Programmed Allee effect in bacteria causes a tradeoff between population spread and survival.
Dispersal is necessary for spread into new habitats, but it has also been shown to inhibit spread. Theoretical studies have suggested that the presence of a strong Allee effect may account for these counterintuitive observations. Experimental demonstration of this notion is lacking due to the difficulty in quantitative analysis of such phenomena in a natural setting. We engineered Escherichia coli to exhibit a strong Allee effect and examined how the Allee effect would affect the spread of the engineered bacteria. We showed that the Allee effect led to a biphasic dependence of bacterial spread on the dispersal rate: spread is promoted for intermediate dispersal rates but inhibited at low or high dispersal rates. The shape of this dependence is contingent upon the initial density of the source population. Moreover, the Allee effect led to a tradeoff between effectiveness of population spread and survival: increasing the number of target patches during dispersal allows more effective spread, but it simultaneously increases the risk of failing to invade or of going extinct. We also observed that total population growth is transiently maximized at an intermediate number of target patches. Finally, we demonstrate that fluctuations in cell growth may contribute to the paradoxical relationship between dispersal and spread. Our results provide direct experimental evidence that the Allee effect can explain the apparently paradoxical effects of dispersal on spread and have implications for guiding the spread of cooperative organisms.


Radiographic and pathologic features of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH).
The vertebral involvement of DISH is described from an evaluation of 215 cadaveric spines and 100 patients with the disease. Radiographic features include linear new bone formation along the anterolateral aspect of the thoracic spine, a bumpy contour, subjacent radiolucency, and irregular and pointed bony excrescences at the superior and inferior vertebral margins in the cervical and lumbar regions. Pathologic features include focal and diffuse calcification and ossification in the anterior longitudinal ligament, paraspinal connective tissue, and annulus fibrosis, degeneration in the peripheral annulus fibrosis fibers, L-T-, and Y-shaped anterolateral extensions of fibrous tissue, hypervascularity, chronic inflammatory cellular infiltration, and periosteal new bone formation on the anterior surface of the vertebral bodies.


Effects of alcohol and initial gambling outcomes on within-session gambling behavior.
Concurrent drinking and gambling is prevalent among young adults and may increase negative consequences associated with each behavior. The effects of alcohol, initial gambling outcomes, gambling-related cognitions, and impulsivity on gambling behavior were evaluated. Initial gambling outcomes, gambling-related cognitions, and impulsivity were also assessed as potential moderators of the relation between alcohol and gambling behavior. Participants (N = 130) were randomly assigned to receive active placebo or alcohol (0.84 g/kg and 0.76 g/kg for men and women, respectively) and were invited to wager on a simulated slot machine programmed to produce 1 of 3 initial outcomes (win, breakeven, or loss) before beginning a progressive loss schedule. Alcohol consumption was associated with larger average bets and more rapid loss of all available funds, though no evidence was found for predicted main effects and interactions for gambling persistence. The effect of impulsivity was moderated by beverage condition, such that higher levels of impulsivity were associated with larger average bets for participants in the placebo but not the alcohol group. Results have direct implications for individual-focused and public-health interventions.


Viable Mycobacterium tuberculosis in sputum after pulmonary tuberculosis cure.
Pulmonary tuberculosis (TB) with detectable Mycobacterium tuberculosis in the sputum is a major source of transmission. In resource limited TB endemic settings, cure is declared through sputum smear examination for acid fast bacilli without performing culture. This may lead to erroneous treatment outcomes as viable bacteria may be missed due to the low sensitivity of direct smear method. The aim of this study was to investigate if sterilizing cure is achieved among the new pulmonary TB cases declared cured by sputum smear conversion and to evaluate the impact of addition of ethambutol in the continuation phase in achieving it. New sputum smear-positive pulmonary TB patients registered at a tertiary care hospital in Pakistan from November 2013 to March 2014 were followed under standard Directly Observed Treatment Short Course strategy for 6 months. Half of these patients received ethambutol in addition to isoniazid and rifampicin in the continuation phase. Sputum specimens were examined on microscopy at 2 months and at the end of treatment. Sputa of patients with negative direct smear examination at the end of treatment were cultured. Among 5746 TB suspects, 1595 were new sputum smear positive pulmonary TB cases, and 533 were registered at our hospital. Among these, 504 converted sputum negative at 2 months and 348 converted at the end of 6 months of treatment and were declared cured. Sputa of 204/348 patients were cultured, and 12/204 (6%) were culture-positive. Culture positivity at 6 months was not associated with bacterial load, smoking, diabetes, presence of cavities, history of contact with TB patients, age, sex, socioeconomic status, or addition of ethambutol in the continuation phase. Viable cultivable bacilli were detected in 6% of cured patients, which would have significant impact on the control of TB. This highlights the need for an inexpensive and accurate surrogate marker for culture as it is not feasible to perform culture in routine for monitoring treatment response in the low-resource settings. The treatment outcome did not improve by addition of ethambutol emphasizing the need to find the optimal duration of treatment for individual or carefully selected groups of patients.


Knowledge, attitude, and practice of patients living with inflammatory bowel disease: A cross-sectional study.
Patients with inflammatory bowel diseases (IBDs) generally have poor knowledge, attitude, and practice of their disease, while the data from China are lacking. To address this knowledge disparity among Chinese patients with IBD. This web-based, cross-sectional study was conducted on a cohort of IBD patients who visited the Second Affiliated Hospital of Wenzhou Medical University between December 2022 and February 2023. Their socio-demographic information and the knowledge, attitude, and practice scores were collected and estimated using a self-designed questionnaire. Pearson's correlation analysis was used to determine the pairwise correlations among knowledge, attitude, and practice scores. A multivariate logistic regression analysis was further performed to determine the independent factors associated with their knowledge, attitude, and practice scores. A total of 353 patients (224 males) with IBD completed the questionnaires. The mean knowledge, attitude, and practice scores were 10.05 ± 3.46 (possible range: 0-14), 41.58 ± 5.23 (possible range: 0-56), 44.20 ± 7.39 (possible range: 0-56), respectively, indicating good knowledge, positive attitude, and proactive practice toward IBD. Pearson's correlation analysis showed that the knowledge score had significant positive correlations with the attitude score (r = 0.371, P < 0.001) and practice score (r = 0.100, P < 0.001). The attitude score had a significant positive correlation with the practice score (r = 0.452, P < 0.001). Moreover, multivariate logistic regression analysis showed that aged 30-40 years [odds ratio (OR) = 4.06, 95% confidence interval (CI): 1.04-15.82, P = 0.043], middle school education (OR = 3.98, 95%CI: 1.29-12.33, P = 0.017), high school/technical secondary school education (OR = 14.06, 95%CI: 3.92-50.38, P < 0.001), and junior college/bachelor's degree and above education (OR = 15.20, 95%CI: 4.15-55.650, P < 0.001) were independently associated with good knowledge. The higher knowledge score was independently associated with a positive attitude (OR = 1.23, 95%CI: 1.11-1.36, P < 0.001). The higher attitude score was independently associated with proactive practice (OR = 1.20, 95%CI: 1.11-1.30, P < 0.001). Chinese patients with IBD might have good knowledge, a positive attitude, and proactive practice toward their disease. However, a small number of specific items require education.


Bone marrow-derived mesenchymal stem cells already express specific neural proteins before any differentiation.
Bone marrow mesenchymal stem cells (MSC) are multipotent cells. To explain their plasticity, we postulated that undifferentiated MSC may express proteins from other tissues such as neuronal tissues. MSC are obtained by two different approaches: plastic adhesion or negative depletion (RosetteSep and magnetic beads CD45/glycophorin A). MSC are evaluated through FACS analysis using a panel of antibodies (SH2, SH3, CD14, CD33, CD34, CD45, etc.). To confirm the multipotentiality in vitro, we have differentiated MSC into adipocytes, chondrocytes, osteocytes, and neuronal/glial cells using specific induction media. We have evaluated neuronal and glial proteins (Nestin, Tuj-I, betaIII Tubulin, tyrosine hydroxylase [TH], MAP-2, and GFAP) by using flow cytometry, Western blots, and RT-PCR. We found that MSC constituently express native immature neuronal proteins such as Nestin and Tuj-1. After only five passages, MSC can already express more mature neuronal or glial proteins, such as TH, MAP-2, and GFAP, without any specific induction. We noticed an increase in the expression of more mature neuronal/glial proteins (TH, MAP-2, and GFAP) after exposure to neural induction medium, thus confirming the differentiation of MSC into neurons and astrocytes. The constitutive expression of Nestin or Tuj-1 by MSC suggests that these cells are "multidifferentiated" cells and thus can retain the ability for neuronal differentiation, enhancing their potentiality to be employed in the treatment of neurological diseases.


Non-Invasive Intravital Imaging of siRNA-Mediated Mutant Keratin Gene Repression in Skin.
Small interfering RNAs (siRNAs) specifically and potently inhibit target gene expression. Pachyonychia congenita (PC) is a skin disorder caused by mutations in genes encoding keratin (K) 6a/b, K16, and K17, resulting in faulty intermediate filaments. A siRNA targeting a single nucleotide, PC-relevant mutation inhibits K6a expression and has been evaluated in the clinic with encouraging results. To better understand the pathophysiology of PC, and develop a model system to study siRNA delivery and visualize efficacy in skin, wild type (WT) and mutant K6a complementary DNAs (cDNAs) were fused to either enhanced green fluorescent protein or tandem tomato fluorescent protein cDNA to allow covisualization of mutant and WT K6a expression in mouse footpad skin using a dual fluorescence in vivo confocal imaging system equipped with 488 and 532 nm lasers. Expression of mutant K6a/reporter resulted in visualization of keratin aggregates, while expression of WT K6a/reporter led to incorporation into filaments. Addition of mutant K6a-specific siRNA resulted in inhibition of mutant, but not WT, K6a/reporter expression. Intravital imaging offers subcellular resolution for tracking functional activity of siRNA in real time and enables detailed analyses of therapeutic effects in individual mice to facilitate development of nucleic acid-based therapeutics for skin disorders.


