Active behaviour during early development shapes glucocorticoid reactivity

TGlucocorticoids are the final effectors of the stress axis, with numerous targets in the central nervous system and the periphery. They are essential for adaptation, yet currently it is unclear how early life events program the glucocorticoid response to stress. Here we provide evidence that involuntary swimming at early developmental stages can reconfigure the cortisol response to homotypic and heterotypic stress in larval zebrafish (Danio rerio), also reducing startle reactivity and increasing spontaneous activity as well as energy efficiency during active behaviour. Collectively, these data identify a role of the genetically malleable zebrafish for linking early life stress with glucocorticoid function in later life

Resident acquisition of knowledge during a noontime conference series.

BACKGROUND AND OBJECTIVES: Noontime conferences are widely used in family practice residencies. This study determined the effectiveness of noontime conferences for increasing residents\u27 knowledge. METHODS: Twenty residents were tested monthly over 6 months and then cumulatively on the content of noontime conferences. RESULTS: Monthly test scores of attendees versus nonattendees were compared using a two-sample, two-tail t test. Results revealed the mean score of attendees for short-term knowledge to be 12.1 points higher than nonattendees. There was no correlation, however, between conference attendance and long-term knowledge retention. CONCLUSIONS: Our findings indicate a lack of correlation between noontime conference attendance and long-term cumulative test scores. The results question the value of noontime conferences as a teaching method

Resident knowledge acquisition during a block conference series.

OBJECTIVE: This study\u27s objective was to determine whether attendance at lectures in a block conference format improves residents\u27 knowledge. METHODS: Seventeen family medicine residents were tested on the content of 27 lectures delivered in a block conference format over a 6-month period. For each lecture, residents completed a pretest, a short-term posttest, and a long-term posttest (1--3 weeks and 1.5--6 months after each lecture, respectively). RESULTS: Mean short-term posttest scores were 10.3 points higher for lecture attendees than nonattendees. Mean long-term posttest scores did not differ significantly for attendees (62.2) versus nonattendees (60.0). CONCLUSIONS: Attendance at didactic lectures in a block conference format did not improve resident knowledge over the long term. These results lead us to question the value of a block conference format and raise the possibility that resident learning might be better served by maximizing clinical experiences and minimizing time in conferences

Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release

The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing αβγ heterotrimer responsible for energy homeostasis. Pharmacological inhibition of AMPK is regarded as a therapeutic strategy in some disease settings including obesity and cancer; however, the broadly used direct AMPK inhibitor compound C suffers from poor selectivity. We have discovered a dihydroxyquinoline drug (MT47-100) with novel AMPK regulatory properties, being simultaneously a direct activator and inhibitor of AMPK complexes containing the β1 or β2 isoform, respectively. Allosteric inhibition by MT47-100 was dependent on the β2 carbohydrate-binding module (CBM) and determined by three non-conserved CBM residues (Ile81, Phe91, Ile92), but was independent of β2-Ser108 phosphorylation. Whereas MT47-100 regulation of total cellular AMPK activity was determined by β1/β2 expression ratio, MT47-100 augmented glucose-stimulated insulin secretion from isolated mouse pancreatic islets via a β2-dependent mechanism. Our findings highlight the therapeutic potential of isoform-specific AMPK allosteric inhibitors