A major gene for host response to porcine reproductive and respiratory syndrome is not unfavorably associated with overall performance under nonchallenging conditions in commercial pig lines.
A QTL for host response to porcine reproductive and respiratory syndrome (PRRS) was identified in a previous study. The SNP WUR10000125 (WUR) is used as a tag SNP for this QTL. The favorable (B) allele at this SNP is in low frequency in commercial populations, possibly because this allele is unfavorably associated with an important trait under nonchallenging conditions and, therefore, may have been selected against. Therefore, objectives of this study were to estimate the effect of WUR on traits under selection in commercial lines under nonchallenging conditions and to estimate the effect of WUR genotype of parents on performance of crossbred progeny in a commercial-like environment. Data were collected on 4 purebred lines: a Landrace dam line (D1), a Large White dam line (D2), a synthetic sire line (S1), and a Pietrain sire line (S2). Traits analyzed included total number born, number stillborn, farrowing survival, lactation survival, litter mortality, daily feed intake (DFI), backfat, average test daily gain (TGR), average lifetime daily gain (LGR), and Topigs Norsvin selection index (TSI) value, indicative of overall economic value. Deregressed EBV were calculated for each trait (except TSI) and analyzed within line. In the S1 line, AB and BB pigs had significantly lower TGR ( = 0.002) and LGR ( = 0.001) than AA pigs but also lower DFI ( = 0.004). Conversely, AB and BB pigs had significantly higher DFI ( < 0.001) and AB pigs had significantly higher TGR ( = 0.03) than AA pigs in the S2 line. The effect of WUR on TSI was not significant for any line ( ≥ 0.15). Analyses of phenotypic records collected on crossbred progeny of S1 sires and D1 × D2 F females showed no significant effect of parent WUR genotype on DFI, backfat, TGR, or LGR ( ≥ 0.07). In conclusion, the effect of WUR was nonsignificant for most traits but the magnitude and direction of the effect differed by trait and by line. The favorable allele for host response to PRRS was associated with greater DFI and a tendency for greater TGR in the S2 line, but the opposite direction of effect was detected for the S1 line. Regardless of the effect on individual traits, no significant effect of WUR on TSI was detected for any line. Therefore, selecting for the B allele is expected to result in progeny with increased resistance to PRRS without compromising overall economic value under normal, nonchallenging conditions.


Previous cocaine exposure makes rats hypersensitive to both delay and reward magnitude.
Animals prefer an immediate over a delayed reward, just as they prefer a large over a small reward. Exposure to psychostimulants causes long-lasting changes in structures critical for this behavior and might disrupt normal time-discounting performance. To test this hypothesis, we exposed rats to cocaine daily for 2 weeks (30 mg/kg, i.p.). Approximately 6 weeks later, we tested them on a variant of a time-discounting task, in which the rats responded to one of two locations to obtain reward while we independently manipulated the delay to reward and reward magnitude. Performance did not differ between cocaine-treated and saline-treated (control) rats when delay lengths and reward magnitudes were equal at the two locations. However, cocaine-treated rats were significantly more likely to shift their responding when we increased the delay or reward size asymmetrically. Furthermore, they were slower to respond and made more errors when forced to the side associated with the lower value. We conclude that previous exposure to cocaine makes choice behavior hypersensitive to differences in the time to and size of available rewards, consistent with a general effect of cocaine exposure on reward valuation mechanisms.


Terminators of transcription with RNA polymerase from Escherichia coli: what they look like and how to find them.
We present here a compilation of prokaryotic transcription terminator sequences (ref. 1-152). The compilation includes 49 independent terminators, 52 speculated independent terminators, 27 sites shown to function in vivo, and some 20 proven or speculated rho-dependent terminators. In addition to the well-known features of independent terminators (dyad symmetry and T-run), two consensus are found: CGGG(C/G) upstream and TCTG downstream of the termination point. A subset of the collection of sequence has been used to construct a computer algorithm to locate independent terminators by sequence analysis.


The Influence of Psychological Stress on HPV Infection Manifestations and Carcinogenesis.
Psychological stress is an important factor involved in disease manifestations of human papillomavirus (HPV) infection, and it can participate in HPV-associated carcinogenesis. The impact or effect which stress can have (exert) depends on a person's genetic pool, experiences and behaviors. Due to inconsistencies in some study results, this issue remains a subject of research. Concerning the course of HPV manifestations, it has been observed that a higher number of life stressors in at least the previous 6 months, the absence of social support and the types of personal coping mechanisms employed, all influence HPV progression. In women with cervical dysplasia, a connection between greater stress experiences and dysregulation of specific immune responses has been observed. Once HPV enters a cell via the α6 integrin there are three possible sequences: latent infection, subclinical infection, and clinically manifest disease. HPV proliferation in differentiated epithelial cells induces morphologically cytopathic changes (koilocytosis, epidermal thickening, hyperplasia, hyperkeratosis). Oncogenic transformation requires the integration of the virus genome into the host genome. In doing so, DNA in the E1 region of E2 breaks down, leading to transcription disorders of E6 and E7. For the formation of irreversible malignancy, the following sequence is necessary: initial expression of E6 and E7 genes followed by suppression of apoptosis and the stabile expression of E6 and E7 proteins that protect transformed cells from apoptosis. A successful immune response is characterized by a strong, local cell-mediated immune response. Several factors are important for the regression of HPV manifestation/infection, among which is psychological stress which can prolong the duration and severity of HPV disease. Stress hormones may reactivate latent tumor viruses, stimulate viral oncogene expression, and inhibit antiviral host responses. In the regression of HPV infection, increased activity of Th1 cells was observed. However, during psychosocial stress, a decrease in the Th1 type of immune response is seen, and there is a shift towards a Th2 response. Understanding perceived stress and biological changes in stress, as well as the evaluation of immune parameters, gives researchers a better picture of how stress influences HPV infections and how to improve disease management and outcomes.


Review of pathology data for regulatory purposes.
This paper describes the review process for pathology data submitted to the Division of Pathology, Center for Food Safety and Applied Nutrition of the Food and Drug Administration. The Division of Pathology independently evaluates the pathology data submitted in support of the safety of a given compound. The submissions are examined for agreement between summarized information and data from individual animals, appropriateness of terminology applied to lesions, and adequacy of information (distribution and severity of observed lesions). Problems and concerns encountered during review sometimes require examination of microscopic slides. The slide review provides an independent characterization of the lesions and a verification of their incidence. We present some problems commonly encountered in our review of the pathology data and describe some recent pathology evaluations. Finally, we suggest some considerations for reporting pathology data that may facilitate regulatory review.


Splanchnic and cerebral vasodilatory effects of calcitonin gene-related peptide I in humans.
The ability of synthetic human calcitonin gene-related peptide (CGRP I) to act as an arterial vasodilator was tested in healthy men by measuring arterial blood flow parameters in carotid, superior mesenteric, celiac, and femoral vessels. Calculated volume flow was significantly increased (140 +/- 21% of basal) in the SMA with a 2-ng/kg/min infusion of CGRP. Carotid artery volume flow increased dose dependently (96 +/- 6%, 122 +/- 15%, 135 +/- 15% of basal, respectively, with 2, 4, or 8 ng/kg/min). With steady-state infusion, carotid and superior mesenteric arterial flow parameters remained significantly elevated for 30 minutes after cessation of peptide administration. Blood pressure was unchanged. Pulse increased dose dependently. Arterial diameters were unchanged, implying activity at the arteriolar level.


Decreased anion gap associated with hypoalbuminemia and polyclonal gammopathy.
Anion gaps were determined in 82 patients with hypoalbuminemia; 24 of these patients had a polyclonal increase in gamma-globulin levels (designated group 5). The 58 patients without the polyclonal increase in gamma-globulin levels were subdivided according to the origin of their serum albumin loss as follows: group 1, renal group 2, gastrointestinal; group 3, skin; and group 4, malignant neoplasms. All groups had a statistically significant reduction in their mean anion gaps when compared with normal control subjects. The greatest decrease was when hypoalbuminemia was accompanied by a polyclonal increase in gamma-globulin levels. Hypoalbuminemia with or without a polyclonal gammopathy is a cause of a low anion gap. No statistically significant correlation was found between the anion gaps and individual serum albumin concentrations.


[Effects of Shugan Hewei Decoction and active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats].
To investigate the effects of Shugan Hewei Decoction and its active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats,and preliminarily explore its possible mechanism. Male SD rats were randomly divided into blank control group,model group,fluoxetine( positive control) group,Shugan Hewei Decoction high and low dose groups,high and low dose groups of three different substance fractions. After 3 weeks' CUMS and social isolation to induce models,intragastrical administration lasted for 7 d. Behavioral experiments( sucrose consumption test,open-field test,and forced swimming test) were then performed to evaluate the depression status of rats. Several neurotransmitters in hypothalamus of rats were determined by LC-MS/MS method,including dapamine( DA),norepinephrine( NE),serotonin( 5-HT),5-indoleacetic acid( 5-HIAA),γ-aminobutyric acid( GABA),and glutamic acid( Glu). As compared with the blank control group,the sucrose consumption was reduced( P<0. 01); the total distance and the number of crossing the central area were also significantly reduced( P< 0. 01,P< 0. 01),while the resting time increased significantly( P<0. 01); the forced swimming time was significantly prolonged( P<0. 01); DA,5-HT,NE,5-HIAA and GABA levels in hypothalamus were significantly reduced( P < 0. 01),while Glue level was significantly increased( P < 0. 01) in model group. As compared with the model group,all the above indexes had changes in fluoxetine group,Shugan Hewei Decoction whole recipe groups,volatile oils group,polysaccharides group,and terpenoids group( P<0. 01 or P<0. 05). Shugan Hewei Decoction whole recipe and its active substance fractions can improve the behavior of depression model rats and may exert anti-depression effects by regulating the content of neurotransmitters in the hypothalamus.


