RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals.
DNA Topoisomerases are essential to resolve topological problems during DNA metabolism in all species. However, the prevalence and function of RNA topoisomerases remain uncertain. Here, we show that RNA topoisomerase activity is prevalent in Type IA topoisomerases from bacteria, archaea, and eukarya. Moreover, this activity always requires the conserved Type IA core domains and the same catalytic residue used in DNA topoisomerase reaction; however, it does not absolutely require the non-conserved carboxyl-terminal domain (CTD), which is necessary for relaxation reactions of supercoiled DNA. The RNA topoisomerase activity of human Top3β differs from that of Escherichia coli topoisomerase I in that the former but not the latter requires the CTD, indicating that topoisomerases have developed distinct mechanisms during evolution to catalyze RNA topoisomerase reactions. Notably, Top3β proteins from several animals associate with polyribosomes, which are units of mRNA translation, whereas the Top3 homologs from E. coli and yeast lack the association. The Top3β-polyribosome association requires TDRD3, which directly interacts with Top3β and is present in animals but not bacteria or yeast. We propose that RNA topoisomerases arose in the early RNA world, and that they are retained through all domains of DNA-based life, where they mediate mRNA translation as part of polyribosomes in animals.


Description of a new Pavlovskyella species (Acari: Argasidae) from Chile.
Soft ticks (Argasidae) of the Pavlovskyella Pospelova-Shtrom subgenus are important vectors of relapsing fever spirochetes, which are agents of disease globally. South American representatives of the Pavlovskyella subgenus include 3 species: Ornithodoros (Pavlovskyella) brasiliensis Aragão, Ornithodoros (Pavlovskyella) furcosus Neumann, and Ornithodoros (Pavlovskyella) rostratus Aragão. Here, we describe a fourth species based on morphological and mitogenomic evidence of ticks collected in burrows of unknown hosts in central Chile. The larva of the new species separates from other South American soft ticks by the following combination of characters: 13 pairs of dorsolateral setae, dorsal plate hexagonal, hypostome blunt with denticles from apex almost to the base. Adults of this new species lack cheeks, possess a dorsoventral groove, and have humps, similar to O. (P.) brasiliensis; however, they lack bulging structures on the flanks of idiosoma. Moreover, females and males differ from O. (P.) rostratus by having 3 humps instead of spurs in tarsi I and from O. (P.) furcosus because of their smaller size and thinner anterior lip of the genital aperture in females. The phylogenetic analysis performed with mitogenomes of the Argasidae family depicts the new Pavlovskyella species from Chile in a monophyletic clade with other South American species in the subgenus, confirming a regional group.


Health implications of body piercing and tattooing: a literature review.
Tattooing and body piercing have become increasingly popular in recent years, particularly among young adults and adolescents. Montgomery and Parks (2001) say tattoos represent attributes such as individualism, risk, sexual fantasies and uniqueness, which are important for adolescents attempting to prove their individuality.


Low-level laser treatment with near-infrared light increases venous nitric oxide levels acutely: a single-blind, randomized clinical trial of efficacy.
The use of near-infrared light in the form of low-level laser therapy (LLLT) has become more popular in the treatment of a variety of conditions where increased peripheral blood flow is desired. The hypothesis behind its working mechanism is its purported ability to generate nitric oxide (NO) in the treated area. We tested the hypothesis that the efficacy of near-infrared light lies in its ability to generate NO at the treatment site. We conducted a single-blind, placebo-controlled, randomized clinical trial to measure NO, by its metabolites nitrite and nitrate, in venous blood draining from tissue receiving LLLT. Fifteen healthy subjects received LLLT to the forearm, and blood samples were taken immediately before treatment; at 1, 5, 15, and 30 mins; as well as 15 mins after the treatment to check for NO content. We found a significant treatment effect (F = 15.75, P = 0.003). A post hoc test showed that minutes 1, 5, and 15 were different compared with the baseline measures (P's < 0.05). The area under the treatment curve was significantly larger than the area under the sham treatment curve (t = 2.26, P = 0.037). A limitation of this study was that the data were collected from healthy subjects. LLLT increased NO levels in venous blood draining from the treatment site in healthy subjects. The peak increase in NO occurred 5 mins into the treatment, after which it slowly waned. Further research is necessary to assess NO increases with LLLT in patients with pathologies.


Lymphoproliferative disorders in patients with chronic myeloproliferative neoplasms: A systematic review.
Patients with a Ph-negative myeloproliferative neoplasm (MPN) may harbor or develop lymphoproliferative disorders (LPD), however, the clinical and molecular determinants of MPN and LPD co-occurrence are still uncertain. To systematically pool the available knowledge, we conducted a scoping review of literature published since January 2005 and analyzed single-patient clinical data from 50 papers reporting 214 individuals harboring both MPN and LPD. Patients had been diagnosed essential thrombocythemia (44%), polycythemia vera (29%), or myelofibrosis (23%) at a median age of 67 years (26-94): half of them incurred a LPD after a median of 72 months from MPN diagnosis, while in 20% the LPD diagnosis was antecedent or synchronous. Patients mainly incurred indolent LPD, particularly chronic lymphocytic leukemia (CLL), while aggressive lymphomas and multiple myeloma were a relevant portion of the LPDs occurring in the follow-up of MPN. CLL was preferentially diagnosed in PV patients and was associated with a very high male-to-female ratio, as well as an older age at MPN diagnosis. On converse, multiple myeloma was rarely reported in PV patients and was preferentially diagnosed in female patients not harboring the JAK2 V617F mutation. Based on the 46 cases reporting follow-up data, median survival after MPN diagnosis was 96 months. This thorough review of published evidence confirms that LPD are relevant clinical events in the history of MPN patients. Controlled studies are needed to better refine individuals at higher risk of developing LPD, to support surveillance programs and to avoid therapies possibly favoring LPD.


Effects of supervisor support and coping on shiftwork tolerance.
This study examines the effects of supervisor support and coping on work/non-work conflict and health in shiftwork. It describes a model of shiftwork tolerance that is tested on samples from two populations of shiftworkers. The samples--of nurses and ambulance workers--differed by occupation, gender and shift schedule. Quantitative (survey questionnaire) and qualitative methods (in-depth interviews) were used to triangulate results and to yield richer data on psychosocial variables. Structural equation modelling, using EQS, was used to describe the common path relationships observed within both samples of shiftworkers. The results demonstrated important relationships between social support from supervisors, coping strategies, work/non-work conflict and symptoms that transferred robustly between the two populations of shiftworkers.


A comparison of word lexicality in the treatment of speech sound disorders.
The goal of this research programme was to evaluate the role of word lexicality in effecting phonological change in children's sound systems. Four children with functional speech sound disorders (SSDs) were enrolled in an across-subjects multiple baseline single-subject design; two were treated using high-frequency real words (RWs) and two were treated using (low-frequency) non-words (NWs). Dependent variables were learning during treatment, generalization of treated and untreated sounds post-treatment and error consistency indices. The oldest child in the NW group demonstrated slightly greater increases in learning during treatment, and both children demonstrated increases in generalization as well as large decreases in sound error variability. In comparison, one child in the RW group demonstrated untreated sound generalization, as well as decreases in sound error variability. These results suggest that NWs may be useful in helping children learn the sound structure of words containing treated sounds. These findings are interpreted within an established connectionist model accounting for phonological and lexical representations.


iMapSplice: Alleviating reference bias through personalized RNA-seq alignment.
Genomic variants in both coding and non-coding sequences can have functionally important and sometimes deleterious effects on exon splicing of gene transcripts. For transcriptome profiling using RNA-seq, the accurate alignment of reads across exon junctions is a critical step. Existing algorithms that utilize a standard reference genome as a template sometimes have difficulty in mapping reads that carry genomic variants. These problems can lead to allelic ratio biases and the failure to detect splice variants created by splice site polymorphisms. To improve RNA-seq read alignment, we have developed a novel approach called iMapSplice that enables personalized mRNA transcriptome profiling. The algorithm makes use of personal genomic information and performs an unbiased alignment towards genome indices carrying both reference and alternative bases. Importantly, this breaks the dependency on reference genome splice site dinucleotide motifs and enables iMapSplice to discover personal splice junctions created through splice site polymorphisms. We report comparative analyses using a number of simulated and real datasets. Besides general improvements in read alignment and splice junction discovery, iMapSplice greatly alleviates allelic ratio biases and unravels many previously uncharacterized splice junctions created by splice site polymorphisms, with minimal overhead in computation time and storage. Software download URL: https://github.com/LiuBioinfo/iMapSplice.


[The fasting regime prior to anaesthesia].
In modern anaesthesiology fasting preoperatively has been introduced in order to minimise the incidence of aspiration to the lungs. Since the 1990's studies have confirmed the safety of the current fasting regime of six hours for solids and two hours for fluids. By allowing the intake of carbohydrate-rich fluids until two hours before induction of anaesthesia, it has been shown that the negative effects of fasting such as thirst, starvation and anxiety are minimised. In the future, ultrasound technology might be used to assess the gastric volume prior to induction of anaesthesia.


A dual indicator set to help farms achieve more sustainable crop protection.
Farmers are being called to use plant protection products (PPPs) more consciously and adopt more sustainable crop protection strategies. Indicators will help farmers to monitor their progress towards sustainability and will support their learning process. Talking the indicators through in farmers' discussion groups and the resulting peer encouragement will foster knowledge acquirement and can lead to changes in attitudes, norms, perception and behaviour. Using a participatory approach, a conceptual framework for on-farm sustainable crop protection practices was created. The same participatory approach was used to design a dual indicator set, which pairs a pesticide impact assessment system (PIAS) with a farm inquiry. The PIAS measures the risk for human health and the environment exerted by chemical crop protection. The inquiry reveals the farmers' response to this risk, both in terms of the actions they take and their knowledge, awareness and attitude. The dual indicator set allows for implementation in four tiers, each representing increased potential for monitoring and social learning. The indicator set can be adjusted on the basis of new findings, and the participatory approach can be extrapolated to other situations.


