Establishing a Rural General Surgery Residency Program: Identifying Community Stakeholder Perception and Obstacles of a de Novo Residency in Rural Appalachia.

BACKGROUND: Rural healthcare has become more challenging over the past several years with increasingly limited access to surgical care in the rural setting. The Accreditation Council for Graduate Medical Education (ACGME) has recently introduced the Rural Track Program (RTP) initiative to combat physician shortage in rural areas. We intend to start the first Rural General Surgery Residency program under the RTP designation in rural Appalachia. STUDY DESIGN: 430 community stakeholders were surveyed regarding the anticipated impact of a new training program. Questions focused on the understanding of a Residency Program, the care provided by residents, impact on availability of local care, current geographical limitation of surgical care, and potential benefits/obstacles of the training program. RESULTS: Over 90% of all surveyed approved of training surgeons locally, with the local government believing that the program would be a good investment for the community. Several locals had been treated by resident physicians at other facilities and the majority were satisfied with the care they received. Several families frequently travel to larger cities for surgical care, with 96% of all respondents believing that the program would provide better access to care locally. CONCLUSION: Our study demonstrated that the community is familiar with healthcare in a training facility and welcoming to a local training program, while believing that trainees will have a positive impact on local surgical care in rural Appalachia. We will continue to work with the local community and healthcare personnel while developing the program and tailor our Residency to the rural setting as able.

Covalent capture and electrochemical quantification of pathogenic E. coli.

Pathogenic E. coli pose a significant threat to public health, as strains of this species cause both foodborne illnesses and urinary tract infections. Using a rapid bioconjugation reaction, we selectively capture E. coli at a disposable gold electrode from complex solutions and accurately quantify the pathogenic microbes using electrochemical impedance spectroscopy.

Site-Selective Protein Immobilization on Polymeric Supports through N-Terminal Imidazolidinone Formation.

Protein immobilization techniques on polymeric supports have enabled many applications in biotechnology and materials science. Attaching the proteins with controlled orientations has inherent advantages, but approaches for doing this have been largely limited to cysteine or noncanonical amino acid targeting. Herein, we report a method to attach the N-terminal positions of native proteins to polymer resins site-specifically through the use of 2-pyridinecarboxyaldehyde (2PCA) derivatives. For high protein loadings and practical synthesis, we initiated this work by preparing highly reactive 2PCA derivatives using Pd-catalyzed cross-coupling amination. The resulting compounds were attached to amine-containing polyethylene glycol acrylamide resin (PEGA-NH2), which subsequently reacted with the N-termini of proteins to produce linkages that were stable over the long term but could be reversed through the addition of hydroxylamine. We envision that this site-selective, 2PCA-based protein immobilization can provide a simple and generalizable immobilization protocol.

Synthesis, Characterization, and Variable-Temperature NMR Studies of Silver(I) Complexes for Selective Nitrene Transfer.

An array of silver complexes supported by nitrogen-donor ligands catalyze the transformation of C═C and C-H bonds to valuable C-N bonds via nitrene transfer. The ability to achieve high chemoselectivity and site selectivity in an amination event requires an understanding of both the solid- and solution-state behavior of these catalysts. X-ray structural characterizations were helpful in determining ligand features that promote the formation of monomeric versus dimeric complexes. Variable-temperature 1H and DOSY NMR experiments were especially useful for understanding how the ligand identity influences the nuclearity, coordination number, and fluxional behavior of silver(I) complexes in solution. These insights are valuable for developing improved ligand designs.

Catalyst-Controlled and Tunable, Chemoselective Silver-Catalyzed Intermolecular Nitrene Transfer: Experimental and Computational Studies.

The development of new catalysts for selective nitrene transfer is a continuing area of interest. In particular, the ability to control the chemoselectivity of intermolecular reactions in the presence of multiple reactive sites has been a long-standing challenge in the field. In this paper, we demonstrate examples of silver-catalyzed, nondirected, intermolecular nitrene transfer reactions that are both chemoselective and flexible for aziridination or C-H insertion, depending on the choice of ligand. Experimental probes present a puzzling picture of the mechanistic details of the pathways mediated by [(tBu3tpy)AgOTf]2 and (tpa)AgOTf. Computational studies elucidate these subtleties and provide guidance for the future development of new catalysts exhibiting improved tunability in group transfer reactions.

A General Catalyst for Site-Selective C(sp(3))-H Bond Amination of Activated Secondary over Tertiary Alkyl C(sp(3))-H Bonds.

The discovery of transition metal complexes capable of promoting general, catalyst-controlled and selective carbon-hydrogen (C-H) bond amination of activated secondary C-H bonds over tertiary alkyl C(sp(3))-H bonds is challenging, as substrate control often dominates when reactive nitrene intermediates are involved. In this letter, we report the design of a new silver complex, [(Py5Me2)AgOTf]2, that displays general and good-to-excellent selectivity for nitrene insertion into propargylic, benzylic, and allylic C-H bonds over tertiary alkyl C(sp(3))-H bonds.

Ligand-controlled, tunable silver-catalyzed C-H amination.

The development of readily tunable and regioselective C-H functionalization reactions that operate solely through catalyst control remains a challenge in modern organic synthesis. Herein, we report that simple silver catalysts supported by common nitrogenated ligands can be used to tune a nitrene transfer reaction between two different types of C-H bonds. The results reported herein represent the first example of ligand-controlled and site-selective silver-promoted C-H amination.

Preconditioning by isoflurane elicits mitochondrial protective mechanisms independent of sarcolemmal KATP channel in mouse cardiomyocytes.

Cardiac mitochondria and the sarcolemmal (sarc)KATP channels contribute to cardioprotective signaling of anesthetic-induced preconditioning. Changes in mitochondrial bioenergetics influence the sarcolemmal ATP-sensitive K (sarcKATP) channel function, but whether this channel has impacts on mitochondria is uncertain. We used the mouse model with deleted pore-forming Kir6.2 subunit of sarcKATP channel (Kir6.2 KO) to investigate whether the functional sarcKATP channels are necessary for isoflurane activation of mitochondrial protective mechanisms. Ventricular cardiomyocytes were isolated from C57Bl6 wild-type (WT) and Kir6.2 KO mouse hearts. Flavoprotein autofluorescence, mitochondrial reactive oxygen species production, and mitochondrial membrane potential were monitored by laser-scanning confocal microscopy in intact cardiomyocytes. Cell survival was assessed using H2O2-induced stress. Isoflurane (0.5 mM) increased flavoprotein fluorescence to 180% ± 14% and 190% ± 15% and reactive oxygen species production to 118% ± 2% and 124% ± 6% of baseline in WT and Kir6.2 KO myocytes, respectively. Tetramethylrhodamine ethyl ester fluorescence decreased to 84% ± 6% in WT and to 86% ± 4% in Kir6.2 KO myocytes. This effect was abolished by 5HD. Pretreatment with isoflurane decreased the stress-induced cell death from 31% ± 1% to 21% ± 1% in WT and from 44% ± 2% to 35% ± 2% in Kir6.2 KO myocytes. In conclusion, Kir6.2 deletion increases the sensitivity of intact cardiomyocytes to oxidative stress, but does not alter the isoflurane-elicited protective mitochondrial mechanisms, suggesting independent roles for cardiac mitochondria and sarcKATP channels in anesthetic-induced preconditioning by isoflurane.