Investigating T cells by polychromatic flow cytometry.
Since its development, flow cytometry gave a relevant contribution to the field of Immunology. Its unique potential to analyse multiple parameters at the single cell level allowed the identification of unknown cell subsets with specific roles in immunoregulation as well as in the pathogenesis of several diseases. More recently, with the advent of new equipments and fluorochromes, the possibility exists to analyse simultaneously a large number (up to 19) of parameters in a single cell. This strategy, defined polychromatic flow cytometry (PFC), has been widely utilised in the last years for the fine analysis of immune cell phenotypes, including antigen-specific T lymphocytes, B cell subsets, and the intracellular phosphoproteome, among others. A huge amount of data can be generated by such an approach, and their interpretation could become a very complex and time-consuming task. Protocols for performing PFC will be discussed in this chapter, together with some guidelines for data interpretation and analysis.


Assessing Implementation of Social Screening Within US Health Care Settings: A Systematic Scoping Review.
Though a growing crop of health care reforms aims to encourage health care-based social screening, no literature has synthesized existing social screening implementation research to inform screening practice and policymaking. Systematic scoping review of peer-reviewed literature on social screening implementation published 1/1/2011-2/17/2022. We applied a 2-concept search (health care-based screening; social risk factors) to PubMed and Embase. Studies had to explore the implementation of health care-based multi-domain social screening and describe 1+ outcome related to the reach, adoption, implementation, and/or maintenance of screening. Two reviewers extracted data related to key study elements, including sample, setting, and implementation outcomes. Forty-two articles met inclusion criteria. Reach (n = 7): We found differences in screening rates by patient race/ethnicity; findings varied across studies. Patients who preferred Spanish had lower screening rates than English-preferring patients. Adoption (n = 13): Workforce education and dedicated quality improvement projects increased screening adoption. Implementation (n = 32): Time was the most cited barrier to screening; administration time differed by tool/workforce/modality. Use of standardized screening tools/workflows improved screening integration. Use of community health workers and/or technology improved risk disclosure and facilitated screening in resource-limited settings. Maintenance (n = 1): Only 1 study reported on maintenance; results showed a drop in screening over 21 months. Critical evidence gaps in social screening implementation persist. These include gaps in knowledge about effective strategies for integrating social screening into clinical workflows and ways to maximize screening equity. Future research should leverage the rapidly increasing number of screening initiatives to elevate and scale best practices.


The stinging impact of the imported fire ant.
Imported fire ants pose a real and present danger to allergic individuals living in endemic areas. This overview examines the impact of their presence, specifics of their venom and approach to the treatment of the hypersensitive individuals. Imported fire ant sting attack rates are high in endemic areas with sensitization occurring early in life among those dwelling in these locations. Once considered an outdoor pest, sting attacks are now known to occur indoors with the very young and the very old being especially susceptible due to the decreased mobility of these age extremes. Immunotherapy with whole body extract appears efficacious with both traditional and rush schedules finding utility among allergists. Both the mobility of the populace and the portability of imported fire ants have broadened the presence of both allergic patients and the ant itself among allergists previously unfamiliar with hypersensitive patients or the imported fire ant. Recent work has focused on achieving more rapid protection in hypersensitive patients given the high sting attack rates in endemic area with sensitization occurring early in life among those exposed to the imported fire ant.


Simple method for locating the optical center of a lens.
This article evaluates an old and little used method, which involves holding a small light in front of the lens and marking the spot where the centers of the images reflected from the front and rear surfaces overlap. The location of the center found this way correlates very well with the marking lensometer method. This method may also be used while the patient is wearing the spectacle. Thus, the examiner may easily see the patient's pupillary center and the optical center simultaneously. Induced prismatic effects from inaccurate lens centering can easily be diagnosed without removing the spectacle from the patient's face.


Meta-Analysis of Microarray Expression Studies on Metformin in Cancer Cell Lines.
Several studies have demonstrated that metformin (MTF) acts with variable efficiency as an anticancer agent. The pleiotropic anticancer effects of MTF on cancer cells have not been fully explored yet. By interrogating the Gene Expression Omnibus (GEO) for microarray expression data, we identified eight eligible submissions, representing five different studies, that employed various conditions including different cell lines, MTF concentrations, treatment durations, and cellular components. A compilation of the data sets of 13 different conditions contained 443 repeatedly up- and 387 repeatedly down-regulated genes; the majority of these 830 differentially expressed genes (DEGs) were associated with higher MTF concentrations and longer MTF treatment. The most frequently upregulated genes include DNA damage inducible transcript 4 (DDIT4), chromodomain helicase DNA binding protein 2 (CHD2), endoplasmic reticulum to nucleus signaling 1 (ERN1), and growth differentiation factor 15 (GDF15). The most commonly downregulated genes include arrestin domain containing 4 (ARRDC4), and thioredoxin interacting protein (TXNIP). The most significantly (p-value < 0.05, Fisher's exact test) overrepresented protein class was entitled, nucleic acid binding. Cholesterol biosynthesis and other metabolic pathways were specifically affected by downregulated pathway molecules. In addition, cell cycle pathways were significantly related to the data set. Generated networks were significantly related to, e.g., carbohydrate and lipid metabolism, cancer, cell cycle, and DNA replication, recombination, and repair. A second compilation comprised genes that were at least under one condition up- and in at least another condition down-regulated. Herein, the most frequently deregulated genes include nuclear paraspeckle assembly transcript 1 (NEAT1) and insulin induced gene 1 (INSIG1). The most significantly overrepresented protein classes in this compilation were entitled, nucleic acid binding, ubiquitin-protein ligase, and mRNA processing factor. In conclusion, this study provides a comprehensive list of deregulated genes and biofunctions related to in vitro MTF application and individual responses to different conditions. Biofunctions affected by MTF include, e.g., cholesterol synthesis and other metabolic pathways, cell cycle, and DNA replication, recombination, and repair. These findings can assist in defining the conditions in which MTF exerts additive or synergistic effects in cancer treatment.


Pulmonary edema. Pathophysiologic mechanisms and new approaches to therapy.
Since the first report by Ashbaugh and Petty in 1967 categorizing patients with acute respiratory failure and labelling the process the adult respiratory distress syndrome (ARDS), this illness has been recognized with increasing frequency. Adult respiratory distress syndrome now afflicts more than 150,000 people a year and the mortality remains in the 70 percent range in spite of significant advances in critical care medicine. As a consequence, research in the area of acute lung injury has intensified resulting in the elucidation of many of the pathophysiologic mechanisms operative in the process. As long as the mortality of ARDS remains high, research of this kind will be needed especially with regard to clinical trials of pharmacologic agents which have appeared promising in the laboratory. An aggressive approach, possibly utilizing multiple drug regimens, seems justified considering the morbidity and mortality with which are dealing. Until success is achieved, supportive intensive care with diligent attention to oxygen and ventilator management, infection control, and fluid therapy will be the mainstay of treatment for ARDS.


The management of severe traumatic brain injury in the initial postinjury hours - current evidence and controversies.
To provide an overview of recent studies discussing novel strategies, controversies, and challenges in the management of severe traumatic brain injury (sTBI) in the initial postinjury hours. Prehospital management of sTBI should adhere to Advanced Trauma Life Support (ATLS) principles. Maintaining oxygen saturation and blood pressure within target ranges on-scene by anesthetist, emergency physician or trained paramedics has resulted in improved outcomes. Emergency department (ED) management prioritizes airway control, stable blood pressure, spinal immobilization, and correction of impaired coagulation. Noninvasive techniques such as optic nerve sheath diameter measurement, pupillometry, and transcranial Doppler may aid in detecting intracranial hypertension. Osmotherapy and hyperventilation are effective as temporary measures to reduce intracranial pressure (ICP). Emergent computed tomography (CT) findings guide surgical interventions such as decompressive craniectomy, or evacuation of mass lesions. There are no neuroprotective drugs with proven clinical benefit, and steroids and hypothermia cannot be recommended due to adverse effects in randomized controlled trials. Advancement of the prehospital and ED care that include stabilization of physiological parameters, rapid correction of impaired coagulation, noninvasive techniques to identify raised ICP, emergent surgical evacuation of mass lesions and/or decompressive craniectomy, and temporary measures to counteract increased ICP play pivotal roles in the initial management of sTBI. Individualized approaches considering the underlying pathology are crucial for accurate outcome prediction.


E-0702, a new cephalosporin, is incorporated into Escherichia coli cells via the tonB-dependent iron transport system.
E-0702, a new cephalosporin with a potent antipseudomonal action, was synthesized. In the study of the mode of action of this antibiotic in Escherichia coli, it was found that mutants which acquired resistance to E-0702 were isolated spontaneously and could be shown to be susceptible to its closely related derivatives, E-0702-060 and E-0702-061, and other representative beta-lactam antibiotics. In these mutants, no increased production of beta-lactamase was detectable. No apparent differences between the resistant mutants and the parental strains were observed in the affinity of E-0702 for penicillin-binding proteins. Furthermore, no significant reduction in or loss of both OmpF and OmpC porin proteins in the outer membrane was observed. The mutation was mapped to the tonB gene, which is known to be essential for the iron transport system of bacteria. The bactericidal action of E-0702 was rapidly expressed against iron-starved cells in which the iron transport system was induced, whereas the bactericidal action against iron-supplemented cells was ineffective. It is suggested that E-0702 is incorporated into bacterial cells as a chelator of iron via the tonB-dependent iron transport system, after which its strong and rapid bactericidal action is manifested.


With strengthened guidelines for health care workers, the CDC ups its game against the deadly Ebola virus.
Informed by the cases of two nurses who contracted Ebola virus disease (EVD) while caring for a patient with the disease in Dallas, TX, the Centers for Disease Control and Prevention (CDC) in Atlanta, GA, has unveiled strengthened guidance for health care workers. Further, nursing organizations are pledging to work together to identify gaps and make system-level improvements to protect both patients and caregivers. The CDC's new recommendations emphasize rigorous training for health care workers in how to put on and take off personal protective equipment (PPE), and they state that this activity should always be carefully supervised by a monitor. The guidance also states that health care workers should use either an N-95' respirator mask or a powered air purifying respirator (PAPR) when they are providing care to a patient with Ebola. Experts stress that the new guidance does not change the fundamental issue that Ebola is transmitted through contact with infectious substances from patients. Nursing organizations are pledging to work together to identify problems and improve safety for both caregivers and patients.


