[Features of the biogenesis of Escherichia coli alkaline phosphatase during its supersynthesis].
The oversynthesis of the secreted alkaline phosphatase (PhoA) in E.coli K12802 cells due to transformation with the PhoA+ plasmid pHI-7 leads to a change in its biogenesis--alternative localization and accumulation of the enzyme intermediate forms corresponding to different stages of the its post-translational modification. Instead of the soluble PhoA available in the parent strain mostly as a completely processed mature metazyme III localized in the periplasm, five enzyme forms were discovered in the PhoA overproducer: a cytoplasmic PhoA precursor (prePhoA) as insoluble aggregates; three soluble metazymes of a mature active form localized in the periplasm as in well as in culture medium; and a soluble high-molecular form in the periplasm. PrePhoA was isolated and purified by removal of soluble cell fractions using differential centrifugation, solubilization of membrane proteins with Triton X100, dissolution of the aggregates in the buffer with 8M urea and FPLC on MonoQ. Extracellular PhoA was purified by ultrafiltration, thermal treatment, and gel chromatography on Sepharose CL-4B. It was shown that the isolated prePhoA can be transformed into a mature form in the presence of a leader peptidase in 0.8 urea and is completely cleaved with proteinase K. Three forms of the mature PhoA vary in resistance to proteinase K and trypsin. Metazyme I, the unprocessed mature PhoA, is the most resistant to proteolysis.


Smoking behaviors and attitudes during adolescence prospectively predict support for tobacco control policies in adulthood.
Several cross-sectional studies have examined factors associated with support for tobacco control policies. The current study utilized a longitudinal design to test smoking status and attitude toward smoking measured in adolescence as prospective predictors of support for tobacco control policies measured in adulthood. Participants (N = 4,834) were from a longitudinal study of a Midwestern community-based sample. Hierarchical multiple regression analyses tested adolescent smoking status and attitude toward smoking as prospective predictors (after controlling for sociodemographic factors, adult smoking status, and adult attitude toward smoking) of support for regulation of smoking in public places, discussion of the dangers of smoking in public schools, prohibiting smoking in bars, eliminating smoking on television and in movies, prohibiting smoking in restaurants, and increasing taxes on cigarettes. Participants who smoked during adolescence demonstrated more support for discussion of the dangers of smoking in public schools and less support for increasing taxes on cigarettes but only among those who smoked as adults. Those with more positive attitudes toward smoking during adolescence demonstrated less support as adults for prohibiting smoking in bars and eliminating smoking on television and in movies. Moreover, a significant interaction indicated that those with more positive attitudes toward smoking as adolescents demonstrated less support as adults for prohibiting smoking in restaurants, but only if they became parents as adults. This study's findings suggest that interventions designed to deter adolescent smoking may have future benefits in increasing support for tobacco control policies.


The genetic basis of quantitative variation in susceptibility of Arabidopsis thaliana to Pseudomonas syringae (Pst DC3000): evidence for a new genetic factor of large effect.
* Pathogens represent an important threat to plant communities and agriculture, and can shape many aspects of plant evolution. Natural variation in plant disease susceptibility is typically quantitative, yet studies on the molecular basis of disease resistance have focused mainly on qualitative variation. * Here we investigated the genetic architecture of quantitative susceptibility to the bacterium Pseudomonas syringae by performing a quantitative trait locus (QTL) analysis on the F2 progeny of two natural accessions of Arabidopsis thaliana under two nutrient treatments. * We found that a single QTL explains most of the variation (77%) in susceptibility between accessions Columbia (Col-0) and San Feliu-2 (Sf-2), and its effect is independent of nutrients. The Sf-2 allele at this QTL is dominant and can reduce the bacterial population size by 31-fold, much like a classical resistance (R) gene. However, minor QTLs, whose effects are altered by nutrient treatment, were also detected. * Surprisingly, we found that none of the QTLs for susceptibility had any effect on fruit production, suggesting that the use of resistance genes for crop improvement and evolutionary analysis of plant-pathogen interactions requires caution.


Continuous models for cell migration in tissues and applications to cell sorting via differential chemotaxis.
Chemotaxis, the guided migration of cells in response to chemical gradients, is vital to a wide variety of biological processes, including patterning of the slime mold Dictyostelium, embryonic morphogenesis, wound healing, and tumor invasion. Continuous models of chemotaxis have been developed to describe many such systems, yet few have considered the movements within a heterogeneous tissue composed of multiple subpopulations. In this paper, a partial differential equation (PDE) model is developed to describe a tissue formed from two distinct chemotactic populations. For a "crowded" (negligible extracellular space) tissue, it is demonstrated that the model reduces to a simpler one-species system while for an "uncrowded" tissue, it captures both movement of the entire tissue (via cells attaching to/migrating within an extracellular substrate) and the within-tissue rearrangements of the separate cellular subpopulations. The model is applied to explore the sorting of a heterogeneous tissue, where it is shown that differential-chemotaxis not only generates classical sorting patterns previously seen via differential-adhesion, but also demonstrates new classes of behavior. These new phenomena include temporal dynamics consisting of a traveling wave composed of spatially sorted subpopulations reminiscent of Dictyostelium slugs.


Genetic variants and effect modifiers of QT interval prolongation in patients with sickle cell disease.
Sickle cell disease (SCD) is a common inherited blood disorder among African Americans (AA), with premature mortality which has been associated with prolongation of the heart rate-corrected QT interval (QTc), a known risk factor for sudden cardiac death. Although numerous genetic variants have been identified as contributors to QT interval prolongation in the general population, their impact on SCD patients remains unclear. This study used an unweighted polygenic risk score (PRS) to validate the previously identified associations between SNPs and QTc interval in SCD patients, and to explore possible interactions with other factors that prolong QTc interval in AA individuals with SCD. In SCD patients, candidate genetic variants associated with the QTc interval were genotyped. To identify any risk SNPs that may be correlated with QTc interval prolongation, linear regression was employed, and an unweighted PRS was subsequently constructed. The effect of PRS on the QTc interval was evaluated using linear regression, while stratification analysis was used to assess the influence of serum alanine transaminase (ALT), a biomarker for liver disease, on the PRS effect. We also evaluated the PRS with the two subcomponents of QTc, the QRS and JTc intervals. Out of 26 candidate SNPs, five risk SNPs were identified for QTc duration under the recessive model. For every unit increase in PRS, the QTc interval prolonged by 4.0 ms (95% CI: [2.0, 6.1]; p-value: <0.001) in the additive model and 9.4 ms in the recessive model (95% CI: [4.6, 14.1]; p-value: <0.001). Serum ALT showed a modification effect on PRS-QTc prolongation under the recessive model. In the normal ALT group, each PRS unit increased QTc interval by 11.7 ms (95% CI: [6.3, 17.1]; p-value: 2.60E-5), whereas this effect was not observed in the elevated ALT group (0.9 ms; 95% CI: [-7.0, 8.8]; p-value: 0.823). Several candidate genetic variants are associated with QTc interval prolongation in SCD patients, and serum ALT acts as a modifying factor. The association of a CPS1 gene variant in both QTc and JTc duration adds to NOS1AP as evidence of involvement of the urea cycle and nitric oxide metabolism in cardiac repolarization in SCD. Larger replication studies are needed to confirm these findings and elucidate the underlying mechanisms.


A combination of serological assays to detect human antibodies to the avian influenza A H7N9 virus.
Human infection with avian influenza A H7N9 virus was first identified in March 2013 and represents an ongoing threat to public health. There is a need to optimize serological methods for this new influenza virus. Here, we compared the sensitivity and specificity of the hemagglutinin inhibition (HI), microneutralization (MN), and Western blot (WB) assays for the detection of human antibodies against avian influenza A (H7N9) virus. HI with horse erythrocytes (hRBCs) and a modified MN assay possessed greater sensitivity than turkey erythrocytes and the standard MN assay, respectively. Using these assays, 80% of tested sera from confirmed H7N9 cases developed detectable antibody to H7N9 after 21 days. To balance sensitivity and specificity, we found serum titers of ≥20 (MN) or 160 (HI) samples were most effective in determining seropositive to H7N9 virus. Single serum with HI titers of 20-80 or MN titer of 10 could be validated by each other or WB assay. Unlike serum collected from adult or elderly populations, the antibody response in children with mild disease was low or undetectable. These combinations of assays will be useful in case diagnosis and serologic investigation of human cases.


Catalytic enantioselective aldol reactions.
Recent developments in catalytic asymmetric aldol reactions have been summarized. Enantioselective aldol reactions are important methods to synthesize β-hydroxy carbonyl compounds in optical pure form, and as such, numerous successful chiral catalysts were designed and applied for asymmetric aldol reactions. This review article is organized under the categories of: (1) catalytic enantioselective aldol reactions of preformed enolates, (2) catalytic enantioselective direct-type aldol reactions using chiral metal catalysts, (3) catalytic enantioselective direct-type aldol reactions using organocatalysts, (4) catalytic enantioselective aldol reactions in aqueous media. Examples of the aldol reactions that employ simple carbonyl compounds will be also the focus of this review.


Local conformational switching of supramolecular networks at the solid/liquid interface.
We use the electric field in a scanning tunneling microscope to manipulate the transition between open and close packed 2D supramolecular networks of neutral molecules in nonpolar media. We found that while the magnitude of the applied field is not decisive, it is the sign of the polarization that needs to be maintained to select one particular polymorph. Moreover, the switching is independent of the solvent used and fully reversible. We propose that the orientation of the surface dipole determined by the electric field might favor different conformation-depended charge transfer mechanisms of the adsorbates to the surface, inducing open (closed) structures for negative (positive) potentials. Our results show the use of local fields to select the polymorphic outcome of supramolecular assemblies at the solid/liquid interface. The effect has potential to locally control the capture and release of analytes in host-guest systems and the 2D morphology in multicomponent layers.


