Characteristics of bacterial and viral contamination of urban waters: a case study in Xi'an, China.
In order to gain knowledge on the presence of bacteria and viruses in urban waters, the authors started a long-term study on the microbiological quality of urban lakes and rivers in Xi'an, China. In the current study, enteroviruses were chosen as typical viruses and RT-nested PCR was conducted for their detection. Universal primers were designed for simultaneous detection of poliovirus, coxsackievirus, and enterovirus 71 which are the most frequently encountered enteroviruses in China. The RT-nested PCR protocol established in this study showed high sensitivity and specificity. The detection limit was equivalent to 0.038 CCID50 per litre by applying a modified adsorption-elution concentration method. No cross-reactivity was observed using the genome of pathogenic bacteria as of PCR template. The occurrence of enteroviruses was compared with fecal coliform count in a 6-month period from July to December 2006 for the urban waters. As a result, it was noticed that the presence of enteroviruses might not relate to the fecal coliform count so much. Statistical analysis also indicated that there was no significant correlation between the presence of enteroviruses and that of total bacteria, total coliform, and fecal coliform.


Septins arrange F-actin-containing fibers on the Chlamydia trachomatis inclusion and are required for normal release of the inclusion by extrusion.
Chlamydia trachomatis is an obligate intracellular human pathogen that grows inside a membranous, cytosolic vacuole termed an inclusion. Septins are a group of 13 GTP-binding proteins that assemble into oligomeric complexes and that can form higher-order filaments. We report here that the septins SEPT2, -9, -11, and probably -7 form fibrillar structures around the chlamydial inclusion. Colocalization studies suggest that these septins combine with F actin into fibers that encase the inclusion. Targeting the expression of individual septins by RNA interference (RNAi) prevented the formation of septin fibers as well as the recruitment of actin to the inclusion. At the end of the developmental cycle of C. trachomatis, newly formed, infectious elementary bodies are released, and this release occurs at least in part through the organized extrusion of intact inclusions. RNAi against SEPT9 or against the combination of SEPT2/7/9 substantially reduced the number of extrusions from a culture of infected HeLa cells. The data suggest that a higher-order structure of four septins is involved in the recruitment or stabilization of the actin coat around the chlamydial inclusion and that this actin recruitment by septins is instrumental for the coordinated egress of C. trachomatis from human cells. The organization of F actin around parasite-containing vacuoles may be a broader response mechanism of mammalian cells to the infection by intracellular, vacuole-dwelling pathogens. Importance: Chlamydia trachomatis is a frequent bacterial pathogen throughout the world, causing mostly eye and genital infections. C. trachomatis can develop only inside host cells; it multiplies inside a membranous vacuole in the cytosol, termed an inclusion. The inclusion is covered by cytoskeletal "coats" or "cages," whose organization and function are poorly understood. We here report that a relatively little-characterized group of proteins, septins, is required to organize actin fibers on the inclusion and probably through actin the release of the inclusion. Septins are a group of GTP-binding proteins that can organize into heteromeric complexes and then into large filaments. Septins have previously been found to be involved in the interaction of the cell with bacteria in the cytosol. Our observation that they also organize a reaction to bacteria living in vacuoles suggests that they have a function in the recognition of foreign compartments by a parasitized human cell.


Liquid chromatography and fluorescence spectroscopy compared with a homogeneous enzyme immunoassay technique for determining quinidine in serum.
Sera from 67 cardiac patients being treated with quinidine were analyzed for this drug by both a homogeneous enzyme immunoassay (EMIT) and a fluorescence procedure (double-extraction method). Of these samples, 47 were also analyzed for quinidine and its major metabolite in serum, (3s)-3-hydroxyquinidine, by liquid chromatography. Results by the EMIT procedure correlated well with those by both the chromatographic and fluorescence procedures, but EMIT gave, on the average, 25% higher values for quinidine than did the chromatographic procedure. The EMIT procedure is therefore not totally specific. (3s)-3-Hydroxyquinidine and dihydroquinidine (a contaminant present in standard quinidine formulations) each show cross reactivity in the EMIT assay for quinidine. Nevertheless, the EMIT assay for quinidine is acceptable for clinical use because these two compounds are also pharmacologically active.


The effects of a fruit and vegetable promotion intervention on unhealthy snacks during mid-morning school breaks: results of the Dutch Schoolgruiten Project.
Ample fruit and vegetable (F&V) intake has been associated with a decreased risk of chronic disease. The health-enhancing effects of increased F&V consumption, however, would be even more apparent if the increased F&V consumption additionally led to a lower intake of unhealthy, high calorie snacks. Therefore, the present study aimed to investigate whether a primary school-based intervention (the Dutch Schoolgruiten Project) that promoted F&V intake could additionally reduce the intake of unhealthy, high calorie snacks during school breaks. The study applied a longitudinal design with baseline and two follow-up measurements. Children were aged 9-10 years old at baseline; 705 children were included. The main strategy was a F&V scheme that improved the availability, accessibility and exposure to F&V at school by providing one serving of fruit or vegetables twice a week at no cost. The amounts of F&V and unhealthy snacks for consumption at school were measured using a single-item question included in a questionnaire. Multilevel autoregressive logistic regression models with a three-level structure (school, child and time) were used to assess the effect of the intervention on both F&V and unhealthy snack consumption. The children of the intervention group brought F&V from home to school at follow-up significantly more often than the children of the control schools [odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.04; 1.90] and brought fewer unhealthy snacks (OR = 0.56, 95% CI = 0.34; 0.92). The present study provides some evidence that the Schoolgruiten intervention effect on F&V intake also reduced unhealthy snacking during school breaks.


Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation.
Mammalian cell invasion by the protozoan parasite, Trypanosoma cruzi, is facilitated by the activation of host cell phosphatidylinositol 3 (PI 3)-kinases. We demonstrate that the well-characterized Ca2+-regulated lysosome-mediated parasite entry pathway is abolished by wortmannin pretreatment. In addition, we have characterized a novel route of T. cruzi invasion unexpectedly revealed in the course of this study. For over a decade, targeted exocytosis of lysosomes at the host cell plasma membrane was considered as the primary mechanism for T. cruzi entry into non-professional phagocytic cells. We now provide evidence that a significant fraction (50% or greater) of invading T. cruzi trypomastigotes exploit an alternate actin-independent entry pathway that involves formation of a tightly associated host cell plasma membrane-derived vacuole enriched in the lipid products of class I PI 3-kinases, PtdInsP3/PtdIns(3,4)P2. Initially devoid of lysosomal markers, the resultant parasite-containing vacuoles gradually acquire lysosome associated membrane protein 1 (lamp-1) and fluid phase endocytic tracer from the lysosomal compartment. In striking contrast to latex bead phagosomes, few T. cruzi vacuoles associate with the early endosomal marker, EEA1 and the 'maturation' process becomes refractory to PI 3-kinase inhibition immediately following parasite internalization. Jointly, these data provide a new paradigm for T. cruzi invasion of non-professional phagocytic cells and reveal a novel vacuole maturation process that appears to bypass the requirement for EEA1.


Validated Bayesian Differentiation of Causative and Passenger Mutations.
In many contexts, the problem arises of determining which of many candidate mutations is the most likely to be causative for some phenotype. It is desirable to have a way to evaluate this probability that relies as little as possible on previous knowledge, to avoid bias against discovering new genes or functions. We have isolated mutants with blocked cell cycle progression in Chlamydomonas and determined mutant genome sequences. Due to the intensity of UV mutagenesis required for efficient mutant collection, the mutants contain multiple mutations altering coding sequence. To provide a quantitative estimate of probability that each individual mutation in a given mutant is the causative one, we developed a Bayesian approach. The approach employs four independent indicators: sequence conservation of the mutated coding sequence with Arabidopsis; severity of the mutation relative to Chlamydomonas wild-type based on Blosum62 scores; meiotic mapping information for location of the causative mutation relative to known molecular markers; and, for a subset of mutants, the transcriptional profile of the candidate wild-type genes through the mitotic cell cycle. These indicators are statistically independent, and so can be combined quantitatively into a single probability calculation. We validate this calculation: recently isolated mutations that were not in the training set for developing the indicators, with high calculated probability of causality, are confirmed in every case by additional genetic data to indeed be causative. Analysis of "best reciprocal BLAST" (BRB) relationships among Chlamydomonas and other eukaryotes indicate that the temperature sensitive-lethal (Ts-lethal) mutants that our procedure recovers are highly enriched for fundamental cell-essential functions conserved broadly across plants and other eukaryotes, accounting for the high information content of sequence alignment to Arabidopsis.


Perioperative Serum 25-Hydroxyvitamin D Levels as a Predictor of Postoperative Opioid Use and Opioid Use Disorder: a Cohort Study.
Vitamin D deficiency is associated with chronic pain syndromes and higher opioid use among cancer patients, but its association with opioid use among opioid-naïve subjects following a major surgical procedure with acute pain has not been explored. To determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels, opioid use, and opioid use disorder. We identified commercially insured subjects aged 18-64 years with available perioperative serum 25-hydroxyvitamin D (25D) levels who underwent one of nine major surgical procedures in 2000-2014. Primary outcomes were dose and duration of opioid use measured using pharmacy claims. Secondary outcome was opioid use disorder captured using diagnosis codes. Multivariable negative binomial models with generalized estimating equations were performed examining the association between 25D levels and postoperative opioid use measures, adjusting for age, sex, race/ethnicity, Charlson score, education, income, latitude, and season of blood draw. Adjusted Cox regression was used to examine the association with opioid use disorder. Among 5446 subjects, serum 25(OH)D was sufficient (≥ 20 ng/mL) among 4349 (79.9%) subjects, whereas 837 (15.4%) had insufficient (12 to < 20 ng/mL) and 260 (4.8%) had deficient (< 12 ng/mL) levels. On multivariable analysis, as compared with subjects with sufficient 25(OH)D levels, subjects with deficient 25(OH)D levels had 1.7 more days (95% CI 0.76, 2.58) of opioid use per year and had 98.7 higher morphine milligram equivalent dose (95% CI 55.7, 141.8) per year. Among 11,713 study cohort, subjects with deficient 25(OH)D levels were more likely to be diagnosed with opioid use disorders (HR 2.41; 95% CI 1.05, 5.52). Patients undergoing common surgical procedures with deficient 25D levels are more likely to have higher opioid use and an increased risk of opioid use disorder compared to those with sufficient levels. Serum 25D levels may serve as a biomarker to identify subjects at increased risk of opioid misuse.