Characterization of the human transferrin receptor produced in a baculovirus expression system.
Recombinant human transferrin receptor has been produced in a baculovirus expression system. Magnetic particles coated with an anti-transferrin receptor monoclonal antibody were used to immunoselect virus-infected Sf9 insect cells expressing the human transferrin receptor on their cell surface. Recombinant virus containing the human transferrin receptor cDNA was then plaque-purified from these cells. Biosynthetic labeling studies of infected cells showed that the human transferrin receptor is one of the major proteins made 2-3 days postinfection. The recombinant receptor made in insect cells is glycosylated and is also posttranslationally modified by the addition of a fatty acid moiety. However, studies with tunicamycin and endoglycosidases H and F showed that the oligosaccharides displayed on the recombinant receptor differ from those found on the naturally occurring receptor in human cells. As a consequence, the human receptor produced in the baculovirus system has an Mr of 82,000 and is smaller in size than the authentic receptor. About 30% of human transferrin receptors made in insect cells do not form intermolecular disulfide bonds, but are recognized by the anti-transferrin receptor antibody, B3/25, and bind specifically to a human transferrin-Sepharose column. Binding studies using 125I-labeled human transferrin showed that insect cells infected with the recombinant virus expressed an average of 5.8 +/- 0.9 X 10(5) transferrin receptors (Kd = 63 +/- 9 nM) on their cell surface. Thus, the human transferrin receptor produced in insect cells is biologically active and appears suitable for structural and functional studies.


The impact of maternal psychiatric illness on infant development.
Maternal depression and anxiety are associated with compromises in infant and maternal social and emotional functioning. In this paper, we briefly review the literature on this topic and present some preliminary findings on a group of mothers in treatment for major depressive disorder, panic disorder, or obsessive-compulsive disorder. The findings suggest that the symptom reports of treated mothers with established DSM diagnoses were similar overall to those of control mothers. However, the mothers' psychiatric illness had a compromising effect on their interactions with their infants and on their infants' social and emotional functioning. The implications of these results are discussed.


Acute and developmental toxicity assessment of erincine A-enriched Hericium erinaceus mycelia in Sprague-Dawley rats.
This study aimed to establish an in vitro model to confirm the efficacy of erinacine A-enriched Hericium erinaceus (EAHE) mycelia and investigate its potential adverse effects in a preclinical experimental setting, including an assessment on the oral administration of EAHE mycelia in acute and prenatal developmental toxicity tests. At a single dose of 5000 mg/kg body weight, EAHE mycelia elicited no death or treatment-related signs of toxicity in ten Sprague-Dawley rats of both sexes during the 14 days of the experimental period. After considering the recommended dose range of EAHE mycelia from the acute toxicity test as well as the therapeutic doses, EAHE mycelia was administered to 66 pregnant rats in the low, medium, and high-dose groups by gavage at 875, 1750, and 2625 mg/kg body weight, respectively. All dams were subjected to a Caesarean section on the 20th day of pregnancy, and the fetuses were examined for any morphological abnormalities. Results indicated that weight of uterus, fetal body weight, number of corpora lutea, implantation sites, pre-implantation loss, and post-implantation loss of the treatment groups and the control group exhibited no statistical difference. In addition, no significant differences were observed in the fetal external, organ, and skeletal examinations. Taken together, it can be concluded that EAHE mycelia is considered safe and practically nontoxic for consumption within the appropriate doses and investigation period in this study.


Scalp flap rotation with primary donor site closure.
A 57-year-old man with a 7-cm defect of the left temple underwent reconstruction with a large scalp rotation flap that shifted the donor defect to the back of the neck so that it could be closed primarily. This approach, also used successfully in 7 other patients with similar defects, avoided the need for an unsightly skin graft in the donor site while providing tissue with a color and texture that blended well with the surrounding forehead and facial skin. Primary closure of the donor site reduces scalp flap morbidity and improves the overall aesthetic outcome.


A novel fluorescent probe-based flow cytometric assay for mineral-containing nanoparticles in serum.
Calciprotein particles, nanoscale aggregates of insoluble mineral and binding proteins, have emerged as potential mediators of phosphate toxicity in patients with Chronic Kidney Disease. Although existing immunochemical methods for their detection have provided compelling data, these approaches are indirect, lack specificity and are subject to a number of other technical and theoretical shortcomings. Here we have developed a rapid homogeneous fluorescent probe-based flow cytometric method for the detection and quantitation of individual mineral-containing nanoparticles in human and animal serum. This method allows the discrimination of membrane-bound from membrane-free particles and different mineral phases (amorphous vs. crystalline). Critically, the method has been optimised for use on a conventional instrument, without the need for manual hardware adjustments. Using this method, we demonstrate a consistency in findings across studies of Chronic Kidney Disease patients and commonly used uraemic animal models. These studies demonstrate that renal dysfunction is associated with the ripening of calciprotein particles to the crystalline state and reveal bone metabolism and dietary mineral as important modulators of circulating levels. Flow cytometric analysis of calciprotein particles may enhance our understanding of mineral handling in kidney disease and provide a novel indicator of therapeutic efficacy for interventions targeting Chronic Kidney Disease-Mineral Bone Disorder.


Alignment, cross linking, and beyond: a collagen architect's guide to the skeletal muscle extracellular matrix.
The muscle extracellular matrix (ECM) forms a complex network of collagens, proteoglycans, and other proteins that produce a favorable environment for muscle regeneration, protect the sarcolemma from contraction-induced damage, and provide a pathway for the lateral transmission of contractile force. In each of these functions, the structure and organization of the muscle ECM play an important role. Many aspects of collagen architecture, including collagen alignment, cross linking, and packing density affect the regenerative capacity, passive mechanical properties, and contractile force transmission pathways of skeletal muscle. The balance between fortifying the muscle ECM and maintaining ECM turnover and compliance is highly dependent on the integrated organization, or architecture, of the muscle matrix, especially related to collagen. While muscle ECM remodeling patterns in response to exercise and disease are similar, in that collagen synthesis can increase in both cases, one outcome leads to a stronger muscle and the other leads to fibrosis. In this review, we provide a comprehensive analysis of the architectural features of each layer of muscle ECM: epimysium, perimysium, and endomysium. Further, we detail the importance of muscle ECM architecture to biomechanical function in the context of exercise or fibrosis, including disease, injury, and aging. We describe how collagen architecture is linked to active and passive muscle biomechanics and which architectural features are acutely dynamic and adapt over time. Future studies should investigate the significance of collagen architecture in muscle stiffness, ECM turnover, and lateral force transmission in the context of health and fibrosis.


The Milton survey: Part 1, General methods, height, weight and 24-hour excretion of sodium, potassium, calcium, magnesium and creatinine.
This paper describes the methods and general aims of a survey carried out on just over 1200 subjects (about 82% of the adult population) in Milton, a small town south of Dunedin. Data were collected on personal and family history, present medication if any, 24-hour dietary recall, psychometric scores, height, weight, skin-fold thickness, anthropometry, blood pressure, heart rate, electrocardiogram, mass miniature X-ray of chest, forced expiratory volume (FEV1), fasting plasma cholesterol and triglycerides, lipoprotein pattern and fasting and post-prandial blood sugar in a selected subgroup, and 24-hour urine volume and excretion of sodium, potassium, calcium, magnesium and creatinine. Mean values are given in the paper for each 10-year age group for height, weight, Quetelet's index, 24-hour urine volume, creatinine, sodium, potassium, calcium and magnesium. These and other results will be discussed in detail in subsequent papers.


Complications Associated With Minimally Invasive Anterior to the Psoas (ATP) Fusion of the Lumbosacral Spine.
Retrospective cohort study. To analyze complications associated with minimally invasive anterolateral retroperitoneal antepsoas lumbosacral fusion (MIS-ATP). MIS-ATP provides anterolateral access to the lumbar spine allowing for safe anterior lumbar interbody fusions between T12-S1. Anecdotally, many surgeons believe that ATP approach is not feasible at L5-S1 level, predisposing to catastrophic vascular injuries. This approach may help overcome limitations associated with conventional straight anterior lumbar interbody fusions, MIS lateral lumbar interbody fusion, and oblique lateral interbody fusion. A detailed retrospective chart review of patients who had underwent MIS-ATP approach for lumbar fusion between T12-S1 was performed. Available electronic data from surgeries performed between January 2008 and March 2017 was carefully screened for surgical patients treated for spondylolisthesis, spondylosis, stenosis, sagittal, and/or coronal deformity. Detailed review of electronic medical records including operative notes, progress notes, discharge summaries, laboratory results, imaging reports, and clinic visit notes performed by a single independent reviewer not involved in patient care for documented complications. A complication is defined as any adverse event related to the index spine procedure for which patient required specific intervention or treatment. Nine hundred forty patients with a total of 2429 interbody fusion levels performed via MIS-ATP were identified during the study period. Sixty-seven patients (7.2%) sustained one or more complications during the perioperative period, of which 25.5% were surgical and 74.5% were medical. Overall, 78 (8.2%) surgical complications pertaining to the index procedure were noted during a postoperative period of 1 year from the date of surgery. No major vascular or direct visceral injuries were encountered. MIS-ATP approach provides a safe access to anterolateral interbody fusions between T12-S1. The ATP approach is performed by the spine surgeon, does not require neuromonitoring, and warrants minimal to no psoas muscle retraction resulting in significantly reduced postoperative thigh pain and rare neurologic injuries. Additionally, the direct and clear visualization of the retroperitoneal vasculature provided by the ATP approach minimizes the risk of inadvertent vascular injury. 4.


[African DNA lineages in mitochondrial gene pool of Europeans].
Mitochondrial DNA (mtDNA) nucleotide sequences of African origin have been found at low frequency (1%, in average) in different European populations. In the present study, data on mtDNA variability in populations of Eurasia and Africa are analyzed and search of African-specific lineages present in Europeans is conducted. The results of analysis indicate that, despite a high diversity of African mtDNA haplotypes found in Europeans, monophyletic clusters of African mtDNA lineages, arisen in Europe and characterized by long-term diversity, are nearly absent in Europe. Only two respective clusters (belonging to haplogroups L1b and L3b), which evolutionary age does not exceed 6.5 thousands years, were revealed. Comparative analysis of distribution of frequencies of autosomal microsatellite alleles found in Russian individuals, carrying the African-specific mitochondrial haplotypes, in populations of Europe and Africa has indicated that autosomal genotypes of those Russian individuals are characterized by the presence of alleles characteristic mostly for Europeans.