[The use of cross-sectional imaging modalities in the diagnosis of valvular heart disease].
Exact visualization of valve morphology seems to be possible with the cross-sectional imaging modalities, magnetic resonance imaging (MRI) and the recently introduced technique of multidetector computed tomography (MDCT). These techniques are used, if other non-invasive imaging modalities, like echocardiography, fail or provide only insufficient information. This commonly occurs in the assessment of right ventricular valves. Quantification of valve stenosis is possible by calculating valve orifice area, which can be performed with MRI and MDCT. An estimation of the instantaneous peak gradient can only be achieved by MR flow measurements. MR flow measurement is a reliable method to quantify the degree of mild to moderate stenoses. Quantification of valve regurgitation is possible by measurement of the regurgitation fraction with MR flow measurements as well as with MR volumetry/CT volumetry. But only the MR flow measurement is suitable for the quantification of valve regurgitation in patients with multiple valves involved or cardiac shunting. MRI and probably MDCT are the most reliable methods in the evaluation of ventricular volumes and therefore suitable for the follow-up in patients with valvular heart disease, because changes in volumes are important for therapeutic decisions in these patients. The crucial advantages of MRI compared to CT in the diagnostic of valvular heart diseases however are the absence of radiation exposure, the possibility of quantitative evaluation of valves function using flow measurements and the higher temporal resolution as compared to MDCT.


Identification and geographical distribution of pyrethroid resistance mutations in the poultry red mite Dermanyssus gallinae.
The poultry red mite (PRM) Dermanyssus gallinae is the most common ectoparasite on poultry and causes high economic losses in poultry farming worldwide. Pyrethroid acaricides have been widely used for its control and, consequently, pyrethroid resistance has arisen. In this study we aim to investigate the occurrence of resistance and study the geographical distribution of pyrethroid resistance mutations across PRM populations in Europe. Full dose-response contact bioassays revealed very high levels of resistance against several pyrethroids (α-cypermethrin, fluvalinate, and cyfluthrin) in two PRM populations from Greece, compared to a susceptible reference strain. Resistance was associated with mutations in the gene encoding the target site of pyrethroids, the voltage-gated sodium channel (VGSC). Mutations, M918L and L925V in domain IIS4-S5 and F1534L in domain IIIS6, were found at positions known to play a role in pyrethroid resistance in other arthropod species. Subsequent screening by sequencing VGSC gene fragments IIS4-S5 and IIIS6 revealed the presence and distribution of these mutations in many European populations. In some populations, we identified additional or different mutations including M918V/T, L925M, T929I, I936F, and F1538L. The latter mutation is a possible alternative for F1538I that has been previously associated with pyrethroid resistance in other Acari species. We report very high levels of pyrethroid resistance in PRM populations from Greece, as well as the identification and geographical distribution of 10 pyrethroid resistance mutations in PRM populations across Europe. Our results draw attention to the need for an evidence-based implementation of PRM control, taking acaricide resistance management into consideration. © 2019 Society of Chemical Industry.


Concurrent or sequential development of medial meniscal and subchondral cystic lesions within the medial femorotibial joint in horses (1996-2006).
Summary Reasons for performing study: Medial meniscal injuries and subchondral cystic lesions (SCL) are known to occur independently within the medial femorotibial (MFT) joint in horses. However, there are no reports of a potential clinical relationship between these 2 types of lesions. To: 1) document the concurrent presence or sequential development of medial meniscal and SCL of the medial femoral condyle within the MFT joint; and 2) determine the prognosis with both types of lesions. Retrospective case series of horses with both a medial meniscal and SCL of the medial femoral condyle identified concurrently or sequentially by radiography, arthroscopy or post mortem examination. Case records and radiographs were reviewed, and a telephone survey of referring veterinarians, owners and trainers was conducted. Twenty-one horses (9.1% of all horses undergoing MFT joint arthroscopy) were identified to have both a medial meniscal injury and SCL of the medial femoral condyle. Thirteen horses had both abnormalities identified concurrently, 6 developed a meniscal lesion subsequent to SCL debridement, and 2 developed a SCL subsequent to a medial meniscal injury. Only 4/19 horses were classified as successful and returned to their intended use. The severity of the meniscal injury was significantly associated with the severity of lameness but not with outcome. A low percentage of horses may develop both a meniscal injury and SCL of the medial femoral condyle within the MFT joint and have a poor prognosis. Trauma to the MFT joint may lead to both meniscal and subchondral bone damage of the medial femoral condyle that may be recognised concurrently or sequentially.


Respiratory mechanics and lung tissue remodeling in a hepatopulmonary syndrome rat model.
Intrapulmonary vasodilation is a hallmark of the hepatopulmonary syndrome (HPS). However, its effects on respiratory mechanical properties and lung morphology are unknown. To determine these effects, 28 rats were randomly divided to control and experimental HPS groups (eHPS). The spontaneous breathing pattern, gas exchange, respiratory system mechanical properties, and lung and liver morphology of the rats were evaluated. Tidal volume, minute ventilation and mean inspiratory flow were significantly reduced in the eHPS group. Chest wall pressure dissipation against the resistive and viscoelastic components and elastic elastance were increased in the eHPS group. The lung resistive pressure dissipation was lower but the viscoelastic pressure was higher in the eHPS group. The airway volume proportion of collagen and elastic fibers was increased in the eHPS animals (16% and 51.7%; P<0.05 and P<0.001, respectively). The proportion of collagen volume in the vasculature increased 29% in the eHPS animals (P<0.01). HPS presents with respiratory system mechanical disarray as well as airway and vascular remodeling.


Bronchogenic carcinoma masquerading as primary esophageal disease.
This report describes our experience with six patients with dysphagia as the sole manifestation of radiographic, inconspicuous primary lung cancer and well-defined esophageal lesion by barium swallow. Esophagograms suggested leiomyoma, benign esophageal stricture, duplication cyst, achalasia, and primary carcinoma of the esophagus. Careful evaluation of the chest radiographs in all patients presenting with dysphagia is emphasized. The majority of esophageal findings are subcarinal and bronchoscopy should be considered essential in the workup of these patients.


Self and other in schizophrenia: a cognitive neuroscience perspective.
Recent basic science data indicate that in healthy individuals, self-referential processing and social cognition rely on common neural substrates. The authors assessed self-referential source memory and social cognition in a large sample of schizophrenia outpatients and healthy comparison subjects in order to compare how these critical processes are associated in the two groups. Ninety-one schizophrenia outpatients and 30 healthy comparison subjects were assessed on measures of basic social cognition and source memory for previously learned word items: self-generated, externally presented, and new words. Partial correlations and multiple regression analysis were used to test the association between social cognition measures and source memory performance and the contributions of source memory and general cognitive abilities to a social cognition composite score. Schizophrenia patients demonstrated significantly lower source memory for self-generated items (self-referential source memory) relative to comparison subjects but showed intact external source memory. In both groups, self-referential source memory and social cognition showed strong correlations. When the effects of general cognitive abilities were controlled for, these correlations were attenuated in the schizophrenia patients. Regression analysis revealed discrepancies between groups in the cognitive functions contributing to social cognition performance. Impaired self-referential source memory represents a unique cognitive deficit in schizophrenia. Moreover, the strong association between self-referential source memory and social cognition seen in healthy subjects is reduced in schizophrenia and is moderated by general cognitive abilities. Impairments in the neurocognitive system that underlies both self-referential and social cognition provide a parsimonious explanation for the disturbances in the sense of self and other that characterize schizophrenia.


Numerical Prediction of the Mechanical Failure of the Intervertebral Disc under Complex Loading Conditions.
Finite element modeling has been widely used to simulate the mechanical behavior of the intervertebral disc. Previous models have been generally limited to the prediction of the disc behavior under simple loading conditions, thus neglecting its response to complex loads, which may induce its failure. The aim of this study was to generate a finite element model of the ovine lumbar intervertebral disc, in which the annulus was characterized by an anisotropic hyperelastic formulation, and to use it to define which mechanical condition was unsafe for the disc. Based on published in vitro results, numerical analyses under combined flexion, lateral bending, and axial rotation with a magnitude double that of the physiological ones were performed. The simulations showed that flexion was the most unsafe load and an axial tensile stress greater than 10 MPa can cause disc failure. The numerical model here presented can be used to predict the failure of the disc under all loading conditions, which may support indications about the degree of safety of specific motions and daily activities, such as weight lifting.


Sources of disseminated Mycobacterium avium infection in AIDS.
To identify the sources of disseminated Mycobacterium avium complex (MAC) infection in AIDS. HIV positive subjects with CD4 counts <100/mm(3) in Atlanta, Boston, New Hampshire and Finland were entered in a prospective cohort study. Subjects were interviewed about potential MAC exposures, had phlebotomy performed for determination of antibody to mycobacterial lipoarabinomannin and for culture. Patient-directed water samples were collected from places of residence, work and recreation. Patients were followed for the development of disseminated MAC. Univariate and multivariate risk factors for MAC were analyzed. Disseminated MAC was identified in 31 (9%) subjects. Significant risks in univariate analysis included prior Pneumocystis carinii pneumonia (PCP) (hazard ratio 1.821), consumption of spring water (4.909), consumption of raw seafood (34.3), gastrointestinal endoscopy (2.894), and showering outside the home (0.388). PCP, showering and endoscopy remained significant in a Cox proportional hazards model. There was no association between M. avium colonization of home water and risk of MAC. In patients with CD4<25, median OD antibody levels to lipoarabinomannin at baseline were 0.054 among patients who did not develop MAC and 0.021 among patients who did develop MAC (P=0.077). MAC infection results from diverse and likely undetectable environmental and nosocomial exposures. Mycobacterial infection before HIV infection may confer protection against disseminated MAC in advanced AIDS.


Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual.
Bone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this dynamic phenotype by modeling longitudinal bone accrual across 11,000 bone scans in a cohort of healthy children and adolescents, followed by genome-wide association studies (GWAS) and variant-to-gene mapping with functional follow-up. We identify 40 loci, 35 not previously reported, with various degrees of supportive evidence, half residing in topological associated domains harboring known bone genes. Of several loci potentially associated with later-life fracture risk, a candidate SNP lookup provides the most compelling evidence for rs11195210 (SMC3). Variant-to-gene mapping combining ATAC-seq to assay open chromatin with high-resolution promoter-focused Capture C identifies contacts between GWAS loci and nearby gene promoters. siRNA knockdown of gene expression supports the putative effector gene at three specific loci in two osteoblast cell models. Finally, using CRISPR-Cas9 genome editing, we confirm that the immediate genomic region harboring the putative causal SNP influences PRPF38A expression, a location which is predicted to coincide with a set of binding sites for relevant transcription factors. Using a new longitudinal approach, we expand the number of genetic loci putatively associated with pediatric bone gain. Functional follow-up in appropriate cell models finds novel candidate genes impacting bone accrual. Our data also raise the possibility that the cell fate decision between osteogenic and adipogenic lineages is important in normal bone accrual.


Involution of retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.
To report the timing of involution of acute retinopathy of prematurity (ROP). An analysis of prospective retinal observational data recorded at infants' eye examinations. Infants from the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) had birth weights less than 1251 g and served as subjects. The study population included 766 children who were examined in 5 of the 23 study centers and who developed at least 1 clock hour of acute ROP, stages 1 through 3. One eye from each patient was randomly chosen for analysis. Investigators documented the location, extent, and severity of ROP during serial retinal examinations. The onset of the ROP's involution was determined from a review of these data, applying a set of predetermined criteria. Acute-phase ROP began to involute at a mean of 38.6 weeks postmenstrual age. In 90% of patients, the ROP began to involute before 44 weeks of postmenstrual age. Acute ROP that demonstrated involution by moving from zone II to zone III was associated with an unfavorable outcome in 2 (1%) of 200 cases. Retinopathy of prematurity that was present only in zone III during a child's serial retinal examinations was never associated with the development of a partial or total retinal detachment. The onset of involution of acute retinopathy of prematurity correlates better with postmenstrual rather than with chronological age. This is reminiscent of the reported similar correlation of postmenstrual age to the time of onset of prethreshold and threshold ROP. Zone III ROP was nearly always associated with a favorable outcome.


Morphometric Study on Male Specimens of Hyalomma anatolicum (Acari: Ixodidae) in West of Iran.
Hyalomma anatolicum is the well-known hard tick, which is one of the most important livestock and human pathogens vector, wide range in host and distributed in all over the Hyalomma geographic fauna as well as in Iran. Taxonomy of the Hyalomma ssp. is debatable whereas their identification is a problematic work. The reasons for this claim is time consuming Delpy's researches in Iran also Schulze School, Feldman-Muhsam and the Russian tick workers. We would like to understand morphometric variation in the field collected H. anatolicum in Iran also validating some morphologic quantitative and qualitative characters. A total 247 field-collected tick specimens from different geographical regions in west of Iran includes Khuzestan and Lorestan Provinces were studied. The morphologic characters of the ticks were measured by the calibrated stereomicroscope armed scaled lens. The measurements were analyzed using SPSS for windows, version 16 on an IBM PC, so varied shapes of species in different geographic regions were drawn by the aid of a drawing tube connected to a light stereomicroscope. One way ANOVA test revealed significant differences among the quantitative parameters in five zones (P < 0.001) also each zone to other zone by Post Hoc Tests e.g. LSD. No significant differences in the lateral grooves length/conscutum length ratio parameter were found. Morphometric variation in Hyalomma spp is poorly studied. The variation in range and quantity of the morphometric parameters of H.anatolicum underlies that the correct recognition and key construction for Hyalomma species dependes on a complement morphometric study on the other species.


Of Disasters and Dragon Kings: A Statistical Analysis of Nuclear Power Incidents and Accidents.
We perform a statistical study of risk in nuclear energy systems. This study provides and analyzes a data set that is twice the size of the previous best data set on nuclear incidents and accidents, comparing three measures of severity: the industry standard International Nuclear Event Scale, the Nuclear Accident Magnitude Scale of radiation release, and cost in U.S. dollars. The rate of nuclear accidents with cost above 20 MM 2013 USD, per reactor per year, has decreased from the 1970s until the present time. Along the way, the rate dropped significantly after Chernobyl (April 1986) and is expected to be roughly stable around a level of 0.003, suggesting an average of just over one event per year across the current global fleet. The distribution of costs appears to have changed following the Three Mile Island major accident (March 1979). The median cost became approximately 3.5 times smaller, but an extremely heavy tail emerged, being well described by a Pareto distribution with parameter α = 0.5-0.6. For instance, the cost of the two largest events, Chernobyl and Fukushima (March 2011), is equal to nearly five times the sum of the 173 other events. We also document a significant runaway disaster regime in both radiation release and cost data, which we associate with the "dragon-king" phenomenon. Since the major accident at Fukushima (March 2011) occurred recently, we are unable to quantify an impact of the industry response to this disaster. Excluding such improvements, in terms of costs, our range of models suggests that there is presently a 50% chance that (i) a Fukushima event (or larger) occurs every 60-150 years, and (ii) that a Three Mile Island event (or larger) occurs every 10-20 years. Further-even assuming that it is no longer possible to suffer an event more costly than Chernobyl or Fukushima-the expected annual cost and its standard error bracket the cost of a new plant. This highlights the importance of improvements not only immediately following Fukushima, but also deeper improvements to effectively exclude the possibility of "dragon-king" disasters. Finally, we find that the International Nuclear Event Scale (INES) is inconsistent in terms of both cost and radiation released. To be consistent with cost data, the Chernobyl and Fukushima disasters would need to have between an INES level of 10 and 11, rather than the maximum of 7.


Getting to Zero: A Demonstration Project of Partner HIV Testing in the Prenatal Setting in Chicago, Illinois.
Women who experience HIV seroconversion during pregnancy are missed during early routine pregnancy HIV screening and are at high risk of perinatal HIV transmission. Male partner HIV testing during routine prenatal care may be an effective primary prevention strategy by identifying women at risk of seroconversion and mitigating their risk. Our objective was to assess interest in and uptake of male partner HIV testing services offered during prenatal care. This demonstration project included all pregnant, English-speaking, HIV-negative women receiving publicly funded prenatal care in an urban hospital-based practice located in a high HIV prevalence area. Women were offered free HIV screening for their male sexual partners. From April 2017 to June 2018, enrolled women completed surveys on social demographics, medical access characteristics, and HIV testing history. Women were invited to bring their partners to a prenatal visit where HIV testing was offered to their male partners. Factors associated with women's interest in testing and completion of partner testing were assessed using bivariable and multivariable analyses. Of 392 women approached, 70% (N = 274) completed study surveys. Although the majority (76%, N = 200 of 264 respondents) of women desired their partner undergo HIV testing, testing was underutilized as only 18 (7%) male partners completed testing. While neither maternal characteristics nor male social or attitudinal factors were associated with interest in or completion of partner HIV testing, sensitivity analyses, performed with multiple imputation, demonstrated some association between interest and completion of partner testing and partner medical care access and utilization. In conclusion, although the majority of low-income women in an urban prenatal clinic expressed interest in having their partners undergo HIV testing, uptake of free partner HIV testing services was uncommon. A focused assessment of implementation and uptake barriers is needed to optimize partner testing and eliminate HIV transmission to mothers and their babies.


[Interactions between nurses and parents of hospitalized children].
With the purpose of supplying subsidies to nurses who work in pediatric wards, and using observation as method, the author attempts to analise and comment the interactions that occur between nurses and parents of hospitalized children in different, but usual situations during the hospitalization of children.


Metal contents in water, sediment, and Oligochaeta-Chironomidae of Lake Uluabat, a Ramsar site of Turkey.
Samples of lake water and sediment, and sediment and two dominant zoobenthic taxa (Oligochaeta: Potamothrix hammoniensis and Chironomidae: Chironomus [Camptochironomus] tentans larvae), were collected from 12 stations in Lake Uluabat and examined from the metal level point of view (cadmium, chromium, lead, copper, nickel, and zinc). Our results showed that the occurrence of metals in water, sediment, and the two zoobenthic taxa are relatively high. The opinion that supports the results of Lake Uluabat shows that certain species of oligochaetes and chironomids accumulate examined metals several times over compared to their surroundings. Therefore, it is concluded that the oligochaetes and the chironomids are suitable candidates to be used in biomonitoring surveys of Lake Uluabat.


Renal function, atherothrombosis extent, and outcomes in high-risk patients.
Although prior data showed an association between chronic kidney disease (CKD) and atherothrombotic events, little is known about the risk profile and specific outcomes of atherothrombotic outpatients with CKD. More than 69,000 outpatients at risk of atherothrombotic events were enrolled in the REACH Registry. Creatinine clearance (CrCl) was available for 51,208 patients divided into 4 groups: normal (CrCl > or =90 mL/min, n = 13,949), mild (60-89 mL/min, n = 19,474), moderate (30-59 mL/min, n = 15,883), and severe CKD (CrCl <30 mL/min, n = 1902). Baseline characteristics, number of arterial beds overtly affected, medications, overall mortality, cardiovascular death, myocardial infarction, stroke, congestive heart failure, peripheral arterial events, and bleeding events were assessed according to renal function. The number of arterial beds affected increased with severity of CKD. However, patients with severe CKD were less likely to receive medications of proven benefit. Severe CKD was an independent correlate of all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, peripheral arterial revascularization, or amputation. One third of outpatients at risk for atherothrombotic events have moderate to severe CKD. They are less likely to receive beneficial therapies despite a higher atherothrombotic burden and worse outcomes.


Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis.
The type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T(3)) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphism is associated with increased risk for DM2. A case-control study with 1057 DM2 and 516 nondiabetic subjects was performed. All participants underwent genotyping of the D2 Thr92Ala polymorphism. Additionally, systematic review and meta-analysis of the literature for genetic association studies of D2 Thr92Ala polymorphism and DM2 were performed in Medline, Embase, LiLacs, and SciELO, and major meeting databases using the terms 'rs225014' odds ratio (OR) 'thr92ala' OR 'T92A' OR 'dio2 a/g'. In the case-control study, the frequencies of D2 Ala92Ala homozygous were 16.4% (n=173) versus 12.0% (n=62) in DM2 versus controls respectively resulting in an adjusted OR of 1.41 (95% confidence intervals (CI) 1.03-1.94, P=0.03). The literature search identified three studies that analyzed the association of the D2 Thr92Ala polymorphism with DM2, with the following effect estimates: Mentuccia (OR 1.40 (95% CI 0.78-2.51)), Grarup (OR 1.09 (95% CI 0.92-1.29)), and Maia (OR 1.22 (95% CI 0.78-1.92)). The pooled effect of the four studies resulted in an OR 1.18 (95% CI 1.03-1.36, P=0.02). Our results indicate that in a case-control study, the homozygosity for D2 Thr92Ala polymorphism is associated with increased risk for DM2. These results were confirmed by a meta-analysis including 11 033 individuals, and support a role for intracellular T(3) concentration in skeletal muscle on DM2 pathogenesis.


Hepatoblastoma and familial adenomatous polyposis.
Eleven children have been identified as having hepatoblastoma and a family history of adenomatous polyposis, and 14 additional instances of this association have been collected from the literature. Among the 11 survivors of hepatoblastoma in the combined series, adenomatous lesions have been sought in seven and detected in six patients at ages 7 to 25 years. Five of these patients also have congenital hypertrophy of the retinal pigment epithelium, a marker for carriers of the polyposis gene. These findings strengthen the association between hepatoblastoma and familial adenomatous polyposis and have led to the establishment of the Hepatoblastoma-Adenomatous Polyposis Registry.


Athletes Can Benefit from Increased Intake of EPA and DHA-Evaluating the Evidence.
Fatty fish, which include mackerel, herring, salmon and sardines, and certain species of algae (e.g., Schizochytrium sp., Crytthecodiniumcohnii and Phaeodactylumtricornutum) are the only naturally rich sources of the omega-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are the most biologically active members of the n-3 PUFA family. Limited dietary sources and fluctuating content of EPA and DHA in fish raise concerns about the status of EPA and DHA among athletes, as confirmed in a number of studies. The beneficial effects of EPA and DHA include controlling inflammation, supporting nervous system function, maintaining muscle mass after injury and improving training adaptation. Due to their inadequate intake and beneficial health-promoting effects, athletes might wish to consider using supplements that provide EPA and DHA. Here, we provide an overview of the effects of EPA and DHA that are relevant to athletes and discuss the pros and cons of supplements as a source of EPA and DHA for athletes.


Current techniques of prenatal screening for Down syndrome.
Prenatal testing for Down Syndrome, the most common human malformation, is possible through three techniques: analysis of historical risk factors, ultrasonography, and evaluation of maternal serum alpha-fetoprotein levels. The authors describe these current screening techniques.


Acyl substrate preferences of an IAA-amido synthetase account for variations in grape (Vitis vinifera L.) berry ripening caused by different auxinic compounds indicating the importance of auxin conjugation in plant development.
Nine Gretchen Hagen (GH3) genes were identified in grapevine (Vitis vinifera L.) and six of these were predicted on the basis of protein sequence similarity to act as indole-3-acetic acid (IAA)-amido synthetases. The activity of these enzymes is thought to be important in controlling free IAA levels and one auxin-inducible grapevine GH3 protein, GH3-1, has previously been implicated in the berry ripening process. Ex planta assays showed that the expression of only one other GH3 gene, GH3-2, increased following the treatment of grape berries with auxinic compounds. One of these was the naturally occurring IAA and the other two were synthetic, α-naphthalene acetic acid (NAA) and benzothiazole-2-oxyacetic acid (BTOA). The determination of steady-state kinetic parameters for the recombinant GH3-1 and GH3-2 proteins revealed that both enzymes efficiently conjugated aspartic acid (Asp) to IAA and less well to NAA, while BTOA was a poor substrate. GH3-2 gene expression was induced by IAA treatment of pre-ripening berries with an associated increase in levels of IAA-Asp and a decrease in free IAA levels. This indicates that GH3-2 responded to excess auxin to maintain low levels of free IAA. Grape berry ripening was not affected by IAA application prior to veraison (ripening onset) but was considerably delayed by NAA and even more so by BTOA. The differential effects of the three auxinic compounds on berry ripening can therefore be explained by the induction and acyl substrate specificity of GH3-2. These results further indicate an important role for GH3 proteins in controlling auxin-related plant developmental processes.


Recent advances in the application of magnetic bio-polymers as catalysts in multicomponent reactions.
Magnetic nanoparticles have attracted significant attention due to their high surface area and superparamagnetic properties. Bio-polymers composed of polysaccharides including alginate, cellulose, glucose, dextrin, chitosan, and starch can be immobilized on magnetic nanoparticles. Bio-polymers can be obtained from natural sources, such as plants, tunicates, algae, and bacteria. Bio-polymers obtained from natural sources have attracted attention due to their various properties including efficient functional groups, non-toxicity, low cost, availability, and biocompatibility. According to the targets of "green chemistry", the application of bio-polymers is effective in reducing pollution. Furthermore, they are excellent agents for the functionalization of magnetic nanoparticles to yield nanomagnetic bio-polymers, which can be applied as recoverable and eco-friendly catalysts in multicomponent reactions.


Tambora and the mackerel year: Phenology and fisheries during an extreme climate event.
Global warming has increased the frequency of extreme climate events, yet responses of biological and human communities are poorly understood, particularly for aquatic ecosystems and fisheries. Retrospective analysis of known outcomes may provide insights into the nature of adaptations and trajectory of subsequent conditions. We consider the 1815 eruption of the Indonesian volcano Tambora and its impact on Gulf of Maine (GoM) coastal and riparian fisheries in 1816. Applying complex adaptive systems theory with historical methods, we analyzed fish export data and contemporary climate records to disclose human and piscine responses to Tambora's extreme weather at different spatial and temporal scales while also considering sociopolitical influences. Results identified a tipping point in GoM fisheries induced by concatenating social and biological responses to extreme weather. Abnormal daily temperatures selectively affected targeted fish species-alewives, shad, herring, and mackerel-according to their migration and spawning phenologies and temperature tolerances. First to arrive, alewives suffered the worst. Crop failure and incipient famine intensified fishing pressure, especially in heavily settled regions where dams already compromised watersheds. Insufficient alewife runs led fishers to target mackerel, the next species appearing in abundance along the coast; thus, 1816 became the "mackerel year." Critically, the shift from riparian to marine fisheries persisted and expanded after temperatures moderated and alewives recovered. We conclude that contingent human adaptations to extraordinary weather permanently altered this complex system. Understanding how adaptive responses to extreme events can trigger unintended consequences may advance long-term planning for resilience in an uncertain future.


Rhizosphere acidification and cadmium uptake by strawberry clover.
Strawberry clover (Trifolium fragiferum L.) is a hardy legume found in indigenous or introduced populations throughout the world. Tolerance to saline and alkaline soils, flooding, and heavy metals make it a good prospect for reclamation projects. The research, described here, was conducted to: (i) characterize the morphological variation in plants from available seed sources, (ii) evaluate cadmium uptake and tolerances over a wide range of morphological variants, and (iii) elucidate the variability in the effects of roots on rhizosphere pH and the relationship to cadmium uptake. Seeds from selected accessions were planted in the greenhouse for comparison of morphological variation. The accessions examined had a mean height of 10.7+/-7 cm. Accessions 254916 and 237925 are tall with high rhizosphere pH values and might be useful in phytoremediation. Strawberry clover accessions were also grown hydroponically to examine differences in cadmium uptake. The ability of strawberry clover roots to change rhizosphere pH and take up cadmium was examined using culture tubes containing nutrient agar, a moderate level of cadmium, and a pH indicator dye. The results provided evidence for a negative correlation between rhizosphere pH and cadmium uptake.


Telethermography: an objective method for evaluating patch test reactions.
Telethermography (TT) is a non-invasive imaging technique which can be used to evaluate the body's thermal gradients. It has recently been used as a diagnostic tool in many medical fields, especially in the study of the skin and other external organs. We assessed the applicability of TT in the objective evaluation of patch tests in allergic contact dermatitis, where clinical assessment is difficult, especially for atopic or brown-skinned individuals. In 34 individuals with a history of allergy to nickel sulphate (NiSO4), we applied a patch containing NiSO4 to the right side of the back and a patch containing 1% sodium-lauryl-sulphate (SLS) to the left side. As a control, we applied a patch containing an irritant (1% SLS) in a second group of 30 non-allergic individuals. A peculiar pattern was found for allergic reactions. This was characterized by a hot area that extended beyond the borders of the patch site and was oriented towards the nearest lymph-node(s), spreading as a hyperthermic line or lines. For the irritant test (SLS), the hot area was limited to the patch area, and the thermal gradients were lower. Thermography can be considered a useful complementary method for the evaluation of patch tests.


