Effects of fibrinogen supplementation on clot formation in blood samples from cardiac surgery patients before and after tranexamic acid administration.

OBJECTIVES: To investigate if supplementation with fibrinogen concentrate to blood samples collected after tranexamic acid administration improve clot formation more than what can be achieved with fibrinogen in the absence of tranexamic acid. BACKGROUND: It is not known if the combination of fibrinogen and tranexamic acid has additional effects than what can be achieved individually. METHODS: Four blood samples were collected from 15 coronary artery bypass patients. Two samples were collected before surgery, before and after 2 g tranexamic acid was administered. The preoperative samples were diluted to haematocrit 21%. Two samples were collected after surgery, before and after a second dose of 2 g tranexamic acid. Fibrinogen concentrate corresponding to a dose of 3 g in a 70-kg patient was added to the samples. Platelet-independent clotting time and maximum clot firmness assessed by thromboelastometry (ROTEM-FIBTEM®) were compared between the samples. RESULTS: Administration of tranexamic acid shortened clotting time marginally (-6%) before surgery, P = 0·029) but did not influence clot firmness. Fibrinogen concentrate shortened clotting time (-14% before and -12% after surgery, both P = 0·003) and increased clot firmness (+51 and +39%, both P < 0·001). The effects of fibrinogen did not differ before and after tranexamic acid administration. Fibrinolysis was not detected in any sample. CONCLUSIONS: The results of this in vitro study suggest that the enhancing effects of fibrinogen on clot firmness in blood samples from cardiac surgery patients are not further increased in the presence of tranexamic acid. Further studies on patients with ongoing bleeding and/or hyperfibrinolysis are necessary to validate the results.

An evaluation of the International Standards to Document Remaining Autonomic Function after Spinal Cord Injury: input from the international community.

STUDY DESIGN: Interactive workshops with a presurvey-postsurvey. OBJECTIVES: To describe a series of workshops held at international meetings to inform the spinal cord injury (SCI) community about the International Standards to Document Remaining Autonomic Function after Spinal Cord Injury (ISAFSCI) and to obtain feedback on both the workshop and the ISAFSCI assessment. SETTING: Three international conferences of SCI practitioners in Toronto, Las Vegas and Vancouver held between 2012 and 2013. METHODS: The workshops included an overview of the ISAFSCI, sharing experiences using it in clinical practice and interactive cases illustrating how to complete the scoring. A presurvey-postsurvey was administered to obtain feedback on the workshops and the ISAFSCI assessment. RESULTS: One hundred and fourteen participants completed the workshop surveys and 96% (109/114) completed both presurvey and postsurvey. Prior to the workshop, 41% (47/114) of those who had completed the survey reported assessing autonomic function in their practice, and of those, 53% (25/47) reported using the ISAFSCI. After the workshop, 74% (84/114) of participants reported that the case studies were helpful, and 57% (65/114) reported that they wanted to start or continue to use the ISAFSCI in their clinical practice. Suggestions for improving the ISAFSCI included providing further areas to consider when performing the assessment, addressing ambiguity of terms and reporting foreseeable implementation challenges. CONCLUSION: Results from this workshop suggest that more work is needed to inform the SCI community on the ISAFSCI assessment and to further clarify its language. Results from this study will inform future revisions to the ISAFSCI.

Quantitative trait locus mapping and functional genomics of an organophosphate resistance trait in the western corn rootworm, Diabrotica virgifera virgifera.

The western corn rootworm, Diabrotica virgifera virgifera, is an insect pest of corn and population suppression with chemical insecticides is an important management tool. Traits conferring organophosphate insecticide resistance have increased in frequency amongst D. v. virgifera populations, resulting in the reduced efficacy in many corn-growing regions of the USA. We used comparative functional genomic and quantitative trait locus (QTL) mapping approaches to investigate the genetic basis of D. v. virgifera resistance to the organophosphate methyl-parathion. RNA from adult methyl-parathion resistant and susceptible adults was hybridized to 8331 microarray probes. The results predicted that 11 transcripts were significantly up-regulated in resistant phenotypes, with the most significant (fold increases ≥ 2.43) being an α-esterase-like transcript. Differential expression was validated only for the α-esterase (ST020027A20C03), with 11- to 13-fold greater expression in methyl-parathion resistant adults (P < 0.05). Progeny with a segregating methyl-parathion resistance trait were obtained from a reciprocal backcross design. QTL analyses of high-throughput single nucleotide polymorphism genotype data predicted involvement of a single genome interval. These data suggest that a specific carboyxesterase may function in field-evolved corn rootworm resistance to organophosphates, even though direct linkage between the QTL and this locus could not be established.

