Higher In Vivo Fecal Concentrations of Clostridioides difficile Toxins A and B in Patients With North American Pulsed-Field Gel Electrophoresis Type 1/Ribotype 027 Strain Infection.

Ultrasensitive, quantitative Clostridioides difficile stool toxin measurement demonstrated significantly higher concentrations of toxins A and B in patients infected with the North American pulsed-field gel electrophoresis type 1/ribotype 027 (NAP-1/027) strain compared with other strains, providing in vivo confirmation of the in vitro association between NAP-1/027 and elevated toxin production.

Ultrasensitive and Quantitative Toxin Measurement Correlates With Baseline Severity, Severe Outcomes, and Recurrence Among Hospitalized Patients With Clostridioides difficile Infection.

BACKGROUND: Stool toxin concentrations may impact Clostridioides difficile infection (CDI) severity and outcomes. We correlated fecal C difficile toxin concentrations, measured by an ultrasensitive and quantitative assay, with CDI baseline severity, attributable outcomes, and recurrence. METHODS: We enrolled 615 hospitalized adults (≥18 years) with CDI (acute diarrhea, positive stool nucleic acid amplification testing, and decision to treat). Baseline stool toxin A and B concentrations were measured by single molecule array. Subjects were classified by baseline CDI severity (4 scoring methods) and outcomes within 40 days (death, intensive care unit stay, colectomy, and recurrence). RESULTS: Among 615 patients (median, 68.0 years), in all scoring systems, subjects with severe baseline disease had higher stool toxin A+B concentrations than those without (P < .01). Nineteen subjects (3.1%) had a severe outcome primarily attributed to CDI (group 1). This group had higher median toxin A+B (14 303 pg/mL [interquartile range, 416.0, 141 967]) than subjects in whom CDI only contributed to the outcome (group 2, 163.2 pg/mL [0.0, 8423.3]), subjects with severe outcome unrelated to CDI (group 3, 158.6 pg/mL [0.0, 1795.2]), or no severe outcome (group 4, 209.5 pg/mL [0.0, 8566.3]) (P = .003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2-4 (60.5%-66.1%) (P = .02). Individuals with recurrence had higher toxin A+B (2266.8 pg/mL [188.8, 29411]) than those without (154.0 pg/mL [0.0, 5864.3]) (P < .001) and higher rates of detectable toxin (85.7% versus 64.0%, P = .004). CONCLUSIONS: In CDI patients, ultrasensitive stool toxin detection and concentration correlated with severe baseline disease, severe CDI-attributable outcomes, and recurrence, confirming the contribution of toxin quantity to disease presentation and clinical course.

Laxative Use Does Not Preclude Diagnosis or Reduce Disease Severity in Clostridiodes difficile Infection.

BACKGROUND: To optimize utility of laboratory testing for Clostridiodes difficile infection (CDI), the 2017 Infectious Diseases Society of America-Society for Healthcare Epidemiology of America (IDSA-SHEA) clinical practice guidelines recommend excluding patients from stool testing for C. difficile if they have received laxatives within the preceding 48 hours. Sparse data support this recommendation. METHODS: Patients with new-onset diarrhea (≥3 bowel movements in any 24-hour period in the 48 hours before stool collection) and a positive stool C. difficile nucleic acid amplification test were enrolled. Laxative use within 48 hours before stool testing, severity of illness (defined by 4 distinct scoring methods), and clinical outcomes were recorded. RESULTS: 209 patients with CDI were studied, 65 of whom had received laxatives. There were no significant differences in the proportion of patients meeting severe CDI criteria by 4 severity scoring methods in patients receiving versus not receiving laxatives (66.2% vs 56.3%, respectively; P = .224) by IDSA-SHEA, the primary scoring system. Similar rates of serious outcomes attributable to CDI, including death, intensive care unit admission, and colectomy, were observed in the laxative and no laxative groups. CONCLUSIONS: Our study found similar rates of severe CDI and serious CDI-attributable clinical outcomes in CDI-diagnosed patients who did or did not receive laxatives. Precluding recent laxative users from CDI testing, as proposed by the IDSA-SHEA guideline, carries a potential for harm due to delayed diagnosis and treatment.

In vitro effect of 20% N-acetylcysteine on the viscosity of normal canine bile.