Reduction of pyocyanin synthesis and antibiotic resistance in Pseudomonas aeruginosa by low concentration ethanol.
Pseudomonas aeruginosa is a common bacteria that may cause a wide range of severe illnesses in humans. One of the nonantibiotic therapies, antivirulence factor therapy, has attracted ongoing interest. Screening for and investigating bacterial virulence factor inhibitors is critical for the development of antivirulence factor treatments. Pyocyanin is P. aeruginosa's distinctive pigment, and it plays a key role in infection. The impact of low concentration ethanol on pyocyanin production was investigated in this research. Pyocyanin production was found both subjectively and quantitatively. The effects of ethanol on the expression of pyocyanin production genes were studied using qRT-PCR and western blotting. The findings demonstrated that low concentrations of ethanol (as little as 0.1%) greatly suppressed pyocyanin production without affecting P. aeruginosa growth. The degree of inhibition increased as the ethanol contentration rose. Ethanol inhibits the expression of genes involved in pyocyanin production. This inhibitory impact was mostly seen at the protein level. Further research revealed that ethanol increased the expression of the post-transcriptional regulator RsmA, which inhibits pyocyanin production. Given the favorable relationship between pyocyanin production and antibiotic resistance, the impact of low concentration ethanol on various antibiotics was investigated. Ethanol lowered antibiotic resistance in P. aeruginosa, presumably by inhibiting pyocyanin.


[Indications for implantable automatic defibrillators].
The automatic implantable defibrillator is an effective therapeutic tool for palliative treatment of severe ventricular arrhythmias. There is a significant reduction in sudden death in implanted patients. However, reliable data on the long term global mortality is not yet available. The indications are difficult to define apart from special cases. A large number of factors has to be taken into consideration: the clinical presentation of the arrhythmia, and the different medical and non-medical therapeutic options. At present, it is not possible to arrive at a consensus on the indications of automatic implantable defibrillators. Therefore, it is illusory to construct decisional algorithms. The authors suggest therapeutic orientations rather than strict clinical indications, based on recommendations published by the working groups on cardiac arrhythmias and pacing of the European Society of Cardiology and on their own personal experience.


Atypical Pectoralis Major Muscle Wasting in a Recreational Weight Lifter.
Pectoralis major injuries are relatively uncommon and can pose a diagnostic challenge. Deformity and weakness of this muscle in weight lifters is typically due to traumatic tendon rupture and often requires surgical repair. However, there are other less common etiologies that can mimic the clinical presentation of pectoralis major wasting and weakness that require different treatment approaches. This article describes a case of a 48-year-old recreational weight lifter who presented with severe pectoralis major wasting and weakness secondary to isolated mononeuropathy of the lateral pectoral nerve possibly due to Parsonage Turner syndrome. The patient was treated nonoperatively and achieved full recovery 18 months after onset. Parsonage Turner syndrome should be included in the differential diagnosis of patients with atraumatic weakness and wasting of the pectoralis major muscle and dysfunction. [Orthopedics. 2016; 39(4):e756-e759.].


CuO Nanoparticles and Microaggregates: An Experimental and Computational Study of Structure and Electronic Properties.
The link between morphology and properties is well-established in the nanoparticle literature. In this report, we show that different approaches in the synthesis of copper oxide can lead to nanoparticles (NPs) of different size and morphology. The structure and properties of the synthesized NPs are investigated with powder X-ray diffraction, scanning electron microscopy (SEM), and diffuse reflectance spectroscopy (DRS). Through detailed SEM analyses, we were able to correlate the synthetic pathways with the particles' shape and aggregation, pointing out that bare hydrothermal pathways yield mainly spheroidal dandelion-like aggregates, whereas, if surfactants are added, the growth of the nanostructures along a preferential direction is promoted. The effect of the morphology on the electronic properties was evaluated through DRS, which allowed us to obtain the electron bandgap in every system synthesized, and to find that the rearrangement of threaded particles into more compact structures leads to a reduction in the energy difference. The latter result was compared with Density Functional Theory (DFT) computational models of small centrosymmetric CuO clusters, cut from the tenorite crystal structure. The computed UV-Vis absorption spectra obtained from the clusters are in good agreement with experimental findings.


High catalytic efficiency of nanostructured molybdenum trioxide in the benzylation of arenes and an investigation of the reaction mechanism.
The synthesis and characterization of nanostructured MoO(3) with a thickness of about 30 nm and a width of about 450 nm are reported. The composition formula of the MP (precipitation method) precursor was estimated to be [(NH(4))(2)O](0.169) x MoO(3) x (H(2)O)(0.239). The calcination of the precursor in air afforded nanostructured pellets of the alpha-MoO(3) phase. The nanostructured MoO(3) catalyst exhibited high efficiency in catalyzing the benzylation of various arenes with substituted benzyl alcohols, which were strikingly different to common bulk MoO(3). Most reactions offered >99% conversion and >99% selectivity to monoalkylated compounds. MoO(3) is a typical acid catalyst. However, the benzylation reaction over nanostructured MoO(3) does not belong to the acid-catalyzed type or defect site-catalyzed type, since the catalyst has no acidity and defect site on surface. Characterization with thermal, spectroscopic, and electronic techniques reveal that the catalyst contains fully oxygen-coordinated MoO(6) octahedrons on the surface but partially reduced species (Mo(5+)) within the bulk phase. The terminal oxygen atoms of Mo=O bonds on the (010) basal plane resemble oxygen anion radicals and act as active sites for the adsorption and activation of benzyl alcohols by electrophilic attack. Such sites are indispensable for catalytic reactions since the blocking of these sites by electron acceptors, such as tetracyanoethylene (TCNE), can greatly decrease catalytic activity. This work represents a successful example of combining a heterogeneous catalysis study with nanomaterial synthesis.


Production of monoclonal antibodies to estriol and their application in the development of a sensitive nonisotopic immunoassay.
The development of highly specific monoclonal antibodies to estriol and a nonisotopic immunoassay (EIA) for unconjugated estriol based on the use of these monoclonal antibodies have been described. The monoclonal antibodies show little cross reactivity with other steroids and steroid conjugates and can be used directly in immunoassays without any purification. The EIA described here can be performed in 96-well microtiter plates or polystyrene tubes that have been coated with estriol-bovine serum albumin conjugate. In this assay, estriol in the standard or clinical samples (serum or saliva) competes with the immobilized steroid on the plate or the tube for binding with the antibody. The assay shows good agreement with radioimmunoassay (RIA) and is highly sensitive and reliable. Since no prior processing or extraction of the clinical samples is necessary, the method is potentially applicable for routine use in fetal monitoring as well as in a steroid laboratory.


β-carbolines norharman and harman in vegetable oils in China.
The beta-carbolines norharman and harman, two heterocyclic aromatic amines with potential mutagenicity, have been determined in vegetable oils. Identification and analysis were carried out by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS). In 88 samples analysed, the concentrations of norharman and harman were < LOD to 336.22 ng/g and < LOD to 505.14 ng/g, respectively. A high variability of norharman and harman levels among different oil types was observed. Sesame-, flaxseed-, sunflower seed-, peanut- and rapeseed oils were most contaminated. Both β-carbolines were most likely formed during roasting of the oilseeds. Oil consumption, especially of oils obtained after roasting of the seeds, was a major dietary source of the β-carbolines norharman and harman. Under existing oil risk factors, this investigation contributes to the unprecedented and essential information for dietary assessments associated with oil consumption.


Patients requiring pediatric palliative care for advanced heart disease in France: A descriptive study.
Pediatric palliative care (PPC) teams address unmet needs and improve the quality of life of patients with life-limiting conditions across pediatric subspecialties. However, little is known about the timing, reasons, and nature of PPC team interventions in advanced heart diseases (AHD). Here we describe how, when, and why PPC teams interact with referred teams of children suffering from AHD. We conducted a retrospective nationwide survey among PPC teams in France. All patients referred to participating PPC teams for a cardiologic disease in 2019 were studied. Among six PPC teams, 18 patients with AHD had a PPC consultation in 2019. Six of these patients had cardiomyopathy and 12 had congenital heart disease (CHD). The median age at referral was 0.9 months for CHD and 72 months for cardiomyopathy. An antenatal diagnosis had been made for six families with CHD, and two of them were referred to PPC before birth allowing for a prenatal palliative care plan. The main reason for referral was ethical considerations (50%) followed by organization for home-based palliative care (28%). PPC teams participated in ethical discussions when asked to but also provided family support (12/18), home-based PPC (9/18), coordination of care (5/18), support of the referred team (4/18), and symptoms management (3/18) CONCLUSION: The main reason for referral to PPC was ethical considerations, but PPC interventions followed a holistic model of care. Prospective outcomes measurement and partnerships should be further developed.


Flcn-deficient renal cells are tumorigenic and sensitive to mTOR suppression.
Deficiency of tumor suppressor FLCN leads to the activation of the mTOR signaling pathway in human BHD-associated renal cell carcinomas (RCC). We have previously developed a renal distal tubule-collecting duct-Henle's loop-specific Flcn knockout (KO) mouse model (Flcnflox/flox/Ksp-Cre). This mouse model can only survive for three weeks after birth due to the development of polycystic kidney and uremia. Whether these cystic solid hyperplasia changes seen in those KO mice are tumorigenic or malignant is unknown. In this study, we demonstrated that genetic disruption of Flcn in mouse kidney distal tubule cells could lead to tumorigenic transformation of these cells to develop allograft tumors with an aggressive histologic phenotype. Consistent with previous reports, we showed that the mTOR pathway plays an important role in the growth of these Flcn-deficient allograft and human UOK 257-1 xenograft tumors. We further demonstrated that the mTOR inhibitor, sirolimus, suppresses the tumor's growth, suggesting that mTOR inhibitors might be effective in control of FLCN-deficient RCC, especially in BHD renal tumorigenesis.


Effect of miR-19b on the protective effect of Exendin-4 on islet cells in non-obese diabetic mice.
This study analyzed the effect of miR-19b on the protective effect of Exendin-4 on islet cells in non-obese diabetic (NOD) mice. Twenty-four NOD/LT mice were randomized, according to the random number table, into a control group (4 µg/kg•day), a low-dose group (2 µg/kg•day Exendin-4), a medium-dose group (4 µg/kg•day Exendin-4) and a high-dose group (8 µg/kg•day Exendin-4) (n=6), with miR-19b expression interfered (an interference group) except for the control group. RT-qPCR was used to detect interference results and different doses of Exendin-4 were given for 8 weeks of intervention after the interference. CD4+ and CD8+ cell levels were detected by flow cytometry, IL-2 and IL-10 levels in the peripheral blood by enzyme-linked immunosorbent assay, and the apoptosis rate of islet cells in the pancreatic tissue by TUNEL. After 4 and 8 weeks of Exendin-4 intervention, mice in the high-dose group had lower blood glucose level than the medium-dose group (P<0.05). The medium-dose group had lower CD4+ cell level than the high-dose group (P<0.05), while the medium-dose group had higher CD8+ cell level than the high-dose group (P<0.05). After 8 weeks of intervention, compared with the medium-dose group, the high-dose group had lower IL-2 level (P<0.05), but higher IL-10 level (P<0.05). After 8 weeks of intervention, the medium-dose group had a higher apoptosis rate than the high-dose group (P<0.05). In conclusion, the decrease in miR-19b expression can improve the therapeutic effect of Exendin-4 on NOD, control blood glucose effectively and improve inflammatory response and immune function, as well as reduce islet cell injury. The increase in the dose of Exendin-4 can further improve its therapeutic effect on NOD.


