A B S T R A C T Inhibitors of erythropoiesis have been found in the blood of uremic patients but their nature has not been identified. These patients have excess blood levels of parathyroid hormone (PTH) and it is possible that PTH inhibits erythropoiesis. The present study was undertaken to examine the effect of intact PTH molecules and some of its fragments on human peripheral blood and mouse bone marrow burst-forming units-erythroid (BFU-E), on mouse bone marrow erythroid colony-forming unit (CFU-E), and granulocyte macrophage progenitors (CFU-GM), and evaluate the interaction between PTH and erythropoietin (Ep) on human BFU-E. Intact PTH (1-84 bPTH) in concentrations (7.5-30 U/ml) comparable to those found in blood of uremic patients produced marked and significant (P < 0.01) inhibition of BFU-E and mouse marrow GFU-GM, but not of mouse marrow CFU-E. Inactivation of 1-84 bPTH abolished its action on erythropoiesis. Increasing the concentration of Ep in the media from 0.67 to 1.9 U/ml overcame the inhibitory effect of 1-84 bPTH on BFU-E. The N-terminal fragment of PTH (1-34 bPTH) and 53-84 hPTH had no effect on BFU-E.The results deomonstrate that (a) either the intact PTH molecule or a C-terminal fragment(s) bigger than 53-84 moiety exerts the inhibitory effect on erythropoiesis, and (b) adequate amounts of Ep can overcome this action of PTH. The data provide one possible pathway for the participation of excess PTH in the genesis of the anemia of uremia.

New Findings What is the central question of this study?Are individual changes in exercise‐induced mRNA expression repeatable (i.e. representative of the true response to exercise rather than random error)? What is the main finding and its importance?Exercise‐induced changes in mRNA expression are not repeatable even under identical experimental conditions, thereby challenging the use of mRNA expression as a biomarker of adaptive potential and/or individual responsiveness to exercise. Abstract It remains unknown if (1) the observed change in mRNA expression reflects an individual's true response to exercise or random (technical and/or biological) error, and (2) the individual responsiveness to exercise is protocol‐specific. We examined the repeatability of skeletal muscle PGC‐1α, PDK4, NRF‐1, VEGF‐A, HSP72 and p53 mRNA expression following two identical endurance exercise (END) bouts (END‐1, END‐2; 30 min of cycling at 65% of peak work rate (WRpeak), n = 11) and inter‐individual variability in PGC‐1α and PDK4 mRNA expression following END and sprint interval training (SIT; 8 × 20 s cycling intervals at ∼170% WRpeak, n = 10) in active young males. The repeatability of key gene analysis steps (RNA extraction, reverse transcription, qPCR) and within‐sample fibre‐type distribution (n = 8) was also determined to examine potential sources of technical error in our analyses. Despite highly repeatable exercise bout characteristics (work rate, heart rate, blood lactate; ICC > 0.71; CV < 10%; r > 0.85, P < 0.01), gene analysis steps (ICC > 0.73; CV < 24%; r > 0.75, P < 0.01), and similar group‐level changes in mRNA expression, individual changes in PGC‐1α, PDK4, VEGF‐A and p53 mRNA expression were not repeatable (ICC < 0.22; CV > 20%; r < 0.21). Fibre‐type distribution in two portions of the same muscle biopsy was highly variable and not significantly related (ICC = 0.39; CV = 26%; r = 0.37, P = 0.37). Since individual changes in mRNA expression following identical exercise bouts were not repeatable, inferences regarding individual responsiveness to END or SIT were not made. Substantial random error exists in changes in mRNA expression following acute exercise, thereby challenging the use of mRNA expression for analysing individual responsiveness to exercise.

An antimicrobial stewardship program with a dedicated ID pharmacist was associated with greater adherence to recommended antimicrobial therapy practices when compared to a stewardship program that relied on ward pharmacists.

Objectives: To determine factors predictive of a severe deep neck space infection (DNSI), defined as those requiring surgery and/or postoperative intensive care unit (ICU) admission. To specifically examine dental practices and socioeconomic factors that may contribute to the development of a DNSI. Study design: Retrospective review. Methods: This study was conducted at 2 tertiary care academic referral centers from January 2007 to September 2011. The study was composed of 2 arms: a prospective questionnaire and data collection to identify modifiable risk factors such as dental practices and socioeconomic considerations for a DNSI, and a retrospective review of deep neck space infections to identify commonly associated risk factors predictive of a severe DNSI, requiring surgery and/or postoperative ICU admission.

