A survey of digitized data from U.S. fish collections in the iDigBio data aggregator.
Recent changes in institutional cyberinfrastructure and collections data storage methods have dramatically improved accessibility of specimen-based data through the use of digital databases and data aggregators. This analysis of digitized fish collections in the U.S. demonstrates how information from data aggregators, in this case iDigBio, can be extracted and analyzed. Data from U.S. institutional fish collections in iDigBio were explored through a strictly programmatic approach using the ridigbio package and fishfindR web application. iDigBio facilitates the aggregation of collections data on a purely voluntary fashion that requires collection staff to consent to sharing of their data. Not all collections are sharing their data with iDigBio, but the data harvested from 38 of the 143 known fish collections in the U.S. that are in iDigBio account for the majority of fish specimens housed in U.S. collections. In the 22 years since publication of the last survey providing information on these 38 collections, 1,219,168 specimen records (lots), 15,225,744 specimens, 3,192 primary types, and 32,868 records of secondary types have been added. This is an increase of 65.1% in the number of cataloged records and an increase of 56.1% in the number of specimens. In addition to providing specimen-based data for research, education, and various outreach activities, data that are accessible via data aggregators can be used to develop accurate, up-to-date reports of information on institutional collections. Such reports present collections data in an organized and accessible fashion and can guide targeted efforts by collections personnel to meet discipline-specific needs and make data more transparent to downstream users. Data from this survey will be updated and published regularly in a dynamic web application that will aid collections staff in communicating collections value while simultaneously giving stakeholders a way to explore collections holdings as they relate to the institutions in which they are housed. It is through this resource that collections will be able to leverage their data against those of similar collections to aid in the procurement of financial and institutional support.


Stem cell therapy in osteoarthritis: a step too far?
Osteoarthritis (OA) is the most common joint disease and, until now, no effective medical treatment has been developed, apart from total joint replacement in end-stage disease. Since mesenchymal stem cells (MSC) can on one hand be the source of newly formed cartilage, and on the other hand inhibit inflammation with their immunomodulatory capacities, these cells are, on a theoretical basis, ideal for the treatment of OA. As a result, MSC-based treatments for OA patients are currently offered worldwide. However, the effectiveness of this treatment and the potential associated risks are not well known. To develop MSC-based treatment of OA into a generally accepted, clinically effective and safe cure, extensive studies have to be performed in controlled experimental and clinical settings. Stem cell therapy is a remedy with the potential for a great future; however, this outlook could be jeopardized if this treatment is introduced too early into clinical practice.


Update on recommendations for use of herpes zoster vaccine.
Herpes zoster vaccine (Zostavax [Merck & Co., Inc.]) was licensed in 2006 and recommended by the Advisory Committee on Immunization Practices (ACIP) in 2008 for prevention of herpes zoster (shingles) and its complications among adults aged ≥60 years. The Food and Drug Administration (FDA) approved the use of Zostavax in 2011 for adults aged 50 through 59 years based on a large study of safety and efficacy in this age group. ACIP initially considered the use of herpes zoster vaccine among adults aged 50 through 59 years in June 2011, but declined to recommend the vaccine in this age group, citing shortages of Zostavax and limited data on long-term protection afforded by herpes zoster vaccine. In October 2013, ACIP reviewed the epidemiology of herpes zoster and its complications, herpes zoster vaccine supply, short-term vaccine efficacy in adults aged 50 through 59 years, short- and long- term vaccine efficacy and effectiveness in adults aged ≥60 years, an updated cost-effectiveness analysis, and deliberations of the ACIP herpes zoster work group, all of which are summarized in this report. No vote was taken, and ACIP maintained its current recommendation that herpes zoster vaccine be routinely recommended for adults aged ≥60 years. Meeting minutes are available at http://www.cdc.gov/vaccines/acip/meetings/meetings-info.html.


Large-scale generation and analysis of expressed sequence tags from porcine ovary.
One method to identify the factors that control ovarian function is to characterize the genes that are expressed in ovary. In the present study, cDNA libraries from fetal, neonatal, and prepubertal porcine ovaries, pubertal ovaries on different days of the estrous cycle (Days 0 [follicle], 5, and 12 [follicle and corpus luteum]), and follicles isolated from weaned sows (diameter, 2, 4, 6, and 8 mm) were constructed and sequenced. A total of 22 176 cDNAs were sequenced, of which 15 613 were of sufficient quality for clustering. Clustering of cDNAs resulted in 8507 contigs, 6294 (74%) of which were comprised of a single sequence. Sixty-eight percent of the contigs had consensus sequences that were homologous to existing Tentative Consensus (TC) sequences or mature transcripts (ET) in The Institute for Genomic Research Porcine Gene Index. The consensus sequences were classified according to the Gene Ontology Index. Most cDNA-encoded proteins were components of the nucleus, ribosome, or mitochondrion. The proteins primarily functioned in binding, catalysis, and transport. Nearly 75% of the proteins were involved in metabolism and cell growth and/or maintenance. Analysis of the cDNA frequency across different libraries demonstrated differential gene expression within different-size follicles, between follicles and corpora lutea, and across developmental time-points. The expression of selected genes (analyzed by ribonuclease protection assay and Northern blotting) was consistent with the frequency of their respective cDNA in the individual libraries. This porcine ovary unigene set will be useful for identifying factors and mechanisms controlling ovarian follicular development in a variety of species.


Immunobiomarkers in small cell lung cancer: potential early cancer signals.
We investigated the presence of autoantibodies as immunobiomarkers to a panel of tumor-associated antigens in a group of individuals with small cell lung cancer (SCLC), a disease group that has a poor overall cancer prognosis and therefore may benefit most from early diagnosis. Sera from 243 patients with confirmed SCLC and normal controls matched for age, sex, and smoking history were analyzed for the presence of these early immunobiomarkers (i.e., autoantibodies to p53, CAGE, NY-ESO-1, GBU4-5, Annexin I, SOX2, and Hu-D) by ELISA. Autoantibodies were seen to at least 1 of 6 antigens in 55% of all the SCLC patients' sera tested, with a specificity of 90% compared with controls. Using a higher assay cutoff to achieve a specificity of 99%, autoantibodies were still detectable in 42% of SCLC patients (receiver operator characteristic area under the curve = 0.76). There was no significant difference in sensitivity when analyzed by stage of the cancer or by patient age or gender. The frequency of autoantibodies to individual antigens varied, ranging from 4% for GBU4-5 to 35% for SOX2. Levels of Annexin I autoantibodies were not elevated in patients with SCLC. Antibodies were also detected in 4 separate patients whose sera were taken up to 3 months before tumor diagnosis. The presence of an autoantibody to one or more cancer-associated antigens may provide an important addition to the armamentarium available to the clinician to aid early detection of SCLC in high-risk individuals.


The action of streptomycin in a mutant of Escherichia coli with increased sensitivity to the antibiotic.
A mutant of Escherichia coli with increased sensitivity to streptomycin has been studied. This strain differed from a normal str(s) strain in that streptomycin produced inhibition of protein synthesis and loss of viability with almost no lag period. Chloramphenicol protected a normal str(s) strain but not the mutant against the bactericidal action of streptomycin. The results obtained support the idea that access of streptomycin to its site of action in a normal cell is restricted, and that this restriction, which is much less effective in the mutant, probably involves a permeability barrier. Comparison of the inhibition of protein synthesis by streptomycin with concomitant changes in the distribution of polyribosomes in both strains suggested that the antibiotic can directly inhibit the translation of mRNA.


Extensive evaluation of the instrumentation laboratory IL test D-Dimer immunoturbidimetric assay on the ACL 9000 determines the D-Dimer cutoff value for reliable exclusion of venous thromboembolism.
The clinical diagnosis of venous thromboembolism (VTE), which includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), is often difficult and requires a number of imaging tests plus clinical assessment. It is now accepted that pretest clinical probability of disease plus a sensitive, quantitative D-Dimer assay can be used to reliably exclude VTE. In design of diagnostic strategies for VTE it is recommended that the D-Dimer assay be evaluated for sensitivity and specificity in well-designed, blinded studies using a cohort of patients for whom the assay will ultimately be used. Therefore we evaluated the IL Test D-Dimer on the ACL 9000 automated coagulation analyzer for its sensitivity and specificity in the diagnosis of VTE. A total of 512 patients admitted to the emergency department of Providence Hospital with suspected VTE were included in the dataset. Our aim was to find the clinically meaningful IL Test D-Dimer cutoff value, which would give us 100% sensitivity and the highest possible specificity for exclusion of VTE. Patients were categorized clinically into low, medium, or high pretest probability and had computed tomographic and/or ventilation-perfusion scans for investigation of PE and ultrasound studies for suspected DVT, with the laboratory blinded to the clinical findings. Of the 511 patients, 28 (5.4%) had confirmed VTE (PE and/or DVT) based on imaging and clinical studies. Applying receiver operating characteristic curve (ROC) analysis, we determined from our study that a cutoff value of 237 ng/mL IL Test D-Dimer gave a 100% sensitivity with a specificity of 38% for detection of VTE. The findings demonstrate that a diagnostic strategy using the IL Test D-Dimer assay as a first-line test in combination with pretest probability is safe and can be used in patients with suspected VTE. In conclusion, patient analysis results indicating low or moderate pretest probability for VTE and a negative IL Test D-Dimer (cutoff value of 237 ng/mL) assay result on the ACL 9000 reliably exclude VTE (both PE and DVT). We expect that inclusion of the rapid IL Test D-Dimer assay for assessment of suspected VTE in the emergency department at Providence will result in improved patient diagnosis and therapy, reduction in unnecessary radiological investigations, and lowering of overall costs associated with investigation of patients suspected of having VTE disease.