Comparison of Scale in a Photosynthetic Reactor System for Algal Remediation of Wastewater.
An experimental methodology is presented to compare the performance of two different sized reactors designed for wastewater treatment. In this study, ammonia removal, nitrogen removal and algal growth are compared over an 8-week period in paired sets of small (100 L) and large (1,000 L) reactors designed for algal remediation of landfill wastewater. Contents of the small and large scale reactors were mixed before the beginning of each weekly testing interval to maintain equivalent initial conditions across the two scales. System characteristics, including surface area to volume ratio, retention time, biomass density, and wastewater feed concentrations, can be adjusted to better equalize conditions occurring at both scales. During the short 8-week representative time period, starting ammonia and total nitrogen concentrations ranged from 3.1-14 mg NH3-N/L, and 8.1-20.1 mg N/L, respectively. The performance of the treatment system was evaluated based on its ability to remove ammonia and total nitrogen and to produce algal biomass. Mean ± standard deviation of ammonia removal, total nitrogen removal and biomass growth rates were 0.95±0.3 mg NH3-N/L/day, 0.89±0.3 mg N/L/day, and 0.02±0.03 g biomass/L/day, respectively. All vessels showed a positive relationship between the initial ammonia concentration and ammonia removal rate (R2=0.76). Comparison of process efficiencies and production values measured in reactors of different scale may be useful in determining if lab-scale experimental data is appropriate for prediction of commercial-scale production values.


Leukocyte adhesion defect.
Leukocyte adhesion defect (LAD) is a rare, autosomal recessive primary immunodeficiency disorder of phagocytes, in which there is defective aggregation at the site of infection due to the absence of surface integrins. Diagnosis is based primarily on flowcytometric analysis of neutrophils for the surface expression of CD11, CD18 and CD15s. We describe here a case of a 7-months-old boy who presented with a characteristic history of recurrent infections, marked leukocytosis and delayed separation of umbilical cord. The diagnosis was established by demonstration of the absence of integrins on the surface of patient's neutrophils by flowcytometric analysis.


Galaninergic mechanisms are involved in the regulation of corticotropin and thyrotropin secretion in the rat.
Galanin (GAL), a 29-amino acid peptide, affects the secretion of several anterior pituitary hormones, including PRL and GH. Since GAL coexists with vasopressin and CRH in the hypothalamic paraventricular nucleus (PVN), we have studied the pharmacological and physiological actions of GAL on ACTH and TSH secretion in freely moving male rats. Cannulae were surgically implanted in the right atria and brain, intraventricular or adjacent to the PVN, of adult Sprague-Dawley rats. Seven days later, GAL (500 or 1000 ng) or saline was infused into the PVN, and serial blood samples were obtained 5, 10, 20, and 40 min after the infusion. Some animals were also stressed by the inhalation of ether vapors for 2 min after the PVN infusion. Basal ACTH concentrations were increased 2-fold in saline-treated rats; however, plasma ACTH levels were unchanged after GAL infusion. The exposure of rats to ether vapors for 2 min after the infusion of saline into the PVN increased plasma ACTH concentrations from 22.8 +/- 6.0 to 596.6 +/- 59.9 pg/ml 10 min later. However, the infusion of GAL into the PVN attenuated stress-induced ACTH secretion. After GAL infusion, peak ACTH levels (332.7 +/- 84.0 pg/ml) were attained 5 min after ether exposure, followed by a rapid decline at 10 min (P less than 0.001) and 20 min (P less than 0.05). Plasma TSH concentrations were unchanged by GAL or saline infusion and were not affected by ether vapor inhalation. To determine the physiological significance of GAL in the control of ACTH and TSH secretion, endogenous GAL was immunoneutralized by the infusion of 3 microliters GAL antiserum (GAL-AS) into the third cerebral ventricle 25 and 1 h before withdrawing blood samples every 15 min for 6 h. Animals treated with normal rabbit serum (NRS) served as controls. Plasma ACTH concentrations were unchanged by NRS during the 6-h period. However, infusion of GAL-AS raised plasma ACTH concentrations to over 400 pg/ml 75 min after infusion in some animals. In general, plasma ACTH concentrations were increased 4 h of the 6-h sampling period compared to levels in NRS-treated controls. In contrast, GAL-AS reduced TSH concentrations by 50% compared to control values. In contrast to these marked actions of centrally administered GAL, ACTH secretion from dispersed anterior pituitary cells in vitro was unaffected by GAL in concentrations up to 10(-6) M. Furthermore, GAL did not alter CRH (1 nM)-induced ACTH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)


Assessment of the patient with known or suspected ischaemic heart disease for non-cardiac surgery.
The perioperative care of the patient with known or suspected ischaemic heart disease requires careful co-ordination among the anaesthetist, surgeon and medical consultant. Careful preoperative evaluation can aid the identification of risk, the selection of preoperative interventions that may reduce risk, and decisions on intraoperative and postoperative monitoring. Although uncontrolled observational data suggest that such careful management allows for improved outcome, more carefully controlled studies are required to determine the precise benefits and cost-effectiveness of many of the expensive and often invasive interventions that are currently available.


Long-term results of aortic valve resuspension in patients with aortic valve insufficiency and aortic root aneurysm.
'The David technique' may provide an alternative to conduit implantation in patients with an aneurysm of the ascending aorta and aortic valve insufficiency. From 1991 to 2013, the David technique was performed in 249 consecutive patients in our department. The patient mean age was 58 ± 14 years; 71 (29%) were female and 178 (71%) male. A modification of the David technique was performed by creating a pseudosinus in 43 patients (17%) and by creating a neosinus in 123 patients (49%). The mean follow-up was 6 ± 4.5 years. There were six in-hospital (2.4%) and 30 late deaths (2.4%/patient-year). Cardiac-related events were the cause of death in three patients. The Kaplan-Meier estimate for 10 years survival was 77%. Four patients had perioperative neurological events, and only eight neurological events occurred during follow-up (0.6%/patient-year). Ten patients (0.8%/patient-year) required aortic valve replacement; one because of combined aortic valve stenosis and insufficiency and nine because of severe aortic valve insufficiency as a result of leaflet prolapse (n = 3), leaflet perforation (n = 1), abridgement of the right coronary leaflet (n = 1) and because of endocarditis (n = 4). Three cases of bleeding were observed (0.24%/patient-year). Freedom from reoperation or aortic valve insufficiency ≥2° was 80% at 10 years. Aortic valve sparing to treat patients with an ascending aortic aneurysm with aortic valve insufficiency is a durable procedure. Aortic valve function remains stable for many years. Valve-related complications are rare, and the rate of reoperations is not increased in comparison to conduit root replacement.


Human drug abuse liability assessment: opioids and analgesics.
Methods are described for assessment of the abuse liability of opioids and analgesics. The methods developed by the USPHS Addiction Research Center for assessment of opioid abuse liability have served as the prototype for most currently used abuse liability assessment approaches. The general method is that of comparing the profile of effects of a test drug to the profiles of placebo and of a known drug of abuse. Drugs with profiles of activity similar to the known drug of abuse are considered pharmacologically equivalent and of similar abuse liability. Specific methods, including the Addiction Research Inventory, adjective- and visual analog rating scales, are described, as are methodological developments that have been introduced to improve the sensitivity of the procedures and to adapt them to modern circumstances. It is concluded that the profile-of-effects methodology has proven extremely useful and should remain a basic element in abuse liability assessments.


Ecdysteroids elicit a rapid Ca2+ flux leading to Akt activation and increased protein synthesis in skeletal muscle cells.
Phytoecdysteroids, structurally similar to insect molting hormones, produce a range of effects in mammals, including increasing growth and physical performance. In skeletal muscle cells, phytoecdysteroids increase protein synthesis. In this study we show that in a mouse skeletal muscle cell line, C(2)C(12), 20-hydroxyecdysone (20HE), a common phytoecdysteroid in both insects and plants, elicited a rapid elevation in intracellular calcium, followed by sustained Akt activation and increased protein synthesis. The effect was inhibited by a G-protein coupled receptor (GPCR) inhibitor, a phospholipase C (PLC) inhibitor, and a phosphoinositide kinase-3 (PI3K) inhibitor.


99mTc-HMPAO as a tracer of cerebral blood flow in newborn infants.
Studies on the kinetics of 99mTc-D,L-hexamethylpropylene amine oxime (99mTc-HMPAO) in adults have shown that it is not an ideal tracer of CBF because it underestimates high-flow areas. Knowledge of the kinetics of the tracer is important in evaluating the studies. The kinetics of 99mTc-HMPAO in infants may be different from that in adults, therefore, we examined the cerebral uptake and retention of 99mTc-HMPAO in neonates and estimated the degree of brain-to-blood back diffusion by comparing corresponding 133Xe flow images and 99mTc-HMPAO distribution images. In addition, we measured the urinary excretion of 99mTc-HMPAO. Regional CBF was measured using a mobile brain-dedicated, fast-rotating, four-head multidetector system specially designed for neonatal studies. Tracers were 99mTc-HMPAO (4 MBq/kg) and 133Xe (500 MBq/kg). Cerebral uptake and leak-out of 99mTc-HMPAO were measured by a single scintillation crystal placed over the frontoparietal part of the infant's head. The cerebral retention of 99mTc-HMPAO was analyzed in 50 infants. The mean gestational age and birth weight (95% confidence interval) were 34.4 weeks (32.2-35.7) and 2,326 g (1,954-2,995), respectively. The cerebral uptake of 99mTc-HMPAO was examined in 16 of the 50 infants, and activity during 24 h was monitored in five. In 11 infants, corresponding 133Xe studies were performed. Urinary excretion was studied in 12 infants. The maximal activity in the brain was reached 90s after i.v. injection and was 104% (98-111) of the stable level, which was reached approximately 3 min after the injection. The decay corrected leakout of the tracer during the following 24 h was 1.0% (0.4-1.5) per hour. The cerebral retention was calculated at 6.8% (6.1-7.6), highest in the group of ictal studies and lowest in premature infants with intracranial hemorrhage. The mean value of the fixation/clearance ratio alpha was estimated at 3.4 (2.8-4.4). The mean urinary excretion over 24 h was 19.5% (11.4-27.7) and was significantly related to renal function as indicated by serum urea (p = 0.02 r2 = 0.55). A four-compartment model describing the kinetics of 99mTc-HMPAO is shown to be valid in neonates. The cerebral retention of the tracer is higher in neonates because of higher extraction and lower initial back diffusion from brain to blood. In linearizing 99mTc-HMPAO distribution images, a smaller correction is necessary, and we propose a value of the correction factor of 3.4. In this way, 99mTc-HMPAO is a more reliable tracer of the distribution of CBF in neonates compared with adults. The urinary excretion is significantly reduced compared with adults, and the radiation dose to the bladder wall is reduced. The effective dose is 0.3 mSv/MBq/kg.