Just-in-time evidence-based e-mail "reminders" in home health care: impact on patient outcomes.
To assess the impact and cost-effectiveness of two information-based provider reminder interventions designed to improve self-care management and outcomes of heart failure (HF) patients. Interview and agency administrative data on 628 home care patients with a primary diagnosis of HF. Patients were treated by nurses randomly assigned to usual care or one of two intervention groups. The basic intervention was an e-mail to the patient's nurse highlighting six HF-specific clinical recommendations. The augmented intervention supplemented the initial nurse reminder with additional clinician and patient resources. Patient interviews were conducted 45 days post admission to measure self-management behaviors, HF-specific outcomes (Kansas City Cardiomyopathy Questionnaire-KCCQ), health-related quality of life (EuroQoL), and service use. Both interventions improved the mean KCCQ summary score (15.3 and 12.9 percent, respectively) relative to usual care (p< or =.05). The basic intervention also yielded a higher EuroQoL score relative to usual care (p< or =.05). In addition, the interventions had a positive impact on medication knowledge, diet, and weight monitoring. The basic intervention was more cost-effective than the augmented intervention in improving clinical outcomes. This study demonstrates the positive impact of targeting evidence-based computer reminders to home health nurses to improve patient self-care behaviors, knowledge, and clinical outcomes. It also advances the field's limited understanding of the cost-effectiveness of selected strategies for translating research into practice.


Salient Features and Outline of the Joint Japanese Guidelines for Safe Handling of Cancer Chemotherapy Drugs.
The purpose of this paper is to introduce the outline and describe the salient features of the "Joint Guidelines for Safe Handling of Cancer Chemotherapy Drugs" (hereinafter, "Guideline"), which were published in July 2015. The purpose of this Guideline is to provide guidance to protect against occupational exposure to hazardous drugs (HDs) to all medical personnel involved in cancer chemotherapy, including physicians, pharmacists, and nurses and home health-care providers. The Guideline was developed according to the Medical Information Network Distribution Service guidance for developing clinical practice guidelines, with reference to five authoritative guidelines used worldwide. PubMed, Cumulative Index to Nursing and Allied Health Literature, Ichushi-Web, and Cochrane Central Register of Controlled Trials were used for a systematic search of the literature. Eight clinical questions (CQs) were eventually established, and the strength of recommendation for each CQ is presented based on 867 references. The salient features of the Guideline are that it was jointly developed by three societies (Japanese Society of Cancer Nursing, Japanese Society of Medical Oncology, and Japanese Society of Pharmaceutical Oncology), contains descriptions including the definition of HDs and the concept of hierarchy of controls, and addresses exposure control measures during handling of chemotherapy drugs. Our future task is to collect additional evidence for the recommended exposure control measures and to assess whether publication of the Guideline has led to adherence of measures to prevent occupational exposure.


V.3. Basic elements of nuclear magnetic resonance for use in medical diagnostics: Magnetic Resonance Imaging (MRI), magnetic resonance spectroscopy (MRS).
Magnetic Resonance Imaging (MRI) has established itself as a major imaging modality in life science research and clinical practice. It is characterized by high spatial resolution, high soft tissue contrast, non-invasiveness, and universal applicability in terms of orientation and location of imaging areas. The procedure allows furthermore the investigation of physiological and pathophysiological processes, in particular in combination with magnetic resonance spectroscopy (MRS). MR methodology is not exhausted, new procedures and areas of application develop widely in life science and medicine. This article is limited to basic physical aspects.


Constraints to nitrogen acquisition of terrestrial plants under elevated CO2.
A key part of the uncertainty in terrestrial feedbacks on climate change is related to how and to what extent nitrogen (N) availability constrains the stimulation of terrestrial productivity by elevated CO2 (eCO2 ), and whether or not this constraint will become stronger over time. We explored the ecosystem-scale relationship between responses of plant productivity and N acquisition to eCO2 in free-air CO2 enrichment (FACE) experiments in grassland, cropland and forest ecosystems and found that: (i) in all three ecosystem types, this relationship was positive, linear and strong (r(2) = 0.68), but exhibited a negative intercept such that plant N acquisition was decreased by 10% when eCO2 caused neutral or modest changes in productivity. As the ecosystems were markedly N limited, plants with minimal productivity responses to eCO2 likely acquired less N than ambient CO2 -grown counterparts because access was decreased, and not because demand was lower. (ii) Plant N concentration was lower under eCO2 , and this decrease was independent of the presence or magnitude of eCO2 -induced productivity enhancement, refuting the long-held hypothesis that this effect results from growth dilution. (iii) Effects of eCO2 on productivity and N acquisition did not diminish over time, while the typical eCO2 -induced decrease in plant N concentration did. Our results suggest that, at the decennial timescale covered by FACE studies, N limitation of eCO2 -induced terrestrial productivity enhancement is associated with negative effects of eCO2 on plant N acquisition rather than with growth dilution of plant N or processes leading to progressive N limitation.


A genetic approach to studies on the synthesis of the complementary RNA's of fowl plague virus.
The rate of incorporation of 5-fluorouracil into complementary strands of replicating RNA of fowl plague virus (FPV) has been studied. The efficiency of incorporation was estimated by determination of the reversion frequency in s-mutants with known types of base transitions in the RNA of the virus particle. It was established that maximum incorporation of 5-fluorouracil into progeny virus particle RNA took place between 2 and 4 h after infection. The maximum incorporation of the mutagen into complementary RNA (plus strands) occurred when the cells were exposed to 5-fluorouracil from 1 to 2 h after infection.


Ceritinib for an anaplastic lymphoma kinase rearrangement-positive patient previously treated with alectinib with poor performance status.
ALK inhibitors are promising for treating ALK rearrangement non-small-cell lung cancer (NSCLC), but secondary mutations of ALK can sometimes inhibit their effectiveness. A 54-year-old woman with lung adenocarcinoma harboring ALK rearrangement previously treated with first-line alectinib and second-line cisplatin/pemetrexed showed poor performance status (PS) with rapid progression. She was treated with ceritinib as salvage treatment, upon which tumor shrinkage was demonstrated on CT and her PS gradually improved. The best supportive care is recommended for patients with advanced NSCLC with poor PS due to lower treatment efficacy and more toxicities than those with good PS. In this case, rapid progression led to a poor PS; however, ceritinib achieved a breakthrough in this case. The optimal treatment sequence and key drugs in ALK-positive NSCLC remain controversial.


Efficacy of para-aortic lymphadenectomy in early-stage endometrioid uterine corpus cancer.
The objective of this study was to assess whether para-aortic lymphadenectomy has therapeutic efficacy for patients with early-stage endometrioid uterine cancer who underwent systematic pelvic lymphadenectomy. The authors retrospectively reviewed the medical records and pathological findings of 547 patients with histologically proven FIGO stage I-II endometrioid uterine cancer, based on comprehensive surgical staging, including pelvic with or without para-aortic lymphadenectomy. Among 547 patients, 330 patients had systematic pelvic lymphadenectomy only, and 217 had systematic pelvic with para-aortic lymphadenectomy. There were no significant differences in histopathological factors in the high-risk group, even though deep myometrial invasion (p = 0.02) and lymphvascular space invasion (p = 0.01) were more common in patients who underwent systematic pelvic with para-aortic lymphadenectomy in all study populations. Within a median follow-up of 31 (range, 5-120) months, there was no significant difference in overall survival between the pelvic lymphadenectomy only and pelvic with para-aortic lymphadenectomy groups in all populations (p = 0.77), even in high-risk patients (p = 0.82). Upon multivariate analysis, patients with lymphvascular space invasion had significantly worse overall survival (odds ratio (OR) = 7.38; 95% confidence interval (CI) = 1.86-29.23; p = 0.004). Although a prospective, randomized study needs to be performed for confirmation, our data suggest that the therapeutic benefit of para-aortic lymphadenectomy is uncertain in stage I and II endometrioid uterine corpus cancer, even in patients at high-risk for recurrence.


Reaching Deeper: Absolute In Vivo Thermal Reading of Liver by Combining Superbright Ag2S Nanothermometers and In Silico Simulations.
Luminescent nano-thermometry is a fast-developing technique with great potential for in vivo sensing, diagnosis, and therapy. Unfortunately, it presents serious limitations. The luminescence generated by nanothermometers, from which thermal readout is obtained, is strongly distorted by the attenuation induced by tissues. Such distortions lead to low signal levels and entangle absolute and reliable thermal monitoring of internal organs. Overcoming both limitations requires the use of high-brightness luminescent nanothermometers and adopting more complex approaches for temperature estimation. In this work, it is demonstrated how superbright Ag2S nanothermometers can provide in vivo, reliable, and absolute thermal reading of the liver during laser-induced hyperthermia. For that, a new procedure is designed in which thermal readout is obtained from the combination of in vivo transient thermometry measurements and in silico simulations. The synergy between in vivo and in silico measurements has made it possible to assess relevant numbers such as the efficiency of hyperthermia processes, the total heat energy deposited in the liver, and the relative contribution of Ag2S nanoparticles to liver heating. This work provides a new way for absolute thermal sensing of internal organs with potential application not only to hyperthermia processes but also to advanced diagnosis and therapy.


Novel mechanism of surface catalysis of protein adduct formation. NMR studies of the acetylation of ubiquitin.
Reactivity of surface lysyl residues of proteins with a broad range of chemical agents has been proposed to be dependent on the catalytic microenvironment of the residue. We have investigated the acetylation of wild type ubiquitin and of the UbH68N mutant to evaluate the potential contribution of His-68 to the reactivity of Lys-6, which is about 4 A distant. These studies were performed using [1-(13)C]acetyl salicylate or [1,1'-(13)C(2)]acetic anhydride, and the acetylated products were detected by two-dimensional heteronuclear multiple quantum coherence spectroscopy. The results demonstrate that His-68 makes a positive contribution to the rate of acetylation of Lys-6 by labeled aspirin. Additionally, a pair of transient resonances is observed after treatment of wild type ubiquitin with the labeled acetic anhydride but not upon treatment of the H68N mutant. These resonances are assigned to the acetylated His-68 residue. The loss of intensity of the acetylhistidine resonances is accompanied by an increase in intensity of the acetyl-Lys-6 peak, supporting the existence of a transacetylation process between the acetylhistidine 68 and lysine 6 residues located on the protein surface. Hence, this may be the first direct demonstration of a catalytic intermediate forming on the protein surface.


