Mapping of susceptibility loci for Ebola virus pathogenesis in mice.

Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference populations, we generate an F2 mapping cohort to identify host susceptibility loci that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible mice display severe liver pathology consistent with EVD-like disease and transcriptional signatures associated with inflammatory and liver metabolic processes. A significant quantitative trait locus (QTL) for virus RNA load in blood is identified in chromosome (chr)8, and a severe clinical disease and mortality QTL is mapped to chr7, which includes the Trim5 locus. Using knockout mice, we validate the Trim5 locus as one potential driver of liver failure and mortality after infection. The identification of susceptibility loci provides insight into molecular genetic mechanisms regulating EVD progression and severity, potentially informing therapeutics and vaccination strategies.

Development of a multidimensional military readiness assessment.

There is a need to be able to accurately evaluate whether an injured service member is able to return to duty. An effective assessment would challenge and measures physical and cognitive performance in a military-relevant context. Current assessments are lacking in one or more of these aspects. The simulation and data capture abilities of virtual reality systems are promising for use as the basis of multidimensional assessments. The team has previously developed a military-specific assessment in the Computer Assisted Rehabilitation Environment (CAREN) called the Readiness Evaluation During simulated Dismounted Operations (REDOp). Due to notable limitations in the original assessment, we have developed the next iteration, REDOp2. The assessment is able to challenge and measure a broader range of physical and cognitive performance domains in a more streamlined fashion. While limited to facilities with a CAREN, REDOp2 has the potential to provide an effective tool for highly trained and experienced wounded service members that require thorough assessment prior to returning to duty to ensure the safety of the team and mission. This methods paper describes the specific limitations in REDOp, how they were addressed in REDOp2, and suggested next steps to prepare the assessment for implementation.

3D printing of heart valves.

3D printing technologies have the potential to revolutionize the manufacture of heart valves through the ability to create bespoke, complex constructs. In light of recent technological advances, we review the progress made towards 3D printing of heart valves, focusing on studies that have utilised these technologies beyond manufacturing patient-specific moulds. We first overview the key requirements of a heart valve to assess functionality. We then present the 3D printing technologies used to engineer heart valves. By referencing International Organisation for Standardisation (ISO) Standard 5840 (Cardiovascular implants - Cardiac valve prostheses), we provide insight into the achieved functionality of these valves. Overall, 3D printing promises to have a significant positive impact on the creation of artificial heart valves and potentially unlock full complex functionality.

Three-Dimensional Bioprinting in Cardiovascular Disease: Current Status and Future Directions.

Three-dimensional (3D) printing plays an important role in cardiovascular disease through the use of personalised models that replicate the normal anatomy and its pathology with high accuracy and reliability. While 3D printed heart and vascular models have been shown to improve medical education, preoperative planning and simulation of cardiac procedures, as well as to enhance communication with patients, 3D bioprinting represents a potential advancement of 3D printing technology by allowing the printing of cellular or biological components, functional tissues and organs that can be used in a variety of applications in cardiovascular disease. Recent advances in bioprinting technology have shown the ability to support vascularisation of large-scale constructs with enhanced biocompatibility and structural stability, thus creating opportunities to replace damaged tissues or organs. In this review, we provide an overview of the use of 3D bioprinting in cardiovascular disease with a focus on technologies and applications in cardiac tissues, vascular constructs and grafts, heart valves and myocardium. Limitations and future research directions are highlighted.

Engineering Heart Valve Interfaces Using Melt Electrowriting: Biomimetic Design Strategies from Multi-Modal Imaging.

Interfaces within biological tissues not only connect different regions but also contribute to the overall functionality of the tissue. This is especially true in the case of the aortic heart valve. Here, melt electrowriting (MEW) is used to engineer complex, user-defined, interfaces for heart valve scaffolds. First, a multi-modal imaging investigation into the interfacial regions of the valve reveals differences in collagen orientation, density, and recruitment in previously unexplored regions including the commissure and inter-leaflet triangle. Overlapping, suturing, and continuous printing methods for interfacing MEW scaffolds are then investigated for their morphological, tensile, and flexural properties, demonstrating the superior performance of continuous interfaces. G-codes for MEW scaffolds with complex interfaces are designed and generated using a novel software and graphical user interface. Finally, a singular MEW scaffold for the interfacial region of the aortic heart valve is presented incorporating continuous interfaces, gradient porosities, variable layer numbers across regions, and tailored fiber orientations inspired by the collagen distribution and orientation from the multi-modal imaging study. The scaffold exhibits similar yield strain, hysteresis, and relaxation behavior to porcine heart valves. This work demonstrates the ability of a bioinspired approach for MEW scaffold design to address the functional complexity of biological tissues.