Autoantibodies against ADP/ATP carrier from patients with dilated cardiomyopathy increase activity of voltage-dependent Ca channels in isolated cardiac myocytes.
The effects of autoantibodies against the ADP/ATP carrier, from sera of patients with dilated cardiomyopathy, on calcium channel current (ICa) were studied in enzymatically-isolated guinea pig ventricular myocytes by using a whole cell patch-clamp method. The results showed that the autoantibodies enhanced ICa in a concentration-dependent manner. Verapamil inhibited enhancement of ICa induced by the autoantibodies. Control sera (without the autoantibodies) did not affect ICa. This study suggests that anti-ADP/ATP carrier autoantibodies from sera of patients with dilated cardiomyopathy may enhance ICa and cause calcium overload. Disturbing Ca-channel gating by autoantibodies may contribute to the pathogenesis of dilated cardiomyopathy.


Association of serotonin levels in patients of vasovagal syncope and postural tachycardia syndrome.
To determine the level of serotonin in patients of vasovagal syncope and postural tachycardia syndrome after head-up tilt test. The cross-sectional analytical study was conducted at the Islamic International Medical College and the Department of Electrophysiology, Armed Forces Institute of Cardiology, Rawalpindi, from April 2017 to March 2018. Group A comprised cases of vasovagal syncope, group B had patients of postural tachycardia syndrome, and group C had healthy controls. Cases were chosen on the basis of history, episodes of syncope and findings of head-up tilt test. After the test, blood samples were taken for hormonal analysis of serotonin using enzyme-linked immunosorbent assay. Data was analysed using SPSS 21. Of the 80 subjects, 35(43.8%) were in group A, 35(43.8%) in group B and 10(12.4%) in group C. Mean serotonin value in group A was 918.39±380.16nM, in group B it was 1188.70±449.55nM., while in control group C the mean value was 771.40±376.14nM (p<0.05). Serotonin was found to have a significant role in syncope pathophysiology.


Methodology: care of the critically ill and injured during pandemics and disasters: CHEST consensus statement.
Natural disasters, industrial accidents, terrorism attacks, and pandemics all have the capacity to result in large numbers of critically ill or injured patients. This supplement provides suggestions for all those involved in a disaster or pandemic with multiple critically ill patients, including front-line clinicians, hospital administrators, professional societies, and public health or government officials. The field of disaster medicine does not have the required body of evidence needed to undergo a traditional guideline development process. In result, consensus statement-development methodology was used to capture the highest-caliber expert opinion in a structured, scientific approach. Task Force Executive Committee members identified core topic areas regarding the provision of care to critically ill or injured patients from pandemics or disasters and subsequently assembled an international panel for each identified area. International disaster medicine experts were brought together to identify key questions (in a population, intervention, comparator, outcome [PICO]-based format) within each of the core topic areas. Comprehensive literature searches were then conducted to identify studies upon which evidence-based recommendations could be made. No studies of sufficient quality were identified. Therefore, the panel developed expert opinion-based suggestions that are presented in this supplement using a modified Delphi process. A total of 315 suggestions were drafted across all topic groups. After two rounds of a Delphi consensus-development process, 267 suggestions were chosen by the panel to include in the document and published in a total of 12 manuscripts composing the core chapters of this supplement. Draft manuscripts were prepared by the topic editor and members of the working groups for each of the topics, producing a total of 11 papers. Once the preliminary drafts were received, the Executive Committee (Writing Committee) then met to review, edit, and promote alignment of all of the primary drafts of the manuscripts prepared by the topic editors and their groups. The topic editors then revised their manuscripts based on the Executive Committee's edits and comments. The Writing Committee subsequently reviewed the updated drafts and prepared the final manuscripts for submission to the Guidelines Oversight Committee (GOC). The manuscripts subsequently underwent review by the GOC, including external review as well as peer review for the journal publication. The Writing Committee received the feedback from the reviewers and modified the manuscripts as required. Based on a robust and transparent process, this project used rigorous methodology to produce clinically relevant, trustworthy consensus statements, with the aim to provide needed guidance on treatment and procedures for practitioners, hospital administrators, and public health and government officials when addressing the care of critically ill or injured patients in disasters or pandemics.


Extraordinary Indentation Strain Stiffening Produces Superhard Tungsten Nitrides.
Transition-metal light-element compounds are a class of designer materials tailored to be a new generation of superhard solids, but indentation strain softening has hitherto limited their intrinsic load-invariant hardness to well below the 40 GPa threshold commonly set for superhard materials. Here we report findings from first-principles calculations that two tungsten nitrides, hP4-WN and hP6-WN_{2}, exhibit extraordinary strain stiffening that produces remarkably enhanced indentation strengths exceeding 40 GPa, raising exciting prospects of realizing the long-sought nontraditional superhard solids. Calculations show that hP4-WN is metallic both at equilibrium and under indentation, marking it as the first known intrinsic superhard metal. An x-ray diffraction pattern analysis indicates the presence of hP4-WN in a recently synthesized specimen. We elucidate the intricate bonding and stress response mechanisms for the identified structural strengthening, and the insights may help advance rational design and discovery of additional novel superhard materials.


Prognostic value and agreement of achieving lactate clearance or central venous oxygen saturation goals during early sepsis resuscitation.
Lactate clearance (LC) and central venous oxygen saturation (ScvO(2)) have been proposed as goals of early sepsis resuscitation. The authors sought to determine the agreement and prognostic value of achieving ScvO(2) or LC goals in septic shock patients undergoing emergency department (ED)-based early resuscitation. This was a preplanned analysis of a multicenter ED randomized controlled trial of early sepsis resuscitation targeting three variables: central venous pressure, mean arterial pressure, and either ScvO(2) or LC. Inclusion criteria included suspected infection, two or more systemic inflammation criteria, and either systolic blood pressure of <90 mm Hg after intravenous fluid bolus or lactate level of >4 mmol/L. Both ScvO(2) and LC were measured simultaneously. The ScvO(2) goal was defined as ≥70%. Lactate was measured at enrollment and every 2 hours until the goal was reached or up to 6 hours. LC goal was defined as a decrease of ≥10% from initial measurement. The primary outcome was in-hospital mortality. A total of 203 subjects were included, with an overall mortality of 19.7%. Achievement of the ScvO(2) goal only was associated with a mortality rate of 41% (9/22), while achievement of the LC goal only was associated with a mortality rate of 8% (2/25; proportion difference = 33%; 95% confidence interval [CI] = 9% to 55%). No agreement was found between goal achievement (κ = -0.02), and exact test for matched pairs demonstrated no significant difference between discordant pairs (p = 0.78). No agreement was found between LC and ScvO(2) goal achievement in early sepsis resuscitation. Achievement of a ScvO(2) ≥ 70% without LC ≥ 10% was more strongly associated with mortality than achievement of LC ≥ 10% with failure to achieve ScvO(2) ≥ 70%.


[Biologic markers of exposure to and effects of fluorine compounds in workers engaged into aluminum industry].
The study in 727 workers exposed to inorganic fluorine compounds revealed through ultrasound densitometry changes in fluorine excretion and bone tissue density in accordance with the length of service, through markers of bone destruction and synthesis features of bone remodelling were specified.


Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study.
The Women's Health Initiative Memory Study (WHIMS) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older. The effect of estrogen-alone therapy, also evaluated in WHIMS, on cognition has not been established for this population. To determine whether conjugated equine estrogen (CEE) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate (CEE plus MPA). A randomized, double-blind, placebo-controlled ancillary study of the Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence of probable dementia among community-dwelling women aged 65 to 79 years with prior hysterectomy from 39 US academic centers that started in June 1995. Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947 (92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women (95.3%) with a baseline and at least 1 follow-up measure of global cognitive function before the trial's termination on February 29, 2004. Participants received 1 daily tablet containing either 0.625 mg of CEE (n = 1387) or matching placebo (n = 1421). Global cognitive function measured annually with the Modified Mini-Mental State Examination (3MSE). During a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26 (0.13) units lower than among women assigned to CEE compared with placebo (P =.04). For pooled hormone therapy (CEE combined with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P =.006). Removing women with dementia, mild cognitive impairment, or stroke from the analyses lessened these differences. The adverse effect of hormone therapy was more pronounced among women with lower cognitive function at baseline (all P<.01). For women assigned to CEE compared with placebo, the relative risk of having a 10-unit decrease in 3MSE scores (>2 SDs) was estimated to be 1.47 (95% confidence interval, 1.04-2.07). For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment.


[Antitumor effect of actinidia chinensis polysaccharide on murine tumor].
A new polysaccharide compound (ACPS-R) has recently been isolated from the root of Actinidia Chinensis Planch. When given intraperitoneally to the transplantable tumor bearing mice at dose of 75-125 mg/kg, the tumor inhibition rate was more than 88.8% in Ehrilich ascitic cancer (EAC) or ascitic form of hepatoma (HepA) and more than 49.6% in solid hepatoma (HepS). The treatment effect of ACPS-R on EAC at dose of 15 mg/kg and 22.5 mg/kg, respectively. ACPS-R could also prolong the life of EAC-or P388-bearing mice, and increase the percentage of EAC-free mice. In addition, when ACPS-R was used in combination with 5-Fu, the antitumor effect was enhanced as compared with 5-Fu alone. A marked increase in cAMP levels and cAMP/cGMP ratio of spleen of EAC-bearing mice were observed after treatment of ACPS-R. The increase of both parameters nearly reached the normal levels of healthy mice. The increases of cAMP, cAMP/cGMP and tumor remission had statistical significance. It showed an intermediate inhibitory effect of ACPS-R on DNA synthesis by incorporating 3H-TdR into EAC cells. The results indicated that ACPS-R acts as a new antitumor polysaccharide, and the treatment effect of Actinidia root in folk medicine is probably related to ACPS-R.