Isolation and Identification of Two l-Azetidine-2-carboxylic Acid-Degrading Soil Microorganisms, Enterobacter agglomerans and Enterobacter amnigenus
Soil samples collected at several times during the growing season and at different locations within Convallaria majalis beds in Ann Arbor, MI, were screened for their ability to grow with the cyclic amino acid, l-azetidine-2-carboxylic acid (l-A-2-C), as their sole nitrogen source (i.e., metabolize l-A-2-C). Two different soil microorganisms were isolated, characterized, and identified using fundamental selection methods, the standard battery of biochemical characterization tests, and scanning electron microscopy. The assignment of the identity of these organisms as Enterobacter agglomerans and Enterobacter amnigenus was further verified by comparison with authentic microbial samples obtained from ATCC that were able to utilize l-A-2-C as their sole nitrogen source.


Assessment of liquid microbead arrays for the screening of newborns for spinal muscular atrophy.
Spinal muscular atrophy is a common neurodegenerative disorder that has recently been considered for inclusion in the next generation of newborn screening regimens. We sought to validate liquid microbead arrays for the identification of affected individuals by direct DNA analysis. Assays were created to detect the homozygous deletions in exon 7 of the SMN1 gene found in approximately 95% of affected individuals by use of 2 different microbead chemistries on the Luminex 200: MultiCode-PLx and Tag-It. A series of 367 blood spots including 164 from affected individuals, 46 from known carriers, and 157 from unaffected individuals were then analyzed with each assay. The MultiCode-PLx assay required 4.2 h to perform and provided correct identification of all 164 samples from affected individuals. Correct exclusion was also made for all 46 carrier and 157 unaffected individual samples. The Tag-It assay required 6.8 h, detected all samples from affected individuals, and excluded all but 1 (99.5%) of the samples from carriers and unaffected individuals. Neither method was sensitive to increasing copy numbers of the SMN2 gene. Both methods showed high sensitivity and specificity for the detection of patients with spinal muscular atrophy. For both methods, ample DNA was extracted from all blood spots for analysis, and SMN2 copy numbers did not interfere. Liquid bead arrays represent a robust method for DNA analysis in newborn screening laboratories.


Shyness and openness--common ground for dialogue between health personnel and women about sexual and intimate issues after gynecological cancer.
In this article we explore shyness and openness related to sexuality and intimacy in long-term female survivors of gynecological cancer, and how these women experienced dialogue with health personnel on these issues. Further analysis on two core themes, based on empirical data presented elsewhere, inspired continued theoretical and philosophical thinking drawing on Løgstrup's expressions of life and unified opposites. The findings show that gynecological cancer survivors and health personnel share common ground as human beings because shyness and openness are basic human phenomena. Health personnel's own movement between these phenomena may represent a resource because it can help women to handle sexual and intimacy challenges following gynecological cancer.


Efficacy and safety of intravenous immunoglobulin in patients with metastatic melanoma.
We have previously reported studies performed both in vitro and in laboratory animals, as well as a case study in humans, suggesting that intravenous immunoglobulin (IVIG) may be beneficial in the treatment of malignancies, including metastatic melanoma. As part of a phase II open label trial, we have administered IVIG to nine patients with metastatic melanoma who had been heavily treated. In two of nine (22%) patients treated every 3 weeks with IVIG (1 g/kg body weight), the disease stabilized. One patient had stable disease for 8 months; the other for 3 months. No serious adverse events (AEs) attributable to IVIG were observed. We conclude that IVIG therapy may be useful for the treatment of metastatic melanoma. Furthermore, we suggest that the effects of IVIG therapy might be enhanced by its use as an adjuvant in patients without evidence of disease following surgery.


Gestational diabetes mellitus and lesser degrees of pregnancy hyperglycemia: association with increased risk of spontaneous preterm birth.
To investigate whether different degrees of maternal glucose intolerance are associated with the risk of spontaneous preterm birth. We performed a cohort study of 46,230 pregnancies screened by a 50-g, 1-hour oral glucose tolerance test between 24 and 28 gestation weeks at the Northern California Kaiser Permanente Medical Care Program. Spontaneous preterm birth was defined as an infant born at less than 37 gestation weeks with at least one of the following: spontaneous labor, preterm premature rupture of membranes, or incompetent cervix. Glucose tolerance status was categorized as normal screening (1-hour plasma glucose less than 140 mg/dL), abnormal screening (1-hour plasma glucose of at least 140 mg/dL with a normal diagnostic 100-g, 3-hour oral glucose tolerance test result), Carpenter-Coustan (plasma glucose measurements during the diagnostic oral glucose tolerance test met the thresholds but were lower than the National Diabetes Data Group thresholds), and gestational diabetes mellitus (GDM) by the National Diabetes Data Group criteria. One thousand nine hundred fifty-six spontaneous preterm births occurred. Age-adjusted incidences of spontaneous preterm birth were 4.0% in normal screening, 5.0% in abnormal screening, 6.7% in Carpenter-Coustan, and 6.7% in GDM. In a logistic regression model adjusted for age, race-ethnicity, preeclampsia-eclampsia-pregnancy-induced hypertension, chronic hypertension, polyhydramnios, and birth weight for gestational age, pregnancies with abnormal screening, Carpenter-Coustan, and GDM had a significantly higher risk of spontaneous preterm birth than pregnancies with normal screening (relative risk [95% confidence interval]: 1.23 [1.08, 1.41], 1.53 [1.16, 2.03], and 1.42 [1.15-1.77], respectively). The risk of spontaneous preterm birth increased with increasing levels of pregnancy glycemia. This association was independent of perinatal complications that could have triggered early delivery.


Primary urachal signet ring cell carcinoma: A case report.
Urachal signet ring cell carcinoma is a kind of rare but aggressive tumor, and a few cases have been reported previously. A 49-year-old male patient with primary complaints of increased frequency of urination, urodynia, and hematuria was diagnosed to have primary urachal signet ring cell carcinoma by our department. Multiple metastases were found in the sigmoid colon, terminal ileum, mesentery, and peritoneum during the operation, and palliative surgery involving partial cystectomy with en bloc resection of the urachus was then performed. A chemotherapy regimen of fluorouracil combined with cisplatin was made for this case. In addition, this patient also received anlotinib for targeted therapy. So far, this patient has done well on regular follow-up for 6 months and is in stable condition. We reported this additional urachal signet ring cell carcinoma case and conducted a literature review to strengthen our cognition of this disease.


Mutation analysis of the EBV-lymphoblastoid cell line cautions their use as antigen-presenting cells.
Lymphoblastoid cell lines (LCLs) have been widely used as professional antigen-presenting cells (APCs). However, neoantigen-loaded LCLs could induce nonspecific T-cell response, which could be due to expression of both Epstein-Barr virus (EBV) antigens and nonsynonymous mutations arising in LCLs. Since the number of passages could influence mutational characteristics of LCLs, and moreover extensive proliferation of LCLs in vitro is necessary to activate T cells for immunotherapy, we comprehensively profiled mutational characteristics by comparing eight sets of B cells and matched high-passage LCLs using whole-exome sequencing in order to assess the effect of nonsynonymous mutations arising in LCLs on nonspecific T-cell response. We found 315 nongermline mutations (approximately 40mut/subject) randomly distributed across all chromosomes including 18 mutations in immunoglobulin V and J genes in eight LCLs, of which 137 candidate neoantigens (approximately 17mut/subject) were identified. The underlying mutational processes linked to EBV-transformed LCLs could be attributed to activation induced cytidine deaminase gene expression which contributes to cytosine mutation clusters in LCLs through cytosine deamination. Pathways significantly enriched by nonsilent mutations of each LCL were totally different among all LCLs. In conclusion, high-passage LCLs may not be suitable to serve as APCs due to random nonsilent mutations, particularly for presentation of neoantigens of low immunogenicity, although further experimental proofs are needed.


Synthesis and interfacial properties of monoacyl glyceric acids as a new class of green surfactants.
Glyceric acid (GA) is one of the most promising functional hydroxyl acids, and it is abundantly obtained from glycerol by a bioprocess using acetic acid bacteria. In this study, several monoacyl GAs were synthesized by esterification of GA and saturated fatty acyl chlorides (C12, C14, C16, and C18), forming a new class of bio-based surfactants. By the present method, a mixture of two isomers, namely 2-O-acyl and 3-O-acyl GAs, was produced, in which the 2-O-acyl derivatives were obtained as a major product. These isomers were isolated, and their surface-active properties were investigated for the first time. The surface tensions of 2-O-acyl GAs with different chain lengths were determined by the Wilhelmy method. At concentrations below 10(-4) M, the 2-O-acyl GAs exhibited higher surface-active properties compared to commercially available synthetic surfactants. For example, 2-O-lauroyl GA reduced the surface tension of water to around 25 mN/m above the critical micelle concentration (3.0×10(-4) M). In addition, 2-O-acyl derivatives showed higher surface-tension-lowering activity than 3-O-acyl GAs. The monoacyl GAs synthesized herein can potentially be used as "green surfactants."