OBJECTIVE To evaluate the in vitro effect of 20% N-acetylcysteine (NAC) on the viscosity of normal canine bile. ANIMALS Bile samples obtained from 10 adult dogs euthanized for reasons unrelated to biliary disease. PROCEDURES Each sample was centrifuged to remove particulates, then divided into 3 aliquots. One aliquot remained untreated (control). Each of the other aliquots was diluted 1:4 with 20% NAC or sterile water. The viscosity of all samples was measured with a rotational viscometer at 25°C. Viscosity of control samples was measured immediately after centrifugation and at 1 and 24 hours after treatment application to the diluted samples. Viscosity of diluted samples was measured at 1 and 24 hours after treatment application. RESULTS Mean viscosity differed significantly among the 3 groups at both 1 and 24 hours after treatment application. Relative to control samples, the addition of NAC and sterile water decreased the viscosity by approximately 3.35 mPa·s (95% confidence interval [CI], 1.58 to 5.12 mPa·s) and 2.74 mPa·s (95% CI, 1.33 to 4.14 mPa·s), respectively. Mean viscosity of the NAC-treated samples was approximately 0.61 mPa·s (95% CI, 0.21 to 1.01 mPa·s) less than that for the sterile water-treated samples. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that in vitro dilution of canine bile 1:4 with 20% NAC significantly decreased the viscosity of the resulting mixture. Further research is necessary to determine whether NAC is a safe and effective noninvasive treatment for dogs with persistent biliary sludge or gallbladder mucoceles.

Implicit Mental Motor Imagery Task Demonstrates a Distortion of the Body Schema in Patients With Eating Disorders.

OBJECTIVES: A rich body of literature has established the role of body image distortion and dissatisfaction in the development and maintenance of eating disorders. However, many of the currently used techniques require explicit comparison of the person's body to an external stimulus. As the body schema is a largely unconscious construct, explicit comparison tasks may reflect a proxy, rather than the body schema itself. METHODS: Here we use an implicit mental motor imagery (MMI) task to interrogate the body schema in healthy control participants (N=40) and participants at a residential eating disorder treatment center (N=42). By comparing the time it takes to imagine making a movement along a part of the body to the time it takes to actually make the same movement, we were able to assess participants' mental image of their body (i.e., body schema). RESULTS: We found that participants with eating disorders, but not healthy controls, exhibited distortions of the body schema such that they believed their abdomen, buttocks, and thighs to be larger than they really are. Additionally, the MMI task used here provided information above and beyond traditional self-report measures (i.e., Body Shape Questionnaire). Together the MMI task and traditional measures provide the most information. CONCLUSIONS: Findings using the novel MMI task are in line with the literature; participants with eating disorders consider themselves to be larger than they truly are. Taken together, results of this study suggest that MMI tasks provide complementary information to traditional self-report measures. (JINS, 2018, 24, 715-723).

Baseline Performance Predicts tDCS-Mediated Improvements in Language Symptoms in Primary Progressive Aphasia.

Primary Progressive Aphasia (PPA) is a neurodegenerative condition characterized by insidious irreversible loss of language abilities. Prior studies suggest that transcranial direct current stimulation (tDCS) directed toward language areas of the brain may help to ameliorate symptoms of PPA. In the present sham-controlled study, we examined whether tDCS could be used to enhance language abilities (e.g., picture naming) in individuals with PPA variants primarily characterized by difficulties with speech production (non-fluent and logopenic). Participants were recruited from the Penn Frontotemporal Dementia Center to receive 10 days of both real and sham tDCS (counter-balanced, full-crossover design; participants were naïve to stimulation condition). A battery of language tests was administered at baseline, immediately post-tDCS (real and sham), and 6 weeks and 12 weeks following stimulation. When we accounted for individuals' baseline performance, our analyses demonstrated a stratification of tDCS effects. Individuals who performed worse at baseline showed tDCS-related improvements in global language performance, grammatical comprehension and semantic processing. Individuals who performed better at baseline showed a slight tDCS-related benefit on our speech repetition metric. Real tDCS may improve language performance in some individuals with PPA. Severity of deficits at baseline may be an important factor in predicting which patients will respond positively to language-targeted tDCS therapies. Clinicaltrials.gov ID: NCT02928848.

Responses of the human motor system to observing actions across species: A transcranial magnetic stimulation study.

Ample evidence suggests that the role of the mirror neuron system (MNS) in monkeys is to represent the meaning of actions. The MNS becomes active in monkeys during execution, observation, and auditory experience of meaningful, object-oriented actions, suggesting that these cells represent the same action based on a variety of cues. The present study sought to determine whether the human motor system, part of the putative human MNS, similarly represents and reflects the meaning of actions rather than simply the mechanics of the actions. To this end, transcranial magnetic stimulation (TMS) of primary motor cortex was used to generate motor-evoked potentials (MEPs) from muscles involved in grasping while participants viewed object-oriented grasping actions performed by either a human, an elephant, a rat, or a body-less robotic arm. The analysis of MEP amplitudes suggested that activity in primary motor cortex during action observation was greatest during observation of the grasping actions of the rat and elephant, and smallest for the human and robotic arm. Based on these data, we conclude that the human action observation system can represent actions executed by non-human animals and shows sensitivity to species-specific differences in action mechanics.