[18]Crown-6 rotator in spin-ladder compound of m-aminoanilinium([18]crown-6)[Ni(dmit)2]-.
Supramolecular cations of HOPD+([18]crown-6) and HMPD+([18]crown-6) were introduced into [Ni(dmit)2]- salts (HOPD+: o-aminoanilinium, HMPD+: m-aminoanilinium, and dmit2-: 2-thioxo-1,3-dithiole-4,5-dithiolate). Alternate layers of cations and anions were observed in the two new salts of (HOPD+)([18]crown-6)[Ni(dmit)2]- (1) and (HMPD+)([18]crown-6)[Ni(dmit)2]- (2). From X-ray crystal structural analyses, solid state 1H nuclear magnetic resonance (NMR) spectra, and dielectric constants, the thermal rotations of [18]crown-6 in both of the (HOPD+)([18]crown-6) and (HMPD+)([18]crown-6) supramolecules occurred at temperatures above approximately 200 K based on the orientational disorder in the crystal structures. The two-fold flip-flop motions of HOPD+ and HMPD+ cations in salts 1 and 2 were suppressed, due to the relatively large potential energy barriers. The [Ni(dmit)2]- anion formed pi-dimer arrangements in both salts, with a layer structure by lateral sulfur-sulfur interatomic contacts. Although the simple dimer model reproduced the magnetic properties of salt 1, the ladder arrangement of the pi-dimer in salt 2 yielded the magnetic behavior of a spin-ladder with a spin-gap of 92.5 K. The temperature dependent magnetic susceptibility of salt 2 was well reproduced by the magnetic anisotropy of J1/J2 approximately = 8 between the ladder-leg (J1: intra-dimer interaction) and ladder-rung (J2: inter-dimer interaction). The [18]crown-6 supramolecular rotator of (HMPD+)([18]crown-6) was coexistent with the spin-ladder chain of [Ni(dmit)2]- anions in salt 2.


Recombinant expression and functional characterization of martentoxin: a selective inhibitor for BK channel (α + β4).
Martentoxin (MarTX), a 37-residue peptide purified from the venom of East-Asian scorpion (Buthus martensi Karsch), was capable of blocking large-conductance Ca2+-activated K+ (BK) channels. Here, we report an effective expression and purification approach for this toxin. The cDNA encoding martentoxin was expressed by the prokaryotic expression system pGEX-4T-3 which was added an enterokinase cleavage site by PCR. The fusion protein (GST-rMarTX) was digested by enterokinase to release hetero-expressed toxin and further purified via reverse-phase HPLC. The molecular weight of the hetero-expressed rMarTX was 4059.06 Da, which is identical to that of the natural peptide isolated from scorpion venom. Functional characterization through whole-cell patch clamp showed that rMarTX selectively and potently inhibited the currents of neuronal BK channels (α + β4) (IC50 = 186 nM), partly inhibited mKv1.3, but hardly having any significant effect on hKv4.2 and hKv3.1a even at 10 μM. Successful expression of martentoxin lays basis for further studies of structure-function relationship underlying martentoxin or other potassium-channel specific blockers.


Defining the acute in acute care nurse practitioner.
The role of the nurse practitioner in the tertiary care or hospital setting has become well established during the course of this decade. With the introduction of a national certifying examination for acute care nurse practitioners in 1995, it is important that the word acute be defined in a way that is acknowledged universally. Should an examination certifying acute care nurse practitioners contain critical care content? Are the terms acute care and critical care synonymous? The existing examination contains critical care content, but a review of relevant literature suggests a conflict. At times acute care and critical care are used interchangeably, and at other times they are discussed in a way that suggests they are two distinct specialties. This article presents the conflicting use of these two terms in the literature and provides a rationale for recognizing the differences. It is suggested that the definition of the word acute, as it is used in the title acute care nurse practitioner, be reexamined, and that either the content or the title of the certifying examination for acute care nurse practitioners be reconsidered.


Transcriptome dynamics-based operon prediction in prokaryotes.
Inferring operon maps is crucial to understanding the regulatory networks of prokaryotic genomes. Recently, RNA-seq based transcriptome studies revealed that in many bacterial species the operon structure vary with the change of environmental conditions. Therefore, new computational solutions that use both static and dynamic data are necessary to create condition specific operon predictions. In this work, we propose a novel classification method that integrates RNA-seq based transcriptome profiles with genomic sequence features to accurately identify the operons that are expressed under a measured condition. The classifiers are trained on a small set of confirmed operons and then used to classify the remaining gene pairs of the organism studied. Finally, by linking consecutive gene pairs classified as operons, our computational approach produces condition-dependent operon maps. We evaluated our approach on various RNA-seq expression profiles of the bacteria Haemophilus somni, Porphyromonas gingivalis, Escherichia coli and Salmonella enterica. Our results demonstrate that, using features depending on both transcriptome dynamics and genome sequence characteristics, we can identify operon pairs with high accuracy. Moreover, the combination of DNA sequence and expression data results in more accurate predictions than each one alone. We present a computational strategy for the comprehensive analysis of condition-dependent operon maps in prokaryotes. Our method can be used to generate condition specific operon maps of many bacterial organisms for which high-resolution transcriptome data is available.


Knockdown of the long noncoding RNA XIST suppresses glioma progression by upregulating miR-204-5p.
Background: Gliomas are the most prevalent primary malignant tumors of the central nervous system. Our previous study showed that miR-204-5p is a tumor suppressor gene in glioma. Bioinformatic analyses suggest that long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) is a potential target gene of miR-204-5p. Methods: We analyzed the expression of XIST and miR-204-5p in glioma tissues and the correlation with glioma grade. A series of in vitro experiments were carried out to elucidate the role of XIST in glioma progression. A mouse xenograft model was established to detect whether knockdown of XIST can inhibit glioma growth. A luciferase assay was performed to determine whether XIST can bind to miR-204-5p and the binding specificity. Cells stably expressing shXIST or shNC were transfected with anti-miR-204-5p or anti-miR-204-5p-NC to evaluate whether XIST mediates the tumor-suppressive effects of miR-204-5p. Results: XIST was upregulated in glioma tissues compared with normal brain tissues (NBTs), while miR-204-5p expression was significantly decreased in glioma tissues compared with NBTs. Both XIST and miR-204-5p expression levels were clearly related to glioma grade, and the expression of XIST was obviously negatively correlated with miR-204-5p expression. Knockdown of XIST inhibited glioma cell proliferation, migration, and invasion, promoted apoptosis of glioma cells, inhibited tumor growth and increased the survival time in nude mice. miR-204-5p could directly bind to XIST and negatively regulate XIST expression. XIST mediated glioma progression by targeting miR-204-5p in glioma cells. XIST crosstalk with miR-204-5p regulated Bcl-2 expression to promote apoptosis. Conclusion: Our results provide evidence that XIST, miR-204-5p and Bcl-2 form a regulatory axis that controls glioma progression and can serve as a potential therapeutic target for glioma.


A screen for mutations in zebrafish that affect myelin gene expression in Schwann cells and oligodendrocytes.
Myelin is the multi-layered glial sheath around axons in the vertebrate nervous system. Myelinating glia develop and function in intimate association with neurons and neuron-glial interactions control much of the life history of these cells. However, many of the factors that regulate key aspects of myelin development and maintenance remain unknown. To discover new molecules that are important for glial development and myelination, we undertook a screen of zebrafish mutants with previously characterized neural defects. We screened for myelin basic protein (mbp) mRNA by in situ hybridization and identified four mutants (neckless, motionless, iguana and doc) that lacked mbp expression in parts of the peripheral and central nervous systems (PNS or CNS), despite the presence of axons. In all four mutants electron microscopy revealed that myelin-forming glia were present and had formed loose wraps around axons but did not form compact myelin. We found that addition of exogenous retinoic acid (RA) rescued mbp expression in neckless mutant embryos, which lack endogenous RA synthesis. Timed application of the RA synthesis inhibitor DEAB to wild type embryos showed that RA signalling is required at least 48 h before the onset of myelin protein synthesis in both CNS and PNS.


[Computer-based determination of red/green color vision defects].
A commonly used method of investigating colour vision, that is, the ability of the human visual system to discriminate colours, is based on the use of isochromatic colour plates, such as those used in the Ishihara test. The present paper describes a new computer-based method of determining red/green colour vision deficiencies. The method involves the presentation of Ishihara colour plates on a computer monitor. It has been verified experimentally that, despite the differences between the spectral emission of the computer screen and the daylight reflected by the Ishihara plates, the method is capable of distinguishing between subjects with from those without colour vision deficiencies. For screening purposes, the use of a reduced number of plates is suggested. This suggestion makes use of nine instead of 14 plates, and the criterion of two incorrectly recognized plates to determine a colour vision deficiency.


Expression sequences of cell adhesion molecules.
A reexamination of the expression of cell adhesion molecules (CAMs) during the development of the chicken embryo was carried out using more sensitive immunocytochemical techniques than had been used previously. While the previously determined sequence of CAM expression was confirmed, neural CAM (N-CAM) was also detected on endodermal structures such as the lung epithelium, gut epithelium, and pancreas and on budding structures such as the pancreatic duct and gall bladder. It was also found on ectodermal derivatives of the skin. In most of these sites, N-CAM expression was transient, but in the chicken embryo lung, the epithelium remained positive for N-CAM and liver CAM (L-CAM) into adult life. Thus, at one time or another, both of these primary CAMs can be expressed on derivatives of all three germ layers. At sites of embryonic induction, epithelial cells expressing both L-CAM and N-CAM, or L-CAM only, were apposed to mesenchymal cells expressing N-CAM. Examples included epiblast (NL) and notochord (N); endodermal epithelium (NL) and lung mesenchyme (N); Wolffian duct (NL) and mesonephric mesenchyme (N); apical ectodermal ridge (NL) and limb mesenchyme (N); and feather placode (L) and dermal condensation (N). The cumulative observations indicate that cell surface modulation of the primary CAMs at induction sites can be classified into two modes. In mode I, expression of N-CAM (or both CAMs) in mesenchyme decreases to low amounts at the cell surface, and then N-CAM is reexpressed. In mode II, one or the other CAM disappears from epithelia expressing both CAMs. As a result of the primary processes of development, collectives of cells linked by N-CAM and undergoing modulation mode I are brought into the proximity of collectives of cells linked by L-CAM plus N-CAM or by L-CAM undergoing modulation mode II. Such adjoining cell collectives or CAM couples were found at all sites of embryonic induction examined.