Overexpression of FT in cotton affects architecture but not floral organogenesis.
Flowering marks the change from indeterminate to determinate plant growth, and this developmental transition involves the activity of the Arabidopsis FLOWERING LOCUS T (FT) gene product and its orthologs. We demonstrated that when FT is ectopically expressed from a viral vector in cotton, a process referred to as virus induced flowering (VIF), it uncouples flowering from photoperiodic regulation and promotes determinate growth in aerial organs. The accelerated switch to determinate growth affected cotton floral buds and sympodial growth, but did not disrupt floral organogenesis. These results can be interpreted in the context of the balance model, which argues that the balance of indeterminate and determinate growth is influenced by the relative abundance of indeterminate and determinate factors in the growing apices. These results emphasize the expanding role of FT in affecting general determinate growth.


Linkage and segregation of unselected markers in matings of Nocardia erythropolis with Nocardia canicruria.
The segregation of unselected genes expressing resistance or susceptibility to acriflavine, erythromycin, streptomycin, and tetracycline was analyzed in selected prototrophic recombinants resulting from matings of Nocardia erythropolis and N. canicruria. The organisms were shown to be functionally haploid and appeared to contain not more than one genome. It was postulated that all observed genes were present in a linear linkage group. The ordering of the genes in N. erythropolis was: tetB10 eryB9 his-3 purA1 acr-2 strA1 (respectively, resistance to tetracycline and erythromycin, deficiency for histidine and for purine, and resistance to acriflavine and streptomycin). The ordering of the genes in N. canicruria was: purB2 tetA9 eryA7 acr-11 strB2 (respectively, deficiency for purine, and resistance to tetracycline, erythromycin, acriflavine, and streptomycin). Excluding the genes for acriflavine resistance, acr-2 and acr-11, resistance loci in N. erythropolis were not allelic to and showed lateral displacement from genes controlling phenotypically similar resistance in N. canicruria. Evidence for some lack of homology between N. erythropolis and N. canicruria genomes was found. Recombination phenomena between the nocardial species was postulated to occur as a result of formation of a heterogenomic zygote in which new combinations were produced. Production of selectable, haploid recombinants was ascribed to subsequent haploidization of the zygote.


Spectral Fingerprints of Cortical Neuromodulation.
Pupil size has been established as a versatile marker of noradrenergic and cholinergic neuromodulation, which has profound effects on neuronal processing, cognition, and behavior. However, little is known about the cortical control and effects of pupil-linked neuromodulation. Here, we show that pupil dynamics are tightly coupled to temporally, spectrally, and spatially specific modulations of local and large-scale cortical population activity in the human brain. We quantified the dynamics of band-limited cortical population activity in resting human subjects using magnetoencephalography and investigated how neural dynamics were linked to simultaneously recorded pupil dynamics. Our results show that pupil-linked neuromodulation does not merely affect cortical population activity in a stereotypical fashion. Instead, we identified three frontal, precentral, and occipitoparietal networks, in which local population activity with distinct spectral profiles in the theta, beta, and alpha bands temporally preceded and followed changes in pupil size. Furthermore, we found that amplitude coupling at ∼16 Hz in a large-scale frontoparietal network predicted pupil dynamics. Our results unravel network-specific spectral fingerprints of cortical neuromodulation in the human brain that likely reflect both the causes and effects of neuromodulation.SIGNIFICANCE STATEMENT Brain function is constantly affected by modulatory neurotransmitters. Pupil size has been established as a versatile marker of noradrenergic and cholinergic neuromodulation. However, because the cortical correlates of pupil dynamics are largely unknown, fundamental questions remain unresolved. Which cortical networks control pupil-linked neuromodulation? Does neuromodulation affect cortical activity in a stereotypical or region-specific fashion? To address this, we quantified the dynamics of cortical population activity in human subjects using magnetoencephalography. We found that pupil dynamics are coupled to highly specific modulations of local and large-scale cortical activity in the human brain. We identified four cortical networks with distinct spectral profiles that temporally predicted and followed pupil size dynamics. These effects likely reflect both the cortical control and effect of neuromodulation.


Best of the Radiosurgery Society® Scientific Meeting 2014: stereotactic radiosurgery/stereotactic body radiotherapy treatment of extracranial and intracranial lesions.
The SRS/SBRT Scientific Meeting 2014, Minneapolis, MN, USA, 7-10 May 2014. The Radiosurgery Society(®), a professional medical society dedicated to advancing the field of stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), held the international Radiosurgery Society Scientific Meeting, from 7-10 May 2014 in Minneapolis (MN, USA). This year's conference attracted over 400 attendants from around the world and featured over 100 presentations (46 oral) describing the role of SRS/SBRT for the treatment of intracranial and extracranial malignant and nonmalignant lesions. This article summarizes the meeting highlights for SRS/SBRT treatments, both intracranial and extracranial, in a concise review.


Sequencing platinum foil matrix removal in postceramic soldering of the collarless veneered retainer.
Postceramic soldering of collarless veneered retainers in which the porcelain margins were formed with a platinum foil matrix technique was investigated. The purpose of the study was to determine if removing the platinum foil matrix before or after indexing and soldering procedures would affect the porcelain margin integrity in fixed partial dentures. Prostheses were fabricated on a nickel-chromium laboratory model using both sequences. Six test cycles were performed. Each cycle included one soldering with matrix support and one without the matrix, for a total of 12 solderings. The fixed partial dentures were compared for degree of marginal seating with a measuring microscope and for configuration changes at the porcelain margins with scanning electron micrographs. In the microscopic analysis of marginal closure, soldering without foil matrix was statistically equal to soldering with foil in place. Removal of the platinum foil matrices prior to indexing provided for no further seating of the metal ceramic retainers. Evaluation by scanning electron microscopy demonstrated distinct configuration changes in the porcelain margins for the specimens soldered without matrix support.


Mutagenic activation of N-2-fluorenylacetamide and N-hydroxy-N-2-fluorenylacetamide in subcellular fractions from X/Gf mice.
The Salmonella mutagenesis test system was used to evaluate the in vitro mutagenic potency of N-2-fluorenylacetamide (2-FAA) and N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) mediated by liver and kidney subcellular fractions from X/Gf mice, a strain resistant to 2-FAA carcinogenesis. Pretreatment of the mice with the microsomal inducers 3-methylcholanthrene (MCA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased the number of revertants from both liver and kidney fractions. Mutagenicity of N-OH-2-FAA mediated by liver or kidney microsomes was partially inhibited at 0.001--0.1 microM Paraxon (diethyl-p-nitrophenyl phosphate), an inhibitor of deacetylase enzyme, and the inhibition was complete (98%) in microsomes from control mice (100 microM Paraoxon). Conversely, the liver and kidney microsomal fractions from MCA- and TCDD-treated X/Gf mice were less sensitive to Paraoxon. The inhibition of kidney or liver cytosol-mediated N-OH-2-FAA mutagenicity by Paraoxon was less than that observed with the microsomal fraction (50% inhibition at 1 x 10(-7) and 1 x 10(-5) M Paraoxon, respectively). The mutagenicity of 2-FAA and N-OH-2-FAA mediated by liver or kidney subcellular fractions from X/Gf mice and its response to inducers and inhibitors of mutagenic activation processes appear similar to those observed in species both resistant (cotton rat) and sensitive (Sprague-Dawley rat, NIH Swiss mice) to 2-FAA carcinogenesis.


The ICM research agenda on critical care ultrasonography.
Critical care ultrasonography has utility for the diagnosis and management of critical illness and is in widespread use by frontline intensivists. As there is a need for research to validate and extend its utility, the Editor of Intensive Care Medicine included critical care ultrasonography as a topic in the ICM Research Agenda issue. Eleven international experts in the field of critical care ultrasonography contributed to the writing project. With the intention of developing a research agenda for the field, they reviewed best standards of care, new advances in the field, common beliefs that have been contradicted by recent trials, and unanswered questions related to critical care ultrasonography. The writing group focused on the provision of training in critical care ultrasonography, technological advances, and some specific clinical applications. The writing group identified several fields of interest for research and proposed ten research studies that would address important aspects of critical care ultrasonography.


Multipartite state generation in quantum networks with optimal scaling.
We introduce a repeater scheme to efficiently distribute multipartite entangled states in a quantum network with optimal scaling. The scheme allows to generate graph states such as 2D and 3D cluster states of growing size or GHZ states over arbitrary distances, with a constant overhead per node/channel that is independent of the distance. The approach is genuine multipartite, and is based on the measurement-based implementation of multipartite hashing, an entanglement purification protocol that operates on a large ensemble together with local merging/connection of elementary building blocks. We analyze the performance of the scheme in a setting where local or global storage is limited, and compare it to bipartite and hybrid approaches that are based on the distribution of entangled pairs. We find that the multipartite approach offers a storage advantage, which results in higher efficiency and better performance in certain parameter regimes. We generalize our approach to arbitrary network topologies and different target graph states.


Experimental Investigation of Calcium-Doped Zinc Aluminate Nanoparticles as a Promising Material for Microwave Applications.
Miniaturization of microstrip patch antennas (MPAs) is vital in applications such as wireless networks, mobile devices, global positioning satellites, and upcoming wireless terminals. This miniaturization has led to a demand for new materials with higher permittivity compared to the existing ones. Zinc aluminate (ZnAl2O4) ceramic is an exceptional and versatile material in this context, thanks to its high dielectric permittivity and low tangent loss, making it suitable for microwave applications. This article explores the feasibility of sol-gel-prepared Ca-doped ZnAl2O4 ceramic nanoparticles to be useful in fabricating a MPA. These nanoparticles were examined using X-ray diffraction, which confirmed their polycrystalline structure, and the morphological investigation evidenced the spherical grains having a mean diameter of 16 nm. The dielectric permittivity of the ZnAl2O4Ca nanoparticles is 21.11, with a tangential loss of 0.0247. A prototype MPA made by using Ca-doped ZnAl2O4 nanoparticles showed a return loss of -20.92 dB at a resonance frequency of 6.8 GHz with a bandwidth of 600 MHz. These results indicate that Ca-doped ZnAl2O4 ceramic nanoparticles possess exceptional dielectric characteristics, which make them a promising candidate for MPA applications.


