Energetics of human muscle: exercise-induced ATP depletion

The energetics of human muscle have been investigated in vivo during and after fatiguing aerobic, dynamic exercise. Changes in cytoplasmic pH and concentrations of phosphocreatine, ATP and Pi were followed using 31P nuclear magnetic resonance spectroscopy. ATP was significantly depleted in 6 out of 12 experiments and in these 6 experiments decreased to 55 +/- 5% of the pre-exercise concentration. Depleted muscle had a lower phosphocreatine concentration (17 +/- 5% of resting value) and lower pH (6.12 +/- 0.04) than fatigued muscle in which ATP loss was not observed (26 +/- 5% for phosphocreatine and 6.37 +/- 0.09 for pH). The free energy of hydrolysis of ATP was not significantly different in the two groups and was also similar in exhausted and nonexhausted muscle. Loss of ATP was associated with altered recovery of the muscle: [phosphocreatine], [Pi], and pH returned more slowly to their pre-exercise values and the initial rate of oxidative phosphorylation was diminished. The restitution of [ATP] to its pre-exercise value was much slower than that of the other metabolites.     

Novel synthetic oleanane and ursane triterpenoids with various enone functionalities in ring A as inhibitors of nitric oxide production in mouse macrophages

We initially randomly synthesized about 60 oleanane and ursane triterpenoids as potential anti-inflammatory and cancer chemopreventive agents. Preliminary screening of these derivatives for inhibition of production of nitric oxide induced by interferon-gamma in mouse macrophages revealed that 3-oxooleana-1, 12-dien-28-oic acid (B-15) showed significant activity (IC(50) = 5.6 microM). On the basis of the structure of B-15, 19 novel olean- and urs-12-ene triterpenoids with a 1-en-3-one functionality having a substituent at C-2 in ring A have been designed and synthesized. Among them, 3-oxooleana-1,12-diene derivatives with carboxyl, methoxycarbonyl, and nitrile groups at C-2 showed higher activity than the lead compound B-15. In particular, 2-carboxy-3-oxooleana-1, 12-dien-28-oic acid (3) had the highest activity (IC(50) = 0.07 microM) in this group of triterpenoids. The potency of 3 was similar to that of hydrocortisone (IC(50) = 0.01 microM), although 3 does not act through the glucocorticoid receptor. Interesting structure-activity relationships of these novel synthetic triterpenoids are also discussed.     

Reliability of personality and values tests: The effects of “high stakes” selection conditions,and of four years in medical school

This study investigated if scores on tests of personal qualities are affected by whether they will determine selection decisions (“high stakes”) or not; and whether they are stable for individuals and groups across a four-year medical course. Two tests, one assessing values and one assessing components of personality, were administered either at the same time as a medical university entrance exam (first cohort; N?=?216), or after entry was confirmed (second cohort; N?=?142). Both cohorts took the tests again after four years of medical school. Analysis of variance was used to compare group mean scores and interactions, and correlation coefficients to measure temporal reliability. The high stakes cohort initially presented themselves in a significantly more positive light on the personality test. After four years of medical school scores on both tests changed significantly, towards more communitarian values and less empathic attitudes. Thus, personality scores were affected by both the conditions under which the initial tests were conducted and by the passage of time, but values only by the passage of time. Before and after scores were significantly correlated.     

It starts at home? Climate policies targeting household consumption and behavioral decisions are key to low-carbon futures

Through their consumption behavior, households are responsible for 72% of global greenhouse gas emissions. Thus, they are key actors in reaching the 1.5 °C goal under the Paris Agreement. However, the possible contribution and position of households in climate policies is neither well understood, nor do households receive sufficiently high priority in current climate policy strategies. This paper investigates how behavioral change can achieve a substantial reduction in greenhouse gas emissions in European high-income countries. It uses theoretical thinking and some core results from the HOPE research project, which investigated household preferences for reducing emissions in four European cities in France, Germany, Norway and Sweden. The paper makes five major points: First, car and plane mobility, meat and dairy consumption, as well as heating are the most dominant components of household footprints. Second, household living situations (demographics, size of home) greatly influence the household potential to reduce their footprint, even more than country or city location. Third, household decisions can be sequential and temporally dynamic, shifting through different phases such as childhood, adulthood, and illness. Fourth, short term voluntary efforts will not be sufficient by themselves to reach the drastic reductions needed to achieve the 1.5 °C goal; instead, households need a regulatory framework supporting their behavioral changes. Fifth, there is a mismatch between the roles and responsibilities conveyed by current climate policies and household perceptions of responsibility. We then conclude with further recommendations for research and policy.     