Oxidant-mediated increases in redox factor-1 nuclear protein and activator protein-1 DNA binding in asbestos-treated macrophages.
Alveolar macrophages have been implicated in the pathogenesis of a number of acute and chronic lung disorders. We have previously shown that normal human alveolar macrophages exhibit decreased DNA binding activity of the transcription factor, AP-1, compared with monocytes. Furthermore, this decrease in AP-1 DNA binding appears to be due to a decrease in the redox active protein, redox factor (Ref)-1. Ref-1 is an important redox regulator of a number of transcription factors, including NF-kappaB and AP-1. In this study we evaluated the role of asbestos, a prototypic model of chronic fibrotic lung disease, in Ref-1 expression and activity. We found that incubation with low concentrations of crocidolite asbestos (0.5-1.25 microg/cm(2)) resulted in an increase in nuclear Ref-1 protein after 5 min, with a persistent elevation in protein up to 24 h. Additionally, an increase in nuclear Ref-1 could be induced by treating the cells with an oxidant-generating stimulus (iron loading plus PMA) and inhibited by diphenyleneiodonium chloride, an inhibitor of NADPH oxidase. The asbestos-induced accumulation of nuclear Ref-1 was associated with an increase in AP-1 DNA binding activity. These findings suggest that an exposure associated with fibrotic lung disease, i.e., asbestos, modulates accumulation of nuclear Ref-1 in macrophages, and that this effect is mediated by an oxidant stimulus.


Disorder-induced rounding of the phase transition in the large-q-state Potts model.
The phase transition in the q -state Potts model with homogeneous ferromagnetic couplings is strongly first order for large q, while it is rounded in the presence of quenched disorder. Here we study this phenomenon on different two-dimensional lattices by using the fact that the partition function of the model is dominated by a single diagram of the high-temperature expansion, which is calculated by an efficient combinatorial optimization algorithm. For a given finite sample with discrete randomness the free energy is a piecewise linear function of the temperature, which is rounded after averaging, however, the discontinuity of the internal energy at the transition point (i.e., the latent heat) stays finite even in the thermodynamic limit. For a continuous disorder, instead, the latent heat vanishes. At the phase transition point the dominant diagram percolates and the total magnetic moment is related to the size of the percolating cluster. Its fractal dimension is found d(f) = ( 5 + square root of 5)/4 and it is independent of the type of the lattice and the form of disorder. We argue that the critical behavior is exclusively determined by disorder and the corresponding fixed point is the isotropic version of the so-called infinite randomness fixed point, which is realized in random quantum spin chains. From this mapping we conjecture the values of the critical exponents as beta=2- d(f), beta(s) =1/2, and nu=1.


[Neonatal screening program for congenital hypothyroidism in northeast of Brazil: criteria, diagnosis and results].
It was evaluated the concentration of TSH in blood spot (TSHneo) of 48,039 children included in the Neonatal Screening Program (NSP) for Congenital Hypothyroidism (CH) of Sergipe (SE), a state in the northeast of Brazil. It was also evaluated the concentration of serum TSH, total T4 and free T4 in the recalled children suspicious of having CH, their age in several phases of the program, the covering and frequency of the NSP in the cases from January 2005 to August 2006, comparing them with literature data. The following parameters were used or the analysis: mean, standard deviation, median, coefficient of variation and frequency distribution. The children's age at the collection in filter-paper specimen was 10 +/- 9 days (mean+/-SD) and the TSHneo execution assay was done in the period of 31 +/- 13 days. In 2005 the covering by the NSP was about 77% in the countryside and 73% in Aracaju, the capital of Sergipe. It was verified that in 99.484% of the children included in the screening, the TSHneo varied from 0,01 to 5.20 microU/ml, decreasing according to the age and stabilizing when they were between 11 and 15 days. 248 children were recalled from the TSHneo (1/194).The concentrations of TSH, T4 and free T4 collected by venous puncture were normal in 119 children (1/404). The frequency of suspected CH was 1/485 (99 cases), of CH was 1/6005 (8 cases) and of hypothyroxinemia was 1/16013 (3 cases). Therapy for CH began within 51 +/- 12 days.


RNA regulatory mechanisms that control antiviral innate immunity.
From the initial sensing of viral nucleotides by pattern recognition receptors, through the induction of type I and III interferons (IFN), upregulation of antiviral effector proteins, and resolution of the inflammatory response, each step of innate immune signaling is under tight control. Though innate immunity is often associated with broad regulation at the level of gene transcription, RNA-centric post-transcriptional processes have emerged as critical mechanisms for ensuring a proper antiviral response. Here, we explore the diverse RNA regulatory mechanisms that modulate the innate antiviral immune response, with a focus on RNA sensing by RIG-I-like receptors (RLR), interferon (IFN) and IFN signaling pathways, viral pathogenesis, and host genetic variation that contributes to these processes. We address the post-transcriptional interactions with RNA-binding proteins, non-coding RNAs, transcript elements, and modifications that control mRNA stability, as well as alternative splicing events that modulate the innate immune antiviral response.


Needs assessment for improving library support for dentistry researchers.
To better support dentistry researchers in the ever-changing landscape of scholarly research, academic librarians need to redefine their roles and discover new ways to be involved at each stage of the research cycle. A needs assessment survey was conducted to evaluate faculty members' research support needs and allow a more targeted approach to the development of research services in an academic health sciences library. The anonymous, web-based survey was distributed via email to full-time researchers at the Faculty of Dentistry, University of Toronto. The survey included twenty questions inquiring about researchers' needs and behaviors across three stages of the research cycle: funding and grant applications, publication and dissemination, and research impact assessment. Data were also collected on researchers' use of grey literature to identify whether current library efforts to support researchers should be improved in this area. Among library services, researchers considered support for funding and grant applications most valuable and grey literature support least valuable. Researcher engagement with open access publishing models was low, and few participants had self-archived their publications in the university's institutional repository. Participants reported low interest in altmetrics, and few used online tools to promote or share their research results. Findings indicate that increased efforts should be made to promote and develop services for funding and grant applications. New services are needed to assist researchers in maximizing their research impact and to increase researcher awareness of the benefits of open access publishing models, self-archiving, and altmetrics.


[A comparative study on the syntheses of DNA, RNA and protein during in vitro organogenesis and somatic embryogenesis of Lycium barbarum L].
After the calli originating from the leaf explant of Lycium barbarum L. were selected and proliferated, the yellowish calli with same origin, similar state were transferred to O medium or E medium and the regenerative systems of organogenesis and somatic embryogenesis might form. By these systems, a comparative study on the synthetic activities of DNA, RNA and protein in the two in vitro regeneration pathways was carried out. The results were as follows: (1) Before meristemoid and embryogenic cells were formed, the synthesis of RNA was activated firstly, followed with the increase of synthesis rates of DNA and protein. During the formation of globular embryo, the synthesis rate of DNA increased quickly and then the activities of syntheses of RNA and protein reached the peak, while it was the contrary during germination of adventitious bud. (2) Components of soluble protein changed regularly. A peptide (153.6 kD) appeared during the initiation of both organogenesis and somatic embryogenesis. Several peptides disappearing gradually in the early-stage of differentiation could regenerate with the formation of shoot primordium and globular embryo. Corresponding to morphogenesis, both regenerative systems had specific peptides (84.9 kD, 46.3 kD and 44 kD, 36.2 kD) as molecular markers of its own development. In addition, the relation and mechanism of the two regenerative systems were discussed.


Metallothionein 3 Controls the Phenotype and Metabolic Programming of Alternatively Activated Macrophages.
Alternatively activated (M2) macrophages promote wound healing but weaken antimicrobial defenses. The mechanisms that enforce macrophage divergence and dictate the phenotypic and metabolic characteristics of M2 macrophages remain elusive. We show that alternative activation with interleukin (IL)-4 induces expression of metallothionein 3 (MT3) that regulates macrophage polarization and function. MT3 was requisite for metabolic reprograming in IL-4-stimulated macrophages or M(IL-4) macrophages to promote mitochondrial respiration and suppress glycolysis. MT3 fostered an M(IL-4) phenotype, suppressed hypoxia inducible factor (HIF)1α activation, and thwarted the emergence of a proinflammatory M1 program in macrophages. MT3 deficiency augmented macrophage plasticity, resulting in enhanced interferon γ (IFNγ) responsiveness and a dampened M(IL-4) phenotype. Thus, MT3 programs the phenotype and metabolic fate of M(IL-4) macrophages.


[Methodological considerations in microdialysis].
Microdialysis has rapidly become popular in recent years as an in vivo technique to monitor endogenous substances in the extracellular space of the local brain region. The combination of this technique with a variety of highly sensitive detection methods has enabled us to measure in vivo release of various neurotransmitters. However, the technique involves several methodological problems. The first is that the concentrations of substances in the dialysate only partially reflect their true concentrations in the extracellular space. Therefore, neurotransmitters such as neuropeptides that are present at very low concentrations in the extracellular space are still difficult to detect. The second problem is the effects of tissue damage by the microdialysis probe. Though the probe has been miniaturized, severe disturbance in tissue metabolism cannot be neglected. Histological examination suggests that the most suitable time for commencing microdialysis is between 24 and 48 h after probe implantation. The third problem is that neurotransmitters recovered in the dialysate are sometimes not involved in neurotransmission. It is suggested that the dialysate concentration of a neurotransmitter which reflects neuronal activity should be both tetrodotoxin-sensitive and calcium-dependent. In the case of a neurotransmitter in the dialysate which does not show these characteristics, its concentration may be related to metabolic rather than neurogenic events. The fourth problem is that microdialysis has poor time resolution. Therefore, the method is not suitable for measurement of neurochemical events that rapidly change in short intervals such as milliseconds or seconds. Thus careful consideration has to be given to these problems in the actual laboratory use of microdialysis technique.


Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer: Summary of epidemiologic evidence of cancer risk and prognosis.
Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and prognosis of ovarian and endometrial cancer. The evidence of a preventive effect of NSAID use on risk of ovarian or endometrial cancer is based primarily on results from observational studies and, consequently, is only suggestive. Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian or endometrial cancer risk and prognosis are warranted. In the present review, we discuss the importance of comprehensive exposure definitions (i.e., duration, timing, consistency and intensity/dose) and evaluation of potential effect modification according to user characteristics, with the aim of identifying women who may experience the largest benefit of aspirin or non-aspirin NSAID use on risk or prognosis of ovarian and endometrial cancer.