Components of contributing conditions to strengthen health system management and leadership capacity building: a systematic review and decision making framework.
The purpose of this study is to identify components of contributing conditions to strengthen leadership and management capacity in the health system. A systematic search was undertaken in databases including PubMed, Scopus, Web of Science and local resources of Scientific Information Database and Magiran in January 2020. Two independent researchers checked the research process, screening of articles and quality assessment. The quality of the studies was assessed by JBI critical appraisal tools for qualitative studies. The components of the dimensions of health system management and leadership capacity were categorized according to the WHO conceptual framework using a content analysis approach. A total of 17 articles were included in this study. In total, 16 categories of components include human resource information system (n = 5); criteria, plans and procedures for selection and appointment (n = 5); development of education system (n = 11); skills (n = 39); knowledge (n = 8); attitudes (n = 6); behaviors (n = 10); resource and critical management system (n = 7); performance and processes management (n = 3); operational planning for critical systems (n = 4); establish control systems (n = 2); inputs and outputs of organizations (n = 2); accountability and responsibility to customers and stakeholders (n = 4); legal authority and requirements to play the role of managers (n = 9); external and internal environment management (n = 7); establish a system of appreciation and encouragement (n = 6). Each of these categories also contains subcategories. Identifying prerequisite conditions are necessary for building leadership and management capacity in health systems. Therefore, extracted components provide a simple but coherent framework that can be adapted or modified for use in local situations. The components have a variety of uses, including mapping current activities, needs assessment, planning leadership and management development strategies and monitoring and evaluation.


Functions of noncoding RNAs in glial development.
Glia are widely distributed in the central nervous system and are closely related to cell metabolism, signal transduction, support, cell migration, and other nervous system development processes and functions. Glial development is complex and essential, including the processes of proliferation, differentiation, and migration, and requires precise regulatory networks. Noncoding RNAs (ncRNAs) can be deeply involved in glial development through gene regulation. Here, we review the regulatory roles of ncRNAs in glial development. We briefly describe the classification and functions of noncoding RNAs and focus on microRNAs (miRNAs) and long ncRNAs (lncRNAs), which have been reported to participate extensively during glial formation. The highlight of this summary is that miRNAs and lncRNAs can participate in and regulate the signaling pathways of glial development. The review not only describes how noncoding RNAs participate in nervous system development but also explains the processes of glial development, providing a foundation for subsequent studies on glial development and new insights into the pathogeneses of related neurological diseases.


Identification of alternatives for the management of foliar nematodes in floriculture.
The foliar nematodes, Aphelenchoides spp, have emerged as important pests of ornamentals in North America during the last decade. Due to the ban on the use of potentially toxic pesticides, there are currently no nematicides registered to manage foliar nematodes on ornamentals. Therefore, we have evaluated a biological [Burkholderia cepacia (syn Pseudomonas cepacia)], two plant products [clove (Syzygium aromaticum) extract and Nimbecidine (azadirachtin)] and twelve chemical pesticides registered for the management of insects, mites, slugs or diseases of ornamentals, against Aphelenchoides fragariae on the most popular ornamental, hosta (Hosta spp), for two consecutive years. We found ZeroTol (270 g liter-1 peroxyacetic acid), currently labeled as a broad-spectrum fungicide/algicide, to be a very potent nematicide that killed 100% of the nematodes in water suspension. It also caused over 70% reduction in A fragariae population in soil and in the leaves without any phytotoxicity. B cepacia caused 67-85% reduction in A fragariae population in leaves and 50% reduction in the soil whereas insecticidal soap caused over 72% reduction in leaves and 61% reduction in the soil. Clove extract and Nimbecidine did not show any potential for the control of A fragariae on hosta. Although all twelve chemical pesticides were effective in reducing the population of A fragariae in the soil 45 days after treatment (DAT), only diazinon 475 g liter-1 EC, trichlorfon 800 g kg-1 SP, ethoprophos 100 g kg-1 GR, oxamyl 100 g kg-1 GR and ZeroTol caused over 70% reduction in nematode population compared with the control. In the leaves, only diazinon EC, trichlorfon SP, insecticidal soap, oxamyl GR and ZeroTol consistently caused over 70% nematode population reduction compared with the control at 45 DAT in both years. Thus, only diazinon EC, trichlorfon SP, oxamyl GR and ZeroTol consistently caused over 70% reduction in nematode population both in soil and leaves. Due to the recent ban by the US Environmental Protection Agency on the use of the first three of these formulations, only ZeroTol would serve as an effective tool to manage foliar nematodes in ornamentals. Although not as effective as ZeroTol in the soil, insecticidal soap is the only other alternative for foliar nematode management.


Lipid Accumulation in the Liver of Rats Fed a Soy Protein Isolate Diet with Excess Cystine, and its Prevention by Methionine or Choline.
The effects on liver and serum lipids of rats of excess cystine added to their casein or soy protein isolate diets were studied. When excess cystine was added to the casein diet, liver lipids were not changed. Using soy protein isolate as a protein source, both food consumption and body weight gain were depressed with increasing levels of dietary cystine. Liver total lipids, cholesterol, triacylglycerols, and phospholipids were increased in rats with 2.5% or 3.5% cystine diets. Serum cholesterol of rats on the 3.5% cystine diet was significantly higher than those of the other groups, which yielded similar values. Serum triacylglycerols were increased by the addition of 0.5% or 1.5% cystine, and decreased by the addition of 2.5% or 3.5% cystine to the diet. Serum free fatty acids increased or tended to increase when liver lipid accumulation was observed. The addition of either methionine or choline to the cystine-excess diet containing soy protein isolate prevented the accumulation of triacylglycerols and phospholipids in the liver although serum triacylglycerols did not return to the levels of rats on the diet without cystine, and serum free fatty acid levels were not changed. Thus, it is surmised that this fatty liver might be due to the choline deficiency induced by the excess cystine.


NeatFreq: reference-free data reduction and coverage normalization for De Novo sequence assembly.
Deep shotgun sequencing on next generation sequencing (NGS) platforms has contributed significant amounts of data to enrich our understanding of genomes, transcriptomes, amplified single-cell genomes, and metagenomes. However, deep coverage variations in short-read data sets and high sequencing error rates of modern sequencers present new computational challenges in data interpretation, including mapping and de novo assembly. New lab techniques such as multiple displacement amplification (MDA) of single cells and sequence independent single primer amplification (SISPA) allow for sequencing of organisms that cannot be cultured, but generate highly variable coverage due to amplification biases. Here we introduce NeatFreq, a software tool that reduces a data set to more uniform coverage by clustering and selecting from reads binned by their median kmer frequency (RMKF) and uniqueness. Previous algorithms normalize read coverage based on RMKF, but do not include methods for the preferred selection of (1) extremely low coverage regions produced by extremely variable sequencing of random-primed products and (2) 2-sided paired-end sequences. The algorithm increases the incorporation of the most unique, lowest coverage, segments of a genome using an error-corrected data set. NeatFreq was applied to bacterial, viral plaque, and single-cell sequencing data. The algorithm showed an increase in the rate at which the most unique reads in a genome were included in the assembled consensus while also reducing the count of duplicative and erroneous contigs (strings of high confidence overlaps) in the deliverable consensus. The results obtained from conventional Overlap-Layout-Consensus (OLC) were compared to simulated multi-de Bruijn graph assembly alternatives trained for variable coverage input using sequence before and after normalization of coverage. Coverage reduction was shown to increase processing speed and reduce memory requirements when using conventional bacterial assembly algorithms. The normalization of deep coverage spikes, which would otherwise inhibit consensus resolution, enables High Throughput Sequencing (HTS) assembly projects to consistently run to completion with existing assembly software. The NeatFreq software package is free, open source and available at https://github.com/bioh4x/NeatFreq .


In Vivo Multicolor Imaging with Fluorescent Probes Revealed the Dynamics and Function of Osteoclast Proton Pumps.
In vivo two-photon fluorescence imaging is a powerful modality to monitor cell dynamics in biomedical studies. To detect protein functions in living animals in real-time, fluorescent probes must show a quick response to the target function in specific tissues. Here, we developed a rhodamine-based small-molecule fluorescent probe called Red-pHocas (red pH-activatable fluorescent probe for osteoclast activity sensing) to reversibly detect the acidic environments for the spatiotemporal analysis of the function of osteoclast proton pumps. The introduction of electron-withdrawing N-alkyl substituents in the rhodamine spirolactam fluorophore remarkably increased the kinetics of the fluorescence response to acidic pHs, which allowed the rapid and reversible monitoring of acidic compartments and the analysis of the dynamics of osteoclast proton pumps during osteoclastic bone resorption. In vivo multicolor two-photon imaging using Red-pHocas in fluorescent reporter mice revealed that bone acidification occurred synchronously with the accumulation of proton pumps onto the bone surfaces. To our knowledge, this is the first study to demonstrate the direct involvement of osteoclast proton pumps in bone acidification under intravital conditions by means of an imaging probe.


Novel Colorimetric Aptasensor for Zearalenone Detection Based on Nontarget-Induced Aptamer Walker, Gold Nanoparticles, and Exonuclease-Assisted Recycling Amplification.
Zearalenone (ZEN) toxicity is a significant risk for human beings. Thus, it is of high importance to develop sensitive, precise, and inexpensive analytical methods for ZEN detection, especially in human serum. Here, a colorimetric aptasensor is presented for the determination of ZEN based on the nontarget-induced aptamer walker, catalytic reaction of gold nanoparticles (AuNPs), exonuclease III (Exo III) as a signal amplifier, and 4-nitrophenol as a colorimetric agent. Low amount of ZEN requirement and signal amplification are some of the distinct advantages of the proposed aptasensor. In the absence of ZEN, the aptamer (Apt) starts walking on the AuNP surface with the help of Exo III and binds to multiple complementary strands of aptamer, leading to the change of sample color from yellow to colorless. Upon the addition of ZEN, both the Apt and complementary strand exist as single-stranded DNAs on the surface of AuNPs, resulting in less access of 4-nitrophenol to the surface of AuNPs and less catalytic performance of AuNPs. In this situation, the color of the sample remains yellow (the color of 4-nitrophenol). The presented aptasensor was capable to detect ZEN in a wide linear dynamic range, 20-80 000 ng/L, with a detection limit of 10 ng/L. The prepared sensing strategy was successfully used for ZEN determination in the human serum sample.