Estimated rate of fatal automobile accidents attributable to acute solvent exposure at low inhaled concentrations.
Acute solvent exposures may contribute to automobile accidents because they increase reaction time and decrease attention, in addition to impairing other behaviors. These effects resemble those of ethanol consumption, both with respect to behavioral effects and neurological mechanisms. These observations, along with the extensive data on the relationship between ethanol consumption and fatal automobile accidents, suggested a way to estimate the probability of fatal automobile accidents from solvent inhalation. The problem can be approached using the logic of the algebraic transitive postulate of equality: if A=B and B=C, then A=C. We first calculated a function describing the internal doses of solvent vapors that cause the same magnitude of behavioral impairment as ingestion of ethanol (A=B). Next, we fit a function to data from the literature describing the probability of fatal car crashes for a given internal dose of ethanol (B=C). Finally, we used these two functions to generate a third function to estimate the probability of a fatal car crash for any internal dose of organic solvent vapor (A=C). This latter function showed quantitatively (1) that the likelihood of a fatal car crash is increased by acute exposure to organic solvent vapors at concentrations less than 1.0 ppm, and (2) that this likelihood is similar in magnitude to the probability of developing leukemia from exposure to benzene. This approach could also be applied to other potentially adverse consequences of acute exposure to solvents (e.g., nonfatal car crashes, property damage, and workplace accidents), if appropriate data were available.


Age, structure, and sexuality: reflections on the anthropological evidence on homosexual relations.
The paper compares selected examples of age-structured homosexuality to understand same-sex eroticism as a "predictable" outcome of particular combinations of age, gender, and kinship. Unlike traditional models of homosexuality which view it as exceptional or abnormal, cross-cultural evidence demonstrates that homosexuality is an inextricable component of the structural codes of the societies in which it appears.


Cognitive Deficits in the THINC-Integrated Tool (THINC-it) Are Associated With Psychosocial Dysfunction in Patients With Major Depressive Disorder.
To evaluate the extent to which cognitive measures in the recently developed THINC-integrated tool (THINC-it) are associated with global and domain specific psychosocial disability in patients with current and remitted major depressive disorder (MDD). Cross-sectional data (N = 127) were obtained from participants with current (n = 105) or remitted (n = 22) MDD who completed the THINC-it between July 2014 and June 2018. Major depressive disorder was diagnostically assessed with DSM-IV and DSM-5 criteria. The THINC-it includes 4 objective cognitive tests: the Spotter (ie, Choice Reaction Time), Symbol Check (ie, n-back), CodeBreaker (ie, Digit Symbol Substitution), and Trails (ie, Trail Making Test part B), as well as a measure of self-perceived cognitive deficits, the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). Psychosocial dysfunction was assessed with the Functioning Assessment Short Test. The whole group analysis (ie, lifetime MDD) indicated that poor objective cognitive performance on the CodeBreaker (β = 0.346, P = .002) and Trails tasks (β = 0.232, P = .017) and greater self-reported cognitive deficits on the PDQ-5-D (β = 0.596, P < .001) were associated with more severe global psychosocial disability. In addition, performance on the CodeBreaker and Trails tasks showed dissociable relationships with specific psychosocial deficits (eg, occupational functioning, daily autonomy). The relationship between cognitive and psychosocial deficits was stronger in participants with current compared to remitted MDD. Cognitive deficits identified by the THINC-it are associated with global and specific psychosocial deficits, highlighting the clinical value and utility of the THINC-it as a cognitive screening instrument in patients with MDD.


Conditional and syllogistic deductive tasks dissociate functionally during premise integration.
Deduction allows us to draw consequences from previous knowledge. Deductive reasoning can be applied to several types of problem, for example, conditional, syllogistic, and relational. It has been assumed that the same cognitive operations underlie solutions to them all; however, this hypothesis remains to be tested empirically. We used event-related fMRI, in the same group of subjects, to compare reasoning-related activity associated with conditional and syllogistic deductive problems. Furthermore, we assessed reasoning-related activity for the two main stages of deduction, namely encoding of premises and their integration. Encoding syllogistic premises for reasoning was associated with activation of BA 44/45 more than encoding them for literal recall. During integration, left fronto-lateral cortex (BA 44/45, 6) and basal ganglia activated with both conditional and syllogistic reasoning. Besides that, integration of syllogistic problems additionally was associated with activation of left parietal (BA 7) and left ventro-lateral frontal cortex (BA 47). This difference suggests a dissociation between conditional and syllogistic reasoning at the integration stage. Our finding indicates that the integration of conditional and syllogistic reasoning is carried out by means of different, but partly overlapping, sets of anatomical regions and by inference, cognitive processes. The involvement of BA 44/45 during both encoding (syllogisms) and premise integration (syllogisms and conditionals) suggests a central role in deductive reasoning for syntactic manipulations and formal/linguistic representations.


Bronchial and gastrointestinal cryptosporidiosis in AIDS.
Cryptosporidiosis is a coccidial protozoan initially reported in domestic animals. It is primarily a gastrointestinal organism that does not invade mucosa. It was first described in 1976 in developing countries as an etiology of infantile diarrhea with inanition and malnutrition. Gastrointestinal involvement in patients with AIDS has been increasingly reported. We report a case of combined gastrointestinal and bronchial cryptosporidiosis. Cryptosporidium is an acid-fast organism which was successfully treated with erythromycin.


Transgenic expression of inclusion body myopathy associated mutant p97/VCP causes weakness and ubiquitinated protein inclusions in mice.
Mutations in p97/VCP cause the autosomal-dominant, inherited syndrome inclusion body myopathy (IBM) associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD) (Watts, G.D., Wymer, J., Kovach, M.J., Mehta, S.G., Mumm, S., Darvish, D., Pestronk, A., Whyte, M.P. and Kimonis, V.E. (2004) Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. p97/VCP is a multi-functional protein with a role in the ubiquitin-proteasome system (UPS) (Wang, Q., Song, C. and Li, C.C. (2004) Molecular perspectives on p97-VCP: progress in understanding its structure and diverse biological functions. To understand how mutations in this protein lead to a myopathy, we generated several lines of transgenic mice expressing p97/VCP-WT (TgVCP-WT) or the most common IBMPFD mutant, p97/VCP R155H (TgVCP-RH), under a muscle-specific promoter. TgVCP-RH animals, but not controls, became progressively weaker in a dose-dependent manner starting at 6 months of age. Abnormal muscle pathology, which included coarse internal architecture, vacuolation and disorganized membrane morphology with reduced caveolin-3 expression at the sarcolemma developed coincident with the onset of weakness. These changes were not associated with alterations in sarcolemmal integrity as measured by muscle fiber uptake of Evan's blue dye. Even before animals displayed measurable weakness, there was an increase in ubiquitin-containing protein inclusions and high-molecular-weight ubiquitinated proteins, markers of UPS dysfunction. We suggest that this early and persistent increase in ubiquitinated proteins induced by IBMPFD mutations in p97/VCP may ultimately lead to animal weakness and the observed muscle pathology. TgVCP-RH animals will be a valuable tool for understanding the pathogenesis of IBM and the role of the UPS in skeletal muscle.


Dopamine-Mediated Assembly of Citrate-Capped Plasmonic Nanoparticles into Stable Core-Shell Nanoworms for Intracellular Applications.
Plasmonic nanochains, derived from the one-dimensional assembly of individual plasmonic nanoparticles (NPs), remain infrequently explored in biological investigations due to their limited colloidal stability, ineffective cellular uptake, and susceptibility to intracellular disassembly. We report the synthesis of polydopamine (PDA)-coated plasmonic "nanoworms" (NWs) by sonicating citrate-capped gold (Cit-Au) NPs in a concentrated dopamine (DA) solution under alkaline conditions. DA mediates the assembly of Cit-Au NPs into Au NWs within 1 min, and subsequent self-polymerization of DA for 60 min enables the growth of an outer conformal PDA shell that imparts stability to the inner Au NW structure in solution, yielding "core-shell" Au@PDA NWs with predominantly 4-5 Au cores per worm. Our method supports the preparation of monometallic Au@PDA NWs with different core sizes and bimetallic PDA-coated NWs with Au and silver cores. The protonated primary amine and catechol groups of DA, with their ability to interact with Cit anions via hydrogen bonding and electrostatic attraction, are critical to assembly. When compared to unassembled PDA-coated Au NPs, our Au@PDA NWs scatter visible light and absorb near-infrared light more intensely and enter HeLa cancer cells more abundantly. Au@PDA NWs cross the cell membrane as intact entities primarily via macropinocytosis, mostly retain their inner NW structure and outer PDA shell inside the cell for 24 h, and do not induce noticeable cytotoxicity. We showcase three intracellular applications of Au@PDA NWs, including label-free dark-field scattering cell imaging, delivery of water-insoluble cargos without pronounced localization in acidic compartments, and photothermal killing of cancer cells.


