Paradigm shift in gastrointestinal surgery − combating sarcopenia with prehabilitation: Multimodal review of clinical and scientific data

A growing body of evidence has demonstrated the prognostic significance of sarcopenia in surgical patients as an independent predictor of postoperative complications and outcomes. These included an increased risk of total complications, major complications, re-admissions, infections, severe infections, 30 d mortality, longer hospital stay and increased hospitalization expenditures. A program to enhance recovery after surgery was meant to address these complications; however, compliance to the program since its introduction has been less than ideal. Over the last decade, the concept of prehabilitation, or “pre-surgery rehabilitation”, has been discussed. The presurgical period represents a window of opportunity to boost and optimize the health of an individual, providing a compensatory “buffer” for the imminent reduction in physiological reserve post-surgery. Initial results have been promising. We review the literature to critically review the utility of prehabilitation, not just in the clinical realm, but also in the scientific realm, with a resource management point-of-view.     

Regulatory cytokine production stimulated by DNA vaccination against an altered form of glutamic acid decarboxylase 65 in nonobese diabetic mice

Nonobese diabetic (NOD) mice develop a T-cell dependent autoimmune form of diabetes, in which glutamic acid decarboxylase 65 (GAD65) is an important islet target antigen. Intramuscular DNA vaccination with a plasmid encoding native GAD65 (a cytosolic antigen) did not significantly alter the incidence of diabetes, but vaccination against an altered form of GAD65 with a signal peptide (spGAD), which is secreted in vitro, was protective. The preventive effect was further enhanced by repeated injections of the spGAD plasmid. Following DNA injection into muscle GAD65 was expressed for several months, and this was not accompanied by an inflammatory response. Immunization against GAD65 was not associated with substantial alterations in cytokine production by splenic lymphocytes stimulated with immunogenic GAD65 peptides. In contrast, spGAD induced increased secretion of both interleukin 10 and interferon gamma and a striking decrease in the interferon gamma/interleukin 10 ratio in culture supernatants. Similarly, spGAD-immunized mice had higher serum interleukin 10 levels and lower serum interferon gamma levels than other groups, suggesting a systemic effect. In nondiabetic mice there was increased basal production of transforming growth factor beta(1), which was enhanced by antigenic stimulation. These alterations in regulatory cytokine production were apparent both early and late after the treatment was initiated. These findings suggest that DNA vaccination against spGAD protects NOD mice by increasing regulatory cytokine production.     

U-50, 488, saline and naltrexone discrimination in U-50, 488-treated pigeons

Pigeons treated with 10.0mg/kg/day of U-50,488 discriminated among intramuscular (i.m.) injections of U-50,488 (10mg/kg), saline, and naltrexone (0.178mg/kg), while responding under a fixed-ratio 20 schedule of food presentation. Training compounds occasioned responding on the appropriate keys with pigeons responding >/=90% on the naltrexone key at doses larger than 0.032mg/kg of naltrexone, >/=90% on the U-50,488 key at doses larger than 3.2mg/kg of U-50,488, and >/=90% on the saline key after saline. Several opioid agonists and antagonists were studied for their discriminative stimulus effects. None of the compounds substituted completely (>/=90%) for either training compound in all pigeons (n = 5); however, bremazocine substituted completely for U-50,488 in three out of five pigeons. Compounds with opioid antagonist actions under other conditions substituted for naltrexone in some subjects: levallorphan, two out of five; nalbuphine, one out of five; nalorphine, two out of five; and quadazocine, three out of four. Morphine did not substitute for naltrexone or U-50,488 in any of the subjects. When U-50,488 treatment was terminated and subjects were studied daily after injections of saline, responding occurred predominantly on the saline key; the absence of naltrexone key responding after termination of U-50,488 treatment suggests that this dosing regimen was not adequate for the development of dependence, or that the discriminative stimulus effects of abstinence-induced withdrawal were qualitatively different from the discriminative stimulus effects of naltrexone under these conditions.     

Discrimination among morphine, saline and naltrexone in rhesus monkeys receiving morphine subchronically

Discriminative control was established among morphine, saline and naltrexone in rhesus monkeys receiving morphine every other day. Three hours prior to sessions subjects received saline or 3.2mg/kg morphine; immediately prior to sessions they received saline or 0.01mg/kg of naltrexone. There were dose-related generalizations to each training condition: morphine generalized to the morphine plus saline lever; small doses of naltrexone reversed effects of morphine and larger doses occasioned responding on the morphine plus naltrexone lever; in one monkey still larger doses occasioned responding on the saline plus saline lever. When saline was administered 3h earlier, naltrexone had no effect in one subject and occasioned responding on the morphine plus naltrexone lever in a second subject. Nalbuphine substituted for morphine plus saline in one monkey and for morphine plus naltrexone in a second monkey; ketamine did not substitute for either training drug. That stimulus control was established between no drug and a combination of morphine and naltrexone suggests the latter condition did not represent the absence of morphine. In addition to demonstrating stimulus control for three conditions in rhesus monkeys, the current study suggests opioid antagonists might have novel discriminative stimulus effects at opioid receptors even under conditions where signs of withdrawal are not evident.     

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165     

A model of whole-body protein turnover based on leucine kinetics in rodents

The measurement of fractional synthesis rate is based on the following assumptions: amino acids for protein synthesis are supplied by an intracellular pool; amino acids from protein degradation are not recycled preferentially to protein synthesis; and proteins turn over at a homogeneous rate. To test these assumptions, a mechanistic, theoretical model of protein turnover for a nongrowing 26-g mouse was developed on the basis of data from the literature. The model consisted of three protein pools turning over at fast (102 micromol Leu, t1/2= 11.5 h), medium (212 micromol Leu, t1/2 = 16.6 h) or slow (536 micromol Leu, t1/2 = 71.5 h) rates and extracellular (1.69 micromol Leu), leucyl-tRNA (0.0226 micromol Leu) and intracellular (5.72 micromol Leu) amino acid pools that exchanged amino acids. The flow of amino acids from the protein pools to the leucyl-tRNA pool determined the amount of recycling. The flow of amino acids from the extracellular pool to aminoacyl tRNA determined the amount of channeling. Two flooding dose data sets were used to evaluate specific radioactivity changes predicted by the model. Predictions of specific radioactivities using flooding dose, pulse dose or continuous infusion methods indicated that the model can be a useful tool in estimating the rates of channeling and recycling. However, it was found that use of data from flooding dose experiments might cause inaccurate predictions of certain fluxes.     

Psychotherapy as an element in supported employment for persons with severe and persistent mental illness

Recent literature has urged that vocational and clinical services for persons with severe and persistent mental illness should be integrated. Unclear in this model is what role psychotherapy could play. In particular, it is unknown whether psychotherapy can make a unique contribution and whether there are issues it might systematically address in the context of vocational rehabilitation. To examine these questions we report on the psychotherapy of six consumers enrolled in supported employment, a prominent form of vocational rehabilitation. Using these cases as illustrations, we suggest that in an integrative team approach, psychotherapy can facilitate vocational rehabilitation by helping consumers reconstruct aspects of personal narratives related to disability and work and by processing painful affects evoked by work. We report how within a reflective and nonhierarchical relationship consumers were allowed to reframe old ideas, question inconsistencies, and keep track of the structure and content of revised narrative until fully integrated into memory. Despite a wide range of severe impairments, this process enabled consumers to incorporate work into a now more complete and coherent life narrative. Implications for practice and research are discussed.