Transmural electrical potential difference in the mammalian esophagus in vivo

A simple, safe, accurate, and reproducible technique for measuring the transmural electrical potential difference (PD) of the esophagus has been developed. This technique, a modification of those previously used, allows simultaneous correlation of the PD profile with the pressure profile obtained during routine manometry. With this technique, a subcutaneous reference bridge was shown to detect accurately a lumen-negative electrical orientation for the esophageal PD in three species: rabbit, opossum, and man. A characteristic and reproducible PD profile was present for each species. In the rabbit the gastric PD was low,--12 mv, relative to the body of the esophagus,--26 to -29 mv. In contrast, both opossum and man had relatively high gastric PD's ( -36 to -43 mv) when compared to esophageal PD's ( -12 to -25 mv). In the rabbit and opossum, the PD in the lower esophageal sphincter ( -5 to -6 mv) was less than both gastric or esophageal PD's, whereas in human beings the lower esophageal sphincter PD ( -22 mv) was between gastric and esophageal values. In vitro PD measurements and histological studies of opossum esophagus revealed differences in the epithelium which correlated with the different in vivo PD's.     

Work satisfaction and career aspirations of internists working in teaching hospital group practices

This paper presents data on the characteristics, work activities, job-related stress, work satisfaction, and career aspirations of 150 faculty and 595 housestaff physicians who regularly provide continuous primary care in 15 teaching hospital-based group practices. The faculty were young, board-certified generalists; they had been recruited from local training programs and spent the majority of their time seeing patients and supervising housestaff. Job satisfaction among faculty and housestaff was generally high. Dissatisfaction occurred most often with aspects of work over which physicians had little control. Although work-related stress was common, it was not related to job satisfaction. Compared with housestaff in traditional residency programs, housestaff enrolled in special Primary Care Training Programs reported significantly greater job satisfaction. For all housestaff, satisfaction with work in the group practice was consistently associated with decreased interest in subspecialty training. assisted in preparing this report. Received from the Department of Medicine and the School of Public Health, UCLA Center for the Health Sciences. Los Angeles. California. Supported by Grant #59082 from the Robert Wood Johnson Foundation. The views expressed herein do not necessarily represent those of the Robert Wood Johnson Foundation.     

Inhibitory neuropeptides and intrinsic inhibitory innervation of descending human colon

The effects of aging on inhibitory neuropeptide concentrations and intrinsic inhibitory innervation of circular muscle were investigated using normal descending colon obtained at surgery. Immunoreactive vasoactive intestinal peptide, peptide histidine-methionine, met⁵-enkephalin, neuropeptide Y, and somatostatin were extracted from specimens of muscularis externa (patient ages: 19–84 years) and measured by radioimmunoassay. Intracellular electrical activity was recorded from strips of circular muscle (patients ages: 49–84 years) using glass microelectrodes; inhibitory junction potentials were evoked by electrical field stimulation. There were no significant differences (t tests:P>0.05) between neuropeptide concentrations in patients<70 years old (N=28) compared to patients70 years old (N=12). However, the amplitude of inhibitory junction potentials declined with increasing patient age (r=–0.58,P=0.02,N=16), with no change in resting membrane potentials (r=0.22;P>0.05). The decline in amplitude in women (r=–0.68,P=0.03,N=9) preceded the decline in men (r=–0.62,P=0.10,N=7). Age-related decline in inhibitory junction potentials could be related to decreased: density of inhibitory nerves, release of inhibitory neurotransmitter, density of binding sites for inhibitory neurotransmitter on smooth muscle, or a combination thereof. Alternatively, this decline might represent a change in interaction of inhibitory neurotransmitter with the smooth muscle membrane, such as a change in coupling of binding site with the potassium channel, decreased number of potassium channels, or altered permeability of the potassium channel.This study was supported in part by the National Institutes of Health (DK 17238 and DK 34988), and by VA Medical Research funds.     

Mutations in the MSH3 gene preferentially lead to deletions within tracts of simple repetitive DNA in Saccharomyces cerevisiae.

Eukaryotic genomes contain tracts of DNA in which a single base or a small number of bases are repeated (microsatellites). Mutations in the yeast DNA mismatch repair genes MSH2, PMS1, and MLH1 increase the frequency of mutations for normal DNA sequences and destabilize microsatellites. Mutations of human homologs of MSH2, PMS1, and MLH1 also cause microsatellite instability and result in certain types of cancer. We find that a mutation in the yeast gene MSH3 that does not substantially affect the rate of spontaneous mutations at several loci increases microsatellite instability about 40-fold, preferentially causing deletions. We suggest that MSH3 has different substrate specificities than the other mismatch repair proteins and that the human MSH3 homolog (MRP1) may be mutated in some tumors with microsatellite instability.     

