Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery.

Unfractionated heparin (UFH) is an effective antithrombotic during surgery but has known adverse effects, in particular on platelets. A marked increase in platelet responsiveness has previously been observed in patients within minutes of receiving UFH, despite adequate inhibition by aspirin prior to heparin. We studied this phenomenon in patients undergoing cardiac artery bypass grafting (n = 17) to determine whether the effects of heparin were systemic or platelet-specific. All patients' platelets were fully inhibited by aspirin prior to surgery, but within 3 min of receiving heparin spontaneous aggregation and responses to arachidonic acid (AA) and ADP increased significantly (p ≥ 0.0002), and activated platelets were found in the circulation. While there was no rise in thromboxane in the plasma following heparin, levels of the major platelet 12-lipoxygenase product, 12-HETE, rose significantly. Mixing experiments demonstrated that the changes caused by heparin resided primarily in the platelets, while addition of AA pathway inhibitors, and analysis of oxylipins provided evidence that, following heparin, aggregating platelets regained their ability to synthesise thromboxane. These findings highlight potentially unrecognised pro-thrombotic and pro-inflammatory changes during CABG surgery, and provide further evidence of adverse effects associated with UFH.

Identification of herbarium specimen sheet components from high-resolution images using deep learning.

Advanced computer vision techniques hold the potential to mobilise vast quantities of biodiversity data by facilitating the rapid extraction of text- and trait-based data from herbarium specimen digital images, and to increase the efficiency and accuracy of downstream data capture during digitisation. This investigation developed an object detection model using YOLOv5 and digitised collection images from the University of Melbourne Herbarium (MELU). The MELU-trained 'sheet-component' model-trained on 3371 annotated images, validated on 1000 annotated images, run using 'large' model type, at 640 pixels, for 200 epochs-successfully identified most of the 11 component types of the digital specimen images, with an overall model precision measure of 0.983, recall of 0.969 and moving average precision (mAP0.5-0.95) of 0.847. Specifically, 'institutional' and 'annotation' labels were predicted with mAP0.5-0.95 of 0.970 and 0.878 respectively. It was found that annotating at least 2000 images was required to train an adequate model, likely due to the heterogeneity of specimen sheets. The full model was then applied to selected specimens from nine global herbaria (Biodiversity Data Journal, 7, 2019), quantifying its generalisability: for example, the 'institutional label' was identified with mAP0.5-0.95 of between 0.68 and 0.89 across the various herbaria. Further detailed study demonstrated that starting with the MELU-model weights and retraining for as few as 50 epochs on 30 additional annotated images was sufficient to enable the prediction of a previously unseen component. As many herbaria are resource-constrained, the MELU-trained 'sheet-component' model weights are made available and application encouraged.

Phytest: quality control for phylogenetic analyses.

MOTIVATION: The ability to automatically conduct quality control checks on phylogenetic analyses is becoming more important with the increase in genetic sequencing and the use of real-time pipelines e.g. in the SARS-CoV-2 era. Implementations of real-time phylogenetic analyses require automated testing to make sure that problems in the data are caught automatically within analysis pipelines and in a timely manner. Here, we present Phytest (version 1.1) a tool for automating quality control checks on sequences, trees and metadata during phylogenetic analyses. RESULTS: Phytest is a phylogenetic analysis testing program that easily integrates into existing phylogenetic pipelines. We demonstrate the utility of Phytest with real-world examples. AVAILABILITY AND IMPLEMENTATION: Phytest source code is available on GitHub (https://github.com/phytest-devs/phytest) and can be installed via PyPI with the command 'pip install phytest'. Extensive documentation can be found at https://phytest-devs.github.io/phytest/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Metaphor-A workflow for streamlined assembly and binning of metagenomes.