Interpretable modeling and discovery of key predictors for pneumonia diagnosis in children based on electronic medical records.
Community-acquired pneumonia is one of the most common infectious diseases in children and is a leading cause of death among children under 5 years of age, resulting in high rates of antibiotic usage and hospitalization. It is of extremely practical significance to make full use of the existing electronic medical records to study pneumonia and to establish automatic diagnosis models for pneumonia. We established pneumonia diagnosis models of Bayesian network using a total of 13,448 electronic medical records. We investigated learning network structure and parameter estimation and evaluated different structure learning strategies and various modeling methods. By identifying the key predictors of model, the pneumonia status was analyzed. The performance of the proposed Bayesian network was evaluated using a set of 3361 cases with a precision of 0.7861, a recall of 0.9889, and an F1-score of 0.8759. On an independent external validation set containing 4925 cases, Bayesian network achieved a precision of 0.7382, a recall of 0.9947, and an F1-score of 0.8475. Our proposed Bayesian network outperformed all other methods, including CatBoost, XGBoost, LightGBM, logistic regression, and ridge classification. The appropriate feature selection improved the performance of Bayesian networks. The proposed Bayesian network had good generalizability and could be directly applied to clinical research centers. And the key predictors identified by the network demonstrated good clinical interpretability, allowing for a better understanding of pneumonia status and complications. This study had important clinical value and practical significance for the research and diagnosis of pediatric pneumonia.


Potassium-induced depolarization stimulates somatostatin gene expression in cultured fetal rat cerebrocortical cells.
The stimulatory effect of potassium depolarization upon somatostatin mRNA (SS mRNA) levels in primary cultures of fetal cerebrocortical cells was analyzed. Depolarizing stimuli, such as 56 mM K+ concentration for 24 hours, elicited an increase in immunoreactive somatostatin (IR-SS) release to the media and SS mRNA levels, suggesting that somatostatin secretion can be coupled to SS mRNA accumulation. These changes were inhibited by the Ca2+ channel antagonist verapamil (VPM). In contrast, Na+ channel blockade by tetrodotoxin (TTX) did not modify the 24 h potassium-induced increase in SS mRNA. These results suggest that the induction of SS mRNA expression by K+ involves the modulation of calcium ion channels.


Development of Second-Generation CDK2 Inhibitors for the Prevention of Cisplatin-Induced Hearing Loss.
There are currently no FDA-approved therapies to prevent the hearing loss associated with the usage of cisplatin in chemotherapeutic regimens. We recently demonstrated that the pharmacologic inhibition with kenpaullone or genetic deletion of CDK2 preserved hearing function in animal models treated with cisplatin, which suggests that CDK2 is a promising therapeutic target to prevent cisplatin-induced ototoxicity. In this study, we identified two lead compounds, AT7519 and AZD5438, from a focused library screen of 187 CDK2 inhibitors, performed in an immortalized cell line derived from neonatal mouse cochleae treated with cisplatin. Moreover, we screened 36 analogues of AT7519 and identified analogue 7, which exhibited an improved therapeutic index. When delivered locally, analogue 7 and AZD5438 both provided significant protection against cisplatin-induced ototoxicity in mice. Thus, we have identified two additional compounds that prevent cisplatin-induced ototoxicity in vivo and provided further evidence that CDK2 is a druggable target for treating cisplatin-induced ototoxicity.


Proteomics analysis of lung tissue reveals protein makers for the lung injury of adjuvant arthritis rats.
Lung injury is one of the common extra‑articular lesions in rheumatoid arthritis (RA). Due to its insidious onset and no obvious clinical symptoms, it can be easily dismissed in the early stage of diagnosis, which is one of the reasons that leads to a decline of the quality of life and subsequent death of patients with RA. However, its pathogenesis is still unclear and there is a lack of effective therapeutic targets. In the present study, tandem mass tag‑labeled proteomics was used to research the lung tissue proteins in RA model (adjuvant arthritis, AA) rats that had secondary lung injury. The aim of the present study was to identify the differentially expressed proteins related to RA‑lung injury, determine their potential role in the pathogenesis of RA‑lung injury and provide potential targets for clinical treatment. Lung tissue samples were collected from AA‑lung injury and normal rats. The differentially expressed proteins (DEPs) were identified by tandem mass spectrometry. Bioinformatic analysis was used to assess the biological processes and signaling pathways associated with these DEPs. A total of 310 DEPs were found, of which 244 were upregulated and 66 were downregulated. KEGG anlysis showed that 'fatty acid degradation', 'fatty acid metabolism', 'fatty acid elongation', 'complement and coagulation cascades', 'peroxisome proliferator‑activated receptor signaling pathway' and 'hypoxia‑inducible factor signaling pathway' were significantly upregulated in the lung tissues of AA‑lung injury. Immunofluorescence staining confirmed the increased expression of clusterin, serine protease inhibitors and complement 1qc in lung tissue of rats with AA lung injury. In the present study, the results revealed the significance of certain DEPs (for example, C9, C1qc and Clu) in the occurrence and development of RA‑lung injury and provided support through experiments to identify potential biomarkers for the early diagnosis and prevention of RA‑lung injury.


Proteolytic activities in plasma membrane preparations from rat liver. 1. Preparation of rat liver plasma membranes and solubilization of membrane bound proteases.
Plasma membranes (PM) were prepared by discontinuous density gradient centrifugation of crude nuclear fractions from 6 rat livers. These "nuclear" PM (PM-n) were 15-fold enriched in plasma membrane marker enzymes and contained an endopeptidase activity degrading azocasein at pH 7. To get larger amounts of plasma membranes, microsomal fractions obtained in large scale subcellular fractionations were subjected to continuous gradient zonal centrifugation. These "microsomal" PM (PM-m) were 22-fold enriched in 5'-nucleotidase, however, the separation of PM from endocellular membranes was not complete. PM-m showed endopeptidase activity degrading azocasein at pH 5.4 faster than at pH 7.5 and exopeptidases degrading Ala-Pro-pNA and Ala-pNA at pH 7.6. The latter two activities were distributed over the gradient similar to PM marker enzymes and can be solubilized by detergent and proteinase treatment. Therefore, dipeptidyl-aminopeptidase IV and Ala-aminopeptidase are intrinsic plasma membrane enzymes and can be used as additional markers for rat liver plasma membranes. The efficiency and selectivity to solubilize plasma membrane bound endopeptidase, DPP IV and aminopeptidase activities are compared.


Histologic predictors of pouchitis in patients with chronic ulcerative colitis.
Inflammation of ileal reservoir mucosa ("pouchitis") is a common sequelae in ulcerative colitis (UC) patients who have had a colectomy with ileal pouch anal-anastomosis (IPAA). Although several clinical, genetic, and laboratory parameters have been evaluated, reliable pathologic predictors for the development of pouchitis are lacking. The purpose of this case-control study was to determine whether there are any pathologic features in UC colectomy specimens that may help predict the subsequent development of pouchitis after an IPAA procedure. The study group consisted of 39 UC patients (male/female ratio: 21/18, mean age: 35 years), who had at least 1 episode of pouchitis after an IPAA procedure during the follow-up period (mean: 57 months, range: 12-121 months). There were 26 control patients (male/female ratio: 11/15, mean age: 37 years), all of whom also underwent a total colectomy and IPAA procedure for UC, but did not develop pouchitis during the follow-up period (mean: 78 months, range: 14-223 months). Routinely processed tissues from each colectomy specimen were evaluated for a variety of histologic features, such as extent of colitis, severity of colitis, extent of severe colitis, type and extent of ulceration, presence and severity of appendiceal inflammation, and the presence of active ileitis, and compared between the study and control patients. Pathologic features that were associated with the subsequent development of pouchitis included the presence of severe colitis that extended into the cecum (severe pancolitis), which was present in 7/39 (18%) pouchitis patients, but in none (0%) of the control patients (P = 0.03), early fissuring ulcers [9/39 (23%) pouchitis cases versus 1/26 (4%) controls (P = 0.04)], active inflammation of the appendix [20/32 (63%) pouchitis patients versus 7/19 (31%) controls (P = 0.03)], and appendiceal ulceration [13/32 (41%) pouchitis patients versus none (0%) of the controls (P = 0.002)]. No significant differences in patient gender or age, depth or extent of ulceration, or the presence or absence of "backwash ileitis" were identified between the 2 groups. In conclusion, there are several histologic features in colectomy specimens from UC patients who have undergone an IPAA procedure that may help predict the subsequent development of pouchitis. Of these features, appendiceal ulceration is highly associated with pouchitis.


Management of Refractory Angina Pectoris.
With improvements in survival from coronary artery disease (CAD) and an ageing population, refractory angina (RA) is becoming an increasingly common clinical problem facing clinicians in routine clinical practice. These patients experience chronic symptoms in the context of CAD, characterised by angina-type pain, which is uncontrolled despite optimal pharmacological, interventional and surgical therapy. Although mortality rates are no worse in this cohort, patients experience a significantly impaired quality of life with disproportionately high utilisation of healthcare services. It has been increasingly recognised that the needs of RA patients are multifactorial and best provided by specialist multi-disciplinary units. In this review, we consider the variety of therapies available to clinicians in the management of RA and discuss the promise of novel treatments.


The Sm protein methyltransferase PRMT5 is not required for primordial germ cell specification in mice.
PRMT5 is a type II protein arginine methyltransferase with roles in stem cell biology, reprograming, cancer and neurogenesis. During embryogenesis in the mouse, it was hypothesized that PRMT5 functions with the master germline determinant BLIMP1 to promote primordial germ cell (PGC) specification. Using a Blimp1-Cre germline conditional knockout, we discovered that Prmt5 has no major role in murine germline specification, or the first global epigenetic reprograming event involving depletion of cytosine methylation from DNA and histone H3 lysine 9 dimethylation from chromatin. Instead, we discovered that PRMT5 functions at the conclusion of PGC reprograming I to promote proliferation, survival and expression of the gonadal germline program as marked by MVH. We show that PRMT5 regulates gene expression by promoting methylation of the Sm spliceosomal proteins and significantly altering the spliced repertoire of RNAs in mammalian embryonic cells and primordial cells.


