Imatinib treatment induces CD5+ B lymphocytes and IgM natural antibodies with anti-leukemic reactivity in patients with chronic myelogenous leukemia.
Imatinib mesylate is a first line treatment of Chronic Myelogenous Leukemia and of a rare form of gastrointestinal stromal cancer, where the response to the drug is also linked to the immune system activation with production of antineoplastic cytokines. In this study, forty patients in the chronic phase of disease, treated with imatinib mesylate, were analyzed. Bone marrow aspirates were drawn at diagnosis, after 3, 6, 12, 18 months for haematological, cytofluorimetric, cytogenetic, biomolecular evaluation and cytokine measurement. Responder and non responder patients were defined according to the European LeukemiaNet recommendations. In responder patients (n = 32), the percentage of bone marrow CD20(+)CD5(+)sIgM(+) lymphocytes, and the plasma levels of IgM, were significantly higher, at 3 months and up to 9 months, than in non responders. These IgM reacted with O-linked sugars expressed by leukemic cells and could induce tumor cell apoptosis. In responder patients the stromal-derived factor-1 and the B-lymphocyte-activating factor of the tumor necrosis factor family significantly raised in the bone marrow after imatinib administration, together with the bone morphogenetic proteins-2 and -7. All patients with high number of CD20(+)CD5(+)sIgM(+) cells and high stromal-derived factor-1 and B lymphocyte activating factor levels, underwent complete cytogenetic and/or molecular remission by 12 months. We propose that CD20(+)CD5(+)sIgM(+) lymphocytes producing anti-carbohydrate antibodies with anti-tumor activity, might contribute to the response to imatinib treatment. As in multivariate analysis bone marrow CD20(+)CD5(+)sIgM(+) cells and stromal-derived factor-1 and B-lymphocyte-activating factor levels were significantly related to cytogenetical and molecular changes, they might contribute to the definition of the pharmacological response.


Drug Information: Prescribers' Need for and Access to Drug Information Resources in Ethiopia.
Rational and cost-effective prescription of drugs requires up-to-date and readily accessible drug information (DI). Availability of and access to DI resources are major factors that affect quality of prescription. The aim of the study was to assess prescribers' DI needs and access to DI resources in Ethiopia. A facility-based, cross-sectional, quantitative study was conducted from February to April 2011 in 4 selected public health facilities in southwest Ethiopia. Data on areas of DI needs, access to DI resources, and attitudes of prescribers toward DI services were collected using a structured, self-administered questionnaire. The study population consisted of 410 of 447 initially contacted prescribers. The majority of the prescribers (93.4%) explained their needs for DI services. About 32.4% of the participants do not frequently refer to DI resources mainly due to the difficulty of acquiring the required information promptly and/or because they do not have access to DI resources. Compared with participants from a health center, participants from specialized referral, zonal, and district hospitals were found to be 6 (adjusted odds ratio [AOR], 5.81; 95% confidence interval [CI], 2.77-12.20), 5 (AOR, 4.77; 95% CI, 2.43-9.38), and 4 (AOR, 4.00; 95% CI, 1.50-10.66) times more likely to consult DI resources, respectively. Lack of access to DI resources and difficulty in acquiring the required information on time were the main reasons that prescribers gave for not frequently referring to DI resources. DI services should be established and expanded in health facilities.


The effect of a tight control regime with monthly follow-up on remission rates and reported pain in early rheumatoid arthritis.
To determine whether a tight control (TC) regime with monthly consultations to the physician for the first 6 months, could increase remission rate and improve reported pain of patients with early rheumatoid arthritis (RA). In this single-centre, TC study, with monthly visits to the physician, a cohort of 100 patients with early RA was consecutively included. They were compared with a reference cohort of 100 patients from the same clinic that had been conventionally managed. The patients were followed for 2 years. The patients in the TC cohort had lower 28- joints disease activity score (DAS28) at three, six, 12 and 24 months, compared with the conventionally managed cohort, p ≤ 0.001. At 12 months, 71% in the TC cohort versus 46% in the conventional cohort were in remission (DAS28 < 2.6) and at 24 months 68% versus 49% respectively, p < 0.05. The TC cohort reported less pain at three, six, 12 and 24 months, p < 0.001. Multiple logistical regression analyses adjusted for, respectively, age, disease duration, pharmacological treatment, DAS28 and visual analogue scale pain at inclusion, revealed that participation in the TC cohort had an independent positive association with remission at 12 and 24 months and with acceptable pain at 24 months. The intensive follow-up schedule for patients with early RA improved remission and led to improvement in reported pain and physical function. The positive effect of a TC regime in early disease may be due to increased empowerment, developed by meeting health professionals frequently.


Multiple venous thromboembolisms in a pregnant patient carrying a novel mutation in SERPINC1 (p.M313T) that causes a transient antithrombin deficiency: a case report.
Congenital antithrombin deficiency is an autosomal dominant disease that results in deep venous thrombosis and pulmonary embolism, which is mainly caused by mutations in the antithrombin gene (SERPINC1). Since SERPINC1 is highly susceptible to alterations, severe structural and functional changes that promote thrombosis may occur. Clinical presentations vary from different alterations. We report a pregnant case with novel mutation in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. We report a case of a 36-year-old pregnant patient who was diagnosed with congenital antithrombin deficiency for carrying a novel heterozygous mutation, NM_000488:exon5:c.T9 38 C:p. M313T in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Thrombolytic with alteplase and anticoagulant therapies with low-molecular-weight heparin and warfarin were administrated. After confirming the genetic analysis and the termination of pregnancy, rivaroxaban was administrated, and the thrombosis reduced. Our study enriched the mutation database of SERPINC1 gene, provided some new theoretical basis for gene diagnosis and genetic counseling of patients with transient antithrombin deficiency. While it still needs for subsequent exploration of molecular pathogenesis.


A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol.
Mitochondrial fidelity is tightly linked to overall cellular homeostasis and is compromised in ageing and various pathologies1-3. Mitochondrial malfunction needs to be relayed to the cytosol, where an integrated stress response is triggered by the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) in mammalian cells4,5. eIF2α phosphorylation is mediated by the four eIF2α kinases GCN2, HRI, PERK and PKR, which are activated by diverse types of cellular stress6. However, the machinery that communicates mitochondrial perturbation to the cytosol to trigger the integrated stress response remains unknown1,2,7. Here we combine genome engineering and haploid genetics to unbiasedly identify genes that affect the induction of C/EBP homologous protein (CHOP), a key factor in the integrated stress response. We show that the mitochondrial protease OMA1 and the poorly characterized protein DELE1, together with HRI, constitute the missing pathway that is triggered by mitochondrial stress. Mechanistically, stress-induced activation of OMA1 causes DELE1 to be cleaved into a short form that accumulates in the cytosol, where it binds to and activates HRI via its C-terminal portion. Obstruction of this pathway can be beneficial or adverse depending on the type of mitochondrial perturbation. In addition to the core pathway components, our comparative genetic screening strategy identifies a suite of additional regulators. Together, these findings could be used to inform future strategies to modulate the cellular response to mitochondrial dysfunction in the context of human disease.


Effects of sub-anesthetic doses of ketamine on rats' spatial and non-spatial recognition memory.
There are experimental evidences indicating that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine impairs cognition and produces a series of schizophrenia-like symptoms in rodents (hyperactivity, stereotypies and ataxia). The present study was designed to investigate the effects of ketamine on rats' non-spatial and spatial recognition memory. For this purpose the object recognition and the object location task were selected. Pre- or post-training systemic administration of ketamine (0.3, 1 and 3 mg/kg; i.p.) in a dose-dependent manner disrupted animals' performance in both these recognition memory paradigms, suggesting that this compound affected pre- and post-training memory components. The current results indicate that the non-competitive NMDA antagonist ketamine may modulate either spatial or non-spatial recognition memory.


Computerized nailfold video capillaroscopy--a new tool for assessment of Raynaud's phenomenon.
To develop a computer based nailfold video capillaroscopy system with enhanced image quality and to assess its disease-subgroup resolving power in patients with primary and secondary Raynaud's phenomenon (RP). Using frame registration software, digitized video images from the microscope were combined to form a panoramic mosaic of the nailfold. Capillary dimensions (apex, arterial, venous, and total width) and density were measured onscreen. Significantly, the new system could guarantee analysis of the same set of capillaries by 2 observers. Forty-eight healthy control subjects, 21 patients with primary RP, 40 patients with limited cutaneous systemic sclerosis (lcSSc), and 11 patients with diffuse cutaneous SSc (dcSSc) were studied. Intra- and interobserver variability were calculated in a subset of 30 subjects. The number of loops/mm was significantly lower, and all 4 capillary dimensions significantly greater, in SSc patients versus controls plus primary RP patients (p < 0.001 for all measures). When comparing control (+ primary RP) patients with SSc patients (lcSSc + dcSSc) the most powerful discriminator was found to be the number of loops/mm. Results for intra- and interobserver reproducibility showed that the limits of agreement were closer when both observers measured the same capillaries. The key feature of the newly developed system is that it improves reproducibility of nailfold capillary measurements by allowing reidentification of the same capillaries by different observers. By allowing access to previous measurements, the new system should improve reliability in longitudinal studies, and therefore has the potential of being a valuable outcome measure of microvessel disease/involvement in clinical trials of scleroderma spectrum disorders.


The hemoglobin of the sea lamprey, Petromyzon marinus.
The blood hemoglobin of the sea lamprey presents a curious mixture of primitive and highly specialized properties. Like muscle hemoglobin, it has a molecular weight of about 17,000, and apparently contains a single heme. Its isoelectric point is like that of a typical invertebrate hemoglobin. Its amino acid composition is partly characteristic of invertebrate) partly of vertebrate hemoglobins (Pedersen; Roche and Fontaine). In the present experiments, the oxygen equilibrium curve of this pigment was measured at several pH's. As expected, it is a rectangular hyperbola, the first such function to be observed in a vertebrate blood hemoglobin. Other hemoglobins known to possess this type of oxygen dissociation curve-those of vertebrate muscle, the worm Nippostrongylus, and the bot-fly larva-appear to serve primarily the function of oxygen storage rather than transport. Lamprey hemoglobin on the contrary is an efficient oxygen-transporting agent. It achieves this status by having, unlike muscle hemoglobin, a relatively low oxygen affinity, and a very large Bohr effect. In these properties it rivals the most effective vertebrate blood hemoglobins.