Recent advances in bioinformatics and high-throughput sequencing have enabled the large-scale recovery of genomes from metagenomes. This has the potential to bring important insights as researchers can bypass cultivation and analyze genomes sourced directly from environmental samples. There are, however, technical challenges associated with this process, most notably the complexity of computational workflows required to process metagenomic data, which include dozens of bioinformatics software tools, each with their own set of customizable parameters that affect the final output of the workflow. At the core of these workflows are the processes of assembly-combining the short-input reads into longer, contiguous fragments (contigs)-and binning, clustering these contigs into individual genome bins. The limitations of assembly and binning algorithms also pose different challenges depending on the selected strategy to execute them. Both of these processes can be done for each sample separately or by pooling together multiple samples to leverage information from a combination of samples. Here we present Metaphor, a fully automated workflow for genome-resolved metagenomics (GRM). Metaphor differs from existing GRM workflows by offering flexible approaches for the assembly and binning of the input data and by combining multiple binning algorithms with a bin refinement step to achieve high-quality genome bins. Moreover, Metaphor generates reports to evaluate the performance of the workflow. We showcase the functionality of Metaphor on different synthetic datasets and the impact of available assembly and binning strategies on the final results.

Profiling oxylipins released from human platelets activated through the GPVI collagen receptor.

In addition to haemostasis, platelets are involved in pathological processes, often driven by material released upon activation. Interaction between collagen and glycoprotein VI (GPVI) is a primary platelet stimulus that liberates arachidonic acid and linoleic acid from membrane phospholipids. These are oxidised by cyclooxygenase-1 (COX-1) and 12-lipoxygenase (12-LOX) to eicosanoids and other oxylipins with various biological properties. Using liquid chromatography-tandem mass spectrometry we found that GPVI-stimulated platelets released significant levels of ten oxylipins; the well documented TxA2 and 12-HETE, PGD2 and PGE2, as well as 8-, 9-, 11-, and 15-HETE, 9- and 13-HODE.1 Levels of oxylipins released from washed platelets mirrored those from platelets stimulated in the presence of plasma, indicating generation from intracellular, rather than exogenous AA/LA. Inhibition of COX-1 with aspirin, as expected, completely abolished production of TxA2 and PGD/E2, but also significantly inhibited the release of 11-HETE (89 ± 3%) and 9-HODE (74 ± 6%), and reduced 15-HETE and 13-HODE by ∼33 %. Inhibition of 12-LOX by either esculetin or ML355 inhibited the release of all oxylipins apart from 15-HETE. These findings suggest routes to modify the production of bioactive molecules released by activated platelets.

Connectomics Analysis Reveals First-, Second-, and Third-Order Thermosensory and Hygrosensory Neurons in the Adult Drosophila Brain.

Animals exhibit innate and learned preferences for temperature and humidity-conditions critical for their survival and reproduction. Leveraging a whole-brain electron microscopy volume, we studied the adult Drosophila melanogaster circuitry associated with antennal thermo- and hygrosensory neurons. We have identified two new target glomeruli in the antennal lobe, in addition to the five known ones, and the ventroposterior projection neurons (VP PNs) that relay thermo- and hygrosensory information to higher brain centers, including the mushroom body and lateral horn, seats of learned and innate behavior. We present the first connectome of a thermo- and hygrosensory neuropil, the lateral accessory calyx (lACA), by reconstructing neurons downstream of heating- and cooling-responsive VP PNs. A few mushroom body-intrinsic neurons solely receive thermosensory input from the lACA, while most receive additional olfactory and thermo- and/or hygrosensory PN inputs. Furthermore, several classes of lACA-associated neurons form a local network with outputs to other brain neuropils, suggesting that the lACA serves as a hub for thermo- and hygrosensory circuitry. For example, DN1a neurons link thermosensory PNs in the lACA to the circadian clock via the accessory medulla. Finally, we survey strongly connected downstream partners of VP PNs across the protocerebrum; these include a descending neuron targeted by dry-responsive VP PNs, meaning that just two synapses might separate hygrosensory inputs from motor circuits. These data provide a comprehensive first- and second-order layer analysis of Drosophila thermo- and hygrosensory systems and an initial survey of third-order neurons that could directly modulate behavior.