Differential adaptation of membranes of two osmotolerant fungi, Aspergillus chevalieri and Penicillium expansum to high sucrose concentrations.
Aspergillus chevalieri and Penicillium expansum were able to tolerate sucrose concentrations in the growth media up to 80% (w/v). At 50% sucrose the growth rate is approximately 1.4 and 1.2 times, respectively, higher than in the control. While at 80% sucrose it drops to 35% and 45% of the control level for both fungi. Lipids and proteins in plasma membranes increased with increasing sucrose concentrations in the growth medium. Phospholipid content in membranes of both organisms being also increased, phosphatidyl glycerol was the major detected phospholipid and represented the highest increase. The fatty acid composition of fraction enriched plasma membrane of both fungi changed when they were grown in high sucrose concentrations. Some fatty acids which had not been detected in control cultures were present and the proportions of other fatty acids changed. At 50% sucrose the unsaturation index of membranes decreased by 20-25% in both fungi, indicating that the plasma membrane is less fluid at this concentration. At 80% sucrose a similar trend was observed for P. expansum but for A. chevalieri the unsaturation index was little changed compared with the control. The fluorescence polarization values of 1,6-diphenyl 1,3,5-hexatriene (DPH) in membranes of both fungi grown at 80% sucrose increased, indicating a decrease in membrane fluidity. At 50% sucrose the increase in saturation of membrane fatty acids would tend to reduce membrane fluidity but in A. chevalieri at 80% sucrose fatty acids did not become more saturated. In this case the marked increase in sterols at this sucrose concentration may be responsible for low membrane fluidity.


The ClC-3 chloride transport protein traffics through the plasma membrane via interaction of an N-terminal dileucine cluster with clathrin.
ClC-3 is a ubiquitously expressed chloride transport protein that is present in synaptic vesicles and endosome/lysosome compartments. It is largely intracellular but has been observed at the plasma membrane as well. The aim of this study was to identify the pathways and regulation of ClC-3 trafficking to intracellular sites. At the steady state, approximately 94% of transfected ClC-3 was localized intracellularly, and only 6% was at the plasma membrane. Pulse labeling with [(35)S]methionine and biotinylation demonstrated that about 25% of newly synthesized ClC-3 traffics through the plasma membrane. We used both immunofluorescence microscopy and biotinylation assays to assess the trafficking of ClC-3. Plasma membrane ClC-3 was rapidly endocytosed (t((1/2)) approximately 9 min); a portion entered a recycling pool that returned to the cell surface after internalization, and the remainder trafficked to more distal intracellular compartments. ClC-3 associated with clathrin at the plasma membrane. Coimmunoprecipitation and glutathione S-transferase pulldown assays demonstrated that the N terminus of ClC-3 binds to clathrin. Alanine replacement of a dileucine acidic cluster within the cytosolic N terminus (amino acids 13-19) resulted in a molecule that had decreased endocytosis and increased surface expression. This replacement also abolished interaction with clathrin as assessed both by coimmunoprecipitation and glutathione S-transferase pulldown assays. We conclude that ClC-3 is primarily an intracellular transport protein that is transiently inserted into the plasma membrane where it is rapidly endocytosed. Internalization of ClC-3 depends on the interaction between an N-terminal dileucine cluster and clathrin.


Comparison of biological and chemical measures of metal bioavailability in field soils: test of a novel simulated earthworm gut extraction.
Bioavailability of metals in soil is a major factor influencing estimates of risk associated with exposure of ecological receptors. Metal concentrations in soil are often compared to ecological screening benchmarks, which are based on total concentrations in soil. Often, the total concentration is not correlated with toxicity. No standardised method exists for determining the bioavailability of metals in soil to ecological receptors. Several surrogate measures of bioavailability were compared to the results of a battery of toxicity tests using copper (Cu), lead (Pb), and zinc (Zn)-contaminated soils collected from a former industrial area. A calcium chloride (CaCl(2)) extraction, cyclodextrin (HPCD) extraction, simulated earthworm gut (SEG) test, and earthworm bioaccumulation test were performed using the soils. Extractable metals using the CaCl(2) solution were not correlated with any biological responses of earthworms (Eisenia andrei), collembola (Folsomia candida), northern wheatgrass (Elymus lanceolatus), or alfalfa (Medicago sativa L.). Concentrations of metals in the HPCD extracts were highly variable and were not adequate for revealing adverse effects. E. andrei tissue concentrations were variable but were predictive of adverse effects to invertebrates. The results of the SEG test correlated with most of the biological endpoints. Bioavailable Cu was correlated with adverse effects to invertebrates and plants using the SEG test. Overall, coefficients of determination associated with the relationships between the biological responses and each measure of bioavailability indicated that those for the SEG test were greater than those for the other surrogate measures of bioavailability. Further validation is required before this test is routinely used to estimate metal bioavailability and toxicity.


Behavior of sperm nuclei injected into intact ripening and ripe toad oocytes and into oocytes ripening after removal of the germinal vesicle.
The behavior of frog sperm nuclei (obtained by treating a sperm suspension with pronase) in the cytoplasm of intact ripening and ripe toad oocytes and in the cytoplasm of oocytes ripening after removal of the germinal vesicle was studied. Sperm nuclei treated with pronase in the cytoplasm of intact ripe oocytes behave like the nuclei of sperm cells penetrating during normal fertilization: they increase in volume, synthesize DNA, and start to divide. They undergo no changes in the cytoplasm of oocytes ripening in the absence of karyoplasm. Transformations of sperm nuclei into pronuclei and DNA synthesis in them are found initially at the metaphase stage of the second maturation division.


Benzodiazepine use among employees of a private company.
This study aimed to identify variables associated to the consumption of benzodiazepine among workers of a private company in the VIII Region, Chile. This is a cross-sectional and correlative study. 40 employees of a private company. The instruments included a questionnaire on socio-demographic variables and a benzodiazepine questionnaire. There was no record of benzodiazepine consumption at the moment of the study. Twenty percent (20%) of the interviewees had already used benzodiazepine in the past, whereas, half of them (10%) in the last year. The bivariate analysis of the last year consumption of benzodiazepine with work hours variables showed no significant relation (p=0.073). No association was found between benzodiazepine consumption and socio-demographic variables among the study participants.


DNA hypomethylation in rheumatoid arthritis synovial fibroblasts.
Rheumatoid arthritis synovial fibroblasts (RASFs) are phenotypically activated and aggressive. We undertook this study to investigate whether the intrinsic activation of RASFs is due to global genomic hypomethylation, an epigenetic modification. Global genomic hypomethylation was assessed by immunohistochemistry, flow cytometry, and L1 promoter bisulfite sequencing. The levels of Dnmt1 were determined in synovial tissue and cultured SFs by Western blotting before and after treatment with cytokines and growth factors. Normal SFs were treated for 3 months with a nontoxic dose of the DNA hypomethylation drug 5-azacytidine (5-azaC), and changes in gene expression were revealed using complementary DNA arrays. The phenotypic changes were confirmed by flow cytometry. In situ and in vitro, RASF DNA had fewer 5-methylcytosine and methylated CG sites upstream of an L1 open-reading frame than did DNA of osteoarthritis SFs, and proliferating RASFs were deficient in Dnmt1. Using 5-azaC, we reproduced the activated phenotype of RASFs in normal SFs. One hundred eighty-six genes were up-regulated>2-fold by hypomethylation, with enhanced protein expression. These included growth factors and receptors, extracellular matrix proteins, adhesion molecules, and matrix-degrading enzymes. The hypomethylating milieu induced irreversible phenotypic changes in normal SFs, which resembled those of the activated phenotype of RASFs. DNA hypomethylation contributes to the chronicity of RA and could be responsible for the limitation of current therapies.


[Isolation of Haemophilus somnus from cattle].
Studied were a total of 220 samples of material taken from the respiratory tract of calves and from fetuses of cows that miscarried for the presence of Haemophilus bacteria. Haemophilus somnus was isolated for the first time in this country from the respiratory tract of calves (10.1 per cent) and from fetuses of cows with abortions (6.2 per cent). Haemophilus somnus was found in calves that had contracted respiratory diseases in 13 per cent of the cases, and in clinically normal calves--in 3.5 per cent of the cases. It was isolated both in pure culture and in mixed culture with P. multocida, M. bovirhinis, M. arginini, V. fetus, and C. pyogenes. As many as 21 strains of Haemophilus somnus were isolated, having the same morphologic, cultural, and biochemical properties characteristic of the species.


Using long-term datasets to assess the impacts of dietary exposure to neonicotinoids on farmland bird populations in England.
Over the last 20 years, a new group of systemic insecticides-the neonicotinoids-has gained prominence in arable systems, and their application globally has risen year on year. Previous modelling studies using long-term data have suggested that neonicotinoid application has had a detrimental impact on bird populations, but these studies were either limited to a single species or neglected to analyse specific exposure pathways in conjunction with observed population trends. Using bird abundance data, neonicotinoid usage records and cropping data for England at a 5x5 km resolution, generalised linear mixed models were used to test for spatio-temporal associations between neonicotinoid use and changes in the populations of 22 farmland bird species between 1994 and 2014, and to determine whether any associations were explained by dietary preferences. We assigned farmland bird species to three categories of dietary exposure to neonicotinoids based on literature data for species diets and neonicotinoid residues present in dietary items. Significant estimates of neonicotinoid-related population change were obtained for 13 of the 22 species (9 positive effects, 4 negative effects). Model estimates for individual species were not collectively explained by dietary risk categories, so dietary exposure to neonicotinoids via ingestion of treated seeds and seedlings could not be confirmed as a causal factor in farmland bird declines. Although it is not possible to infer any generic effect of dietary exposure to neonicotinoids on farmland bird populations, our analysis identifies three species with significant negative estimates that may warrant further research (house sparrow Passer domesticus, skylark Alauda arvensis and red-legged partridge Alectoris rufa). We conclude that there was either no consistent effect of dietary exposure to neonicotinoids on farmland bird populations in England, or that any over-arching effect was not detectable using our study design. The potential for indirect effects of insecticide use on bird populations via reduced food availability was not considered here and should be a focus for future research.