Relationship Between a Vitamin D Genetic Risk Score and Autoantibodies Among First-Degree Relatives of Probands With Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Objective: Higher 25-hydroxyvitamin D (25(OH)D) levels have been associated with reduced risk for autoimmune diseases and are influenced by vitamin D metabolism genes. We estimated genetically-determined vitamin D levels by calculating a genetic risk score (GRS) and investigated whether the vitamin D GRS was associated with the presence of autoantibodies related to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in those at increased risk for developing RA and SLE, respectively. Methods: In this cross-sectional study, we selected autoantibody positive (aAb+) and autoantibody negative (aAb-) individuals from the Studies of the Etiologies of Rheumatoid Arthritis (SERA), a cohort study of first-degree relatives (FDRs) of individuals with RA (189 RA aAb+, 181 RA aAb-), and the Lupus Family Registry and Repository (LFRR), a cohort study of FDRs of individuals with SLE (157 SLE aAb+, 185 SLE aAb-). Five SNPs known to be associated with serum 25(OH)D levels were analyzed individually as well as in a GRS: rs4588 (GC), rs12785878 (NADSYN1), rs10741657 (CYP2R1), rs6538691 (AMDHD1), and rs8018720 (SEC23A). Results: Both cohorts had similar demographic characteristics, with significantly older and a higher proportion of males in the aAb+ FDRs. The vitamin D GRS was inversely associated with RA aAb+ (OR = 0.85, 95% CI = 0.74-0.99), suggesting a possible protective factor for RA aAb positivity in FDRs of RA probands. The vitamin D GRS was not associated with SLE aAb+ in the LFRR (OR = 1.09, 95% CI = 0.94-1.27). The SEC23A SNP was associated with RA aAb+ in SERA (OR = 0.65, 95% CI = 0.43-0.99); this SNP was not associated with SLE aAb+ in LFRR (OR = 1.41, 95% CI = 0.90 - 2.19). Conclusion: Genes associated with vitamin D levels may play a protective role in the development of RA aAbs in FDRs of RA probands, perhaps through affecting lifelong vitamin D status. The GRS and the SEC23A SNP may be of interest for future investigation in pre-clinical RA. In contrast, these results do not support a similar association in SLE FDRs, suggesting other mechanisms involved in the relationship between vitamin D and SLE aAbs not assessed in this study.

The role of spatial alignment in posture-cognition dual task interaction.

BACKGROUND: A range of cognitive tasks can interfere with postural control, particularly in older adults. In the case of spatial tasks, the spatial alignment between the task and postural control can incur dual-task costs separately from task load. It has been suggested that spatial tasks incur dual-task costs because accessing the visuospatial sketchpad component of working memory reduces the capacity to utilize external visual information for postural control. RESEARCH QUESTION: We investigated whether the spatial alignment between a cognitive and a postural control task can affect postural stability even when visual perception is not involved in either task and task load does not differ between aligned and non-aligned conditions. We predicted that any such effect would be greater in older people and in a more challenging stance. METHODS: Fifty healthy adults (27 aged 20-35, 23 aged 59-88) with no history of balance or cognitive difficulties performed a mental navigation task while standing in open or closed stance with eyes closed. The mental navigation task was presented in a reference plane that was either aligned or non-aligned to the horizontal reference plane in which the posture control system controlled the position of the body's center of gravity. Task performance was measured as accuracy and response time and postural sway as anteroposterior (AP) and mediolateral (ML) sway velocity. RESULTS: The older group were less accurate in the mental navigation task, and both groups had higher AP and ML sway velocity in closed stance. When standing in the more challenging stance, the older group had higher AP sway velocity while performing the mental navigation task in the non-aligned than the aligned reference plane condition. SIGNIFICANCE: The spatial configuration compatibility between a cognitive task and postural control can affect postural stability even when visual information is not being used for either task and task load is unchanged.

