Molecular characterization of the tdc operon of Escherichia coli K-12.
The nucleotide sequence of a 2-kilobase DNA fragment of the tdc region of Escherichia coli K-12, previously cloned in this laboratory, revealed two open reading frames, tdcC and ORFX, downstream from the tdcB gene (formerly designated tdc) encoding biodegradative threonine dehydratase. A 24-base-pair sequence separated tdcC from the dehydratase coding region, and an untranslated region of 60 nucleotides, which contains a recognizable -10 consensus sequence, was found between tdcC and ORFX. The deduced amino acid sequence of tdcC showed it to be a large hydrophobic polypeptide of 431 amino acid residues, whereas ORFX coded for a small 135-residue polypeptide lacking glutamine and tryptophan. A computer-assisted sequence analysis revealed no similarity among the tdcB, tdcC, and ORFX polypeptides, and a search of the GenBank database failed to detect similarity with any other known proteins. The tdc genes and ORFX showed similar codon usage and, in analogy with other bacterial genes, showed codon usage typical for genes expressed at an intermediate level. Transcriptional analysis with S1 nuclease indicated two distinct transcription start sites upstream of the tdcB gene in regions previously identified as promoterlike elements P1 and P2. Interestingly, expression of tdcB and tdcC, but not ORFX, was contingent upon the presence of P1. These results taken together tend to suggest that the biodegradative threonine dehydratase is the second gene in a polycistronic transcription unit constituting a novel operon (tdcABC) in E. coli implicated in anaerobic threonine metabolism.


Expression of functional leptin receptors in rodent Leydig cells.
Several studies indicate that the size of body fat stores and the circulating levels of the adipocyte-derived hormone leptin are able to influence the activity of the hypothalamic-pituitary-gonadal axis. The leptin-hypothalamic-pituitary-gonadal interactions have been mainly studied at the level of the central nervous system. In this study, we investigated the possibility that leptin may have direct effects on the rodent Leydig cell function. To probe this hypothesis, we first analyzed the expression of leptin receptors (OB-R) in rodent Leydig cells in culture. RT-PCR studies showed that rat Leydig cells express both the long (OB-Rb) and short isoform (OB-Ra) of leptin receptor, whereas MLTC-1 cells (a murine Leydig tumor cell line) express only the long isoform. Short-term (30-90 min) incubation of rat Leydig cells with increasing concentrations ofleptin (2-500 ng/ml) led to a significant and dose-dependent inhibition of human (h)CG-stimulated testosterone (T) production (approximately 60% reduction, IC50 = 20 ng/ml) but no change in basal androgen release. Also, leptin (150 ng/ml) amplified hCG-induced intracellular cAMP formation (1- to 2-fold) without modifying basal cAMP levels. Subsequent experiments showed that leptin inhibited 8Br-cAMP-stimulated T production, indicating that leptin's effect is exerted beyond cAMP. The inhibitory effect of leptin on hCG-induced T secretion was accompanied by a significant reduction of androstenedione and a concomitant rise of the precursor metabolites pregnenolone, progesterone, and 17-OH-progesterone, conceivable with a leptin-induced lesion of 17,20 lyase activity. Separate experiments performed with the MLTC-1 cells (not expressing cytochrome P450-17alpha) showed that leptin, though amplifying hCG-stimulated cAMP production, did not modify hCG-stimulated pregnenolone and progesterone release. These results further indicate that leptin action on steroidogenesis occurs downstream of progesterone synthesis. Northern Blot experiments showed no acute effect of leptin on cytochrome P450-17alpha messenger RNA accumulation in rat Leydig cells in basal and hCG-stimulated conditions, excluding that the rapid changes observed were caused by messenger RNA degradation. In conclusion, these findings, for the first time, show that leptin has direct, receptor-mediated actions on rodent Leydig cells in culture, at concentrations within the range of obese men.


The impact of the French soda tax on prices and purchases. An ex post evaluation.
We estimate the price and consumption effects of the 2012 French tax on sweetened non-alcoholic drinks using a difference-in-difference approach. Our identification strategy exploits Italian data as a natural control group. We use French and Italian Consumer Price Indices, purchase prices and quantities from the 2011 and 2012 Kantar and GfK home-scan surveys for two French regions and two neighbouring Italian regions, and expenditure data from the 2011 and 2012 Italian Expenditure Survey. We check for the robustness of our results by applying the difference-in-difference models using only French data and considering water as the benchmark (control) good. We find that the tax is transmitted to the prices of taxed drinks, with full transmission for soft drinks and partial transmission for fruit juices. The evidence on purchase responses is mixed and less robust, indicating at most a very small reduction in soft drink purchases (about half a litre per capita per year), an impact which would be consistent with the low tax rate. We find suggestive evidence of a larger response by the sub-sample of heavy purchasers. Fruit juices and water do not seem to have been affected by the tax.


Depression care management: impact of implementation on health system costs.
This study examined the mental health care costs associated with implementation of a collaborative care management (CCM) of treatment for depression in primary care. A retrospective review of all costs was performed over a 2-year period associated with providing care to adult patients at clinical sites with CCM versus those with usual care, comparing total and mental health per member per month (PMPM) costs for 2008 and 2009 (patient population = 103,000). The mental health-PMPM costs as a percentage of total health care costs at the clinic without CCM were 4.65% in 2008 and 4.5% in 2009 (p = .085). In the clinics with CCM, there was a significant difference between the 2 years with a decrease noted in 2009 of 4.91% compared with 4.36% in 2008 (p < .0001). This study demonstrated that, on a population basis with the implementation of CCM, the metric of mental health-PMPM (using the actual costs of delivering care) suggested that an increased short-term cost of care is not always realized. Collaborative care management treatment for depression may be a more cost-efficient method of care for the population as a whole, even in the short term.


