Isometric exercise facilitates attention to salient events in women via the noradrenergic system.

The locus coeruleus (LC) regulates attention via the release of norepinephrine (NE), with levels of tonic LC activity constraining the intensity of phasic LC responses. In the current fMRI study, we used isometric handgrip to modulate tonic LC-NE activity in older women and in young women with different hormone statuses during the time period immediately after the handgrip. During this post-handgrip time, an oddball detection task was used to probe how changes in tonic arousal influenced functional coordination between the LC and a right frontoparietal network that supports attentional selectivity. As expected, the frontoparietal network responded more to infrequent target and novel sounds than to frequent sounds. Across participants, greater LC-frontoparietal functional connectivity, pupil dilation, and faster oddball detection were all positively associated with LC MRI structural contrast from a neuromelanin-sensitive scan. Thus, LC structure was related to LC functional dynamics and attentional performance during the oddball task. We also found that handgrip influenced pupil and attentional processing during a subsequent oddball task. Handgrip decreased subsequent tonic pupil size, increased phasic pupil responses to oddball sounds, speeded oddball detection speed, and increased frontoparietal network activation, suggesting that inducing strong LC activity benefits attentional performance in the next few minutes, potentially due to reduced tonic LC activity. In addition, older women showed a similar benefit of handgrip on frontoparietal network activation as younger women, despite showing lower frontoparietal network activation overall. Together these findings suggest that a simple exercise may improve selective attention in healthy aging, at least for several minutes afterwards.

Osteoporosis: A Review of Treatment Options.

Approximately 10 million men and women in the U.S. have osteoporosis,1 a metabolic bone disease characterized by low bone density and deterioration of bone architecture that increase the risk of fractures.2 Osteoporosis-related fractures can increase pain, disability, nursing home placement, total health care costs, and mortality.3 The diagnosis of osteoporosis is primarily determined by measuring bone mineral density (BMD) using noninvasive dual-energy x-ray absorptiometry. Osteoporosis medications include bisphosphonates, receptor activator of nuclear factor kappa-B ligand inhibitors, estrogen agonists/antagonists, parathyroid hormone analogues, and calcitonin.3-6 Emerging therapies utilizing novel mechanisms include a cathepsin K inhibitor and a monoclonal antibody against sclerostin.7,8 While professional organizations have compiled recommendations for the management of osteoporosis in various populations, a consensus has yet to develop as to which is the gold standard; therefore, economic evaluations have been increasingly important to help guide decision-makers. A review of cost-effectiveness literature on the efficacy of oral bisphosphonates has shown alendronate and risedronate to be most cost-effective in women with low BMD without previous fractures.9 Guidelines are inconsistent as to the place in therapy of denosumab (Prolia, Amgen). In economic analyses evaluating treatment of postmenopausal women, denosumab outperformed risedronate and ibandronate; its efficacy was comparable to generic alendronate, but it cost more.10 With regard to older men with osteoporosis, denosumab was also found to be cost-effective when compared with bisphosphonates and teriparatide (Forteo, Lilly).11.

Pharmacological Treatment of Insomnia.

Up to 70 million U.S. adults have chronic sleep and wakefulness disorders. Therapies may include prescription medications approved by the Food and Drug Administration, off-label treatments, over-the-counter drugs, and herbal therapies.

Can Medical Students Learn and Perform POCUS in the Pediatric Emergency Department? Implementation of a Short Curriculum.

Purpose: To determine medical student ability to accurately obtain and interpret POCUS exams of varying difficulty in the pediatric population after a short didactic and hands-on POCUS course. Methods: Five medical students were trained in four POCUS applications (bladder volume, long bone for fracture, limited cardiac for left ventricular function, & inferior vena cava collapsibility) and enrolled pediatric ED patients. Ultrasound-fellowship-trained emergency medicine physicians reviewed each scan for image quality and interpretation accuracy using the American College of Emergency Physicians' quality assessment scale. We report acceptable scan frequency and medical student vs. Ultrasound-fellowship-trained emergency medicine physician interpretation agreement with 95% confidence intervals (CI). Results: Ultrasound-fellowship-trained emergency medicine physicians graded 51/53 bladder volume scans as acceptable (96.2%; 95% CI 87.3-99.0%) and agreed with 50/53 bladder volume calculations (94.3%; 95% CI 88.1-100%). Ultrasound-fellowship-trained emergency medicine physicians graded 35/37 long bone scans as acceptable (94.6%; 95% CI 82.3-98.5%) and agreed with 32/37 medical student long bone scan interpretations (86.5%; 95% CI 72.0-94.1%). Ultrasound-fellowship-trained emergency medicine physicians graded 116/120 cardiac scans as acceptable (96.7%; 95% CI 91.7-98.7%) and agreed with 111/120 medical student left ventricular function interpretations (92.5%; 95% CI 86.4-96.0%). Ultrasound-fellowship-trained emergency medicine physicians graded 99/117 inferior vena cava scans as acceptable (84.6%; 95% CI 77.0-90.0%) and agreed with 101/117 medical student interpretations of inferior vena cava collapsibility (86.3%; 95% CI 78.9-91.4%). Conclusions: Medical students demonstrated satisfactory ability within a short period of time in a range of POCUS scans on pediatric patients after a novel curriculum. This supports the incorporation of a formal POCUS education into medical school curricula and suggests that novice POCUS learners can attain a measure of competency in multiple applications after a short training course.

