was an extensive hematoma around the aorta and beneath the adventitial layer of the pulmonary artery, with no evidence of flow obstruction.

Conclusion

This is the first time that this rare complication is reported in the scenario of acute intramural hematoma and with the transesophageal echocardiogram as the diagnostic tool.