Preoperative supplementation with fibrinogen concentrate in cardiac surgery: A randomized controlled study.

BACKGROUND: Bleeding remains a severe complication in cardiac surgery. Several studies have found an association between the preoperative plasma concentration of fibrinogen and postoperative bleeding in cardiac surgery patients. This raises the question of whether preoperative supplementation with fibrinogen concentrate can reduce postoperative blood loss. METHODS: An investigator-initiated, prospective, randomized double-blind placebo-controlled study, was performed in 48 low-risk, coronary artery bypass grafting patients. Subjects were randomized to infusion of 2 g fibrinogen or placebo immediately before surgery, after induction of anaesthesia. The primary endpoint was blood loss during the first 12 h postoperatively. Secondary endpoints included the proportion of transfused subjects, the number of transfused allogeneic blood products (red blood cells, plasma and platelets), and haemoglobin concentration after surgery. Student's t-test and Mann-Whitney U-test was used to compare continuous data and χ(2)-test to compare categorical data between groups. RESULTS: Median postoperative bleeding was not significantly different between the fibrinogen and placebo groups [650 (25/75th percentile 500‒835) ml compared with 730 (543‒980) ml, P=0.29]. The proportion of transfused subjects (33 vs 29%, P=0.76), number of perioperative transfusions of allogeneic blood products (0 (0-2 vs 0 (0-3), P=0.76) and haemoglobin concentration 24 h after surgery (107 (sd 11) vs 100 (12) g L-1, P=0.07) were not significantly different between the fibrinogen and placebo group, respectively. CONCLUSION: Preoperative supplementation with 2 g fibrinogen concentrate did not significantly influence postoperative bleeding, in coronary artery bypass grafting patients without documented hypofibrinogenaemia. CLINICAL TRIAL REGISTRATION: NCT 00968045.

Development and validation of a computerized algorithm for International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI).

STUDY DESIGN: Validation study. OBJECTIVES: To describe the development and validation of a computerized application of the international standards for neurological classification of spinal cord injury (ISNCSCI). SETTING: Data from acute and rehabilitation care. METHODS: The Rick Hansen Institute-ISNCSCI Algorithm (RHI-ISNCSCI Algorithm) was developed based on the 2011 version of the ISNCSCI and the 2013 version of the worksheet. International experts developed the design and logic with a focus on usability and features to standardize the correct classification of challenging cases. A five-phased process was used to develop and validate the algorithm. Discrepancies between the clinician-derived and algorithm-calculated results were reconciled. RESULTS: Phase one of the validation used 48 cases to develop the logic. Phase three used these and 15 additional cases for further logic development to classify cases with 'Not testable' values. For logic testing in phases two and four, 351 and 1998 cases from the Rick Hansen SCI Registry (RHSCIR), respectively, were used. Of 23 and 286 discrepant cases identified in phases two and four, 2 and 6 cases resulted in changes to the algorithm. Cross-validation of the algorithm in phase five using 108 new RHSCIR cases did not identify the need for any further changes, as all discrepancies were due to clinician errors. The web-based application and the algorithm code are freely available at www.isncscialgorithm.com. CONCLUSION: The RHI-ISNCSCI Algorithm provides a standardized method to accurately derive the level and severity of SCI from the raw data of the ISNCSCI examination. The web interface assists in maximizing usability while minimizing the impact of human error in classifying SCI. SPONSORSHIP: This study is sponsored by the Rick Hansen Institute and supported by funding from Health Canada and Western Economic Diversification Canada.

Posterior versus frontal theta activity indexes approach motivation during affective autobiographical memories.