Parsing brain activity associated with acupuncture treatment in Parkinson's diseases.
Acupuncture, a common treatment modality within complementary and alternative medicine, has been widely used for Parkinson's disease (PD). Using functional magnetic resonance imaging (fMRI), we explored the neural mechanisms underlying the effect of specific and genuine acupuncture treatment on the motor function in patients with PD. Three fMRI scans were performed in random order in a block design, one for verum acupuncture (VA) treatment, another one for a covert placebo (CP), and the third one for an overt placebo (OP) at the motor function implicated acupoint GB34 on the left foot of 10 patients with PD. We calculated the contrast that subtracts the blood-oxygen-level dependent (BOLD) response for the acupuncture effect (VA vs. CP) and the placebo effect (CP vs. OP). We found a significant improvement in the motor function of the affected hand after acupuncture treatment. The putamen and the primary motor cortex were activated when patients with PD received the acupuncture treatment (VA vs. CP) and these activations correlated with individual enhanced motor function. Expectation towards acupuncture modality (CP vs. OP) elicited activation over the anterior cingulate gyrus, the superior frontal gyrus, and the superior temporal gyrus. These findings suggest that acupuncture treatment might facilitate improvement in the motor functioning of patients with PD via the basal ganglia-thalamocortical circuit.


Efficacy of tramadol in preventing postoperative shivering using thiopentone or propofol as induction agent: A randomized controlled trial.
Postoperative shivering (POS) is a common and distressing experience occurring in up to 60% patients postoperatively. This study was designed to compare the efficacy of tramadol in preventing POS when used with two different induction agent, propofol or thiopentone. One hundred and twenty-four ASA I and II adult patients, aged between 18-60 years, undergoing general anesthesia of intermediate duration (60-240 min) for orthopedic, gynecological, and general surgical procedures were randomly divided to receive either thiopentone or propofol as induction agent. Each group was further subdivided (31 patients in each group) to receive either tramadol or saline 15 min before wound closure. Presence of POS after extubation till discharge from post anesthesia care unit (PACU) was recorded at six different time intervals. The highest incidence of POS was observed in thiopentone-saline (TS) group 77.4%, while the lowest (12.9%) was in propofol-tramadol (PT) group (P > 0.001). Total number of shivering episodes was 122 out of which, 35 (28.7%) were of grade 2 and 3 (significant shivering) requiring treatment. The incidence of significant shivering was similar to the episodes of POS, highest in TS group and lowest being in PT group (P > 0.05). The prophylactic use of tramadol in a dose of 1 mg/kg with propofol as an induction agent significantly reduces the incidence of POS in patients recovering from general anesthesia of intermediate duration.


Recent advances in visible light-activated photocatalysts for degradation of dyes: A comprehensive review.
The rapid development in industrialization and urbanization coupled with an ever-increasing world population has caused a tremendous increase in contamination of water resources globally. Synthetic dyes have emerged as a major contributor to environmental pollution due to their release in large quantities into the environment, especially owing to their high demand in textile, cosmetics, clothing, food, paper, rubber, printing, and plastic industries. Photocatalytic treatment technology has gained immense research attention for dye contaminated wastewater treatment due to its environment-friendliness, ability to completely degrade dye molecules using light irradiation, high efficiency, and no generation of secondary waste. Photocatalytic technology is evolving rapidly, and the foremost goal is to synthesize highly efficient photocatalysts with solar energy harvesting abilities. The current review provides a comprehensive overview of the most recent advances in highly efficient visible light-activated photocatalysts for dye degradation, including methods of synthesis, strategies for improving photocatalytic activity, regeneration and their performance in real industrial effluent. The influence of various operational parameters on photocatalytic activity are critically evaluated in this article. Finally, this review briefly discusses the current challenges and prospects of visible-light driven photocatalysts. This review serves as a convenient and comprehensive resource for comparing and studying the fundamentals and recent advancements in visible light photocatalysts and will facilitate further research in this direction.


Utility of thrombophilia screening in pediatric renal transplant recipients.
Thrombosis after kidney transplantation may result in catastrophic outcomes, including graft loss. Thrombophilia has been implicated in post-transplant thrombosis; data, however, are inconclusive on the impact of acquired and inherited thrombophilia and resultant thrombosis in renal graft recipients. We aimed to evaluate whether identifying children with thrombophilia during the pretransplant evaluation predicted post-transplant outcomes. We reviewed 100 kidney transplants performed in 100 children, aged 1-18 years, in a single-center retrospective study. Routine pretransplant comprehensive thrombophilia evaluation was completed. Thrombophilia was demonstrated in 36% patients (N = 36). TEs occurred in 11 patients before kidney transplant. Low PS and antithrombin were found in 9/86 (10.5%) and 2/89 (2.2%) children, respectively. Heterozygosity for FLV and PGM were found in 5/81 (6.2%) and 1/93(1.1%) children, respectively. A post-transplant thrombotic event occurred in 10 children (10%); six involved the renal transplant. The association between a history of a pretransplant thrombotic event and post-operative renal graft thrombosis approached, but did not reach significance (P = 0.071). There was no association between preoperative screening abnormalities and post-operative TEs. Graft loss due to a thrombotic event occurred in two patients; none had underlying thrombophilia. Our data suggest that the utility of universal, comprehensive preoperative thrombophilia testing is not beneficial in determining risk of post-operative graft thrombosis. Thrombophilia testing may be considered in a select population with a history of pretransplant thrombotic event.


Modeling risk stratification in human cancer.
Despite huge prognostic promises, gene expression-based survival assessment is rarely used in clinical routine. Main reasons include difficulties in performing and reporting analyses and restriction in most methods to one high-risk group with the vast majority of patients being unassessed. The present study aims at limiting these difficulties by (i) mathematically defining the number of risk groups without any a priori assumption; (ii) computing the risk of an independent cohort by considering each patient as a new patient incorporated to the validation cohort and (iii) providing an open-access Web site to freely compute risk for every new patient. Using the gene expression profiles of 551 patients with multiple myeloma, 602 with breast-cancer and 460 with glioma, we developed a model combining running log-rank tests under controlled chi-square conditions and multiple testing corrections to build a risk score and a classification algorithm using simultaneous global and between-group log-rank chi-square maximization. For each cancer entity, we provide a statistically significant three-group risk prediction model, which is corroborated with publicly available validation cohorts. In constraining between-group significances, the risk score compares favorably with previous risk classifications. Risk assessment is freely available on the Web at https://gliserv.montp.inserm.fr/PrognoWeb/ for personal or test data files. Web site implementation in Perl, R and Apache.


Naval training command mishaps and instructor experience.
Naval Training Command mishaps involving instructor error for a 7-year period were analyzed to determine the specific underlying causes and the relationships with previous instructor experience. The data show that mishap potential is correlated with previous fleet operational and training flight experience. Moreover, certain types of errors tend to manifest themselves at specific experience levels.


[Enzyme immunoassay for rotavirus using nylon as the solid phase].
An enzyme-linked immunoassay (EIA) to detect Rotavirus in stools is described. Antibodies prepared in rabbits were immobilized on small nylon cubes as capture phase and enzyme conjugated antibodies were used to reveal the reaction. The conjugate was prepared with horseradish peroxidase by the Nakane periodate oxidation method. The solid phase consisted of 3 mm nylon cubes (66 CNL Du-cilo) previously submitted to partial acid hydrolysis to liberate amino-reactive groups. Glutaraldehyde was employed to couple the capturing antibody to the solid phase resulting in a covalent linkage between the gamma-globulin and the nylon. Phenylenediamine in citrate buffer pH 5.0 with 0.5% hydrogen peroxide was used as revealing substrate. EIA was performed as follows: stools watery extracts were incubated 1 h at 37 degrees C with antibody-treated nylon cubes, and then with enzyme conjugate, rinsed with distilled water and substrate-added. Samples developing colour, with optical density of at least 0.350 at 492 nm, were considered positive. The method showed good correlation with a commercial kit.


Diagnosis of Crimean-Congo hemorrhagic fever.
Crimean-Congo hemorrhagic fever (CCHF) virus is the most extensive tick-borne virus, it causes a severe infection, which occurs widely in Africa, Eastern Europe and Asia. In recent years, the dramatic increase in the global distribution of CCHF, with the high mortality rates, highlights the importance of improving diagnostic capacity. Clinical and epidemiological data play a crucial role for early recognition of CCHF. However, CCHF is clinically difficult to diagnose and to distinguish, a rapid and reliable laboratory confirmation is necessary. Confirmation of infection in the acute phase of the disease can be made by detection of viral nucleic acid using reverse transcription-PCR, by demonstration of viral antigen or by virus isolation. In the convalescent phase of the disease, the diagnosis is confirmed by demonstration of an antibody response. The consideration of viral replication kinetics and antiviral humoral immune responses facilitates the selection of appropriate laboratory tests and accurate interpretation of laboratory findings.


[Construction and identification of lentiviral vector containing human ILK-shRNA and mda7 gene].
To construct and identify lentiviral vector containing human ILK-shRNA and mda7 gene. Based on the human ILK gene sequences, RNAi target sequences were designed and cloned into the lentiviral vector pSicoR-eGFP by restriction endonuclease HpaI and XhoI double digestion and T4 DNA ligase ligation. Based on the human mda7 gene sequences, PCR primers were designed to clone the full-length mda7, and were cloned into the lentiviral vector pLVX-Puro. After the candidate clones were identified by DNA sequencing, the recombinant plasmid and the three packaging plasmids were co-transfected into the human embryonic kidney 293T cells by lipofectamine 2000 to produce the lentiviral particles. Human prostate cancer PC-3 cells were infected with the constructed lentiviral vector. The ILK and mda7 expression levels in PC-3 cells were quantified by qPCR and Western blot, respectively. The effect of ILK and mda7 on proliferation and migration of PC-3 cells were assessed by MTT method and Transwell assay, respectively. ILK-pSicoR-eGFP and mda7-pLVX-Puro lentiviral vectors were successfully constructed. Strong green fluorescence was observed in the 293T cells under the fluorescent microscope after co-transfection of 293T cells with 4 plasmids of lentiviral vector. The transfection efficiency of the collected virus exceeded 90% in the 293T cells and the PC-3 cells were infected with the lentiviral particles with high efficiency. The A and B lentiviral vector inhibited the expression of ILK at both the mRNA and protein levels in PC-3 cells significantly. The mda7-pLVX-Puro lentiviral vector increased the expression of mda7 in PC-3 cells, and the ability was maintained for one month. Within 96 h, ILK and mad7 significantly inhibited the proliferation and migration of PC-3 cells (Ps<0.05). The lentiviral vectors of ILK knockdown and mda7 over-expression have been successfully constructed and identified. The recombinant lentivirus can efficiently infect human prostate cancer PC-3 cells, in which ILK expression is inhibited and mda7 is over-expressed.