Complete Connectomic Reconstruction of Olfactory Projection Neurons in the Fly Brain.

Nervous systems contain sensory neurons, local neurons, projection neurons, and motor neurons. To understand how these building blocks form whole circuits, we must distil these broad classes into neuronal cell types and describe their network connectivity. Using an electron micrograph dataset for an entire Drosophila melanogaster brain, we reconstruct the first complete inventory of olfactory projections connecting the antennal lobe, the insect analog of the mammalian olfactory bulb, to higher-order brain regions in an adult animal brain. We then connect this inventory to extant data in the literature, providing synaptic-resolution "holotypes" both for heavily investigated and previously unknown cell types. Projection neurons are approximately twice as numerous as reported by light level studies; cell types are stereotyped, but not identical, in cell and synapse numbers between brain hemispheres. The lateral horn, the insect analog of the mammalian cortical amygdala, is the main target for this olfactory information and has been shown to guide innate behavior. Here, we find new connectivity motifs, including axo-axonic connectivity between projection neurons, feedback, and lateral inhibition of these axons by a large population of neurons, and the convergence of different inputs, including non-olfactory inputs and memory-related feedback onto third-order olfactory neurons. These features are less prominent in the mushroom body calyx, the insect analog of the mammalian piriform cortex and a center for associative memory. Our work provides a complete neuroanatomical platform for future studies of the adult Drosophila olfactory system.

The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure.

MiDAC is one of seven distinct, large multi-protein complexes that recruit class I histone deacetylases to the genome to regulate gene expression. Despite implications of involvement in cell cycle regulation and in several cancers, surprisingly little is known about the function or structure of MiDAC. Here we show that MiDAC is important for chromosome alignment during mitosis in cancer cell lines. Mice lacking the MiDAC proteins, DNTTIP1 or MIDEAS, die with identical phenotypes during late embryogenesis due to perturbations in gene expression that result in heart malformation and haematopoietic failure. This suggests that MiDAC has an essential and unique function that cannot be compensated by other HDAC complexes. Consistent with this, the cryoEM structure of MiDAC reveals a unique and distinctive mode of assembly. Four copies of HDAC1 are positioned at the periphery with outward-facing active sites suggesting that the complex may target multiple nucleosomes implying a processive deacetylase function.

Renal transplant anastomotic pseudoaneurysms: Case report of open repair and endovascular management.

INTRODUCTION: Anastomotic pseudoaneurysm is one of the rarest vascular complications after renal transplant surgery. Therapeutic options include open surgical repair or endovascular stenting. CASE PRESENTATION: Case 1 had pseudoaneurysm involving external iliac artery and was managed by jump graft to allograft using cadaveric donor iliac arteries and patch angioplasty repair of external iliac artery after excising pseudoaneurysm. Case 2 had undergone orthotopic renal transplant with spleno-renal arterial anastomosis and developed a massive pseudoaneurysm proximal to spleno-renal arterial anastomosis. This patient underwent endovascular stenting preserving allograft vascularity and graft function. Outcome in both patients was successful with normalization of renal function to baseline levels. CONCLUSION: Treatment of renal transplant anastomotic pseudoaneurysms is difficult and associated with high rates of graft loss. Open surgery is the gold standard providing several possibilities for arterial reconstruction preserving graft and limb circulation. Endovascular treatment should be considered in high-risk surgical patients with favorable anatomy.

Impact of grazing dairy steers on winter rye (Secale cereale) versus winter wheat (Triticum aestivum) and effects on meat quality, fatty acid and amino acid profiles, and consumer acceptability of organic beef.