Treatment of Mal de Debarquement Syndrome in a Computer-Assisted Rehabilitation Environment.

Individuals with mal de debarquement syndrome (MdDS) describe symptoms of swaying, rocking, and/or bobbing after sea or air travel. These symptoms may be because of maladaptation of the vestibulo-ocular reflex (VOR) to roll of the head during rotation. Dai and colleagues have developed a treatment paradigm that involves passive roll of the patient's head while watching optokinetic stripes, resulting in adaption of the VOR and improvement of MdDS. The purpose of this case report is to describe replication of this treatment paradigm in a virtual reality environment with successful resolution of symptoms in two visits. A 39-year-old female reported swaying and rocking after returning from a 7-day cruise. The patient was treated with two sessions in a computer-assisted rehabilitation environment (CAREN). The patient canceled her third visit because of complete resolution of her symptoms. Her Global Rating of Change was +7 (on a 15-point scale of -7 to +7). She had returned to her prior level of function. This case report is the first to describe use of the CAREN for effective treatment of MdDS by replicating the treatment paradigm developed by Dai and colleagues.

Proof-of-Concept Study: a Mobile Application to Derive Clinical Outcome Measures from Expression and Speech for Mental Health Status Evaluation.

This proof-of-concept study aimed to assess the ability of a mobile application and cloud analytics software solution to extract facial expression information from participant selfie videos. This is one component of a solution aimed at extracting possible health outcome measures based on expression, voice acoustics and speech sentiment from video diary data provided by patients. Forty healthy volunteers viewed 21 validated images from the International Affective Picture System database through a mobile app which simultaneously captured video footage of their face using the selfie camera. Images were intended to be associated with the following emotional responses: anger, disgust, sadness, contempt, fear, surprise and happiness. Both valence and arousal scores estimated from the video footage associated with each image were adequate predictors of the IAPS image scores (p < 0.001 and p = 0.04 respectively). 12.2% of images were categorised as containing a positive expression response in line with the target expression; with happiness and sadness responses providing the greatest frequency of responders: 41.0% and 21.4% respectively. 71.2% of images were associated with no change in expression. This proof-of-concept study provides early encouraging findings that changes in facial expression can be detected when they exist. Combined with voice acoustical measures and speech sentiment analysis, this may lead to novel measures of health status in patients using a video diary in indications including depression, schizophrenia, autism spectrum disorder and PTSD amongst other conditions.

Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging.

OBJECTIVE: Systemic activation of the complement system in intermediate age-related macular degeneration (AMD) is understudied. Moreover, links between the presence of reticular pseudodrusen (RPD) and systemic complement dysregulation have not been studied. The aim of this study was to determine if there is a difference in plasma complement factor levels in intermediate AMD compared with controls, and if complement levels are related to the presence of RPD. METHODS AND ANALYSIS: Levels of complement factors C1q (µg/mL), C4 (µg/mL), C2 (µg/mL), Mannose Binding Lectin (ng/mL), C4b (µg/mL), C3 (µg/mL), factor B (µg/mL), factor D (µg/mL), properdin (µg/mL), C3a (ng/mL), iC3b/C3b (ng/mL), Ba (ng/mL), factor H (µg/mL), factor I (µg/mL), C5 (µg/mL), C5a (pg/mL) and SC5b-9 (ng/mL) were measured in plasma. RESULTS: 109 cases and 65 controls were included in the study. Thirty-nine (36%) cases had RPD. Significantly lower systemic levels of: C1q (OR 0.96, 95% CI 0.94 to 0.98), factor B (OR 0.98, 95% CI 0.96 to 0.99), iC3b/C3b (OR 0.97, 95% CI 0.95 to 0.98), factor H (OR 0.99, 95% CI 0.98 to 0.99), factor I (OR 0.83, 95% CI 0.77 to 0.89) and C5 (OR 0.94, 95% CI 0.90 to 0.98) were found in cases versus controls. Significantly elevated levels of: C2 (OR 1.29, 95% CI 1.07 to 1.59), C3a (OR 1.03, 95% CI 1.01 to 1.05) Ba (OR 1.03, 95% CI 1.01 to 1.05) and C5a (OR 1.04, 95% CI 1.02 to 1.07) were found in cases versus controls. Systemic levels of complement factors measured were not related to the presence of RPD. CONCLUSIONS: Levels of several systemic complement pathway factors were found to be altered in intermediate AMD. Systemic levels of complement factors were not related to RPD.

