Plos One
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The hippocampus plays a central role in memory formation in the mammalian brain. Its ability to encode information is thought to depend on the plasticity of synaptic connections between neurons. In the pyramidal neurons constituting the primary hippocampal output to the cortex, located in area CA1, firing of presynaptic CA3 pyramidal neurons produces monosynaptic excitatory postsynaptic potentials (EPSPs) followed rapidly by feedforward (disynaptic) inhibitory postsynaptic potentials (IPSPs). ⋯ Using whole-cell recording in hippocampal slices from adult rats, we find that the efficacy of synaptic transmission from CA3 to CA1 can be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, we show that the induction of GABAergic plasticity at feedforward inhibitory inputs results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials. Like classic LTP, disinhibition-mediated LTP requires NMDAR activation, suggesting a role in types of learning and memory attributed primarily to the former and raising the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain.
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Spontaneous thought processes (STPs), also called daydreaming or mind-wandering, occur ubiquitously in daily life. However, the functional significance of STPs remains largely unknown. ⋯ These findings strengthen a view that offline memory reprocessing and STPs share the brain's default network, and thus implicate that offline memory reprocessing may be a predetermined function of STPs. This supports the perspective that memory can be consolidated and modified during STPs, and thus gives rise to a dynamic behavior dependent on both previous external and internal experiences.
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Several anti-viral drugs have demonstrated efficacy in preventing Cytomegalovirus (CMV) infections in solid organ transplant (SOT) patients. The recently approved valganciclovir is the most commonly used and most expensive drug for CMV prevention. The safety and efficacy data have been drawn from a single trial. We hypothesized that valganciclovir may not be as safe as nor more effective than other therapies for CMV prevention. ⋯ Valganciclovir shows no superior efficacy and significantly higher risk of absolute neutropenia, CMV late-onset disease, and CMV tissue-invasive disease compared to other standard therapies. Due to the availability of efficacious, safer, and lower cost drugs (high-dose acyclovir, valacyclovir, ganciclovir), our results do not favor the use of valganciclovir as a first-line agent for CMV preemptive or universal prophylaxis in SOT patients.
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We previously showed that in the absence of a formal emergency system, lay people face a heavy burden of injuries in Kampala, Uganda, and we demonstrated the feasibility of a basic prehospital trauma course for lay people. This study tests the effectiveness of this course and estimates the costs and cost-effectiveness of scaling up this training. ⋯ Lay first-responders effectively retained knowledge on prehospital trauma care and confidently used their first-aid skills and supplies for at least six months. The costs of scaling up this intervention to cover Kampala are very modest. This may be a cost-effective first step toward developing formal emergency services in Uganda other resource-constrained settings. Further research is needed in this critical area of trauma care in low-income countries.
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To answer five research questions: Do Norwegian physicians know about the three important aspects of EBM? Do they use EBM methods in their clinical practice? What are their attitudes towards EBM? Has EBM in their opinion changed medical practice during the last 10 years? Do they use EBM based information sources? ⋯ The results of the study indicate that Norwegian physicians have a limited knowledge of the key aspects of EBM but a positive attitude towards the concept. They had limited experience in the practice of EBM and were rather indifferent to the impact of EBM on medical practice. For solving a patient problem, physicians would rather consult a colleague than searching evidence based resources such as the Cochrane Library.