Aerobic and anoxic biodegradation of benzoate: stability of biodegradative capability under endogenous conditions.
Aromatic organic compounds are degraded by different enzyme systems under aerobic and anoxic conditions. This raises the question of how bacteria in biological nitrogen removal processes, which cycle bacteria between aerobic and anoxic environments, regulate their enzyme systems for degrading aromatic compounds. As a first step in answering that question, mixed microbial communities were grown on benzoate as sole carbon source in chemostats under fully aerobic and fully anoxic (nitrate as the electron acceptor) conditions and tested for their ability to degrade benzoate in batch reactors after exposure to aerobic or anoxic conditions in the absence of substrate. Aerobically grown biomass retained its ability to degrade benzoate without loss of activity after endogenous exposure to aerobic conditions for up to 8 h. However, when exposed to anoxic conditions, the biomass rapidly lost its aerobic benzoate degrading activity, retaining less than 20% of the initial activity after 8 h. Similarly, anoxically grown biomass retained its ability to degrade benzoate without loss of activity after endogenous exposure to anoxic conditions for up to 8 h. However, when anoxically grown biomass was exposed to aerobic conditions, only 20% of its initial activity was lost in the first 2 h, after which the remaining activity was retained for up to 8 h. Similar experiments with pyruvate showed that the 20% loss of activity was not due to loss of denitrifying enzymes, suggesting that it was due to loss of catabolic enzymes.


Evaluation of Vaso-occlusive Crisis Management With Patient-Controlled Analgesia in Children With Sickle Cell Disease Requiring Hospitalization.
The aim of this study was to review the use of patient-controlled analgesia (PCA) in sickle cell disease (SCD) for pediatric patients with vaso-occlusive crisis (VOC) in our institution and to compare the effect of early vs late PCA start on pain relief and LOS. This retrospective study included all pediatric patients treated with PCA for a severe VOC from 2010 to 2016. "Early-PCA" was defined as start of PCA within 48 hours of arrival. Time to reach adequate analgesia was defined as the time to reach 2 consecutive pain scores less than 5/10 at 4-hour interval. During the study period, 46 patients presented 87 episodes of VOC treated with PCA. Sixty-three patients with VOC were treated with Early-PCA and 24 with Late-PCA. Both groups were comparable except for median pain score at admission; the Early-PCA group had higher scores: 9.0/10 vs 7.0/10. Time to reach adequate analgesia could be evaluated only in a subset of patients (n = 32) but was shorter in the Early-PCA group with a median difference of 41.0 hours (95% CI -82.0 to -6.0). Early-PCA was associated with a median reduction in LOS of 3.4 days (95% CI -4.9 to -1.9). There was no difference between the 2 groups in terms of side effects and occurrence of acute chest syndrome during hospitalization. In this study, a reduced time to reach adequate analgesia and LOS was noted in the Early-PCA group for severe VOC. A prospective study is required to confirm these results.


Intention of dog owners to participate in rabies control measures in Flores Island, Indonesia.
The success of a rabies control strategy depends on the commitment and collaboration of dog owners. In this study the theory of planned behaviour (TPB) was used to identify the factors, which are associated with the intention of dog owners to participate in rabies control measures in the Manggarai and Sikka regencies of Flores Island, Indonesia. Questionnaires were administered to 450 dog owners from 44 randomly selected villages in the two regencies. Ninety-six percent of the dog owners intended to participate in a free-of-charge vaccination campaign. The intention decreased to 24% when dog owners were asked to pay a vaccination fee equal to the market price of the vaccine (Rp 18.000 per dose=US$2). Approximately 81% of the dog owners intended to keep their dogs inside their house or to leash them day and night during a period of at least three months in case of an incidence of rabies in the dog population within their village. Only 40% intended to cull their dogs in case of a rabies incident within their village. Using multivariable logistic regression analysis, the attitude item 'vaccinating dogs reduces rabies cases in humans', and the perceived behavioural control items 'availability of time' and 'ability to confine dogs' were shown to be significantly associated with the intention to participate in a free-of-charge vaccination campaign. The attitude item 'culling dogs reduces rabies cases in humans' was significantly associated with the intention to participate in a culling measure. The attitude item 'leashing of dogs reduces human rabies cases' and perceived behavioural controls 'availability of time' and 'money to buy a leash' were associated with the intention to leash dogs during a rabies outbreak. As the attitude variables were often significantly associated with intention to participate in a rabies control measure, an educational rabies campaign focusing on the benefit of rabies control measures is expected to increase the intention of dog owners to participate in future rabies control measures. The significant association between perceived behavioural controls and intention to participate points to other relevant policy interventions. Providing dog owners with a skill to confine dogs and creating a subsidy program for the vaccine and leash costs, by involving non-governmental organisations or charitable organisations, may be useful policy interventions. Moreover appropriate time management, such as implementing vaccination campaigns during the weekend, could increase the intention to participate in vaccination campaigns, by relaxing the constraints on the availability of dog owners' time.


The SON RNA splicing factor is required for intracellular trafficking structures that promote centriole assembly and ciliogenesis.
Control of centrosome assembly is critical for cell division, intracellular trafficking, and cilia. Regulation of centrosome number occurs through the precise duplication of centrioles that reside in centrosomes. Here we explored transcriptional control of centriole assembly and find that the RNA splicing factor SON is specifically required for completing procentriole assembly. Whole genome mRNA sequencing identified genes whose splicing and expression are affected by the reduction of SON, with an enrichment in genes involved in the microtubule (MT) cytoskeleton, centrosome, and centriolar satellites. SON is required for the proper splicing and expression of CEP131, which encodes a major centriolar satellite protein and is required to organize the trafficking and MT network around the centrosomes. This study highlights the importance of the distinct MT trafficking network that is intimately associated with nascent centrioles and is responsible for procentriole development and efficient ciliogenesis.


The specificity of bovine spleen cathepsin S. A comparison with rat liver cathepsins L and B.
The peptide-bond-specificity of bovine spleen cathepsin S in the cleavage of the oxidized insulin B-chain and peptide methylcoumarylamide substrates was investigated and the results are compared with those obtained with rat liver cathepsins L and B. Major cleavage sites in the oxidized insulin B-chain generated by cathepsin S are the bonds Glu13-Ala14, Leu17-Val18 and Phe23-Tyr26; minor cleavage sites are the bonds Asn3-Gln4, Ser9-His10 and Leu15-Tyr16. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L and cathepsin N. Larger differences are discernible in the reaction with synthetic peptide substrates. Cathepsin S prefers smaller neutral amino acid residues in the subsites S2 and S3, whereas cathepsin L efficiently hydrolyses substrates with bulky hydrophobic residues in the P2 and P3 positions. The results obtained from inhibitor studies differ somewhat from those based on substrates. Z-Phe-Ala-CH2F (where Z- represents benzyloxycarbonyl-) is a very potent time-dependent inhibitor for cathepsin S, and inhibits this proteinase 30 times more efficiently than it does cathepsin L and about 300 times better than it does cathepsin B. By contrast, the peptidylmethanes Z-Val-Phe-CH3 and Z-Phe-Lys(Z)-CH3 inhibit competitively both cathepsin S and cathepsin L in the micromolar range.


Early Disassembly of Femoral Head and Neck Components After Total Hip Arthroplasty Revision.
Modular femoral and acetabular components are frequently used in hip arthroplasty. Although the use of modular components offers many advantages, the increased number of components leads to a high risk of disassembly. Disassociation of the femoral head and neck is a rarely reported complication in the literature. This case report depicts a patient with non-traumatic early disassociation of the femoral head and neck components following total hip revision arthroplasty. Femoral head-neck disassembly in early postoperative period may occur due to manufacturing error or insufficient impaction. If sufficient impaction is thought to be achieved, manufacturing errors should be kept in mind as potential underlying reasons for femoral head-neck dissociation.


Single-stage hybrid total arch replacement for extended arch aneurysms.
The therapeutic strategy for extended aortic arch aneurysms remains controversial and has changed substantially since thoracic endovascular aortic repair was introduced. We applied single-stage hybrid (s-hybrid) total arch replacement (TAR), which involved ascending aorta replacement and debranching of arch vessels, consecutively performed with thoracic endovascular aortic repair for extended arch aneurysms. The aim of this study was to investigate the short-term results of s-hybrid TAR and to clarify the benefit of this method. We reviewed the operative results of 62 patients who underwent elective s-hybrid TAR or conventional TAR (c-TAR) through the median approach from 2008 to 2017. We used the s-hybrid approach in 15 patients and the c-TAR approach in 47 patients. In both groups, axillary arterial perfusion and selective antegrade cerebral perfusion under moderate hypothermia were applied for brain protection. We compared the perioperative outcomes of the two groups. We completed s-hybrid TAR in all 15 patients with extended aneurysms. The s-hybrid group required shorter times for myocardial ischemia, selective antegrade cerebral perfusion, and circulatory arrest of the lower body compared with the c-TAR group. The patients with complicated recurrent laryngeal nerve palsy and long ventilation support times were fewer in the s-hybrid group. No patient had substantial endoleaks or permanent paraplegia. The in-hospital mortality rates were 6.7% in the s-hybrid group and 0% in the c-TAR group. The s-hybrid TAR has the same or better perioperative outcomes compared with the c-TAR approach. For extended aneurysms, this technique could resolve the problem of respiratory failure induced by left thoracotomy and also resolve the problem of rupture during the waiting period in staged surgery.


Strong photosynthetic acclimation and enhanced water-use efficiency in grassland functional groups persist over 21 years of CO2 enrichment, independent of nitrogen supply.
Uncertainty about long-term leaf-level responses to atmospheric CO2 rise is a major knowledge gap that exists because of limited empirical data. Thus, it remains unclear how responses of leaf gas exchange to elevated CO2 (eCO2 ) vary among plant species and functional groups, or across different levels of nutrient supply, and whether they persist over time for long-lived perennials. Here, we report the effects of eCO2 on rates of net photosynthesis and stomatal conductance in 14 perennial grassland species from four functional groups over two decades in a Minnesota Free-Air CO2 Enrichment experiment, BioCON. Monocultures of species belonging to C3 grasses, C4 grasses, forbs, and legumes were exposed to two levels of CO2 and nitrogen supply in factorial combinations over 21 years. eCO2 increased photosynthesis by 12.9% on average in C3 species, substantially less than model predictions of instantaneous responses based on physiological theory and results of other studies, even those spanning multiple years. Acclimation of photosynthesis to eCO2 was observed beginning in the first year and did not strengthen through time. Yet, contrary to expectations, the response of photosynthesis to eCO2 was not enhanced by increased nitrogen supply. Differences in responses among herbaceous plant functional groups were modest, with legumes responding the most and C4 grasses the least as expected, but did not further diverge over time. Leaf-level water-use efficiency increased by 50% under eCO2 primarily because of reduced stomatal conductance. Our results imply that enhanced nitrogen supply will not necessarily diminish photosynthetic acclimation to eCO2 in nitrogen-limited systems, and that significant and consistent declines in stomatal conductance and increases in water-use efficiency under eCO2 may allow plants to better withstand drought.


