40Ar/39Ar geochronology of Burdigalian paleobotanical localities in the central Paratethys (south Slovakia)

The Lipovany and Mučín paleobotanical localities contain important floral associations within the tuff horizons, which were used for determination of subtropical to tropical climatic conditions during the Early Miocene. Based on the combination of results from plagioclase and biotite 40Ar/39Ar dating, the age of the tuff deposition is around 17.3Ma. For the Lipovany locality, single-grain 40Ar/39Ar convergent ages of 17.49±0.54Ma and 17.28±0.06Ma, for plagioclase and biotite were obtained, respectively. The Mučín locality only provide an imprecise convergent age of 16.5±1.4Ma due to the small size of the analyzed plagioclase crystals. The results thus allowed to include the fossil subtropical flora of the studied localities in the late Ottnangian regional stage (upper part of the Burdigalian). Additionally, these age data indicate that deposition of the overlaying Salgótarján Formation starts much later than originally thought (during Ottnangian-Karpatian boundary)

Pro-BDNF–induced synaptic depression and retraction at developing neuromuscular synapses

Postsynaptic cells generate positive and negative signals that retrogradely modulate presynaptic function. At developing neuromuscular synapses, prolonged stimulation of muscle cells induces sustained synaptic depression. We provide evidence that pro–brain-derived neurotrophic factor (BDNF) is a negative retrograde signal that can be converted into a positive signal by metalloproteases at the synaptic junctions. Application of pro-BDNF induces a dramatic decrease in synaptic efficacy followed by a retraction of presynaptic terminals, and these effects are mediated by presynaptic pan-neurotrophin receptor p75 (p75NTR), the pro-BDNF receptor. A brief stimulation of myocytes expressing cleavable or uncleavable pro-BDNF elicits synaptic potentiation or depression, respectively. Extracellular application of metalloprotease inhibitors, which inhibits the cleavage of endogenous pro-BDNF, facilitates the muscle stimulation–induced synaptic depression. Inhibition of presynaptic p75NTR or postsynaptic BDNF expression also blocks the activity-dependent synaptic depression and retraction. These results support a model in which postsynaptic secretion of a single molecule, pro-BDNF, may stabilize or eliminate presynaptic terminals depending on its proteolytic conversion at the synapses

40Ar/39Ar geochronology of Burdigalian paleobotanical localities in the central Paratethys (south Slovakia)

The Lipovany and Mučín paleobotanical localities contain important floral associations within the tuff horizons, which were used for determination of subtropical to tropical climatic conditions during the Early Miocene. Based on the combination of results from plagioclase and biotite 40Ar/39Ar dating, the age of the tuff deposition is around 17.3Ma. For the Lipovany locality, single-grain 40Ar/39Ar convergent ages of 17.49±0.54Ma and 17.28±0.06Ma, for plagioclase and biotite were obtained, respectively. The Mučín locality only provide an imprecise convergent age of 16.5±1.4Ma due to the small size of the analyzed plagioclase crystals. The results thus allowed to include the fossil subtropical flora of the studied localities in the late Ottnangian regional stage (upper part of the Burdigalian). Additionally, these age data indicate that deposition of the overlaying Salgótarján Formation starts much later than originally thought (during Ottnangian-Karpatian boundary)

A Randomized Multicenter Study Assessing the Educational Impact of a Computerized Interactive Hysterectomy Trainer on Gynecology Residents

Study Objective: To assess the improvement of cognitive surgical knowledge of laparoscopic hysterectomy in postgraduate year (PGY) 1 and 2 gynecology residents who used an interactive computer-based Laparoscopic Hysterectomy Trainer (Red Llama, Inc., Seattle, WA). Design: A multicenter, randomized, controlled study (Canadian Task Force classification I). Setting: Five departments of obstetrics and gynecology: Keck School of Medicine of the University of Southern California, Los Angeles, CA; University of California, Los Angeles, Los Angeles, CA; University of Washington, Seattle, WA; University of British Columbia, Vancouver, British Columbia, Canada; and University of Toronto, Toronto, Ontario, Canada. Participants: Gynecology residents, fellows, faculty, and minimally invasive surgeons. Interventions: The use of an interactive computer-based Laparoscopic Hysterectomy Trainer. Measurements and Main Results: In phase 1 of this 3-phase multicenter study, 2 hysterectomy knowledge assessment tests (A and B) were developed using a modified Delphi technique. Phase 2 administered these 2 online tests to PGY 3 and 4 gynecology residents, gynecology surgical fellows, faculty, and minimally invasive surgeons (n = 60). In phase 3, PGY 1 and 2 gynecology residents (n = 128) were recruited, and 101 chose to participate, were pretested (test A), and then randomized to the control or intervention group. Both groups continued site-specific training while the intervention group additionally used the Laparoscopic Hysterectomy Trainer. Participant residents were subsequently posttested (test B). Phase 2 results showed no differences between cognitive tests A and B when assessed for equivalence, internal consistency, and reliability. Construct validity was shown for both tests (p < .001). In phase 3, the pretest mean score for the control group was 242 (standard deviation [SD] = 56.5), and for the intervention group it was 217 (SD = 57.6) (nonsignificant difference, p = .089). The t test comparing the posttest control group (mean = 297, SD = 53.6) and the posttest intervention group (mean = 343, SD = 50.9) yielded a significant difference (p < .001, 95% confidence interval, 48.4-108.8). Posttest scores for the intervention group were significantly better than for the control group (p < .001). Conclusion: Using the Laparoscopic Hysterectomy Trainer significantly increased knowledge of the hysterectomy procedure in PGY 1 and 2 gynecology residents