High Gene Family Turnover Rates and Gene Space Adaptation in the Compact Genome of the Carnivorous Plant Utricularia gibba.
Utricularia gibba is an aquatic carnivorous plant with highly specialized morphology, featuring fibrous floating networks of branches and leaf-like organs, no recognizable roots, and bladder traps that capture and digest prey. We recently described the compressed genome of U. gibba as sufficient to control the development and reproduction of a complex organism. We hypothesized intense deletion pressure as a mechanism whereby most noncoding DNA was deleted, despite evidence for three independent whole-genome duplications (WGDs). Here, we explore the impact of intense genome fractionation in the evolutionary dynamics of U. gibba's functional gene space. We analyze U. gibba gene family turnover by modeling gene gain/death rates under a maximum-likelihood statistical framework. In accord with our deletion pressure hypothesis, we show that the U. gibba gene death rate is significantly higher than those of four other eudicot species. Interestingly, the gene gain rate is also significantly higher, likely reflecting the occurrence of multiple WGDs and possibly also small-scale genome duplications. Gene ontology enrichment analyses of U. gibba-specific two-gene orthogroups, multigene orthogroups, and singletons highlight functions that may represent adaptations in an aquatic carnivorous plant. We further discuss two homeodomain transcription factor gene families (WOX and HDG/HDZIP-IV) showing conspicuous differential expansions and contractions in U. gibba. Our results 1) reconcile the compactness of the U. gibba genome with its accommodation of a typical number of genes for a plant genome, and 2) highlight the role of high gene family turnover in the evolutionary diversification of U. gibba's functional gene space and adaptations to its unique lifestyle and highly specialized body plan.


The predictive nature of transcript expression levels on protein expression in adult human brain.
Next generation sequencing methods are the gold standard for evaluating expression of the transcriptome. When determining the biological implications of such studies, the assumption is often made that transcript expression levels correspond to protein levels in a meaningful way. However, the strength of the overall correlation between transcript and protein expression is inconsistent, particularly in brain samples. Following high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses of adult human brain samples, we compared the correlation in the expression of transcripts and proteins that support various biological processes, molecular functions, and that are located in different areas of the cell. Although most categories of transcripts have extremely weak predictive value for the expression of their associated proteins (R2 values of < 10%), transcripts coding for protein kinases and membrane-associated proteins, including those that are part of receptors or ion transporters, are among those that are most predictive of downstream protein expression levels. The predictive value of transcript expression for corresponding proteins is variable in human brain samples, reflecting the complex regulation of protein expression. However, we found that transcriptomic analyses are appropriate for assessing the expression levels of certain classes of proteins, including those that modify proteins, such as kinases and phosphatases, regulate metabolic and synaptic activity, or are associated with a cellular membrane. These findings can be used to guide the interpretation of gene expression results from primate brain samples.


Split light up aptamers as a probing tool for nucleic acids.
Aptamers that bind non-fluorescent dyes and increase their fluorescence can be converted to fluorescent sensors. Here, we discuss and provide guidance for the design of split (binary) light up aptameric sensors (SLAS) for nucleic acid analysis. SLAS consist of two RNA or DNA strands and a fluorogenic organic dye added as a buffer component. The two strands hybridize to the analyzed DNA or RNA sequence and form a dye-binding pocket, followed by dye binding, and increase in its fluorescence. SLAS can detect nucleic acids in a cost-efficient label-free format since it does not require conjugation of organic dyes with nucleic acids. SLAS design is preferable over monolith fluorescent sensors due to simpler assay optimization and improved selectivity. RNA-based SLAS can be expressed in cells and used for intracellular monitoring and imaging biological molecules.


Identification of differentially expressed genes for time-course microarray data based on modified RM ANOVA.
The regulation of gene expression is a dynamic process, hence it is of vital interest to identify and characterize changes in gene expression over time. We present here a general statistical method for detecting changes in microarray expression over time within a single biological group and is based on repeated measures (RM) ANOVA. In this method, unlike the classical F-statistic, statistical significance is determined taking into account the time dependency of the microarray data. A correction factor for this RM F-statistic is introduced leading to a higher sensitivity as well as high specificity. We investigate the two approaches that exist in the literature for calculating the p-values using resampling techniques of gene-wise p-values and pooled p-values. It is shown that the pooled p-values method compared to the method of the gene-wise p-values is more powerful, and computationally less expensive, and hence is applied along with the introduced correction factor to various synthetic data sets and a real data set. These results show that the proposed technique outperforms the current methods. The real data set results are consistent with the existing knowledge concerning the presence of the genes. The algorithms presented are implemented in R and are freely available upon request.


Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.
Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells. In the clinical setting, PDPK1 was active in myeloma cells of approximately 90% of symptomatic patients at diagnosis, and the smaller population of patients with multiple myeloma exhibiting myeloma cells without active PDPK1 showed a significantly less frequent proportion of the disease stage III by the International Staging System and a significantly more favorable prognosis, including the longer overall survival period and the longer progression-free survival period by bortezomib treatment, than patients with active PDPK1, suggesting that PDPK1 activation accelerates the disease progression and the resistance to treatment in multiple myeloma. Our study demonstrates that PDPK1 is a potent and a universally targetable signaling mediator in multiple myeloma regardless of the types of cytogenetic/molecular profiles.


[Criteria for expert assessment of the injured cervical spine from the neurosurgical viewpoint].
The assessment of cervical injuries in medical expertises can be difficult, because there are sometimes little objective clinical symptoms and radiological signs though the patients pretend to suffer from multiple complaints. A series of 40 neurosurgical expertises has been evaluated: 19 patients (47.5%) had clinical signs of cervical myelopathy, 13 patients (32.5%) had clear radicular syndromes, 7 patients (17.5%) suffered from local cervical syndromes. Clinical symptoms can be objectified by radiological methods, such as MRI, which occasionally can directly show lesions of the cervical cord or the brain stem. Sometimes even in patients with severe neurological deficits there are little radiological alterations. Local pain syndromes were assessed at a reduction in earning capacity of about 20%, radicular syndromes at 20 to 30%, minor grades of myelopathy at 30 to 40% respectively disability, and severe grades of myelopathy at up to 100% resp. incapacity of gainful employment. In our opinion adequate assessment of cervical cord injuries should predominantly base on clinical neurological findings, secondarily on radiological findings.


[Non epileptic paroxysmal movements disorders in infant].
Paroxysmal non-epileptic disorders may cause episodic and paroxysmal symptoms that mimic true epileptic seizures and they must be considered in the differential diagnosis. Paroxysmal movement disorders are not uncommon in infants, but are probably under-recognised. These phenomena represent various clinical situations, characterised by intermitted and episodic disturbances of movement. Clinical experience and a detailed history and careful observation with video recording are often helpful to establish the correct diagnosis. In the large majority of the cases, paroxysmal movement disorders are benign situation. Most of the time, no treatment will be required, and the families will be informed of the good prognosis. These disorders in infants are discussed in the present review.


Incidence and etiology of intracerebral hemorrhage following carotid endarterectomy.
In a consecutive series of 1930 carotid endarterectomies there were eight cases of postoperative intracerebral hemorrhage. One of these patients was operated on 2 weeks following cerebral infarction and had severe uncontrollable hypertension after surgery. A second patient had an intraoperative embolus and bled while fully heparinized on the 3rd postoperative day. Only one patient in the series bled into an area of documented cerebral infarction. The remainder of the cases represented hemorrhage into essentially normal brain. Seven of the eight patients with intracerebral hemorrhage had high-grade internal carotid artery stenosis preoperatively. Although several factors have contributed to the brain hemorrhages in this series of patients, postoperative cerebral hyperperfusion which often follows endarterectomy may have played an important role. Defective cerebrovascular autoregulation in chronically ischemic brain regions may predispose patients to intracerebral hemorrhage after removal of a high-grade stenosis of the internal carotid artery.


Naproxen induces cell-cycle arrest and apoptosis in human urinary bladder cancer cell lines and chemically induced cancers by targeting PI3K.
Naproxen [(S)-6-methoxy-α-methyl-2-naphthaleneacetic acid] is a potent nonsteroidal anti-inflammatory drug that inhibits both COX-1 and COX-2 and is widely used as an over-the-counter medication. Naproxen exhibits analgesic, antipyretic, and anti-inflammatory activities. Naproxen, as well as other nonsteroidal anti-inflammatory drug, has been reported to be effective in the prevention of urinary bladder cancer in rodents. However, potential targets other than the COX isozymes have not been reported. We examined potential additional targets in urinary bladder cancer cells and in rat bladder cancers. Computer kinase profiling results suggested that phosphoinositide 3-kinase (PI3K) is a potential target for naproxen. In vitro kinase assay data revealed that naproxen interacts with PI3K and inhibits its kinase activity. Pull-down binding assay data confirmed that PI3K directly binds with naproxen in vitro and ex vivo. Western blot data showed that naproxen decreased phosphorylation of Akt, and subsequently decreased Akt signaling in UM-UC-5 and UM-UC-14 urinary bladder cancer cells. Furthermore, naproxen suppressed anchorage-independent cell growth and decreased cell viability by targeting PI3K in both cell lines. Naproxen caused an accumulation of cells at the G1 phase mediated through cyclin-dependent kinase 4, cyclin D1, and p21. Moreover, naproxen induced significant apoptosis, accompanied with increased levels of cleaved caspase-3, caspase-7, and PARP in both cell types. Naproxen-induced cell death was mainly because of apoptosis in which a prominent downregulation of Bcl-2 and upregulation of Bax were involved. Naproxen also caused apoptosis and inhibited Akt phosphorylation in rat urinary bladder cancers induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine.