Objectives Our objectives were (1) to use in situ simulation to assess the clinical environment and identify latent safety threats (LSTs) related to the management of pediatric tracheostomy patients and (2) to analyze the effects of systems interventions and team factors on LSTs and simulation performance. Methods A multicenter, prospective study to assess LSTs related to pediatric tracheostomy care management was conducted in emergency departments (EDs) and intensive care units (ICUs). LSTs were identified through equipment checklists and in situ simulations via structured debriefs and blinded ratings of team performance. The research team and unit champions developed action plans with interventions to address each LST. Reassessment by equipment checklists and in situ simulations was repeated after 6 to 9 months. Results Forty-one LSTs were identified over 21 simulations, 24 in the preintervention group and 17 in the postintervention group. These included LSTs in access to equipment (ie, availability of suction catheters, lack of awareness of the location of tracheostomy tubes) and clinical knowledge gaps. Mean equipment checklist scores improved from 76% to 87%. Twenty-one unique teams (65 participants) participated in the simulations. The average simulation score was 6.19 out of 16 points. Discussion In situ simulation is feasible and effective as an assessment tool to identify latent safety threats and thus measure the system-level performance of a clinical care environment. Implications for Practice In situ simulation can be used to identify and reassess latent safety threats related to pediatric tracheostomy management and thereby support quality improvement and educational initiatives.

Although resistive pulse sensing using solid-state nanopores is capable of single-molecule sensitivity, previous work has shown that nanoparticles, such as proteins, pass through nanopores too quickly for accurate detection with typical measurement apparatus. As a result, nanopore measurements of these particles significantly deviate from theoretically estimated current amplitudes and detection rates. Here, we show that a hydrogel placed on the distal side of a nanopore can increase the residence time of nanoparticles within the nanopore, significantly increasing the detection rate and allowing improved resolution of blockage currents. The method is simple and inexpensive to implement while being label-free and applicable to a wide range of nanoparticle targets. Using hydrogel-backed nanopores, we detected the protein IgG with event frequencies several orders of magnitude higher than those in the absence of the hydrogel and with larger measured currents that agree well with theoretical models. We also show that the improved measurement also enables discrimination of IgG and bovine serum albumin in a mixed solution. Finally, we show that measurements of IgG with the hydrogel-backed nanopores can also yield current amplitude distributions that can be analyzed to infer its approximate shape.

This study tested the hypotheses that 1) skeletal muscle biopsies performed with the Bergström needle evoke larger perceptions of pain and greater hemodynamic reactivity compared to biopsies performed with the microbiopsy needle, and 2) both needles yield samples with similar fibre type compositions when samples are collected at similar skeletal muscle depths. Fourteen healthy (age: 21.6 ± 3.2 years; VO 2 peak: 41.5 ± 5.8 mL/kg/min) males (n = 7) and females (n = 7) provided two resting skeletal muscle biopsies, one with each needle type, following a randomized crossover design. Participants completed the short-form McGill Pain Questionnaire and the Brief Pain Inventory before, during, and after the skeletal muscle biopsies. Hemodynamic reactivity was assessed by measuring heart rate (HR) and mean arterial pressure (MAP) at rest and during the biopsy procedures. Immunofluorescence analysis was used to assess fibre type composition in vastus lateralis samples. Compared to the microbiopsy needle, the Bergström needle elicited a larger perception of pain but similar hemodynamic reactivity during the biopsy. Both needles yielded skeletal muscle samples with similar fibre type composition and resulted in similar perceptions of pain and pain-related interference during the post-biopsy recovery period. Collectively, these findings suggest that studies should consider using the microbiopsy needle rather than the Bergström needle unless large amounts of muscle tissue or certain muscle fibre lengths are required. However, future work should determine whether our findings are generalizable to biopsies performed with different procedures and/or types of Bergström/microbiopsy needles.

Studies have interpreted a wide range of morphological and molecular changes in human skeletal muscle as evidence of interindividual differences in trainability.However, these interpretations fail to account for the influence of random measurement error and within-subject variability. The purpose of the present study was to use the standard deviation of individual response (SD IR ) statistic to test the hypothesis that interindividual differences in trainability are present for some but not all skeletal muscle outcomes. Twenty-nine recreationally active males (age: 21 ± 2 years; BMI: 24 ± 3 kg/m 2 ; VO 2 peak ; 45 ± 7 ml/kg/min) completed 4 weeks of continuous training (REL; n = 14) or control (n = 15). Maximal enzyme activities (citrate synthase and β-hydroxyacyl-CoA dehydrogenase), capillary density, fibre type composition, fibre-specific succinate dehydrogenase activity and substrate storage (intramuscular triglycerides and glycogen), and markers of mitophagy (BCL2interacting protein 3 (BNIP3), BNIP3-like protein, parkin and PTEN-induced kinase 1)were measured in vastus lateralis samples collected before and after the intervention.We also calculated SD IR values for VO 2 peak , peak work rate and the onset of blood lactate accumulation for the REL group and a separate group that exercised at the negative talk test stage. Although positive SD IR values -indicating interindividual differences in trainability -were obtained for aerobic capacity outcomes, maximal enzyme activities, capillary density, all fibre-specific outcomes and BNIP3 protein content, the remaining outcomes produced negative SD IR values indicating a large degree of random measurement error and/or within-subject variability. Our findings question the interpretation of heterogeneity in observed responses as evidence of interindividual differences in trainability and highlight the importance of including control groups when analysing individual skeletal muscle response to exercise training.