Research has recently identified a promising neurophysiological marker of approach motivation involving posterior versus frontal (Pz - Fz) electroencephalographic (EEG) theta activity PFTA; Wacker, Chavanon, & Stemmler (Journal of Personality and Social Psychology 91:171-187, 2006). Preliminary evidence indicated that PFTA is modulated by dopaminergic activity, thought to underlie appetitive tendencies, and that it indexes self-reported behavioral activation system (BAS) sensitivity. To date, research has largely relied on resting indices of PFTA and has yet to examine the relationship between PFTA and specific approach-related affective states generated by emotionally salient laboratory tasks. Accordingly, the present study evaluated PFTA both at rest and during an ecologically valid autobiographical memory task in which participants recalled personal life experiences involving a goal-striving, an anxious apprehension, a low-point (i.e., difficult), and a neutral memory while EEG data were recorded. In line with prediction, elevated PFTA was observed during both goal-striving and anxious apprehension autobiographical memories. PFTA was particularly elevated during anxious apprehension memories coded as being high on approach-related tendencies. Elevated PFTA during anxious apprehension is consistent with a growing literature indicating that anxious apprehension is associated with elevated approach- and reward-related brain function. Lastly, elevated resting PFTA was positively correlated with self-reported trait anger, a negatively valenced emotion characterized by approach-related tendencies. These results have implications for (a) enhancing our understanding of the neurophysiology of approach-related emotions, (b) establishing PFTA as an index of appetitive motivational states, and (c) clarifying our understanding of the neurophysiology and approach-related tendencies associated with both anxious apprehension and anger.

Multi-strain probiotic improves subjective sleep quality with no impact on body composition, hemodynamics, and physical activity.

The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved ( P < 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased ( P < 0.05) after 6 weeks of supplementation with no change in MSP. No changes ( P > 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation. Registered at clinicaltrials.gov: NCT05343533.

Expression of lacunin, a large multidomain extracellular matrix protein, accompanies morphogenesis of epithelial monolayers in Manduca sexta.

Morphogenesis is a complex process operating at several levels of organization--organism, tissues, cells, and molecules. Complex interactions occur between and within these levels. Many of the molecules that mediate these interactions are predictably turning out to be large multidomain proteins. Here we describe one such novel protein associated with remodeling of epithelial monolayers in embryos and developing wings of the moth Manduca sexta. On the basis of its sequence and its expression pattern along lacunae of developing wings, we propose the name lacunin for this extracellular matrix protein that contains nine different types of domains, most of which are present in multiple copies. These include domains of various types: Kunitz proteinase inhibitors, thrombospondin type I, immunoglobulin-like, and several newly defined domains of unknown function (PAL, PLAC, and lagrin domains). This rich patchwork of distinct domains probably exerts multiple effects on a variety of cell behaviors associated with the complex phenomenon of epithelial morphogenesis.

Bilateral implantation of asymmetrical diffractive multifocal intraocular lenses.

OBJECTIVE: To evaluate visual results after bilateral implantation of multifocal intraocular lenses (IOLs) with asymmetrical light distribution for the far and near focus. METHODS: Twenty-nine patients underwent bilateral implantation of silicone-optic, foldable, diffractive IOLs in a prospective, 2-center, noncontrolled interventional study. Each patient had a distant-dominant multifocal IOL implanted in 1 eye and a near-dominant multifocal IOL implanted in the fellow eye. Refractive and visual results, including contrast acuity and binocular visual function, were determined. Patients were questioned for postoperative spectacle usage. RESULTS: Visual and contrast acuity in the dominant focus of either lens was superior to that in the nondominant focus at 3.5 to 12 months postoperatively, i.e., performance was best at distance for the distant-dominant and at near for the near-dominant lens. In binocular viewing, the monocular maximal results added up to an improved binocular visual performance. Binocular visual function was within normal limits. Eighty percent of patients reported no use of spectacles at any time postoperatively. CONCLUSIONS: Bilateral implantation of asymmetrical diffractive IOLs is an effective alternative for restoring simultaneous distance and near vision with a potential for improved contrast sensitivity compared with conventional multifocal IOLs.

Vitreous-stabilizing, single-piece, mini-loop, plate-haptic silicone intraocular lens.