Reptilase clot retraction test. (Its cofactors and relation to other platelet functions).
C-PRP clotted by reptilase does not retract due to the lack of activation of platelets. In order to support retraction, the platelets must undergo membrane changes resulting in contractile system activation. Only in the presence of aggregating agents capable of eliciting these membrane changes in vitro (e.g. ADP, adrenaline and collagen but not bovine fibrinogen or ristocetin), strong reptilase clot retraction (RCR) occurs. During RCR an aggregating activity, platelet factor 4, and retraction stimulating factor (RSF) were released, but acid phosphatase was not available. Not only inhibitors of platelet adhesion-aggregation reaction (PAAR) but also specific blockers of release are capable of inhibiting RCR. In coagulation disorders RCR was normal in most cases, but in thrombopathies different abnormalities of RCR were found. The RCR defect may be associated not only with a defect in the initial stages of PAAR, but in some instances also with a specific defect in release reaction. Besides inducer--"activated" platelets and their adhesion to polymerizing fibrin, the presence of divalent cations and free thrombocytar--SH groups is necessary for the retraction of reptilase clots.


Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.
The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10-6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.


Surface-expressed insulin receptors as well as IGF-I receptors both contribute to the mitogenic effects of human insulin and its analogues.
There is a medical need for new insulin analogues. Yet, molecular alterations to the insulin molecule can theoretically result in analogues with carcinogenic effects. Preclinical carcinogenicity risk assessment for insulin analogues rests to a large extent on mitogenicity assays in cell lines. We therefore optimized mitogenicity assay conditions for a panel of five cell lines. All cell lines expressed insulin receptors (IR), IGF-I receptors (IGF-IR) and hybrid receptors, and in all cell lines, insulin as well as the comparator compounds X10 and IGF-I caused phosphorylation of the IR as well as IGF-IR. Insulin exhibited mitogenicity EC(50) values in the single-digit nanomolar to picomolar range. We observed correlations across cell types between (i) mitogenic potency of insulin and IGF-IR/IR ratio, (ii) Akt phosphorylation and mitogenic potency and (iii) Akt phosphorylation and IR phosphorylation. Using siRNA-mediated knockdown of IR and IGF-IR, we observed that in HCT 116 cells the IR appeared dominant in driving the mitogenic response to insulin, whereas in MCF7 cells the IGF-IR appeared dominant in driving the mitogenic response to insulin. Together, our results show that the IR as well as IGF-IR may contribute to the mitogenic potency of insulin. While insulin was a more potent mitogen than IGF-I in cells expressing more IR than IGF-IR, the hyper-mitogenic insulin analogue X10 was a more potent mitogen than insulin across all cell types, supporting that the hyper-mitogenic effect of X10 involves the IR as well as the IGF-IR. These results are relevant for preclinical safety assessment of developmental insulin analogues.


Phosphatidic acid binding to Patched contributes to the inhibition of Smoothened and Hedgehog signaling in Drosophila wing development.
Hedgehog (Hh) signaling controls growth and patterning during embryonic development and homeostasis in adult tissues. Hh binding to the receptor Patched (Ptc) elicits intracellular signaling by relieving Ptc-mediated inhibition of the transmembrane protein Smoothened (Smo). We uncovered a role for the lipid phosphatidic acid (PA) in the regulation of the Hh pathway in Drosophila melanogaster. Deleting the Ptc C-terminal tail or mutating the predicted PA-binding sites within it prevented Ptc from inhibiting Smo in wing discs and in cultured cells. The C-terminal tail of Ptc directly interacted with PA in vitro, an association that was reduced by Hh, and increased the amount of PA at the plasma membrane in cultured cells. Smo also interacted with PA in vitro through a binding pocket located in the transmembrane region, and mutating residues in this pocket reduced Smo activity in vivo and in cells. By genetically manipulating PA amounts in vivo or treating cultured cells with PA, we demonstrated that PA promoted Smo activation. Our findings suggest that Ptc may sequester PA in the absence of Hh and release it in the presence of Hh, thereby increasing the amount of PA that is locally available to promote Smo activation.


Phase I study using combination of hydroxyurea and 5-azacytidine (NSC-102816).
Thirteen patients were treated with a hydroxyurea -- 5-azacytidine combination in an attempt to show an increase in therapeutic efficacy of 5-azacytidine without increased bone marrow toxicity. Leukemic and nonleukemic patients were selected in order to compare the effect of a combination therapy on bone marrow. There was no clear-cut tumor response observed in evaluable patients. Overall activity of the combination, as judged by the onset of myelosuppression, appears to be higher than that of 5-azacytidine given alone.


Safe and Robust Map Updating for Long-Term Operations in Dynamic Environments.
Ensuring safe and continuous autonomous navigation in long-term mobile robot applications is still challenging. To ensure a reliable representation of the current environment without the need for periodic remapping, updating the map is recommended. However, in the case of incorrect robot pose estimation, updating the map can lead to errors that prevent the robot's localisation and jeopardise map accuracy. In this paper, we propose a safe Lidar-based occupancy grid map-updating algorithm for dynamic environments, taking into account uncertainties in the estimation of the robot's pose. The proposed approach allows for robust long-term operations, as it can recover the robot's pose, even when it gets lost, to continue the map update process, providing a coherent map. Moreover, the approach is also robust to temporary changes in the map due to the presence of dynamic obstacles such as humans and other robots. Results highlighting map quality, localisation performance, and pose recovery, both in simulation and experiments, are reported.


Iterative Sequencing and Variant Screening (ISVS) as a novel pathogenic mutations search strategy - application for TMPRSS3 mutations screen.
Autosomal recessive diseases (ARD) are typically caused by a limited number of mutations whose identification is challenged by their low prevalence. Our purpose was to develop a novel approach allowing an efficient search for mutations causing ARD and evaluation of their pathogenicity without a control group. We developed Iterative Sequencing and Variant Screening (ISVS) approach based on iterative cycles of gene sequencing and mutation screening, and ISVS Simulator software ( http://zsibio.ii.pw.edu.pl/shiny/isvs/ ) for assessment of detected variants' significance. As shown by simulations, ISVS efficiently identifies and correctly classifies pathogenic mutations except for cases where the gene of interest has extremely high number of low frequency nonpathogenic variants. By applying ISVS, we found 4 known and 9 novel (p.C73Y, p.S124L, p.C194Mfs*17, c.782 + 2 T > A, c.953-5 A > G, p.L325Q, p.D334Mfs*24, p.R436G, p.M448T) TMPRSS3 variants among deaf patients. For 3 known and 5 novel variants the disease association was supported by ISVS Simulator odds >90:1. Pathogenicity of 6 novel mutations has been supported by in-silico predictions of variants' deleteriousness. By directly comparing variant prevalence in patients and controls, disease association was demonstrated only for two variants and it was relatively weak (P < 0.05). Summarizing, ISVS strategy and ISVS Simulator are useful for detection of genetic variants causing AR diseases.


Preparation of a BiVO4 nanoporous photoanode based on peroxovanadate reduction and conversion for efficient photoelectrochemical performance.
A unique, controllable and facile method based on peroxovanadate reduction and conversion to prepare BiVO4 nanoporous films is presented. In this method, a slow and controllable reduction of peroxovanadate with ethanol was used, which was the crucial step to ensure the uniform deposition of V2O5·xH2O on an F-doped tin oxide substrate, and subsequently the annealed V2O5·xH2O film was converted to a BiVO4 film by a simple impregnation method with Bi3+ under the oriented effect of polyethylene glycol. The converted BiVO4 film possessed a single monoclinic scheelite structure and exhibited an optimal water splitting photocurrent density of 1.10 mA cm-2 at 1.23 V vs. RHE in 0.1 M KH2PO4 (pH 7) under AM 1.5G illumination with an incident photon-to-current conversion efficiency of ∼22.4% at 400 nm using an annealed V2O5·xH2O film deposited for 3 hours. The BiVO4 film also showed excellent water splitting performance and degradation efficiency in the PEC degradation of methylene blue and tetracycline hydrochloride with a rate constant of 0.63 h-1 and 0.21 h-1, respectively.


Binding of chara Myosin globular tail domain to phospholipid vesicles.
Binding of Chara myosin globular tail domain to phospholipid vesicles was investigated quantitatively. It was found that the globular tail domain binds to vesicles made from acidic phospholipids but not to those made from neutral phospholipids. This binding was weakened at high KCl concentration, suggesting that the binding is electrostatic by nature. The dissociation constant for the binding of the globular tail domain to 20% phosphatidylserine vesicles (similar to endoplasmic reticulum in acidic phospholipid contents) at 150 mM KCl was 273 nM. The free energy change due to this binding calculated from the dissociation constant was -37.3 kJ mol(-1). Thus the bond between the globular tail domain and membrane phospholipids would not be broken when the motor domain of Chara myosin moves along the actin filament using the energy of ATP hydrolysis (DeltaG degrees ' = -30.5 kJ mol(-1)). Our results suggested that direct binding of Chara myosin to the endoplasmic reticulum membrane through the globular tail domain could work satisfactorily in Chara cytoplasmic streaming. We also suggest a possible regulatory mechanism of cytoplasmic streaming including phosphorylation-dependent dissociation of the globular tail domain from the endoplasmic reticulum membrane.


