Genotypic correlation between post discharge Clostridiodes difficle infection (CDI) and previous unit-based contacts.

BACKGROUND: Cases of Clostridiodes difficile infection (CDI) diagnosed after hospital discharge account for a substantial proportion of new infections. It is unclear whether post-discharge infections originate from hospital-based transmission. METHODS: This was a Retrospective cohort study at a tertiary-care cancer center (non-outbreak setting). For all laboratory-identified cases of CDI in 2015-2016, patients with post-discharge (PD) CDI within eight weeks of their hospital stay were included in the study. Isolates from PD-CDI cases and their CDI-positive unit-based contacts were first genotyped by multilocus sequence typing (MLST). Common strains were further examined by core genome sequencing (CGS) to evaluate transmission links. RESULTS: Of 173 cases examined by MLST, 50% of PD cases matched previous unit contacts. Next, 34 isolates, including 16 PD cases and their 18-unit contacts were examined by CGS. None were ≤3 single-nucleotide variants apart. Seventy percent of PD cases had in-hospital antibiotic exposure before CDI onset in the community. CONCLUSION: Our study results suggest that symptomatic CDI cases are not a substantial source of transmission to PD cases. Frequent antibiotic exposure in post-discharge CDI cases is an important target for surveillance and stewardship efforts.

Evaluation of the Aries Bordetella Assay for Detection and Identification of Bordetella pertussis in Nasopharyngeal Swab Specimens.

The Aries Bordetella assay (Aries BA) (Luminex Corporation) recently received FDA clearance for the detection and differentiation of Bordetella pertussis and Bordetella parapertussis nucleic acids in nasopharyngeal swab (NPS) samples. The objective of this study was to evaluate the performance of the Aries BA in comparison to that of the BioFire FilmArray respiratory panel (RP). The Aries BA was evaluated using retrospective, remnant nasopharyngeal swabs (NPS), previously tested by FilmArray RP. Performance characteristics evaluated included positive percent agreement (PPA) and negative percent agreement (NPA) with the FilmArray RP. Discordant analysis was performed using bidirectional sequencing. A time and motion study was performed to compare the laboratory workflow of the two tests. Three hundred samples were included in the study. There were no samples positive for B. parapertussis The PPA and NPA of the Aries BA were 61.1% (95% confidence interval [CI], 35.8 to 82.7%) and 100% (95% CI, 98.7 to 100%). Discordant results included five Bordetella bronchiseptica results that were incorrectly identified as B. pertussis by the FilmArray RP and one false-negative result for both the Aries BA and the FilmArray RP. The overall agreement between the Aries BA and FilmArray RP for the detection of B. pertussis was considered good at 97.7% with a kappa value of 0.71 (95% CI, 0.51 to 0.9). The Aries BA offers a new diagnostic option for the rapid and targeted approach to the diagnosis of pertussis. Unlike the FilmArray RP, the Aries BA did not cross-react with B. bronchiseptica in our study, although a larger sample set should be tested to confirm this finding.

Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice.

BACKGROUND: Obesity is associated with reduced levels of circulating high-density lipoproteins (HDLs) and its major protein, apolipoprotein (apo) A-I. As a result of the role of HDL and apoA-I in cellular lipid transport, low HDL and apoA-I may contribute directly to establishing or maintaining the obese condition. METHODS: To test this, male C57BL/6 wild-type (WT), apoA-I deficient (apoA-I(-/-)) and apoA-I transgenic (apoA-I(tg/tg)) mice were fed obesogenic diets (ODs) and monitored for several clinical parameters. We also performed cell culture studies. RESULTS: ApoA-I(-/-) mice gained significantly more body weight and body fat than WT mice over 20 weeks despite their reduced food intake. During a caloric restriction regime imposed on OD-fed mice, apoA-I deficiency significantly inhibited the loss of body fat as compared with WT mice. Reduced body fat loss with caloric restriction in apoA-I(-/-) mice was associated with blunted stimulated adipose tissue lipolysis as verified by decreased levels of phosphorylated hormone-sensitive lipase (p-HSL) and lipolytic enzyme mRNA. In contrast to apoA-I(-/-) mice, apoA-I(tg/tg) mice gained relatively less weight than WT mice, consistent with other reports. ApoA-I(tg/tg) mice showed increased adipose tissue lipolysis, verified by increased levels of p-HSL and lipolytic enzyme mRNA. In cell culture studies, HDL and apoA-I specifically increased catecholamine-induced lipolysis possibly through modulating the adipocyte plasma membrane cholesterol content. CONCLUSIONS: Thus, apoA-I and HDL contribute to modulating body fat content by controlling the extent of lipolysis. ApoA-I and HDL are key components of lipid metabolism in adipose tissue and constitute new therapeutic targets in obesity.

