Reduced in vivo skeletal muscle oxygen consumption in patients with chronic heart failure--a study using Near Infrared Spectrophotometry (NIRS)

AIM: We used Near Infrared Spectrophotometry (NIRS) during arterial occlusion to measure resting skeletal muscle oxygen consumption in chronic heart failure (CHF) patients and in age-matched healthy volunteers (HVs). METHODS: Fifteen CHF patients (ten males) and eleven HVs (six males) had echocardiographic evaluation followed by measurement of the oxygen consumption of the brachioradialis muscle using NIRS. This involved continuous measurement of the oxygenated haemoglobin concentration ([Oxy-Hb]) and deoxy-haemoglobin concentration ([Deoxy-Hb]) with an Oxiplex TS NIRS probe first under basal overnight fasted resting conditions followed by 1 min of forearm arterial occlusion. A linear decline was observed in [Oxy-Hb-Deoxy-Hb] during the arterial occlusion and the oxygen consumption rate was calculated from the initial slope observed. RESULTS: CHF patients were 59+/-2.8 years old with Left Ventricular Ejection Fraction (LVEF) 31%+/-2.2 and the HVs were 52+/-4.8 years old with LVEF 62%+/-2.5. The resting muscle oxygen consumption rate was significantly reduced in CHF patients versus HVs (0.04+/-0.01 mlO(2)/min/100 g versus 0.07+/-0.01 mlO(2)/min/100 g) p<0.005. CONCLUSIONS: There is a significant reduction in resting oxygen consumption per gram of tissue in skeletal muscle of patients with CHF.     

On the translocation of proteins across membranes.

Many proteins of intracellular organelles are first synthesized in the cytoplasm and are then specifically transferred across the membranes of the organelles. On the assumption that these transfers all occur by the same basic mechanism, we enumerate the rather stringent requirements that the mechanism must satisfy. A unitary molecular mechanism is then proposed that meets these requirements.     

Back to the Future with Phenotypic Screening

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Optimizing study design for interobserver reliability: IUGA–ICS classification of complications of prostheses and graft insertion

Introduction and hypothesis

Results of interobserver reliability studies for the International Urogynecological Association–International Continence Society (IUGA-ICS) Complication Classification coding can be greatly influenced by study design factors such as participant instruction, motivation, and test-question clarity. We attempted to optimize these factors.

Methods

After a 15-min instructional lecture with eight clinical case examples (including images) and with classification/coding charts available, those clinicians attending an IUGA Surgical Complications workshop were presented with eight similar-style test cases over 10 min and asked to code them using the Category, Time and Site classification. Answers were compared to predetermined correct codes obtained by five instigators of the IUGA-ICS prostheses and grafts complications classification. Prelecture and postquiz participant confidence levels using a five-step Likert scale were assessed.

Results

Complete sets of answers to the questions (24 codings) were provided by 34 respondents, only three of whom reported prior use of the charts. Average score [n (%)] out of eight, as well as median score (range) for each coding category were: (i) Category: 7.3 (91 %); 7 (4–8); (ii) Time: 7.8 (98 %); 7 (6–8); (iii) Site: 7.2 (90 %); 7 (5–8). Overall, the equivalent calculations (out of 24) were 22.3 (93 %) and 22 (18–24). Mean prelecture confidence was 1.37 (out of 5), rising to 3.85 postquiz. Urogynecologists had the highest correlation with correct coding, followed closely by fellows and general gynecologists.

Conclusions

Optimizing training and study design can lead to excellent results for interobserver reliability of the IUGA-ICS Complication Classification coding, with increased participant confidence in complication-coding ability.     

Microphysical space of a liver sinusoid device enables simplified long-term maintenance of chimeric mouse-expanded human hepatocytes

While many advanced liver models support hepatic phenotypes necessary for drug and disease studies, these models are characterized by intricate features such as co-culture with one of more supporting cell types or advanced media perfusion systems. These systems have helped elucidate some of the critical biophysical features missing from standard well-plate based hepatocyte culture, but their advanced designs add to their complexity. Additionally, regardless of the culture system, primary hepatocyte culture systems suffer from reproducibility issues due to phenotypic variation and expensive, limited supplies of donor lots. Here we describe a microfluidic bilayer device that sustains primary human hepatocyte phenotypes, including albumin production, factor IX production, cytochrome P450 3A4 drug metabolism and bile canaliculi formation for at least 14 days in a simple monoculture format with static media. Using a variety of channel architectures, we describe how primary cell phenotype is promoted by spatial confinement within the microfluidic channel, without the need for perfusion or co-culture. By sourcing human hepatocytes expanded in the Fah, Rag2, and Il2rg-knockout (FRG?-KO) humanized mouse model, utilizing a few hundred hepatocytes within each channel, and maintaining hepatocyte function for weeks in vitro within a relatively simple model, we demonstrate a basic primary human hepatocyte culture system that addresses many of the major hurdles in human hepatocyte culture research.