Director/barycentric rotation in cholesteric droplets under temperature gradient.
When a chiral liquid crystal is given a transport current, a unidirectional molecular motion is known to take place, which is called the Lehmann effect. In this paper, we study the mysterious heat-current-driven Lehmann effect using two types of hemispherical cholesteric droplets using polarizing, reflecting, confocal and fluorescent microscopies. Both the droplets, coexisting with the isotropic phase and contacting on a glass substrate, are characterized by the concavo-convex modulated surface and the inside orientational helix. Further, the only difference between them is the helical axis direction; i.e., one is perpendicular and the other is parallel to the substrate. Under the temperature gradient perpendicular to the substrate, the droplet whose helical axis is parallel to the heat current exhibited pure director rotation, while that with the axis perpendicular to the current rotated independently as a rigid body. In the two droplets, the rotational conversion efficiency from the temperature gradient into the angular velocity showed very different dependences on the chirality strength and on the droplets' size, suggesting that the rotations of the two droplets may be driven by independent torques with different origins. This is the first observation that the cholesteric droplets under the temperature gradient exhibit the two rotational modes, the pure director rotation and the molecular barycentric motion, which can be switched to each other by changing the heat-current direction parallel and perpendicular to the helical axis.


Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity.
The parasympathetic nervous system, whose main neural substrate is the vagus nerve, exerts a fundamental antinociceptive role and influences gastrointestinal sensori-motor function. Our research question was to whether combined electrical and physiological modulation of vagal tone, using transcutaneous electrical vagal nerve stimulation (t-VNS) and deep slow breathing (DSB) respectively, could increase musculoskeletal pain thresholds and enhance gastroduodenal motility in healthy subjects. Eighteen healthy subjects were randomized to a subject-blinded, sham-controlled, cross-over study with an active protocol including stimulation of auricular branch of the vagus nerve, and breathing at full inspiratory capacity and forced full expiration. Recording of cardiac derived parameters including cardiac vagal tone, moderate pain thresholds to muscle, and bone pressure algometry, conditioned pain modulation using a cold pressor test and a liquid meal ultrasonographic gastroduodenal motility test were performed. Cardiac vagal tone increased during active treatment with t-VNS and DSB compared to sham (p = 0.009). In comparison to sham, thresholds to bone pain increased (p = 0.001), frequency of antral contractions increased (p = 0.004) and gastroduodenal motility index increased (p = 0.016) with active treatment. However, no effect on muscle pain thresholds and conditioned pain modulation was seen. This experimental study suggests that this noninvasive approach with combined electrical and physiological modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity. These findings warrant further investigation in patients with disorders characterized with chronic pain and gastrointestinal dysmotility such as functional dyspepsia and irritable bowel syndrome.


Simian virus 40 can overcome the antiproliferative effect of wild-type p53 in the absence of stable large T antigen-p53 binding.
In simian virus 40 (SV40)-transformed cells, a tight complex is formed between the viral large T antigen (large T) and p53. It has been proposed that this complex interferes with the antiproliferative activity of p53. This notion was tested in primary rat fibroblasts by assessing the ability of SV40-mediated transformation to be spared from the inhibitory effect of wild-type (wt) p53. The data indicate that relative to transformation induced by myc plus ras, SV40-plus-ras-mediated focus formation was indeed much less suppressed by p53 plasmids. A majority of the resultant cell lines made a p53 protein with properties characteristic of a wt conformation. Furthermore, cell lines expressing stably both SV40 large T and a temperature-sensitive p53 mutant continued to proliferate at a temperature at which this p53 assumes wt-like properties and normally causes a growth arrest. Surprisingly, at least partial resistance to the growth-inhibitory effect of wt p53 was also evident when transformation was mediated by an SV40 deletion mutant, encoding a large T which does not bind p53 detectably. In addition to supporting the idea that SV40 can overcome the growth-restrictive activity of wt p53, these findings strongly suggest that at least part of this effect does not require a stable association between p53 and large T.


Differential effects of coadministration of fluoxetine and WAY-100635 on serotonergic neurotransmission in vivo: sensitivity to sequence of injections.
Serotonin 5-HT(1A) receptor antagonists potentiate the effects of serotonin reuptake inhibitors on extracellular serotonin levels in a variety of brain regions. These effects are quite variable, however, with reports indicating potentiations of anywhere from 100-1900%. One factor that might impact the magnitude of such potentiations is the timing of administration of the two agents; reports in which the reuptake inhibitor is given prior to the serotonin receptor antagonist consistently report larger potentiations than reports in which the antagonist is given first. To test this relationship directly, microdialysis and electrophysiology studies were performed to assess the magnitude of increase in extracellular serotonin and changes in cellular activity produced by the serotonin reuptake inhibitor fluoxetine and the 5-HT(1A) receptor antagonist WAY-100635 under various dosing regimens. In microdialysis studies, when WAY-100635 (0.5 mg/kg s.c.) was administered 80 min after fluoxetine (10 mg/kg i.p.) the increase in serotonin was more than twice that observed when the compounds were coadministered. In electrophysiology studies in vivo, WAY-100635 reversed the depression of cell firing produced by fluoxetine when administered 30 min after fluoxetine, but when the two compounds were coadministered, a depression in firing rate was observed comparable to that produced by fluoxetine alone. In contrast, slice recording studies showed that WAY-100635 blocked the effects of fluoxetine regardless of the order of administration. These results indicate that fluoxetine and WAY-100635 can interact in a fashion not predicted by the currently accepted model. It is likely that neuronal circuitry outside of the raphe nuclei underlies this relationship.


QTL for survival to UV-C radiation in Drosophila melanogaster.
The aim of this study was to investigate tolerance to UV-C (ultraviolet C, 280-100 nm) radiation in Drosophila melanogaster, implementing a quantitative trait locus (QTL) mapping approach. This is of interest to test for genetic variation in survival to UV (ultraviolet) radiation. We performed a QTL scan in D. melanogaster recombinant inbred lines (RIL) constructed from parental stocks derived from a crossing between northern and southern hemisphere populations that segregated substantial genetic variation in thermal resistance in a previous study. Here, two experimental treatments were implemented: Continuous and cyclic UV-C radiation. Significant QTL were detected on all three major chromosomes. Among these, multiple trait composite interval mapping revealed a significant QTL in the pericentromeric region of chromosome 2, a genome region consistently implicated in thermotolerance in previous studies. This study shows substantial genetic variation for UV-C radiation resistance in D. melanogaster, with QTL for survival to UV-C radiation generally overlapping with major thermotolerance QTL. The genetic architecture of UV-C radiation resistance appears to be more complex in continuously irradiated individuals.


Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: a population-based case-control study and meta-analyses.
Epidemiological evidence suggests that intake of folate and other B-vitamins and genetic variants in the one-carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. In a large population-based case-control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 one-carbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) = 0.84 (0.73-0.96) and 0.85 (0.62-1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p-trend = 0.01, false discovery rate = 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Meta-analyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one-carbon metabolism pathway and breast cancer risk.


Dioxin removal from contaminated soils by ethanol washing.
The aim of this study was to investigate the potential utility of ethanol washing for remediating soils contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), as a cost-efficient alternative to conventional remediation methods of PCDD/F-contaminated soils. Initially, screening experiments were performed with a two-level full factorial design to examine the effects of temperature, extraction time and ethanol concentration on the removal efficiency. The screening experiments showed that the ethanol concentration was the most important parameter. In addition, repeated washing cycles considerably improved the results. Ethanol washing conditions were then selected (10 wash cycles with 75% ethanol at 60 degrees C), and applied to four soils with different soil characteristics and contamination levels to test the robustness of the selected method. Treatment efficiencies of 81% and 85% were obtained for a lightly contaminated sandy-silty soil and a highly contaminated clay soil rich in graphite particles, respectively. Even higher treatment efficiencies (> or = 97%) were obtained for two other highly contaminated soils, one of which contained high amounts of organic matter. PCDD/Fs were found to both dissolve in the solvent and migrate into it as species adsorbed to particles. The relative contributions of these mechanisms and the overall efficiency of the removal seem to depend on contaminant concentration, the types of carbon in the soil matrix and the particle size distribution. The study shows that ethanol washing has effective remediation potential for a variety of PCDD/F-contaminated soils.


The mitral L wave: a marker of pseudonormal filling and predictor of heart failure in patients with left ventricular hypertrophy.
We sought to examine the relationship of the mitral L wave with echocardiographic indexes of diastolic function and heart failure (HF) events in patients with left ventricular (LV) hypertrophy (LVH). The L wave, representing middiastolic transmitral flow, is of unknown clinical and prognostic significance in patients with LVH. Methods Consecutive echocardiograms performed during a 6-month period were screened for patients with LVH, normal LV ejection fraction, in sinus rhythm, and no significant valvular disease. Clinical and echocardiographic characteristics were analyzed, and patients were followed up for incident HF. Of 177 patients, the L wave was present in 35 (20%) (group I) and absent in 142 (group II). Patients in group I had higher early (E) to late (A) transmitral flow velocity (E/A) ratio (1.2 vs 0.8), shorter mitral E wave deceleration time (201 vs 225 milliseconds), lower pulmonary venous systolic/diastolic velocity ratio (1.1 vs 1.6), shorter LV isovolumic relaxation time (83 vs 94 milliseconds), larger left atrial volume (36 vs 23 mL/m 2 ), and higher E to early mitral annular velocity (E/E') ratio (septal E/E', 12.2 vs 9.1; lateral annular E/E', 10.9 vs 7.8) compared with group II (all P < .05). The difference between pulmonary venous atrial reversal and mitral A wave durations was > or = 30 milliseconds in more patients of group I (70% vs 6%, P < .001). During a mean follow-up of 12.0 months, 11 patients were hospitalized for HF. The L wave was associated with a hazard ratio of 4.7 ( P = .011) for incident HF, and remained a significant predictor (hazard ratio 4.2, P = .026) after adjustment for cardiovascular risk factors. In patients with LVH, the mitral L wave appears to be a marker of pseudonormal LV filling and predictor of future HF events.