Atherosclerosis and cardiac function assessment in low-density lipoprotein receptor-deficient mice undergoing body weight cycling.

BACKGROUND: Obesity has become an epidemic in many countries and is supporting a billion dollar industry involved in promoting weight loss through diet, exercise and surgical procedures. Because of difficulties in maintaining body weight reduction, a pattern of weight cycling often occurs (so called 'yo-yo' dieting) that may result in deleterious outcomes to health. There is controversy about cardiovascular benefits of yo-yo dieting, and an animal model is needed to better understand the contributions of major diet and body weight changes on heart and vascular functions. Our purpose is to determine the effects of weight cycling on cardiac function and atherosclerosis development in a mouse model. METHODS: We used low-density lipoprotein receptor-deficient mice due to their sensitivity to metabolic syndrome and cardiovascular diseases when fed high-fat diets. Alternating ad libitum feeding of high-fat and low-fat (rodent chow) diets was used to instigate weight cycling during a 29-week period. Glucose tolerance and insulin sensitivity tests were done at 22 and 24 weeks, echocardiograms at 25 weeks and atherosclerosis and plasma lipoproteins assessed at 29 weeks. RESULTS: Mice subjected to weight cycling showed improvements in glucose homeostasis during the weight loss cycle. Weight-cycled mice showed a reduction in the severity of atherosclerosis as compared with high-fat diet-fed mice. However, atherosclerosis still persisted in weight-cycled mice as compared with mice fed rodent chow. Cardiac function was impaired in weight-cycled mice and matched with that of mice fed only the high-fat diet. CONCLUSION: This model provides an initial structure in which to begin detailed studies of diet, calorie restriction and surgical modifications on energy balance and metabolic diseases. This model also shows differential effects of yo-yo dieting on metabolic syndrome and cardiovascular diseases.

Nonlinear muscles, passive viscoelasticity and body taper conspire to create neuromechanical phase lags in anguilliform swimmers.

Locomotion provides superb examples of cooperation among neuromuscular systems, environmental reaction forces, and sensory feedback. As part of a program to understand the neuromechanics of locomotion, here we construct a model of anguilliform (eel-like) swimming in slender fishes. Building on a continuum mechanical representation of the body as an viscoelastic rod, actuated by a traveling wave of preferred curvature and subject to hydrodynamic reaction forces, we incorporate a new version of a calcium release and muscle force model, fitted to data from the lamprey Ichthyomyzon unicuspis, that interactively generates the curvature wave. We use the model to investigate the source of the difference in speeds observed between electromyographic waves of muscle activation and mechanical waves of body curvature, concluding that it is due to a combination of passive viscoelastic and geometric properties of the body and active muscle properties. Moreover, we find that nonlinear force dependence on muscle length and shortening velocity may reduce the work done by the swimming muscles in steady swimming.

An elastic rod model for anguilliform swimming.

We develop a model for anguilliform (eel-like) swimming as an elastic rod actuated via time-dependent intrinsic curvature and subject to hydrodynamic drag forces, the latter as proposed by Taylor (in Proc Roy Proc Lond A 214:158-183, 1952). We employ a eometrically exact theory and discretize the resulting nonlinear partial differential evolution both to perform numerical simulations, and to compare with previous models consisting of chains of rigid links or masses connected by springs, dampers, and prescribed force generators representing muscles. We show that muscle activations driven by motoneuronal spike trains via calcium dynamics produce intrinsic curvatures corresponding to near-sinusoidal body shapes in longitudinally-uniform rods, but that passive elasticity causes Taylor's assumption of prescribed shape to fail, leading to time-periodic motions and lower speeds than those predicted Taylor (in Proc Roy Proc Lond A 214:158-183, 1952). We investigate the effects of bending stiffness, body geometry, and activation patterns on swimming speed, turning behavior, and acceleration to steady swimming. We show that laterally-uniform activation yields stable straight swimming and laterally differential activation levels lead to stable turns, and we argue that tapered bodies with reduced caudal (tail-end) activation (to produce uniform intrinsic curvature) swim faster than ones with uniform activation.