PURPOSE: To evaluate the clinical and visual results of the Medevec VS5 intraocular lens (IOL) with mini-loops, determine the incision size required for its implantation and its usable optical zone size, and compare the sizes with those of other foldable lenses. SETTING: Ophthalmology Department, St. Johannes Hospitals, Dortmund, Germany. METHODS: The VS5 lens was folded with a forceps and implanted into an intact bag in 27 patients; incision size was measured. Postoperatively, centration was recorded after dilation and the lens periphery observed to ascertain whether the loops were fixed in the capsular bag. Postoperative A-scans were done in 22 eyes, and the preoperative and postoperative vitreous cavity lengths were compared. The size of the optical zone was compared with that of other foldable lenses. RESULTS: Forceps implantation of the VS5 lens required a 2.7 to 3.0 mm incision; all lenses were fixated in the bag. A-scans in 22 eyes showed that the vitreous cavity was shortened by an average of 0.51 mm. Uncorrected visual acuity was 20/40 or better in 96% of eyes. One week postoperatively, the IOLs remained centered and there was no flare or cells. The usable optical zone was larger than that of the staked long-loop lenses. CONCLUSION: The Medevec VS5 fixated in the bag, consistently locating in the posterior bag space and stabilizing the vitreous. It had a full 5.0 mm optical zone and could be implanted through an incision smaller that that required by other foldable IOLs.

Which asymptomatic patients should undergo routine screening carotid duplex scan?

The benefits of obtaining a routine screening carotid duplex scan have not been established for patients with peripheral vascular disease but no signs or symptoms of carotid artery disease. We retrospectively reviewed all carotid duplex scans (4,000) performed at our institution between 1985 through 1989 and found for analysis 91 scans in 78 patients who underwent a screening duplex scan because of the presence of peripheral vascular disease. Patients with carotid bruits, abnormal carotid pulses, and focal or nonspecific neurologic symptoms were excluded. Thirty-three percent of these patients had carotid stenosis of 16% to 50%, 14% had carotid stenosis greater than or equal to 50%, and 5% had stenosis greater than or equal to 75%. Individual risk factors for atherosclerosis, including elderly age, coronary artery disease, hypertension, diabetes, smoking, and a recent or past history of cardiac or vascular surgery, did not predict the detection of high-grade carotid stenosis. However, all 11 of the patients with carotid stenosis greater than or equal to 50% were 68 years of age and older, and this age range, in combination with the various risk factors, increased the incidence of significant carotid artery stenosis (greater than or equal to 50%) to as high as 45%. We conclude that routine screening carotid duplex scan is indicated in elderly patients (age greater than or equal to 68 years) with peripheral vascular disease, even in the absence of any signs or symptoms of carotid artery disease, when other atherosclerotic risk factors are present.

Body image and psychological sequelae of silicone breast explantation: preliminary findings.

Twenty-two breast explantation (implant removal) and 20 cholecystectomy patients were assessed preoperatively and postoperatively and compared with 20 nonsurgical control subjects on several body-image measures, depression, self-esteem, and self-reported health status. Explantation patients had higher breast anxiety and upper torso dissatisfaction than either control group and levels were unaffected by implant removal. The discrepancy between self-rated ideal and current breast size increased substantially after implant removal for the explantation group, but did not change for controls. Overall appearance satisfaction level and positive appearance-related cognitions decreased as a function of surgery for explantation patients, but remained unchanged in cholecystectomy and nonsurgical controls. Depression levels were elevated in explantation patients and did not change as a function of surgery; self-reported health status level improved for the explantation group, but levels still remained below those of both control groups after explantation. Therapeutic indications for the elevated depression levels and unique body-image issues that patients undergoing explantation experience are discussed.

Bmmar6, a second mori subfamily mariner transposon from the silkworm moth Bombyx mori.