IL-1β dominates the promucin secretory cytokine profile in cystic fibrosis.
Cystic fibrosis (CF) lung disease is characterized by early and persistent mucus accumulation and neutrophilic inflammation in the distal airways. Identification of the factors in CF mucopurulent secretions that perpetuate CF mucoinflammation may provide strategies for novel CF pharmacotherapies. We show that IL-1β, with IL-1α, dominated the mucin prosecretory activities of supernatants of airway mucopurulent secretions (SAMS). Like SAMS, IL-1β alone induced MUC5B and MUC5AC protein secretion and mucus hyperconcentration in CF human bronchial epithelial (HBE) cells. Mechanistically, IL-1β induced the sterile α motif-pointed domain containing ETS transcription factor (SPDEF) and downstream endoplasmic reticulum to nucleus signaling 2 (ERN2) to upregulate mucin gene expression. Increased mRNA levels of IL1B, SPDEF, and ERN2 were associated with increased MUC5B and MUC5AC expression in the distal airways of excised CF lungs. Administration of an IL-1 receptor antagonist (IL-1Ra) blocked SAMS-induced expression of mucins and proinflammatory mediators in CF HBE cells. In conclusion, IL-1α and IL-1β are upstream components of a signaling pathway, including IL-1R1 and downstream SPDEF and ERN2, that generate a positive feedback cycle capable of producing persistent mucus hyperconcentration and IL-1α and/or IL-1β-mediated neutrophilic inflammation in the absence of infection in CF airways. Targeting this pathway therapeutically may ameliorate mucus obstruction and inflammation-induced structural damage in young CF children.


A spliced antigenic peptide comprising a single spliced amino acid is produced in the proteasome by reverse splicing of a longer peptide fragment followed by trimming.
Peptide splicing is a novel mechanism of production of peptides relying on the proteasome and involving the linkage of fragments originally distant in the parental protein. Peptides produced by splicing can be presented on class I molecules of the MHC and recognized by CTLs. In this study, we describe a new antigenic peptide, which is presented by HLA-A3 and comprises two noncontiguous fragments of the melanoma differentiation Ag gp100(PMEL17) spliced together in the reverse order to that in which they appear in the parental protein. Contrary to the previously described spliced peptides, which are produced by the association of fragments of 3-6 aa, the peptide described in this work results from the ultimate association of an 8-aa fragment with a single arginine residue. As described before, peptide splicing takes place in the proteasome by transpeptidation involving an acyl-enzyme intermediate linking one of the peptide fragment to a catalytic subunit of the proteasome. Interestingly, we observe that the peptide causing the nucleophilic attack on the acyl-enzyme intermediate must be at least 3 aa long to give rise to a spliced peptide. The spliced peptide produced from this reaction therefore bears an extended C terminus that needs to be further trimmed to produce the final antigenic peptide. We show that the proteasome is able to perform the final trimming step required to produce the antigenic peptide described in this work.


Late-onset Tay-Sachs disease.
We discuss the assessment and differential diagnoses of a young adult Hungarian man with a 1-year history of a progressive and symmetric amyotrophic lateral sclerosis-like syndrome, along with irregular action tremor and stimulus-sensitive myoclonus of the arms. MR scan of the brain showed isolated cerebellar atrophy and formal neuropsychometric testing identified significant subclinical deficits in attention, processing speed and memory. We suspected a form of GM2 gangliosidosis, and white cell enzyme analysis showed markedly reduced enzymatic activity of β-hexosaminidase A. Genetic testing subsequently revealed two heterozygous pathogenic mutations in the HEXA gene (c.1499delT p.(Leu500fs) and c.805G>A p.(Gly269Ser)), confirming the very rare diagnosis of adult-onset Tay-Sachs disease.


Identification and functional characterization of the putative members of the CTDK-1 kinase complex as regulators of growth and development in Aspergillus nidulans and Aspergillus fumigatus.
Asexual spores are the main vehicle used by fungi to disperse to new niches. The Eurotiomycete Aspergillus nidulans is the main reference for the study of the genetic/molecular control of asexual development. In this species, Flb proteins control the expression of the master gene brlA, and thus, loss-of-function mutations in flb (upstream developmental activation [UDA]) genes block brlA transcription and, consequently, the production of conidiophores, the structures bearing asexual spores known as conidia. However, the aconidial phenotype of specific flb mutants, such as that of the ΔflbB strain, is reverted under salt-stress conditions. Previously, we generated a collection of second-site mutants of ΔflbB unable to conidiate on culture medium supplemented with NaH2PO4 (0.65 M). Here, we identified a Gly347Stop mutation within flpA as responsible for the FLIP57 phenotype and characterized the role of the putative cyclin FlpA and the remaining putative components of the C-terminal domain kinase-1 (CTDK-1) complex in A. nidulans and Aspergillus fumigatus. FlpA, Stk47, and FlpB are necessary (i) for timely germination, (ii) in the transition from metulae to phialides (the cells generating conidia) during conidiophore development, and (iii) for the development of sexual structures (cleistothecia) in A. nidulans. The three proteins are nuclear, and the nucleoplasmic localization of Stk47 depends on the activity of FlpA, which correlates with the retention of Stk47 by FlpA in pull-down assays. Overall, this work links the putative CTDK-1 complex of aspergilli with growth and developmental control. Identification of a mutation in flpA as inhibitor of conidiation in A. nidulans and functional characterization of FlpA, Stk47 and FlpB as putative members of the C-terminal domain kinase complex CTDK-1 in A. nidulans and A. fumigatus.IMPORTANCEAspergillus fumigatus has been included by the World Health Organization in the priority list of fungal pathogens because (i) it causes 90% of invasive aspergillosis cases, with a high mortality rate, and (ii) infections are becoming increasingly resistant to azole antifungals. A. nidulans is an opportunistic pathogen and a saprotroph which has served during the last 80 years as a reference system for filamentous fungi. Here, we characterized the role in morphogenesis and development of the putative transcriptional cyclin/kinase complex CTDK-1 in both aspergilli. The null mutants of the corresponding genes showed delayed germination, aberrant conidiophore development, and inhibition of cleistothecia production. While in higher eukaryotes this complex is formed only by a cyclin and a kinase, the fungal complex would incorporate a fungal-specific third component, FlpB, which would enable the interaction between the kinase (Stk47) and the cyclin (FlpA) and may be used as a target for antifungals.


The hippocampus: part of an interactive posterior representational system spanning perceptual and memorial systems.
The hippocampus has frequently been viewed as a core long-term memory structure, separate from brain structures mediating other cognitive functions such as working memory and perception. Much the same is true of other medial temporal lobe (MTL) structures such as the parahippocampal gyrus and the perirhinal cortex. Recent evidence suggests, instead, that these latter structures are also important for certain perceptual functions, leading many to propose a representational account of MTL that defines its functions in terms of what is being represented, rather than how long this representation lasts, or which psychological function is being invoked. We discuss a common framework within which perception and memory are seen as involving many, if not most, of the structures in the ventral representational stream, critically dependent on extensive feedforward and feedback processes. A variety of perceptual and memorial phenomena are discussed within this framework, and it is concluded that the hippocampus is in many ways like its neighbors in the MTL, yet has some distinct properties that account for its unique role in episodic memory.


Carbon dioxide induced disassembly of gap-junctional plaques.
When sheep ovarian follicle cells are maintained in an O2-rich environment their cells are metabolically coupled, as monitored by observing the exchange of [3H]choline; choline metabolites were detected up to 4 mm from the explant under these control conditions. When the tissues were placed in a CO2-rich environment the cells became uncoupled physiologically and choline metabolites were no longer exchanged. The cells in these two states, coupled and uncoupled, were examined by freeze-fracture. The initial controls were characteristic of ovarian follicular tissue exhibiting large macular plaques with regular outlines composed of PF intra-membranous particles (IMPs), which were arrayed in rows with IMP-free aisles. With uncoupling, the junctional plaques became irregular at the periphery, they became loosely packed and IMPs began to 'stream' out laterally across the membrane. Ultimately they were reduced to negligible IMP clusters or free IMPs. Analyses of the IMPs with an image analyser confirmed that in the uncoupled state the gap-junctional IMPs were dispersed over the membranes. On return to an O2-rich environment, the cells became recoupled as monitored by physiological criteria and in freeze-fracture replicas IMPs reclustered into macular, albeit smaller, plaques. These results support the contention that with uncoupling, gap-junctional particles are free to move and hence may become dispersed over the membrane face, with the possibility of being re-utilized to form junctions anew when conditions for coupling are re-established.


Chemical phosphorus removal to extremely low levels: experience of two plants in the Washington, DC area.
Chemical phosphorus removal using metal (iron and aluminium) salts is frequently used to control effluent soluble phosphorus levels in wastewater treatment plants. In the Washington DC area effluent phosphorus requirements are extremely stringent to protect the Chesapeake Bay. Full-scale data from two plants in the area were analysed to establish phosphate behaviour in the presence of iron. Titration experiments and mathematical modelling were performed to determine the role of ferric phosphate and hydroxide precipitation and other mechanisms that may potentially be involved in phosphorus removal. Iron addition is described in the model using a chemical equilibrium approach extended with surface charges and adsorption. The model verifies key observations from full-scale data: (a) extremely low orthophosphate levels can be achieved over a wide range of pH values, (b) a mixture of ferric phosphate and ferric hydroxide precipitate is forming with the hydroxide acting as sorbent, (c) molar ratios of Fe/P (iron dosed to phosphate removed) vary widely (1.0-3.9) based on the technology used and residual phosphate levels. The model will be a useful tool for engineers to optimise preliminary, simultaneous and tertiary P removal, both for design and plant operation.