Safe abortion in Latin America: a look at abortion accompaniment collectives from the perspective of their activists.
Over the last decade, activists in Latin America have expanded access to safe abortion through processes of accompaniment. Abortion accompaniment is characterised by activism and community-based strategies to facilitate access to, and safe use of, medication abortion, mainly outside clinical contexts. Drawing on findings from a survey of 515 activists who were part of Accompaniment Collectives in Latin America, this study describes the organisation of these collectives, barriers and facilitators to their activism, and how accompaniers perceive the impact and future of abortion accompaniment. Accompaniment Collectives are organised and flexible and operate in diverse social and legal contexts. The main goals of accompaniment are the normalisation and social decriminalisation of abortion culturally (84%); the social construction of autonomy (79%); and the protection of people's freedom (73%), life (71%) and health (67%). Activists in legally restrictive settings identified limited access to abortion medication (73%) and restrictive laws (71%) as the main barriers to accompaniment, while health care personnel objecting to abortion provision on grounds of conscience was most common in legally permissive settings (64%). Collectives have developed strategies to overcome such barriers to and expanding access to abortion care. Activists expect accompaniment to continue regardless of the legal status of abortion.


[Pregnancy, micro-chimerism and autoimmune diseases].
Microchimerism is defined by the presence within an individual of a low level of cells derived from a different individual. The main, natural source of microchimerism is pregnancy. The migration of fetal cells into maternal blood during pregnancy has become an accepted fact. The maternal cells can also be found in the fetal circulation. Recent studies indicate that cells can persist in the maternal circulation for years after pregnancy. Maternal cells can also persist in her progeny. The autoimmune diseases are a diverse group of disorders. Many of them are of unknown etiology. Women are disproportionately affected by autoimmune disease and the incidence of some autoimmune disease in women peak following childbearing years. The integration of observation from differing fields of medicine has led to the consideration that microchimerism may be involved in the pathogenesis of some autoimmune diseases. Early results offer support for a potential role of microchimerism in SSc. The aim of this paper is to present current knowledge about this problem.


Isolation and Characterization of acetate kinase and phosphotransacetylase mutants of Escherichia coli and Salmonella typhimurium.
Mutations in the ack (acetate kinase) and pta (phosphotransacetylase) genes in Salmonella typhimurium were characterized and determined to be analogous to those of previously described Escherichia coli mutants. We established that in both bacterial species these genes were cotransducible with the neighboring histidine transport operon and were distally located relative to purF. pta mutants were sensitive to the dye alizarin yellow and were unable to grow on medium containing inositol as a carbon source. We selected mutants of both species with deletions covering both the ack and the pta genes; some deletions extended into the histidine transport operon.


Mosquito microbiota cluster by host sampling location.
Microbial communities that inhabit the mosquito body play an import role in host biology and may have potential for mosquito control. However, the forces that shape these microbial communities are poorly understood. To gain a better understanding of how host location influences the composition and diversity of mosquito microbiota, we performed a survey of microbial communities in mosquito samples collected from six USA states using HiSeq sequencing of the 16S rRNA gene. A total of 284 bacterial operational taxonomic units (OTUs) belonging to 14 phyla were detected in nine mosquito species, with Proteobacteria, Firmicutes and Actinobacteria accounting for 95% of total sequences. OTU richness varied markedly within and between mosquito species. The microbial composition and diversity was heavily influenced by the site of mosquito collection, suggesting that host location plays an important role in shaping the mosquito microbiota. Variation in microbial composition and diversity between mosquitoes from different locations may have important implications on vector competence and transmission dynamics of mosquito-borne pathogens. Future studies should investigate the environmental factors responsible for these variations and the role of key bacteria characterized in this study on mosquito biology and their potential application in symbiotic control of mosquito-borne diseases.


Fill rates and access to self-injectable epinephrine prescribed in a pediatric emergency department.
Despite its life-saving potential in anaphylaxis, self-injectable epinephrine (SIE) is frequently not administered by caregivers prior to arrival in the emergency department (ED). Prescriptions from the ED often go unfilled which may contribute to the failure to receive SIE when needed. To determine the prescription filling rate and accessibility of SIE devices among families discharged from the Pediatric ED with an SIE prescription. A phone survey was administered to parents of children <18 years of age prescribed SIE in the pediatric ED over 12 months. The survey inquired if they own an SIE device, the device's expiration date as confirmation, and details of their child's allergy. Variables were analyzed for association with owning SIE, having SIE accessible when prompted, and having unexpired SIE accessible. 170 children received prescriptions for SIE and 100 (59%) completed the survey. Eighty-four of 100 (84%) had filled the initial SIE prescription. Sixty-five of 100 (65%) had proof of having SIE, of which 29% (19/65) were expired. Only 46% (46/100) of all respondents had an accessible unexpired SIE. Patients with food allergies and those who'd visited an allergist after their ED visit had higher odds of having unexpired accessible devices. A majority of patients prescribed SIE from the ED fill their prescription; however, less than half have unexpired SIE readily available despite high rates of recurrent anaphylactic emergencies. Focusing on post-discharge planning, particularly follow-up, may prevent children with allergies from being left dangerously unprepared.


Baicalin Inhibits Human Cervical Cancer Cells by Suppressing Protein Kinase C/Signal Transducer and Activator of Transcription (PKC/STAT3) Signaling Pathway.
BACKGROUND Like other human cancers, the malignancy of cervical cancer is also characterized by abilities of proliferation, migration, and invasion. Protein kinase C-zeta (PKCζ) has been highly correlated with several human cancers. Baicalin was proven to regulate PKC. This study aimed to investigate the anti-cancer effect and involved molecular mechanisms of baicalin on human cervical cancer. MATERIAL AND METHODS Baicalin at various concentrations was used to treat 2 human cervical cancer cell lines HeLa and SiHa. The proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenylterazolium bromide (MTT) assay. The apoptosis was detected by terminal transferase UTP nick end labeling (TUNEL) assay. Wound healing assay and Transwell assay were used to evaluate the migration and invasion respectively. Western blotting was performed to assess the protein expression levels. RESULTS Baicalin administration significantly reduced the viability by facilitating the apoptosis in HeLa and SiHa cells. Baicalin treatment also significantly reduced the wound closure and cell amount invaded as measured by Transwell assay. The expression levels of PKCζ, survivin, matrix metalloproteinase (MMP)2, MMP9 as well as the phosphorylation of signal transducer and activator of transcription (STAT) 3 were reduced in baicalin administrated cervical cancer cells. CONCLUSIONS Baicalin exerted anti-cancer effects on human cervical cancer cells by targeting STAT3 regulated signaling pathways.


Sox7 in vascular development: review, insights and potential mechanisms.
Cardiovascular development is crucial to the survival of higher organisms, integrally transporting oxygen and nutrients and in later life, facilitating immune function. Only in recent years has the molecular basis of the formation of this ancient conduit system been explored. While transcription factors are essential to specify and differentiate core cellular and structural components of the developing heart and vessels, only a subset of these essential factors are currently known. A transcription factor of emerging importance in the cardiovascular system is Sox7, a member of the F group of Sox genes, as Sox7 removal in recent animal and cellular studies has resulted in disruptions of cardiovascular development. However, the molecular mechanisms of Sox7 action have largely remained obscure. In this paper, we first review the highly conserved and robust cardiovascular expression pattern of Sox7 across multiple species. We then provide evidence of a compelling role for Sox7 in vascular development, elucidating major pathways in which Sox7 functions, including VEGF/Flk1 signaling, Wnt signaling, and Notch pathway. Furthermore, we propose mechanisms connecting all of these important developmental pathways through Sox7, in a way not previously postulated in the developing vascular system. The emerging picture reveals Sox7 as an important developmental gene that connects other vascular regulators and that has significance in human disease.


The psychoanalytic research interview: preliminary suggestions.
Psychoanalytically informed interview techniques and interview analysis can yield useful psychoanalytic insights about a particular research subject within the space of a few interviews. Basic hermeneutic principles, often used to understand the research interview, are not sufficient for understanding unconscious meaning and intrapsychic processes; they pay little attention to the particular theoretical and technical aspects of the interview needed to create the best conditions for understanding unconscious meaning. The portability of psychoanalytic concepts and their applicability outside the therapeutic setting are considered, after which four epistemological principles are outlined, derived mainly from the narrative tradition in psychoanalysis, that can inform interview technique and the analysis of the interview. Careful attention to feeling states, the search for core narratives, and the exploration of identifications and object relations are isolated as key analytic tasks in the interview analysis. A brief verbatim interview is used to illustrate this process, and methods are suggested to prevent the "wild analysis" of the interview encounter.


Deterioration of exercise capacity after neonatal extracorporeal membrane oxygenation.
Extracorporeal membrane oxygenation (ECMO) provides life support in acute reversible cardiorespiratory failure. Assessment of long-term morbidity is essential to confirm survival advantage. This study aimed to assess exercise capacity in the first 12 yrs of life after neonatal ECMO, and to evaluate the effect of primary diagnosis, lung function or perinatal characteristics on exercise capacity. 120 children who, as neonates, underwent ECMO performed 191 reliable exercise tests according to the Bruce treadmill protocol at ages 5, 8 and/or 12 yrs between 2001 and 2010. Primary diagnoses were meconium aspiration syndrome (n=66), congenital diaphragmatic hernia (n=18) and other diagnoses (n=36). At ages 5, 8 and 12 yrs, ANOVA resulted in mean ± se standard deviation score endurance time on the treadmill of -0.5 ± 0.1, -1.1 ± 0.1, and -1.5 ± 0.2, respectively, all significantly less than zero (p<0.001). Exercise capacity declined significantly over time irrespective of the primary diagnosis. Neonates treated with ECMO are at risk of decreased exercise capacity at school age. We therefore propose prolonged follow-up. Proactive advice on sports participation or referral to a physical therapist is recommended, especially when either the parents or the children themselves report impaired exercise capacity.


