The politics of valuation and payment for regenerative medicine products in the UK

The field of regenerative medicine (RM) faces many challenges, including funding. Framing the analysis in terms of institutional politics, valuation studies and “technologies of knowledge”, the paper highlights growing debates about payment for RM in the UK, setting this alongside escalating policy debates about “value”. We draw on interviews and publicly available material to identify the interacting and conflicting positions of institutional stakeholders. It is concluded that while there is some common ground between institutional stakeholders such as industry and health system gatekeepers, there is significant conflict about reward systems, technology assessment methodologies and payment scenarios; a range of mostly conditional payment schemes and non-mainstream routes are being experimented with. We argue that current developments highlight a fundamental conflict between a concern for the societal value of medical technologies in a resource-limited system and a concern for engineering new reward and payment models to accommodate RM innovations.     

Effect of aging on the recovery following contraction-induced injury in muscles of female mice.

By the age of 80 yr, the skeletal muscles of men and women decrease in mass and maximum force by approximately 30%. Severe contraction-induced injury may contribute to these age-related declines. One to two months after a 225 lengthening contraction protocol (LCP), muscles of young/adult male mice recovered completely, whereas those of old male mice sustained deficits of approximately 15% in mass and approximately 25% in maximum force. Although gender-related differences in the early events of contraction-induced injury have been reported, the recovery phase of muscles in old female animals has not been investigated. The hypothesis tested was that 2 mo after a severe LCP to the plantar flexor muscle group, the magnitude of recovery of mass and force for old female mice is less than that for adult female mice. The LCP was administered to muscles of adult and old, female C57BL/6 mice. At 3 days, 1 mo, and 2 mo following the LCP, maximum isometric force was measured, and muscles were removed and weighed. Two months following the LCP, the muscles of adult female mice recovered mass and force. In contrast, for old female mice, even after 2 mo, muscle masses were decreased by 11% and maximum forces by 38%. We conclude that, as reported previously for old male mice, a severe contraction-induced injury to muscles of old female mice results in prolonged deficits in mass and force.     

Amiloride does not alter NaCl avoidance in Fischer-344 rats

Fischer-344 (F-344) rats differ from other common rat strains in that they fail to show any preference for NaCl at any concentration in two- bottle preference tests. Because 100 microM amiloride partially blocks the NaCl-evoked chorda tympani (CT) response in electrophysiological studies, we tested NaCl preference (0.068-0.273 M) in F-344 rats with and without 100 microM amiloride solution as the solvent. A third group was tested with unadulterated NaCl solutions following CT transection. Amiloride had no significant effect on the NaCl preference-aversion function, whereas CT transection significantly reduced NaCl avoidance. These results suggest that the amiloride-sensitive component of the NaCl response is not necessary for F-344 rats to display avoidance of NaCl, but the entire CT input is.      

Collagenase in carcinoma cells

Collagenolytic enzyme activity has been found in high levels in homogenates of a tumor (ascitic V₂ carcinoma) implanted in rabbit muscle. Unlike other mammalian collagenases, this enzyme was not actively synthesized and released by primary cultures of the tumor. Most of the collagenolytic activity in tumor homogenates was found to sediment at 1000–4000 × g along with 5′-nucleotidase activity indicating that it might be bound to a membraneous component of the cell.     

Acquisition and Distribution of Nematodes in Irrigation Waterways of the Columbia Basin in Eastern Washington

The primary source of plant parasitic nematodes in irrigation waterways in the Columbia Basin Project of eastern Washington is irrigation runoff returned into the irrigation system. This has contributed to the rapid spread of plant parasitic nematodes observed during eight years of study.     

Diaphragm adaptations in patients with COPD

Inspiratory muscle weakness in patients with COPD is of major clinical relevance. For instance, maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered pathologic of nature. Whereas the fiber type shift towards oxidative type I fibers in COPD diaphragm is regarded beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single fiber level is associated with loss of myosin content in these fibers. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. This review postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients appear not limited in their daily life activities. Treatment of diaphragm dysfunction in COPD is complex since its etiology is unclear, but recent findings indicate the ubiquitin-proteasome pathway as a prime target to attenuate diaphragm wasting in COPD.     

Passage through Tetrahymena tropicalis triggers a rapid morphological differentiation in Legionella pneumophila

The intracellular bacterial pathogen Legionella pneumophila follows a developmental cycle in which replicative forms (RFs) differentiate into infectious stationary-phase forms (SPFs) in vitro and in vivo into highly infectious mature intracellular forms (MIFs). The potential relationships between SPFs and MIFs remain uncharacterized. Previously we determined that L. pneumophila survives, but does not replicate, while it transiently resides (for 1 to 2 h) in food vacuoles of the freshwater ciliate Tetrahymena tropicalis before being expelled as legionellae-laden pellets. We report here that SPFs have the ability to rapidly (<1 h) and directly (in the absence of bacterial replication) differentiate into MIFs while in transit through T. tropicalis, indicating that SPFs and MIFs constitute a differentiation continuum. Mutant RFs lacking the sigma factor gene rpoS, or the response regulator gene letA, were unable to produce normal SPFs in vitro and did not fully differentiate into MIFs in vivo, further supporting the existence of a common mechanism of differentiation shared by SPFs and MIFs. Mutants with a defective Dot/Icm system morphologically differentiated into MIFs while in transit through T. tropicalis. Therefore, T. tropicalis has allowed us to unequivocally conclude that SPFs can directly differentiate into MIFs and that the Dot/Icm system is not required for differentiation, two events that could not be experimentally addressed before. The Tetrahymena model can now be exploited to study the signals that trigger MIF development in vivo and is the only replication-independent model reported to date that allows the differentiation of Dot/Icm mutants into MIFs.