Topographical relationship of the amygdaloid body to the hippocampal formation and lateral ventricle - MRI study.
The relationship of the amygdaloid body to the hippocampal formation and lateral ventricle was studied on MRI slabs of brains of 25 volunteers. Considering the presence of the hippocampal formation and/or uncal sulcus on a cross-section three segments of the amygdaloid body were distinguished in rostro-caudal order: prehippocampal, suprahippocampal anterior (preuncal) and suprahippocampal posterior (uncal), each one presenting characteristic features. The lengths of the amygdaloid body and of its segments were calculated. In each segment the great variability of the topographical relations was found. Especially in the suprahippocampal anterior segment the relation of the lateral ventricle to both, the amygdaloid body and hippocampus shows great differences, even between the right and left side.


Native and exotic pests of eucalyptus: a worldwide perspective.
Eucalyptus species, native to Australia, Indonesia, the Philippines, and New Guinea, are the most widely planted hardwood timber species in the world. The trees, moved around the globe as seeds, escaped the diverse community of herbivores found in their native range. However, a number of herbivore species from the native range of eucalypts have invaded many Eucalyptus-growing regions in North America, Europe, Africa, Asia, and South America in the last 30 years. In addition, there have been shifts of native species, particularly in Africa, Asia, and South America, onto Eucalyptus. There are risks that these species as well as generalist herbivores from other parts of the world will invade Australia and threaten the trees in their native range. The risk to Eucalyptus plantations in Australia is further compounded by planting commercially important species outside their endemic range and shifting of local herbivore populations onto new host trees. Understanding the mechanisms underlying host specificity of Australian insects can provide insight into patterns of host range expansion of both native and exotic insects.


Human T-lymphotropic virus type I transcriptional regulation by methylation.
While human T-lymphotropic virus type I (HTLV-I) proviral genome is readily detected in leukemic lymphocytes from adult T-cell leukemia patients, viral antigens or viral RNA are not expressed unless these cells are cultured. To address the problem of possible restriction mechanism of HTLV-I replication, we studied the methylation state of provirus in four HTLV-I transformed cell lines. These cell lines are chronically infected with HTLV-I and carry several copies of proviruses but are characterized by different viral expression. Molecular analysis showed that in MT4 cell line, which expresses a low level of viral RNA and proteins, not only are the HTLV-I proviruses heavily methylated but methylation also involves large regions around and within the long terminal repeats. MT4 cells treatment with 5-azacytidine led to an increase in both total viral RNA and p24 gag protein expression. These findings indicate that proviral methylation is responsible for the low viral expression in MT4 cells and also suggest that this phenomenon may be relevant to HTLV-I in vivo latency.


Biodegradation of anionic surfactant, sodium dodecyl sulphate by Pseudomonas aeruginosa MTCC 10311.
The anionic surfactant sodium dodecyl sulphate (SDS), the core components of detergent and cosmetic product formulations, contributes significantly to the pollution profile of sewage and wastewater of all kinds. In this study, 44 SDS degrading strains were isolated by soil enrichment methods and the utilization efficiency was assessed by methylene blue active substances (MBAS) assay and High performance liquid chromatography (HPLC) method. Isolate S2 which showed maximum degradation was identified as Pseudomonas aeruginosa MTCC 10311 based on phenotypic features and 16 S rDNA typing. The isolate was found to harbor plasmid within the size range of 9-10 kb. The cured derivative of SDS degrading Pseudomonas aeruginosa was obtained at a frequency of 10.7% by incubation with ethidium bromide (500 mg ml(-1) at 40 degrees C. 96% of SDS degradation occurred at 1500 ppm level within 48 hr of incubation, whereas higher concentration of SDS (10000 ppm) showed only 20% degradation. The optimum temperature and pH was 30 degrees C and 7.5, respectively. The additional supplementation of carbon and nitrogen source increased the degradation capacity from 93 to 95% and 90 to 96% respectively within 36 hrs of incubation.


Thermodynamical stability of substoichiometric plutonium monocarbide from first-principles calculations.
Plutonium monocarbide, which contains a considerable amount of vacancies in the carbon sublattice, has never been synthesized in a stoichiometric form. The intriguing substoichiometric behavior of plutonium monocarbide is investigated here using first-principles calculations combined with the special quasirandom structure. It is found that the NaCl-type substoichiometric plutonium monocarbide is stable for PuC0.741-0.923, which is in good agreement with the experiment. From the electronic structure calculations and chemical bond analyses, the stabilization of PuC1-x in this range is attributed to strengthened Pu-C bonds opposite the carbon vacancies.


Natural selection and the predictability of evolution in Timema stick insects.
Predicting evolution remains difficult. We studied the evolution of cryptic body coloration and pattern in a stick insect using 25 years of field data, experiments, and genomics. We found that evolution is more difficult to predict when it involves a balance between multiple selective factors and uncertainty in environmental conditions than when it involves feedback loops that cause consistent back-and-forth fluctuations. Specifically, changes in color-morph frequencies are modestly predictable through time (r2 = 0.14) and driven by complex selective regimes and yearly fluctuations in climate. In contrast, temporal changes in pattern-morph frequencies are highly predictable due to negative frequency-dependent selection (r2 = 0.86). For both traits, however, natural selection drives evolution around a dynamic equilibrium, providing some predictability to the process.


Non-IgE-mediated gastrointestinal food allergies.
We focus on recent advances regarding the epidemiology, physiopathology, diagnosis and managements of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs), particularly food protein-induced enterocolitis syndrome (FPIES). The first international FPIES diagnostic and management guidelines have been recently published. Although FPIES largely remains a diagnosis of exclusion, it may be more prevalent than previously thought. Ondansetron has emerged as a major tool for the treatment of FPIES acute reactions. Recent data also suggest an important role for innate immune cells in FPIES pathogenesis. Despite major advances in the diagnosis and management of non-IgE-GI-FAs, particularly FPIES, the lack of specific diagnostic tests and biomarkers to guide clinical management remains challenging.


Fenofibrate effectively reduces remnants, and small dense LDL, and increases HDL particle number in hypertriglyceridemic men - a nuclear magnetic resonance study.
Hypertriglyceridemia is often associated with small dense low density lipoprotein (LDL), elevated remnants, and decreased high density lipoprotein (HDL)-cholesterol (C), which comprise the dyslipidemic triad. The objective of this study was to investigate the effect of fenofibrate on the lipoprotein subfraction profile and inflammation markers in hypertriglyceridemic men. Twenty hypertriglyceridemic men were administered fenofibrate, 200 mg daily, for 8 weeks. Lipoprotein subclasses were measured by nuclear magnetic resonance (NMR) spectroscopy. Inflammation markers including C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were also determined. Fenofibrate lowered triglyceride (TG) by 58% and increased HDL-C by 18%. NMR analysis revealed that very low density lipoprotein (VLDL), particularly large VLDL, intermediate density lipoprotein (IDL), and small LDL, were significantly decreased, and LDL distribution shifted towards the larger particles. HDL distribution was altered; there was an increase in small HDL and a decrease in large HDL, resulting in a significant decrease in HDL particle size, from 9.1 to 8.9 nm, as well as a 27% increase in HDL particle number. Among inflammation markers, CRP was significantly decreased by 42%. In conclusion, fenofibrate effectively improves atherogenic dyslipidemia by reducing remnants and small LDL, as well as by increasing HDL particles. These effects, together with the favorable effect on inflammation, might provide a clinical benefit in hypertriglyceridemic subjects.


Perception and apperception in autism: rejecting the inverse assumption.
In addition to those with savant skills, many individuals with autism spectrum conditions (ASCs) show superior perceptual and attentional skills relative to the general population. These superior skills and savant abilities raise important theoretical questions, including whether they develop as compensations for other underdeveloped cognitive mechanisms, and whether one skill is inversely related to another weakness via a common underlying neurocognitive mechanism. We discuss studies of perception and visual processing that show that this inverse hypothesis rarely holds true. Instead, they suggest that enhanced performance is not always accompanied by a complementary deficit and that there are undeniable difficulties in some aspects of perception that are not related to compensating strengths. Our discussion emphasizes the qualitative differences in perceptual processing revealed in these studies between individuals with and without ASCs. We argue that this research is important not only in furthering our understanding of the nature of the qualitative differences in perceptual processing in ASCs, but can also be used to highlight to society at large the exceptional skills and talent that individuals with ASCs are able to contribute in domains such as engineering, computing and mathematics that are highly valued in industry.


Adolescent pregnancies managed at KK Hospital.
The aim was to analyse the pregnancy outcome among girls, aged 17 and below, at KK Hospital. This is a retrospective study. A total of 108 adolescent pregnancies were analysed with regards to pregnancy order, antenatal complications, mode of delivery and pregnancy outcome. The 2 most common antenatal complications were anaemia and preterm labour. The repeat pregnancy rate was 15.7%. Vaginal delivery was achieved in 7.2%; 21.2% of babies born weighed less than 2.5 kg. Adolescent pregnancies accounted for only a small proportion of all deliveries in our hospital. Late or non-existent antenatal care was a feature in most pregnancies. The incidence of repeat pregnancies reflects the need for a more effective counselling on contraception.


Unique Communication: A Case Report of Acquired Esophageal Pulmonary Fistula.
Esophageal respiratory fistula represents a connection between esophagus and the respiratory system. Esophageal tracheal and esophageal bronchial fistulas are common whereas esophageal pulmonary fistula is rarely seen. We report a case of esophageal pulmonary fistula in a middle aged African American male with a history of bronchoesophageal fistula who presented with pneumonia. The diagnosis was confirmed with fluoroscopy esophagram. Management with endoscopic stent placement was planned however the patient refused treatment. A diagnosis of esophageal pulmonary fistula should be kept in mind for patients with pulmonary symptoms and dysphagia. Early diagnosis and treatment are required to prevent complications and improve quality of life in these patients.