Cannabis law reform in Western Australia: an opportunity to test theories of marginal deterrence and legitimacy.
'Marginal deterrence' refers to deterrence of a more harmful act because its expected sanction exceeds that for a less harmful act. 'Legitimacy of the law' predicts that laws perceived as fair will generate compliance and laws perceived as unfair will generate defiance. The introduction of the Cannabis Infringement Notice (CIN) scheme in Western Australia provided an opportunity to test these theories by assessing whether perceptions of certainty, severity and fairness of punishments dictated by the CIN scheme would affect how regular cannabis users intended to obtain cannabis after legislative change. One hundred Perth residents (mean age 32.2 years; two-thirds male) who reported using cannabis at least once a week were given semi-structured interviews before the CIN scheme came into effect. There was limited opportunity for the CIN scheme to effect marginal deterrence, as most of the sample were already purchasing or growing within the lower penalty thresholds. However, of the minority who were purchasing and growing outside the CIN scheme, a significant proportion reported intending to change their behaviour to fit within the scheme, including the only purchaser of more than 30 g and six of 14 non-hydroponic growers of three or more plants. Perceived certainty, severity and fairness of penalties were not as important in determining purchasing and growing behaviour as factors such as 'meeting needs', 'cost' and 'preference'. The results suggest that under the CIN scheme, marginal deterrence and legitimacy will probably play only a small or selective role in decisions about obtaining cannabis, although in some areas, such as the numbers of non-hydroponic plants, marginal deterrence may be evident.


Day care management of severe ovarian hyperstimulation syndrome avoids hospitalization and morbidity.
Severe ovarian hyperstimulation syndrome (OHSS) is a dreaded complication of ovulation induction for assisted reproduction treatment. In the past, conservative management has been recommended and this leads to prolonged hospitalization. A total of 18 patients who developed severe OHSS were managed according to two protocols. The first group (n = 8) was managed conservatively with hospitalization, i.v. hydration and supportive therapy. The average duration of hospitalization was 11 days and the patients were uncomfortable throughout. A second group (n = 10) was managed on an out-patient basis with early, ultrasound-guided trans-abdominal paracentesis. While the patient was hydrated intravenously, 1-3 1 of fluid were removed over 2-3 h. The duration of hospitalization was between 6 and 7 h and no in-patient stay was required. Prompt relief of symptoms was reported and none of the patients required re-tapping. Pregnancy was achieved in 68% of all patients. Day care management with easy abdominal paracentesis was found to be simple, safe and effective; patients found it more acceptable as it avoided in-patient hospitalization.


Clinical features and genetic biomarkers associated with different phenotypes of systemic lupus erythematosus in Paraguayan patients.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by a heterogeneous clinical picture that makes the diagnosis and follow-up of these patients difficult. This study aimed to identify correlations between clinical, immunological, and genetic biomarkers and clinical manifestations in SLE. A retrospective study of data from medical records and immunological and genetic studies of SLE patients in Paraguay was carried out. A descriptive analysis was performed based on the type of variable. Human leukocyte antigen (HLA) allele frequencies (DPA1, DPB1, DQA1, DQB1, and DRB1) were calculated, and univariate logistic regression analyses were performed between each of the explanatory variables and the presence or absence of each phenotype. Odds ratios, 95% confidence intervals, and p values were recorded. Associations with p<0.05 were considered statistically significant. 104 SLE patients were included: 86% were female, with a mean age of 32.80±10.36 years. An association was identified between anti-double stranded DNA (anti-dsDNA) and the presence of the renal phenotype and between anti-dsDNA and the absence of the joint and hematological phenotypes. Immunoglobulin M isotype rheumatoid factor was associated with the absence of a renal phenotype. HLA-DQB1*02:02 and HLA-DRB1*07:01 were associated with the cutaneous phenotype. An association was identified between age at disease onset over 30 years and the presence of the joint phenotype. No other associations were identified. Potential clinical, immunological, and genetic biomarkers of phenotypes have been identified in SLE Paraguayan patients.


The role of design patterns in the development and legal assessment of lawful technologies.
Novel technologies such as smart personal assistants integrate digital services into everyday life. These services use personal data to offer personalized services. While they are subject to special data protection regulations at the time of development, there are few guidelines describing the transition from legal requirements to implementation. To reduce risks, services depend on external legal assessments. With developers and legal experts often missing either legal or technical knowledge, the challenge lies in bridging this gap. We observe that design patterns support both developers and legal experts, and we present an approach in which design patterns are leveraged to provide twofold value for both developers and legal experts when dealing with novel technologies. We conducted a revelatory case study for smart personal assistants and scaffolded the case interpretation through cognitive fit theory. On the basis of the findings, we develop a theoretical model to explain and predict the twofold value of design patterns to develop and assess lawful technologies.


[Contralateral suboccipital approach for clipping of an unruptured vertebral artery-posterior inferior cerebellar artery aneurysm].
Numerous approaches have been used to access aneurysms of the vertebral artery(VA)-posterior inferior cerebellar artery(PICA)complex for microsurgical clipping. Here, we report the case of a patient with an unruptured aneurysm of the left VA-PICA complex that was successfully treated using a contralateral suboccipital approach. Computed tomography angiography demonstrated a small saccular aneurysm arising from the lateral aspect of the left V4 segment just distal to the PICA origin. The aneurysm deviated to the right from the midline at the level of the jugular tubercle on angiographic evaluation, so we selected a contralateral suboccipital approach. The aneurysm was completely obliterated by neck clipping. After surgery, slight dysphagia and hoarseness appeared, but dysphagia disappeared within several days and hoarseness disappeared within 5 months. VA-PICA aneurysms can vary in their relationship to cranial nerves, brainstem, and bones of the skull base. Neurosurgeons should consider using a contralateral approach for certain aneurysms arising from a tortuous VA that has crossed the midline.


Immunohistochemical staining of retrobulbar adipose tissue in Graves' ophthalmopathy.
An increase of retrobulbar adipose tissue has been shown by imaging techniques in patients with Graves' ophthalmopathy (GO). Immunohistochemical staining was applied to investigate the involvement of different retrobulbar (especially adipose) tissue components in the autoimmune process of the disease. Cryostat sections from retrobulbar tissues of 15 GO patients and 11 controls were analyzed with a battery of monoclonal antibodies against CD2, CD4, CD8, CD11a, CD19/22, CD25, CD54, CD57, CD68, C3b, HLA-A, B, C, and HLA-DR. In contrast to controls, the retrobulbar adipose tissue showed an increase of HLA-DR expression, an activation of intercellular adhesion molecule I (ICAM-1, CD54), as well as a marked infiltration of activated T-cells (especially CD4) and macrophages (CD68), whereas a positive staining for interleukin-2 receptors (CD25), T-cells (CD2), B-cells (CD19/22), complement factors (C3b), and LFA-1 (CD11a) was present only in a few patients' specimens. Staining for natural killer cells (CD57) was negative in fat tissue of patients and controls. The perimuscular connective tissue sections of GO patients showed an accumulation of T-cells (CD4/CD8), an enhanced display of ICAM-1, LFA-1, HLA-DR-positive cells, and B-cells. Retrobulbar muscle tissue of GO patients exhibited an increase of CD4, CD8, CD54, CD68, and HLA-DR-positive cells, located in the intramuscular connective tissue, exclusively. In conclusion, the present study underlines the involvement of retrobulbar adipose tissue in the immunopathogenesis of Graves' ophthalmopathy.


Frequency of Human Papillomavirus (HPV) 16 and 18 Detection in Paraffin- Embedded Laryngeal Carcinoma Tissue
Background and Objective: Human papilloma virus (HPV) 16 and HPV18 have been detected in head and neck squamous cell carcinomas (HNSCC) and there is evidence that detection of HPVs would have better prognostic value than patients with HNSCC negative for HPVs. Thus, this study was conducted to evaluate frequency of HPV 16 and HPV 18 genotypes in patients with laryngeal carcinoma. Materials and methods: Fifty formalin-fixed, paraffin-embedded (FFPE) tissue blocks of laryngeal cancers were collected. Sections were prepared at 5 μm and DNA was extracted from each sample and subjected to the polymerase chain reaction (PCR) to detect HPV-16/18 DNA s. Results: All samples were squamous cell carcinomas (SCCs). Overall 14/50 (28%) were positive for HPVs, 8 (18%) with HPV-16 and 6 (12%) with HPV-18. Additionally, 2 (4%) mixed infections of HPV 16 and 18 genotypes were observed among these cases. Conclusions: Overall, 28% of HNSCC samples proved positive for HPV16 and HPV18 genotypes, two high-risk HPV types. It is important to further assess whether such viral infection, could be a risk factor in HNSCC progression.


Thin film lithium niobate electric field sensors.
We present our results for using thin film lithium niobate devices for electric field sensing applications. Micro-ring modulator and Mach-Zehnder modulator-based electric field sensors are demonstrated. Micro-ring resonator sensors can be used for low frequency (up to several GHz) electric field sensing applications and achieve a high sensitivity of 80 mV/(m Hz1/2) with a very compact size of 300 μm, as limited by the intensity and phase noise of the used distributed feedback laser. A measurement bandwidth of 2.5 GHz is measured for these sensors and is limited by the detector bandwidth. Alternatively, Mach-Zehnder modulators allow for perfect phase matching between the radio frequency signals and optical signals, and they can be used for electric field sensing up to several THz. A sensitivity of 2.2 V/(m Hz1/2) was obtained using our Mach-Zehnder electric field sensor with an interaction length of 600 μm. The Mach-Zehnder sensor can sense electric fields with frequencies reaching 0.6 THz based on the calculated results.


Lithium-compatible and air-stable vacancy-rich Li9N2Cl3 for high-areal capacity, long-cycling all-solid-state lithium metal batteries.
Attaining substantial areal capacity (>3 mAh/cm2) and extended cycle longevity in all-solid-state lithium metal batteries necessitates the implementation of solid-state electrolytes (SSEs) capable of withstanding elevated critical current densities and capacities. In this study, we report a high-performing vacancy-rich Li9N2Cl3 SSE demonstrating excellent lithium compatibility and atmospheric stability and enabling high-areal capacity, long-lasting all-solid-state lithium metal batteries. The Li9N2Cl3 facilitates efficient lithium-ion transport due to its disordered lattice structure and presence of vacancies. Notably, it resists dendrite formation at 10 mA/cm2 and 10 mAh/cm2 due to its intrinsic lithium metal stability. Furthermore, it exhibits robust dry-air stability. Incorporating this SSE in Ni-rich LiNi0.83Co0.11Mn0.06O2 cathode-based all-solid-state batteries, we achieve substantial cycling stability (90.35% capacity retention over 1500 cycles at 0.5 C) and high areal capacity (4.8 mAh/cm2 in pouch cells). These findings pave the way for lithium metal batteries to meet electric vehicle performance demands.