Complementary and Alternative Medicine Use Among US Adults With Headache or Migraine: Results from the 2012 National Health Interview Survey.
Given the safety concerns regarding pharmacological agents, and the considerable impact of headache and migraine on the sufferer's quality of life, many people seek other treatment options beyond conventional medication and care to address their symptoms; this includes complementary and alternative medicine (CAM). Some CAM interventions have shown promising results in clinical trials of headache and migraine management. Nonetheless, there has been little research exploring the reasons for using CAM, and the types of CAM used, among this population. The study aimed to answer the following questions: (1) Which CAM modalities are used most frequently among migraine/headache sufferers? and (2) What are the self-reported reasons for CAM use among migraine/headache sufferers? This secondary analysis of data from the 2012 U.S. NHIS (a national cross-sectional survey) examined the use of CAM among migraine/headache sufferers, including the main reasons related to CAM use. Data were weighted and analyzed using STATA 14.0. The sample of 34,525 adults included 6558 (18.7%) headache/migraine sufferers. Of the headache/migraine sufferers, a substantial proportion (37.6%, n = 2427) used CAM for various conditions; however, CAM use specifically for headache/migraine was much less prevalent (3.3%, n = 216). Of those who used CAM for headache/migraine, about half used CAM in conjunction with prescription (47.8%, n = 100) or over-the-counter medication (55.1%, n = 113). As severity of headache/migraine increased so did the likelihood of using CAM (severe migraine odds ratio [OR] = 2.32; 95% confidence interval [CI]: 1.41, 3.82; both recurring headache/severe migraine OR = 3.36; 95% CI: 2.08, 5.43; when compared to those with recurring headache only). The most frequently used CAM modality among all headache/migraine sufferers (N = 6558) was manipulative therapy (22.0%, n = 1317), herbal supplementation (21.7%, n = 1389) and mind-body therapy (17.9%, n = 1100). The top 3 reasons for using CAM for headache were general wellness (28.7%, n = 60/209), improving overall health (26.8%, n = 56/209), and reducing stress (16.7%, n = 35/209). Although CAM is used by many sufferers of headache/migraine, the use of CAM specifically for the treatment of headache/migraine is relatively low in the United States. The study also assesses the key differences of CAM use among headache/migraine sufferers in NHIS 2012 compared with those in NHIS 2007, and identifies shortfalls in the evidence-base of several CAM modalities used by U.S. adults for headache/migraine. This information may assist health providers and consumers in making informed decisions about the safest and most appropriate approach to managing headache/migraine.


Large fresh osteochondral allografts of the knee: a systematic clinical and basic science review of the literature.
The aim of this study was to conduct an updated review of the literature regarding the clinical and basic science knowledge on osteochondral allograft transplantation in the knee for the treatment of large defects. According to specific criteria, 2 investigators systematically reviewed the literature for clinical and basic science reports regarding osteochondral allograft transplantation; data were independently extracted, pooled, and analyzed. Clinical and functional outcomes, International Knee Documentation Committee and Western Ontario and McMaster Universities Osteoarthritis Index scores, return to sport, quality of life, and survivorship of the grafts were assessed from the clinical articles. Regarding the basic science articles, the effects of allograft storage time, temperature, and different storage media were assessed. Eleven articles reporting on clinical data and 14 articles reporting on basic science data (animal, cell, and biomechanical studies) were selected. The articles included in the review were not homogeneous, and different outcome measures were adopted. Overall excellent results were achieved, with improvement in all objective and subjective clinical scores, a high rate of return to sport, and a survivorship rate of 89% at 5 years. When multiple plugs were implanted, posterior grafts seemed to fail. Only 1 article compared fresh versus frozen grafts, with a greater improvement in scores in the frozen group. Cellular viability and number were reduced during storage, even at low temperatures; polyphenol from green tea and arbutin and higher temperatures favorably influenced cell viability of the cartilage during storage. On the other hand, the structural properties of the extracellular matrix were not influenced by the storage at low temperatures. Integration of the graft to the host was also important, and bony integration was usually achieved; however, on the cartilage side, integration was scant or did not occur, especially in the frozen grafts. Fresh osteochondral allografts of the knee showed good clinical and functional outcomes even at longer-term follow-up. No other effective treatment exists, at the moment, for large osteochondral lesions. This surgical procedure is burdened by cost and difficulty in finding matching fresh donors. A new method to establish chondrocyte viability before the implantation of a new allograft would be a useful decision-making instrument. Level IV, systematic review of Level IV studies.


Outfoxing FoxO transcription factors: HTLV-1 Tax oncoprotein inactivates FoxO4 via the ubiquitin-proteasome pathway.
Evaluation of: Oteiza A, Mechti N. The human T-cell leukemia virus type 1 oncoprotein tax controls forkhead box O4 activity through degradation by the proteasome. J. Virol. 85(13), 6480-6491 (2011). This study examines downstream signaling events of PI3K/AKT in the context of human T cell leukemia virus type 1 (HTLV-1) infection. The authors have demonstrated that the HTLV-1 Tax oncoprotein triggers the ubiquitination and proteasomal degradation of the FoxO4 transcription factor. Phosphorylation by AKT is requisite for Tax-induced FoxO4 degradation since mutation of the AKT phosphorylation sites abrogates FoxO4 degradation. Furthermore, Tax enhances the interaction between FoxO4 and the E3 ubiquitin ligase MDM2 which presumably leads to FoxO4 ubiquitination. Consistently, knockdown of MDM2 with a shRNA plasmid attenuates FoxO4 ubiquitination, revealing an important role for MDM2 in Tax-induced FoxO4 ubiquitination. Finally, Tax represses FoxO4 transcriptional activity in a dose-dependent manner. Taken together, the findings by Oteiza et al. suggest that Tax inactivates the tumor suppressor FoxO4 downstream of PI3K/AKT, which may play a role in HTLV-1-induced oncogenesis.


Long-term consequences of early linear growth retardation (stunting) in Swedish children.
Linear growth retardation (stunting) is prevalent (10-80%) in developing countries. It takes place between 6 and 18 mo of age and can be characterized by the delayed onset of the childhood phase of growth. The objective of this work was to study the existence of stunting in early life and, when present, its lifelong effects on final height in a normal healthy population in a developed country. A total of 2432 children with longitudinal height data from birth to adulthood were analyzed. The series represents a normal healthy population-based sample of full-term children born around 1974 in Göteborg, Sweden. We found the incidence of stunting to be about 10% as indicated by delayed onset of the childhood phase of growth (>12 mo of age): 14% in boys and 8% in girls. In a multiple linear regression model, final height was described by length at 6 mo of age, age at onset of the childhood phase of growth, and age at peak height velocity during puberty. All three measures contributed significantly (p < 0.05) to final height with a total R2 of 0.33. A final height difference of 5.0 cm could be explained by abnormal onset of the childhood phase of growth in this normal population. The timing of the childhood onset of growth did not correlate with the timing of puberty. For the first time, we can conclude that stunting in early life is not only a problem in developing countries. Its importance on final height achieved is clearly shown, even after controlling for the timing of puberty.


Associations among perceptual anomalies, social anxiety, and paranoia in a college student sample.
Recent evidence suggests that normal-range paranoid ideation may be particularly likely to develop in individuals disposed to both social anxiety and perceptual anomalies. This study was designed to test the hypothesis that among college students in an unselected sample, social anxiety and experience of perceptual anomalies would not only each independently predict the experience of self-reported paranoid ideation, but would also interact to predict paranoid patterns of thought. A diverse sample of 644 students completed a large battery of self-report measures, as well as the five-factor Paranoia/Suspiciousness Questionnaire (PSQ). We conducted hierarchical multiple regression analyses predicting scores on each PSQ factor from responses on measures of social anxiety, perceptual aberration, and the interaction between the two constructs. Current general negative affect was covaried in all analyses. We found that both social anxiety and perceptual aberrations, along with negative affect, predicted multiple dimensions of paranoia as measured by the PSQ; the two constructs did not, however, interact significantly to predict any dimensions. Our findings suggest that perceptual aberration and anxiety may contribute to normal-range paranoid ideation in an additive rather than an interactive manner.


Hormonal changes in burned hamsters.
Burned male Syrian hamsters (burn size 23% of body surface) exhibited reduced total (T4) and free (FT4) serum concentrations, a defect in T4 binding to serum proteins manifested by the T4 dialyzable fraction but not the in vitro T3 charcoal uptake, and reduced serum testosterone concentration. These changes are similar to those noted previously in burned humans. Unlike such patients, burned hamsters did not exhibit reduced serum T3 nor elevated rT3 concentrations in a reproducible manner. Pinealectomy performed before burning in hamsters did not prevent the burn-induced depression in serum T4 and testosterone.


An Epidemiologic Study on Emergency Department Mortality.
Epidemiologic evaluation generally starts with recording the raw data regarding mortality, and healthcare managers should have a national plan executed for this purpose. The present study was planned and performed with the aim of epidemiologically evaluating mortality cases among patients admitted to the emergency department (ED) of a major hospital in Tehran, Iran in order to plan and provide proper equipment for decreasing the mortality of patients. This cross-sectional study was performed in Shohadaye Tajrish Hospital, Tehran, Iran. All cases of mortality, recorded in the ED of the studied hospital from 20 March 2016 until 21 June 2016, were included in the study. A checklist was prepared for gathering data and the clinical profiles of all the considered patients were reviewed. Using this checklist, demographic data, chief complaint, history of underlying disease, pathologic findings of imaging modalities, and cause of death were extracted from the patients' profiles. Over the mentioned period of time, in total, the data of 8420 admissions to the ED were recorded. Out of these patients, 76 (0.9%) had died, the mean age of whom was 67.66 ± 21.40 years. Based on these findings, among patients who had presented to the ED, 42.1% died due to the complications of heart attack and 13.2% died from complications caused by cancer. Based on the findings of the present study, cardiovascular complications were the most leading cause of mortality in the studied ED and complications resulting from malignancy were in the second place. Trauma and accidents leading to intracranial hemorrhage were in the next places.