Cerebral processing of auditory stimuli in patients with irritable bowel syndrome.
To determine by brain functional magnetic resonance imaging (fMRI) whether cerebral processing of non-visceral stimuli is altered in irritable bowel syndrome (IBS) patients compared with healthy subjects. To circumvent spinal viscerosomatic convergence mechanisms, we used auditory stimulation, and to identify a possible influence of psychological factors the stimuli differed in their emotional quality. In 8 IBS patients and 8 controls, fMRI measurements were performed using a block design of 4 auditory stimuli of different emotional quality (pleasant sounds of chimes, unpleasant peep (2000 Hz), neutral words, and emotional words). A gradient echo T2*-weighted sequence was used for the functional scans. Statistical maps were constructed using the general linear model. To emotional auditory stimuli, IBS patients relative to controls responded with stronger deactivations in a greater variety of emotional processing regions, while the response patterns, unlike in controls, did not differentiate between distressing or pleasant sounds. To neutral auditory stimuli, by contrast, only IBS patients responded with large significant activations. Altered cerebral response patterns to auditory stimuli in emotional stimulus-processing regions suggest that altered sensory processing in IBS may not be specific for visceral sensation, but might reflect generalized changes in emotional sensitivity and affective reactivity, possibly associated with the psychological comorbidity often found in IBS patients.


[Structural and electrical characteristics of myocardial remodeling in pulmonary diseases with obstructive and restrictive ventilation disorders].
Myocardial changes were studied in 239 patients with different diseases of the lungs associated with obstructive (84 patients) and restrictive (155 patients) ventilation disorders and in 109 healthy subjects (control group). Structural and electrical indices of the myocardium taken at echo- and vectorcardiography in patients with chronic pulmonary diseases differed from those of healthy subjects, depended on the type and severity of the ventilation disorders. Remodeling of the myocardium in obstructive ventilation disorders is accompanied by a moderate staged enlargement of atrial cavities, right ventricle, thickening of the walls of both ventricles in enhanced electric activity of all the heart compartment. The restrictive ventilation disorders are characterized by an early significant enlargement of both atria's cavities, and of both ventricles with maximal thickening of ventricular walls. Electric activity of the heart rose maximally at the initial stage, later it lowered. Variants of myocardial remodeling in abnormal external respiration were determined by differences in compensatory heart reactions. In the obstructive type, heart remodeling had better compensatory opportunities which manifested itself at all the stages of the ventilatory disorders. In the restrictive type, effective compensatory hyperfunction of the heart was seen only at the first stage of ventilatory disorders, at later stages it weakened.


Choosing to encourage or discourage: perceived effectiveness of prescriptive versus proscriptive messages.
The estimated cost of repairing damage caused to recreational sites annually is in the hundreds of millions of dollars. These depreciative activities also reduce the quality of visitors' experiences in the damaged areas. Indirect methods, such as visitor education through brochures and signs, continue to be the least controversial management approaches to depreciative acts. Yet, the literature on studies examining the most effective message presentations remains sparse. A survey mailed to randomly selected National Association for Interpretation members assessed the perceived effectiveness of communications that encouraged positive conduct (prescriptive messages) versus those that discouraged negative conduct (proscriptive messages) in wildland and urban settings. Almost invariably, respondents viewed the encouragement-based prescriptive messages as more effective than the discouragement-based proscriptive messages. This finding stands in sharp contrast to an earlier study that discovered a preponderance of proscriptive versus prescriptive messages on signs in both wildland and urban recreational environments. Thus, although the great majority of interpreters see the encouragement of positive conduct as more effective, in practice, messages on signs are much more likely to discourage negative conduct. Reasons for this discrepancy are considered.


What sample sizes are required for pooling surgical case durations among facilities to decrease the incidence of procedures with little historical data?
Better predictions of each case's duration would reduce operating room labor costs and patient waiting times. A barrier to using historical case duration data to predict the duration of future cases is the absence for some cases of previous data for the same scheduled procedure from the same facility. The authors examined sample size requirements for pooling case duration data from several facilities to create a 90% chance of having case duration data for almost all procedures. Four academic medical centers provided data, totaling 200,401 cases classified by the scheduled Current Procedural Terminology codes. The 12% of cases in which procedures occurred once or twice accounted for 79% of procedures or combinations of procedures. When a procedure was being performed for the first time at a facility, that same procedure had been performed previously at least once at one or more of the other three facilities only 13-25% of the time. More than 1 million cases would be needed to have a 90% chance of having at least 3 cases for each procedure observed in the original 200,401 cases. However, with N = 200,401 cases in our initial data set, we observed less than one third of the estimated total number of possible procedures. The lack of historical case duration data for scheduled procedures is an important cause of inaccuracy in predicting case durations. However, millions of cases probably would be required to provide historical case duration data for almost all procedures.


Electronic and Morphological Dual Modulation of Cobalt Carbonate Hydroxides by Mn Doping toward Highly Efficient and Stable Bifunctional Electrocatalysts for Overall Water Splitting.
Developing bifunctional efficient and durable non-noble electrocatalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is highly desirable and challenging for overall water splitting. Herein, Co-Mn carbonate hydroxide (CoMnCH) nanosheet arrays with controllable morphology and composition were developed on nickel foam (NF) as such a bifunctional electrocatalyst. It is discovered that Mn doping in CoCH can simultaneously modulate the nanosheet morphology to significantly increase the electrochemical active surface area for exposing more accessible active sites and tune the electronic structure of Co center to effectively boost its intrinsic activity. As a result, the optimized Co1Mn1CH/NF electrode exhibits unprecedented OER activity with an ultralow overpotential of 294 mV at 30 mA cm-2, compared with all reported metal carbonate hydroxides. Benefited from 3D open nanosheet array topographic structure with tight contact between nanosheets and NF, it is able to deliver a high and stable current density of 1000 mA cm-2 at only an overpotential of 462 mV with no interference from high-flux oxygen evolution. Despite no reports about effective HER on metal carbonate hydroxides yet, the small overpotential of 180 mV at 10 mA cm-2 for HER can be also achieved on Co1Mn1CH/NF by the dual modulation of Mn doping. This offers a two-electrode electrolyzer using bifunctional Co1Mn1CH/NF as both anode and cathode to perform stable overall water splitting with a cell voltage of only 1.68 V at 10 mA cm-2. These findings may open up opportunities to explore other multimetal carbonate hydroxides as practical bifunctional electrocatalysts for scale-up water electrolysis.


RRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor.
The NLRP3 inflammasome plays a crucial role in innate immune-mediated inflammation and contributes to the pathogenesis of multiple autoinflammatory, metabolic and neurodegenerative diseases, but medications targeting the NLRP3 inflammasome are not available for clinical use. RRx-001 is a well-tolerated anticancer agent currently being investigated in phase III clinical trials, but its effects on inflammatory diseases are not known. Here, we show that RRx-001 is a highly selective and potent NLRP3 inhibitor that has strong beneficial effects on NLRP3-driven inflammatory diseases. RRx-001 inhibits the activation of the canonical, noncanonical, and alternative NLRP3 inflammasomes but not the AIM2, NLRC4 or Pyrin inflammasomes. Mechanistically, RRx-001 covalently binds to cysteine 409 of NLRP3 via its bromoacetyl group and therefore blocks the NLRP3-NEK7 interaction, which is critical for the assembly and activation of the NLRP3 inflammasome. More importantly, RRx-001 treatment attenuates the symptoms of lipopolysaccharide (LPS)-induced systemic inflammation, dextran sulfate sodium (DSS)-induced colitis and experimental autoimmune encephalomyelitis (EAE) in mice. Thus, our study identifies RRx-001 as a new potential therapeutic agent for NLRP3-driven diseases.


Sex-specific prefrontal-hypothalamic control of behavior and stress responding.
Depression and cardiovascular disease are both augmented by daily life stress. Yet, the biological mechanisms that translate psychological stress into affective and physiological outcomes are unknown. Previously, we demonstrated that stimulation of the ventromedial prefrontal cortex (vmPFC) has sexually divergent outcomes on behavior and physiology. Importantly, the vmPFC does not innervate the brain regions that initiate autonomic or neuroendocrine stress responses; thus, we hypothesized that intermediate synapses integrate cortical information to regulate stress responding. The posterior hypothalamus (PH) directly innervates stress-effector regions and receives substantial innervation from the vmPFC. In the current studies, circuit-specific approaches examined whether vmPFC synapses in the PH coordinate stress responding. Here we tested the effects of optogenetic vmPFC-PH circuit stimulation in male and female rats on social and motivational behaviors as well as physiological stress responses. Additionally, an intersectional genetic approach was used to knock down synaptobrevin in PH-projecting vmPFC neurons. Our collective results indicate that male vmPFC-PH circuitry promotes positive motivational valence and is both sufficient and necessary to reduce sympathetic-mediated stress responses. In females, the vmPFC-PH circuit does not affect social or preference behaviors but is sufficient and necessary to elevate neuroendocrine stress responses. Altogether, these data suggest cortical regulation of stress reactivity and behavior is mediated, in part, by projections to the hypothalamus that function in a sex-specific manner.


The effect of deception on motor cortex excitability.
Although a number of recent neuroimaging studies have examined the relationship between the brain and deception, the neurological correlates of deception are still not well understood. The present study sought to assess differences in cortical excitability during the act of deception by measuring motor evoked potentials (MEPs) during transcranial magnetic stimulation (TMS). Sports fanatics and low-affiliation sports fans were presented with preferred and rival team images and were asked to deceptively or honestly identify their favored team. Hemispheric differences were found including greater excitability of the left motor cortex during the generation of deceptive responses. In contrast to current physiological measures of deception, level of arousal was not found to differentiate truthful and deceptive responses. The results are presented in terms of a complex cognitive pattern contributing to the generation of deceptive responses.