Sufentanil Sublingual Tablet System for the Management of Postoperative Pain after Knee or Hip Arthroplasty: A Randomized, Placebo-controlled Study.
Complications with IV patient-controlled analgesia include programming errors, invasive access, and impairment of mobility. This study evaluated an investigational sufentanil sublingual tablet system (SSTS) for the management of pain after knee or hip arthroplasty. This prospective, randomized, parallel-arm, double-blind study randomized postoperative patients at 34 U.S. sites to receive SSTS 15 μg (n = 315) or an identical placebo system (n = 104) and pain scores were recorded for up to 72 h. Adult patients with American Society of Anesthesiologists status 1 to 3 after primary total unilateral knee or hip replacement under general anesthesia or with spinal anesthesia that did not include intrathecal opioids were eligible. Patients were excluded if they were opioid tolerant. The primary endpoint was the time-weighted summed pain intensity difference to baseline over 48 h. Secondary endpoints included total pain relief, patient and healthcare professional global assessments, and patient and nurse ease-of-care questionnaires. Summed pain intensity difference (standard error) was higher (better) in the SSTS group compared with placebo (76 [7] vs. -11 [11], difference 88 [95% CI, 66 to 109]; P < 0.001). In the SSTS group, more patients and nurses responded "good" or "excellent" on the global assessments compared with placebo (P < 0.001). Patient and nurse ease-of-care ratings for the system were high in both groups. There was a higher incidence of nausea and pruritus in the SSTS group. SSTS could be an effective patient-controlled pain management modality in patients after major orthopedic surgery and is easy to use by both patients and healthcare professionals.


Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations.
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Only two changes were made to clinical diagnostic criteria reported in 2013: "multiple cortical tubers and/or radial migration lines" replaced the more general term "cortical dysplasias," and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals. Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families.


Student/faculty practice and research in occupational health: health promotion and outcome evaluation.
Faculty strive to connect theory and practice with real life situations for students. This study evolved from student intervention with small industries as part of their undergraduate community health nursing clinical experience. A pre-experimental static group design was used to explore the impact of health service availability on selected cardiovascular risk factors. Levels of health service: a) no service; b) student service; and c) formal health care service were compared. Chi-square, t-tests and MANOVA analyses supported three hypotheses that student intervention was equally as successful as formal health care service in reducing the selected cardiovascular risk factors of high weight to height ratios, blood pressure readings above 140/90 on three separate measurements, total cholesterol readings above accepted norms and a health risk profile which identifies risk for cardiovascular disease.


Interactions of normal and mutant vesicular stomatitis virus matrix proteins with the plasma membrane and nucleocapsids.
We demonstrated recently that a fraction of the matrix (M) protein of vesicular stomatitis virus (VSV) binds tightly to cellular membranes in vivo when expressed in the absence of other VSV proteins. This membrane-associated M protein was functional in binding purified VSV nucleocapsids in vitro. Here we show that the membrane-associated M protein is largely associated with a membrane fraction having the density of plasma membranes, indicating membrane specificity in the binding. In addition, we analyzed truncated forms of M protein to identify regions responsible for membrane association and nucleocapsid binding. Truncated M protein lacking the amino-terminal basic domain still associated with cellular membranes, although not as tightly as wild-type M protein, and could not bind nucleocapsids. In contrast, deletion of the carboxy-terminal 14 amino acids did not disrupt stable membrane association or nucleocapsid interaction. These results suggest that the amino terminus of M protein either interacts directly with membranes and nucleocapsids or stabilizes a conformation that is required for M protein to mediate both of these interactions.


Mechano-redox control of integrin de-adhesion.
How proteins harness mechanical force to control function is a significant biological question. Here we describe a human cell surface receptor that couples ligand binding and force to trigger a chemical event which controls the adhesive properties of the receptor. Our studies of the secreted platelet oxidoreductase, ERp5, have revealed that it mediates release of fibrinogen from activated platelet αIIbβ3 integrin. Protein chemical studies show that ligand binding to extended αIIbβ3 integrin renders the βI-domain Cys177-Cys184 disulfide bond cleavable by ERp5. Fluid shear and force spectroscopy assays indicate that disulfide cleavage is enhanced by mechanical force. Cell adhesion assays and molecular dynamics simulations demonstrate that cleavage of the disulfide induces long-range allosteric effects within the βI-domain, mainly affecting the metal-binding sites, that results in release of fibrinogen. This coupling of ligand binding, force and redox events to control cell adhesion may be employed to regulate other protein-protein interactions.


Presentation of a meningioma in a transwoman after nine years of cyproterone acetate and estradiol intake: case report and literature review.
The administration of cyproterone acetate (CPA) and estradiol is a common regimen used by male-to-female transsexuals (transwoman) to adjust their body to their gender identity. Major adverse events are uncommon in these subjects in spite of long-term, high dose cross-sex steroid treatments. We describe the occurrence of a meningioma in a transwoman treated with estrogens and CPA over a period of nine years. The meningioma was revealed during a magnetic resonance imaging (MRI) scan performed as follow-up of a previous surgery for ganglioglioma. CPA intake was discontinued and tumor resection was performed. Histological diagnosis confirmed a strong progesterone receptor-positive and slight estrogen positive meningioma. After surgery, the patient continued her treatment with leuprorelina acetate and estradiol. At one-year follow-up, the MRI scan reveals no recurrence of the tumor. This is the ninth case in literature of a meningioma in a transwoman treated with estrogens and CPA, confirming a possible association between female sex steroids and meningioma. Although there is no still strong evidence of an association between meningioma and CPA, this report may suggest use of alternative treatment for transwomen. This report highlights the importance to record all the cases of meningiomas in high dose CPA-users, in order to improve data.


Oscillations of fatty acid and glycerol release from human subcutaneous adipose tissue in vivo.
We sought evidence for pulsatility of lipolysis in human subcutaneous adipose tissue in vivo. Arterialized and adipose tissue venous blood samples were drawn at 2-min intervals from nine healthy subjects. This procedure was repeated during hyperinsulinemic-euglycemic clamp to remove insulin pulsatility. We found evidence for pulsatile release of both nonesterified fatty acids (NEFAs) (seven of nine subjects) and glycerol (five of six subjects) with a period of approximately 12-14 min. This pulsatility was maintained even during the hyperinsulinemic clamp. Checks were made for spurious pulse detection, including the creation of "mock" venoarterialized differences by subtracting one subject's arterialized concentrations from another's venous; the peaks detected were less consistent in character than with real data (peak width, P = 0.006; peak interval, P < 0.004). Significant cross-correlations between NEFA and glycerol release also provided evidence of a real effect. Arterialized norepinephrine concentrations were also pulsatile, but the period did not match that of NEFA and glycerol release. Insulin concentrations were pulsatile with a typical period of 12 min, but this was not significantly cross-correlated with lipolysis. We conclude that release from adipose tissue of the products of lipolysis is pulsatile in humans.


Emergence of Organisms.
Since early cybernetics studies by Wiener, Pask, and Ashby, the properties of living systems are subject to deep investigations. The goals of this endeavour are both understanding and building: abstract models and general principles are sought for describing organisms, their dynamics and their ability to produce adaptive behavior. This research has achieved prominent results in fields such as artificial intelligence and artificial life. For example, today we have robots capable of exploring hostile environments with high level of self-sufficiency, planning capabilities and able to learn. Nevertheless, the discrepancy between the emergence and evolution of life and artificial systems is still huge. In this paper, we identify the fundamental elements that characterize the evolution of the biosphere and open-ended evolution, and we illustrate their implications for the evolution of artificial systems. Subsequently, we discuss the most relevant issues and questions that this viewpoint poses both for biological and artificial systems.


Demonstration of a multichannel, multiresolution imaging system.
In conventional multichannel imaging systems, all channels have similar imaging properties [field-of-view (FOV) and angular resolution]. In our approach, channels are designed to have different imaging properties which add multiresolution capability to the system. We have experimentally demonstrated, for the first time to our knowledge, a three-channel imaging system which simultaneously captures multiple images having different magnifications and FOVs on an image sensor. Each channel consists of four aspherical lens surfaces fabricated from four PMMA plates by ultraprecision diamond tooling and of a baffle made from a titanium (Ti) and aluminum (Al) based metal alloy. The integrated imaging system is able to record a FOV of 7.6° with the first channel and 73° with the third channel while having a magnification ratio of about 6 between them. The experimental and simulation results, specifically the FOV and magnification ratios, are comparable, and this paves a way for low-cost, compact imaging systems which can embed smart imaging functionalities.


Instrumentation and examination procedures for a clinical vascular laboratory.
Instrumentation and examination procedures used in the clinical vascular Laboratory of the Massachusetts General Hospital are outlined and recommended for use in other similar laboratories. The arterial system is studied by the analysis of blood flow direction, segmental plethysmography, and systolic pressure measurements obtained at rest and following a measured exercise stress. The effect of induced reactive hyperemia on systolic pressure, obtained by direct intra-arterial measurement, is used to demonstrate the hemodynamic importance of stenotic lesions within the aorto-iliac system. Maximum venous outflow studies are combined with analyses of venous Doppler signals for purposes of screening patients with suspected deep venous thrombosis. The laboratory contributes important objective physiologic information to the examination of the arterial and venous systems. Experience obtained through the evaluationof more than 2500 patients resulted in the development of this recommended program.


