Solvent- and transition metal-free amide synthesis from phenyl esters and aryl amines

A general, economical, and environmentally friendly method of amide synthesis from phenyl esters and aryl amines was developed. This new method has significant advantages compared to previously reported palladium-catalyzed approaches. The reaction is performed transition metal- and solvent-free, using a cheap and environmentally benign base, NaH. This approach enabled us to obtain target amides in high yields with high atom economy.

A new environmentally friendly approach to transition metal- and solvent-free amide synthesis from aryl esters and aryl amines is described.     

Implementing and Evaluating a Four-Year Integrated End-of-Life Care Curriculum for Medical Students

Problem: Meeting the needs of patients with life-limiting and terminal illness requires effectively trained physicians in all specialties to provide skillful and compassionate care. Despite mandates for end-of-life (EoL) care education, graduating medical students do not consistently feel prepared to provide this care. Intervention: We have developed a longitudinal, integrated, and developmental 4-year curriculum in EoL care. The curriculum's purpose is to teach basic competencies in EoL care. A variety of teaching strategies emphasize experiential, skill-building activities with special attention to student self-reflection. In addition, we have incorporated interprofessional learning and education on the spiritual and cultural aspects of care. We created blended learning strategies combining interactive online modules with live workshops that promote flexibility, adaptability, and interprofessional learning opportunities. Context: The curriculum was implemented and evaluated in the 4-year program of studies at Yale School of Medicine. Outcome: A mixed-method evaluation of the curriculum included reviews of student written reflections and questionnaires, graduating student surveys, and demonstration of 4th-year students’ competency in palliative care with an observed structured clinical examination (OSCE). These evaluations demonstrate significant improvements in students’ self-reported preparedness in EoL care and perceptions of the adequacy in their instruction in EoL and palliative care, as well as competency in primary palliative care in a newly developed OSCE. Lessons Learned: A 4-year longitudinal integrated curriculum enhances students’ skills and preparedness in important aspects of EoL care. As faculty resources, clinical sites, and curricular structure vary by institution, proven and adaptable educational strategies as described in this article may be useful to address the mandate to improve EoL care education. Teaching strategies and curricular components and design as just described can be adapted to other programs.     

Anterograde TNFα Transport From Rat Dorsal Root Ganglion To Spinal Cord And Injured Sciatic Nerve

Spontaneous activity originating in the injured nerve or the dorsal root ganglion (DRG) has been implicated in the development and maintenance of neuropathic pain. The inherent characteristics of spontaneous activity and the causal factors that modulate its firing pattern and frequency are not fully understood. We attempted to assess the thermosensitivity of spontaneous activity in dorsal root ganglion (DRG) neurons in normal rats and in rat, with cl-ironic compression of the DRG (CCD) in an in vitro nerve-DRG preparation. Extracellular, dorsal root recording from 66 spontaneously active CCD Abeta fibers indicate that: (1) decreasing bath temperature from 37 to 36-26 °C significantly decreased the firing rate (FR) in 85% (56/66) of fibers tested, of which 19 fibers (34%) responded to temperature change at physiological range (36-37 °C), whereas the remaining fibers responded at lower temperature levels (26-36 °C); (2) cooling of the DRG increased the FR in 12% (8/66) of fibers tested; (3) similarly, the firing rate of 21/26 spontaneously active Abeta fibers from normal rats was decreased following temperature decrease; (4) intracellular recordings from 38 normal neurons revealed that cooling the DRG significantly increased the action potential (AP) threshold, A-P duration, AP amplitude and afterhyperpolarization (AHP) duration, but decreased AHP amplitude, maximal depolarizing and repolarizing rates. There was no significant change in the rheobase currents or the resting membrane potential. The present study indicates that large sensory neurons with myelinated axons are temperature dependent. It also suggests that maintenance of a stable temperature is critical for reliable characterization of spontaneous activity of sensory neurons.