Science of composite tissue allotransplantation.
The science of composite tissue allotransplantation (CTA) is rooted in progressive thinking by surgeons, fueled by innovative solutions, and aided by understanding the immunology of tolerance and rejection. These three factors have allowed CTA to progress from science fiction to science fact. Research using preclinical animal models has allowed an understanding of the antigenicity of complex tissue transplants and mechanisms to promote graft acceptance. As a result, translation to the clinic has shown that CTA is a viable treatment option well on the way of becoming a standard of care for those who have lost extremities and suffered large tissue defects. The field of CTA has been progressing exponentially over the past decade. Transplantation of hands, larynx, vascularized knee, trachea, face, and abdominal wall has been performed. Several important observations have emerged from translation to the clinic. Although it was predicted that rejection would pose a major limitation, this has not proven true. In fact, steroid-sparing protocols for immunosuppression that have been successfully used in renal transplantation are sufficient to prevent rejection of limbs. Although skin is highly antigenic when transplanted alone in animal models, when part of a CTA, it has not proven to be. Chronic rejection has not been conclusively demonstrated in hand transplant recipients and is difficult to induce in rodent models of CTA. This review focuses on the science of CTA, provides a snapshot of where we are in the clinic, and discusses prospects for the future to make the procedures even more widely available.


Allosuppressors that enhance the efficiency of omnipotent suppressors in Saccharomyces cerevisiae.
Two recessive Mendelian-allosuppressors have been isolated and have been shown to enhance the efficiency of omnipotent suppressors thought to be translational ambiguity mutations. These allosuppressors are unlinked to each other or to the omnipotent suppressors on which they act. They also increase the efficiency of the serine-inserting UAA-suppressor, SUP16. One allosuppressor is allelic or tightly linked to the previously isolated sal2. Another allosuppressor, called sal6, represents a new locus, unlinked to the previously isolated sal1-sal5 that enhance the efficiency of the UAA-suppressors. When present singly in the absence of suppressors or other modifiers the sal2 and sal6 mutations do not have suppressor activity. However, when sal2 and sal6 are combined together in a haploid cell they do suppress weakly. In addition sal2 becomes a weak suppressor in the presence of the [eta +] modifying factor.


Review of veterinary cases received by the Hennepin Poison Center in 1984.
During 1984 the Hennepin Poison Center documented 28, 141 poison exposures. Of these, 1,092 or 3.88% were veterinary exposures. In this study we review those animal cases and present data on the relative number of species involved, the nature of the contaminants, frequency of calls during different times of the day and different times of year. We also report on the number of symptomatic animals, routes of exposure and referral patterns. We will also give brief reports on veterinary cases of particular interest.


Multiple androgen response elements and a Myc consensus site in the androgen receptor (AR) coding region are involved in androgen-mediated up-regulation of AR messenger RNA.
The androgen receptor (AR) gene is transcriptionally regulated by AR (autoregulation); however, the androgen response elements (AREs) required for this process have not been found in the AR promoter or in the 5'-flanking region. We previously showed that the AR cDNA contains AREs involved in AR mRNA autoregulation and that auto(up)regulation is reproduced in PC3 cells (a human prostate cancer cell line) expressing the human AR cDNA driven by a heterologous promoter. A 350-bp fragment of the AR cDNA contains the requisite AREs (ARE-1 and ARE-2) and, when linked upstream of a reporter gene, confers androgen inducibility in a cell-specific manner. Here we report that, although an AR cDNA harboring silent mutations of ARE-1 and ARE-2 produces a transcriptionally active AR, AR mRNA encoded by this mutant cDNA is not up-regulated in androgen-treated PC3 cells. Thus, ARE-1 and ARE-2 are essential for androgen-mediated up-regulation of AR mRNA in this model. Since ARE-1 and ARE-2 are located on separate exons (exons D and E) in the AR gene, we evaluated these AREs in their native context, a 6.5-kb AR genomic fragment. Androgen regulated the 6.5-kb AR genomic fragment and the 350-bp region of the AR cDNA at comparable levels, suggesting that sequences in exons D and E are likely to be involved in androgen-mediated up-regulation of the native AR gene. Furthermore, androgen regulated both responsive regions in U2OS cells, a human osteoblastic cell line that exhibits androgen-mediated up-regulation of native AR mRNA. DNAse I footprinting of the 350-bp region with recombinant AR (DNA- and ligand-binding domains) suggested the presence of additional AREs. Gel shift analyses and mutational studies showed that maximal androgen regulation and AR binding were dependent on the integrity of four AREs (ARE-1, ARE-1A, IVSARE, and ARE-2). While the presence of multiple, nonconsensus AREs is common among other androgen-regulated enhancers, the androgen-responsive region of the AR gene is unique because it contains exonic AREs. DNA binding studies with nuclear extracts were performed to determine whether non-AR transcription factors contribute to androgen regulation of the 350-bp region. These studies, in conjunction with mutational analysis and reporter gene assays with dominant negative Myc and Max expression vectors, showed that Myc and Max interaction with a Myc consensus site is required for androgen regulation of the 350-bp fragment. These results represent a novel interaction between AR and the Myc family of proteins and support a model of androgenic control of AR mRNA via AR and Myc family interaction with a unique internal androgen-responsive region harboring multiple exonic regulatory sequences.


Mastoid osteoma: A rare incidental finding in an orthodontic patient.
Mastoid osteomas of the temporal bone are rare, benign, and usually asymptomatic tumors. However, depending on their size and extension, mastoid osteomas may cause facial palsy, a sensation of ear fullness, pressure-related pain, hearing loss, recurrent external ear infections, and chronic discharge. The etiology of mastoid osteomas is still unknown, but congenital, infectious, and traumatic factors have been proposed. Surgical treatment may be performed with minimal postoperative morbidity. In this article, the authors report a case of a 48-year-old woman seeking orthodontic treatment with an unusual retroauricular protruding mass, including the diagnostic process and differential diagnosis. This case supports the essential role of cone-beam computed tomography to analyze and identify the lesion as a mastoid osteoma.


A pulsed diagonal-beam ultrasonic airflow meter.
The construction and specific function of a new ultrasonic flowmeter are described. The mean velocity of the respiratory airflow is calculated by measuring the transit times of short ultrasonic pulse trains, simultaneously transmitted upstream and downstream at a 500-Hz rate. The flowmeter system consists of a control unit and a separate flow head. The former includes the power supplies, a controlling microprocessor, most of the signal-processing circuitry, and three analog outputs for flow, volume, and temperature. The flow head contains the respiratory tube with a constant circular cross section (length 90 mm, diam 20 mm, dead space 35 ml), a fast temperature sensor, two electronic circuits for processing of flow and temperature data, and a sound transmission channel with two capacitive ultrasonic wide-band transducers. This respiratory airflow meter, suitable for spirometric maneuvers (vital capacity, forced vital capacity) as well as for long-term breath-by-breath respiratory analysis, is extremely fast (response time 1-2 ms) and accurate (volume accuracy with room air +/- 0.7%), with low noise (below 9 ml/s), a wide flow range (bidirectional from 0 to 9 l/s), and a flat frequency response up to 70 Hz.


The impact of respiratory viruses on lung health after preterm birth.
Children born preterm, less than 37 weeks' gestation, are at increased risk of viral respiratory infections and associated complications both during their initial birth hospitalisation and in their first years following discharge. This increased burden of viral respiratory infections is likely to have long term implications for lung health and function in individuals born preterm, particularly those with bronchopulmonary dysplasia. Several hypotheses have been put forward to explain the association between early life viral respiratory infection and development of suboptimal lung health and function later in life following preterm birth. Although preterm infants with diminished lung function, particularly small airways, might be particularly susceptible to asthma and wheezing disorders following viral infection, there is evidence that respiratory viruses can activate number of inflammatory and airway re-modelling pathways. Therefore, the aim of this review is to highlight the perinatal and early life risk factors that may contribute to increased susceptibility to viral respiratory infections among preterm infants during early life and to understand how respiratory viral infection may influence the development of abnormal lung health and function later in life.


A comparison of the Giardia lamblia trophozoite and cyst transcriptome using microarrays.
Compared with many protists, Giardia lamblia has a simple life cycle alternating between cyst and trophozoite. Most research on the molecular biology of Giardia parasites has focused on trophozoites and the processes of excystation and encystation, whereas cysts have attracted less interest. The striking morphological differences between the dormant cyst and the rapidly dividing and motile trophozoite implies profound changes in the metabolism as the parasite encysts in the host's intestine and excysts upon ingestion by a new host. To investigate the magnitude of the transcriptional changes occurring during the G. lamblia life cycle we compared the transcriptome of G. lamblia trophozoites and cysts using single-color oligonucleotide microarrays. Cysts were found to possess a much smaller transcriptome, both in terms of mRNA diversity and abundance. Genes encoding proteins related to ribosomal functions are highly over-represented. The comparison of the transcriptome of cysts generated in culture or extracted from feces revealed little overlap, raising the possibility of significant biological differences between the two types of cysts. The comparison of the G. lamblia cyst and trophozoite transcriptome showed that transcripts of most genes are present at a lower level in cysts. This global view of the cyst and trophozoite transcriptome complements studies focused on the expression of selected genes during trophozoite multiplication, encystation and excystation.


Pre-Operative, Intra-Operative, and Post-Operative Factors Associated with Post-Discharge Venous Thromboembolism Following Colorectal Cancer Resection.
Venous thromboembolism (VTE) is the most common preventable cause of 30-day post-operative mortality, with many events occurring after hospital discharge. High-level evidence supports post-discharge VTE chemoprophylaxis following abdominal/pelvic cancer resection; however, some studies support a more tailored approach. Our objectives were to (1) identify risk factors associated with post-discharge VTE in a large cohort of patients undergoing colorectal cancer resection and (2) develop a post-discharge VTE risk calculator. Patients who underwent colorectal cancer resection from 2012 to 2016 were identified from ACS NSQIP colectomy and proctectomy procedure-targeted modules. Multivariable logistic regression was used to identify factors associated with post-discharge VTE. Incorporating pre-operative, intra-operative, and post-operative variables, a post-discharge VTE risk calculator was constructed and validated. Of 51,139 patients, 387 (0.76%) developed post-discharge VTE. Pre-operative factors associated with post-discharge VTE included BMI (e.g., morbidly obese OR 2.27, 95% CI 1.65-3.12 vs. normal BMI), and thrombocytosis (OR 1.41, 95% CI 1.03-1.92). Intra-operative factors included operative time (4-6 h OR 1.56, 95% CI 1.12-2.17; > 6 h, OR 1.85, 95% CI 1.21-2.84, vs. < 2 h), and type of operation (e.g., open partial colectomy OR 1.67, 95% CI 1.30-2.16 vs. laparoscopic partial colectomy). Post-operative factors included anastomotic leak (OR 2.05, 95% CI 1.31-3.21) and post-operative ileus (OR 1.39, 95% CI 1.07-1.79). Using the risk calculator, the predicted probability of post-discharge VTE ranged from 0.04 to 10.29%. On a 10-fold cross validation, the calculator's mean C-Statistic was 0.65. Patient-specific factors are associated with varying rates of post-discharge VTE. We present the first post-discharge VTE risk calculator designed for use at the time of discharge following colorectal cancer resection.