Meat from Holstein and crossbred organic dairy steers finished on winter rye and winter wheat pastures was evaluated and compared for meat quality, fatty acid and amino acid profiles, and consumer acceptability. Two adjacent 4-ha plots were established with winter rye or winter wheat cover crops in September 2015 at the University of Minnesota West Central Research and Outreach Center (Morris, MN). During spring of 2015, 30 steers were assigned to one of three replicate breed groups at birth. Breed groups were comprised of: Holstein (HOL; n = 10), crossbreds comprised of Montbéliarde, Viking Red, and HOL (MVH; n = 10), and crossbreds comprised of Normande, Jersey, and Viking Red (NJV; n = 10). Dairy steers were maintained in their respective replicate breed group from three days of age until harvest. After weaning, steers were fed an organic total mixed ration of organic corn silage, alfalfa silage, corn, soybean meal, and minerals until spring 2016. Breed groups were randomly assigned to winter rye or winter wheat and rotationally grazed from spring until early summer of 2016. For statistical analysis, independent variables were fixed effects of breed, forage, and the interaction of breed and forage, with replicated group as a random effect. Specific contrast statements were used to compare HOL versus crossbred steers. Fat from crossbreds had 13% greater omega-3 fatty acids than HOL steers. Furthermore, the omega-6/3 ratio was 14% lower in fat from crossbreds than HOL steers. For consumer acceptability, steaks from steers grazed on winter wheat had greater overall liking than steers grazed on winter rye. Steak from crossbreeds had greater overall liking than HOL steers. The results suggest improvement in fatty acids and sensory attributes of beef from crossbred dairy steers compared to HOL steers, as well as those finished on winter wheat compared to winter rye.

A unique case of isolated, spontaneous, symptomatic celiac trunk dissection.

Cases of isolated spontaneous celiac trunk dissections have been appearing in the literature more recently with the increased availability of high-resolution computerized tomography angiograms. We report a unique case of this entity. A 48-year-old woman presented with acute abdominal pain that radiated to the back and worsened with breathing. This was diagnosed as a celiac trunk dissection by computerized tomography angiogram. She was treated conservatively with antihypertensive medications, anticoagulants, and opioid medication for pain control.

Identifying patients with AAA with the highest risk following endovascular repair.

INTRODUCTION: It has been demonstrated that endovascular repair of arterial disease results in reduced perioperative morbidity and mortality compared to open surgical repair. The rates of complications and need for reinterventions, however, have been found to be higher than that in open repair. The purpose of this study was to identify the predictors of endograft complications and mortality in patients undergoing endovascular abdominal aortic aneurysm (AAA) repair; specifically, our aim was to identify a subset of patients with AAA whose risk of periprocedure mortality was so high that they should not be offered endovascular repair. METHODS: We undertook a prospective review of patients with AAA receiving endovascular therapy at a single institution. Collected variables included age, gender, date of procedure, indication for procedure, size of aneurysm (where applicable), type of endograft used, presence of rupture, American Society of Anesthesiologists (ASA) class, major medical comorbidities, type of anesthesia (general, epidural, or local), length of intensive care unit (ICU) stay, and length of hospital stay. These factors were correlated with the study outcomes (overall mortality, graft complications, morbidity, and reintervention) using univariate and multivariate logistic regression. RESULTS: A total of 199 patients underwent endovascular AAA repair during the study period. The ICU stay, again, was significantly correlated with the primary outcomes (death and graft complications). In addition, length of hospital stay greater than 3 days, also emerged as a statistically significant predictor of graft complications in this subgroup (P = .024). Survival analysis for patients with AAA revealed that age over 85 years and ICU stay were predictive of decreased survival. Statistical analysis for other subgroups of patients (inflammatory AAA or dissection) was not performed due to the small numbers in these subgroups. CONCLUSIONS: Patients with AAA greater than 85 years of age are at a greater risk of mortality following endovascular repair. In addition, patients who are expected to require postprocedure ICU admission are also at an increased risk of mortality following endovascular repair.

99mTc-WBC scintigraphy with SPECT/CT in the evaluation of arterial graft infection.