FOXP3 promoter demethylation reveals the committed Treg population in humans.
Naturally occurring thymus derived regulatory T cells (Tregs) are central in the maintenance of self-tolerance. The transcription factor FOXP3 is crucial for the suppressive activity of Tregs and is considered the most specific marker for this population. However, human non regulatory T cells upregulate FOXP3 transiently upon activation which calls for other means to identify the Treg population. Since epigenetic mechanisms are involved in the establishment of stable gene expression patterns during cell differentiation, we hypothesized that the methylation profile of the FOXP3 promoter would allow the distinction of truly committed Tregs. Human CD4(+)CD25(hi) Tregs displayed a demethylated FOXP3 promoter (1.4%+/-0.95% SEM methylated) in contrast to CD4(+)CD25(lo) T cells which were partially methylated (27.9%+/-7.1%). Furthermore, stimulated CD4(+)CD25(lo) T cells transiently expressed FOXP3 but remained partially methylated, suggesting promoter methylation as a mechanism for regulation of stable FOXP3 expression and Treg commitment. In addition, transient FOXP3 expressing cells exhibited suppressive abilities that correlate to the methylation status of the FOXP3 promoter. As an alternative to bisulphite sequencing, we present a restriction enzyme based screening method for the identification of committed Tregs and apply this method to evaluate the effect of various culturing conditions. We show that a partial demethylation occurs in long-term cultures after activation, whereas the addition of TGF-beta and/or IL-10 does not induce any additional change in methylation level. The unique FOXP3 promoter methylation profile in Tregs suggests that a demethylated pattern is a prerequisite for stable FOXP3 expression and suppressive phenotype. Presently, FOXP3 is used to identify Tregs in several human diseases and there are future implications for adoptive Treg transfer in immunotherapy. In these settings there is a need to distinguish true Tregs from transiently FOXP3(+) activated T cells. The screening method we present allows this distinction and enables the identification of cells suitable for in vitro expansions and clinical use.


Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial.
Effective treatment of trauma-induced coagulopathy is important; however, the optimal therapy is still not known. We aimed to compare the efficacy of first-line therapy using fresh frozen plasma (FFP) or coagulation factor concentrates (CFC) for the reversal of trauma-induced coagulopathy, the arising transfusion requirements, and consequently the development of multiple organ failure. This single-centre, parallel-group, open-label, randomised trial was done at the Level 1 Trauma Center in Innsbruck Medical University Hospital (Innsbruck, Austria). Patients with trauma aged 18-80 years, with an Injury Severity Score (ISS) greater than 15, bleeding signs, and plasmatic coagulopathy identified by abnormal fibrin polymerisation or prolonged coagulation time using rotational thromboelastometry (ROTEM) were eligible. Patients with injuries that were judged incompatible with survival, cardiopulmonary resuscitation on the scene, isolated brain injury, burn injury, avalanche injury, or prehospital coagulation therapy other than tranexamic acid were excluded. We used a computer-generated randomisation list, stratification for brain injury and ISS, and closed opaque envelopes to randomly allocate patients to treatment with FFP (15 mL/kg of bodyweight) or CFC (primarily fibrinogen concentrate [50 mg/kg of bodyweight]). Bleeding management began immediately after randomisation and continued until 24 h after admission to the intensive care unit. The primary clinical endpoint was multiple organ failure in the modified intention-to-treat population (excluding patients who discontinued treatment). Reversal of coagulopathy and need for massive transfusions were important secondary efficacy endpoints that were the reason for deciding the continuation or termination of the trial. This trial is registered with ClinicalTrials.gov, number NCT01545635. Between March 3, 2012, and Feb 20, 2016, 100 out of 292 screened patients were included and randomly allocated to FFP (n=48) and CFC (n=52). Six patients (four in the FFP group and two in the CFC group) discontinued treatment because of overlooked exclusion criteria or a major protocol deviation with loss of follow-up. 44 patients in the FFP group and 50 patients in the CFC group were included in the final interim analysis. The study was terminated early for futility and safety reasons because of the high proportion of patients in the FFP group who required rescue therapy compared with those in the CFC group (23 [52%] in the FFP group vs two [4%] in the CFC group; odds ratio [OR] 25·34 [95% CI 5·47-240·03], p<0·0001) and increased needed for massive transfusion (13 [30%] in the FFP group vs six [12%] in the CFC group; OR 3·04 [0·95-10·87], p=0·042) in the FFP group. Multiple organ failure occurred in 29 (66%) patients in the FFP group and in 25 (50%) patients in the CFC group (OR 1·92 [95% CI 0·78-4·86], p=0·15). Our results underline the importance of early and effective fibrinogen supplementation for severe clotting failure in multiple trauma. The available sample size in our study appears sufficient to make some conclusions that first-line CFC is superior to FFP. None.


Cerebral Oxygenation of Premature Lambs Supported by an Artificial Placenta.
An artificial placenta (AP) using venovenous extracorporeal life support (VV-ECLS) could represent a paradigm shift in the treatment of extremely premature infants. However, AP support could potentially alter cerebral oxygen delivery. We assessed cerebral perfusion in fetal lambs on AP support using near-infrared spectroscopy (NIRS) and carotid arterial flow (CAF). Fourteen premature lambs at estimated gestational age (EGA) 130 days (term = 145) underwent cannulation of the right jugular vein and umbilical vein with initiation of VV-ECLS. An ultrasonic flow probe was placed around the right carotid artery (CA), and a NIRS sensor was placed on the scalp. Lambs were not ventilated. CAF, percentage of regional oxygen saturation (rSO2) as measured by NIRS, hemodynamic data, and blood gases were collected at baseline (native placental support) and regularly during AP support. Fetal lambs were maintained on AP support for a mean of 55 ± 27 hours. Baseline rSO2 on native placental support was 40% ± 3%, compared with a mean rSO2 during AP support of 50% ± 11% (p = 0.027). Baseline CAF was 27.4 ± 5.4 ml/kg/min compared with an average CAF of 23.7 ± 7.7 ml/kg/min during AP support. Cerebral fractional tissue oxygen extraction (FTOE) correlated negatively with CAF (r = -0.382; p < 0.001) and mean arterial pressure (r = -0.425; p < 0.001). FTOE weakly correlated with systemic O2 saturation (r = 0.091; p = 0.017). Cerebral oxygenation and blood flow in premature lambs are maintained during support with an AP. Cerebral O2 extraction is inversely related to carotid flow and is weakly correlated with systemic O2 saturation.


Core-Substituted Naphthalenediimides: LUMO Levels Revisited, in Comparison with Preylenediimides with Sulfur Redox Switches in the Core.
Core-substituted naphthalenediimides (NDIs) attract increasing attention to bind, transport, and transform electrons, anions, anionic intermediates, and anionic transition states, and to shine as most colorful rainbow fluorophores. The energy level of their lowest unoccupied molecular orbital (LUMO) is decisive for many of these applications. Here, differential pulse voltammetry (DPV) measurements for a consistent series of NDIs are reported to extract exact LUMO levels under identical conditions. The influence of primary and secondary substituents in the core and on the primary imides is compared with general trends for the reliable prediction of LUMO levels in functional systems. Emphasis is on sulfur redox switches in the NDI core because of their frequent use as isostructural probes for π acidity. The same sulfur redox chemistry is expanded to perylenediimides (PDIs), and LUMO engineering is discussed in a broader context, including also fullerenes, aminonaphthalimides (ANIs), and aminoperyleneimides (APIs). The result is a comprehensive reference table that graphically maps out the LUMO space covered by the leading families of electronaccepting aromatics. This graphical summary of general trends in the π-acidic space is expected to be both inspiring and quite useful in practice.


Influence of urethane and of hydrostatic pressure on the growth of bacteriophages T2, T5, T6, and T7.
In 0.5 per cent NaCl, nutrient broth at 35 degrees C., urethane in a concentration of 0.4 M stops the reproduction of Escherichia coli, strain B. On dilution with 20 volumes of sterile medium, growth is resumed at its former rate after a short lag. In the one-step growth of T2, 15, T6, or T7, in the same medium at the same temperature, 0.4 M urethane, when added at the time of infection, had no apparent effect on adsorption and caused no decrease in titer throughout the latent period of the control, but completely prevented a rise in titer. If diluted 1:20 with sterile medium prior to a certain critical time in the latent period, however, bacteriophage was liberated at the same time, and in the same amount as in the control. The initial stage of apparent insensitivity to the drug lasts from the time of infection until the approximate critical times of 7 minutes with T7, T2, or T6, or 13 minutes with T5. Under the conditions described, the normal latent periods were 14, 23, 30, and 44 minutes for T7, T2, T6, and T5, respectively. At the critical times referred to above, there begins a stage characterized by complete sensitivity, rather than complete insensitivity, to 0.4 M urethane, in the sense that no active phage is subsequently liberated in continued presence of the drug. The length of this completely sensitive stage, as judged by addition of the drug at successive intervals during the latent period, extends from approximately 7 until 9 minutes after infection with T7, 7 until 15 minutes with T2 or T6, or 13 until 25 minutes with T5. When the urethane is added late in this stage of T2, a decrease in initial titer takes place as judged by assays made 40 minutes after infection, the maximum effect occurring when the drug is added between 14 and 15 minutes after infection. When added subsequently to the completely sensitive stage of each type, i.e. subsequently to 9 minutes after infection with T7, 15 minutes with T2 or T6, or 25 minutes with T5, liberation of the bacteriophage takes place in presence of the drug, but the yield is reduced, the amount of reduction being greater the sooner it is added. The yield increases as addition of the drug is delayed, but it is measurably reduced when added late in the rise period. Macroscopic lysis with T7 is delayed by 0.4 M urethane, when present from the time of infection. The delay is less with increased multiplicities of infection. A similar delay occurs with T6r at a multiplicity of 4. The application of hydrostatic pressures of 7,000 to 9,000 p.s.i. early in the latent period, within 5 to 8 minutes after infection, prevents a yield in each of the four phage types, and if maintained for lengthy periods of time a reduction in initial titer occurs. If released at various times shortly after the latent period, a rise in the titer occurred after a certain interval whose length was characteristic of the phage type. The yield was less the longer the release of pressure was delayed. When the pressure was first applied late in the latent period, large amounts of phage were liberated either under pressure or explosively when pressure was released to make the assays. Hydrostatic pressure at 6,000 p.s.i. had little effect on the rate or amount of macroscopic clearing with T7 in relatively high multiplicity of infection, when applied at the start of lysis, but slowed the rate and reduced the amount of clearing when applied shortly after infection.