The echocardiographic assessment of pulmonary artery pressure and pulmonary vascular resistance.
Serial assessment of the status of the pulmonary vascular bed requires bed requires cardiac catheterization. We have demonstrated the right ventricular systolic time intervals (RVSTI) may be measured from the pulmonary valve echo. The right ventricular ejection time (RVET) and right pre-ejection period (RPEP) were measured in 45 normal patients. The RVET and RPEP decreased with increasing heart rate but increased with age. The RPEP/RVET, however, was uninfluenced by either age or heart rate. The RPEP/RVET was, therefore, determined from the pulmonary valve echo in 64 patients with congenital heart disease who underwent cardiac catheterization. Increased pulmonary artery diastolic pressure (PADP), pulmonary vascular resistance (PADP), pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (MPAP) resulted inan increased RPEP/RVET. The use of the RPEP/RVET permitted the serial echographic evaluation of the pulmonary vascular bed in selected patients; marked elevation of the ratio indicated the presence of pulmonary hypertension.


Immunolocalization of steroidogenic enzymes and their expression during the breeding season in the testes of wild raccoon dogs (Nyctereutes procyonoides).
The objective of this study was to investigate immunolocalization of steroidogenic enzymes 3βHSD, P450c17 and P450arom and their expression during the breeding season in wild male raccoon dogs. The testicular weight, size and seminiferous tubule diameters were measured, and histological and immunohistochemical observations of testes were performed. The messenger RNA expression (mRNA) of 3βHSD, P450c17 and P450arom was measured in the testes during the breeding season. 3βHSD was found in Leydig cells during the breeding and non-breeding seasons with more intense staining in the breeding season. P450c17 was identified in Leydig cells and spermatids in the breeding season, whereas it was present only in Leydig cells in the non-breeding season. The localization of P450arom changed seasonally: no immunostaining in the non-breeding season; more extensive immunostaining in Leydig cells, Sertoli cells and elongating spermatids in the breeding season. In addition, 3βHSD, P450c17 and P450arom mRNA were also expressed in the testes during the breeding season. These results suggested that seasonal changes in testicular weight, size and seminiferous tubule diameter in the wild raccoon dog were correlated with spermatogenesis and immunoreactivity of steroidogenic enzymes and that steroidogenic enzymes may play an important role in the spermatogenesis and testicular recrudescence and regression process.


Patent ductus arteriosus in neonates.
Patency of the ductus arteriosus is one of the more common problems of the neonate. Although the ductus arteriosus usually closes within the first days of life, persistent patency can complicate the clinical status of a newborn. The ductus arteriosus also may play a role in the pathophysiology of persistent pulmonary hypertension of the newborn and in some forms of congenital heart disease. Diagnosis of patent ductus arteriosus can be suspected clinically but should be verified by echocardiography before treatment. Accurate diagnosis, early intervention and proper treatment are necessary to decrease the immediate risks and minimize the potential for long-term complications.


Mobile-BAT-A Novel Ultra-Low Power Wildlife Tracking System.
We introduce a novel ultra-low power system for tracking animal movements over long periods with an unprecedented high-temporal-resolution. The localization principle is based on the detection of cellular base stations using a miniaturized software-defined radio, weighing 2.0 g, including the battery, and having a size equivalent to two stacked 1-euro cent coins. Therefore, the system is small and lightweight enough to be deployed on small, wide-ranging, or migrating animals, such as European bats, for movement analysis with an unprecedented spatiotemporal resolution. The position estimation relies on a post-processing probabilistic RF pattern-matching method based on the acquired base stations and power levels. In several field tests, the system has been successfully verified, and a run-time of close to one year has been demonstrated.


A baseline study for the development of an instrument for the assessment of pain.
This study was designed to establish a foundation for the further development of a pain assessment tool for use in clinical practice. It was earlier reported that there existed a significant difference in the intensity of the words pain, ache and hurt and that each of these concepts had their own specific sensory and affective word descriptors. This study was designed to: 1 find out if the above results could be verified by using subjects with a different background from those included in the previous study; 2 determine the intensity of word descriptors; and 3 determine if patients, nurses and nursing students use the same word descriptors to describe pain-like experiences. Pain assessment tools used were the McGill Pain Questionnaire, a visual analogue scale and a pain, ache and hurt questionnaire. The results of the earlier reported study were confirmed. In addition, a significant difference was found in intensity of the word descriptors. Patients, nurses and nursing students used basically the same word descriptor to describe pain-like experiences. The sensory word descriptors (crushing, sharp, tearing, cutting, penetrating, gnawing, dull, pulling, sore, stinging, pricking and pinching) and the affective word descriptors (dreadful, torturing, killing, unbearable, terrifying, suffocating, exhausting, unhappy, troublesome, annoying, irritating and fearful) are suggested as a foundation upon which a pain assessment tool could be developed for use in clinical practice.


Bacterial culture of perfusion blood after open-heart surgery.
The results of routine culture of 595 consecutive specimens of perfusion blood are presented. Ten per cent of the specimens yielded bacteria overall, but it was found that the isolation rate was increased to 17.7% when the prophylactic antibodies being given during the bypass were specifically neutralised. Coagulase-negative staphylococci and diphtheroids formed the majority of organisms isolated, but Gram negative bacilli or "coliform" type were also occasionally found. A comparison of the relative findings in patients receiving prophylactic flucloxacillin or cephradine showed that the isolation rates of coagulase-negative staphylococci and diphtheroids were lower in the group receiving flucloxacillin. The origin of the bacteria isolated from perfusion blood remains uncertain but speciation of coagulase-negative staphylococci from perfusion blood and similar organisms isolated subsequently from catheter tips in the same patients revealed no evidence that the two sources of organisms were linked. Although organisms are easily and commonly found in perfusion blood, the relevance of this phenomenon to post-operative endocarditis is not clear.


[Ukrainian break-through in the European and world strategy of individual prophylaxis of ischemic stroke in patients with arterial hypertension].
To reduce of epidemic of an ischemic stroke often developed in patients with arterial hypertension, we have developed the program of individual diagnostics of a clinical risk factor and a method to optimize the treatment directed on prophylactic of cardio-vascular complications. The main predictor of blood clot formation, hypercoagulation, had been detected by means of our laboratory technology "Coaguloscop-TC" (Ukraine patent) which allows registration 36 biomarkers of coagulation cascade and the fibrinolysys system. It can calculate coagulation module (MC) and fibrinolysis module (MF). These biomarkers corresponded to new (2009) requirements of the American Heart Association. After analysis of results of 818 patients we have defined an interval line of MC and MF disorders located within degree (from I to X) of their dysfunction. Patients with hypertension (400) of II-III stage and concomitant ischemic heart disease (44.2% of cases) without antiplatelet therapies, hypercoagulation was found in 61% of patients. Very high risk factor (MC IX-X degree) took place in all patients with acute stroke. The high risk factor (MC VI-VIII degree) testified presence of urgent situation, for its correction we administered an antiplatelet agent (acelisin) intramuscularly once a day for 4-6 days in an individual dosis which was calculated based on MC level and body weight. After the treatment MC usually decreased to 2 degrees (low risk factor). The dislipidemia negatively effects efficiency of the treatment as its biomarkers have direct correlation (P < 0.001) with density of blood clot which increase inhibits the fibrinolysis system to dissolve blood clot. The use of effective complex treatment of patients with arterial hypertension ( antihypertensive, antiplatelet and hypolipidemic (statin) medications) is supposed to decrease the development of ischemic stroke by 80% that four times higher than in the 2006-2020 program assigned by Ministry of Health of Ukraine.


The desirability of transitions in demand: Incorporating behavioural and societal transformations into energy modelling.
Quantitative systems modelling in support of climate policy has tended to focus more on the supply side in assessing interactions among technology, economy, environment, policy and society. By contrast, the demand side is usually underrepresented, often emphasising technological options for energy efficiency improvements. In this perspective, we argue that scientific support to climate action is not only about exploring capacity of "what", in terms of policy and outcome, but also about assessing feasibility and desirability, in terms of "when", "where" and especially for "whom". Without the necessary behavioural and societal transformations, the world faces an inadequate response to the climate crisis challenge. This could result from poor uptake of low-carbon technologies, continued high-carbon intensive lifestyles, or economy-wide rebound effects. For this reason, we propose a framing for a holistic and transdisciplinary perspective on the role of human choices and behaviours in influencing the low-carbon transition, starting from the desires of individuals and communities, and analysing how these interact with the energy and economic landscape, leading to systemic change at the macro-level. In making a case for a political ecology agenda, we expand our scope, from comprehending the role of societal acceptance and uptake of end-use technologies, to co-developing knowledge with citizens from non-mainstream and marginalised communities, and to defining the modelling requirements to assess the decarbonisation potential of shifting lifestyle patterns in climate change and action.


Evaluation of photopatch test allergens for Indian patients of photodermatitis: preliminary results.
There is a strong need to develop a photopatch test tray suitable for Indian patients of photodermatitis as European/Scandinavian photopatch test trays may not be wholly relevant for them. We carried out this study using photoallergens relevant in the Indian context to determine their relevance in patients of photodermatitis. Thirty patients (M:F, 23:7) between 19 and 76 years of age of photodermatitis and 10 controls were patch- and photopatch tested with 20 common photoallergens. In addition, the patients were also (photo) patch tested with articles of daily use as and when these were suspected to be the cause. Forty-three positive reactions to one or more antigens were seen in 22 (74%) patients. Fourteen positive photopatch tests to seven allergens were observed in 10 (33%) patients, and nine (30%) of them had a definite relevance. The most common contact allergen was fragrance mix (FM) (30%), followed by p-phenylenediamine (20%) and Parthenium hysterophorous (17%). The definite relevance of the patch- and photopatch tests could be correlated in 47% of these patients. FM is the most common contact and photocontact allergen among the various photopatch test antigens. Although differences in technique and evaluation make direct comparison between different centers difficult, still photopatch testing remains an integral part and gold standard for the work-up of the photosensitive patients.