A Randomized Multicenter Study Assessing the Educational Impact of a Computerized Interactive Hysterectomy Trainer on Gynecology Residents

Study Objective: To assess the improvement of cognitive surgical knowledge of laparoscopic hysterectomy in postgraduate year (PGY) 1 and 2 gynecology residents who used an interactive computer-based Laparoscopic Hysterectomy Trainer (Red Llama, Inc., Seattle, WA). Design: A multicenter, randomized, controlled study (Canadian Task Force classification I). Setting: Five departments of obstetrics and gynecology: Keck School of Medicine of the University of Southern California, Los Angeles, CA; University of California, Los Angeles, Los Angeles, CA; University of Washington, Seattle, WA; University of British Columbia, Vancouver, British Columbia, Canada; and University of Toronto, Toronto, Ontario, Canada. Participants: Gynecology residents, fellows, faculty, and minimally invasive surgeons. Interventions: The use of an interactive computer-based Laparoscopic Hysterectomy Trainer. Measurements and Main Results: In phase 1 of this 3-phase multicenter study, 2 hysterectomy knowledge assessment tests (A and B) were developed using a modified Delphi technique. Phase 2 administered these 2 online tests to PGY 3 and 4 gynecology residents, gynecology surgical fellows, faculty, and minimally invasive surgeons (n = 60). In phase 3, PGY 1 and 2 gynecology residents (n = 128) were recruited, and 101 chose to participate, were pretested (test A), and then randomized to the control or intervention group. Both groups continued site-specific training while the intervention group additionally used the Laparoscopic Hysterectomy Trainer. Participant residents were subsequently posttested (test B). Phase 2 results showed no differences between cognitive tests A and B when assessed for equivalence, internal consistency, and reliability. Construct validity was shown for both tests (p < .001). In phase 3, the pretest mean score for the control group was 242 (standard deviation [SD] = 56.5), and for the intervention group it was 217 (SD = 57.6) (nonsignificant difference, p = .089). The t test comparing the posttest control group (mean = 297, SD = 53.6) and the posttest intervention group (mean = 343, SD = 50.9) yielded a significant difference (p < .001, 95% confidence interval, 48.4-108.8). Posttest scores for the intervention group were significantly better than for the control group (p < .001). Conclusion: Using the Laparoscopic Hysterectomy Trainer significantly increased knowledge of the hysterectomy procedure in PGY 1 and 2 gynecology residents

Inhibitors of fatty acid amide hydrolase reduce carrageenan-induced hind paw inflammation in pentobarbital-treated mice: comparison with indomethacin and possible involvement of cannabinoid receptors

1. The in vivo effect of inhibitors of fatty acid amide hydrolase (FAAH) upon oedema volume and FAAH activity was evaluated in the carrageenan induced hind paw inflammation model in the mouse. Oedema was measured at two time points, 2 and 4 h, after intraplantar injection of carrageenan to anaesthetised mice. 2. Intraperitoneal (i.p.) injections of the FAAH inhibitor URB597 (0.1, 0.3, 1 and 3 mg kg(−1)) 30 min prior to carrageenan administration, dose-dependently reduced oedema formation. At the 4 h time point, the ED(50) for URB597 was ∼0.3 mg kg(−1). Indomethacin (5 mg kg(−1) i.p.) completely prevented the oedema response to carrageenan. 3. The antioedema effects of indomethacin and URB597 were blocked by 3 mg kg(−1) i.p. of the CB(2) receptor antagonist SR144528. The effect of URB597 was not affected by pretreatment with the peroxisome proliferator-activated receptor γ antagonist bisphenol A diglycidyl ether (30 mg kg(−1) i.p.) or the TRPV1 antagonist capsazepine (10 mg kg(−1) i.p.), when oedema was assessed 4 h after carrageenan administration. The CB(1) receptor antagonists AM251 (3 mg kg(−1) i.p.) and rimonabant (0.5 mg kg(−1) i.p.) gave inconsistent effects upon the antioedema effect of URB597. 4. FAAH measurements were conducted ex vivo in the paws, spinal cords and brains of the mice. The activities of FAAH in the paws and spinal cords of the inflamed vehicle-treated mice were significantly lower than the corresponding activities in the noninflamed mice. PMSF treatment almost completely inhibited the FAAH activity in all three tissues, as did the highest dose of URB597 (3 mg kg(−1)) in spinal cord samples, whereas no obvious changes were seen ex vivo for the other treatments. 5. In conclusion, the results show that in mice, treatment with indomethacin and URB597 produce SR144528-sensitive anti-inflammatory effects in the carrageenan model of acute inflammation