Graduate entry to medicine: widening psychological diversity

Background  

At Nottingham University more than 95% of entrants to the traditional 5-year medical course are school leavers. Since 2003 we have admitted graduate entrants (GEM) to a shortened (4-year) course to 'widen access to students from more disadvantaged backgrounds'. We have recently shown that the GEM course widens academic and socio-demographic diversity of the medical student population. This study explored whether GEM students also bring psychological diversity and whether this could be beneficial.     

Should we abandon regional anesthesia in open inguinal hernia repair in adults?

Inguinal hernia repair is a common worldwide surgical procedure usually done in the outpatient setting. The purpose of this systematic review is to make an evidence-based meta-analysis to determine the possible benefits of regional (neuraxial block) anesthesia compared to general anesthesia in open inguinal hernia repair in adults. Cochrane Library, Medline, EMBASE, CINAHL, SCI-EXPANDED, SCOPUS as well as trial registries, conference proceedings and reference lists were searched. Only randomized controlled trials (RCT) that compare neuraxial block (spinal or/and epidural) anesthesia (NABA) and general anesthesia (GA) were included. Main outcome measures were postoperative complications, urinary retention and postoperative pain. Seven RCTs were included in this review. A total of 308 patients were analyzed with 154 patients in each group. Overall complications were evenly distributed in NABA and in GA group [OR 1.17, 95 % CI (0.52–2.66)]. Urinary retention was statistically less frequent in GA group compared to NABA group [OR 0.25, 95 % CI (0.08–0.74)]. Movement-associated pain score 24 h after surgery was significantly lower in NABA group [SMD 5.59, 95 % CI (3.69–7.50)]. Time of first analgesia application was shorter in GA group [SMD 8.99, 95 % CI 6.10–11.89]. Compared to GA, NABA appears to be a more adequate technique in terms of postoperative pain control. However, when GA is applied, patients seem to have less voiding problems.     

Dyspnea of effort with an unusual cause: diagnostic significance of stress echocardiography

Left intra ventricular obstruction occurring during doubutamine stress echography is not exceptional but its clinical significance is controversial, notably due to the non-reproducibility of such a phenomenon during physical exercise in a certain number of patients. Moreover, in the studies which demonstrate a link between symptoms of effort and left intra ventricular obstruction during dobutamine echography, an echography with effort was not systematically performed in order to confirm this relationship. We describe the case of two patients, aged 50 and 62 years respectively, with no notable cardiovascular past history except hypertension, who had dyspnoea of effort in the absence of underlying cardiopathy in resting conditions. Dobutamine stress echography provoked a systolic anterior movement of the mitral valve (SAM) responsible for mitral insufficiency and significant left intra ventricular obstruction (maximum gradient of 77 mmHg for one, 130 mmHg for the other), with reproduction of spontaneous symptoms, in the absence of myocardial ischaemia. An effort echography performed several weeks later confirmed these data, even though a sublingual trinitrate (0.3 mg) test was without effect. In the absence of underlying hypertrophic cardiomyopathy the SAM (with left intra ventricular obstruction and mitral insufficiency) occurring during dobutamine stress echography could have clinical significance in selected cases, notably in hypertensive patients with effort intolerance who have normal systolic and diastolic function in the resting state, and absence of myocardial ischaemia during stress, as illustrated in our two observations. The therapeutic implications are clear, with patients like this successfully treated with beta-blockers.     

Are quenches dangerous?

There exists some uncertainty about the hazards which the quenching of a superconducting magnet would present to a subject undergoing an NMR examination. To investigate this problem, a 1.6-T whole-body magnet was quenched with an anesthetized pig lying in the bore. This paper reports our findings which, in the circumstances of this experiment, suggest that the risks are small.