Effects of molecular adsorption on the spin-wave spectrum and magnon relaxation in two-dimensional Cr2Ge2Te6.
In this work, we performed detailed first-principles calculation and theoretical analysis to investigate the effect of molecular adsorption on the spin-wave spectrum and magnon relaxation in a Cr2Ge2Te6 (CGT) monolayer. It is found that NH3, NO, and NO2 adsorption can enhance the exchange constant of CGT, which can result in a blue-shift in the spin-wave spectrum. At 30 K, by means of a thorough investigation of many possible lattice configurations excited by thermal fluctuation, we identify the magnon scattering rate from the intrinsic lattice vibrational modes, and find that the relaxation of optical and acoustic magnons exhibits a completely different wave vector dependence. Moreover, although the adsorption of NO2 and NH3 molecules has a negligible influence on the magnon-phonon interaction, the adsorption of NO molecules results in a significant increase in magnon scattering strength. In the long-wavelength limit, the interlayer vibrational modes induced by NO adsorption increase the magnon-phonon scattering strength by ∼12.7%. The remarkable interlayer magnon-phonon interaction is ascribed to the strong CGT-NO coupling and large molecular vibration amplitude. Considering the importance of magnon relaxation time in the application of spin devices, we suggest that both the impacts on the exchange interaction and scattering rate must be considered when manipulating two-dimensional magnets by surface functionalization.


CNP optical metamaterials.
Simulation results for optical metamaterials (MTMs) derived from active coated nano-particle (CNP) inclusions for operation in the visible range of the spectrum between 400nm and 700nm are presented. Several examples of optical MTMs designed with these inclusions are characterized, including two-dimensional (2D) CNP metafilms; three-dimensional (3D) periodic CNP arrays; and 3D random CNP distributions. The properties of these optical MTMs are explored using effective medium theories that are applicable to these inclusion configurations. The effective permittivities and refractive indexes of these optical MTMs are compared and contrasted to the scattering properties of their active CNP inclusions.


Thyrotoxicosis after massive triiodothyronine (LT3) overdose: a coast-to-coast case series and review.
Excessive exogenous thyroid hormone ingestion may lead to severe thyrotoxicosis and cause potential harm. We have reviewed the literature and suggested that thyroid hormone supplementation should not be used to alleviate nonspecific complaints in patients with normal endogenous thyroid function. Failure to do so may cause serious harm, as demonstrated in one of the cases described here. In addition, treatment based on symptom relief only without biochemical measure may lead to overmedication - as reported from academic hospitals both in Canada and the United States. Given the risk of severe thyrotoxicosis from potential compounding errors, pharmacies providing a compounding service should be subject to more rigorous monitoring by the food and drug administration. Clinicians should also use local biochemical markers when titrating thyroid hormone supplements even though the normal thyroid function reference range has its limitation, failure to do so may result in iatrogenic thyrotoxicosis.


Immunohistochemical study of HLA-DR antigen in endometrial tissue of patients with endometriosis.
In order to evaluate the expression of HLA-DR antigen in glandular cells in eutopic and ectopic endometrium in patients with endometriosis, 19 infertile patients with endometriosis were analyzed immunohistochemically by labelled streptavidin biotin (LSAB) method. Nineteen infertile patients without endometriosis were studied as controls. The results showed that the expression of HLA-DR antigen in the glandular cells in both eutopic and ectopic endometrium was increased significantly as compared with that in the controls (P < 0.01). It is likely that aberrant expression of HLA-DR antigen in endometriotic tissue is involved in abnormal immunogenesis of endometriosis.


[Ovarian thecoma with amyloidosis].
A case of diagnosis of a variety of ovarian thecoma, a thecoma with amyloidosis of the stroma, in a patient with fibromyoma of the uterus is described. Brief clinical data, characteristics of the tumor morphology including polarization microscopy and histochemistry, and differential diagnosis of forms of amyloidosis are presented. The presence of amyloid in the thecoma is considered to reflect the capacity of the tumor theca-cells of mesenchymal origin to produce amyloid.


Liquid droplets on a free-standing glassy membrane: Deformation through the glass transition.
In this study, micro-droplets are placed on thin, glassy, free-standing films where the Laplace pressure of the droplet deforms the free-standing film, creating a bulge. The film's tension is modulated by changing temperature continuously from well below the glass transition into the melt state of the film. The contact angle of the liquid droplet with the planar film as well as the angle of the bulge with the film are measured and found to be consistent with the contact angles predicted by a force balance at the contact line.


In vitro synergistic activities of tobramycin and selected beta-lactams against 75 gram-negative clinical isolates.
The microdilution checkerboard technique was utilized to distinguish synergistic activity between tobramycin and four beta-lactams: piperacillin-tazobactam, ticarcillin-clavulanate, ceftazidime, and ceftriaxone. Beta-lactam-aminoglycoside combinations were tested against 75 clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumanii, Citrobacterfreundii, Serratia marcescens, and Enterobacter cloacae. Despite in vitro susceptibilities, all isolates demonstrated either synergism or indifference; no antagonism was observed. Against pathogenic gram-negative nosocomial isolates, a greater percentage of synergy was consistently observed with combination regimens containing tobramycin and piperacillin-tazobactam or ticarcillin-clavulanate than with the cephalosporin-containing regimens.


Growth disturbances without growth arrest after ACL reconstruction in children.
Growth arrest is a major concern after ACL reconstruction in children. It usually occurs in patients near to closure of the growth plates. Growth disturbances without growth arrest are also possible and more vicious; the authors analyse the mechanism of two patients with growth disturbance due to overgrowth following ACL reconstruction. One was a symmetrical overgrowth process with 15 mm limb length discrepancy treated with percutaneous epiphysiodesis. Full correction at the time of skeletal maturity was achieved. The second patient developed an asymmetrical overgrowth with progressive tibial valgus deformity. This mechanism was similar to a posttraumatic tibial valgus deformity. After nonoperative treatment, a spontaneous correction of the deformity was noticed. Both children were young (7 and 10 years old) at the time of ACL reconstruction with an autologous iliotibial band graft. The clinical relevance of overgrowth disturbance is usually limited when compared to growth arrest but could require a second surgical procedure as reported in this study. Parents must be informed that even in experienced hands, and despite the use of a physeal sparing technique, this specific risk of growth disturbance is still present.


Perspective: Novel Commercial Packaging and Devices for Complementary Feeding.
In recent years, so-called baby food pouches and other novel packaging and devices have been marketed for complementary feeding. To date, no experimental studies have been conducted to determine health and nutrition effects or the safety of baby food pouches and related feeding devices. Yet, these products hold the potential to fundamentally change the ways in which infants and children consume solid foods in infancy and early childhood. In this review, a selection of complementary feeding devices and their potential effects on breastfeeding, formula-feeding, safe and appropriate complementary feeding, and the timely transition to family foods are explored. Because manufacturers have innovated older designs of traditional feeding bottles and pacifiers for complementary feeding, perspectives on potential health effects and the safety of devices are drawn from research on feeding bottles and pacifiers. Recommendations include scaling up research on the safety, nutrition, and health impacts of commercial packaging and devices. In addition, manufacturers should ensure that devices conform to consumer product safety commission specifications and that instructions for use are in line with policies protecting pediatric dental health. Marketing of commercial devices and packaging should conform to the International Code of Marketing of Breastmilk Substitutes.


Modulatory-antibiotic activity of the essential oil from Eucalyptus citriodora against MDR bacterial strains.
The growing number of bacterial strains resistant to therapeutic agents has been surpassing the various antibiotics developed by the chemical and pharmaceutical industries. This problem has driven the development of research using agents with antimicrobial potential, with an emphasis on plant-derived natural products. This study evaluated the chemical compounds present in Eucalyptus citriodora essential oil (EOEc) cultivated in northeastern Brazil and its properties as an antibacterial agent and resistance modifier against methicillin-resistant Staphylococcus aureus (MRSA) and β-lactamase-producing strains. The EOEc was obtained using the hydrodistillation method, later analyzed by GC/MS, presenting a total of twelve compounds, with citronellal (65.45%); citronellol (14.87%); isopulegol (11.80%) and citronellyl acetate (2.51%) as its main constituents. The microdilution test was used to determine the minimum inhibitory concentration (MIC) and the bacterial resistance modulation of the essential oil. The EOEc did not present significant activity against the tested strains (MIC > 1000 µg mL-1). However, when evaluating the capacity of the EOEc to modify the resistance of S. aureus and E. coli strains to different antimicrobials, synergistic effects were obtained with reduced MIC values for all tested antibiotics being obtained. The EOEc showed antimicrobial and β-lactam optimizing potential against resistant strains, presenting itself as a possible alternative for the use of these drugs at concentrations lower than those indicated against resistant strains.


Pharmacokinetics of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis).
To evaluate the pharmacokinetics of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine decanoate (37.5 mg/kg) was administered IM to all birds. Plasma samples were obtained from blood collected before (time 0) and 0.25, 1, 2, 3, 6, 12, 24, 48, and 96 hours after drug administration. Plasma samples were used for measurement of nalbuphine concentrations via liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated with computer software. Plasma concentrations of nalbuphine increased rapidly after IM administration, with a mean concentration of 46.1 ng/mL at 0.25 hours after administration. Plasma concentrations of nalbuphine remained > 20 ng/mL for at least 24 hours in all birds. The maximum plasma concentration was 109.4 ng/mL at 2.15 hours. The mean terminal half-life was 20.4 hours. In Hispaniolan Amazon parrots, plasma concentrations of nalbuphine were prolonged after IM administration of nalbuphine decanoate, compared with previously reported results after administration of nalbuphine hydrochloride. Plasma concentrations that could be associated with antinociception were maintained for 24 hours after IM administration of 37.5 mg of nalbuphine decanoate/kg. Safety and analgesic efficacy of nalbuphine treatments in this species require further investigation to determine the potential for clinical use in pain management in psittacine species.