Retinal Nerve Fiber Layer Thickness in Human T-cell Lymphotropic Virus Type 1 Patients.
To determine whether there is an optic neuropathy (ON) in patients with human T-cell lymphotropic virus type 1 (HTLV-1) infection. We included HTLV-1 asymptomatic carriers (a.c.HTLV-1) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) patients between January 1st, 2014 and March 31st, 2015. All patients had complete eye examination. The visual acuity (VA) and retinal nerve fiber layer (RNFL) thickness were measured and compared to age- and sex-matched control groups including patients seen in our refraction clinic with no previous medical or surgical history. Thirty-one a.c.HTLV-1 (group 1) and 29 TSP/HAM patients (group 2) were included. The average RNFL thickness was 99.9 ± 14.3 µm in group 1 and 87.8 ± 19.2 µm in group 2. The average RFNL thicknesses were lower in both groups, when compared to controls. The difference was significant in patients with TSP/HAM (87.8 ± 19.2 µm vs. 97 ± 7.8 µm; p = 0.003) who also had significantly decreased VA. We report here the first study about the RNFL thickness in patients with TSP/HAM. In these patients, there is decrease of the RNFL thickness with subtle but definite decrease of VA. This suggests that subclinical ON occurs in the natural history of the disease. The diagnosis of TSP/HAM must be evoked as a differential of primary progressive multiple sclerosis in a population at risk. Moreover, RNFL thinning with no evidence of glaucoma should raise suspicion for HTLV-1 infection and TSP/HAM in a population at risk.


Microwave-assisted hydrodistillation of essential oil from rosemary.
Effects of microwave assisted hydrodistillation (MAHD) and conventional hydrodistillation (HD) methods on yield, composition, specific gravity, refractive index, and antioxidant and antimicrobial activities of essential oil of Rosmarinus officinalis L were studied. The main aroma compounds of rosemary essential oil were found as 1,8-cineole and camphor. Trolox equivalent antioxidant capacity (TEAC) values for essential oils extracted by MAHD and HD were 1.52 mM/ml oil and 1.95 mM/ml oil, respectively. DPPH radical scavenging activity of the oils obtained by MAHD and HD were found as 60.55% and 51.04% respectively. Inhibitory effects of essential oils obtained by two methods on linoleic acid peroxidation were almost the same. Essential oils obtained by two methods inhibited growth of Esherichia coli O157:H7, Salmonella typhimurium NRRLE 4463 and Listeria monocytogenes Scott A with the same degree. However, inhibitory activity of essential oil obtained by MAHD on Staphylococcus aureus 6538P was stronger than that of obtained by HD (p < 0.05).


A NSQIP study comparing surgical outcomes between primary and non-primary TEPs after total laryngectomy.
Tracheoesophageal puncture with voice prosthesis (TEP) is considered the gold standard for voice rehabilitation after total laryngectomy; however, there is debate as to whether it should be inserted concurrently with removal of the larynx (primary TEP), or as a separate, additional procedure at a later date (secondary TEP). We utilized the National Surgical Quality Improvement Program Database (NSQIP) to compare postoperative complications, readmission rates, and reoperation rates among individuals who underwent total laryngectomy with or without concurrent TEP placement. We conducted a retrospective study using the American College of Surgeons National Surgical Quality Improvement Program database (ACS-NSQIP) from 2012 to 2019. Patients were categorized into primary and non-primary TEP groups using a variation of CPT codes for total laryngectomy, tracheoesophageal prosthesis, and type of reconstruction. Univariate analyses were performed and significance was determined at p < 0.05. A total of 1974 patients who underwent total laryngectomy were identified from the database: 1505 (77.3 %) in the non-primary TEP group and 442 (22.7 %) in the primary TEP group. Patients in the non-primary TEP group were more likely to have an ASA class greater than or equal to three (91.2 % primary vs. 84.6 % non-primary, p < 0.001). Patients in the non-primary TEP group were also more likely to require intraoperative or postoperative blood transfusions within the first 72 h of surgery (20.5 % non-primary vs. 15.3 % primary, p = 0.016). Both groups had similar rates of wound breakdown and dehiscence. There remained no significant difference based on type of reconstruction. This study suggests that patients receiving primary TEPs are not at a greater risk of developing wound complications such as pharyngocutaneous fistulas in the 30-day postoperative period. This remained true when patients were stratified by type of flap reconstruction. Patients in the non-primary TEP group were more likely to have an ASA category of 3 or greater, which may explain why they experienced higher rates of complications such as blood transfusions intra-operatively or post-operatively.


Interpretability of the PedsQL™ Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales in Pediatric Patients With Functional and Organic Gastrointestinal Diseases.
The present study investigates the clinical interpretability of the Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales and Worry Scales in pediatric patients with functional gastrointestinal disorders or organic gastrointestinal diseases in comparison with healthy controls. The PedsQL™ Gastrointestinal Scales were completed by 587 patients with gastrointestinal disorders/diseases and 685 parents, and 513 healthy children and 337 parents. Minimal important difference (MID) scores were derived from the standard error of measurement (SEM). Cut-points were derived based on one and two standard deviations (SDs) from the healthy reference means. The percentages of patients below the scales' cut-points were significantly greater than the healthy controls (most p values ≤ .001). Scale scores 2 SDs from the healthy reference means were within the range of scores for pediatric patients with a gastrointestinal disorder. MID values were generated using the SEM. The findings support the clinical interpretability of the new PedsQL™ Gastrointestinal Symptoms Scales and Worry Scales.


The ancient lunar core dynamo.
Lunar paleomagnetism provides evidence for the existence of an ancient lunar magnetic field generated in an iron core. Paleointensity experiments give a surface field of 1.3 gauss, 4.0 x 10(9) years ago, subsequently decreasing exponentially. Thermodynamic arguments give a minimum value of the heat source in the core at that time: known sources, radioactive and other, are quantitatively implausible, and it is suggested that superheavy elements were present in the early moon.


[Infective endocarditis].
Two different series of patients with Infectious Endocarditis (IE), hospitalized in the same ward of Curry Cabral Hospital in Lisbon, are presented and compared. The two series were separated by a ten-year period--the first included patients observed from 1970 to 1976 and the second from 1988 to 1998. In the first series (20 patients), IE occurred mainly in patients with previous cardiac valvular lesion, the course was subacute and Streptococcus viridans was the predominant agent. In the last series (65 patients), most of the patients were young and had no previous valvular lesions. Right side endocarditis predominated and the course was acute. Most of patients were drug addicts and had HIV infection. Staphylococcus aureus was the predominant agent. The ages of the two series were significantly different (p < 0.005). The diagnostic value of transthoracic and transesophageal echocardiography is stressed. The details of the evolution of patients with HIV infection are presented according to the values of CD4+ lymphocyte counts. The relatively good prognosis of IE in drug addicts with antibiotic treatment, even with HIV infection, is emphasized.


Molecular cloning and sequence of the thdF gene, which is involved in thiophene and furan oxidation by Escherichia coli.
Our previous work resulted in the isolation of mutant strains of Escherichia coli K-12 which were able to oxidize furans and thiophenes as a result of mutations in several novel genes. Some of the genes involved in thiophene oxidation were cloned into the multicopy vector pUC19. The plasmid pKA10 carries a 3.8-kb chromosomal fragment which encodes a previously undiscovered gene involved in thiophene oxidation. Three proteins with approximate molecular sizes of 48, 30, and 26 kDa were overproduced by cells carrying pKA10. Maxicell experiments and DNA sequence analysis indicated that the 48- and 26-kDa proteins are encoded by pKA10, whereas the 30-kDa protein is apparently chromosomally derived. A cassette specifying kanamycin resistance was inserted into various sites on pKA10. An insertion which abolished the 48-kDa protein also abolished thiophene oxidation. Chromosomal integration of pKA10::Kan allowed us to locate the chromosomal insert of pKA10 at 84 min on the E. coli genetic map by transduction. Since no previously identified genes involved in thiophene metabolism are located in this region, we designated the gene for the 48-kDa protein as thdF. Sequencing of the 3.8-kb insert revealed an overlap of several hundred bases with the regulatory and structural regions of the tnaA gene, which is also located at 84 min. The 26-kDa protein is probably truncated tnaA protein. An open reading frame corresponding to the 48-kDa thdF protein was located next to the tnaA gene, which encodes tryptophanase, but was transcribed in the opposite sense.


Preregistration house officers in eight English regions: survey of quality of training.
To assess the quality of preregistration house officer training in eight English regions. Postal questionnaire. Thames, East Anglian, Mersey, Northern, and Wessex regions. 1670 preregistration house officers. Education, hours of work, workload, conditions of work, and attitudes to job and medicine as a career. Response rate was 69% (1146 replies). Most house officers had attended induction courses (1036/1129 (92%)); 74% (757/1024) found them satisfactory. The proportions who had never received adequate guidance on how to break bad news and how to control pain were 59% (670/1135) and 56% (634/1136) respectively. There was much variation between regions. Overall, 65% (736/1138) reported confidence in performing cardiopulmonary resuscitation. Most respondents (95% (1089/1142)) worked an on call rota, 3% (36) a partial shift, and 0.6% (seven) a full shift; 19% (202) were on duty for average weekly hours that exceeded the targets for 1 April 1993. House officers had a median of 20 patients under their care and clerked a median of 10 emergency cases, six routine cases, and two day cases a week. Over half (690/1128 (61%)) could not obtain hot food after 8 pm, 20% (223/1095) did not always have clean sheets available in their on call room, and 45% (462/1036) did not consider the protection of staff against violence to be adequate at their hospital. The most important problems with the preregistration year were inappropriate or non-medical tasks (ranked first by 360 respondents), hours of work (359), and pay for out of hours work (167). Overall 57% (646/1125) would encourage a friend to apply for their post, but only 24% (266/1112) would encourage a friend to take up medicine and 44% (494/1112) would discourage the idea. House officers' training is deficient in important respects, with inappropriate tasks and heavy clinical workloads impeding the provision of proper education.


Inorganic-organic hybrid high-dimensional polyoxotantalates and their structural transformations triggered by water.
The first two inorganic-organic hybrid three-dimensional (3D) polyoxotantalates (POTas) and the first two inorganic-organic hybrid 2D POTas have been obtained. All of these high-dimensional POTas are built from a new-type POTa dimeric cluster {Cu(en)(Ta6O19)}2/{Cu(enMe)(Ta6O19)}2 (en = ethylenediamine, enMe = 1,2-diaminopropane) bridged by copper complexes. Interestingly, extended POTas 1 and 3 can undergo single-crystal to single-crystal structural transformations triggered by water.