A test of the embodied simulation theory of object perception: potentiation of responses to artifacts and animals.

Theories of embodied object representation predict a tight association between sensorimotor processes and visual processing of manipulable objects. Previous research has shown that object handles can 'potentiate' a manual response (i.e., button press) to a congruent location. This potentiation effect is taken as evidence that objects automatically evoke sensorimotor simulations in response to the visual presentation of manipulable objects. In the present series of experiments, we investigated a critical prediction of the theory of embodied object representations that potentiation effects should be observed with manipulable artifacts but not non-manipulable animals. In four experiments we show that (a) potentiation effects are observed with animals and artifacts; (b) potentiation effects depend on the absolute size of the objects and (c) task context influences the presence/absence of potentiation effects. We conclude that potentiation effects do not provide evidence for embodied object representations, but are suggestive of a more general stimulus-response compatibility effect that may depend on the distribution of attention to different object features.

Electrophysiological markers of biological motion and human form recognition.

Current models suggest that human form and motion information are initially processed through separate pathways, then integrated in action perception. Testing such a sequential model requires techniques with high temporal resolution. Prior work demonstrated sensitivity of a posterior temporal event-related potential (ERP) effect - the N2 - to biological motion, but did not test whether the N2 indexes biological motion perception specifically, or human form/action perception more generally. We recorded ERPs while participants viewed stimuli across 3 blocks: (1) static (non-moving) point-light displays of humans performing actions; (2) static stick figures with clear forms; and (3) point-light biological motion. A similar sequence of ERP components was elicited by human forms in all blocks (stationary and moving), and reliably discriminated between human and scrambled forms. The N2 showed similar scalp distribution and sensitivity to stimulus manipulations for both stick figures and biological motion, suggesting that it indexes integration of form and motion information, rather than biological motion perception exclusively - and that form and motion information are therefore integrated by approximately 200ms. We identified a component subsequent to the N2, which we label the medial parietal positivity/ventral-anterior negativity (MPP/VAN), that was also sensitive to both human form and motion information. We propose that the MPP/VAN reflects higher-order human action recognition that occurs subsequent to the integration of form and motion information reflected by the N2.

Communicative and noncommunicative point-light actions featuring high-resolution representation of the hands and fingers.

We describe the creation of a set of point-light movies depicting 43 communicative gestures and 43 noncommunicative, pantomimed actions. These actions were recorded using a motion capture system that is worn on the body and provides accurate capture of the positions and movements of individual fingers. The movies created thus include point-lights on the fingers, allowing for representation of actions and gestures that would not be possible with a conventional, line-of-sight-based motion capture system. These videos would be suitable for use in cognitive and cognitive neuroscientific studies of biological motion and gesture perception. Each video is described, along with an H statistic indicating the consistency of the descriptive labels that 20 observers gave to the actions. We also produced a scrambled version of each movie, in which the starting position of each point was randomized but its local motion vector was preserved. These scrambled movies would be suitable for use as control stimuli in experimental studies. As supplementary materials, we provide QuickTime movie files of each action, along with text files specifying the three-dimensional coordinates of each point-light in each frame of each movie.

Emerging battery-ingestion hazard: clinical implications.

OBJECTIVES: Recent cases suggest that severe and fatal button battery ingestions are increasing and current treatment may be inadequate. The objective of this study was to identify battery ingestion outcome predictors and trends, define the urgency of intervention, and refine treatment guidelines. METHODS: Data were analyzed from 3 sources: (1) National Poison Data System (56535 cases, 1985-2009); (2) National Battery Ingestion Hotline (8648 cases, July 1990-September 2008); and (3) medical literature and National Battery Ingestion Hotline cases (13 deaths and 73 major outcomes) involving esophageal or airway button battery lodgment. RESULTS: All 3 data sets signal worsening outcomes, with a 6.7-fold increase in the percentage of button battery ingestions with major or fatal outcomes from 1985 to 2009 (National Poison Data System). Ingestions of 20- to 25-mm-diameter cells increased from 1% to 18% of ingested button batteries (1990-2008), paralleling the rise in lithium-cell ingestions (1.3% to 24%). Outcomes were significantly worse for large-diameter lithium cells (> or = 20 mm) and children who were younger than 4 years. The 20-mm lithium cell was implicated in most severe outcomes. Severe burns with sequelae occurred in just 2 to 2.5 hours. Most fatal (92%) or major outcome (56%) ingestions were not witnessed. At least 27% of major outcome and 54% of fatal cases were misdiagnosed, usually because of nonspecific presentations. Injuries extended after removal, with unanticipated and delayed esophageal perforations, tracheoesophageal fistulas, fistulization into major vessels, and massive hemorrhage. CONCLUSIONS: Revised treatment guidelines promote expedited removal from the esophagus, increase vigilance for delayed complications, and identify patients who require urgent radiographs.