How chromosomal inversions reorient the evolutionary process.
Inversions are structural mutations that reverse the sequence of a chromosome segment and reduce the effective rate of recombination in the heterozygous state. They play a major role in adaptation, as well as in other evolutionary processes such as speciation. Although inversions have been studied since the 1920s, they remain difficult to investigate because the reduced recombination conferred by them strengthens the effects of drift and hitchhiking, which in turn can obscure signatures of selection. Nonetheless, numerous inversions have been found to be under selection. Given recent advances in population genetic theory and empirical study, here we review how different mechanisms of selection affect the evolution of inversions. A key difference between inversions and other mutations, such as single nucleotide variants, is that the fitness of an inversion may be affected by a larger number of frequently interacting processes. This considerably complicates the analysis of the causes underlying the evolution of inversions. We discuss the extent to which these mechanisms can be disentangled, and by which approach.


Views of health care professionals and policy-makers on the use of surveillance data to combat antimicrobial resistance.
Providing healthcare professionals with health surveillance data aims to support professional and organisational behaviour change. The UK Five Year Antimicrobial Resistance (AMR) Strategy 2013 to 2018 identified better access to and use of surveillance data as a key component. Our aim was to determine the extent to which data on antimicrobial use and resistance met the perceived needs of health care professionals and policy-makers at national, regional and local levels, and how provision could be improved. We conducted 41 semi-structured interviews with national policy makers in the four Devolved Administrations and 71 interviews with health care professionals in six locations across the United Kingdom selected to achieve maximum variation in terms of population and health system characteristics. Transcripts were analysed thematically using a mix of a priori reasoning guided by the main topics in the interview guide together with themes emerging inductively from the data. Views were considered at three levels - primary care, secondary care and national - and in terms of availability of data, current uses, benefits, gaps and potential improvements. Respondents described a range of uses for prescribing and resistance data. The principal gaps identified were prescribing in private practice, internet prescribing and secondary care (where some hospitals did not have electronic prescribing systems). Some respondents under-estimated the range of data available. There was a perception that the responsibility for collecting and analysing data often rests with a few individuals who may lack sufficient time and appropriate skills. There is a need to raise awareness of data availability and the potential value of these data, and to ensure that data systems are more accessible. Any skills gap at local level in how to process and use data needs to be addressed. This requires an identification of the best methods to improve support and education relating to AMR data systems.


Defining the Minimal Clinically Important Difference for Patients With Vestibular Schwannoma: Are all Quality-of-Life Scores Significant?
The diagnosis of vestibular schwannomas (VS) is associated with reduced patient quality of life (QOL). Minimal clinically important difference (MCID) was introduced as the lowest improvement in a patient-reported outcome (PRO) score discerned as significant by the patient. We formerly presented an MCID for the Penn Acoustic Neuroma QOL (PANQOL) battery based on cross-sectional data from 2 tertiary referral centers. To validate the PANQOL MCID values using prospective data. A prospective registry capturing QOL was queried, comprising patients treated at the authors' institution and Acoustic Neuroma Association members. Anchor- and distribution-based techniques were utilized to determine the MCID for domain and total scores. We only included anchors with Spearman's correlation coefficient larger than 0.3 in the MCID threshold calculations. Most domains had multiple anchors with which to estimate the MCID. A total of 1254 patients (mean age: 57.4 yr, 65% females) were analyzed. Anchor-based methods produced a span of MCID values (median, 25th-75th percentile) for each PANQOL domain and the total score: hearing (13.1, 13-16 points), balance (14, 14-19 points), pain (21, 20-28 points), face (25, 16-36 points), energy (16, 15-18 points), anxiety (16 [1 estimate]), general (13 [1 estimate]), and total (12.5, 10-15 points). Current findings corroborate our formerly shared experience using multi-institutional, cross-sectional information. These MCID thresholds can serve as a pertinent outcome when deciphering the clinical magnitude of VS QOL endpoints in cross-sectional and longitudinal studies.


Enzymic, phylogenetic, and structural characterization of the unusual papain-like protease domain of Plasmodium falciparum SERA5.
Serine repeat antigen 5 (SERA5) is an abundant antigen of the human malaria parasite Plasmodium falciparum and is the most strongly expressed member of the nine-gene SERA family. It appears to be essential for the maintenance of the erythrocytic cycle, unlike a number of other members of this family, and has been implicated in parasite egress and/or erythrocyte invasion. All SERA proteins possess a central domain that has homology to papain except in the case of SERA5 (and some other SERAs), where the active site cysteine has been replaced with a serine. To investigate if this domain retains catalytic activity, we expressed, purified, and refolded a recombinant form of the SERA5 enzyme domain. This protein possessed chymotrypsin-like proteolytic activity as it processed substrates downstream of aromatic residues, and its activity was reversed by the serine protease inhibitor 3,4-diisocoumarin. Although all Plasmodium SERA enzyme domain sequences share considerable homology, phylogenetic studies revealed two distinct clusters across the genus, separated according to whether they possess an active site serine or cysteine. All Plasmodia appear to have at least one member of each group. Consistent with separate biological roles for members of these two clusters, molecular modeling studies revealed that SERA5 and SERA6 enzyme domains have dramatically different surface properties, although both have a characteristic papain-like fold, catalytic cleft, and an appropriately positioned catalytic triad. This study provides impetus for the examination of SERA5 as a target for antimalarial drug design.


Design and baseline characteristics of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) study.
Evidence suggests that statin therapy reduces the risk of stroke in patients with coronary heart disease (CHD), but its benefit for patients with cerebrovascular disease and no history of CHD remains uncertain. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study is a prospective, multi-centre, double-blind, randomised, placebo-controlled trial designed to evaluate the effects of atorvastatin 80 mg/day in patients who previously experienced a stroke or transient ischaemic attack, but who have no known CHD. A total of 4732 patients have been enrolled, and the data collection phase of the study is expected to be completed by October 2004. SPARCL is the first study primarily designed to prospectively evaluate the effect of statin treatment in secondary stroke prevention.


Cross-functionality of nitrogenase components NifH1 and VnfH in Anabaena variabilis.
Anabaena variabilis fixes nitrogen under aerobic growth conditions in differentiated cells called heterocysts using either a Mo nitrogenase or a V nitrogenase. The nifH1 gene, which encodes the dinitrogenase reductase of the Mo nitrogenase that is expressed only in heterocysts, is cotranscribed with nifD1 and nifK1, which together encode the Mo dinitrogenase. These genes were expressed in the presence or absence of molybdate or vanadate. The vnfH gene, which encodes the dinitrogenase reductase of the V nitrogenase, was located about 23 kb from vnfDGK, which encodes the V dinitrogenase; however, like vnfDGK, vnfH was expressed only in the absence of molybdate, with or without vanadate. Like nifH1, the vnfH gene was expressed exclusively in heterocysts under either aerobic or anaerobic growth conditions and thus is under the control of developmental factors. The vnfH mutant was able to grow diazotrophically using the V nitrogenase, because NifH1, which was also made in cells starved for molybdate, could substitute for VnfH. Under oxic conditions, the nifH1 mutant grew in the absence of molybdate but not in its presence, using VnfH, while the nifH1 vnfH double mutant did not grow diazotrophically with or without molybdate or vanadate. A nifH1 mutant that expressed nifDK and vnfH but not vnfDGK was able to grow and fix nitrogen normally, indicating that VnfH could substitute for NifH in the Mo nitrogenase and that these dinitrogenase reductases are not involved in determining the metal specificity of the Mo nitrogenase or the V nitrogenase.


Chronic low-dose exposure to imidacloprid potentiates high fat diet-mediated liver steatosis in C57BL/6J male mice.
Hepatic steatosis is known to precede a continuum of events that lead to hepatic metabolic dysfunction, inflammation and carcinogenesis. Recently, studies have linked xenobiotic exposures to hepatic steatogenesis and its associated metabolic disorders; however, the underlying mechanisms remain elusive. This study aimed to elucidate the mechanistic role of imidacloprid in the prevalence of high fat diet (HFD)-induced liver steatosis, using a C57BL/6J mice model. Mice (3 weeks old) were fed with HFD and treated with 0.6 mg/kg bw/day (one-tenth of the NOAEL) of imidacloprid through water or diet, for 24 weeks. In a controlled group, mice were fed with only HFD. At the end of the study, imidacloprid treatment significantly potentiated HFD-induced body weight gain in mice. Also, imidacloprid increased the liver weights of mice, with complimentary reductions in mesenteric and gonadal white adipose tissue weights. Histopathological analysis of liver revealed a drastic steatosis in imidacloprid treated mice. Following a real-time qPCR analysis, imidacloprid upregulated transcriptions of hepatic fatty acid biosynthesis-related transcription factors and genes. Imidacloprid also induced hepatic expression of the gene encoding pregnane X receptor; but had no significant effect on hepatic expressions of liver X receptor and aryl hydrocarbon receptor. The imidacloprid treatment further enhanced serum alanine aminotransferase levels but downregulated hepatic antioxidant mRNA expressions. Ultimately, this study suggested an imidacloprid-potentiation effects on prevalence of HFD-induced liver steatosis via transcriptional modulations of the hepatic FA biosynthesis pathway.