A novel assessment for Readiness Evaluation during Simulated Dismounted Operations: A reliability study.

OBJECTIVE: To determine the intersession reliability of the Readiness Evaluation during Simulated Dismounted Operations (REDOp), a novel ecologically-based assessment for injured Service Members, provide minimal detectable change values, and normative reference range values. To evaluate the ability to differentiate performance limitations between able-bodied and injured individuals using the REDOp. DESIGN: Repeated measures design and between group comparison. SETTING: Outpatient rehabilitative care setting. PARTICIPANTS: Service Members who were able-bodied (n = 32) or sustained a traumatic lower extremity injury (n = 22). INTERVENTIONS: During the REDOp, individuals walked over variable terrain as speed and incline progressively increased; they engaged targets; and carried military gear. MAIN OUTCOME MEASURES: Endurance measured using total distance traveled; walking stability measured using range of full-body angular momentum; and shooting accuracy, precision, reaction time and acquisition time. RESULTS: Intersession reliability analyses were conducted on a sub-group of 18 able-bodied Service Members. Interclass correlation coefficient values were calculated for distance traveled (0.91), range of angular momentum about three axes (0.78-0.93), shooting accuracy (0.61), precision (0.47), reaction time (0.21), and acquisition time (0.77). Service Members with lower extremity injury demonstrated significantly less distance traveled with a median distance of 0.89 km compared to 2.73 km for the able-bodied group (p < 0.001). Service Members with lower extremity injury demonstrated significantly less stability in the frontal and sagittal planes than the able-bodied group (p < 0.001). The primary performance limiter was endurance followed by pain for both groups. There was no evidence of ceiling effects. CONCLUSIONS: The REDOp is a highly reliable, military-relevant assessment that can be used to measure performance and identify deficits across the domains of activity tolerance, gait stability, and shooting performance.

Stress During Development of Experimental Endometriosis Influences Nerve Growth and Disease Progression.

PURPOSE: We have previously shown that stress prior to induction worsens clinical presentation and inflammatory parameters in a rat model of endometriosis. This study was designed to examine whether stress during the development of endometriosis can affect the growth of endometriotic implants through nerve growth and immune alterations. METHODS: Endometriosis was surgically induced in female Sprague-Dawley rats by suturing uterine horn implants onto the small intestine mesentery. Two weeks later, one group of rats (endo-stress) was subjected to a 10-day swim stress protocol. Controls had no stress (endo-no stress) or sutures only and stress (sham-stress). On day 60, all rats were killed and examined for the presence of endometriotic vesicles. The size of each vesicle was measured. The uterus and colon were removed and assessed for damage, cell infiltration, and expression of nerve growth factor (NGF), its receptors (p75 and Tropomyosin receptor kinase A (Trk-A)/pTrk-A), and calcitonin gene-related peptide, a sensory fiber marker. A differential analysis of peritoneal fluid white blood cell count was performed. RESULTS: Stress significantly increased endometriotic vesicle size but not colonic damage and increased infiltration of mast cells. Significantly increased expression of NGF and its receptors was found in the uterus of animals with endometriosis receiving stress. CONCLUSIONS: Stress stimulates the development of ectopic endometrial vesicles in an animal model of endometriosis and increases inflammatory cell recruitment to the peritoneum. In addition, stress promotes nerve fiber growth in the uterus.

Timed written picture naming in 14 European languages.