OBJECTIVE: The goals of our study were to retrospectively review our experience in using Tc-white blood cell (WBC) single-photon emission computed tomography/computed tomography (SPECT/CT) imaging in the evaluation of possible arterial graft infection and to attempt to establish objective criteria for assessment. METHODS: Eleven Tc-WBC SPECT/CT studies performed for the evaluation of clinically suspected arterial graft infection were retrospectively reviewed and compared with reference outcomes. In an attempt to define objective criteria for interpretation, comparison was also made with background liver and bone marrow activity. RESULTS: When compared with reference outcomes, the subjective scan interpretations showed 6 of 11 true positives (TP), 4 of 11 true negatives (TN), and 1 of 11 false positive (FP). Using the liver as a comparator resulted in 4 of 10 TP, 5 of 10 TN, and 1 of 10 FN. Using the bone marrow as a comparator resulted in 3 of 10 TP, 5 of 10 TN, and 2 of 10 FN. In one patient neither the liver nor the bone marrow was in the field of view. CONCLUSION: These findings suggest a high accuracy for Tc-WBC SPECT/CT in assessing clinically suspected arterial graft infection. Furthermore, the liver may be the best objective comparator for standardized interpretation.

Endovascular repair in traumatic thoracic aortic injuries: comparison with open surgical repair.

PURPOSE: Thoracic endovascular aortic repair (TEVAR) has emerged as an alternative to open surgical repair (OSR) of traumatic thoracic aortic injury (TTAI). Herein immediate and midterm outcomes of TEVAR are compared with those of OSR. MATERIALS AND METHODS: Health records were used to identify patients with TTAI presenting between April 1995 and September 2006. Preoperative patient characteristics, intraoperative variables, procedural costs, and outcomes were recorded. RESULTS: A total of 103 patients were identified. Twenty-two died before treatment, 19 were treated conservatively, 36 received OSR, and 26 received TEVAR. In the OSR group, time from diagnosis to treatment was 8 hours, the 30-day mortality rate was 11.1%, and all deaths occurred intraoperatively. Thoracic nerve injury occurred in four patients (12.5%), pneumonia in 12 (37.5%), temporary renal failure in one (3%), paraparesis in three (9.4%), and paraplegia in five (15.6%). On follow-up (mean, 61 months), postthoracotomy pleural reaction was seen in three cases (9.4%). In the TEVAR group, time to treatment was 38 hours (P < .01) and the 30-day mortality rate was 7.4% with no intraoperative deaths. Pneumonia was seen in two cases (8.3%) and left arm ischemia was seen in two of 17 patients in whom the left subclavian artery was covered. On midterm follow-up (mean, 17 months), there were no graft failures or repeat aortic interventions. Costs of each procedure were initially comparable, but follow-up expenses with TEVAR were $1,284 (Canadian) greater per year. CONCLUSIONS: TEVAR of TTAI is associated with lower perioperative mortality and morbidity rates than OSR, with no significant graft-related complications on midterm follow-up. The study data support the continued use of TEVAR in this context.

Longer term assessment of photodynamic therapy for intimal hyperplasia: a pilot study.

PURPOSE: To determine the potential long term (three or six months) effectiveness of photodynamic therapy (PDT) in reducing intimal hyperplasia in swine. METHODS: Intimal hyperplasia in the abdominal aortae of swine was created by a combination of fat-supplemented diet and balloon catheter injury prior to PDT. Swine were randomly allocated into one of three groups which received either: (i) both drug and light (PDT), (ii) drug only, or (iii) light only. Twenty-four hours following administration of the photosensitizer PHOTOFRIN (porfimer sodium) at 2.5 mg/kg, two distinct 1 cm spots on the posterior wall of the abdominal aorta were illuminated by an argon pumped dye laser tuned to 630 nm for an energy fluence of 120 J/cm2. After three or six months, swine were sacrificed, perfusion fixed, and had their aortae removed for light and electron microscopy. RESULTS: Intimal hyperplasia reduction following PDT persisted for the three or six months follow up period. Experimental vessels receiving PDT showed a 26.0+/-4.5% ( n = 2, ie. four spots) and 30.8+/-5.4% ( n = 1, ie. two spots) smaller percent intimal area after three or six months of recovery, respectively. Control groups receiving either light or drug only showed less than a 6% difference in percent intimal area. Medial and adventitial layers were unaffected in all groups. Electron microscopy demonstrated that the endothelium or endothelial-like cells had regenerated in both the posterior and adjacent areas of the abdominal aortae with no clear difference between them. CONCLUSIONS: These findings suggest that PDT may be beneficial in reducing intimal hyperplasia for up to three or six months in swine.