Parasitoses with central nervous system involvement.
Most of the parasitoses manifest systemically, including the central nervous system (CNS). Among the most prevalent parasitoses in Central Europe (cysticercosis, toxocarosis, echinococcosis, and toxoplasmosis), cerebral involvement is well recognized and part of the clinical presentation, which cannot be neglected. CNS involvement results from invasion of larvae of these parasites via the blood stream or by direct migration into the CNS. Most frequently larvae reside within the cerebral parenchyma, but sometimes also within the ventricles, in the meningeas within cerebral aneurysms, or in the parenchyma of the spinal cord. Depending on the stage of their development, they cause a local defect or more widespread damage, such as encephalitis, ventriculitis, ependymitis, arachnoiditis, meningitis, myelitis, polyradiculitis, mechanical obstruction of the arterial or cerebrospinal fluid (CSF) flow, or vasculitis with appropriate clinical presentations. These include epilepsy, headache, impaired consciousness, orientation, cognition, focal neurological motor, sensory, or vegetative deficits, or visual impairment. CNS involvement is diagnosed on the clinical presentation, the epidemiological background, blood and CSF investigations, imaging studies, and sometimes biopsy. Treatment is based on various antihelminthic agents and, occasionally, surgery.


Current concepts in anterior glenohumeral instability: diagnosis and treatment.
The glenohumeral joint is the most dislocated articulation, accounting for more than 50% of all joint dislocations. The reason behind shoulder instability should be investigated in detail for successful management, and the treatment plan should be individualized for all patients. Several classification systems have been proposed for glenohumeral instability. A physical exam is mandatory no matter what classification system is used. When treating patients with anterior shoulder instability, surgeons need to be aware of the critical size of the bone loss, which is commonly seen. The glenoid track concept was clinically adopted, and the measurement of the glenoid track for surgical decision-making is recommended. Detailed assessment of existing soft tissue injury to the labrum, capsule, glenohumeral ligaments, and rotator cuff is also mandatory as their presence influences the surgical outcome. Rehabilitation, arthroscopic repair techniques, open Bankart procedure, capsular plication, remplissage, Latarjet technique, iliac crest, and other bone grafts offer the surgeon different treatment options according to the type of patient and the lesions to be treated. Three-dimensional (3D) technologies can help to evaluate glenoid and humeral defects. Patient-specific guides are low-cost surgical instruments and can be used in shoulder instability surgery. 3D printing will undoubtedly become an essential tool to achieve the best results in glenohumeral instability surgery.


Immune Checkpoint Inhibitors in Pediatric Solid Tumors: Status in 2018.
Checkpoint inhibitors have transformed the treatment of cancer in adults. This class of drugs has demonstrated encouraging results in various malignancies such as metastatic melanoma, bladder cancer, renal cancer, and non-small cell lung carcinoma. However, researchers have only begun investigating the effectiveness and tolerability of checkpoint inhibitors in pediatric patients. We conducted a review of PubMed indexed literature and clinicaltrials.gov using combinations of the keywords checkpoint, inhibitor, pediatric, CTLA-4 (cytotoxic T lymphocyte antigen-4), PD-1 (programmed cell death-1), and PD-L1 (programmed cell death receptor-1 ligand) to find every recently completed and ongoing trial evaluating checkpoint inhibitors in patients younger than 21 years old. Pertinent articles and clinical trials discussing the role of immune checkpoint inhibitors in the pediatric population were selected for final analysis and manuscript citation. This review presents an overview of the cellular mechanisms involved in checkpoint inhibition and of studies evaluating checkpoint inhibitors in humans. The review also details results and side effects from studies conducted with pediatric patients, current pediatric clinical trials, and future implications. Immune checkpoint inhibitors have the potential to further therapeutic advances in pediatric oncology; however, we need more clinical trials and combination drug strategies targeted toward pediatric cancers.


Single-cell molecular analysis defines therapy response and immunophenotype of stem cell subpopulations in CML.
Understanding leukemia heterogeneity is critical for the development of curative treatments as the failure to eliminate therapy-persistent leukemic stem cells (LSCs) may result in disease relapse. Here we have combined high-throughput immunophenotypic screens with large-scale single-cell gene expression analysis to define the heterogeneity within the LSC population in chronic phase chronic myeloid leukemia (CML) patients at diagnosis and following conventional tyrosine kinase inhibitor (TKI) treatment. Our results reveal substantial heterogeneity within the putative LSC population in CML at diagnosis and demonstrate differences in response to subsequent TKI treatment between distinct subpopulations. Importantly, LSC subpopulations with myeloid and proliferative molecular signatures are proportionally reduced at a higher extent in response to TKI therapy compared with subfractions displaying primitive and quiescent signatures. Additionally, cell surface expression of the CML stem cell markers CD25, CD26, and IL1RAP is high in all subpopulations at diagnosis but downregulated and unevenly distributed across subpopulations in response to TKI treatment. The most TKI-insensitive cells of the LSC compartment can be captured within the CD45RA- fraction and further defined as positive for CD26 in combination with an aberrant lack of cKIT expression. Together, our results expose a considerable heterogeneity of the CML stem cell population and propose a Lin-CD34+CD38-/lowCD45RA-cKIT-CD26+ population as a potential therapeutic target for improved therapy response.


Impact of COVID-19 on American Family Physicians' Intent to Retreat from Clinical Care.
This survey evaluated whether the COVID-19 pandemic was a traumatic stress event for family physicians associated with burnout, changes in life priorities, and intentions to retreat from clinical practice. We report on 683 clinically active family physicians surveyed through the Council of Academic Family Medicine's Educational Research Alliance (CERA) in the fall of 2021. Overall, 35.2% of family physicians experienced the pandemic as a traumatic stress like event. This was associated with changing life priorities (OR 2.6, CI 1.8-3.9), burnout (OR 1.6, CI 1.1 to 2.4), and withdrawal from clinical practice in various ways. Those who changed their priorities in life were more likely to restrict scope of practice (OR 3.9, CI 2.6-5.9), reduce clinical work effort (OR 3.4, 2.3 to 5.1), relocate (OR 3.1, CI 2.0 to 4.8), retire (OR 2.7, CI 1.4-4.9), reroute their career away from patient care (OR 2.1, CI 1.4-3.1) and less likely to avoid redesigning the practice to improve well-being (OR 0.3, CI 0.2-0.7). Those who experienced burnout were more likely to retire (OR 5.5, CI 2.8 to 10.5), reduce clinical work effort (OR 4.2, CI 2.9-6.1), reroute their career away from patient care (OR 3.9, CI 2.6-5.8), relocate (OR 3.8, CI 2.4 to 5.9), and restrict scope of practice (OR 3.3, CI 2.3 to 4.9). Overall, 48.5% of family physicians expressed some intention to retreat from clinical practice. The COVID-19 pandemic impacted family physician's career plans. Remedying burnout is a high-yield opportunity for retaining clinically active family physicians. Physicians retreating from clinical medicine related to changing life's priorities needs further exploration.


Selective outcome reporting across psychopharmacotherapy randomized controlled trials.
Selective reporting impairs the valid interpretation of trials and leads to bias with regards to the clinical evidence. We aimed to examine factors associated with selective reporting in psychopharmacotherapy trials and thus enable solutions to prevent such selective reporting in the future. We retrieved all registry records of trials investigating medication for depressive, bipolar and psychotic disorders. Multivariate logistic regression was performed with selective reporting as outcome, and funding source, psychiatric disorder, year of study start date, participating centers, and anticipated sample size as explanatory variables, after testing for multicollinearity. Adjusted odds ratios (AOR) were calculated. Two-sided Fisher exact test was used to compare the proportions of newly added positive primary outcomes with the proportions of positive results in the overall group of primary outcomes. Of 151 included trials (N = 94,303 participants), 21 (14%) showed irregularities between registered and published primary outcomes. Higher odds of such irregularities were associated with non-industry-funded RCTs (AOR 5.3; p = 0.014) and trials investigating major depressive disorder (AOR 12.7; p = 0.024) or schizophrenia (AOR 14.5; p = 0.016; Table 1). We demonstrate discrepancies between trial registrations and publications across RCTs investigating debilitating psychiatric disorders, especially in non-industry funded RCTs.


Triple therapy with azithromycin, omeprazole, and amoxicillin is highly effective in the eradication of Helicobacter pylori: a controlled trial versus omeprazole plus amoxicillin.
Azithromycin is a new-generation, acid-stable macrolide antibiotic that achieves remarkably high concentrations in gastric tissue, persisting above the MIC90 for Helicobacter pylori over a 5-day period after a single 500-mg oral dose. We evaluated a new metronidazole-free triple therapy with omeprazole 20 mg b.i.d. plus amoxicillin 1 g b.i.d. (both for 14 days) and azithromycin 500 mg mane (for the first 3 days only) (group I) versus double therapy with omeprazole 20 mg b.i.d. plus amoxicillin 1 g t.i.d., both for 14 days (group II). H. pylori status was determined by urease test and histology before and 6 wk after completion of therapy. Ninety-two patients with peptic ulcer disease or nonulcer dyspepsia completed the study. H. pylori infection was eradicated in 44 (91.6%) of 48 patients randomized to receive triple therapy versus 26 (59.1%) of 44 who received double therapy (p < 0.001). Smoking, but not omeprazole pretreatment, proved to be a risk factor for treatment failure only in the double-therapy group (p = 0.05). All ulcers healed by the time of the 8-wk endoscopic control. Side effects, usually minor, were recorded in 12.5% and 9.1% of patients, respectively (NS), but therapy had to be discontinued in one patient in group I and in three in group II (NS). Two-week triple therapy with omeprazole, amoxicillin, and (for the first 3 days) low-dose azithromycin is highly effective in eradicating H. pylori. This regimen is safe and well-tolerated, and we recommend that it be used as first-line treatment, as an alternative to less-effective omeprazole-amoxicillin double therapy. Moreover, azithromycin appears to be a new, promising antibiotic for future innovative anti-H. pylori combinations.