We describe the Multilanguage Written Picture Naming Dataset. This gives trial-level data and time and agreement norms for written naming of the 260 pictures of everyday objects that compose the colorized Snodgrass and Vanderwart picture set (Rossion & Pourtois in Perception, 33, 217-236, 2004). Adult participants gave keyboarded responses in their first language under controlled experimental conditions (N = 1,274, with subsamples responding in Bulgarian, Dutch, English, Finnish, French, German, Greek, Icelandic, Italian, Norwegian, Portuguese, Russian, Spanish, and Swedish). We measured the time to initiate a response (RT) and interkeypress intervals, and calculated measures of name and spelling agreement. There was a tendency across all languages for quicker RTs to pictures with higher familiarity, image agreement, and name frequency, and with higher name agreement. Effects of spelling agreement and effects on output rates after writing onset were present in some, but not all, languages. Written naming therefore shows name retrieval effects that are similar to those found in speech, but our findings suggest the need for cross-language comparisons as we seek to understand the orthographic retrieval and/or assembly processes that are specific to written output.

ASRM standard embryo transfer protocol template: a committee opinion.

Standardization improves performance and safety. A template for standardizing the embryo transfer procedure is presented here with 12 basic steps supported by published scientific literature and a survey of common practice of SART programs; it can be used by ART practices to model their own standard protocol.

The new frontier of diagnostics: Molecular assays and their role in infection prevention and control.

Recent advances in technology over the last decade have propelled the microbiology laboratory into a pivotal role in infection prevention and control. The rapid adaptation of molecular technologies to the field of clinical microbiology now greatly influences infectious disease management and significantly impacts infection control practices. This review discusses recent developments in molecular techniques in the diagnosis of infectious diseases. It describes the basic concepts of molecular assays, discusses their advantages and limitations, and characterizes currently available commercial assays with respect to cost, interpretive requirements, and clinical utility.

Outbreak of Pantoea agglomerans Bloodstream Infections at an Oncology Clinic-Illinois, 2012-2013.

OBJECTIVE To determine the source of a healthcare-associated outbreak of Pantoea agglomerans bloodstream infections. DESIGN Epidemiologic investigation of the outbreak. SETTING Oncology clinic (clinic A). METHODS Cases were defined as Pantoea isolation from blood or catheter tip cultures of clinic A patients during July 2012-May 2013. Clinic A medical charts and laboratory records were reviewed; infection prevention practices and the facility's water system were evaluated. Environmental samples were collected for culture. Clinical and environmental P. agglomerans isolates were compared using pulsed-field gel electrophoresis. RESULTS Twelve cases were identified; median (range) age was 65 (41-78) years. All patients had malignant tumors and had received infusions at clinic A. Deficiencies in parenteral medication preparation and handling were identified (eg, placing infusates near sinks with potential for splash-back contamination). Facility inspection revealed substantial dead-end water piping and inadequate chlorine residual in tap water from multiple sinks, including the pharmacy clean room sink. P. agglomerans was isolated from composite surface swabs of 7 sinks and an ice machine; the pharmacy clean room sink isolate was indistinguishable by pulsed-field gel electrophoresis from 7 of 9 available patient isolates. CONCLUSIONS Exposure of locally prepared infusates to a contaminated pharmacy sink caused the outbreak. Improvements in parenteral medication preparation, including moving chemotherapy preparation offsite, along with terminal sink cleaning and water system remediation ended the outbreak. Greater awareness of recommended medication preparation and handling practices as well as further efforts to better define the contribution of contaminated sinks and plumbing deficiencies to healthcare-associated infections are needed. Infect Control Hosp Epidemiol 2017;38:314-319.

Hepatic resection is associated with reduced postoperative opioid requirement.