[Perception of emotions in speech. A review of psychological and physiological research].
The article is a review of the general concepts and approaches in research of recognition of emotions in speech: psychological concepts, principles and methods of study and physiological data in studies on animals and human. The concepts of emotional intelligence (ability to understand and recognize emotions of other people and to understand and regulate personal emotions), emotional hearing (ability to recognize emotions in speech) are discussed, general review of the paradigms is presented. The research of brain mechanisms of speech emotions differentiation is based on the study of local injuries and dysfunctions, along with the study on healthy subjects.


Integrating Autism Care through a School-Based Intervention Model: A Pilot Study.
The purpose of this pilot study is to determine the feasibility of monitoring the progress of children with an autism spectrum disorder (ASD) both in school and at home to promote a school-based integrated care model between parents, teachers, and medical providers. This is a prospective cohort study. To monitor progress, outcome measures were administered via an online platform developed for caregivers and teachers of children (n = 30) attending a school specializing in neurodevelopmental disorders and using an integrated medical and education program. Longitudinal analysis showed improvements in a novel scale, the Teacher Autism Progress Scale (TAPS), which was designed to measure key autism-related gains in a school environment (2.1-point improvement, p = 0.004, ES = 0.324). The TAPS showed a strong and statistically significant correlation, with improvement in aberrant behavior (r = -0.50; p = 0.008) and social responsiveness (r = -0.70; p < 0.001). The results also showed non-statistically significant improvements in aberrant behavior, social responsiveness, and quality of life over time at both school and home. To assess feasibility of ongoing progress measurement, we assessed missing data, which showed caregivers were more likely to miss surveys during summer. Results demonstrate the value and feasibility of online, longitudinal data collection in school to assist with individualized education planning and collaborative care for children with ASD. Lessons learned in this pilot will support school outcomes researchers in developing more efficacious, collaborative treatment plans between clinicians, caregivers, and teachers.


Genomic prediction of serum biomarkers of health in early lactation.
In this study, we estimated genetic parameters and genomic prediction accuracies of serum biomarkers of health in early-lactation dairy cows. A single serum sample was taken from 1,393 cows, located on 14 farms in southeastern Australia, within 30 d after calving. Sera were analyzed for biomarkers of energy balance (β-hydroxybutyrate and fatty acids), macromineral status (Ca and Mg), protein nutritional status (urea and albumin), and immune status (globulins, albumin-to-globulin ratio, and haptoglobin). After editing, 47,162 SNP marker genotypes were used to estimate genomic heritabilities and breeding values (GEBV) for these traits in ASReml. Heritabilities were low for β-hydroxybutyrate, fatty acids, Ca, Mg, and urea (0.09 ± 0.04, 0.18 ± 0.05, 0.07 ± 0.04, 0.19 ± 0.06, and 0.18 ± 0.05, respectively), and moderate for albumin, globulins, and albumin-to-globulin ratio (0.27 ± 0.06, 0.46 ± 0.06, and 0.41 ± 0.06, respectively). The heritability of haptoglobin concentration was close to 0. The magnitude of genetic correlations between traits (estimated using bivariate models) varied considerably (0.01 to 0.96), and standard errors of these correlations were high (0.02 to 0.44). Interestingly, the direction of most genetic correlations was favorable, suggesting that selecting for more optimal concentrations of one biomarker may result in more optimal concentrations of other biomarkers. Correlations between biomarker GEBV and existing breeding values for survival, somatic cell count, and daughter fertility were small to moderate (0.07 to 0.45) and favorable, whereas correlations with breeding values for milk production traits were small (≤0.15). Accuracies of GEBV were evaluated by using 5-fold cross validation, and by calculating accuracies from prediction error variances associated with the GEBV. Accuracies of GEBV predicted using 5-fold cross validation were low (0.05 to 0.27), whereas the means of individual accuracies were greater, ranging from 0.31 to 0.51. Although increasing the size of the reference population should theoretically improve accuracies, our results suggest that genomic prediction of health biomarkers may allow identification of cows that are less susceptible to diseases in early lactation.


Dietary fatty acids and flight-training influence the expression of the eicosanoid hormone prostacyclin in songbirds.
Diet shifts can alter tissue fatty acid composition in birds, which is subsequently related to metabolic patterns. Eicosanoids, short-lived fatty acid-derived hormones, have been proposed to mediate these relationships but neither baseline concentrations nor the responses to diet and exercise have been measured in songbirds. We quantified a stable derivative of the vasodilatory eicosanoid prostacyclin in the plasma of male European Starlings (Sturnus vulgaris, N = 25) fed semisynthetic diets with either high (PUFA) or low (MUFA) amounts of n6 fatty acid precursors to prostacyclin. Plasma samples were taken from each bird before, immediately after, and two days following a 15-day flight-training regimen that a subset of birds (N = 17) underwent. We found elevated prostacyclin levels in flight-trained birds fed the PUFA diet compared to those fed the MUFA diet and a positive relationship between prostacyclin and body condition, indexed by fat score. Prostacyclin concentrations also significantly decreased at the final time point. These results are consistent with the proposed influences of precursor availability (i.e., dietary fatty acids) and regulatory feedback associated with exercise (i.e., fuel supply and inflammation), and suggest that prostacyclin may be an important mediator of dietary influence on songbird physiology.


The genetics and evolution of the mariner transposable element in Drosophila simulans: worldwide distribution and experimental population dynamics.
We have studied both the frequency and biogeographical distribution of the transposable DNA element mariner in natural populations of Drosophila simulans and the short-term evolutionary characteristics of mariner in experimental populations. The mariner element has been identified in natural populations of D. simulans from Africa, Europe, the Middle East, Japan, Australia, several Pacific islands, North America, and South America. Only four lines out of 296 were devoid of active mariner elements, as measured by the presence of functional mariner transposase. A slight correlation was found between the latitudinal coordinate of the collection sites and the level of mariner activity in the populations; this correlation became highly significant in Australia where a cline in mariner activity was observed along the eastern coast of the continent. We also observed that wild-type laboratory strains kept for several years as small populations might lose mariner activity over time. Using experimental populations, we modeled what might happen when naturally occurring populations exhibiting high and low levels of mariner activity encounter one another. We found that active mariner elements either will tend to lose their activity over time and gradually become inactive or possibly will be lost from the population; in either case, this will lead to the pattern seen in this experiment of a significant loss of mariner activity over time.


Restoration of KCC2 Membrane Localization in Striatal Dopamine D2 Receptor-Expressing Medium Spiny Neurons Rescues Locomotor Deficits in HIV Tat-Transgenic Mice.
People infected with HIV (PWH) are highly susceptible to striatal and hippocampal damage. Motor and memory impairments are common among these patients, likely as behavioral manifestations of damage to these brain regions. GABAergic dysfunction from HIV infection and viral proteins such as transactivator of transcription (Tat) have been well documented. We recently demonstrated that the neuron specific Cl- extruder, K+ Cl- cotransporter 2 (KCC2), is diminished after exposure to HIV proteins, including Tat, resulting in disrupted GABAAR-mediated hyperpolarization and inhibition. Here, we utilized doxycycline (DOX)-inducible, GFAP-driven HIV-1 Tat transgenic mice to further explore this phenomenon. After two weeks of Tat expression, we found no changes in hippocampal KCC2 levels, but a significant decrease in the striatum that was associated with hyperlocomotion in the open field assay. We were able to restore KCC2 activity and baseline locomotion with the KCC2 enhancer, CLP290. Additionally, we found that CLP290, whose mechanism of action has yet to be described, acts to restore phosphorylation of serine 940 resulting in increased KCC2 membrane localization. We also examined neuronal subpopulation contributions to the noted effects and found significant differences. Dopamine D2 receptor-expressing medium spiny neurons (MSNs) were selectively vulnerable to Tat-induced KCC2 loss, with no changes observed in dopamine D1 receptor-expressing MSNs. These results suggest that disinhibition/diminished hyperpolarization of dopamine D2 receptor-expressing MSNs can manifest as increased locomotion in this context. They further suggest that KCC2 activity might be a therapeutic target to alleviate motor disturbances related to HIV.


On seeing yellow: the case for, and against, short-wavelength light-absorbing intraocular lenses.
The normal human crystalline lens absorbs UV and short-wavelength visible electromagnetic radiation. Early intraocular lenses (IOLs) permitted the transmission of such radiation to the retina following cataract extraction. Experimental studies of the absorption profile of the crystalline lens and animal studies demonstrating the deleterious effects of short-wavelength radiation on the retina led to the development of UV-absorbing, and later, short-wavelength light-absorbing (SLA) IOLs. Short-wavelength light-absorbing IOLs were designed to mimic the absorption properties of the normal crystalline lens by absorbing some short-wavelength light in addition to UV radiation; however, debate continues regarding the relative merits of such lenses over UV-absorbing IOLs. Advocates of SLA IOLs suggest that they may theoretically offer increased photoprotection and decreased glare sensitivity and draw on in vitro, animal, and limited clinical studies that infer possible benefits. Detractors suggest that there is no direct evidence supporting a role for SLA IOLs in preventing retinal dysfunction in humans and suggest that they may have negative effects on color perception, scotopic vision, and circadian rhythms. This article examines the theoretical and empirical evidence for, and against, such lenses.


Data mining in bone marrow transplant records to identify patients with high odds of survival.
Patients undergoing a bone marrow stem cell transplant (BMT) face various risk factors. Analyzing data from past transplants could enhance the understanding of the factors influencing success. Records up to 120 measurements per transplant procedure from 1751 patients undergoing BMT were collected (Shariati Hospital). Collaborative filtering techniques allowed the processing of highly sparse records with 22.3% missing values. Ten-fold cross-validation was used to evaluate the performance of various classification algorithms trained on predicting the survival status. Modest accuracy levels were obtained in predicting the survival status (AUC = 0.69). More importantly, however, operations that had the highest chances of success were shown to be identifiable with high accuracy, e.g., 92% or 97% when identifying 74 or 31 recipients, respectively. Identifying the patients with the highest chances of survival has direct application in the prioritization of resources and in donor matching. For patients where high-confidence prediction is not achieved, assigning a probability to their survival odds has potential applications in probabilistic decision support systems and in combination with other sources of information.