Xerostomia: clinical aspects and treatment.

Xerostomia or dry mouth is a condition that is frequently encountered in dental practice. The most common cause is the use of certain systemic medications, which make the elderly at greater risk because they are usually more medicated. Other causes include high doses of radiation and certain diseases such as Sjogren's syndrome. Xerostomia is associated with difficulties in chewing, swallowing, tasting or speaking. This results in poor diet, malnutrition and decreased social interaction. Xerostomia can cause oral discomfort, especially for denture wearers. Patients are at increased risk of developing dental caries. A thorough intraoral and extra-oral clinical examination is important for diagnosis. Treatment may include the use of salivary substitutes (Biotene), salivary stimulants such as pilocarpine, ongoing dental care, caries prevention, a review of the current prescription drug regimen and possible elimination of drugs having anticholinergic effects. Because of the ageing population, and the concomitant increase in medicated individuals, dentists can expect to be presented with xerostomia in an increasing number of patients in the coming years and therefore should be familiar with its diagnosis and treatment. Therefore, the purpose of this review is to outline for clinicians the common aetiologies, clinical identification, and routine therapeutic modalities available for individuals with xerostomia.

Risk indicators for periodontal disease in a remote Canadian community--a dental practice-based study.

OBJECTIVES: The purpose of this cross-sectional study was to identify risk markers and risk indicators for periodontal attachment loss in a remote Canadian community. Of special interest was the association between smoking and periodontal disease experience. METHODS: Data were collected from a convenience sample of 187 adult patients attending a dental office in a rural community located in Northern Ontario. Information was obtained via a questionnaire and a periodontal examination. The questionnaire included the use of dental services, self-care behaviors, general health status, smoking, and personal characteristics. Periodontal health was assessed using the mean periodontal attachment loss (MPAL), measured at two sites on all remaining teeth and the proportions of sites examined with loss of 2 mm or more and 5 mm or more. Plaque scores and measures of the number of missing teeth also were obtained. The relationships between mean periodontal attachment loss, the proportion of sites with 5 mm or more of loss and independent variables such as age, sex, current smoking status, mean tooth plaque scores, flossing frequency, and regularity of preventive dental visits were examined in bivariate and multivariate analyses. RESULTS: The data revealed a mean periodontal attachment loss of 3.9 mm (SD=1.5). The mean proportion of sites examined with loss of 2 mm or more was 0.89 and the mean proportion with loss of 5 mm or more was 0.35. In linear regression analysis, plaque scores, the number of missing teeth, age, current smoking status, regularity of dental visits, and flossing frequency had statistically significant independent effects and explained 60.0 percent of the variance in mean periodontal attachment loss. Just over 30 percent of subjects had severe periodontal disease, defined as 50 percent or more of sites examined with loss of 5 mm or more. In logistic regression analysis, missing teeth, dental visiting, smoking status, age, and flossing frequency had significant independent effects. The strongest association observed was with smoking, which had an odds ratio of 6.3. The logistic regression model correctly predicted 64.3 percent of cases with severe disease. CONCLUSIONS: The data indicate that the periodontal health of these patients is poor. Risk indicators or markers of poor periodontal health in the population studied included missing teeth, plaque scores, age, current smoking status, regularity of dental visits, and flossing frequency. This supports previous findings that behavioral factors play an important role in periodontal disease.