Injectable success: from fillers to Botox.
The educated consumer seeks minimal downtime options to address the early signs of aging. These signs include a deepening of facial folds, an increase in muscle-induced wrinkling, and even a loss of facial volume. The use of fillers both dermal and subdermal and the use of the neurotoxin Botox have grown tremendously. The increase demand for these nonsurgical options for facial rejuvenation has created an added responsibility for physicians to remain current in injection technique and product safety. My technique has evolved, along with the predictability of the current fillers and our understanding of the actions of these products, from a safe and conservative fellowship base. A successful injector is one who understands the limitations and possibilities of the available fillers as well as the neurotoxin Botox. The happy patient is one who finds that doctor.


S100P in Duodenal Fluid Is a Useful Diagnostic Marker for Pancreatic Ductal Adenocarcinoma.
The development of an effective screening method for pancreatic ductal adenocarcinoma (PDAC) is of paramount importance. This study assessed the diagnostic utility in pancreatic diseases of duodenal markers during upper gastrointestinal endoscopy (GIE) or endoscopic ultrasonography. This study prospectively enrolled 299 consecutive participants, including 94 patients with PDACs, 144 patients with other pancreatic diseases, and 61 normal individuals as control subjects. All subjects underwent upper GIE or endoscopic ultrasonography either at Kyushu University Hospital (Fukuoka, Japan) or the Mayo Clinic (Jacksonville, Fla) from October 2011 to July 2014. Duodenal fluid (DF) was collected without secretin stimulation and of carcinoembryonic antigen and S100 calcium-binding protein P (S100P) concentrations were measured. Concentrations of S100P in DF were significantly higher in patients with PDAC and chronic pancreatitis than in control subjects (P < 0.01). A logistic regression model that included age found that the sensitivity and specificity of S100P concentration in diagnosing stages 0/IA/IB/IIA PDAC were 85% and 77%, respectively, with an area under the receiver operating characteristic curve of 0.82. Carcinoembryonic antigen concentrations in DF of patients with pancreatic disease did not differ significantly from control subjects. Analysis of S100P concentration in DF, in combination with routine screening upper GIE, may facilitate the detection of PDAC.


Phytofiltration of arsenic and cadmium from the water environment using Micranthemum umbrosum (J.F. Gmel) S.F Blake as a hyperaccumulator.
Arsenic (As) and cadmium (Cd) pollution in water is an important global issue. Phytofiltration is an eco-friendly technology that helps clean up pollutants using ornamental plants, such as Micranthemum umbrosum (J.F. Gmel) S.F. Blake. After a seven-day hydroponic experiment, M. umbrosum removed 79.3-89.5% As and 60-73.1% Cd from 0 to 1.0 microg As mL(-1) and 0.3 to 30.0 microg Cd mL(-1) solutions, respectively. For As treatment, root to stem and stem to leaf translocation factors greater than 1.0 indicated that accumulation of As in leaves was large compared to that in stem and roots. However, the accumulation of Cd in roots was higher than that in the leaves and stem. In addition, M. umbrosum completely removed Cd within three days from 0.38 to around 0 microg mL(-1) Cd in the solution when the plant was exchanged daily. Bio-concentration factors (2350 for As and 3027 for Cd) for M. umbrosum were higher than for other As and Cd phytoremediators. The results show that M. umbrosum can be an effective accumulator of Cd and a hyper-accumulator of As, as it can lower As toxicity to a level close to the limit recommended by the World Health Organization (0.01 microg As mL(-1)).


Sex differences in the impact of Affordable Care Act Medicaid expansion on colorectal cancer screening.
Access to care varies by sex such that interactions with insurance status result in mixed patterns of preventive services utilization. We examined sex-specific effects of ACA Medicaid expansions on receipt of CRC screening. We used Behavioral Risk Factor Surveillance System data (2008-2016) for adults aged 50-64 years with household income ≤138% of federal poverty level to examine self-reported lifetime use of guideline-recommended CRC screening services overall and by screening modality. We employed difference-in-difference models comparing changes in CRC screening in 20 Medicaid expansion states before and after the ACA to changes in 18 states that did not expand Medicaid during our study period. We divided the expansion period into implementation (2014) and post-expansion (2016) periods to account for possible lagged effects. We observed time-varying effects of Medicaid expansion that revealed relative increases in CRC screening occurring during the post-expansion period. Heterogeneous effects by sex and by screening modality were also observed: there was a significant relative increase of 16.2 percentage points (95% CI [2.2, 30.2]; p-value = 0.023) in lifetime colonoscopy use among women in expansion states relative to non-expansion states in the post-expansion period. There were no significant effects of Medicaid expansion among men. Health insurance expansion had a lagged but significant effect on CRC screening among low-income non-elderly women in Medicaid expansion states, but no effect for men. The observed increase in CRC screening among women suggests that barriers to CRC screening may differ by sex, and tailored interventions to increase CRC screening improve outcomes.


Long-term safety of polypropylene knots under scleral flaps for transsclerally sutured posterior chamber lenses.
To evaluate the safety of polypropylene knots used in TS-SPCL combined with PK and AV over time. A retrospective review of 26 consecutive cases of TS-SPCL by one surgeon (WSVM) with at least 12 months follow-up (mean 26, range 12-62). All patients had a double strand polypropylene knot buried under partial thickness scleral flaps at 2 and 8 o'clock. Knots were rotated into the globe (R) in 10 cases, and could not be buried (N) in 13 cases, and in 3 cases 1 knot was buried. No cases of suture erosion occurred in R or N. One or more polypropylene sutures were visible in 17 patients (8 R, 9 T) at last exam. Twenty-three of 52 knots were rotated into the globe, and 70% of rotated knots were not even visible at the slit lamp at final visit. There was no evidence of conjunctival erosion in any patient. There was no lens dislocation and no endophthalmitis. The combination of partial thickness scleral flaps with double strand polypropylene knots reduces the incidence of suture erosion through the conjunctive if knots cannot be rotated into the globe.


Spiking Neural Networks and online learning: An overview and perspectives.
Applications that generate huge amounts of data in the form of fast streams are becoming increasingly prevalent, being therefore necessary to learn in an online manner. These conditions usually impose memory and processing time restrictions, and they often turn into evolving environments where a change may affect the input data distribution. Such a change causes that predictive models trained over these stream data become obsolete and do not adapt suitably to new distributions. Specially in these non-stationary scenarios, there is a pressing need for new algorithms that adapt to these changes as fast as possible, while maintaining good performance scores. Unfortunately, most off-the-shelf classification models need to be retrained if they are used in changing environments, and fail to scale properly. Spiking Neural Networks have revealed themselves as one of the most successful approaches to model the behavior and learning potential of the brain, and exploit them to undertake practical online learning tasks. Besides, some specific flavors of Spiking Neural Networks can overcome the necessity of retraining after a drift occurs. This work intends to merge both fields by serving as a comprehensive overview, motivating further developments that embrace Spiking Neural Networks for online learning scenarios, and being a friendly entry point for non-experts.


3D Printing and 3D Bioprinting in Pediatrics.
Additive manufacturing, commonly referred to as 3D printing, is a technology that builds three-dimensional structures and components layer by layer. Bioprinting is the use of 3D printing technology to fabricate tissue constructs for regenerative medicine from cell-laden bio-inks. 3D printing and bioprinting have huge potential in revolutionizing the field of tissue engineering and regenerative medicine. This paper reviews the application of 3D printing and bioprinting in the field of pediatrics.


Assessment of the Need to Integrate Academic Electronic Medical Records Into the Undergraduate Clinical Practicum: A Focus Group Interview.
As healthcare systems demand that nurses be competent in using electronic medical records for patient care, the integration of electronic medical records into nursing curricula has become necessary. The purpose of this study was to explore how students, new nurses, clinical instructors, and faculty perceive the integration of academic electronic medical records into the undergraduate clinical practicum. From January to February 2014, four focus group interviews with 18 participants were conducted based on purposive sampling. Content analysis was used on the unabridged transcripts to extract themes and develop meaningful categories. Three major themes and eight subthemes were revealed from the focus group interviews. The major themes were "electronic medical record as a learning tool for clinical practicum," "essential functions of academic electronic medical records," and "expected outcomes of academic electronic medical record." Participants expected academic electronic medical records to enhance students' nursing informatics competencies. The findings of this study can inform the process of developing academic electronic medical records for clinical practicum, which will then augment students' informatics competencies.


Imaging of Clival Hypoplasia in CHARGE Syndrome and Hypothesis for Development: A Case-Control Study.
We present the largest case series to date on basiocciput abnormalities in CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and/or deafness). We aimed to show that basiocciput abnormalities are common and may aid in diagnosis. We furthermore explored whether clivus size correlates with the type of chromodomain-helicase-DNA binding protein 7 gene (CHD7) mutation, which causes CHARGE syndrome, and with clinical criteria according to Blake et al and Verloes. We retrospectively analyzed the clivus of 23 patients with CHARGE syndrome with CHD7 mutations on MR imaging or CT. We recorded the size of the clivus, the Welcher angle, basilar invagination, and Chiari I malformations. We compared the clival size and Welcher angle of patients with CHARGE syndrome with those of 72 age-matched controls. Additionally, we tested for correlations between clivus size and mutation type or clinical criteria. Eighty-seven percent of the patients with CHARGE syndrome had an abnormal clivus; 61% had a clivus >2.5 SD smaller than that of age-matched controls. An abnormally large Welcher angle was observed in 35%. Basiocciput hypoplasia was found in 70%, and basilar invagination, in 29%. None of the patients had a Chiari I malformation. At the group level, patients with CHARGE syndrome had a smaller clivus and larger Welcher angle than controls. No significant correlation between clivus size and mutation type or clinical criteria was found. Most patients with CHARGE syndrome have an abnormal clivus. This suggests that clivus abnormalities may be used as an additional diagnostic tool. Our results provide evidence that CHD7, which is expressed in the presomitic mesoderm during somitogenesis, plays an important role in the formation of the clivus.