BACKGROUND AND AIMS: Postoperative pain can significantly affect surgical outcomes. As opioid metabolism is liver-dependent, any reduction in hepatic volume can lead to increased opioid concentrations in the blood. The hypothesis of this retrospective study was that patients undergoing open hepatic resection would require less opioid for pain management than those undergoing open pancreaticoduodenectomy. MATERIAL AND METHODS: Data from 79 adult patients who underwent open liver resection and eighty patients who underwent open pancreaticoduodenectomy at our medical center between January 01, 2010 and June 30, 2013 were analyzed. All patients received both general and neuraxial anesthesia. Postoperatively, patients were managed with a combination of epidural and patient-controlled analgesia. Pain scores and amount of opioids administered (morphine equivalents) were compared. A multivariate lineal regression was performed to determine predictors of opioid requirement. RESULTS: No significant differences in pain scores were found at any time point between groups. Significantly more opioid was administered to patients having pancreaticoduodenectomy than those having a hepatic resection at time points: Intraoperative (P = 0.006), first 48 h postoperatively (P = 0.001), and the entire length of stay (LOS) (P = 0.002). Statistical significance was confirmed after controlling for age, sex, body mass index, and American Society of Anesthesiologists physical status classification (adjusted P = 0.006). Total hospital LOS was significantly longer after pancreaticoduodenectomy (P = 0.03). A multivariate lineal regression demonstrated a lower opioid consumption in the hepatic resection group (P = 0.03), but there was no difference in opioid use based on the type of hepatic resection. CONCLUSION: Patients undergoing open hepatic resection had a significantly lower opioid requirement in comparison with patients undergoing open pancreaticoduodenectomy. A multicenter prospective evaluation should be performed to confirm these findings.

Lack of Transmission among Close Contacts of Patient with Case of Middle East Respiratory Syndrome Imported into the United States, 2014.

In May 2014, a traveler from the Kingdom of Saudi Arabia was the first person identified with Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States. To evaluate transmission risk, we determined the type, duration, and frequency of patient contact among health care personnel (HCP), household, and community contacts by using standard questionnaires and, for HCP, global positioning system (GPS) tracer tag logs. Respiratory and serum samples from all contacts were tested for MERS-CoV. Of 61 identified contacts, 56 were interviewed. HCP exposures occurred most frequently in the emergency department (69%) and among nurses (47%); some HCP had contact with respiratory secretions. Household and community contacts had brief contact (e.g., hugging). All laboratory test results were negative for MERS-CoV. This contact investigation found no secondary cases, despite case-patient contact by 61 persons, and provides useful information about MERS-CoV transmission risk. Compared with GPS tracer tag recordings, self-reported contact may not be as accurate.

New Delhi metallo-ß-lactamase-producing carbapenem-resistant Escherichia coli associated with exposure to duodenoscopes.

IMPORTANCE: Carbapenem-resistant Enterobacteriaceae (CRE) producing the New Delhi metallo-ß-lactamase (NDM) are rare in the United States, but have the potential to add to the increasing CRE burden. Previous NDM-producing CRE clusters have been attributed to person-to-person transmission in health care facilities. OBJECTIVE: To identify a source for, and interrupt transmission of, NDM-producing CRE in a northeastern Illinois hospital. DESIGN, SETTING, AND PARTICIPANTS: Outbreak investigation among 39 case patients at a tertiary care hospital in northeastern Illinois, including a case-control study, infection control assessment, and collection of environmental and device cultures; patient and environmental isolate relatedness was evaluated with pulsed-field gel electrophoresis (PFGE). Following identification of a likely source, targeted patient notification and CRE screening cultures were performed. MAIN OUTCOMES AND MEASURES: Association between exposure and acquisition of NDM-producing CRE; results of environmental cultures and organism typing. RESULTS: In total, 39 case patients were identified from January 2013 through December 2013, 35 with duodenoscope exposure in 1 hospital. No lapses in duodenoscope reprocessing were identified; however, NDM-producing Escherichia coli was recovered from a reprocessed duodenoscope and shared more than 92% similarity to all case patient isolates by PFGE. Based on the case-control study, case patients had significantly higher odds of being exposed to a duodenoscope (odds ratio [OR], 78 [95% CI, 6.0-1008], P < .001). After the hospital changed its reprocessing procedure from automated high-level disinfection with ortho-phthalaldehyde to gas sterilization with ethylene oxide, no additional case patients were identified. CONCLUSIONS AND RELEVANCE: In this investigation, exposure to duodenoscopes with bacterial contamination was associated with apparent transmission of NDM-producing E coli among patients at 1 hospital. Bacterial contamination of duodenoscopes appeared to persist despite the absence of recognized reprocessing lapses. Facilities should be aware of the potential for transmission of bacteria including antimicrobial-resistant organisms via this route and should conduct regular reviews of their duodenoscope reprocessing procedures to ensure optimal manual cleaning and disinfection.