A second member of the divergent mori subfamily of mariner transposons, Bmmar6, is described from the silkworm moth Bombyx mori genome. A confident consensus sequence for Bmmar6 was obtained from a single genomic copy, 17 EST sequences, and the direct sequencing of a 'family' sequence from an amplification of all full-length genomic copies. Bmmar6 is most similar to Bmmar1 in the mori subfamily, which now also includes several fly and nematode transposons. These might be viewed as a discrete family of transposons within the IS630-Tc1-mariner superfamily with a distinctive D,D37D catalytic motif, and another small divergent D,D41D clade is recognized as their sister group of transposons.

The genomes of most animals have multiple members of the Tc1 family of transposable elements.

A PCR assay was employed to detect sequence homologous to the transposase gene of the Tc1 family of transposable elements in a wide variety of animals. Amplification products of the appropriate size were obtained from most insects (92 of 108 examined; 85%), most other invertebrates (33 of 43; 77%), and many vertebrates (18 of 36; 50%). Sequencing a sample of cloned PCR products from eight insects, one hydra, and two frogs revealed that each had multiple distinct members of the family in their genomes. In the most extreme case, the horn fly Haematobia irritans yielded evidence of seventeen distinct types of Tc1 family elements. Most of the sequences obtained indicate that the elements are within the range of variation already known from fungi, nematodes, flies, fish and frogs. Some, however, had novel length variants or divergent sequences, indicating that they represent new subfamilies of these transposons. These results indicate that this family of transposons is extremely common in animal genomes, with multiple representatives in most genomes.

Loss of transposase-DNA interaction may underlie the divergence of mariner family transposable elements and the ability of more than one mariner to occupy the same genome.

Mariners are a large family of eukaryotic DNA-mediated transposable elements that move via a cut-and-paste mechanism. Several features of the evolutionary history of mariners are unusual. First, they appear to undergo horizontal transfer commonly between species on an evolutionary timescale. They can do this because they are able to transpose using only their own self-encoded transposase and not host-specific factors. One consequence of this phenomenon is that more than one kind of mariner can be present in the same genome. We hypothesized that two mariners occupying the same genome would not interact. We tested the limits of mariner interactions using an in vitro transposition system, purified mariner transposases, and DNAse I footprinting. Only mariner elements that were very closely related to each other (ca. 84% identity) cross-mobilized, and then inefficiently. Because of the dramatic suppression of transposition between closely related elements, we propose that to isolate elements functionally, only minor changes might be necessary between elements, in both inverted terminal repeat and amino acid sequence. We further propose a mechanism to explain mariner diversification based on this phenomenon.

beta-Hydroxybutyrate decreases adenosine triphosphate degradation products in human subjects.

Many disease states decrease intracellular adenosine triphosphate (ATP) levels and elevate body fluid purine levels. The use of specific metabolic substrates may reverse this process. This study was designed to test the hypothesis that beta-hydroxybutyrate, a substrate for ATP synthesis, decreases body fluid purine levels during interventions that induce ATP degradation. Decreases in these purine levels are metabolic markers for diminished ATP degradation. Two human models for stimulating ATP degradation were used to test the hypothesis. Rapid fructose infusion causes acute degradation of hepatic ATP, and ischemic exercise stimulates ATP consumption in skeletal muscle. The activity of beta-hydroxybutyrate was used in combination with phosphate, another important substrate for ATP synthesis. The studies were performed during a low-phosphate state in 10 normal subjects and during a high-phosphate state in 7 normal subjects. Metabolic variables, such as serum or urinary phosphate level, blood beta-hydroxybutyrate level, blood acetoacetate level, plasma or urinary purine level, blood lactate level, and blood ammonia level, were monitored during the study. After ischemic exercise of the forearm muscle, beta-hydroxybutyrate decreased the level of plasma total purines, blood lactate, and blood ammonia during the low-phosphate state but not during the high-phosphate state. During fructose-induced hepatic ATP breakdown, beta-hydroxybutyrate decreased late phase plasma purine increases under low-phosphate conditions only and decreased urinary total and radiolabeled purine elevations under both phosphate conditions. These data indicate that the infusion of beta-hydroxybutyrate may alter the balance from ATP degradation toward ATP resynthesis in muscle and liver by providing an immediate source of fuel and reducing equivalents under under specific metabolic conditions. This activity in combination with other metabolic interventions may have therapeutic value by restoring ATP pools in ATP-depleted tissues.