Left side clot in transit in double-lung transplantation diagnosticated by transesophageal echocardiography: what´s next?
A 61-year-old man with no predisposition to thrombosis underwent sequential double lung transplantation without extracorporeal membrane oxygenation (ECMO) support due to terminal stage COPD. After implantation and reperfusion of both lungs, a complete transoesophageal echocardiography study was performed to check the pulmonary venous anastomosis. The study showed a large, heterogeneous, dense, hyperechoic free-floating mass in the left atrium compatible with a clot in transit from the pulmonary circulation. The surgical team were notified of this finding so that they could reopen the anastomosis and remove the clot to prevent a major complication. There were no clinical manifestations when the patient was awakened.


CTNNBIP1-CLSTN1 Functions as a Housekeeping Chimeric RNA, and Regulates Cell Proliferation through SERPINE2.
The conventional wisdom that chimeric RNAs being peculiarity of carcinoma, and the products of chromosomal rearrangement is being challenged, However, experimental evidence supporting chimeric RNAs in normal physiology being functional is scarce. We decided to focus on one particular chimeric RNA, CTNNBIP1-CLSTN1 . We examined its expression among various tissues and cell types, and compared quantitatively among cancer and non-cancer cells. We further investigated its role in a panel of non-cancer cells and probed the functional mechanism. We found that this fusion transcript is expressed in almost all tissues, and a wide range of cell types including fibroblasts, epithelial, stem, vascular endothelial cells, and hepatocytes. The expression level in non-cancerous cell lines is also not evidently different from that in the cancer cell lines. Furthermore, silencing CTNNBIP1-CLSTN1 significantly reduces cell proliferation rate, by inducing G2/M arrest in cell cycle progress and apoptosis in at least three cell types. Importantly, rescue experiments confirmed that the cell cycle arrest can be regained by exogenous expression of the chimera, but not the wild type parental gene. Further evidence is provided that CTNNBIP1-CLSTN1 regulates cell proliferation through SERPINE2 . Thus, CTNNBIP1-CLSTN1 represents an example of a new class of fusion RNA, dubbed "housekeeping chimeric RNAs".


[Determination of glucose in hemolysed blood samples (author's transl)].
The determination of glucose in hemolysed and stabilized blood samples by the hexokinase/glucose-6-phosphate-dehydrogenase-method is described. The glucose concentration in hemolysed blood samples was stable for 7 days. Even at high glucose concentrations (linear range up to 60 mmol/l), the reaction came to completion within 5 minutes. No interference by lipemia, bilirubin and drugs was observed; the interference of fructose was slight. Compared with deproteinized samples there was a very good correlation between this method and the reference method. Precision and recovery were good. This method is also suited for the analysis of few samples and offers the possibility of blood sugar self-profiles in diabetic out-patients and gives an increasing improvement of diabetic control.


SELECTIVE ATTENTIVENESS AND CORTICAL EVOKED RESPONSES TO VISUAL AND AUDITORY STIMULI.
Cortical evoked responses to flashes and clicks were recorded from human subjects performing visual or auditory tasks under three conditions of selective attentiveness. The subjects were required to attend to the flashes and to ignore alternating clicks, or vice versa. Responses to flashes recorded from the occipital area were larger when attention was directed toward visual stimuli, and responses to click stimuli recorded from the temporal area were larger when attention was directed toward auditory stimuli.


A Complication in Hypospadias Surgery Due to Anchoring Suture.
The complication rates are still 1-90% both in proximal and distal hypospadias regardless of the surgeon's experience and the usage of most developed techniques. The literature survey revealed few complications of glans penis including meatal stenosis, prolapsus and retraction. Despite our literature survey, we could not find any article concerning the permanent scar tissue at the dorsal part of glans following hypospadias surgeries. A new complication can be added to these, concerning glans which is the formation of postoperative scar tissue as a reaction to suture material used in traction, stent anchoring or both. The aim of this paper is to demonstrate four cases which had glanular scar due to traction suture following the surgical procedures for hypospadias repair.


Assessing the sensitivity of surveillance for pneumonia in rural Thailand.
We conducted a household survey among Sa Kaeo residents to characterize self-reported health-seeking behavior for pneumonia and the proportion of individuals who seek care at a hospital to determine the coverage of a surveillance system. A 2-stage cluster sample was used to select households. A case of pneumonia was defined as a self-reported history of cough and difficulty breathing for at least 2 days or being given a diagnosis of pneumonia by a healthcare provider in the 12-month period beginning February 1, 2002, and ending January 31, 2003. Interviewers administered a structured questionnaire that asked about clinical illness and utilization of healthcare services. Among 1,600 households, 5,658 persons were surveyed, of whom 62 persons met the case definition. Of the 59 persons with complete data, 53 (90%, 95% CI: 79-96) sought medical care and 47 (80%, 95% CI: 67-89) sought care at a hospital facility in the province. Neither distance nor cost was reported as a barrier to seeking care. Most individuals with self-reported pneumonia sought care at the hospital level. Population-based surveillance can provide reliable estimates of hospitalized, chest radiograph-confirmed pneumonia in Sa Kaeo if adjustments are made to account for the proportion of individuals who access a hospital where radiologic assessment is available.


Introduced plants of Lupinus polyphyllus are larger but flower less frequently than conspecifics from the native range: Results of the first year.
Introduced species, which establish in novel environments, provide an opportunity to explore trait evolution and how it may contribute to the distribution and spread of species. Here, we explore trait changes of the perennial herb Lupinus polyphyllus based on 11 native populations in the western USA and 17 introduced populations in Finland. More specifically, we investigated whether introduced populations outperformed native populations in traits measured in situ (seed mass) and under common garden conditions during their first year (plant size, flowering probability, and number of flowering shoots). We also explored whether climate of origin (temperature) influenced plant traits and quantified the degree to which trait variability was explained collectively by country and temperature as compared to other population-level differences. Three out of four plant traits differed between the native and introduced populations; only seed mass was similar between countries, with most of its variation attributed to other sources of intraspecific variation not accounted for by country and temperature. Under common garden conditions, plants originating from introduced populations were larger than those originating from native populations. However, plants from the introduced range flowered less frequently and had fewer flowering shoots than their native-range counterparts. Temperature of a population's origin influenced plant size in the common garden, with plant size increasing with increasing mean annual temperature in both native and introduced populations. Our results of the first year reveal genetic basis for phenotypic differences in some fitness-related traits between the native and introduced populations of L. polyphyllus. However, not all of these trait differences necessarily contribute to the invasion success of the species and thus may not be adaptive, which raises a question how persistent the trait differences observed in the first year are later in individuals' life for perennial herbs.


"We're tough, but so is quitting." Barriers to Smoking Cessation: The Royal Malaysian Navy Perspective.
Tobacco kills half of its users. Despite this, there are over 1.1 billion smokers worldwide. Its harmful effects impair performance and readiness. Unfortunately, smoking has deeply ingrained in the military culture, as evidenced by the high prevalence. Hence, this study aims to identify the barriers to smoking cessation among this population. A study involving two groups of current smokers (commissioned officers and non-commissioned officers) was conducted using the modified nominal group technique (mNGT), a qualitative research method of judgmental decision-making involving four phases: Generating ideas, recording, evaluation, and prioritization. The mNGT was used to solicit respondents' barriers to smoking cessation. The mNGT yielded seven main barriers to smoking cessation: (1) Addiction, (2) difficulty in staying focused without the usage of cigarettes, (3) smoking has been incorporated into an individual's lifestyle, (4) environmental influence, (5) coping mechanism, (6) the long-interval period between orders and duties exacerbates the desire to smoke, and (7) smoking has evolved into a permanent habit. Although nicotine addiction and habit were ranked as the most important barriers, the military working environment and nature of the job exposed them physically and mentally to unfavorable situations, complicating the quitting attempt. Furthermore, the acceptance of smoking in military culture leads to a positive smoker identity, further hindering cessation. The findings indicate that in addition to barriers affecting the general population, military-specific barriers related to the nature of the job exist, complicating cessation. Hence, any intervention program should address these barriers to achieve positive outcomes.


[The effect of a nonspecific immunostimulant on the phagocytosis of erythrocytes and ink by the reticulohistiocyte system in the isolated, perfused liver of rats of various ages].
By the help of the isolated perfused rat liver the influence of a non-specific immune stimulant on the phagocytic activity of Kupffer cells was tested. It was shown that the phagocytosis of colloidal ink is not influenced. The phagocytosis of erythrocytes is improved significantly by the treatment in young as well as in aged animals independent whether they were pretreated or not. These data, together with the behaviour of the liver function parameters, indicate a positive influence of the plant immunstimulant on the receptor- or immunoglobulin-dependent first phase of phagocytosis and, because of the redox quotients, an activation of the second phase of phagocytosis.


Binding of NADP+ triggers an open-to-closed transition in a mycobacterial FabG β-ketoacyl-ACP reductase.
The ketoacyl-acyl carrier protein (ACP) reductase FabG catalyzes the NADPH/NADH dependent reduction of β-ketoacyl-ACP substrates to β-hydroxyacyl-ACP products, the first reductive step in the fatty acid biosynthesis elongation cycle. FabG proteins are ubiquitous in bacteria and are part of the type II fatty acid synthase system. Mining the Mycobacterium smegmatis genome uncovered several putative FabG-like proteins. Among them, we identified M. smegmatis MSMEG_6753 whose gene was found adjacent to MSMEG_6754, encoding a recently characterized enoyl-CoA dehydratase, and to MSMEG_6755, encoding another potential reductase. Recombinantly expressed and purified MSMEG_6753 exhibits ketoacyl reductase activity in the presence of acetoacetyl-CoA and NADPH. This activity was subsequently confirmed by functional complementation studies in a fabG thermosensitive Escherichia coli mutant. Furthermore, comparison of the apo and the NADP+-bound MSMEG_6753 crystal structures showed that cofactor binding induces a closed conformation of the protein. A ΔMSMEG_6753 deletion mutant could be generated in M. smegmatis, indicating that this gene is dispensable for mycobacterial growth. Overall, these results showcase the diversity of FabG-like proteins in mycobacteria and new structural features regarding the catalytic mechanism of this important family of enzymes that may be of importance for the rational design of specific FabG inhibitors.


