Microglia are dispensable for experience-dependent refinement of visual circuitry.

Microglia are proposed to be critical for the refinement of developing neural circuitry. However, evidence identifying specific roles for microglia has been limited and often indirect. Here we examined whether microglia are required for the experience-dependent refinement of visual circuitry and visual function during development. We ablated microglia by administering the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622, and then examined the consequences for retinal function, receptive field tuning of neurons in primary visual cortex (V1), visual acuity, and experience-dependent plasticity in visual circuitry. Eradicating microglia by treating mice with PLX5622 beginning at postnatal day (P) 14 did not alter visual response properties of retinal ganglion cells examined three or more weeks later. Mice treated with PLX5622 from P14 lacked more than 95% of microglia in V1 by P18, prior to the opening of the critical period. Despite the absence of microglia, the receptive field tuning properties of neurons in V1 were normal at P32. Similarly, eradicating microglia did not affect the maturation of visual acuity. Mice treated with PLX5622 displayed typical ocular dominance plasticity in response to brief monocular deprivation. Thus, none of these principal measurements of visual circuit development and function detectibly differed in the absence of microglia. We conclude that microglia are dispensable for experience-dependent refinement of visual circuitry. These findings challenge the proposed critical role of microglia in refining neural circuitry.

Monocular deprivation during the critical period alters neuronal tuning and the composition of visual circuitry.

Abnormal visual experience during a developmental critical period degrades cortical responsiveness. Yet how experience-dependent plasticity alters the response properties of individual neurons and composition of visual circuitry is unclear. Here, we measured with calcium imaging in alert mice how monocular deprivation (MD) during the developmental critical period affects tuning for binocularity, orientation, and spatial frequency for neurons in primary visual cortex. MD of the contralateral eye did not uniformly shift ocular dominance (OD) of neurons towards the fellow ipsilateral eye but reduced the number of monocular contralateral neurons and increased the number of monocular ipsilateral neurons. MD also impaired matching of preferred orientation for binocular neurons and reduced the percentage of neurons responsive at most spatial frequencies for the deprived contralateral eye. Tracking the tuning properties for several hundred neurons before and after MD revealed that the shift in OD is complex and dynamic, with many previously monocular neurons becoming binocular and binocular neurons becoming monocular. Binocular neurons that became monocular were more likely to lose responsiveness to the deprived contralateral eye if they were better matched for orientation prior to deprivation. In addition, the composition of visual circuitry changed as population of neurons more responsive to the deprived eye were exchanged for neurons with tuning properties more similar to the network of responsive neurons altered by MD. Thus, plasticity during the critical period adapts to recent experience by both altering the tuning of responsive neurons and recruiting neurons with matching tuning properties.

Single-site robotic cholecystectomy: efficiency and cost analysis.

BACKGROUND: Single-incision surgery has gained in popularity, and the recent development of specialized robotic and laparoscopic instruments may remove some of the ergonomic and technical difficulties associated with this approach. However, questions of cost and efficiency remain. METHODS: We prospectively collected perioperative outcome and efficiency (operative time, case volume) data for our single-site robotic cholecystectomy cases and retrospectively reviewed data for our single-incision laparoscopic cholecystectomy cases. RESULTS: There were no differences in patient characteristics or perioperative outcomes between the robotic (n = 20) and laparoscopic (n = 10) groups; operative times were equivalent (84.6 vs 85.5 min; p = 0.8737) and blood loss and complications were minimal. There was a higher robotic case volume, with an average of two robotic cases (range 1-4)/day vs one/day for laparoscopic cases (range 1-1; p = 0.0306). Streamlined instrument costs were essentially equivalent. CONCLUSIONS: Robotic single-site cholecystectomy is a safe, cost-effective alternative to single-incision laparoscopic cholecystectomy in a robot-existing model.

Current trends in hospital mergers and acquisitions.

Healthcare reform will impact hospital consolidation in three key areas: Payment rates will decrease, indirectly encouraging consolidation by forcing hospitals to find new ways to reduce costs and increase negotiating clout with suppliers and payers. The cost of doing business will increase as hospitals spend more on compliance, technology, and physician employment. The ACO model will encourage hospital network formation by rewarding integrated healthcare systems that can reduce costs and improve quality.

Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand dermatitis in patients refractory to standard therapy: results of a randomized, double-blind, placebo-controlled, multicenter trial.

OBJECTIVE: To assess the efficacy and safety of oral alitretinoin (9-cis-retinoic acid), 10 mg/d, 20 mg/d, and 40 mg/d, compared with placebo control, in the treatment of chronic hand dermatitis. DESIGN: Multicenter, randomized, double-blind, placebo-control, prospective trial. SETTING: A total of 43 outpatient clinics in 10 European countries. PATIENTS: Of 348 patients screened, 319 with moderate or severe refractory chronic hand dermatitis were randomized, in the ratio of 1:1:1:1, to 4 treatment groups and received allocated intervention. Of 75 patients who withdrew, 24 withdrew owing to adverse events. INTERVENTIONS: Placebo or 10 mg, 20 mg, or 40 mg of oral alitretinoin (9-cis-retinoic acid) taken once daily for 12 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for a follow-up period of 3 months. MAIN OUTCOME MEASURE: Physician's global assessment of overall chronic hand dermatitis severity. RESULTS: Alitretinoin led to a significant and dose-dependent improvement in disease status, with responses in up to 53% of patients, and up to a 70% mean reduction in disease signs and symptoms. Treatment was generally well tolerated, with dose-dependent effects comprising headache, flushing, mucocutaneous events, hyperlipidemia, and decreased hemoglobin and decreased free thyroxin levels. Three months after discontinuation of treatment, the rate of relapse was 26%, independent of dose. CONCLUSION: Alitretinoin given at well-tolerated doses induced substantial clearing of chronic hand dermatitis in patients refractory to conventional therapy.

Explaining the discrepancy between intentions and actions: the case of hypothetical bias in contingent valuation.

An experiment was designed to account for intention-behavior discrepancies by applying the theory of planned behavior to contingent valuation. College students (N = 160) voted in hypothetical and real payment referenda to contribute $8 to a scholarship fund. Overestimates of willingness to pay in the hypothetical referendum could not be attributed to moderately favorable latent dispositions. Instead, this hypothetical bias was explained by activation of more favorable beliefs and attitudes in the context of a hypothetical rather than a real referendum. A corrective entreaty was found to eliminate this bias by bringing beliefs, attitudes, and intentions in line with those in the real payment situation. As a result, the theory of planned behavior produced more accurate prediction of real payment when participants were exposed to the corrective entreaty.