Levothyroxine supplementation in hypothyroid bitches during pregnancy.
Hypothyroidism is the most common endocrine disease in dogs and has been shown to have a hereditary nature in many breeds. Previous studies have documented decreased fertility in bitches with experimentally-induced hypothyroidism, decreased viability at birth, increased periparturient mortality, and reduced birth weight in pups born to hypothyroid dogs. Hypothyroid women have an increased demand for exogenous thyroxine throughout gestation in order to maintain normal plasma concentrations of thyroid hormones and produce neuropsychologically normal children. This study was performed to determine if pregnancy causes a similar need for increased levothyroxine dosages in dogs to maintain a euthyroid state. Serum was harvested from blood collected from six bitches with experimentally-induced hypothyroidism that were receiving standard thyroid hormone replacement therapy and from four euthyroid control bitches. Thyroid function tests performed on these samples included total thyroxine (T4), free T4 (fT4), thyroid stimulating hormone (TSH), and 3,5,3'-triiodothyronine (T3). Thyroid function tests were measured from ovulation through the end of pregnancy. All bitches whelped normal litters. Euthyroid bitches had no significant alterations in their hormone concentrations throughout pregnancy. None of the supplemented hypothyroid bitches had clinical signs of hypothyroidism throughout the study. Serum concentrations of T4 and fT4 were elevated compared to ovulation at multiple sample points during gestation in supplemented dogs. The results from this study indicate that standard levothyroxine supplementation is adequate to maintain a euthyroid state during pregnancy in experimentally-induced hypothyroid dogs. In addition, there is no evidence that canine thyroid profiles in euthyroid dogs are altered during gestation.


BCL10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma.
BCL10 is an apoptotic regulatory molecule identified through its direct involvement in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. We examined BCL10 protein expression in various normal tissues and B-cell lymphomas by immunohistochemistry of formalin-fixed and paraffin-embedded tissues using mouse BCL10 monoclonal antibodies. BCL10 protein was expressed in lymphoid tissue but not in 21 various other tissues with the exception of breast. In normal B-cell follicles, the protein was expressed abundantly in the germinal center B cells, moderately in the marginal zone, but only weakly in the mantle zone B cells. Irrespective of their stage of B-cell maturation, BCL10 was predominantly expressed in the cytoplasm. In contrast, each of the four MALT lymphomas with t(1;14)(p22;q32) showed strong BCL10 expression in both the nucleus and cytoplasm. Twenty of 36 (55%) MALT lymphomas lacking the translocation exhibited BCL10 expression in both the nucleus and cytoplasm although at a much lower level, whereas the remaining 16 cases displayed only cytoplasmic BCL10. Unlike MALT lymphoma, both follicular and mantle cell lymphomas generally displayed BCL10 expression compatible to their normal cell counterparts. Our results show differential expression of BCL10 protein among various B-cell populations of the B-cell follicle, indicating its importance in B-cell maturation. The subcellular localization of BCL10 was frequently altered in MALT lymphoma in comparison with its normal cell counterparts, suggesting that ectopic BCL10 expression may be important in the development of this type of tumor.


Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway.
Low concentrations of As(2)O(3) (</=1 micromol/L) induce long-lasting remission in patients with acute promyelocytic leukemia (APL) without significant myelosuppressive side effects. Several groups, including ours, have shown that 0.5 to 1 micromol/L As(2)O(3) induces apoptosis in APL-derived NB4 cells, whereas other leukemic cells are resistant to As(2)O(3) or undergo apoptosis only in response to greater than 2 micromol/L As(2)O(3). In this report, we show that the ability of As(2)O(3) to induce apoptosis in leukemic cells is dependent on the activity of the enzymes that regulate cellular H(2)O(2) content. Thus, NB4 cells have relatively low levels of glutathione peroxidase (GPx) and catalase and have a constitutively higher H(2)O(2) content than U937 monocytic leukemia cells. Glutathione-S-transferase pi (GSTpi), which is important for cellular efflux of As(2)O(3), is also low in NB4 cells. Moreover, As(2)O(3) further inhibits GPX activity and increases cellular H(2)O(2) content in NB4 but not in U937 cells. Selenite pretreatment of NB4 cells increases the activity of GPX, lowers cellular H(2)O(2) levels, and renders NB4 cells resistant to 1 micromol/L As(2)O(3). In contrast, concentrations of As(2)O(3) that alone are not capable of inducing apoptosis in NB4 cells induce apoptosis in the presence of the GPx inhibitor mercaptosuccinic acid. Similar effects are observed by modulating the activity of catalase with its inhibitor, aminotriazol. More important from a therapeutic point of view, U937 and HL-60 cells, which require high concentrations of As(2)O(3) to undergo apoptosis, become sensitive to low, clinically acceptable concentrations of As(2)O(3) when cotreated with these GPx and catalase inhibitors. The induction of apoptosis by As(2)O(3) involves an early decrease in cellular mitochondrial membrane potential and increase in H(2)O(2) content, followed by cytochrome c release, caspase 3 activation, DNA fragmentation, and the classic morphologic changes of apoptosis.


Homologated aza analogs of arabinose as antimycobacterial agents.
A series of hydrolytically-stable aza analogs of arabinofuranose was prepared and evaluated against Mycobacterium tuberculosis and M. avium. The compounds were designed to mimic the putative arabinose donor involved in biogenesis of the essential cell wall polysaccharide, arabinogalactan. Though most compounds displayed little activity in cell culture, one compound showed significant activity in infected macrophage models.


Japanese encephalitis vaccine (inactivated, BIKEN) in U.S. soldiers: immunogenicity and safety of vaccine administered in two dosing regimens.
The safety and immunogenicity of Japanese encephalitis (JE) vaccine (Nakayama strain, monovalent / BIKEN) was studied in 538 U.S. soldiers in 1990. Three doses of vaccine from three consecutively manufactured lots were given on days 0, 7, and either 14 or 30. Serum for antibody determination was drawn at months 0, 2, and 6. Japanese encephalitis plaque reduction neutralization tests were performed by three laboratories on each specimen. Five hundred twenty-eight (98%) participants completed the immunization series. All recipients without antibody before immunization developed neutralizing antibody against JE virus. There were no differences in geometric mean titer among the three test lots at months 2 and 6. Soldiers who received the third dose on day 30 had higher titers at both time points. Antibody to yellow fever had no significant effect on immune response to vaccine. Conclusions drawn from analysis of serologic data from the three labs were nearly identical. Symptoms were generally limited to mild local effects and were reduced in frequency with each subsequent does in the series (21% to 11%; P < 0.0001). Generalized symptoms were rare (e.g., fever = 5%) with no reported cases of anaphylaxis.


Challenges in mass drug administration for treating lymphatic filariasis in Papua, Indonesia.
The World Health Organization (WHO) Global Program to Eliminate Lymphatic Filariasis relies on mass drug administration (MDA) of two drugs annually for 4 to 6 years. The goal is to reduce the reservoir of microfilariae in the blood to a level insufficient to maintain transmission by the mosquito vector. In 2008, the international medical aid organization Médecins Sans Frontières (MSF) performed the first round of a MDA in the high-burden area of Asmat district, in Papua, Indonesia. We report the challenges faced in this MDA on a remote Indonesian island and propose solutions to overcome these hurdles in similar future contexts. During the MDA, we encountered difficult challenges in accessing as well as persuading the patient population to take the antifilarial drugs. Health promotion activities supporting treatment need to be adapted and repetitive, with adequate time and resources allocated for accessing and communicating with local, seminomadic populations. Distribution of bednets resulted in an increase in MDA coverage, but it was still below the 80-85% target. MDA for lymphatic filariasis is how the WHO has planned to eliminate the disease from endemic areas. Our programmatic experience will hopefully help inform future campaign planning in difficult-to-access, high-burden areas of the world to achieve target MDA coverage for elimination of lymphatic filariasis.


Engineering of functional replication protein a homologs based on insights into the evolution of oligonucleotide/oligosaccharide-binding folds.
The bacterial single-stranded DNA-binding protein (SSB) and the archaeal/eukaryotic functional homolog, replication protein A (RPA), are essential for most aspects of DNA metabolism. Structural analyses of the architecture of SSB and RPA suggest that they are composed of different combinations of a module called the oligonucleotide/oligosaccharide-binding (OB) fold. Members of the domains Bacteria and Eukarya, in general, contain one type of SSB or RPA. In contrast, organisms in the archaeal domain have different RPAs made up of different organizations of OB folds. Interestingly, the euryarchaeon Methanosarcina acetivorans harbors multiple functional RPAs named MacRPA1 (for M. acetivorans RPA 1), MacRPA2, and MacRPA3. Comparison of MacRPA1 with related proteins in the publicly available databases suggested that intramolecular homologous recombination might play an important role in generating some of the diversity of OB folds in archaeal cells. On the basis of this information, from a four-OB-fold-containing RPA, we engineered chimeric modules to create three-OB-fold-containing RPAs to mimic a novel form of RPA found in Methanococcoides burtonii and Methanosaeta thermophila. We further created two RPAs that mimicked the RPAs in Methanocaldococcus jannaschii and Methanothermobacter thermautotrophicus through fusions of modules from MacRPA1 and M. thermautotrophicus RPA. Functional studies of these engineered proteins suggested that fusion and shuffling of OB folds can lead to well-folded polypeptides with most of the known properties of SSB and RPAs. On the basis of these results, different models that attempt to explain how intramolecular and intermolecular homologous recombination can generate novel forms of SSB or RPAs are proposed.


Identification of Kiwellin-like Proteins in Fruits by Using In Silico Tools.
Identification of allergen proteins by using wet-lab technology is a time-consuming and also costly process. In recent years, thanks to the developments in the field of bioinformatics, it is now possible to estimate the allergen proteins by using in silico tools. In the present study, it is aimed to find kiwellin-like proteins from different fruits samples by using bioinformatics tools. According to the results of the study, six proteins from Corchorus olitorius, Cucumis sativus, Capsicum chinense, Carica papaya, Morus notabilis and Jatropha curcas were defined as the allergens. In conclusion, in silico tools developed under the field of bioinformatics can provide a big contribution to the estimation of unknown allergen proteins in different fruits. Based on the in silico results, physicians can suggest people who have allergenicity to kiwellin not to consume the fruits that contain kiwellin-like proteins.


Pentagonal Bipyramidal Ln(III) Complexes Containing an Axial Phosphine Oxide Ligand: Field-induced Single-ion Magnetism Behavior of the Dy(III) Analogues.
A series of neutral homologous complexes [(L)Ln(Cy3PO)Cl] {where Ln = Gd (1), Tb (2), Dy (3), and Er (5)} and [(L)Dy(Ph3PO)Cl] (4) [H2L = 2,6-diacetylpyridine bis-benzoylhydrazone] were isolated. In these complexes, the central lanthanide ion possesses a pentagonal bipyramidal geometry with an overall pseudo D5h symmetry. The coordination environment around the lanthanide ion comprises of three nitrogen and two oxygen donors in an equatorial plane. The axial positions are taken up by a phosphine oxide (O donor) and a chloride ion. Among these compounds, the Dy(III) (3 and 4) analogues were found to be field-induced single-ion magnets.