Health care's service fanatics.
The Cleveland Clinic has long had a reputation for medical excellence. But in 2009 the CEO acknowledged that patients did not think much of their experience there and decided to act. Since then the Clinic has leaped to the top tier of patient-satisfaction surveys, and it now draws hospital executives from around the world who want to study its practices. The Clinic's journey also holds Lessons for organizations outside health care that must suddenly compete by creating a superior customer experience. The authors, one of whom was critical to steering the hospital's transformation, detail the processes that allowed the Clinic to excel at patient satisfaction without jeopardizing its traditional strengths. Hospital leaders: Publicized the problem internally. Seeing the hospital's dismal service scores shocked employees into recognizing that serious flaws existed. Worked to understand patients' needs. Management commissioned studies to get at the root causes of dissatisfaction. Made everyone a caregiver. An enterprisewide program trained everyone, from physicians to janitors, to put the patient first. Increased employee engagement. The Clinic instituted a "caregiver celebration" program and redoubled other motivational efforts. Established new processes. For example, any patient, for any reason, can now make a same-day appointment with a single call. Set patients' expectations. Printed and online materials educate patients about their stays--before they're admitted. Operating a truly patient-centered organization, the authors conclude, isn't a program; it's a way of life.


Evaluation of rosette inhibition test in renal transplantation.
Serial rosette inhibition tests were performed on 11 renal transplant patients in an attempt to predict graft rejection. The rosette inhibition titre was higher in immunosuppressed patients than in normal subjects. The test was of predictive value in only two out of 12 rejection episodes, where a fall in titre to normal levels occurred 48 hours and 24 hours, respectively, before biochemical evidence of rejection. In two further rejection episodes the titre fell at the time of rejection. The titre changes in all tests were small and there were frequent inconsistencies in the results of individual tests. A study of the variables was undertaken, with standardization of the technique, and improvements were made in reading the test. Despite these changes the test was still not sufficiently accurate or reliable to be used as the basis of treatment of rejection episodes.


The reliability, validity, and feasibility of multisource feedback physician assessment: a systematic review.
The use of multisource feedback (MSF) or 360-degree evaluation has become a recognized method of assessing physician performance in practice. The purpose of the present systematic review was to investigate the reliability, generalizability, validity, and feasibility of MSF for the assessment of physicians. The authors searched the EMBASE, PsycINFO, MEDLINE, PubMed, and CINAHL databases for peer-reviewed, English-language articles published from 1975 to January, 2013. Studies were included if they met the follow ing inclusion criteria: used one or more MSF instruments to assess physician performance in practice; reported psychometric evidence of the instrument(s) in the form of reliability, generalizability coefficients, and construct or criterion-related validity; and provided information regarding the administration or feasibility of the process in collecting the feedback data. Of the 96 full-text articles assessed for eligibility, 43 articles were included. The use of MSF has been shown to be an effective method for providing feedback to physicians from a multitude of specialties about their clinical and nonclinical (i.e., professionalism, communication, interpersonal relationship, management) performance. In general, assessment of physician performance was based on the completion of the MSF instruments by 8 medical colleagues, 8 coworkers, and 25 patients to achieve adequate reliability and generalizability coefficients of α ≥ 0.90 and Ep ≥ 0.80, respectively. The use of MSF employing medical colleagues, coworkers, and patients as a method to assess physicians in practice has been shown to have high reliability, validity, and feasibility.


Digestive bioavailability to a deposit feeder (Arenicola marina) of polycyclic aromatic hydrocarbons associated with anthropogenic particles.
Marine sediments around urban areas serve as catch basins for anthropogenic particles containing polycyclic aromatic hydrocarbons (PAHs). Using incubations with gut fluids extracted from a deposit-feeding polychaete (Arenicola marina), we determined the digestive bioavailability of PAHs from fly ashes, coal dusts, diesel soots, tire tread materials, and urban particulates. We found that gut fluids solubilize significant concentrations of PAHs from two tire treads, two diesel soots, and the urban particulates. However, PAHs in fly ashes and coal dusts were not available to the digestive agents in gut fluid. Potential digestive exposure to PAHs is much greater than that predicted to be available from these materials using equilibrium partitioning theory (EqP). Amending an already-contaminated sediment with fly ash decreased phenanthrene solubilization by gut fluid. In contrast, addition of tire tread to the sediment resulted in increased solubilization of four PAHs by gut fluid. Therefore, addition of certain types of anthropogenic particles to sediments may result in an increase in bioavailable PAHs rather than a net decrease, as predicted by EqP. Difficulty in predicting the amount of change due to amendment may be due to interactions occurring among the mixture of compounds solubilized by gut fluid.


Exact Coherent Structures and Phase Space Geometry of Preturbulent 2D Active Nematic Channel Flow.
Confined active nematics exhibit rich dynamical behavior, including spontaneous flows, periodic defect dynamics, and chaotic "active turbulence." Here, we study these phenomena using the framework of exact coherent structures, which has been successful in characterizing the routes to high Reynolds number turbulence of passive fluids. Exact coherent structures are stationary, periodic, quasiperiodic, or traveling wave solutions of the hydrodynamic equations that, together with their invariant manifolds, serve as an organizing template of the dynamics. We compute the dominant exact coherent structures and connecting orbits in a preturbulent active nematic channel flow, which enables a fully nonlinear but highly reduced-order description in terms of a directed graph. Using this reduced representation, we compute instantaneous perturbations that switch the system between disparate spatiotemporal states occupying distant regions of the infinite-dimensional phase space. Our results lay the groundwork for a systematic means of understanding and controlling active nematic flows in the moderate- to high-activity regime.


SNR in photocounting images of rough objects in partially coherent light.
Image irradiance distributions from objects illuminated with partially coherent, quasi-monochromatic light, viewed against a spatially uniform background and received with a photosensitive detector are analyzed. A general expression for the SNR at the detector output is obtained as a function of the coherence of the illuminating light, the object surface roughness, the width of the telescope point spread function, and the aperture and integration time of the detector. The expression is evaluated for several limiting cases of coherence of illumination and of object surface roughness.


Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase.
Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.


Corneal thickness measured by interferometry.
An optical method for measuring the thickness of transparent structures has been developed, and has been used to measure, in vivo, the thickness of the human cornea. The thickness is measured by placing the anterior surface of the cornea at the focus of a beam of coherent laser light and then measuring the spacing between the interference fringes generated by the reflected light. The thickness is then calculated from the fringe spacing. The method has been used to measure corneal thickness in frog and human corneas. These measurements have been correlated with histologic and pachometer measurements of corneal thickness. A significant capability of this technique is to measure the thickness of optically opaque corneas.


Simulation study of anisotropic random sequential adsorption of extended objects on a triangular lattice.
The properties of the anisotropic random sequential adsorption (RSA) of objects of various shapes on a two-dimensional triangular lattice are studied numerically by means of Monte Carlo simulations. The depositing objects are formed by self-avoiding lattice steps, whereby the first step determines the orientation of the object. Anisotropy is introduced by positing unequal probabilities for orientation of depositing objects along different directions of the lattice. This probability is equal p or (1-p)/2, depending on whether the randomly chosen orientation is horizontal or not, respectively. Approach of the coverage θ(t) to the jamming limit θ(jam) is found to be exponential θ(jam)-θ(t)is proportional to exp(-t/σ), for all probabilities p. It was shown that the relaxation time σ increases with the degree of anisotropy in the case of elongated and asymmetrical shapes. However, for rounded and symmetrical shapes, values of σ and θ(jam) are not affected by the presence of anisotropy. We finally analyze the properties of the anisotropic RSA of polydisperse mixtures of k-mers. Strong dependencies of the parameter σ and the jamming coverage θ(jam) on the degree of anisotropy are obtained. It is found that anisotropic constraints lead to the increased contribution of the longer k-mers in the total coverage fraction of the mixture.


Genetic analysis of dietary intake identifies new loci and functional links with metabolic traits.
Dietary intake is a major contributor to the global obesity epidemic and represents a complex behavioural phenotype that is partially affected by innate biological differences. Here, we present a multivariate genome-wide association analysis of overall variation in dietary intake to account for the correlation between dietary carbohydrate, fat and protein in 282,271 participants of European ancestry from the UK Biobank (n = 191,157) and Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 91,114), and identify 26 distinct genome-wide significant loci. Dietary intake signals map exclusively to specific brain regions and are enriched for genes expressed in specialized subtypes of GABAergic, dopaminergic and glutamatergic neurons. We identified two main clusters of genetic variants for overall variation in dietary intake that were differently associated with obesity and coronary artery disease. These results enhance the biological understanding of interindividual differences in dietary intake by highlighting neural mechanisms, supporting functional follow-up experiments and possibly providing new avenues for the prevention and treatment of prevalent complex metabolic diseases.


A survey on the incidence and cause of ovine abortion in Hawkes Bay.
The results of a postal survey which yielded a 57% response and which examined the incidence and cause of abortions in central Hawkes Bay flocks, is presented. Data were provided from a total of 3,952,000 ewes from 1975-80. Overall, highly significant differences in the incidence of abortion were recorded between properties (range 0-16%); years (1975-0.86%, 1976-0.75%, 1977-0.86%, 1978-2.42%, 1979-2.78%, 1980-2.04%); ewe age (maiden 2-year -5.3%, mixed age -1.6%);flock size (higher incidence in smaller flocks); and winter management systems (of the flocks which were experiencing greater than a 2% abortion rate, 73.2% were being rotationally mob stocked during the winter compared with only 23.8% being set stocked). Bacteriological examination of aborted lambs during 1979 revealed that Campylobacter spp. were involved exclusively. In the 1980 survey, only half of the lambs examined showed Campylobacter infection, the other half yielding Toxoplasma either as pure or mixed infections. The results of a trial which utilised 10,592 2-year ewes demonstrated significant differences between animals vaccinated with a killed Campylobacter vaccine and non-vaccinated controls in the following reproductive parameters: ewes aborting, dry dry ewes, total lambs born and lambs marked.