Inhalant abuse: monitoring trends by using poison control data, 1993-2008.

PURPOSE: To demonstrate the value of poison control data as an adjunct to national drug abuse surveys and a source of data to inform and focus prevention efforts. METHODS: National Poison Data System (NPDS) data are collected and compiled in real time by the 60 US poison centers as callers seek guidance for poison exposures. Demographic, geographic, product, outcome, and treatment-site data for the 35453 inhalant cases reported between 1993 and 2008 were analyzed. RESULTS: The prevalence of inhalant cases reported to US poison control centers decreased 33% from 1993 to 2008. Prevalence was highest among children aged 12 to 17 years and peaked in 14-year-olds. In contrast to national survey data showing nearly equal use of inhalants by both genders, 73.5% of NPDS inhalant cases occurred in boys, which suggests that boys may pursue riskier usage behaviors. Most cases (67.8%) were managed in health care facilities. More than 3400 different products were reported. Propellants, gasoline, and paint were the most frequent product categories. Propellants were the only product category that substantially increased over time. Butane, propane, and air fresheners had the highest fatality rates. Prevalence for all inhalants was highest in western mountain states and West Virginia, but geographic distribution varied according to product type. Gasoline was a proportionately greater problem for younger children; propellants were an issue for older children. CONCLUSIONS: NPDS should be used to monitor inhalant abuse because it provides unique, timely, and clinically useful information on medical outcomes experienced by users, includes detailed product information (brand and formulation), and can potentially be used to identify real-time demographic, geographic, and product trends. Focusing inhalant prevention efforts on the most hazardous products and most seriously affected users may improve and facilitate strategic prevention, enabling interventions such as targeted education, product reformulation, repackaging, relabeling, or prohibition of sales of especially hazardous inhalant products to youth.

The impact of bittering agents on pediatric ingestions of antifreeze.

BACKGROUND: Legislation requiring bittering of antifreeze enables assessment of the impact on frequency, volume, and severity of pediatric antifreeze ingestions. METHODS: US poison control data for antifreeze ingestions in children younger than 5 years were analyzed comparing 232 ingestions occurring in states after enactment of bittering requirements with 6218 cases occurring in states (or at times) where bittering was not required. RESULTS: The frequency of pediatric antifreeze ingestions was unchanged after implementation of bittering in Oregon and California. The medical outcome distribution, median volume ingested, and observed clinical effects were no different in bittered compared with nonbittered groups. Likewise, the rates of hospital admission, critical care treatment, and use of alkalinization, hemodialysis, or intubation showed no differences with bittering. CONCLUSION: Despite the appealing logic of limiting the ingested volume and thereby the severity of poisonings by adding aversive agents, and despite promising results in volunteer studies, bittering agents do not decrease the frequency or severity of pediatric antifreeze poisonings. The addition of bittering agents to household products cannot be justified based on actual poisoning data.

The impact of bittering agents on suicidal ingestions of antifreeze.

BACKGROUND: Legislation requiring the addition of bittering agents to antifreeze enables assessment of the impact on frequency, volume and severity of suicidal antifreeze ingestions. METHODS: U.S. poison control data were analyzed comparing 130 suicidal antifreeze ingestions occurring in two states after enactment of bittering requirements with 3,493 cases occurring in states (or at times) where bittering was not required. RESULTS: The frequency of suicidal antifreeze ingestions was unchanged after implementation of bittering. The volume implicated, medical outcome distribution, and use of antidotes, hemodialysis, intubation, or critical care, showed no significant difference between bittered and non-bittered groups. Bittering was not a significant contributor (positively or negatively) in predicting lethal or life-threatening medical outcomes. CONCLUSION: The addition of bittering agents to antifreeze for the purpose of limiting the frequency or severity of suicidal ingestions could not be justified using U.S. poison control data.