Iridium Clusters Encapsulated in Carbon Nanospheres as Nanocatalysts for Methylation of (Bio)Alcohols.
C-H methylation is an attractive chemical transformation for C-C bonds construction in organic chemistry, yet efficient methylation of readily available (bio)alcohols in water using methanol as sustainable C1 feedstock is limited. Herein, iridium nanocatalysts encapsulated in yolk-shell-structured mesoporous carbon nanospheres (Ir@YSMCNs) were synthesized for this transformation. Monodispersed Ir clusters (ca. 1.0 nm) were encapsulated in situ and spatially isolated within YSMCNs by a silica-assisted sol-gel emulsion strategy. A selection of (bio)alcohols (19 examples) was selectively methylated in aqueous phase with good-to-high yields over the developed Ir@YSMCNs. The improved catalytic efficiencies in terms of activity and selectivity together with the good stability and recyclability were contributable to the ultrasmall Ir clusters with oxidation chemical state as a consequence of the confinement effect of YSMCNs with interconnected nanostructures.


Haematology and erythrocyte metabolism in man at high altitude: an Aymara-Quechua comparison.
In the course of haematological and biological investigations among Aymara and Quechua populations in Bolivia, an anthropological study of the erythrocytary respiratory function was carried out on the two groups at two altitudes: 3,600 m and 450 m. A difference in the intensity of the biological variations of the two populations is observed at high altitude. In the Quechuas, as in any lowland native, the adaptative phenomena are totally and quickly reversible. In the Aymaras, we detected the existence of more marked haematological and biochemical characters: moderate polycythemia, hyperhaemoglobinemia, microcytosis, metabolical hyperactivity with accumulation of 2-3 di-phosphoglycerate and ATP, and methaemoglobinemia with a drop in the activity of the methaemoglobin reductases. The Aymaras preserve some of those characters (methaemoglobinemia excepted) when they settle in lowlands.


Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth.
AML is a heterogenous disease caused by different mutations. We have previously shown that each mutational sub-type develops its specific gene regulatory network (GRN) with transcription factors interacting with multiple gene modules, many of which are transcription factor genes themselves. Here we hypothesized that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We tested this hypothesis using FLT3-ITD mutated AML as a model and conducted an shRNA drop-out screen informed by this analysis. We show that AML-specific GRNs predict identifying crucial regulatory modules required for AML but not normal cellular growth. Furthermore, our work shows that all modules are highly connected and regulate each other. The careful multi-omic analysis of the role of one (RUNX1) module by shRNA and chemical inhibition shows that this transcription factor and its target genes stabilize the GRN of FLT3-ITD AML and that its removal leads to GRN collapse and cell death.


Improving Tongue Command Accuracy: Unlocking the Power of Electrotactile Feedback Training.
People with spinal cord injury or neurological disorders frequently require aid in performing daily tasks. Utilizing hand-free assistive technologies (ATs), particularly tongue-controlled ATs, may offer a feasible solution as the tongue is controlled by a cranial nerve and remains functional in the presence of spinal cord injury. However, existing intra-oral ATs require a significant level of training to accurately issuing these commands. To minimize the training process, we have designed intuitive tongue commands for our Multifunctional intraORal Assistive technology (MORA). Our prior works demonstrated that electrotactile feedback outperformed visual feedback in tasks involving tongue motor learning. In this study, we implement electrical stimulation (E-stim) as electrotactile feedback on the tongue to teach new tongue commands of MORA, and quantitatively analyze the efficacy of the electrotactile feedback in command accuracy and precision. The random command task was adopted to evaluate tongue command accuracy with 14 healthy participants. The average sensors contacted per trial dropped significantly from 1.57 ± 0.15 to 1.16 ± 0.05 with electrotactile feedback. After training with electrotactile feedback, 83% of the trials were completed with only one command having been activated. These results suggest that E-stim enhanced both the accuracy and precision of subjects' tongue command training. The results of this study pave the way for the implementation of electrotactile feedback as an accurate and precise command training technique for MORA.


[Genetico-demographic characteristics of the population from three districts of the Bryansk region].
Results of genetic demographic investigation of three nations located in west Bryanskaya oblast (Klintsovskii, Klimovskii, and Starodubskii nations) are presented. A comparison is made with respect to a number of demographic parameters of "southern" (Krasnodar) and "northern" (Kirov) Russian populations. A low level of the Crow index, which is associated with a differential mortality rate, Im = 0.07, was established in the population studied. This fact significantly distinguishes the population of Bryanskaya oblast from other studied Russian populations. With respect to sex and age structure and the Crow index, the Bryansk population is comparable to the southern Krasnodar population, while in terms of level of isolation and inbreeding, the Bryansk population is similar to the northern Kirov population. Moreover, it was found that the Chernobyl meltdown in 1986 did not lead to any change in the genetic demographic situation in the three studied nations.


Regulation of macrophage function by adenosine.
Following its release into the extracellular space in response to metabolic disturbances, the endogenous nucleoside adenosine exerts a range of immunomodulatory effects and cells of the mononuclear phagocyte system are among its major targets. Adenosine governs mononuclear phagocyte functions via 4 G-protein-coupled cell membrane receptors, which are denoted A(1), A(2A), A(2B), and A(3) receptors. Adenosine promotes osteoclast differentiation via A(1) receptors and alters monocyte to dendritic cell differentiation through A(2B) receptors. Adenosine downregulates classical macrophage activation mainly through A(2A) receptors. In contrast A(2B) receptor activation upregulates alternative macrophage activation. Adenosine promotes angiogenesis, which is mediated by inducing the production of vascular endothelial growth factor by mononuclear phagocytes through A(2A), A(2B), and A(3) receptors. By regulating mononuclear phagocyte function adenosine dictates the course of inflammatory and vascular diseases and cancer.


Fetal Cardiodynamics by Echocardiography in Insulin Dependent Maternal Diabetes and Its Correlation with Pregnancy Outcome.
Maternal diabetes mellitus is associated with an increased risk of fetal and neonatal morbidity and mortality. Usual screening tests have not proved to be good prognostic indicators of fetal distress. Fetal cardiodynamics is potentially a useful screening tool. To determine if cardiodynamics of the fetus differ in pregnancy with diabetes requiring insulin than those without and to determine whether cardiodynamics predict fetal and neonatal outcomes. This prospective case control study was carried out in 40 pregnant women with diabetes who required insulin for blood sugar control. Twenty uncomplicated pregnant women were taken as controls. Systolic and diastolic cardiac functions along with interventricular septal thickness were assessed at 26-28 weeks and again at 34-36 weeks of gestation in fetuses by echocardiography. Fetal and neonatal adverse outcomes were evaluated in terms of major and minor morbidity. Among all parameters, E/A ratio across both mitral and tricuspid valves, myocardial performance index and cardiac output were significantly different in fetuses of diabetic mothers at both gestations. However, pulmonary vein pulsatility index and interventricular septal thickness were similar between the two groups. At 26-28 weeks of gestation myocardial performance index correlated with abnormal biophysical profile whereas cardiac output correlated with minor morbidity. At 34-36 weeks of gestation, cardiac output correlated with abnormal biophysical profile while both MPI and cardiac output correlated with minor morbidity. Echocardiographic parameters of fetuses of diabetic women significantly differed from those of uncomplicated non-diabetic women. However, only myocardial performance index and cardiac output correlated with adverse fetal and neonatal outcomes.


Polymorphism at the self-incompatibility locus in Solanaceae predates speciation.
Sequences of 11 alleles of the gametophytic self-incompatibility locus (S locus) from three species of the Solanaceae family have recently been determined. Pairwise comparisons of these alleles reveal two unexpected observations: (i) amino acid sequence similarity can be as low as 40% within species and (ii) some interspecific similarities are higher than intraspecific similarities. The gene genealogy clearly illustrates this unusual pattern of relationships. The data suggest that some of the polymorphism at the S locus existed prior to the divergence of these species and has been maintained to the present. In support of this hypothesis, the number of shared polymorphic sites was found to exceed the number found in simulations with independent accumulation of mutations. Strictly neutral evolution is exceedingly unlikely to maintain the polymorphism for such a long time. The allele multiplicity and extreme age of the alleles is consistent with Wright's classic one-locus population genetic model of gametophytic self-incompatibility. Similarities between the plant S locus and the mammalian major histocompatibility complex are discussed.


Serum metabolome responses induced by long-term inoculation of suspended PM2.5 in chicken.
The adverse effects of exposure to fine particulate matter (PM2.5) on body health have attracted global public attention. However, there is limited research on PM2.5 in animal houses. Numerous studies have indicated that long-term exposure to high levels of PM2.5 can cause damage to multiple systems in animals. Poultry houses are one of the primary sources of PM2.5 emissions. However, there is limited research on the effects of PM2.5 exposure on poultry organisms. This study analyzed the histopathological changes in the lung tissue of poultry under PM2.5 exposure conditions. It used the LC-MS method to analyze the alterations in the serum metabolomic profile of poultry. This study confirmed that long-term exposure to high levels of PM2.5 had significantly reduced the growth performance of poultry. Histopathological slides of the lung tissue in chickens exposed to long-term retention of PM2.5 clearly showed significant damage. Furthermore, the serum metabolome analysis revealed significant changes in the serum metabolic profile of chickens exposed to long-term PM2.5 exposure. Specifically, there were notable alterations in the Glycerophospholipid metabolism, Steroid hormone biosynthesis, and Phenylalanine, tyrosine, and tryptophan biosynthesis pathways.


Food preparation with mucoralean fungi: A potential biosafety issue?
Mucorales have been used for production of fermented food in Asia and Africa since time immemorial. Particularly Rhizopus species are rapidly growing, active producers of lipases and proteases and occur naturally during the first stages of soybean fermentation. Two biosafety issues have been raised in recent literature: (1) pathogenicity, Rhizopus species being prevalent opportunists causing erosive infections in severely compromised patients, and (2) toxicity, strains harbouring endosymbiotic Burkholderia producing toxic secondary metabolites. At the molecular level, based on different gene markers, species identity was found between strains used for food processing and clinical strains. In this study, we screened for bacterial symbionts in 64 Rhizopus strains by light microscopy, 16S rRNA sequencing, and HPLC. Seven strains (11 %) carried bacteria identified as Burkholderia rhizoxinica and Burkholderia endofungorum, and an unknown Burkholderia species. The Burkholderia isolates proved to be able to produce toxic rhizoxins. Strains with endosymbionts originated from food, soil, and a clinical source, and thus their presence could not be linked to particular habitats. The presence of Burkholderia in Rhizopus producing toxins could not be excluded as a potential risk for human health. In contrast, given the type of diseases caused by Rhizopus species, we regard the practical risk of infection via the food industry as negligible.