[Mycobacterium gordonae as potential cause of granulomatous lesions of the toe tips in the South African clawed frog (Xenopus laevis)].
During regular health status monitoring of the colony of amphibian, Mycobacterium (M.) gordonae were isolated from granulomatous lesions of the tiptoes from the South African clawed frog (Xenopus laevis) maintained at the Tierforschungszentrum of the University of Ulm. During a period of three years a total of 21 animals of the colony, consisting of 350-400 frogs, showed granuloma of the tip of the toes and a loss of the claws. The general condition and the behavior of the frogs appeared to be unchanged. Using a selective medium one isolate was cultured and identified by sequencing of the 16S rRNA gene. To apply a rapid diagnostic method for detecting mycobacteria, in particular M. gordonae in the health monitoring programme of the Xenopus laevis colony, we established the rpoB gene PCR followed by HaeIII restriction analysis of the PCR product. We identified M. gordonae from granuloma of the tiptoes and from unaltered tissue samples of the lungs and skin by PCR restriction analysis. Since mycobacterial species apparently are widespread in granulomatous lesions of the tiptoes of Xenopus laevis, we hypothesize a pathogenic potential. This view is supported by an increasing number of reports in the literature on infections with nontuberculous, "non-pathogenic" mycobacteria in Xenopus laevis.


A framework for targeting water, sanitation and hygiene interventions in pastoralist populations in the Afar region of Ethiopia.
Globally, many populations face structural and environmental barriers to access safe water, sanitation and hygiene (WASH) services. Among these populations are many of the 200 million pastoralists whose livelihood patterns and extreme environmental settings challenge conventional WASH programming approaches. In this paper, we studied the Afar pastoralists in Ethiopia to identify WASH interventions that can mostly alleviate public health risks, within the population's structural and environmental living constraints. Surveys were carried out with 148 individuals and observational assessments made in 12 households as part of a Pastoralist Community WASH Risk Assessment. The results show that low levels of access to infrastructure are further compounded by risky behaviours related to water containment, storage and transportation. Additional behavioural risk factors were identified related to sanitation, hygiene and animal husbandry. The Pastoralist Community WASH Risk Assessment visually interprets the seriousness of the risks against the difficulty of addressing the problem. The assessment recommends interventions on household behaviours, environmental cleanliness, water storage, treatment and hand hygiene via small-scale educational interventions. The framework provides an approach for assessing risks in other marginal populations that are poorly understood and served through conventional approaches.


Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts.
Direct reprogramming of one cell type into another has recently emerged as a powerful paradigm for regenerative medicine, disease modeling, and lineage specification. In particular, the conversion of fibroblasts into induced cardiomyocyte-like myocytes (iCLMs) by Gata4, Hand2, Mef2c, and Tbx5 (GHMT) represents an important avenue for generating de novo cardiac myocytes in vitro and in vivo. Recent evidence suggests that GHMT generates a greater diversity of cardiac subtypes than previously appreciated, thus underscoring the need for a systematic approach to conducting additional studies. Before direct reprogramming can be used as a therapeutic strategy, however, the mechanistic underpinnings of lineage conversion must be understood in detail to generate specific cardiac subtypes. Here we present a detailed protocol for generating iCLMs by GHMT-mediated reprogramming of mouse embryonic fibroblasts (MEFs). We outline methods for MEF isolation, retroviral production, and MEF infection to accomplish efficient reprogramming. To determine the subtype identity of reprogrammed cells, we detail a step-by-step approach for performing immunocytochemistry on iCLMs using a defined set of compatible antibodies. Methods for confocal microscopy, identification, and quantification of iCLMs and individual atrial (iAM), ventricular (iVM), and pacemaker (iPM) subtypes are also presented. Finally, we discuss representative results of prototypical direct reprogramming experiments and highlight important technical aspects of our protocol to ensure efficient lineage conversion. Taken together, our optimized protocol should provide a stepwise approach for investigators to conduct meaningful cardiac reprogramming experiments that require identification of individual CM subtypes.


Longitudinal Magnetic Resonance Imaging-Based Superficial Femoral Artery Velocity Measurements in Diabetic and Nondiabetic Patients With Peripheral Artery Disease.
Longitudinal associations of noninvasive 2-dimensional phase-contrast magnetic resonance imaging (2D-PC-MRI) velocity markers of the superficial femoral artery (SFA) were analyzed along with the characteristics of peripheral artery disease (PAD). We hypothesized that the 2-year differences in MRI-based measures of SFA velocity were associated with longitudinal changes in markers of PAD. A total of 33 (11 diabetic, 22 nondiabetic) patients with PAD with baseline and 2-year follow-up MRI scans were included in this secondary analysis of the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically gated 2D-PC-MRI was performed at a proximal and a distal location of the distal SFA territory. SFA lumen, wall, and total vessel volumes and the normalized wall index (NWI) were analyzed. Baseline characteristics did not differ between diabetic and nondiabetic PAD patients. Maximum proximal and distal SFA velocity measures did not differ between baseline and 2 years (41.98 interquartile range (IQR) (23.58-72.6) cm/s vs. 40.31 IQR (26.69-61.29) cm/s; P = 0.30). Pooled analysis (N = 33) showed that the 24-month change in the NWI was inversely associated with the 24-month change in the proximal maximal SFA velocity (beta = -168.36, R2 = 0.150, P value = 0.03). The 24-month change of the maximum velocity differences between the proximal and distal SFA locations was inversely associated with the 24-month changes in peak walking distance (beta = -0.003, R2 = 0.360, P value = 0.011). The 2-year change of SFA plaque burden is inversely associated with the 2-year change of proximal peak SFA blood flow velocity. 2D-PC-MRI measured SFA velocity may be of interest in assessing PAD longitudinally.


Inotropic and chronotropic profile of MCI-154: comparison with isoproterenol and imazodan in guinea pig cardiac preparations.
Although recent studies indicate that MCI-154 exerts novel positive inotropic actions in heart muscle, the chronotropic properties of this new drug remain undefined. The present study compared the inotropic/chronotropic profile of MCI-154 with those of a nonselective beta 1/beta 2-agonist (isoproterenol, Iso) and a type III phosphodiesterase inhibitor (imazodan, CI-914) in cardiac preparations isolated from guinea pigs. The inotropic efficacy of MCI-154 was approximately equal to that of Iso and CI-194 in electrically paced (1 Hz) atrial muscle, with each agent increasing isometric contractile tension approximately 170% above basal (predrug) values. The inotropic EC50 for Iso (2.9 +/- 0.7 x 10(-9) M) was several orders of magnitude less than that for MCI-154 (1.4 +/- 0.4 x 10(-4) M) and CI-914 (1.1 +/- 0.2 x 10(-4) M). The inotropic potency of MCI-154 was equivalent in atrial and left ventricular myocardium. Both Iso and CI-194 substantially increased spontaneous beating frequency of sinoatrial preparations, and the inotropic/chronotropic potency ratio for each was unity. In contrast, MCI-154 exerted a slight negative chronotropic action on basal sinoatrial rate. Moreover, the negative chronotropic influence of MCI-154 was increased several-fold in the presence of Iso-stimulated maximal increases in heart rate (HR), and this inhibitory chronotropic action of MCI-154 was not prevented by muscarinic receptor blockade with atropine. These findings indicate that MCI-154 has a unique inotropic/chronotropic profile in cardiac tissues of guinea pigs in that this drug (a) efficaciously increased myocardial contractility, (b) had minimal effect on basal sinoatrial automaticity and yet (c) markedly inhibited sympathetically mediated sinus tachycardia.


Microalbuminuria is associated with all-cause and AIDS mortality in women with HIV infection.
Prevalence of microalbuminuria is increased in patients with HIV. Microalbuminuria is associated with increased mortality in other populations, including diabetics, for whom microalbuminuria testing is standard of care. We investigated whether microalbuminuria is associated with mortality in HIV-infected women not receiving antiretroviral therapy. Urinalysis for proteinuria and semiquantitative testing for microalbuminuria were performed in specimens from 2 consecutive visits in 1547 HIV-infected women enrolled in the Women's Interagency HIV Study in 1994-1995. Time to death was modeled using proportional hazards analysis. Compared with women without albuminuria, the hazard ratio (HR) for all-cause mortality was increased in women with 1 (HR: 3.4; 95% CI: 2.2 to 5.2) or 2 specimens positive for either proteinuria or microalbuminuria (HR: 3.9; 95% CI: 2.1 to 7.0). The highest risk was observed in women with both specimens positive for proteinuria (HR: 5.8; 95% CI: 3.4 to 9.8). The association between albuminuria and all-cause mortality risk remained significant after adjustment for demographics, HIV disease severity, and related comorbidities. Similar results were obtained for AIDS death. We identified a graded relationship between albuminuria and the risk of all-cause and AIDS mortality.