The effects of isoniazid on hippocampal NMDA receptors: protective role of erdosteine.
Isoniazid (INH) has neurotoxic effects such as seizure, poor concentration, subtle reduction in memory, anxiety, depression and psychosis. INH-induced toxic effects are thought to be through increased oxidative stress, and these effects have been shown to be prevented by antioxidant therapies in various organs. Increased oxidative stress may be playing a role in these neurotoxic effects. N-methyl D-aspartat receptors (NMDA) are a member of the ionotropic group of glutamate receptors. These receptors are involved in a wide variety of processes in the central nervous system including synaptogenesis, synaptic plasticity, memory and learning. Erdosteine is a potent antioxidant and mucolytic agent. We aimed to investigate adverse effects of INH on rat hippocampal NMDAR receptors, and to elucidate whether erdosteine prevents possible adverse effects of INH. In the present study, compared to control group, NMDAR2A (NR2A) receptors were significantly decreased and malondialdehyde (MDA), end product of lipid peroxidation, production was significantly increased in INH-treated group. On the other hand, administration of erdosteine to INH-treated group significantly increased NR2A receptors and decreased MDA production. In conclusion, decreasing NR2A receptors in hippocampus and increasing lipid peroxidation correlates with the degree of oxidative effects of INH and erdosteine protects above effect of INH on NR2A receptors and membrane damage due to lipid peroxidation by its antioxidant properties.


Thyroid-Like Follicular Carcinoma of the Kidney With Oncocytic Cells: A Case Report and Review of Metastatic and Non-metastatic Tumors.
Thyroid-like follicular carcinoma of kidney (TLFCK) is a morphological subtype of renal cell carcinoma, which is included as an emerging/provisional entity in the classification of renal tumors, with only about 40 cases reported in literature. It has a distinct histological appearance and immunohistochemical profile as compared with other renal cell cancers. However, these tumors, while appearing distinctive, have not been characterized fully either morphologically or by ancillary techniques. The reported cases show variable demographical and clinical features. Most are indolent, while some present with metastasis. The histological, immunohistochemical, and ultrastructural features of a case of TLFCK with clusters of oncocytic cells and pseudosarcomatous stroma are presented. Follow-up of 5 years was uneventful. A review of literature to analyze features in metastatic as compared with non-metastatic TLFCK is discussed. We report a patient of TLFCK and compare the clinicopathological features of metastatic and non-metastatic tumors.


Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls.
Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic-pituitary-adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity.


Survey of phthalate pollution in arable soils in China.
The problem of pollution by phthalates is of global concern due to their widespread occurrence, toxicity and endocrine disruption properties. The contamination by phthalates such as dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) in 23 arable soils throughout China was investigated to evaluate the present pollution situation. The survey results demonstrated that phthalates were ubiquitous pollutants in soils in China. The total concentrations of phthalates differed from one location to another, and ranged from 0.89 to 10.03 mg kg(-1) with a median concentration of 3.43 mg kg(-1). Among the phthalates, DEHP was dominant and detected in all 23 soils. DEP and DBP were also in abundance, and DMP was rarely detected. Similar contamination patterns were observed in all 23 soils. A distinct feature of phthalate pollution in China was that the average concentration in northern China was higher than that in southern China. In addition, a close relationship was observed between the concentration of phthalates in soils and the consumption of agricultural film. The correlation showed that the application of agriculture film might be a significant pollution source of phthalates in arable soils of China. The potential risk of phthalates in soils was assessed on the basis of current guide values and limits.


Cultural safety, diversity and the servicer user and carer movement in mental health research.
This study will be of interest to anyone concerned with a critical appraisal of mental health service users' and carers' participation in research collaboration and with the potential of the postcolonial paradigm of cultural safety to contribute to the service user research (SUR) movement. The history and nature of the mental health field and its relationship to colonial processes provokes a consideration of whether cultural safety could focus attention on diversity, power imbalance, cultural dominance and structural inequality, identified as barriers and tensions in SUR. We consider these issues in the context of state-driven approaches towards SUR in planning and evaluation and the concurrent rise of the SUR movement in the UK and Australia, societies with an intimate involvement in processes of colonisation. We consider the principles and motivations underlying cultural safety and SUR in the context of the policy agenda informing SUR. We conclude that while both cultural safety and SUR are underpinned by social constructionism constituting similarities in principles and intent, cultural safety has additional dimensions. Hence, we call on researchers to use the explicitly political and self-reflective process of cultural safety to think about and address issues of diversity, power and social justice in research collaboration.


Prediction of novel ground-state structures and analysis of phonon transport in two-dimensional GexSy compounds.
We conducted this study to explore the ground-state structures of two-dimensional (2D) variable-composition GexSy compounds, driven by the polymorphic characteristics of bulk germanium sulfides and the promising thermoelectric performance of 2D GeS (Pmn21). To accomplish this, we utilized the highly successful evolutionary-algorithm-based code USPEX in conjunction with VASP for total energy calculations, leading to the discovery of three previously unexplored structures of Ge2S (P2/c), GeS (P3̄m1), and GeS2 (P21/c). These 2D materials exhibit significantly lower formation energies compared to their reported counterparts. We thoroughly scrutinized the structural stability and subsequently analyzed their electronic structures. Our analysis reveals a nearly direct band gap of 0.12/0.84 eV with the PBE/HSE06 functional for 2D Ge2S and an indirect band gap for 2D GeS and GeS2. Their semiconducting nature highlights the crucial importance of lattice thermal conductivity (κl), which we determined by solving the Boltzmann transport equation for phonons. Importantly, we predict a room temperature κl value of 6.82 W m-1 K-1 for GeS, lower than its 2D orthorhombic counterpart. In the case of GeS2, we observed an anisotropic κl value of 16.95/10.68 W m-1 K-1 along the zigzag/armchair directions at 300 K, with an in-plane anisotropy ratio of 1.59, surpassing that of 2D IV-VI compounds. We delve into detailed discussions regarding the role of lattice anharmonicity, group velocities, phonon lifetimes, and three-phonon weighted phase space in the overall thermal conductivity analysis.


A butyrolactone derivative 3BDO alleviates memory deficits and reduces amyloid-β deposition in an AβPP/PS1 transgenic mouse model.
Excessive extracellular deposition of amyloid- peptide (Aβ) in the brain is the pathological hallmark of Alzheimer's disease (AD). Cumulative evidence indicates that autophagy is involved in the metabolism of Aβ and pathogenesis of AD. However, the molecular mechanism underlying the pathogenesis of AD is not yet well defined, and there has been no effective treatment for AD. We recently found that long-term treatment with a butyrolactone derivative 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran- 2(3 H)-one (3BDO) increased levels of insulin-degrading enzyme and neprilysin, suppressed autophagy via an mTOR pathway, lowered levels of Aβ, and prevented AD-like cognitive deficits in the AβPP/PS1 double transgenic mouse model. Therefore, our findings suggest that 3BDO may be beneficial in the prevention and treatment of AD.


Transplanting kidneys from donation after cardiac death donors with acute kidney injury.
Donation after cardiac death (DCD) and acute kidney injury (AKI) donors have historically been considered independent risk factors for delayed graft function (DGF), allograft failure, and inferior outcomes. With growing experience, updated analyses have shown good outcomes. There continues to be limited data, however, on outcomes specific to DCD donors who have AKI. Primary outcomes for this study were post-kidney transplant patient and allograft survival comparing two donor groups: DCD AKIN stage 2-3 and DBD AKIN stage 2-3. In comparing these groups, there were no short- or long-term differences in patient (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.54-1.93, P = .83) or allograft survival (HR 1.47, 95% CI 0.64-2.97, P = .32). In multivariate models, the DCD/DBD status had no significant impact on the estimated GFR (eGFR) at 1 (P = .38), 2 (P = .60), and 3 years (P = .52). DGF (57.9% vs 67.9%, P = .09), rejection (12.1% vs 13.9%, P = .12), and progression of interstitial fibrosis/tubular atrophy (IFTA) on protocol biopsy (P = .16) were similar between the two groups. With careful selection, good outcomes can be achieved utilizing severe AKI DCD kidneys. Historic concerns regarding primary nonfunction, DGF resulting in interstitial fibrosis and rejection, and inferior outcomes were not observed. Given the ongoing organ shortage, increased effort should be undertaken to further utilize these donors.


Early initiation of renal replacement therapy in critically ill patients: a meta-analysis of randomized clinical trials.
Acute kidney injury (AKI) is strongly associated with high morbidity and mortality of critically ill patients. In the last years several different biological markers with higher sensitivity and specificity for the occurrence of renal impairment have been developed in order to promptly recognize and treat AKI. Nonetheless, their potential role in improving patients' outcome remains unclear since the effectiveness of an "earlier" initiation of renal replacement therapy (RRT) is still debated. Since one large, high-quality randomized clinical trial has been recently pubblished, we decided to perform a meta-analysis of all the RCTs ever performed on "earlier" initiation of RRT versus standard RRT in critically ill patients with AKI to evaluate its effect on major outcomes. Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and Cochrane Central Register of clinical trials. The following inclusion criteria were used: random allocation to treatment ("earlier" initiation of RRT versus later/standard initiation); critically ill patients. Ten trials randomizing 2214 patients, 1073 to earlier initiation of RRT and 1141 to later initiation were included. No difference in mortality (43.3% (465 of 1073) for those receiving early RRT and 40.8% (466 of 1141) for controls, p = 0.97) and survival without dependence on RRT (3.6% (34 of 931) for those receiving early RRT and 4.2% (40 of 939) for controls, p = 0.51) were observed in the overall population. On the contrary, early initiation of RRT was associated with a significant reduction in hospital length of stay. No differences in occurrence of adverse events were observed. Our study suggests that early initiation of RRT in critically ill patients with AKI does not provide a clinically relevant advantage when compared with standard/late initiation.