Intranasal coadministration of live lactococci producing interleukin-12 and a major cow's milk allergen inhibits allergic reaction in mice.
The Th1/Th2 balance deregulation toward a Th2 immune response plays a central role in allergy. We previously demonstrated that administration of recombinant Lactococcus lactis strains expressing bovine beta-lactoglobulin (BLG), a major cow's milk allergen, partially prevents mice from sensitization. In the present study, we aimed to improve this preventive effect by coadministration of L. lactis BLG and a second recombinant L. lactis strain producing biologically active interleukin-12 (IL-12). This L. lactis strain producing IL-12 was previously used to enhance the Th1 immune response in a tumoral murine model (L. G. Bermúdez-Humarán et al., J. Immunol. 175:7297-7302, 2005). A comparison of the administration of either BLG alone or BLG in the presence of IL-12 was conducted. A BLG-specific primary Th1 immune response was observed only after intranasal coadministration of both L. lactis BLG and IL-12-producing L. lactis, as demonstrated by the induction of serum-specific immunoglobulin G2a (IgG2a) concomitant with gamma interferon secretion by splenocytes, confirming the adjuvanticity of IL-12-producing L. lactis. Immunized mice were further sensitized by intraperitoneal administration of purified BLG, and the allergic reaction was elicited by intranasal challenge with purified BLG. Mice pretreated with BLG in either the presence or the absence of IL-12 were rendered completely tolerant to further allergic sensitization and elicitation. Pretreatment with either L. lactis BLG or L. lactis BLG and IL-12-producing L. lactis induces specific anti-BLG IgG2a production in serum and bronchoalveolar lavage (BAL) fluid. Although specific serum IgE was not affected by these pretreatments, the levels of eosinophilia and IL-5 secretion in BAL fluid were significantly reduced after BLG challenge in the groups pretreated with L. lactis BLG and L. lactis BLG-IL-12-producing L. lactis, demonstrating a decreased allergic reaction. Our data demonstrate for the first time (i) the induction of a protective Th1 response by the association of L. lactis BLG and IL-12-producing L. lactis which inhibits the elicitation of the allergic reaction to BLG in mice and (ii) the efficiency of intranasal administration of BLG for the induction of tolerance.


Semen of spinal cord injured men freezes reliably.
The objectives of the present study were to: 1) determine the effect of cryopreservation on the percent and the grade of motility of sperm from spinal cord injured (SCI) men and 2) determine which method of freezing yields the best post-thaw motility in sperm from SCI men. Antegrade semen samples were obtained from 9 SCI subjects and 10 age-matched healthy control subjects. Motility in fresh samples was determined and cryopreservative medium was added to each sample. Aliquots of each sample were frozen according to three methods: 1) liquid nitrogen vapor only (V); 2) vapor for 12 minutes followed by submersion into liquid nitrogen (V+N2); and 3) direct submersion into liquid nitrogen (N2). Samples were frozen for 1 week, then thawed. The post-thaw percent and grade of motility was determined. The mean percent motility of fresh samples for SCI subjects (21.0%) was significantly lower than for control subjects (55.7%). After thawing, the mean percent drop in motility for V, V+N2, and N2 for controls was 65.2%, 73.5%, and 79.4%, respectively, and for SCI subjects, it was 64.7%, 74.5%, and 81.6%, respectively. There was no statistically significant difference between control and SCI subjects by method of freezing. Vapor only as a freezing method was superior to all other methods for retention of sperm motility in both control and SCI subjects. We conclude that the semen of SCI men may be frozen reliably and that their sperm retain motility similar to that of normal men. Vapor only, being the most gentle method used, gives the best recovery of sperm motility in either group.


Towards developing high-fidelity simulated learning environment training modules in audiology.
This discussion paper reviews and synthesises the literature on simulated learning environment (SLE) from allied health sciences, medical and nursing in general and audiology specifically. The focus of the paper is on discussing the use of high-fidelity (HF) SLE and describing the challenges for developing a HF SLE for clinical audiology training. Through the review of the literature, this paper discusses seven questions, (i) What is SLE? (ii) What are the types of SLEs? (iii) How is SLE classified? (iv) What is HF SLE? (v) What types of SLEs are available in audiology and their level of fidelity? (vi) What are the components needed for developing HF SLE? (vii) What are the possible types of HF SLEs that are suitable for audiology training? Publications were identified by structured searches from three major databases PubMed, Web of Knowledge and PsychInfo and from the reference lists of relevant articles. The authors discussed and mapped the levels of fidelity of SLE audiology training modules from the literature and the learning domains involved in the clinical audiology courses. The discussion paper has highlighted that most of the existing SLE audiology training modules consist of either low- or medium-fidelity types of simulators. Those components needed to achieve a HF SLE for audiology training are also highlighted. Overall, this review recommends that the combined approach of different levels and types of SLE could be used to obtain a HF SLE training module in audiology training.


[Spectral characteristics of soluble metabolites during endogenous respiration].
Endogenous respiration phase plays an important role in the sewage treatment process. In order to clearly understand the endogenous respiration process of the activated sludge process, three-dimensional fluorescence spectroscopy, ultraviolet spectroscopy and respirogram were employed for the analysis of endogenous respiration process. Results showed that the three-dimensional fluorescence spectroscopy and UV spectroscopy could identify all stages significantly. The following conclusions could be drawn: (1) Rapid decline phase of endogenous respiration:the excitation wavelength (EX) and emission wavelength (Em) of humic peak showed blue shift of 5 nm and 6 nm, respectively, the fluorescence index f450/500 and HIX (humification index) were reduced by 9. 3% and 0.2%, respectively, UV253/203 and UV254 increased by 37.5% and 200%, respectively. These results indicated the presence of bioavailable organics; (2)Slow decline phase of endogenous respiration: f450/500 was increased by 0. 5% , HIX was reduced by 0. 2% , UV253/203 was reduced by 20% , UV254 was increased by 16. 7%. These results indicated that hydrolysis or autolysis of cells might occur; (3)Stable phase of endogenous respiration: humic acid peak remained unchanged, indicating the adaption of microorganisms to starving environment. The analysis of the endogenous respiration process from the perspective of metabolites provides a new way for control of microbial wastewater treatment process.


Cost-effectiveness of ambulatory blood pressure monitoring in the initial evaluation of hypertension in children.
The goal was to determine the cost-effectiveness of ambulatory blood pressure monitoring in the initial evaluation of stage 1 hypertension. Retrospective chart review of data for children referred to Texas Children's Hospital hypertension clinic between January 2005 and August 2006 was performed. We compared the costs of standard evaluations versus the initial use of ambulatory blood pressure monitoring for children with clinic blood pressure measurements suggesting stage 1 hypertension. Charges for clinic visits, laboratory tests, and imaging were obtained from the Texas Children's Hospital billing department. A total of 267 children were referred. One hundred thirty-nine children did not receive ambulatory blood pressure monitoring; 54 met clinical indications for ambulatory blood pressure monitoring but did not receive it because it was not a covered expense (44 children) or the family refused the study (10 children). One hundred twenty-six children received clinically indicated ambulatory blood pressure monitoring, paid for either through insurance or by the family. Fifty-eight children (46%) had confirmed white-coat hypertension, 62 (49%) stage 1 hypertension, and 6 (5%) stage 2 hypertension. With the observed prevalence of white-coat hypertension, initial ambulatory blood pressure monitoring use yielded net savings after evaluation of 3 patients, with projected savings of $2.4 million per 1000 patients. Ambulatory blood pressure monitoring in the initial evaluation of suspected childhood hypertension is highly cost-effective. Awareness of cost saving potential may increase the availability of ambulatory blood pressure monitoring for evaluation of new-onset hypertension.


Elimination of the Mound-Building Termite, Nasutitermes exitiosus (Isoptera: Termitidae) in South-Eastern Australia Using Bistrifluron Bait.
Bistrifluron, a benzoylphenylurea compound, was evaluated for efficacy against Nasutitermes exitiosus (Hill), a mound-building species in southern Australia. Bistrifluron bait (trade name Xterm) was delivered as containerized pellets inserted into plastic feeding stations implanted in the sides of mounds-60 g for bistrifluron bait-treated mounds and 120 g of blank bait for untreated mounds. Termites actively tunneled in the gaps between pellets and removed bait from the canisters. All five treated mounds were eventually eliminated, and all five untreated mounds remained active at the end of the trial. Four of the five treated mounds were considered dead and excavated after 26 wk, but there were earlier signs of mound distress-reduced repair of experimental casement damage and reduced activity in bait canisters by 22 wk and reduced internal mound temperature after 11 wk. One treated mound showed activity in the bait station right through until almost the end of the trial (47 wk), but excavation at 49 wk showed no further activity in the mound. The five untreated colonies removed on average 97% of blank bait offered, while the five treated colonies removed on average 39.1% of bait offered. There was a wide variation in temperature profiles of mounds (up to 15°C for both minimum and maximum internal temperatures), from the beginning of the trial and even before the effects of baiting were evident.


Oxidation of polyunsaturated fatty acids to produce lipid mediators.
The chemistry, biochemistry, pharmacology and molecular biology of oxylipins (defined as a family of oxygenated natural products that are formed from unsaturated fatty acids by pathways involving at least one step of dioxygen-dependent oxidation) are complex and occasionally contradictory subjects that continue to develop at an extraordinarily rapid rate. The term includes docosanoids (e.g. protectins, resolvins and maresins, or specialized pro-resolving mediators), eicosanoids and octadecanoids and plant oxylipins, which are derived from either the omega-6 (n-6) or the omega-3 (n-3) families of polyunsaturated fatty acids. For example, the term eicosanoid is used to embrace those biologically active lipid mediators that are derived from C20 fatty acids, and include prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and related oxygenated derivatives. The key enzymes for the production of prostanoids are prostaglandin endoperoxide H synthases (cyclo-oxygenases), while lipoxygenases and oxidases of the cytochrome P450 family produce numerous other metabolites. In plants, the lipoxygenase pathway from C18 polyunsaturated fatty acids yields a variety of important products, especially the jasmonates, which have some comparable structural features and functions. Related oxylipins are produced by non-enzymic means (isoprostanes), while fatty acid esters of hydroxy fatty acids (FAHFA) are now being considered together with the oxylipins from a functional perspective. In all kingdoms of life, oxylipins usually act as lipid mediators through specific receptors, have short half-lives and have functions in innumerable biological contexts.


Fat/water separation in single acquisition steady-state free precession using multiple echo radial trajectories.
Phase detection in fully refocused SSFP imaging has recently allowed fat/water separation without preparing the magnetization or using multiple acquisitions. Instead, it exploits the phase difference between fat and water at an echo time at the midpoint of the TR. To minimize the TR for improved robustness to B0 inhomogeneity, a 3D projection acquisition collecting two half echoes at the beginning and end of each excitation was previously implemented. Since echoes are not formed at the midpoint of the TR, this method still requires two passes of k-space for fat/water separation. A new method is presented to linearly combine the half echoes to separate fat and water in a single acquisition. Separation using phase detection provides superior contrast between fat and water voxels. Results from high resolution angiography and musculoskeletal studies with improved robustness to inhomogeneity and a 50% scan time reduction compared to the two pass method are presented.