Internal Nitrogen Pools Shape the Infection of Aureococcus anophagefferens CCMP 1984 by a Giant Virus.
The pelagophyte Aureococcus anophagefferens blooms annually in shallow bays around the world, where it is hypothesized to outcompete other phytoplankton in part by using alternative nitrogen sources. The high proportion of natural populations that are infected during the late stages of the bloom suggest viruses cause bloom collapse. We hypothesized that the Aureococcus anophagefferens Virus (AaV) infection cycle would be negatively influenced in cultures acclimated to decreasing external nitrogen conditions, but that the real-time external nitrogen concentration would not influence the infection cycle. Cultures acclimated in NO 3 - concentrations (0.0147 mM; N:P = 0.1225) that showed reduced end point cell abundances, forward scatter (a proxy for size) and red fluorescence (a proxy for chlorophyll a), also produced fewer viruses per cell at a slower rate. Decreasing the external concentration of nitrogen post infection did not alter burst size or time to lysis. These data suggest that the nitrogen used for new viral progeny is present within host cells at the time of infection. Flow cytometric data of an infection cycle showed a reduction in red fluorescence around twelve hours post infection, consistent with degradation of nitrogen-rich chloroplasts during the infection cycle. Using cell and virus quota estimates, we determined that A. anophagefferens cells had sufficient nitrogen and carbon for the lower ranges of burst sizes determined but did not contain enough phosphorous. Consistent with this observation, expression of nitrate and sugar transporters did not increase in the publicly available transcriptome data of the infection cycle, while several phosphorus transporters were. Our data demonstrate that dynamics of viruses infecting Aureococcus over the course of a bloom is dictated by the host cell state upon infection, which is set a priori by external nutrient supplies.


Supporting autonomy for people with aphasia: use of the Life Interests and Values (LIV) Cards.
People with aphasia (PWA) are frequently disregarded as reliable respondents because their language problems may restrict their responses to oral and written questioning. Consequently, family members are often asked to speak on their behalf. The Life Interests and Values (LIV) Cards are a nonlinguistic, picture-based instrument designed for communicating directly with PWA about their current and desired life activities. The goals of this study were to (1) explore utility of LIV Cards for interviewing PWA and (2) examine congruence between responses of PWA and proxies. Study participants were 10 PWA with varying language and cognitive abilities and 10 family member proxies. Both groups participated in LIV Card interviews to identify current and preferred activities of the PWA. Core interview times for the PWA and percentage of selected activities for 4 activity categories were calculated, as was item-by-item response congruency between PWA and proxies. All 10 PWA completed LIV Cards interviews in 45 minutes or less. There were individualized response patterns regarding activity participation and preferences. Mean point-to-point agreement between PWA and their proxies was 74% for current activities and 71% for activity preferences of the PWA. PWA were able to provide information about their current and preferred involvement in life activities through use of the LIV Cards. Family members did not predict activity choices and desires of PWA with full accuracy. The LIV Cards appear to be a viable tool for setting goals and discussing life priorities of PWA.


Osteointegration of an uncemented modular revision stem implanted during revision hip surgery.
Though mid-term survival rates of over 95% in several series have been published, there is still a paucity of related literature regarding the role of vertical stem instability in the osteointegration of fluted tapered stems. This paper presents a comprehensive and prospective assessment on short-term experiences with uncemented modular femoral stem in the treatment of defective femur during revision surgery of total hip replacement. Clinical and radiological monitoring of 20 consecutive patients with implanted tapered fluted revision stem (Lima Corporate, Udine, Italy) was of 27 months in average (20-35 months). The average pre-operative Merle d'Aubigné and Postel method score was 6.3 points (3-10 points). The frequency of femur defects, classified according to Paprosky, was IIIA = 9 and IIIB = 11. During last follow-up, the Merle d'Aubigné and Postel hip score was on average 11.7 (6-16 points). Compared to post-operation radiograph, stem migration of 1.9 mm (0-11 mm) on average was found. This vertical stem migration was observed only when comparing hip radiographs immediately after surgery, and at 6 weeks post-surgery. The Paprosky IIIA defects group, presented a subsided stem by an average of 1.5 mm. In the group of Paprosky IIIB defects, the stem subsidence was on average 2.3 mm. All 20 patients in the study showed excellent osteointegration of the uncemented revision modular stem. This study found and excellent osteointegration of the Lima uncemented tapered fluted revision modular stem in defective femur with a cortical bone segment present in the diaphyseal isthmus area. The initial vertical instability leading to stem migrating during the first six weeks following surgery did not, however, affect its osteointegration.


Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits.
The endothelium-derived relaxing factor is rapidly inactivated by superoxide radicals, and atherosclerotic vessels generate excess radical species. We tested the hypothesis that an imbalance between intrinsic superoxide dismutase (SOD) activity and the generation of superoxide radicals in atherosclerotic arteries may result in augmented inactivation of endothelium-derived relaxing factor. Vascular SOD was increased in normal and cholesterol-fed (1% cholesterol for 4 months) rabbits approximately twofold by treatment with polyethylene-glycolated SOD (PEG-SOD; 41,000 units/kg/day i.m.) for 1 week. Aortic rings from these animals and nontreated control and atherosclerotic rabbits subsequently were studied in organ chambers. Endothelium-dependent relaxations to acetylcholine and the calcium ionophore A23187 were improved by PEG-SOD in atherosclerotic but not in normal rabbits. PEG-SOD pretreatment did not alter endothelium-independent relaxations to nitroprusside. Thus, treatment with PEG-SOD can partially restore impaired endothelium-dependent relaxation of atherosclerotic arteries. We conclude that generation of oxygen-derived radicals likely contributes to endothelial dysfunction of atherosclerotic arteries.


Craniocervical anomalies in Dubowitz syndrome. Three cases and a literature review.
Dubowitz syndrome is a disorder involving craniofacial abnormalities, growth retardation and mental retardation. Approximately 142 cases have been reported, with various associated other anomalies. These include cardiovascular, urogenital and endocrine abnormalities, as well as a predisposition to infections and hematological malignancies. Scoliosis has been described in association with this syndrome, as have isolated vertebral abnormalities. There has, however, been no description of craniocervical abnormalities. We describe three Dubowitz patients with significant craniocervical abnormalities.


PGE2 inhibits water permeability at a post-cAMP site in rat terminal inner medullary collecting duct.
To assess sites and mechanism of action of prostaglandin E2 (PGE2) on water permeability (PF), we determined PGE2 effects on antidiuretic hormone (ADH)- and adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated PF in rat terminal inner medullary collecting ducts perfused in vitro. PGE2 (10(-7) M) reversibly inhibited ADH-stimulated PF (1.131 +/- 192 to 532 +/- 208 microns/s). In contrast to that observed in rabbit, PGE2 also inhibited an established PF response to the exogenous cAMP analogue 8-p-(chlorophenylthio)-cAMP (696 +/- 107 to 399 +/- 99 microns/s). PGE2 alone had no effect on PF. The protein kinase C inhibitor staurosporine (10(-8) M) blocked PGE2-mediated inhibition of cAMP-stimulated PF. PGE2 caused a rapid spikelike increase in intracellular calcium [( Ca2+]i) followed by a stable elevation above basal values. Only the latter effect was abolished in a zero calcium bath. Neither staurosporine nor cAMP altered the [Ca2+]i response. These studies are the first to demonstrate PGE2-mediated inhibition of an established PF response to cAMP independent of changes in intracellular cAMP. The pattern of [Ca2+]i release and sensitivity to staurosporine suggests that this effect is mediated via signaling through phospholipase C. The results underscore the importance of species differences, axial heterogeneity, and/or in vivo conditioning for functional expression of cellular signaling pathways.


Psychiatric assessment of patients with "20th-century disease" ("total allergy syndrome").
"Twentieth-century disease", or "total allergy syndrome", is a condition attributed to hypersensitivity to the environment that may sometimes be seen as so serious that the patient is incapable of living in the modern world. Although the popular media frequently carry stories about it, there is little scientific literature. It is diagnosed by clinical ecologists, who maintain, among other theories, that susceptible individuals experience an overload in assaults by artificial materials in the environment. The patients usually have multiple ill defined symptoms for which no organic cause can be found, but they vigorously resist psychiatric referral, as they attribute their symptoms to allergy. A group of 18 patients who were purportedly suffering from 20th-century disease were referred to a university psychiatric consultation liaison service. They virtually all had a long history of visits to physicians, and their symptoms were characteristic of several well known psychiatric disorders. The case histories and management of three of them are presented. Although this group of patients may have been atypical in that they had more severe psychologic symptoms, the experience indicates that a psychiatric diagnosis ought to be considered. The symptoms of 20th-century disease have much in common with other conditions known to physicians for centuries.


Hickman catheter embolism in a child during stem cell transplantation.
The majority of stem cell recipients rely on indwelling central venous catheters situated in superior vena cava or right atrium. Semi-permanent tunneled silicone rubber Hickman catheters are widely used to provide durable central venous access for patients undergoing stem cell transplantation. A case of 5 years old child with diagnosis of severe aplastic anemia is reported. The patient received peripheral blood stem cells (PBSC) and had successful engraftment with complete hematological recovery. He had Hickman catheter embolism in the pulmonary circulation following unsuccessful attempt to remove the line. The catheter was successfully removed by midsternostomy operation. The child is normal with sustained remission on day +218 post stem cell transplant.


Impaired fasting glucose and impaired glucose tolerance do not predict hypertension: a community cohort study.
Insulin resistance has an important role in the pathogenesis of hypertension. We hypothesized that impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) which represents insulin resistance would predict the development of hypertension. A total of 4,039 subjects without hypertension or diabetes (1,847 men and 2,192 women; age 49.9±8.2 years), from the Ansan-Ansung cohorts within the Korean Genome Epidemiology Study, were enrolled in 2001-2002 and restudied in 2005-2006. The association between the incidence of hypertension and IFG, IGT, or other metabolic factors was studied. During the 4-year follow-up period, 582 of the 4,039 subjects developed hypertension. At baseline, the prevalence of abdominal obesity, dyslipidemia, and IGT was higher in subjects who became hypertensive compared to those that remained normotensive. The prevalence of IFG was not significantly different between the 2 groups. In a multivariate analysis, abdominal obesity and high serum triglyceride were significant risk factors for the development of hypertension. Neither IFG nor IGT were significantly associated with new-onset hypertension. Although the risk of hypertension was higher with the number of metabolic components present at baseline, IFG and IGT were not significant components compared to other metabolic components, especially when abdominal obesity was taken into account. While metabolic syndrome components related to insulin resistance present at baseline are important risk factors of hypertension, we conclude that coexisting metabolic component, mainly abdominal obesity, rather than IFG and IGT have more predictive value for determining the development of hypertension in a Korean population.