Brain activity during a post-stress working memory task differs between the hormone-present and hormone-absent phase of hormonal contraception.

Taking hormonal contraceptives (HCs) affects the magnitude of the hormonal stress response and cognition. HCs are usually administered in a monthly cycle with both synthetic-hormone-containing and synthetic-hormone-absent phases. The synthetic hormones contained in HCs affect a wide range of neurophysiological systems, suggesting that effects of the medication might only be observed during the synthetic-hormone-containing phase of the HC cycle. To test this, women were seen twice, once during the hormone-present phase and once during the hormone-absent phase of the HC cycle. In each session, women performed an n-back working memory task to assess pre-stress performance outside of the magnetic resonance imaging scanner, were then exposed to cold pressor stress, and again completed the n-back task during functional magnetic resonance imaging. The free cortisol response to stress remained the same across the HC cycle. Women also performed comparably on the n-back task after stress exposure across the two phases. However, despite these similarities, women displayed greater disengagement of default mode network as task demands increased during the hormone-present phase only, a pattern more in line with working memory-related brain activation under non-stressful conditions reported in other studies. The results suggest that the synthetic hormones contained in HCs may mitigate stress-related disruptions of typical brain activation patterns during the hormone-present phase of the HC cycle, despite exhibiting comparable cortisol responses across the HC cycle. Additional research is required to determine the mechanisms contributing to, and the extent of, such mitigating effects.

The effects of lovastatin on proteasome activities in highly purified rabbit 20 S proteasome preparations and mouse MC3T3-E1 osteoblastic cells.

A number of clinical studies suggest that the use of the lipid-lowering agents collectively referred to as statins (hydroxymethyl glutaryl coenzyme A [HMG-CoA] reductase inhibitors) is associated with increased bone density, reduced fracture risk, and net bone anabolism. Statins (< or =5 micromol/L) stimulate rodent bone formation, but the mechanistic basis remains unclear. Since statins and the proteasome inhibitor lactacystin are structurally similar, and high doses (> or =40 micromol/L) of statins can inhibit the chymotryptic activity of the proteasome, it has been hypothesized that statins exert their anabolic effects on bone, in part, by inhibiting the proteasome, the major eukaryotic intracellular regulatory protease. This hypothesis conflicts with reports that statins stimulate proteasome activity and that proteasome-catalyzed degradation of specific substrates is required for cell proliferation, differentiation, and survival. Our chief objective was to determine the effects of statins (< or =10 micromol/L) on the chymotryptic activity of the proteasome in the 20 S proteasome and intact murine MC3T3-E1 cells cultured to low density (preosteoblasts) or high density (differentiated osteoblasts). Lovastatin (0.001 micromol/L to 5.0 micromol/L) stimulated the chymotryptic activity of the highly purified 20 S proteasome. Preosteoblasts and differentiated osteoblasts treated with 1, 5, or 10 micromol/L lovastatin for 1 hour exhibited morphologic abnormalities that were ameliorated by preincubation and treatment with 20 micromol/L mevalonate. The chymotryptic activity of the preosteoblast proteasome increased after 2 days of 1.0 micromol/L or 5.0 micromol/L lovastatin treatment. In addition, the DNA and protein contents of 1.0 micromol/L or 5.0 micromol/L lovastatin-treated preosteoblast cultures were lower those that observed in vehicle-, 0.01 micromol/L lovastatin-, or 0.10 micromol/L lovastatin-treated cultures. The chymotryptic activity of the proteasome was much lower in differentiated osteoblasts than in preosteoblasts. Two days of treatment with 1 micromol/L lovastatin modestly stimulated the chymotryptic activity of the proteasome in differentiated osteoblasts, but had no effects on total protein or DNA, compared to cultures treated with vehicle or lower doses of lovastatin. Thus, the data support the hypothesis that statins stimulate proteasome activities in highly purified proteasome preparations and preosteoblastic cells. Treating preosteoblastic or differentiated MC3T3-E1 cells with lovastatin concentrations > or = 1 micromol/L resulted in abnormal morphology and reduced the DNA and protein levels in preosteoblastic cultures, confirming the adverse effects of statins previously reported for other cells. In conclusion, the hypothesis that lovastatin exerts its anabolic effects on bone by inhibiting the proteasome activity of the osteoblast was refuted, and the effects of lovastatin on MC3T3-E1 cells were found to be highly dose- and development-dependent.