Parametric analysis of lignocellulosic ultrafiltration in lab scale cross flow module using pore blocking and artificial neural network model.
In this study, fouling mechanism and modelling analysis of synthetic lignocellulose biomass and agricultural palm oil effluent was studied using polyethersulfone (PES) ultrafiltration (UF) 10 kDa membrane. The impact of process variables (transmembrane pressure (TMP), pH and concentration of feed solution) on lignocellulosic flux was analysed using pore blocking model. The feasible approaches on utilising deep learning artificial neural network (ANN) to predict smaller flux datasets are studied. Among the input variables, pH of lignin feed solution has significant control towards flux and lignin rejection coefficient for both lignin and lignocellulosic solution. Alteration in the structure of lignin at different pH conditions contributed in the improvement of lignin rejection coefficient to 0.98 at the feed pH of 9. A maximum steady state flux of 52.03 L/m2h was observed at the lower lignin concentration (0.25 g/L), TMP of 200 kPa and feed pH of 3. At high TMP and concentration, lignin rejection decreased due to enhancement of feed concentration on membrane surface. The mechanistic model exhibited that cake layer phenomena was dominant in both lignin and lignocellulosic solution. The proposed ANN model showed good correlation (R2-1.00) with experimental non-linear flux dynamic data of both lignin and synthetic lignocellulosic solution. In ANN analysis, activation function, algorithm and neuron effect have significant effect in design of accurate model for prediction of small flux datasets. Aerobically-treated palm oil mill filtration analysis also showed that cake layer phenomenon was dominant. A water recovery of 82 % was achieved even at low TMP under short durations.


Georges Brohee Prize 1996. Major cytochrome P-450 families: implications in health and liver diseases.
Cytochromes P-450 are a superfamily of hemoproteins which represent the main pathway for drug and chemical oxidation. This superfamily is divided into families, subfamilies and/or single enzymes. The majority of P-450s involved in drug metabolism appear to belong to three distinct families termed CYP1, CYP2 and CYP3. Numerous invasive and non-invasive methodologies have been developed to study these enzymes. Their activities are modulated by genetic and nongenetic factors as well as pathological conditions. In this work, the significance of genetic and nongenetic control of P-450s activities in normal subjects is described. Thereafter, the impact of P-450s on the apparition of liver diseases and the effects of liver disease on P-450s activities is emphasized. In conclusion, future perspectives on this field are presented.


N-Fluorobenzenesulfonimide-Mediated Intermolecular Carboselenenylation of Olefins with Aromatics and Diselenides.
Intermolecular carboselenenylation of easily accessible alkenes by utilizing diselenides and N-fluorobenzenesulfonimide (NFSI) under metal-free and mild conditions is reported. Preliminary mechanistic studies indicate that the oxidation of diselenide by NFSI through a single-electron-transfer process produces an active selenenyl cationic radical species that initiates the intermolecular carboselenenylation of olefins, forming key Se-C and C-C bonds. Under optimized conditions, a broad spectrum of functionally and structurally diverse selenoether derivatives with promising yields is accessed with a very high functional group tolerance.


Novel thermostable glycosidases in the extracellular matrix of the terrestrial cyanobacterium Nostoc commune.
The cyanobacterium Nostoc commune is adapted to the terrestrial environment and forms a visible colony in which the cells are embedded in extracellular polysaccharides (EPSs), which play a crucial role in the extreme desiccation tolerance of this organism. When natural colonies were immersed in water, degradation of the colonies occurred within 2 days and N. commune cells were released into the water. The activities that hydrolyze glycoside bonds in various N. commune fractions were examined using artificial nitrophenyl-linked sugars as substrates. A beta-D-glucosidase purified from the water-soluble fraction was resistant to 20 min of boiling. The beta-D-glucosidase, with a molecular mass of 20 kDa, was identified as a cyanobacterial fasciclin protein based on its N-terminal amino-acid sequence. The 36-kDa major protein in the water-soluble fraction was purified, and the N-terminal amino-acid sequence of the protein was found to be identical to that of the water-stress protein (WspA) of N. commune. This WspA protein also showed heat-resistant beta-D-galactosidase activity. The fasciclin protein and WspA in the extracellular matrix may play a role in the hydrolysis of the EPSs surrounding the cells, possibly as an aid in the dispersal of cells, thus expanding the colonies of this cyanobacterium.


Determination of subgroup, serotype and electropherotype of human rotaviruses obtained from diarrheic patients in the Philippines.
A total of 40 rotavirus specimens obtained from infants with acute gastroenteritis in Metro Manila, Philippines, were analyzed for their subgroup and serotype specificities and RNA electropherotype. A half (50%) of the specimens contained subgroup I human rotaviruses (HRVs), while 45% of them contained subgroup II HRVs. All subgroup II HRVs were determined to be serotype 1, except one specimen belonging to serotype 3, by an enzyme-linked immunosorbent assay with serotype specific monoclonal antibodies. However, serotype specificity of all subgroup I specimens failed to be determined. In polyacrylamide gel electrophoresis, RNAs extracted from HRVs of either subgroup showed long electropherotype. At least two electropherotypes were distinguished in subgroup I viruses, while five different patterns of viral RNA were found in subgroup II viruses.


Corneal topometric, aberrometric and biomechanical parameters in mucopolysaccharidosis patients.
To report corneal topometric and aberrometric values in mucopolysaccharidosis (MPS) and to investigate their correlation with biomechanical corneal parameters. One randomly chosen eye of 20 MPS patients with no to moderate corneal clouding and one eye of 23 healthy controls with comparable age were prospectively included into this study. Corneal surface regularity was assessed by index of surface variance (ISV), -vertical asymmetry (IVA), -height asymmetry (IHA), -height decentration (IHD); keratoconus index (KI), central keratoconus index (CKI) and Zernike indices of anterior and posterior corneal surface using Scheimpflug imaging (Pentacam). Corneal resistance factor (CRF) and corneal hysteresis (CH) were assessed by Ocular Response Analyzer. Statistical analyses were performed using Mann-Whitney-Test and Spearman Correlation Coefficients. IVA, ISV, IHD, IHA, but not KI and CKI were significantly higher in MPS patients compared to age matched healthy controls. Spherical aberration and asphericity coefficients either at the anterior or at the posterior corneal surface differed significantly between both groups. The grade of the MPS-associated corneal opacity correlated significantly with ISV (rho = 0.52), IVA (rho = 0.54), IHA (rho = 0.57) and IHD (rho = 0.48). Density of the MPS-affected corneas correlated significantly with ISV (rho = 0.52), IVA (rho = 0.72), IHA (rho = 0.57), IHD (rho = 0.69), 3rd order horizontal trefoil aberration at the posterior (rho = 0.62) and anterior surface (rho = 0.48) as well as with CH (rho = 0.55) and CRF (rho = 0.57). Spherical aberration at the back surface correlated with CRF and CH in MPS and in healthy controls. This is the first study analyzing shape of the corneal surface in MPS patients. Topometric indices of corneal asymmetry are significantly increased and correlate with MPS-related corneal opacity and density. Spherical aberration and asphericity coefficient at the front and at the back corneal surface differ significantly between MPS and healthy controls.


Exposure Cessation During Adulthood Did Not Prevent Immunotoxicity Caused by Developmental Exposure to Low-Level Trichloroethylene in Drinking Water.
Exposure to the water pollutant trichloroethylene (TCE) can promote autoimmunity in both humans and rodents. Using a mouse model we have shown that chronic adult exposure to TCE at 500 μg/ml in drinking water generates autoimmune hepatitis in female MRL+/+ mice. There is increasing evidence that developmental exposure to certain chemicals can be more toxic than adult exposure. This study was designed to test whether exposure to a much lower level of TCE (0.05 μg/ml) during gestation, lactation, and early life generated autoimmunity similar to that found following adult exposure to higher concentrations of TCE. When female MRL+/+ mice were examined at postnatal day (PND) 259 we found that developmental/early life exposure [gestational day 0 to PND 154] to TCE at a concentration 10 000 fold lower than that shown to be effective for adult exposure triggered autoimmune hepatitis. This effect was observed despite exposure cessation at PND 154. In concordance with the liver pathology, female MRL+/+ exposed during development and early life to TCE (0.05 or 500 μg/ml) generated a range of antiliver antibodies detected by Western blotting. Expression of proinflammatory cytokines by CD4+ T cells was also similarly observed at PND 259 in the TCE-exposed mice regardless of concentration. Thus, exposure to TCE at approximately environmental levels from gestational day 0 to PND 154 generated tissue pathology and CD4+ T cell alterations that required higher concentrations if exposure was limited to adulthood. TCE exposure cessation at PND 154 did not prevent the immunotoxicity.


The Preterm Prediction Study: the value of serum alkaline phosphatase, alpha-fetoprotein, plasma corticotropin-releasing hormone, and other serum markers for the prediction of spontaneous preterm birth.
High levels of a number of analytes are found in maternal blood; alkaline phosphatase,alpha-fetoprotein, and corticotropin-releasing hormone have been associated with spontaneous preterm birth. We investigated the relationship between 8 potential blood markers and subsequent spontaneous preterm birth in asymptomatic pregnant women. We performed a nested case control study that involved 127 women who were enrolled in the preterm prediction study and who had a singleton spontaneous preterm birth at <35 weeks and 127 women who had a term birth and served as matched (age, parity, center) controls. Serum that was collected at 24 and 28 weeks was analyzed for alkaline phosphatase, alpha-fetoprotein, corticotropin-releasing hormone, and 5 other analytes. Alkaline phosphatase, alpha-fetoprotein, and corticotropin-releasing hormone, but not other analytes, were significantly elevated in pregnancies that ended in spontaneous preterm birth. For alkaline phosphatase at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 6.8 (range, 1.4-32.8) and for spontaneous preterm birth at <35 weeks 5.1 (range, 1.7-15.6). Similar results were found at 28 weeks. For alpha-fetoprotein at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 8.3 (range,2.2-30.9) and for spontaneous preterm birth at <35 weeks was 3.5 (range, 1.8-6.7). The levels at 28 weeks were still predictive but less so than at 24 weeks. Corticotropin-releasing hormone, at 28 weeks but not at 24 weeks, was predictive for spontaneous preterm birth at <35 weeks, with an odds ratio 3.4 (range, 1.0-10.9). Elevated alkaline phosphatase and alpha-fetoprotein are associated with subsequent spontaneous preterm birth in asymptomatic pregnant women at 24 and 28 weeks. Elevated corticotropin-releasing hormone levels at 28 weeks are associated with spontaneous preterm birth at <35 weeks.