Management of Posttraumatic Ankle Arthritis: Literature Review

Purpose of Review

Trauma is the principle cause of osteoarthritis in the ankle, which is associated with significant morbidity. This review highlights the current literature for the purpose of bringing the reader up-to-date on the management of posttraumatic ankle arthritis, describing treatment efficacy, indications, contraindications, and complications.

Recent Findings

Recent studies on osteoarthritis have demonstrated variability among anatomic locations regarding the mechanisms and rates of development for posttraumatic osteoarthritis, which are attributed to newly discovered biological differences intrinsic to each joint. Regarding surgical management of posttraumatic ankle arthritis, osteochondral allograft transplantation of the talus, and supramalleolar osteotomies have demonstrated promising results. Additionally, the outpatient setting was found to be appropriate for managing pain following total ankle arthroplasty, associated with low complication rates and no readmission.

Summary

Management for posttraumatic ankle arthritis is generally progressive. Initial treatment entails nonpharmacologic options with surgery reserved for posttraumatic ankle arthritis refractory to conservative treatment. Patient demographics and lifestyles should be carefully considered when formulating a management strategy, as outcomes are dependent upon the satisfaction of each set of respective criteria. Ultimately, the management of posttraumatic ankle arthritis should be individualized to satisfy the needs and desires, which are specific to each patient.

     

Intramolecular radical cyclization approach to access highly substituted indolines and 2,3-dihydrobenzofurans under visible-light

The combination of visible-light and tris(trimethylsilyl)silane promoting intramolecular reductive cyclization protocol for the synthesis of functionalized indolines and 2,3-dihydrobenzofurans has been developed. The transformations occur in the absence of transition metal and additional photocatalyst. In addition, quantum yield (Φ) was determined and electron paramagnetic resonance spectroscopy was performed to better understand the reaction pathway.

The combination of visible-light and tris(trimethylsilyl)silane promoting intramolecular reductive cyclization protocol for the synthesis of functionalized indolines and 2,3-dihydrobenzofurans has been developed.     

Public Health Intelligence: Learning From the Ebola Crisis

Today’s public health crises, as exemplified by the Ebola outbreak, lead to dramatic calls to action that typically include improved electronic monitoring systems to better prepare for, and respond to, similar occurrences in the future. Even a preliminary public health informatics evaluation of the current Ebola crisis exposes the need for enhanced coordination and sharing of trustworthy public health intelligence.We call for a consumer-centric model of public health intelligence and the formation of a national center to guide public health intelligence gathering and synthesis.Sharing accurate and actionable information with government agencies, health care practitioners, policymakers, and, critically, the general public, will mark a shift from doing public health surveillance on people to doing public health surveillance for people.The Ebola crisis continues to have a major impact on the nation and much of the world. Ebola and similar critical public health and health care delivery crises lead to dramatic calls to action that seek to understand the nature of the problem, to develop strategic intelligence on the scope and reach of the problem, to develop tactical responses, and to build protections to manage future risk. Typically, the creation of electronic monitoring systems to better prepare for, and respond to, similar occurrences in the future is indicated.Public health crises can expose failures in (1) the process (e.g., events, task performance, or actions), (2) policy (e.g., absent, outdated, poorly disseminated, or unevenly implemented guidelines), and (3) responsiveness (e.g., poorly coordinated or deployed resources, inadequate, ineffective strategic responses, etc.). The common thread underlying failures associated with such public health crises is deficiencies in actionable intelligence that inform process, policy, and responsiveness. Once actionable intelligence has been appropriately gathered and disseminated, adequate resources must be deployed to implement containment and preventive interventions.Public health system informatics is the field designed specifically to assess the national capability of our combined network of public health departments and health care delivery sites to intelligently manage crises and ensure population safety. Public health informatics activity builds, maintains, and evaluates the national intelligence required to address the full spectrum of decision-making needs and includes: individual health consumers seeking information about their individual risk and the resources to assist them in times of need; health care providers seeking to understand and interpret practice guidelines; public health program managers seeking to organize proper responses, deploy resources, and communicate the progress in mitigating and eventually eliminating the threat; and policymakers governing national public health system integrity.Even a preliminary public health system informatics evaluation of the current Ebola crisis highlights several failures in the gathering, management, dissemination, and responsiveness of national public health intelligence. Such an examination offers some critical lessons and helps us to better understand the fundamental components of maintaining a heightened national public health intelligence capability, not only for Ebola, but in general, for all public health crises.     

The Return of Actionable Variants Empirical (RAVE) Study,a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results

Objectives

To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers.