Fetal hyperechoic kidney cohort study and a meta-analysis.
Objective: To investigate the positive rate of chromosomal and monogenic etiologies and pregnancy outcomes in fetuses with hyperechoic kidney, and to provide more information for genetic counseling and prognosis evaluation. Methods: We performed a retrospective analysis of 25 cases of hyperechoic kidney diagnosed prenatal in the Second Affiliated Hospital of Harbin Medical University and Harbin Red Cross Central Hospital (January 2017-December 2022). Furthermore, we conducted a meta-analysis of a series of hyperechoic kidneys (HEK) in the literature to assess the incidence of chromosomal and monogenic etiologies, mortality, and pooled odds ratio (OR) estimates of the association between the incidence of these outcomes and other associated ultrasound abnormalities. Results: 25 fetuses of HEK were enrolled in the cohort study, including 14 with isolated hyperechoic kidney (IHK) and 11 with non-isolated hyperechoic kidney (NIHK). Chromosomal aneuploidies were detected in 4 of 20 patients (20%). The detection rate of pathogenic or suspected pathogenic copy number variations (CNVs) was 29% (4/14) for IHK and 37% (4/11) for NIHK. Whole exome sequencing (WES) was performed in 5 fetuses, and pathogenic genes were detected in all of them. The rate of termination of pregnancy was 56% in HEK. 21 studies including 1,178 fetuses were included in the meta-analysis. No case of abnormal chromosome karyotype or (intrauterine death)IUD was reported in fetuses with IHK. In contrast, the positive rate of karyotype in NIHK was 22% and that in HEK was 20%, with the ORs of 0.28 (95% CI 0.16-0.51) and 0.25, (95% CI 0.14-0.44), respectively. The positive rate of (chromosome microarray analysis) CMA in IHK was 59% and that in NIHK was 32%, with the ORs of 1.46 (95% CI 1.33-1.62) and 0.48 (95% CI, 0.28-0.85), respectively. The positive rate of monogenic etiologies in IHK was 31%, with the OR of 0.80 (95% CI 0.25-2.63). In IHK, the termination rate was 21% and neonatal mortality was 13%, with the ORs of 0.26 (95% CI, 0.17-0.40), 1.72 (95% CI, 1.59-1.86), and that in NIHK was 63%, 0.15 (95% CI, 0.10-0.24); 11%, 0.12 (95% CI, 0.06-0.26), respectively. The intrauterine mortality in NIHK group was 2%, with the OR of 0.02 (95% CI, 0.01-0.05). HNF1B variant has the highest incidence (26%) in IHK. Conclusion: The positive rate of karyotype was 20% in HEK and 22% in NIHK. The positive rate of CMA was 32% in NIHK and 59% in IHK. The positive rate of IHK monogenic etiologies was 31%. HNF1B gene variation is the most common cause of IHK. The overall fetal mortality rate of NIHK is significantly higher than that of IHK. The amount of amniotic fluid, kidney size and the degree of corticomedullary differentiation have a great impact on the prognosis, these indicators should be taken into consideration to guide clinical consultation and decision-making.


Analysis of multiple enteric viral targets as sewage markers in coral reefs.
Water and coral mucus samples were collected from throughout the Florida Keys National Marine Sanctuary and the Dry Tortugas for three years and were analyzed for human enteric viruses (enteroviruses, noroviruses, hepatitis A virus and adenoviruses) as conservative markers of human sewage using molecular methods. Of the 100 coral and water samples collected, 40 contained genetic material from one or more human enteric viruses. DNA-based adenoviruses were detected widely, in 37.8% of samples and at 91% of stations, including 'pristine' reefs in the Dry Tortugas; however, the detection rate was < or =12% for the RNA-based enteroviruses and noroviruses (hepatitis A virus was never detected). The disparity between the prevalence of RNA- and DNA-based viruses suggests the need for additional work to determine the utility of adenovirus as marker of human sewage.


Recombinant cytokines from plants.
Plant-based platforms have been successfully applied for the last two decades for the efficient production of pharmaceutical proteins. The number of commercialized products biomanufactured in plants is, however, rather discouraging. Cytokines are small glycosylated polypeptides used in the treatment of cancer, immune disorders and various other related diseases. Because the clinical use of cytokines is limited by high production costs they are good candidates for plant-made pharmaceuticals. Several research groups explored the possibilities of cost-effective production of animal cytokines in plant systems. This review summarizes recent advances in this field.


A new ultrasonic technique for quantifying blood echogenicity.
The echogenicity of blood varies with the conditions of flow. This study introduces a new technique for quantifying blood echogenicity and includes digitalization of the signal from an A-mode ultrasound scanner, integration, subtraction, and computer analysis of the signal. Shear rate (directly proportional to velocity) had an inverse relationship to the blood echogenicity. Hemodilution with Ringer's solution and with low-molecular-weight dextran 1 decreased blood echogenicity, whereas the addition of a macromolecular protein (dextran 70) increased blood echogenicity. This technique makes possible a quantitative analysis of the factors affecting blood echogenicity.


Effect of Alpha 1-Adrnoceptor Antagonists on Postsynaptic Sensitivity in Substantia Gelatinosa Neurons From Lumbosacral Spinal Cord in Rats Using Slice Patch-Clamp Technique for mEPSC.
Alpha1-adrenoceptors participate in improving storage symptoms of male lower urinary tract symptoms (LUTS). However, the mechanism of action of these compounds remains unclear. To clarify the mechanism of the α1-adrenoceptor antagonists, the amplitude of miniature excitatory postsynaptic currents (mEPSCs) was analyzed in the lumbosacral spinal cord in rats. Male adult Sprague-Dawley rats were used. Blind whole-cell patch-clamp recordings were performed on substantia gelatinosa (SG) neurons in spinal cord slice preparations. The amplitude of mEPSCs was recorded in individual SG neurons to which α1-adrenoceptors (100μM naftopidil, 100μM tamsulosin, and 30μM silodosin) were applied sequentially with intervening washout periods. Individual amplitudes were analyzed. Pearson correlation coefficients (r) for the amplitudes of mEPSCs between the baseline and postadministration of α1- adrenoceptor antagonists indicated changes of the amplitude ranked in the order of naftopidil (r =0.393), tamsulosin (r=0.738), and silodosin (r=0.944). Together, the α1-adrenoceptor antagonists yielded significant increases in the amplitude of mEPSCs in SG neurons (n=108, P=0.012). However, the effects of each α1-adrenoceptor antagonist on the amplitude were as follows (relative to the baseline; n=36 each): naftopidil, P=0.129; tamsulosin, P=0.201; and silodosin, P=0.005. The rate of response to naftopidil for the outward current was relatively high among the α1-adrenoceptor blockers. An inward current was observed only with the naftopidil application. Alpha1-adrenoceptor antagonists changed the amplitudes of mEPSCs in a subset of SG neurons in slices prepared from the L6-S1 levels of rat spine. Although the α1-adrenoceptor antagonists generated inward or outward currents in the SG neurons, different rates of response were observed with each antagonist. These results are important for understanding the mechanisms of action (at the spinal level) of α1-adrenoceptor antagonists for the storage symptoms of male LUTS.


Screening of Genes Related to Early and Late Flowering in Tree Peony Based on Bulked Segregant RNA Sequencing and Verification by Quantitative Real-Time PCR.
Tree peony (Paeonia suffruticosa Andrews) is a perennial woody shrub bearing large and colorful flowers. However, the flowering period is short and relatively uniform, which to an important extent hinders the cultivation and exploitation of ornamental peonies. In this study, the segregation of an F₁ population derived from P. ostti 'Feng Dan' (an early-flowering cultivar) × P. suffruticosa 'Xin Riyuejin' (a late-flowering cultivar) was used to screen and analyze candidate genes associated with flowering period of the two parents. Extreme early- and late-flowering genotypes of the F₁ population at full-bloom stage were sampled to establish an early-flowering mixed pool (T03), a late-flowering mixed pool (T04), a late-flowering male pool (T01), and an early-flowering female pool (T02), using the Sequencing By Synthesis (SBS) technology on the Illumina HiSeq TM2500 platform. A total of 56.51 Gb of clean reads data, comprising at least 87.62% of Quality30 (Q30), was generated, which was then combined into 173,960 transcripts (N50 = 1781) and 78,645 (N50 = 1282) unigenes, with a mean length of 1106.76 and 732.27 base pairs (bp), respectively. Altogether, 58,084 genes were annotated by comparison with public databases, based on an E-value parameter of less than 10-5 and 10-10 for BLAST and HMMER, respectively. In total, 291 unigene sequences were finally screened out by BSR-seq (bulked segregant RNA-seq) association analysis. To validate these unigenes, we finally confirmed seven unigenes that were related to early and late flowering, which were then verified by quantitative real-time PCR (qRT-PCR). This is the first reported study to screen genes associated with early and late flowering of tree peony by the BSA (bulked sample analysis) method of transcriptome sequencing, and to construct a high-quality transcriptome database. A set of candidate functional genes related to flowering time was successfully obtained, providing an important genetic resource for further studies of flowering in peony and the mechanism of regulation of flowering time in tree peony.


Developmental study of miniature IPSCs of CA3 hippocampal cells: modulation by midazolam.
Maturation of GABAA/benzodiazepine receptors is associated with changes in their subunit composition. We have investigated whether these changes are accompanied by a developmental modification in the kinetic properties of miniature IPSCs (mIPSCs) and sensitivity to midazolam, a benzodiazepine agonist. In the presence of TTX (10 microM) and excitatory amino acid antagonists, AP5 (50 microM) and CNQX (50 microM), we whole-cell recorded mIPSCs in CA3 cells of hippocampal slices of adult and young (4-8 days) rats. mIPSCs were mediated by GABAA receptors as they were suppressed by bicuculline (10 microM). In both the adult and young rats, mIPSCs were similar in amplitude and kinetic properties. However, the mIPSCs frequency markedly increased with age from 4+/-3 Hz in the young rats to 20+/-9 Hz in the adult rats. In both age groups, midazolam (0.01 microM(-10) microM) and pentobarbital (30 microM) did not affect the amplitude, frequency and rise time of the mIPSCs but they increased to a similar extent their decay time constant. The current responses to isoguvacine, a GABAA agonist, were potentiated by 0.1 microM midazolam in both age groups. It is concluded that in immature and adult rats, synaptic GABAA receptors of CA3 were not different in their kinetic properties and sensitivity to midazolam.


Reduction of neurological damage by a peptide segment of the amyloid beta/A4 protein precursor in a rabbit spinal cord ischemia model.
Although found as a precursor of Alzheimer amyloid, substantial evidence suggests that beta/A4 protein precursor (APP) is involved in regulation of neuronal growth and survival. Recently, we have obtained evidence that the trophic properties of APP are fully preserved in a 17-amino acid sequence. If APP is neurotrophic, then it would be anticipated that administration of the growth-promoting segment of the APP 17-mer peptide might attenuate the neuronal dysfunction or loss or behavioral deficits associated with neuronal injury, such as that accompanying central nervous system ischemia. We evaluated this 17-mer peptide in a rabbit spinal cord ischemia model and found that this peptide alleviates paraplegia resulting from ischemia/reperfusion. Ischemia of the distal lumbar cord was produced by temporary occlusion of the abdominal aorta. Saline, 17-mer APP peptide, or a control peptide (200, 500, or 1000 nM) was administered intrathecally 20 min prior to ischemia and once daily for 3 days thereafter. The neurologic and morphologic outcomes were evaluated after 4 days. Durations of ischemia encompassing all grades of neurologic function were included. The 500 nM dose of 17-mer APP peptide significantly reduced neurologic damage. The average ischemia duration necessary to produce permanent neurologic damage increased from 27.9 +/- 1.9 min in saline-injected controls and 27.7 +/- 2.0 in scrambled sequence peptide-injected controls to 40.2 +/- 4.0 min in the 500 nM 17-mer APP-injected group. The 200 nM dose produced a nonsignificant trend toward reduced neurologic damage.(ABSTRACT TRUNCATED AT 250 WORDS)


RRV: A Spatiotemporal Descriptor for Rigid Body Motion Recognition.
The motion behaviors of a rigid body can be characterized by a six degrees of freedom motion trajectory, which contains the 3-D position vectors of a reference point on the rigid body and 3-D rotations of this rigid body over time. This paper devises a rotation and relative velocity (RRV) descriptor by exploring the local translational and rotational invariants of rigid body motion trajectories, which is insensitive to noise, invariant to rigid transformation and scale. The RRV descriptor is then applied to characterize motions of a human body skeleton modeled as articulated interconnections of multiple rigid bodies. To show the descriptive ability of our RRV descriptor, we explore its potentials and applications in different rigid body motion recognition tasks. The experimental results on benchmark datasets demonstrate that our RRV descriptor learning discriminative motion patterns can achieve superior results for various recognition tasks.


Transportation and public health.
This article investigates various ways that transportation policy and planning decisions affect public health and better ways to incorporate public health objectives into transport planning. Conventional planning tends to consider some public health impacts, such as crash risk and pollution emissions measured per vehicle-kilometer, but generally ignores health problems resulting from less active transport (reduced walking and cycling activity) and the additional crashes and pollution caused by increased vehicle mileage. As a result, transport agencies tend to undervalue strategies that increase transport system diversity and reduce vehicle travel. This article identifies various win-win strategies that can help improve public health and other planning objectives.


Long-term functional outcome following transient middle cerebral artery occlusion in the rat: correlation between brain damage and behavioral impairment.
The assessment of both histological and functional long-term outcomes after cerebral ischemia is increasingly recommended for preclinical studies. Whereas correlations between behavioral impairments and primary ischemic lesion are documented, little is known about their relationships with remote nonischemic regions that undergo secondary degeneration, such as the thalamus. Anesthetized rats were subjected to mild (30 min) or severe (60 min) occlusion of the middle cerebral artery. Two months after ischemia, sensorimotor behavior was assessed according to the neurological score, limb-placing, adhesive-removal, and staircase tests; the final histological lesion was measured after this assessment. Cortical damage was correlated to all transient and long-lasting sensorimotor deficits, whereas striatal lesion was more consistently reflected by the forelimb-placing reflexes and adhesive-removal motor deficits. By contrast, the thalamic atrophy was not correlated to early neurological impairment, but rather to the late sensory deficit at the adhesive-removal test and to the skilled forepaw reaching alteration at the staircase test. This suggests that thalamus contributes, albeit moderately, to the ischemia-induced long-lasting sensorimotor deficits, some of which represent relevant targets for therapeutic interventions.


Mechanisms of photo-induced vitreous liquefaction.
To understand the mechanisms of photo-induced vitreous liquefaction, this study investigated the effects of free radicals on collagen and hyaluronic acid (HA). Bovine vitreous collagen or HA was irradiated by visible light in the presence of riboflavin (RF) as a photosensitizer. The changes in the molecular weight of collagen and HA were monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-performance liquid chromatography, respectively. Free radicals were shown to cause an increase in the high-molecular-weight components and insolubilization of the vitreous collagen and a decrease in the molecular weight of HA. The change in molecular properties of the vitreous collagen could be attributed to extensive crosslinks of the molecules. Since RF is present in the vitreous, which is irradiated by visible light over a lifetime, both cross-links of vitreous collagen and degradation of HA may contribute to age-related vitreous liquefaction.


Winter is coming-The role of seasonality through the lens of the rodent virome.
Rodent virus communities (viromes) are overrepresented with zoonotic viruses, and as such are a key host system for the study of zoonotic viruses. However, the extent of viral diversity beyond characterized zoonotic viruses, and the factors that modulate the viromes of rodents remain opaque. In this issue of Molecular Ecology, Raghwani et al. (2023) use rodents as a model to understand the role of seasonality in dictating virome abundance and composition-a factor known to play an important role in most animal one-host, one-pathogen systems. These data are not only highly relevant to rodents, but have broad applications across understanding and disentangling animal virome ecology.


[Can the number of donor kidneys for children be increased by using the kidneys of dead newborn infants?].
The donor pool for kidney transplantation in small children may be extended by the use of kidneys from deceased newborns. From 1973 to 1983 at our institution 189 mature newborns died, of which were 105 from the clinical point of view and 82 from the pathological-anatomical sight suitable as organ donors. The most frequent causes of death were disorders of the heart and circulation (60) and of the respiratory system (46). It is pointed to the problem of the establishment of brain death in newborns.


The RWJ Executive Nurse Fellows Program, Part 1: Leading change.
This article is the first of a 3-part series describing the RWJ Executive Nurse Fellows Program, an advanced leadership program for nurses in senior executive roles who aspire to help lead and shape the US healthcare system of the future. This article describes the RWJ Executive Nurse Fellows program, its core leadership competencies, and the primary program components. Part 2 (December 2005) will focus on the nontraditional mentor relationships developed by fellows as part of the fellowship experience and lessons learned regarding best practices. Part 3 (February 2006) will explain how fellows are required to create a business plan for their leadership project because it is so important for nurse leaders to offer a strong business case for proceeding with a new initiative, service, or program.


Structural evolution of 2D microporous covalent triazine-based framework toward the study of high-performance supercapacitors.
A series of nitrogen-containing micropore-donimated materials, porous triazine-based frameworks (PTFs), are constructed through the structural evolution of a 2D microporous covalent triazine-based framework. The PTFs feature predictable and controllable nitrogen doping and pore structures, which serve as a model-like system to more deeply understand the heteroatom effect and micropore effect in ionic liquid-based supercapacitors. The experimental results reveal that the nitrogen doping can enhance the supercapacitor performance mainly through affecting the relative permittivity of the electrode materials. Although microspores' contribution is not as obvious as the doped nitrogen, the great performances of the micropore-dominated PTF suggest that micropore-dominated materials still have great potential in ionic liquid-based supercapacitors.


Monitoring parameters of dialysis dose.
In order to deliver a specific dialysis dose (Kt/V) to all patients, their product Kt (urea clearance K multiplied by dialysis time t) should be individually adjusted according to total body water (V) of each patient. With dialysis time being fixed in most centres for organisational reasons, such individualization can be accomplished by individually set blood flow (QB). For a given t, the value of QB also defines the magnitude of the cumulative blood volume (VB = QB*t), i.e. the volume of blood perfused through the dialyser during the whole dialysis time. VB is displayed by every contemporary dialysis machine but not used. The aim of this work was to derive an easy to use approach to QB individualization based on patient's body weight and dialysis time to obtain a desired Kt/V value which would also be easy to check after dialysis by looking at the obtained VB value. Statistically significant correlation was found between the QB-based Kt/V estimation and Kt/V determined by the other two methods demonstrating practical feasibility of the novel approach. Kt/V values obtained with the QB prescribed according to patient's body weight tended to be better in females and patients with higher body mass index.


Do Our Means of Inquiry Match our Intentions?
A key stage of the scientific method is the analysis of data, yet despite the variety of methods that are available to researchers they are most frequently distilled to a model that focuses on the average relation between variables. Although research questions are frequently conceived with broad inquiry in mind, most regression methods are limited in comprehensively evaluating how observed behaviors are related to each other. Quantile regression is a largely unknown yet well-suited analytic technique similar to traditional regression analysis, but allows for a more systematic approach to understanding complex associations among observed phenomena in the psychological sciences. Data from the National Education Longitudinal Study of 1988/2000 are used to illustrate how quantile regression overcomes the limitations of average associations in linear regression by showing that psychological well-being and sex each differentially relate to reading achievement depending on one's level of reading achievement.


Biosafety in acquired immunodeficiency syndrome (AIDS) studies using nonhuman primates.
The safety recommendations for studies on acquired immunodeficiency syndrome (AIDS) using nonhuman primates are based on knowledge about the epidemiology of the disease in humans, characteristics of the virus, and standard methods for handling nonhuman primates in the laboratory. Appropriate procedures avoid exposure to potentially infectious materials by skin puncture or to mucous membranes by using appropriate disinfecting agents, physical containment, protective clothing, and animal handling techniques.


How worthwhile is plasma primidone level measurement?
Simultaneous steady-state plasma levels of primidone and phenobarbitone were studied in 43 patients receiving primidone therapy. Primidone and phenobarbitone levels in the individual appeared to be linearly related but steady-state plasma phenobarbitone levels correlated better with primidone dose than did steady-state plasma levels of primidone itself. This pattern of correlation is probably due to primidone being more rapidly eliminated than the phenobarbitone that is derived from it. Steady-state plasma primidone levels showed more inter-dosage fluctuation than steady-state plasma phenobarbitone levels in the same patients. In the subjects studied age, sex, and concurrent anticonvulsant therapy did not alter the relation between plasma levels of primidone or phenobarbitone and primidone dose. The study suggested that knowledge of steady-state plasma primidone levels adds little to knowledge of plasma phenobarbitone levels in guiding the therapy of epilepsy with primidone.


A left nonrecurrent inferior laryngeal nerve in a patient with right-sided aorta, truncus arteriosus communis, and an aberrant left innominate artery.
The identification and prevention of injury to the inferior laryngeal nerve is one of the main issues in thyroid surgery. Sound knowledge of anatomic variants of the nerve is of major importance. In rare cases the nerve does not run the recurrent way and it is therefore difficult to identify the nerve. Abnormal developments of the aortic arch during embryogenesis include malformation of the great vessels and can be the reason for anatomic abnormalities. A cause for a nonrecurrent nerve on the right side is the so-called lusorian artery, a right retroesophageal subclavian artery. Left-sided nonrecurrent nerves are seldom if ever documented. Only two cases have been published so far of patients with situs inversus viscerum, where left nonrecurrent nerves were associated with inverse, left-sided lusorian arteries.


Effect of PM characterization on PM oxidative potential by acellular assays: a review.
The health risks brought by particles cannot be present via a sole parameter. Instead, the particulate matter oxidative potential (PM OP), which expresses combined redox properties of particles, is used as an integrated metric to assess associated hazards and particle-induced health effects. OP definition provides the capacity of PM toward target oxidation. The latest technologies of a cellular OP measurement has been growing in relevant studies. In this review, OP measurement techniques are focused on discussing along with PM characterization because of many related studies via OP measurements investigating relationship with human health. Many OP measurement methods, such as dithiothreitol (DTT), ascorbic acid (AA), glutathione (GSH) assay and other a cellular assays, are used to study the association between PM toxicity and PM characterization that make different responses, including PM components, size and sources. Briefly, AA and DTT assays are sensitive to metals (such as copper, manganese and iron etc.) and organics (quinones, VOCs and PAH). Measured OP have significant association with certain PM-related end points, for example, lung cancer, COPD and asthma. Literature has found that exposure to measured OP has higher risk ratios than sole PM mass, which may be containing the PM health-relevant fraction. PM characterization effect on health via OP measurement display a promising method.


Distribution of amylase and chymotrypsin in four regions of the rat pancreas.
Recent observations have confirmed the existence of more than one pool of secretory proteins in the rat pancreatic tissue. To determine if these different pools could be located in the different regions of the rat pancreas, the amylase and chymotrypsin contents have been measured in the biliary, duodenal, gastric, and splenic regions. On a tissue DNA content, protein content, or a fresh weight basis, the proportions of these two enzymes are comparable in the four regions. It is therefore postulated that heterogeneity of enzyme composition exists either within these regions or within the acinar cell itself.


Molecular Testing of Non-Small Cell Lung Carcinoma Diagnosed by Endobronchial Ultrasound-Guided Transbronchial Fine-Needle Aspiration: The Cleveland Clinic Experience.
Given the increasing demand for molecular testing of non-small cell lung carcinoma specimens to guide therapeutic decision-making and the trend toward minimally invasive techniques for obtaining diagnostic tissue, cytopathology laboratories must devise strategies to maximize DNA yield for necessary molecular testing. To describe our experience at Cleveland Clinic with epidermal growth factor receptor (EGFR) mutation testing by next-generation sequencing and anaplastic lymphoma kinase (ALK) gene rearrangement testing by fluorescence in situ hybridization of non-small cell lung carcinomas diagnosed by cytology, with an emphasis on specimens obtained by endobronchial ultrasound-guided transbronchial fine-needle aspiration. Data sources include a review of the current literature, including published articles from our institution. At our institution, liquid-based cytology specimens are the primary resource used for molecular testing of non-small cell lung carcinomas; in most instances, adequate DNA can be extracted from the residual cell pellet for next-generation sequencing, and ThinPrep slides can be used reliably for fluorescence in situ hybridization testing for ALK gene rearrangements. In occasional cases where the cell pellet material is not adequate for molecular testing, cell blocks and/or surgical pathology specimens are secondary options. The cytopathologist's role in specimen handling and triage is essential to ensure that molecular testing can be carried out successfully.


[Radioiodine therapy for Graves' disease: problems and new developments].
In Germany, patients with Graves' disease are usually treated with radioiodine after unsuccessful antithyroid drug medication, occurrence of side effects from antithyroid drugs or an increased risk from surgery. In patients with normal or only slightly enlarged thyroid glands (volume < or = 50 ml), radioiodine therapy is particularly effective. Radioiodine is the preferential treatment for Graves' patients with high titres of TSH-receptor antibodies and cigarette smoking. Children are still rarely treated with radioiodine in Germany. In contrast, treatment with radioiodine should be more liberally applied in elderly patients with subclinical hyperthyroidism and cardiac symptoms. Individual dosimetry to determine the therapeutic activity is mandatory in Germany. Patients with large goitres obviously need higher organ doses than patients with smaller goitres or normal thyroid glands. Antithyroid drug treatment may interfere with radioiodine therapy. Therefore, it is recommendable to withdraw antithyroid drugs several days before treatment with radioiodine is initiated (and a preceding radioiodine uptake test is performed). In patients with Graves' orbitopathy prophylaxis with corticosteroids can prevent the worsening of symptoms that may be induced by radioiodine treatment. Currently, a risk adapted procedure is recommended according to which prophylactic medication with corticosteroids before applying radioiodine treatment is not necessary in patients with symptoms of orbitopathy and lack of other risk factors (cigarette smoking, in particular). Present results suggest that the risks of radioiodine treatment in Graves' disease patients are very low, while at the same time the cost-effectiveness of this treatment regimen is high.


Powered vs manual tooth brushing in fixed appliance patients: a short term randomized clinical trial.
Sixty-three orthodontic patients wearing upper and lower fixed appliances were randomly assigned to use either a powered toothbrush fitted with a modified orthodontic brush head (Braun Oral-B Plaque Remover 3D) or a manual toothbrush (Reach Compact Medium). A trained hygienist instructed each patient on the proper use of the allocated brush. Measurements of plaque and gingival health were made at baseline, at four weeks, and at eight weeks. Data for each group were analyzed using paired t-tests. Patients using the powered toothbrush showed a significant reduction in percentage interdental bleeding scores from baseline to four weeks (-12.7, P = .003) and this was still apparent at eight weeks (-8.6, P = .028), although there were no statistically significant changes in either plaque or gingivitis scores for this group. Those patients using a manual toothbrush showed a significant reduction in mean plaque score from baseline (four weeks = -0.18, P = < .001; eight weeks = -0.12, P = .016), but gingivitis scores were only reduced significantly at four weeks. In this group, interdental bleeding scores reduced significantly at four weeks (P = .028), but were not significantly different from baseline at eight weeks (P = .0319). When the two patient groups were compared using two sample t-tests, there were no significant differences in any of the parameters measured at any time point in the study. Over an eight-week period, there were no measurable differences between the powered toothbrush with modified orthodontic brush head and a manual toothbrush with respect to mean change in plaque, gingivitis, or interdental bleeding scores when used by patients wearing fixed appliances.


Clinical evaluation and sequence analysis of the complete mitochondrial genome of three Chinese patients with hearing impairment associated with the 12S rRNA T1095C mutation.
Mutations in mitochondrial DNA (mtDNA), particularly those in the 12S rRNA gene, have been shown to be associated with sensorineural hearing loss. Here we report the clinical and sequence analysis of the entire mitochondrial genome in three Chinese subjects with aminoglycoside-induced and non-syndromic hearing impairment. Clinical evaluation showed a variable phenotype of hearing impairment including the age of onset and audiometric configuration in these subjects. Sequence analysis of the complete mitochondrial genomes in three subjects showed the distinct sets of mtDNA polymorphism, in addition to the identical mitochondrial 12S rRNA T1095C mutation. This mutation was previously identified to be associated with hearing impairment in three families from different genetic backgrounds. The T1095C mutation was absent in 364 Chinese control. In fact, the occurrence of the T1095C mutation in these several genetically unrelated subjects affected by hearing impairment strongly indicates that this mutation is involved in the pathogenesis of hearing impairment. Among other nucleotide changes, the A2238G and T2885C mutations in the 16S rRNA, the I175V mutation in the CO2, the F16L mutation in the A6 and the V112M mutation in the ND6 exhibited a high evolutionary conservation. These data suggest that the T1095C mutation may be associated with aminoglycoside-induced and non-syndromic hearing impairments and A2238G and T2885C mutations in the 16S rRNA, the I175V mutation in the CO2, the F16L mutation in the A6 and the V112M mutation in the ND6 may contribute to the phenotypic expression of the T1095C mutation in these subjects.


Selective inhibition of the C-domain of angiotensin I converting enzyme by bradykinin potentiating peptides.
Somatic angiotensin I converting enzyme (ACE) contains two functional active sites. Up to now, most of the studies aimed at characterizing the selectivity of inhibitors toward the two ACE active sites relied on the use of ACE mutants containing a single functional active site. By developing new fluorogenic synthetic substrates of ACE, we demonstrated that inhibitor selectivity can be assessed directly by using somatic ACE. This useful screening approach led us to discover that some bradykinin potentiating peptides turned out to be selective inhibitors of the C-domain of ACE. The peptide pGlu-Gly-Leu-Pro-Pro-Arg-Pro-Lys-Ile-Pro-Pro, with K(i)(app) values of 30 nM and 8 microM, respectively, for the C- and N-domain of ACE, is to our knowledge the most highly selective C-domain inhibitor of ACE so far reported. Inhibitors able to block selectively either the N- or C-domain of ACE will represent unique tools to probe the function of each domain in the regulation of blood pressure or other physiopathological events involving ACE activity.


Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant.
The present study evaluated soybean oil (SO) containing vitamin E (VE) and ginseng saponins (GS) (SO-VE-GS) for their adjuvant effect on foot-and-mouth disease (FMD) vaccine. Since mineral oil ISA 206 is a common adjuvant used in the FMD vaccine, it was used as a control adjuvant in this study. VE and GS were found to have a synergistic adjuvant effect. When mice were immunized with the FMD vaccine emulsified in SO with VE and GS, significantly higher serum IgG, IgG1, and IgG2a were found than VE and GS used alone. SO-VE-GS and ISA 206 behaved differently in adjuvant activities. When mice were immunized with the FMD vaccine adjuvanted with SO-VE-GS, significantly higher and earlier production of serum IgG was found than that adjuvanted with ISA 206. Although both adjuvants significantly increased the number of bone marrow plasma cells, a stimulation index of lymphocytes (SI) as well as the production of IL-4 and IL-6, SO-VE-GS promoted significantly higher SI and the ratio of CD4+/CD8+ T cells with production of increased IFN-γ and decreased TGF-β1 as compared with the ISA 206 group. The data suggested that SO-VE-GS activated Th1/Th2 immune responses. Transcriptome analysis of splenocytes showed that differentially expressed genes (DEGs), immune-related gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the SO-VE-GS group. Therefore, the potent adjuvant effect of SO-VE-GS on the FMD vaccine may be attributed to the immune-related gene profile expressed in lymphocytes. Due to its plant origin and due to being much cheaper than imported mineral oil ISA 206, SO-VE-GS deserves further study in relation to vaccines used in food animals.


Diffusion-weighted magnetic resonance imaging of ovarian tumors: differentiation of benign and malignant solid components of ovarian masses.
We evaluated the feasibility of diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurement in differentiating benign and malignant ovarian tumors. Surgically proven 49 ovarian tumors (39 malignant/borderline malignant and 10 benign) were examined. The solid portion of all 39 malignant tumors showed homogeneous or heterogeneous high intensity on DWI, whereas only 3 of the 10 benign tumors (3 thecomas) showed high intensity. The mean (SD) ADC value in the 39 malignant tumors (1.03 [0.19]) was significantly lower than that in 10 benign tumors (1.38 [0.30]). A relatively low ADC (1.08-1.20) in the 3 thecomas may reflect their abundant cellular nature, and the presence of low intensity on T2-weighted images was suggestive for benign fibrous tumor. Low intensity on DWI with high ADC may suggest benign lesions; however, it may be occasionally difficult to differentiate benign and malignant lesions only on the basis of DWI.


Addition of beta1-6 GlcNAc branching to the oligosaccharide attached to Asn 772 in the serine protease domain of matriptase plays a pivotal role in its stability and resistance against trypsin.
beta1-6 GlcNAc branching, a product of N-acetylglucosaminyltransferase V (GnT-V), is a key structure that is associated with malignant transformations and cancer metastasis. Although a number of reports concerning tumor metastasis-related glycoproteins that contain beta1-6 GlcNAc branching have appeared, the precise function of beta1-6 GlcNAc branching on glycoproteins remains to be elucidated. We previously reported on the importance of beta1-6 GlcNAc branching on matriptase in terms of proteolytic degradation in tumor metastasis. We report here that matriptase purified from GnT-V transfectant (beta1-6 GlcNAc matriptase) binds strongly to L4-PHA, which preferentially recognizes beta1-6 GlcNAc branches of tri- or tetraantennary sugar chains, indicating that the isolated matriptase contains beta1-6 GlcNAc branching. The beta1-6 GlcNAc matriptase was resistant to autodegradation, as well as trypsin digestion, compared with matriptase purified from mock-transfected cells. Furthermore, N-glycosidase-F treatment of beta1-6 GlcNAc matriptase greatly reduced its resistance to degradation. An analysis of matriptase mutants that do not contain potential N-glycosylation sites clearly shows that the beta1-6 GlcNAc branching on N-glycans attached to Asn 772 in the serine protease domain plays a major role in trypsin resistance. This is the first example of a demonstration of a direct relationship between beta1-6 GlcNAc branching and a biological function at the protein level.


Plasma carnitine levels in patients receiving home parenteral nutrition.
Patients on long-term home parenteral nutrition (HPN) are known to frequently develop hepatic steatosis or steatohepatitis. The etiology of this steatosis or steatohepatitis is unknown, but carnitine deficiency has been one of the postulated mechanisms. The importance of L-carnitine in hepatic fatty acid oxidation and the steatosis observed in primary and acquired carnitine deficiencies prompted us to determine plasma carnitine levels in 37 patients receiving long-term HPN. Thirteen patients (35%) had low total and free plasma carnitine levels. Fifteen of the 37 HPN patients were matched for age and sex with 15 patients with Crohn's disease who did not require HPN. Mean total and free plasma carnitine values were significantly lower (p less than 0.001) in these 15 HPN patients (32.2 +/- 11.9 and 28.4 +/- 10.8) when compared to Crohn's patients not requiring HPN (49.1 +/- 10.9 and 46.4 +/- 11.5). Associations were not detected between plasma carnitine and clinical or biochemical parameters that might have explained the low values.


Coronary artery calibre after direct intra-arterial infusion of epoprostenol (prostacyclin).
Because epoprostenol (prostacyclin) is a prostaglandin that causes vasodilatation and inhibits platelet function it may be of benefit during coronary artery angioplasty. The safety and capacity of intracoronary epoprostenol to dilate coronary arteries were assessed in 16 patients undergoing routine coronary angiography. The view that best displayed the left epicardial coronary arteries was selected as a control for each patient. Intracoronary epoprostenol was then given and the angiogram was repeated in the chosen view. The procedure was repeated twice: once with a higher dose of epoprostenol and once after intracoronary isosorbide dinitrate. Angiograms were coded and analysed by an observer who was unaware of the treatment. The calibre of the arteries was measured from traced projections of the angiograms. The blood pressure, heart rate, and electrocardiogram were recorded throughout. The first two patients were given epoprostenol infusions of 2.5 and 5.0 ng/kg per minute to assess safety, and there were no untoward reactions. The next ten patients had epoprostenol infusions of 5.0 and 7.5 ng/kg per minute followed by intracoronary isosorbide dinitrate. No haemodynamic disturbances occurred and coronary luminal calibre did not change with epoprostenol (mean (SD) luminal diameter: 2.85 (0.62) mm control, 2.80 (0.61) mm at 5.0 ng/kg, and 2.80 (0.54) mm at 7.5 ng/kg), but it did increase significantly with isosorbide dinitrate (to 3.17 (0.36) mm). The last four patients had epoprostenol infusions of 7.5 and 10 ng/kg followed by intracoronary isosorbide dinitrate and two of them became hypotensive (one after epoprostenol and one after isosorbide dinitrate). Coronary luminal calibre did not change significantly (3.5 (0.45) mm control, 2.96 (0.81) mm at 7.5 ng/kg, 3.45 (0.96) mm at 10 ng/kg, and 3.20 (0.61) mm with isosorbide dinitrate). Eight patients developed tall T waves on the electrocardiogram during epoprostenol infusion but none had arrhythmias. The results indicate that clinically tolerable doses of intracoronary epoprostenol do not significantly dilate the epicardial coronary arteries. This route of administration is therefore unlikely to be of use during coronary angioplasty, although the antiplatelet action of intravenous epoprostenol might help to prevent restenosis.


Weight-bearing knee flexion angle better correlates with patient-reported outcome measures than non-weight-bearing condition in total knee arthroplasty: a three-dimensional analysis study.
This study aims to elucidate and compare the relationship between the knee flexion angle and patient-reported outcome measures (PROM) in both non-weight-bearing (NWB) and weight-bearing (WB) conditions. This retrospective cohort study included 61 knees (47 patients) who underwent total knee arthroplasty. The knee flexion angle was measured by three conditions: NWB in manual goniometer, NWB in fluoroscopic three-dimensional (3D) analysis and WB in the fluoroscopic 3D analysis. The PROM was evaluated by postoperative 2011 Knee Society Score (2011 KSS) and Knee injury and Osteoarthritis Outcome Score (KOOS). Correlations between the knee flexion angle and PROM was analyzed using Spearman's correlation coefficient. Additionally, whether the angular difference between NWB and WB correlated with the PROM or not was evaluated. The NWB knee flexion angle in a goniometer, NWB in 3D analysis, and WB in 3D analysis were 124.6° ± 8.4°, 118.0° ± 10.5°, and 109.5° ± 13.3°, respectively. The angular difference was 8.5° ± 12.8°. No PROM correlation existed in NWB using a goniometer. Moreover, significant positive correlations in 2011 KSS symptoms (r = 0.35) and 2011 KSS functional activities (r = 0.27) were noted in NWB using 3D analysis. Significant positive correlations existed in 2011 KSS symptoms (r = 0.32), 2011 KSS functional activities (r = 0.57), KOOS pain (r = 0.37), KOOS activity of daily living (ADL; r = 0.45), KOOS sports (r = 0.42), and KOOS quality of life (r = 0.36) in WB using 3D analysis. Significant negative correlations were noted in 2011 KSS functional activities (r = - 0.45), KOOS ADL (r = - 0.30), and KOOS sports (r = - 0.38) in angular difference. The WB knee flexion angle better correlated with PROM compared with NWB by evaluation of 3D analysis. The larger the angular difference existed between NWB and WB, the lower the PROM score.


The rationale for the use of risk calculators in pressure sore prevention, and the evidence of the reliability and validity of published scales.
Recent studies have shown an increase in pressure sore prevalence rates. However, methodological inconsistencies and demographic considerations, which include an ageing population, make it difficult to interpret and compare results. A multiplicity of intrinsic and extrinsic factors are thought to be associated with increased risk. The development of risk calculators which incorporate these factors has been an attempt to identify which subjects are most at risk so that equipment and nursing interventions can be allocated appropriately. Since the 1960s there has been a proliferation of risk assessment scales which have not been subjected to rigorous scrutiny of their reliability and validity, and this is held to represent a failure of nursing research. Recent evidence suggests that if critical cut-off points for 'at-risk' vs. 'no risk' are adjusted for particular patient populations the validity of existing scales can be improved. Missing from the literature are research reports of studies carried out in the community. As a result of demographic changes and community care policies, more 'at-risk' patients are likely to be nursed at home. Future research needs to include community studies, and a more systematic approach in general, to the study of the predictive value of existing scales.


The diagnosis of reversible dementia in the elderly. A critical review.
Evaluation of the elderly demented patient includes a search for treatable diseases; recommendations for this approach have been based on reports of a high prevalence of "reversible" dementia in several series of patients in the medical literature. A critical review of the methodology of these reports was undertaken to determine their validity as sources for the protocols often recommended. Several methodologic flaws were found in many studies that recommended extensive "screening" of the demented elderly, limiting their usefulness as resources. More carefully designed studies are needed to understand better the frequency and etiology of reversible causes of dementia.


Glassy dynamics in the adaptive immune response prevents autoimmune disease.
The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system's search for antibodies, a balance has evolved between binding affinity and specificity.


Direct detection of guidance receptor activity during border cell migration.
Guidance receptor signaling is crucial for steering migrating cells. Despite this, we generally lack direct measurements of such signaling. Border cells in Drosophila migrate as a tightly associated group, but dynamically, with front and rear cells exchanging places. They use the receptor tyrosine kinase (RTK) PDGF/VEGF receptor (PVR) as a guidance receptor, perceiving the attractant Pvf1. Here we determine the spatial distribution of PVR signaling by generating an antibody that specifically detects activated PVR in situ. PVR activity is very low in migrating border cells, due to strong activity of cellular phosphatases. Measurements of signal at the cell cortex show variability but a strong bias for both total active PVR and specific activity of PVR to be elevated at the front versus side of the leading cell, often with several-fold difference in signal levels. This polarized active PVR signal requires the E3 ubiquitin ligase Cbl and the recycling regulator Rab11, indicating a dependency on receptor trafficking. The endogenous ligand gradient contributes to shaping of signaling by increasing the specific activity of PVR toward the source in front cells. Surprisingly, signaling is also elevated at the back versus the side of rear cells. This distally polarized distribution of active PVR is ligand independent. Thus the actual guidance signal transmitted in border cells appears to integrate perceived ligand distribution with cell polarity or cell orientation with respect to the cluster. A general implication is that both group configuration and extrinsic cues can directly modulate guidance receptor signaling during collective cell migration.


Head group and chain length dependence of phospholipid self-assembly studied by spin-label electron spin resonance.
The critical micelle concentrations (cmc's) of a variety of spin-labeled phospholipids, 1-acyl-2-[4-(4,4-dimethyloxazolidine-N-oxyl)valeryl]-sn-glycero-3-pho sph o derivatives, have been determined by electron spin resonance (ESR) spectroscopy. The narrow, three-line ESR spectra of the rapidly tumbling monomers are clearly distinguished from the spin-spin broadened spectra of the micellar aggregates, allowing a direct determination of the concentrations of the two species. The influence of both the hydrocarbon chain length and the polar head group on the energetics of self-assembly has been studied. For phosphatidylcholine, 1n [cmc] decreases linearly with the length of the sn-1 chain. The gradient of this linear dependence corresponds to a free energy of transfer of the monomer from the aqueous phase to the micelle of delta Gtr = -1.1RT per CH2 group. The cmc's of the 1-lauroyl derivatives of both phosphatidylcholine and phosphatidylglycerol have relatively shallow, biphasic temperature dependences with a minimum at approximately 20 degrees C. Both of these properties are characteristic of the hydrophobic effect, with the free energy of transfer being slightly less than that for the solubility of n-hydrocarbons in water, corresponding to the reduced configurational entropy of the lipid chains in the micellar state. The cmc's of the 1-lauroyl derivatives of the phospholipids in 0.15 M NaCl, for their various charge states, are as follows: phosphatidic acid(2-), 0.77 mM; phosphatidic acid(1-), 0.13 mM; phosphatidylserine(1-), 0.24 mM; phosphatidylglycerol(1-), 0.17 mM; phosphatidylcholine, 0.10 mM; phosphatidylethanolamine, 0.05 mM.(ABSTRACT TRUNCATED AT 250 WORDS)


Cardiac thromboxane A2 receptor activation does not directly induce cardiomyocyte hypertrophy but does cause cell death that is prevented with gentamicin and 2-APB.
We have previously shown that the thromboxane (TXA2) receptor agonist, U46619, can directly induce ventricular arrhythmias that were associated with increases in intracellular calcium in cardiomyocytes. Since TXA2 is an inflammatory mediator and induces direct calcium changes in cardiomyocytes, we hypothesized that TXA2 released during ischemia or inflammation could also cause cardiac remodeling. U46619 (0.1-10 μM) was applied to isolated adult mouse ventricular primary cardiomyocytes, mouse ventricular cardiac muscle strips, and cultured HL-1 cardiomyocytes and markers of hypertrophy and cell death were measured. We found that TXA2 receptors were expressed in ventricular cardiomyocytes and were functional via calcium imaging. U46619 treatment for 24 h did not increase expression of pathological hypertrophy genes (atrial natriuretic peptide, β-myosin heavy chain, skeletal muscle α-actin) and it did not increase protein synthesis. There was also no increase in cardiomyocyte size after 48 h treatment with U46619 as measured by flow cytometry. However, U46619 (0.1-10 μM) caused a concentration-dependent increase in cardiomyocyte death (trypan blue, MTT assays, visual cell counts and TUNEL stain) after 24 h. Treatment of cells with the TXA2 receptor antagonist SQ29548 and inhibitors of the IP3 pathway, gentamicin and 2-APB, eliminated the increase in cell death induced by U46619. Our data suggests that TXA2 does not induce cardiac hypertrophy, but does induce cell death that is mediated in part by IP3 signaling pathways. These findings may provide important therapeutic targets for inflammatory-induced cardiac apoptosis that can lead to heart failure.


In situ evaluation of sodium hexametaphosphate-containing dentifrices.
The purpose of this investigator-blinded, five-treatment, crossover human intraoral study was to evaluate the effects of two experimental dentifrice formulations containing either stannous fluoride (SnF(2)) or sodium fluoride (NaF) packaged with sodium hexametaphosphate in a dual-phase delivery system on demineralization-remineralization using an in situ model system. The experimental dentifrice formulations' ability to alter demineralization-remineralization was compared to a series of three controls: SnF(2)-positive control, NaF-positive control and no-fluoride placebo-negative control. The single-section crown model, developed at the University of Iowa, was used to assess the fluoride efficacy of two experimental products versus the placebo containing no fluoride and positive controls. The results of the current in situ study suggest a clinical level of anticaries activity for the experimental SnF(2) and NaF dentifrice formulations that was as good as either of the positive controls, when evaluated using polarized light microscopy. This supports the conclusion that the use of the sodium hexametaphosphate ingredient does not interfere with the normal fluoride activity of these toothpastes. In addition, the experimental SnF(2) product was numerically better than both the NaF and placebo controls at preventing demineralization of sound root surfaces.


Molecular characterization of Pacific white shrimp (Litopenaeus vannamei) sodium bicarbonate cotransporter (NBC) and its role in response to pH stress.
The sodium bicarbonate cotransporter (NBC) is an integral membrane ion transporter that can transport HCO3- (or a related species, such as CO32-) across the plasma membrane. Previous researches revealed that NBC might play an important role in the regulation of intracellular pH in vertebrates. In the present study, an NBC cDNA was identified from Pacific white shrimp (Litopenaeus vannamei) and designated as Lv-NBC. The full-length Lv-NBC cDNA is 4479 bp in size, containing a 5'-untranslated region (UTR) of 59 bp, a 3'-UTR of 835 bp and an open reading frame (ORF) of 3585 bp that encodes a protein of 1194 amino acids with a deduced molecular weight of 134.34 kDa. The Lv-NBC protein contains two functional domains (Band_3_cyto and HCO3_cotransp) and twelve transmembrane (TM) domains. Expression of the Lv-NBC mRNA was ubiquitously detected in all selected tissues, with the highest level in the gill. By in situ hybridization (ISH) with Digoxigenin-labeled probe, the Lv-NBC positive cells were shown mainly located in the secondary gill filaments. After low or high pH challenge, the transcript levels of Lv-NBC in the gill were found to be up-regulated. After knockdown of the Lv-NBC level by siRNA, the mortality of shrimp significantly increased under pH stress. Our study, as a whole, may provide evidences for the role of NBC in shrimp responding to pH stress, and give a new insight of the acid/base homeostasis mechanism in crustaceans.


Epigenetic gene expression noise and phenotypic diversification of clonal cell populations.
Spontaneous emergence of phenotypic heterogeneity in cultures of genetically identical cells is a frequently observed phenomenon that provides a simple in vitro experimental system to model the problems of in vivo differentiation. In the present study, we have investigated whether stochastic variation of gene expression levels could contribute to phenotypic change in human cells. We have applied the two fluorescence-coding gene method and the expression variability of the two reporter genes to human cells in culture. We have quantified the portion of gene expression variation determined by global, promoter-specific, or by epigenetic sources. These two types of variation appear to contribute, in different ways, to the phenotypic diversification of clonal cell populations. Global, or promoter-specific, gene expression noise increases with cellular stress and contributes to the emergence of cellular diversity by diversifying the gene-expression levels. Epigenetic mechanisms act to increase the robustness of the cellular state by stabilizing gene transcription levels or by reinforcing the silenced state.


Comparison of inoculum sources for long-term process performance and fate of ANAMMOX bacteria niche in poly(vinyl alcohol)/sodium alginate gel beads.
The process performance and microbial niche of anaerobic ammonia oxidation (ANAMMOX) bacteria were compared in two identical bioreactors inoculated with different inoculum sources (i.e., pre-cultured ANAMMOX bacteria: PAB and activated sludge: AS) entrapped in poly(vinyl alcohol)/sodium alginate (PVA/SA) gel beads for a long-term period (i.e., 1.5 years). The start-up period with AS was longer than that with PAB; however, both bioreactors were successfully operated over the long-term with stable ANAMMOX activity. After long-term operation, the 16S rRNA gene concentration of ANAMMOX bacteria in both bioreactors was significantly increased, and thereby became comparable. In addition, Candidatus Jettenia sp. became the dominant ANAMMOX species in both bioreactors. Our results suggested that the ANAMMOX performance and microbial niche of ANAMMOX bacteria became nearly identical during long-term operation despite the use of different inoculum sources. Therefore, the use of PVA/SA gel beads entrapping AS appears to be a relevant option for constructing an ANAMMOX process in places where a full-scale ANAMMOX process has never been done previously.


Producing gestures facilitates route learning.
The present study investigates whether producing gestures would facilitate route learning in a navigation task and whether its facilitation effect is comparable to that of hand movements that leave physical visible traces. In two experiments, we focused on gestures produced without accompanying speech, i.e., co-thought gestures (e.g., an index finger traces the spatial sequence of a route in the air). Adult participants were asked to study routes shown in four diagrams, one at a time. Participants reproduced the routes (verbally in Experiment 1 and non-verbally in Experiment 2) without rehearsal or after rehearsal by mentally simulating the route, by drawing it, or by gesturing (either in the air or on paper). Participants who moved their hands (either in the form of gestures or drawing) recalled better than those who mentally simulated the routes and those who did not rehearse, suggesting that hand movements produced during rehearsal facilitate route learning. Interestingly, participants who gestured the routes in the air or on paper recalled better than those who drew them on paper in both experiments, suggesting that the facilitation effect of co-thought gesture holds for both verbal and nonverbal recall modalities. It is possibly because, co-thought gesture, as a kind of representational action, consolidates spatial sequence better than drawing and thus exerting more powerful influence on spatial representation.


The prostate as a reservoir for HIV-1.
As the prostate can harbor bacterial and fungal pathogens, it was investigated as a reservoir for HIV. Nine men chronically infected with HIV participated in a crossover trial in which weekly semen samples were collected with and without previous prostate massage (PM). Six of the nine participants had undetectable seminal plasma(SP) HIV RNA in all samples without previous PM, but had detectable SP HIV RNA (> 25 copies/ml) in one to three samples collected after PM.


[Pulmonary emphysema induced by elastase: influence of the dose and effect of added collagenase].
The endotracheal deposition of pancreatic porcine elastase (EPP) at 40 u X kg-1 body weight provokes a typical pulmonary emphysema (alveoli disruption) in rats. This emphysema is significant (p less than 0.001) when quantitatively compared to a placebo (100% increase of the mean linear intercept, ILM). The EPP-treated lungs are very heterogeneous and the size of the alveoli vary as much as 30% versus 19% in controls. The emphysema is more effective at a 80 u X kg-1 dose and the individual disparities are reduced (dose effect). When bacterial collagenase (200 u X kg-1 body weight) is added to EPP, the pulmonary abnormalities (disruptions, ILM) are in no way increased (no enzymatic synergy, repair by collagenesis?). In contrast, alveolar dilation is slightly reduced 8 weeks after enzyme administration (p less than 0.05): EPP is not altered in vitro by collagenase and despite several hypothesis, the moderating effect of collagenase in vivo still remains unexplained. This result suggests that the joint presence of several proteases is not necessarily an aggravating factor in the etiopathogenesis of emphysema.


A comparative study of bronchopulmonary slowly adapting receptors between rabbits and rats.
Pulmonary mechanosensory receptors provide important inputs to the respiratory center for control of breathing. However, what is known about their structure-function relationship is still limited. In these studies, we explored this relationship comparing bronchopulmonary slowly adapting receptor (SAR) units in rabbits and rats. In morphological studies, sensory units in tracheobronchial smooth muscle labeled with anti-Na+ /K+ -ATPase (α3 subunit) were found to be larger in the rabbit. Since larger structures may result from increased receptor size or more numerous receptors, further examination showed receptor size was the same in both species, but more receptors in a structure in rabbits than rats, accounting for their larger structure. In functional studies, SAR units were recorded electrically in anesthetized, open-chest, and artificially ventilated animals and responses to lung inflation were compared at three different constant airway pressures (10, 20, and 30 cmH2 O). At each level of the inflation, SAR discharge frequencies were found to be higher in rabbits than rats. We conclude that a relatively larger number of receptors in a sensory unit may be responsible for higher SAR activities in rabbit SAR units.


[Genetic diversity of yam (Dioscorea opposita Thunb) detected by ISSR markers].
Genetic diversity of 28 cultivars of yam (Dioscorea opposita Thunb) was assessed by means of Inter-simple sequence repeat (ISSR) markers. The results showed that seven proper primers, with rich polymorphism, could be selected from a total of forty four ISSR ones; distinct differences appeared among 28 cultivars amplified bands, and the rate of polymorphic bands was 83.01%; Shannon's Information index was 0.3191; a Jaccard's genetic similarity matrix and a dendrogram for these cultivars were formed, in which they could be divided into four groups: Group 1 was composed of D. opposita. cv. Ribenbai, D. opposita. cv. Huashanyao and D. opposita. cv. Ribenyuan; Group2 contained D. opposita. cv. Xiaoye; Group 3 contained D. opposita. cv. No.1 Songye; other 23 cultivars were put into Group4. PCA(Principal component analysis) was employed to evaluate the resolving power of the markers to differentiate among them. This laid the foundation of the identification of yam cultivars and the efficient use of its germplasm resources.


Structural organization and chromosomal assignment of the gene encoding the human heparin-binding epidermal growth factor-like growth factor/diphtheria toxin receptor.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently identified, potent smooth muscle cell mitogen of macrophage origin. It is expressed in a highly regulated fashion in vascular endothelial and smooth muscle cells, indicating a potentially important role for this gene in atherosclerosis. In addition, the HB-EGF precursor has recently been found to function as a receptor for diphtheria toxin. Using an HB-EGF cDNA probe, we cloned the human gene encoding HB-EGF. The HB-EGF gene contains six exons and five intervening sequences spanning 14 kb of DNA. By primer extension and S1 nuclease analysis, we located a major transcription start site (corresponding to an A residue) 14 bp beyond the 5' end of the HB-EGF cDNA. There were no TATAAA or CCAAT consensus sequences upstream of the transcription start site. The density of primer extension bands generated by RNA from endothelial cells treated with tumor necrosis factor-alpha (TNF-alpha) was 10 times higher than that of bands generated by the control, indicating that TNF-alpha increased the level of HB-EGF mRNA. Using transient reporter gene transfection experiments, we show that 2.0 kb of HB-EGF 5'-flanking sequence has promoter activity in bovine aortic endothelial cells. By analysis of DNA isolated from human-mouse somatic hybrid cell lines, we assign the HB-EGF gene to chromosome 5. By functional study, chromosome 5 has been associated with diphtheria toxin susceptibility.


Somatotopic organization in the sensory innervation of the rat hindlimb during development, using half dorsal root ganglia as subsegmental units.
The aim of the present study was to determine the somatotopy of the sensory innervation of the rat hindlimb at the level of the dorsal root ganglia (DRGs) during the fetal and postnatal period. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made into the hindlimb of fetal and postnatal rats. These injections result in completely and partially labeled DRGs. Partial labeling always concerns the rostral or caudal half of a DRG. Using half DRGs as subsegmental units, a description is given of a somatotopic organization of the sensory innervation of the rat hindlimb during development.


[Cloning and analysis of human alpha-1B glycoprotein precursor gene: a novel member of human immunoglobulin superfamily].
A cDNA of 1694 bp was cloned from human liver Marathon cDNA by means of Rapid Amplification of cDNA Ends (RACE). The cDNA has an open reading frame at 43-1530 bp encoding 495 amino acid residues and a 17-residue signal peptide. There are four Igc2 domains in the translated polypeptide, which is highly homologous to the human alpha-1B glycoprotein isolated from human plasma. Upon this, we conclude that this cDNA is the alpha-1B glycoprotein precursor gene which has never been cloned before, and it may be a novel member of immunoglobulin superfamily and may involved in the cell recognition and the regulation of cell behavior.


Roles of p63 in epidermal development and tumorigenesis.
Epidermis is composed mainly of keratinocytes and is the ma-jor barrier of human body. The development and maintenance of normal epithelial structures and functions require the transcription factor p63. The p63 gene encodes proteins with structures similar to that of p53, including an N-terminal transactivation (TA) domain, a DNA-binding domain and a carboxy-oligomerization domain. TAp63 and ΔNp63 (p63 isoforms without TA domain) regulate a wide range of target genes that are important for embryonal development and epithelial integrity. Mutations of p63 gene cause epidermal abnormalities characterized by ectodermal dysplasia. Recent reports have indicated that p63 plays important role in tumorigenesis as well. However, the relative importance of TAp63 and ΔNp63 in epidermal development and tumorigenesis re-mains mostly unclear and awaits further investigation. In this review, we summarize the current knowledge on the structure and function of p63 and its isoforms.


Identification of sendai virus L protein amino acid residues affecting viral mRNA cap methylation.
Viruses of the order Mononegavirales all encode a large (L) polymerase protein responsible for the replication and transcription of the viral genome as well as all posttranscriptional modifications of viral mRNAs. The L protein is conserved among all members of the Mononegavirales and has six conserved regions ("domains"). Using vesicular stomatitis virus (VSV) (family Rhabdoviridae) experimental system, we and others recently identified several conserved amino acid residues within L protein domain VI which are required for viral mRNA cap methylation. To verify that these critical amino acid residues have a similar function in other members of the Mononegavirales, we examined the Sendai virus (SeV) (family Paramyxoviridae) L protein by targeting homologous amino acid residues important for cap methylation in VSV which are highly conserved among all members of the Mononegavirales and are believed to constitute the L protein catalytic and S-adenosylmethionine-binding sites. In addition, an SeV L protein mutant with a deletion of the entire domain VI was generated. First, L mutants were tested for their abilities to synthesize viral mRNAs. While the domain VI deletion completely inactivated L, most of the amino acid substitutions had minor effects on mRNA synthesis. Using a reverse genetics approach, these mutations were introduced into the SeV genome, and recombinant infectious SeV mutants with single alanine substitutions at L positions 1782, 1804, 1805, and 1806 or a double substitution at positions 1804 and 1806 were generated. The mutant SeV virions were purified, detergent activated, and analyzed for their abilities to synthesize viral mRNAs methylated at their cap structures. In addition, further studies were done to examine these SeV mutants for a possible host range phenotype, which was previously shown for VSV cap methylation-defective mutants. In agreement with a predicted role of the SeV L protein invariant lysine 1782 as a catalytic residue, the recombinant virus with a single K1782A substitution was completely defective in cap methylation and showed a host range phenotype. In addition, the E1805A mutation within the putative S-adenosylmethionine-binding site of L resulted in a 60% reduction in cap methylation. In contrast to the homologous VSV mutants, other recombinant SeV mutants with amino acid substitutions at this site were neither defective in cap methylation nor host range restricted. The results of this initial study using an SeV experimental system demonstrate similarities as well as differences between the L protein cap methylation domains in different members of the Mononegavirales.


Admissions with atrial fibrillation in a multiracial population in Kuala Lumpur, Malaysia.
There are established differences in cardiovascular disease in different racial groups. Worldwide, the literature regarding the clinical epidemiology of atrial fibrillation in non-white populations is scarce. To document the prevalence of atrial fibrillation (AF) in the multiracial population of Malaysia, and to describe the clinical features and management of these patients. Busy city centre general hospital in Kuala Lumpur, Malaysia, over a 1-month period. One-thousand four hundred and thirty-five acute medical admissions, of whom 40 patients (2.8%) had AF. Of 1435 acute medical admissions to Kuala Lumpur General Hospital over the 4-week study period, 40 had AF (21 male, 19 female; mean age 65 years). Of these, 18 were Malay, 16 Chinese and six Indian. Nineteen patients had previously known AF (seven with paroxysmal AF) and 21 were newly diagnosed cases. The principal associated medical conditions were ischaemic heart disease (42.5%), hypertension (40%) and heart failure (40%). Dyspnoea was the commonest presentation, whilst stroke was the cause of presentation in only two patients. Investigations were under-utilised, with chest X-ray and echocardiography in only 62.5% of patients and thyroid function checked in 15%. Only 16% of those with previously diagnosed AF were on warfarin, with a further three on aspirin. Anticoagulant therapy was started in 13.5% of patients previously not on warfarin, and aspirin in 8%. Records of contraindications to warfarin were unreliable, being identified in only 25%. For those with known AF, 58% were on digoxin. For new onset AF, digoxin was again the most common rate-limiting treatment, initiated in 38%, whilst five patients with new onset AF were commenced on amiodarone. DC cardioversion was not used in any of the patients with new onset AF. Amongst acute medical admissions to a single centre in Malaysia the prevalence of AF was 2.8%. Consistent with previous similar surveys in mainly western (caucasian) populations, standard investigations in this Malaysian cohort were also inadequate and there was underuse of anticoagulation, medication for ventricular rate control and cardioversion to sinus rhythm.


Importance of controlling mesocotyl elongation in the development of rice seedlings intended for mechanical transplantation.
The mesocotyl facilities the emergence of deep-sown rice. However, the effects of mesocotyl elongation on mechanically transplanted rice seedlings remain unclear. In this study, the indica three-line hybrid rice Chuanyou 6709 (CY6709) and the indica conventional rice Guichao II (GCII) were selected as experimental materials. The seedlings were grouped based on mesocotyl lengths of 1.0 and 2.0 cm (M1 and M2, respectively), and seedlings without mesocotyl elongation were used as a control (M0). Seedling morphology, root morphology and physiology, and dynamic changes in soluble sugar and protein, malondialdehyde (MDA), and antioxidant enzyme activity in the mesocotyl were evaluated. The results showed that the elongation of mesocotyl is not conducive to improving the quality of mechanically transplanted seedlings, resulting in weak seedlings and poor root coiling force. The mesocotyl lengths of the seedlings showed a single peak with increasing seedling age, which gradually disappeared. The longer the mesocotyls, the slower their senescence. The MDA content of M2 was significantly lower than that of M1, and the activities of soluble sugar, soluble protein, and antioxidant enzymes of M2 were higher than those of M1, implying that seedlings with longer mesocotyls yielded lower-quality seedlings, reducing their suitability for mechanized transplantation. Compared with those of M0, the root-shoot ratio, stem base width, leaf age, leaf area, white root number, root coiling force, root length, root surface area, and root volume of M1 and M2 were reduced. Therefore, in the raising of rice seedlings, excessive elongation of the rice mesocotyl is not conducive to optimum root growth and development of aboveground structures for seedlings that are suitable for mechanized transplantation. Controlling the mesocotyl elongation can facilitate the cultivation of high-quality mechanically transplanted seedlings.


Wnt Signaling in Cancer Metabolism and Immunity.
The Wingless (Wnt)/β-catenin pathway has long been associated with tumorigenesis, tumor plasticity, and tumor-initiating cells called cancer stem cells (CSCs). Wnt signaling has recently been implicated in the metabolic reprogramming of cancer cells. Aberrant Wnt signaling is considered to be a driver of metabolic alterations of glycolysis, glutaminolysis, and lipogenesis, processes essential to the survival of bulk and CSC populations. Over the past decade, the Wnt pathway has also been shown to regulate the tumor microenvironment (TME) and anti-cancer immunity. Wnt ligands released by tumor cells in the TME facilitate the immune evasion of cancer cells and hamper immunotherapy. In this review, we illustrate the role of the canonical Wnt/β-catenin pathway in cancer metabolism and immunity to explore the potential therapeutic approach of targeting Wnt signaling from a metabolic and immunological perspective.


Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.
Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease progression in Stargardt disease. It can be very useful in the evaluation of novel therapeutic modalities in rare disorders.


Overview of advanced technologies for volatile organic compounds measurement in food quality and safety.
Food quality and nutrition have received much attention in recent decades, thanks to changes in consumer behavior and gradual increases in food consumption. The demand for high-quality food necessitates stringent quality assurance and process control measures. As a result, appropriate analytical tools are required to assess the quality of food and food products. VOCs analysis techniques may meet these needs because they are nondestructive, convenient to use, require little or no sample preparation, and are environmentally friendly. In this article, the main VOCs released from various foods during transportation, storage, and processing were reviewed. The principles of the most common VOCs analysis techniques, such as electronic nose, colorimetric sensor array, migration spectrum, infrared and laser spectroscopy, were discussed, as well as the most recent research in the field of food quality and safety evaluation. In particular, we described data processing algorithms and data analysis captured by these techniques in detail. Finally, the challenges and opportunities of these VOCs analysis techniques in food quality analysis were discussed, as well as future development trends and prospects of this field.


[A case of renal cell carcinoma in a nonfunctioning kidney caused by staghorn calculus].
A 62-year-old man was referred to our clinic with a chief complaint of gross hematuria. He had bilateral renal staghorn calculi at the age of 50 years and had undergone left nephrolithotomy. However, no treatment had been given to the right staghorn calculi associated with nonfunctioning kidney. Imaging diagnosis demonstrated no mass lesions in the bilateral kidneys. Right nephrectomy revealed renal cell carcinoma, tubular type, mixed subtype, G2, INF-beta with lymph node metastasis to the renal hilum. Cancer cells infiltrated diffusely throughout the entire renal parenchyma. He died of progressive metastases 15 months postoperatively.


Sensitivity of Nocardia to trimethoprim and sulphonamides in vitro.
Studies in vitro of the sensitivity to trimethoprim and sulphonamides of nine strains of N. asteroides, two strains of N. caviae, and one of N. blackwellii are presented. No unequivocal evidence of synergism was found. Despite this, the inclusion of trimethoprim in the drug regime when sulphonamides are used in the treatment of nocardiosis is suggested on empirical grounds.


Comparative genomics of the Hedgehog loci in chordates and the origins of Shh regulatory novelties.
The origin and evolution of the complex regulatory landscapes of some vertebrate developmental genes, often spanning hundreds of Kbp and including neighboring genes, remain poorly understood. The Sonic Hedgehog (Shh) genomic regulatory block (GRB) is one of the best functionally characterized examples, with several discrete enhancers reported within its introns, vast upstream gene-free region and neighboring genes (Lmbr1 and Rnf32). To investigate the origin and evolution of this GRB, we sequenced and characterized the Hedgehog (Hh) loci from three invertebrate chordate amphioxus species, which share several early expression domains with Shh. Using phylogenetic footprinting within and between chordate lineages, and reporter assays in zebrafish probing >30 Kbp of amphioxus Hh, we report large sequence and functional divergence between both groups. In addition, we show that the linkage of Shh to Lmbr1 and Rnf32, necessary for the unique gnatostomate-specific Shh limb expression, is a vertebrate novelty occurred between the two whole-genome duplications.


Evaluating the Function of the Foot Core System in the Elderly.
As a complex structure to link the body and the ground, the foot contributes to postural control in human static and dynamic activities. The foot core is rooted in the functional interdependence of the passive, active, and neural subsystems, which combine into the foot core system controlling foot motion and stability. The foot arch (passive subsystem), responsible for load, is considered the functional core of the foot, and its stability is necessary for normal foot functions. The functional abnormalities of the foot have been widely reported in the elderly, such as weakness of toe flexor muscles, abnormal foot postures, and decreased plantar sensory sensitivity. In this paper, a comprehensive approach is introduced for evaluating the foot function based on foot core subsystems. The strength and morphology of the foot intrinsic and extrinsic muscles were used to evaluate the foot muscle (active subsystem) function. The doming strength test was applied to determine the function of foot intrinsic muscles, while the toe flexion strength test focused more on the function of extrinsic muscles. The navicular drop test and foot posture index were applied to evaluate foot arch (passive subsystem) function. For the neural subsystem, the plantar light touch threshold test and two-point discrimination test were used to assess plantar tactile sensitivity at nine regions of the foot. This study provides new insights into the foot core function in the elderly and other populations.


Alternate indices of electric and magnetic field exposures among Ontario electrical utility workers.
Epidemiologic studies examining the risk of cancer among occupational groups exposed to electric fields (EF) and or magnetic fields (MF) have relied on traditional summaries of exposure such as the time weighted arithmetic or geometric mean exposure. Findings from animal and cellular studies support the consideration of alternative measures of exposure capable of capturing threshold and intermittent measures of field strength. The main objective of this study was to identify a series of suitable exposure metrics for an ongoing cancer incidence study in a cohort of Ontario electric utility workers. Principal components analysis (PCA) and correlational analysis were used to explore the relationships within and between series of EF and MF exposure indices. Exposure data were collected using personal monitors worn by a sample of 820 workers which yielded 4247 worker days of measurement data. For both EF and MF, the first axis of the PCA identified a series of intercorrelated indices that included the geometric mean, median and arithmetic mean. A considerable portion of the variability in EF and MF exposures were accounted for by two other principal component axes. The second axes for EF and MF exposures were representative of the standard deviation (standard deviation) and thresholds of field measures. To a lesser extent, the variability in the exposure variable was explained by time dependent indices which consisted of autocorrelations at 5 min lags and average transitions in field strength. Our results suggest that the variability in exposure data can only be accounted for by using several exposure indices, and consequently, a series of metrics should be used when exploring the risk of cancer owing to MF and EF exposure in this cohort. Furthermore, the poor correlations observed between indices of MF and EF reinforce the need to be take both fields into account when assessing the risk of cancer in this occupational group.