Automated description of the mandible shape by deep learning.
The shape of the mandible has been analyzed in a variety of fields, whether to diagnose conditions like osteoporosis or osteomyelitis, in forensics, to estimate biological information such as age, gender, and race or in orthognathic surgery. Although the methods employed produce encouraging results, most rely on the dry bone analyses or complex imaging techniques that, ultimately, hamper sample collection and, as a consequence, the development of large-scale studies. Thus, we proposed an objective, repeatable, and fully automatic approach to provide a quantitative description of the mandible in orthopantomographies (OPGs). We proposed the use of a deep convolutional neural network (CNN) to localize a set of landmarks of the mandible contour automatically from OPGs. Furthermore, we detailed four different descriptors for the mandible shape to be used for a variety of purposes. This includes a set of linear distances and angles calculated from eight anatomical landmarks of the mandible, the centroid size, the shape variations from the mean shape, and a group of shape parameters extracted with a point distribution model. The fully automatic digitization of the mandible contour was very accurate, with a mean point to the curve error of 0.21 mm and a standard deviation comparable to that of a trained expert. The combination of the CNN and the four shape descriptors was validated in the well-known problems of forensic sex and age estimation, obtaining 87.8% of accuracy and a mean absolute error of 1.57 years, respectively. The methodology proposed, including the shape model, can be valuable in any field that requires a quantitative description of the mandible shape and a visual representation of its changes such as clinical practice, surgery management, dental research, or legal medicine.


Photoinduced reduction of the medial FeS center in the hydrogenase small subunit HupS from Nostoc punctiforme.
The small subunit from the NiFe uptake hydrogenase, HupSL, in the cyanobacterium Nostoc punctiforme ATCC 29133, has been isolated in the absence of the large subunit (P. Raleiras, P. Kellers, P. Lindblad, S. Styring, A. Magnuson, J. Biol. Chem. 288 (2013) 18,345-18,352). Here, we have used flash photolysis to reduce the iron-sulfur clusters in the isolated small subunit, HupS. We used ascorbate as electron donor to the photogenerated excited state of Ru(II)-trisbipyridine (Ru(bpy)3), to generate Ru(I)(bpy)3 as reducing agent. Our results show that the isolated small subunit can be reduced by the Ru(I)(bpy)3 generated through flash photolysis.


Troponin T for the detection of dialysis-induced myocardial stunning in hemodialysis patients.
Circulating troponin T levels are frequently elevated in patients undergoing long-term dialysis. The pathophysiology underlying these elevations is controversial. In 70 prevalent hemodialysis (HD) patients, HD-induced myocardial stunning was assessed echocardiographically at baseline and after 12 months. Nineteen patients were not available for the follow-up analysis. The extent to which predialysis troponin T was associated with the occurrence of HD-induced myocardial stunning was assessed as the primary endpoint. The median troponin T level in this hemodialysis cohort was 0.06 ng/ml (interquartile range, 0.02-0.10). At baseline, 64% of patients experienced myocardial stunning. These patients showed significantly higher troponin T levels than patients without stunning (0.08 ng/ml [0.05-0.12] versus 0.02 ng/ml [0.01-0.05]). Troponin T levels were significantly correlated to measures of myocardial stunning severity (number of affected segments: r=0.42; change in ejection fraction from beginning of dialysis to end of dialysis: r=-0.45). In receiver-operating characteristic analyses, predialytic troponin T achieved an area under the curve of 0.82 for the detection of myocardial stunning. In multivariable analysis, only ultrafiltration volume (odds ratio, 4.38 for every additional liter) and troponin T (odds ratio, 9.33 for every additional 0.1 ng/ml) were independently associated with myocardial stunning. After 12 months, nine patients had newly developed myocardial stunning and showed a significant increase in troponin T over baseline (0.03 ng/ml at baseline versus 0.05 ng/ml at year 1). Troponin T levels in HD patients are associated with the presence and severity of HD-induced myocardial stunning.


Genital human papillomavirus lesions of the male sexual partners: the diagnostic accuracy of peniscopy.
To evaluate the accuracy of peniscopy for identifying human papillomavirus (HPV) lesions in male sexual partners of women with HPV infection. The predictive value of the medical history for HPV infection was also evaluated. Examination of voluntary male partners of the women with HPV infection using colposcopy (peniscopy after acetic acid), cytology and surgical biopsy, the latter being analysed by light microscopy, in situ hybridisation (ISH) and polymerase chain reaction (PCR) for HPV DNA. A detailed medical history was to be taken, too. Department of Gynaecology and Obstetrics, Kuopio University Central Hospital, Finland. A series of 101 voluntary male partners of 101 women invited for examination, treatment and follow-up for their genital HPV infections on the basis of abnormal Papanicolaou (PAP) smears. On peniscopy 64 (63.4%) of the men presented with lesions either typical of (34.7%) or suspicious for (28.7%) HPV infection. Of the latter, 89% were flat lesions mostly undetectable by the naked eye. The cytologic smear was positive in only nine men. On light microscope, 85.7% of the peniscopically typical lesions were found to be consistent with (68.6%) or suspicious for (17.1%) HPV infection. HPV DNA was found in 33 (34.5%) of the 96 typed biopsies, and never in biopsies from peniscopically healthy areas. In logistic regression analysis of the historical data recorded, only the contact time with the current sexual partner was of predictive value for histologically proven HPV infection. Peniscopy is an applicable means for the identification of penile lesions due to HPV infection, but it is not a conclusive diagnostic tool capable of differentiating HPV from non-HPV findings.


Nursing First: Promoting Academic and Professional Success Through a Seamless Transition Program for Registered Nurses to Baccalaureate Students.
The Nursing First Program was established to provide students in an associate of science in nursing program at a downstate New York community college a seamless transition into the registered nurse to baccalaureate program of a nearby university while promoting academic performance and professional excellence. Selected students attend mandatory seminars designed to provide academic support and a sense of camaraderie, with the aim of ensuring success in both programs. Initial outcomes indicate that the program inspired participants to reach their highest potential, academically and professionally. Nursing First scholars have excelled as newly employed registered nurses and as students in the university program.


Long-term follow-up of argon laser trabeculoplasty for uncontrolled open-angle glaucoma.
Between May 1978 and October 1981, 82 phakic eyes in 72 patients with uncontrolled open-angle glaucoma underwent 360 degrees argon laser trabeculoplasty. Continued long-term follow-up has shown a decreasing pressure-lowering effect. The peak pressure lowering was 9.7 mm Hg at two months, 7.3 mm Hg at two years, 6.8 mm Hg at four years, and 4.9 mm Hg at five years. In 1982, we reported a 77% success rate, but, after five years of observation, the success rate is 46%. However, our clinical population is unique in that the majority of our patients (57%) are black. The most important factor in the long-term success rate appears to be race. Only 32% of cases involving black patients were successful, while 65% of cases involving white patients were successful. A Kaplan-Meier survival curve analysis revealed that the median time to an intraocular pressure greater than 21 mm Hg was 12 months for black patients and 60 months for white patients.


Animal models of inhibin action.
The physiology of inhibin has been investigated using rodent and ruminant animal models in both in vitro and in vivo studies. Inhibin was originally defined as a substance that causes selective suppression of follicle-stimulating hormone (FSH) secretion by pituitary gonadotropes. Although this definition is still valid, it fails to encompass the breadth of inhibin's actions. In addition to its endocrine action on pituitary FSH secretion, inhibin has a local paracrine action in its target tissues. The inhibin alpha subunit appears to play an important role in determining whether inhibin or activin is produced in cells. More recently, transgenic and knockout mouse models have highlighted the importance of inhibin for fertility and the inhibin alpha subunit for tumor suppression. Whether inhibin exerts its effects by a direct action on the gonad or by regulating FSH secretion, it is clear that inhibin is essential for normal reproductive function. In this article, we review the rodent and ruminant models employed to investigate inhibin physiology and examine the potential of inhibin-based vaccines to enhance gonadal function.


Sleep Problems in Pediatric Disorders of Gut-Brain Interaction: A Systematic Review.
Disorders of gut-brain interaction (DGBIs) are common, and findings are mixed on rates of sleep problems (e.g., sleep quality) in pediatric populations. A clear understanding of sleep problems in pediatric DGBIs is needed as sleep challenges might negatively impact symptoms and prognoses. The aims of this systematic review are to (1) describe the prevalence and types of sleep problems in pediatric patients with DGBIs and examine differences by DGBI diagnosis and (2) examine the relationship among sleep problems and pain, mood, and functional outcomes in pediatric patients with DGBIs. We searched PubMed, PsycInfo, CINAHL, and Medline in June 2022; articles were included if they enrolled ≤19 years old with a DGBI, used a quantitative assessment of sleep problems, and were available in English. The Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies was used to assess study quality. We used a protocol to systematically pull and tabulate data across articles with quality assessment ratings. Twenty-four articles with 110,864 participants across 9 countries were included, with most studies being of moderate to weak quality. Patients with DGBIs reported more sleep problems than healthy peers, and some research reviewed found that patients with IBS had more sleep problems than other DGBI diagnoses. Sleep problems in DGBIs were related to worse mood, pain, and functional outcomes. Pediatric patients with DGBIs are experiencing sleep problems that can impact outcomes. Screening for sleep problems and targeted treatment is needed to best support these patients.


Mental and behavioral effects of brain stem and hypothalamic stimulation in man.
Electrical stimulation of deep brain regions in man yields specific and reproducible physiological and behavioral effects. Stimulation of the rostral midbrain in the dorsal and periaqueductal regions results in a variety of effects such as somatosensory, ocular, emotional, and vasomotor responses. These responses are somatotopically organized in the dorsal midbrain suggesting this region is of great importance to humans' experience of pain and suffering.