Real time measurement of intramuscular pH during routine knee arthroscopy using a tourniquet

Funding statement This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.Peer reviewedPublisher PD

A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF

The respiratory response to inspiratory resistive loading during rapid eye movement sleep in humans

We investigated the respiratory response to an added inspiratory resistive load (IRL) during rapid eye movement (REM) sleep in humans and compared this with those in non-REM (NREM) sleep and wakefulness.Results were obtained from 7 out of 15 healthy subjects (n = 7; 32 ± 9 years, mean ± s.d.). Linearised IRLs (4 and 12 cmH2O l−1 s−1) were applied for five breaths during NREM sleep (4-10 trials per subject; total 101), REM sleep (2-5 trials; total 46) and wakefulness (2-3 trials; total 40). Respiratory variables were compared, between unloaded breathing (UL: mean of 5 breaths preceding IRL) and the 1st (B1) and 5th (B5) loaded breaths in each state.During wakefulness, 12 cmH2O l−1 s−1 IRL produced an immediate respiratory compensation with prolongation of inspiratory time (TI; UL: 2.0 ± 0.6; B1: 2.6 ± 0.7 s) and an increase in tidal volume (VT; UL: 0.49 ± 0.12; B1: 0.52 ± 0.12 l). During REM sleep, TI was prolonged (UL: 2.0 ± 0.3; B1: 2.2 ± 0.5 s), although VT fell (UL: 0.27 ± 0.15; B1: 0.22 ± 0.10 l). For both wakefulness and REM sleep the TI response was significantly greater than seen in NREM sleep (UL: 1.9 ± 0.3; B1: 1.9 ± 0.3 s.). For VT, only the wakefulness response was significantly different from NREM sleep (UL: 0.31 ± 0.14; B1: 0.21 ± 0.10 l). The B5 responses were not significantly different between states for any of the variables.REM sleep is associated with partial respiratory load compensation suggesting that exacerbation of sleep disordered breathing in REM (compared to NREM) sleep is unlikely to be secondary to an inability to overcome increases in upper airway resistance

Modeling Distribution Channel Dynamics of North American Cars in the Spanish Automobile Industry

Channels of distribution, Satisfaction, Performance, Partial Least Squares (PLS).,  ,

Mouse Models of Liver Fibrosis Mimic Human Liver Fibrosis of Different Etiologies

The liver has the amazing capacity to repair itself after injury; however, the same processes that are involved in liver regeneration after acute injury can cause serious consequences during chronic liver injury. In an effort to repair damage, activated hepatic stellate cells trigger a cascade of events that lead to deposition and accumulation of extracellular matrix components causing the progressive replacement of the liver parenchyma by scar tissue, thus resulting in fibrosis. Although fibrosis occurs as a result of many chronic liver diseases, the molecular mechanisms involved depend on the underlying etiology. Since studying liver fibrosis in human subjects is complicated by many factors, mouse models of liver fibrosis that mimic the human conditions fill this void. This review summarizes the general mouse models of liver fibrosis and mouse models that mimic specific human disease conditions that result in liver fibrosis. Additionally, recent progress that has been made in understanding the molecular mechanisms involved in the fibrogenic processes of each of the human disease conditions is highlighted