Identification of a member of a new RNase a family specifically secreted by epididymal caput epithelium.
In this study, we purified the first member of a new ribonuclease (RNase) A family from fluid of the proximal caput of the boar epididymis. This protein, named "Train A," is the most abundant compound secreted in the anterior part of the boar epididymis. After 2D electrophoresis, it is characterized by more than 10 isoforms ranging in size from 26 to 33 kDa and pI from 5 to 8.5. Several tryptic peptides were N-terminal sequenced, and an antiserum against one of these peptides was obtained. The protein was immunolocalized in the epididymal epithelium of the proximal caput, especially in the Golgi zone and the apical cytoplasm of the principal cells. In the lumen, spermatozoa were negative but droplets of reaction product were observed within the lumen. Full lengths of Train A cDNA were obtained from a lambdagt11 boar caput epididymis library and sequenced. The deduced protein is composed of 213 amino acids, including a 23-amino acid peptide signal and a potential N-glycosylation site. The mRNA of this protein has been retrieved and partially sequenced in the bull, horse, and ram, and homologous cDNA is found in databanks for the rat, mouse, and human. All the sequences are highly conserved between species. This protein and its mRNA are male-specific and exclusively expressed in the proximal caput of the epididymis, the only site where they have been found. Train A presents an RNase A family motif in its sequence. The RNase A family is a group of several short proteins (20-14 kDa) with greater and lesser degrees of ribonucleolytic activity and with supposed different roles in vivo. However, the presence of a long-conserved N-terminal specific sequence and the absence of RNase catalytic site for Train A indicate that Train A protein is a member of a new family of RNase A.


A randomized controlled trial of COMPASS web-based and face-to-face teacher coaching in autism.
Most children with autism rely on schools as their primary source of intervention, yet research has suggested that teachers rarely use evidence-based practices. To address the need for improved educational outcomes, a previously tested consultation intervention called the Collaborative Model for Promoting Competence and Success (COMPASS; Ruble, Dalrymple, & McGrew, 2010; Ruble, Dalrymple, & McGrew, 2012) was evaluated in a 2nd randomized controlled trial, with the addition of a web-based group. Forty-nine teacher-child dyads were randomized into 1 of 3 groups: (1) a placebo control (PBO) group, (2) COMPASS followed by face-to-face (FF) coaching sessions, and (3) COMPASS followed by web-based (WEB) coaching sessions. Three individualized goals (social, communication, and independence skills) were selected for intervention for each child. The primary outcome of independent ratings of child goal attainment and several process measures (e.g., consultant and teacher fidelity) were evaluated. Using an intent-to-treat approach, findings replicated earlier results with a very large effect size (d = 1.41) for the FF group and a large effect size (d = 1.12) for the WEB group relative to the PBO group. There were no differences in overall change across goal domains between the FF and WEB groups, suggesting the efficacy of videoconferencing technology. COMPASS is effective and results in improved educational outcomes for young children with autism. Videoconferencing technology, as a scalable tool, has promise for facilitating access to autism specialists and bridging the research-to-practice gap.


Does cocoa/dark chocolate supplementation have favorable effect on body weight, body mass index and waist circumference? A systematic review, meta-analysis and dose-response of randomized clinical trials.
Background: Cocoa and dark chocolate (DC) have been reported to be effective for health promotion; however the exact effect of cocoa/DC on anthropometric measures have not been yet defined. Methods: A comprehensive search to identify randomized clinical trials investigating the impact of cocoa/DC on body weight, body mass index (BMI) and waist circumference (WC) was performed up to December 2017. A meta-analysis of eligible studies was performed using random effects model to estimate pooled effect size. Fractional polynominal modeling was used to explore dose-response relationships. Results: A total of 35 RCTs investigated the effects of cocoa/DC on weight, BMI and WC were included. Meta-analysis did not suggest any significant effect of cocoa/DC supplementation on body weight (-0.108 kg, 95% CI -0.262, 0.046 P = 0.168), BMI (-0.014 kg/m2 95% CI -0.105, 0.077, P: 0.759,) and WC (0.025 cm 95% CI -0.083, 0.129, P = 0.640). Subgroup analysis revealed that that weight and BMI were reduced with cocoa/DC supplementation ≥ 30 g chocolate per day in trials between 4-8 weeks. Cocoa/DC consumption resulted in WC reduction in non-linear fashion (r = 0.042, P-nonlinearity = 0.008).Conclusion: Cocoa/DC supplementation does not reduce anthropometric measures significantly. However subgroup analysis regarding dose (≥ 30 g/day) and duration (between 4 to 8 weeks) revealed significant reduction of body weight and BMI.


Fetal internal carotid artery flow velocity time waveforms in twin pregnancies.
The fetal internal carotid artery and umbilical artery flow velocity time waveforms were studied in 17 consecutive twin pregnancies. The pulsatility index was calculated for each fetus in each artery as an index of vascular resistance. All studies were done within 14 days before delivery. In 8 pregnancies both fetuses were of birthweight appropriate for gestational age; whereas, in 9 patients one or both of the infants were small for gestational age (SGA). From ultrasound criteria and Doppler studies of the umbilical and fetal internal carotid arteries, decreased fetal internal carotid artery pulsatility index (cut off value less than or equal to 1.2) was found to be the best predictor of SGA (sensitivity 83%, specificity 95%, positive predictive value 91%, negative predictive value 91%).


Cutaneous malignant melanoma incidence and mortality trends in Canada: A comprehensive population-based study.
The incidence of cutaneous malignant melanoma (CMM) is on the rise in many parts of the world. However, there is limited knowledge on the epidemiology of CMM in Canada. To conduct a comprehensive population-based study of CMM in Canada. We examined patient clinical and pathologic characteristics as well as the incidence and mortality trends of CMM in Canada using 3 independent population-based registries. In total, 72,565 Canadian patients were given CMM diagnoses during 1992-2010; 47.5% were women. Average age at the time of diagnosis was 56.5 years for women and 60.4 years for men. We report a steady increase in CMM incidence and mortality rates in both sexes. The overall incidence rate of CMM in Canada was 12.29 cases/100,000 person-years. We also report important differences in the incidence and mortality rates between Canadian provinces and territories; the highest incidence of this cancer was documented in Nova Scotia and Prince Edward Island. Data on race, clinical disease stage, and Breslow depth of CMM was not available. This study, for the first time, defines the disease burden of CMM in Canada and highlights important longitudinal, geographic, and spatial differences in the distribution of CMM in this country.


Light-wave dynamic control of magnetism.
The enigmatic interplay between electronic and magnetic phenomena observed in many early experiments and outlined in Maxwell's equations propelled the development of modern electromagnetism1. Today, the fully controlled evolution of the electric field of ultrashort laser pulses enables the direct and ultrafast tuning of the electronic properties of matter, which is the cornerstone of light-wave electronics2-7. By contrast, owing to the lack of first-order interaction between light and spin, the magnetic properties of matter can only be affected indirectly and on much longer timescales, through a sequence of optical excitations and subsequent rearrangement of the spin structure8-16. Here we introduce the regime of ultrafast coherent magnetism and show how the magnetic properties of a ferromagnetic layer stack can be manipulated directly by the electric-field oscillations of light, reducing the magnetic response time to an external stimulus by two orders of magnitude. To track the unfolding dynamics in real time, we develop an attosecond time-resolved magnetic circular dichroism detection scheme, revealing optically induced spin and orbital momentum transfer in synchrony with light-field-driven coherent charge relocation17. In tandem with ab initio quantum dynamical modelling, we show how this mechanism enables the simultaneous control of electronic and magnetic properties that are essential for spintronic functionality. Our study unveils light-field coherent control of spin dynamics and macroscopic magnetic moments in the initial non-dissipative temporal regime and establishes optical frequencies as the speed limit of future coherent spintronic applications, spin transistors and data storage media.


Neural crest-derived cells migrate from nerve to participate in Achilles tendon remodeling.
During tendon injury, nerve ingrowth is one of the earliest events of tendon repair and remodeling. Since peripheral neurons and associated cells are mostly derived from neural crest (NC) cells, we sought to investigate the role of NC-derived cells in tendon regeneration. Thus, we used Sox10-Cre/ROSA26-Flox-Red Fluorescent Protein (RFP) transgenic mice to trace these cells during tendon regeneration. After 4 weeks of Achilles tendon rupture, the injured tendon tissues were harvested for immunohistological analyses, cell isolation, and phenotype identification. In addition, the tenocytes were co-cultured with RFP labeled cells to examine cellular functions. Following the injury, a significant number of RFP-labeled cells penetrated into the wound site and reached a peak (∼30% of cells) after 2 weeks, and then stabilized at a level of approximately 20%. Interestingly, 36.9% RFP labeled cells in the injured area expressed Tuj1, suggesting that most of the cells are peripheral neurons. Some RFP+ /Tuj1+ cells were also found adjacent to newly formed blood vessels in the tendon. Importantly, the existing neuropeptide Y (NPY) and neuropeptide Y receptor (NPYr) in the invading nerve and blood vessels were directly correlated. In addition, there were also RFP+ cells (∼30%) negative for neuronal markers but positive for fibroblast markers, that is, FAP (34.7%) and Vimentin (Vmt) (27.2%), and approximately 10% positive for Sox10. Indeed, many RFP+ cells isolated from the ruptured Achilles tendon showed long spindle shapes and expressed fibroblast phenotypic markers FSP1 and FAP. Part of the Sox10+ RFP-labeled cells exhibited osteogenic and adipogenic differentiation ability. It is concluded that after Achilles tendon injury, nerves sprout into the wound site. The NC-derived Vmt+ /FAP+ mesenchymal cells and peripheral nerves participate in tendon regeneration.