[Health effects of migration].
Migration may have a negative impact on the health status of migrants due to the multiple physical and psychosocial strains affecting them during the entire process of migration. Being exposed to these strains and suffering different kinds of losses might lead to stress and increase in risk behaviour among migrants, thereby impacting negatively on their somatic and mental health. The negative health effects of migration are mediated by the individual's resources e.g. social support.


Changing incidence of inflammatory bowel disease: environmental influences and lessons learnt from the South asian population.
Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract associated with significant morbidity. While IBD occurs in genetically susceptible individuals, the etiology is multifactorial, involving environmental influences, intestinal dysbiosis, and altered immune responses. The rising incidence of IBD in industrialized countries and the emergence of IBD in countries with traditionally low prevalence underscore the importance of environmental influences in the pathobiology of the disease. Moreover the high incidence of IBD observed in the South Asian immigrant population in the United Kingdom and Canada further supports the influence of environmental factors.


Flexible behavioral capture-recapture modeling.
We develop alternative strategies for building and fitting parametric capture-recapture models for closed populations which can be used to address a better understanding of behavioral patterns. In the perspective of transition models, we first rely on a conditional probability parameterization. A large subset of standard capture-recapture models can be regarded as a suitable partitioning in equivalence classes of the full set of conditional probability parameters. We exploit a regression approach combined with the use of new suitable summaries of the conditioning binary partial capture histories as a device for enlarging the scope of behavioral models and also exploring the range of all possible partitions. We show how one can easily find unconditional MLE of such models within a generalized linear model framework. We illustrate the potential of our approach with the analysis of some known datasets and a simulation study.


Association between population structure and allele frequencies of the glycogen synthase 1 mutation in the Austrian Noriker draft horse.
The aim of this study was to determine the allele frequency of the glycogen synthase 1 (GYS1) mutation associated with polysaccharide storage myopathy type 1 in the Austrian Noriker horse. Furthermore, we examined the influence of population substructures on the allele distribution. The study was based upon a comprehensive population sample (208 breeding stallions and 309 mares) and a complete cohort of unselected offspring from the year 2014 (1553 foals). The mean proportion of GYS1 carrier animals in the foal cohort was 33%, ranging from 15% to 50% according to population substructures based on coat colours. In 517 mature breeding horses the mutation carrier frequency reached 34%, ranging on a wider scale from 4% to 62% within genetic substructures. We could show that the occurrence of the mutated GYS1 allele is influenced by coat colour; genetic bottlenecks; and assortative, rotating and random mating strategies. Highest GYS1 carrier frequencies were observed in the chestnut sample comprising 50% in foals, 54% in mares and 62% in breeding stallions. The mean inbreeding of homozygous carrier animals reached 4.10%, whereas non-carrier horses were characterized by an inbreeding coefficient of 3.48%. Lowest GYS1 carrier frequencies were observed in the leopard spotted Noriker subpopulation. Here the mean carrier frequency reached 15% in foals, 17% in mares and 4% in stallions and inbreeding decreased from 3.28% in homozygous non-carrier horses to 2.70% in heterozygous horses and 0.94% in homozygous carriers. This study illustrates that lineage breeding and specified mating strategies result in genetic substructures, which affect the frequencies of the GYS1 gene mutation.


Psychotic experiences and mood episodes predict each other bidirectionally: a 6-year follow-up study in a community-based population.
Psychotic experiences (PEs) are not exclusive to psychotic disorders and highly correlated with mood episodes. In this representative general population-based study, longitudinal bidirectional associations between the extended psychosis phenotype and mood episodes were investigated, accounting for other possible causes. Households were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighbourhoods at baseline (n = 4011) and at 6-year follow-up (n = 2185). Participants were interviewed with the relevant sections of the composite international diagnostic interview both at baseline and at follow-up. Sociodemographic, familial and environmental risk factors associated with the extended psychosis phenotype and mood episodes were assessed. Logistic regression and cross-lagged panel correlation models were used for the associations between the extended psychosis phenotype and mood episodes. PEs were associated with subsequent depressive and manic episodes. There was bidirectionality in that mood episodes were associated with subsequent PEs, and PEs were associated with subsequent mood episodes. The associations occurred in a sub-additive pattern. There were substantial synchronous and cross-lagged correlations between these psychopathology domains, with reciprocally similar cross-lagged correlations. Familial risk and adverse life events were associated with both psychopathology domains, whereas some sociodemographic risk factors and alcohol/cannabis use were associated with only one domain. The sub-additive bidirectional associations between PEs and mood episodes over time and the similarity of cross-lagged correlations are suggestive of mutually causal connections between affective and psychotic domains of psychopathology.


The Ste20-like kinase SLK is required for cell cycle progression through G2.
We have previously shown that the Ste20-like kinase SLK is a microtubule-associated protein that can regulate actin reorganization during cell adhesion and spreading (Wagner, S., Flood, T. A., O'Reilly, P., Hume, K., and Sabourin, L. A. (2002) J. Biol. Chem. 277, 37685-37692). Because of its association with the microtubule network, we investigated whether SLK plays a role in cell cycle progression, a process that requires microtubule dynamics during mitosis. Consistent with microtubule association in exponentially growing cells, our results showed that SLK co-localizes with the mitotic spindle in cells undergoing mitosis. Expression of a kinase-inactive mutant or SLK small interfering RNAs inhibited cell proliferation and resulted in an accumulation of quiescent cells stimulated to re-enter the cell cycle in the G2 phase. Cultures expressing the mutant SLK displayed a normal pattern of cyclin D, E, and B expression but failed to down-regulate cyclin A levels, suggesting that they cannot proceed through M phase. In addition, these cultures displayed low levels of both phospho-H3 and active p34/cdc2 kinase. Overexpression of active SLK resulted in ectopic spindle assembly and the induction of cell cycle re-entry of Xenopus oocytes, suggesting that SLK is required for progression through G2 upstream of H1 kinase activation.


Effect of malaria on HIV/AIDS transmission and progression.
Malaria and HIV are among the two most important global health problems of developing countries. They cause more than 4 million deaths a year. These two infections interact bidirectionally and synergistically with each other. HIV infection increases the risk of an increase in the severity of malaria infection and burdens of malaria, which in turn facilitates the rate of malaria transmission. Malaria infection is also associated with strong CD4+ cell activation and up-regulation of proinflammatory cytokines and it provides an ideal microenvironment for the spread of the virus among the CD4+ cells and for rapid HIV-1 replication. Additionally, malaria increases blood viral burden by different mechanisms. Therefore, high concentrations of HIV-1 RNA in the blood are predictive of disease progression, and correlate with the risk of blood-borne, vertical, and sexual transmission of the virus. Therefore, this article aims to review information about HIV malaria interactions, the effect of malaria on HIV transmission and progression and the implications related to prevention and treatment of coinfection.


Antigenic studies on mouse lymphomas bearing the T190 translocation chromosome.
Heterozygous mice of the T190/tf translocation stock, having one superlong and one short marker chromosome, involving the H-2-bearing ninth linkage group, were typed by membrane fluorescence and cytotoxicity tests against a panel of H-2 antisera. Marker-positive segregants differed serologically from their marker-negative siblings. Lymphomas were induced by the Moloney virus in (A.CA x T190/tf)F1 mice. A combined serological and cytogenetic analysis showed that the tumors could be subdivided into two main classes, corresponding to marker-positive and marker-negative types. Each lymphoma was relatively stable with regard to karyologic and correlated antigenic characteristics during serial passage in (A.CA x T190/tf)F1 mice. This system opens new possibilities to study the genetic mechanisms of H-2 antigenic variation, demonstrated previously in heterozygous tumors.


A distinct new species of riparian rock-dwelling gecko (genus: Hemidactylus) from the southern Western Ghats.
We describe a new species of rock-dwelling gecko, Hemidactylus paaragowlipaaragowli sp. nov., from the Agastyamalai Hill Range, in the southern Western Ghats. Morphological and molecular data support the distinctiveness of the species and its close relationship to other large-bodied, tuberculate Hemidactylus spp. from the H. prashadi group from India and Sri Lanka. This species belongs to a rupicolous complex and can be distinguished from other members of the group based on the following characters: 22-24 longitudinal rows of fairly regularly arranged, subtrihedral, weakly keeled, striated tubercles at midbody; 9-11 and 10-12 subdigital lamellae on the first and fourth digits, respectively, of both manus and pes; tail with transverse series of four enlarged tubercles on each tail segment; 10-12 femoral pores on each side separated by 16-18 scales without pores; 11-13 supralabials and 9-10 infralabials.


Robust Perception and Precise Segmentation for Scribble-Supervised RGB-D Saliency Detection.
This paper proposes a scribble-based weakly supervised RGB-D salient object detection (SOD) method to relieve the annotation burden from pixel-wise annotations. In view of the ensuing performance drop, we summarize two natural deficiencies of the scribbles and try to alleviate them, which are the weak richness of the pixel training samples (WRPS) and the poor structural integrity of the salient objects (PSIO). WRPS hinders robust saliency perception learning, which can be alleviated via model design for robust feature learning and pseudo labels generation for training sample enrichment. Specifically, we first design a dynamic searching process module as a meta operation to conduct multi-scale and multi-modal feature fusion for the robust RGB-D SOD model construction. Then, a dual-branch consistency learning mechanism is proposed to generate enough pixel training samples for robust saliency perception learning. PSIO makes direct structural learning infeasible since scribbles can not provide integral structural supervision. Thus, we propose an edge-region structure-refinement loss to recover the structural information and make precise segmentation. We deploy all components and conduct ablation studies on two baselines to validate their effectiveness and generalizability. Experimental results on eight datasets show that our method outperforms other scribble-based SOD models and achieves comparable performance with fully supervised state-of-the-art methods.