"Invisible" conformers of an antifungal disulfide protein revealed by constrained cold and heat unfolding, CEST-NMR experiments, and molecular dynamics calculations.
Transition between conformational states in proteins is being recognized as a possible key factor of function. In support of this, hidden dynamic NMR structures were detected in several cases up to populations of a few percent. Here, we show by two- and three-state analysis of thermal unfolding, that the population of hidden states may weight 20-40 % at 298 K in a disulfide-rich protein. In addition, sensitive (15) N-CEST NMR experiments identified a low populated (0.15 %) state that was in slow exchange with the folded PAF protein. Remarkably, other techniques failed to identify the rest of the NMR "dark matter". Comparison of the temperature dependence of chemical shifts from experiments and molecular dynamics calculations suggests that hidden conformers of PAF differ in the loop and terminal regions and are most similar in the evolutionary conserved core. Our observations point to the existence of a complex conformational landscape with multiple conformational states in dynamic equilibrium, with diverse exchange rates presumably responsible for the completely hidden nature of a considerable fraction.


Dietary histidine supplementation prevents cataract development in adult Atlantic salmon, Salmo salar L., in seawater.
The aim of the present study was to investigate the cataract preventive effect of dietary histidine regimes in adult Atlantic salmon (Salmo salar L.) in seawater, both through manipulating the dietary histidine level and feeding period. Mean body weight of individually tagged Atlantic salmon at the start of the experiment was 1662 (sd 333) g. Low prevalence of mild cataracts were recorded in the beginning of June. Three fishmeal and fish oil-based extruded diets (crude protein: 375 g/kg and fat: 342 g/kg), differing only in histidine content (low (L): 9.3, medium (M): 12.8 and high (H): 17.2 g histidine/kg diets), were fed to duplicate net pens in seawater. The experimental period was divided into three seasons (June-July; July-September; September-October), each starting and ending with individual cataract examination, assessment of somatic data, and sampling of lens and muscle tissues for analysis of histidine and histidine derivatives. In July and September, a part of the population fed L- and H-histidine feeds were transferred (crossed over) to respective series of replicate net pens fed L-, M- and H-histidine diets (i.e. eleven experimental feeding groups at trial conclusion). The fish doubled their body weight from June to October, with no systematic effects on weight gain of dietary histidine feeding regimes. Development of severe cataracts was observed between July and September. The cataract severity was directly related to the dietary histidine level fed during the first and second periods. Feeding histidine-supplemented diets (M or H) in the first period from June to July mitigated later cataract outbreaks. The status of selected free imidazoles in muscle and lens tissues reflected the dietary histidine feeding regimes, relative to both feed concentration and feeding duration. The study shows the risk for cataract development for adult Atlantic salmon, 1 year after the transfer of salmon smolts from freshwater to seawater, which to a major extent can be prevented by histidine supplementation just before and during the early phase of cataract development.


Effect of Muscular Exercise on Patients With Muscular Dystrophy: A Systematic Review and Meta-Analysis of the Literature.
Background: Muscular dystrophy causes weakness and muscle loss. The effect of muscular exercise in these patients remains controversial. Objective: To assess the effects of muscular exercise vs. no exercise in patients with muscular dystrophy. Methods: We performed a comprehensive systematic literature search in the Medline, Embase, Web of Science, Scopus, and Pedro electronic databases, as well as in the reference literature. We included randomized clinical trials (RCTs) that reported the effect of muscular exercise on muscle strength, endurance during walking, motor abilities, and fatigue. Data were extracted independently by two reviewers. Mean difference (MD) and 95% confidence intervals (CI) were used to quantify the effect associated with each outcome. We performed pairwise meta-analyses and trial sequential analyses (TSA) and used GRADE to rate the overall certainty of evidence. Results: We identified 13 RCTs involving 617 patients. The median duration of exercise interventions was 16 weeks [interquartile range [IQR] 12-24]. In the patients with facio-scapulo-humeral dystrophy and myotonic dystrophy, no significant difference in extensor muscle strength was noted between the exercise and the control groups [four studies, 115 patients, MD 4.34, 95% CI -4.20 to 12.88, I 2 = 69%; p = 0.32; minimal important difference [MID] 5.39 m]. Exercise was associated with improved endurance during walking [five studies, 380 patients, MD 17.36 m, 95% CI 10.91-23.81, I 2 = 0; p < 0.00001; MID 34 m]. TSA excluded random error as a cause of the findings for endurance during walking. Differences in fatigue and motor abilities were small. Not enough information was found for other types of dystrophy. Conclusions: Muscular exercise did not improve muscle strength and was associated with modest improvements in endurance during walking in patients with facio-scapulo-humeral and myotonic dystrophy. Future trials should explore which type of muscle exercise could lead to better improvements in muscle strength. PROSPERO: CRD42019127456.


Paranormal experience and the COMT dopaminergic gene: a preliminary attempt to associate phenotype with genotype using an underlying brain theory.
Paranormal belief and suggestibility seem related. Given our recent findings outlining a putative association between suggestibility and a specific dopaminergic genetic polymorphism, we hypothesized that similar exploratory genetic data may offer supplementary insights into a similar correlation with paranormal belief. With more affordable costs and better technology in the aftermath of the human genome project, genotyping is increasingly ubiquitous. Compelling brain theories guide specific research hypotheses as scientists begin to unravel tentative relationships between phenotype and genotype. In line with a dopaminergic brain theory, we tried to correlate a specific phenotype concerning paranormal belief with a dopaminergic gene (COMT) known for its involvement in prefrontal executive cognition and for a polymorphism that is positively correlated with suggestibility. Although our preliminary findings are inconclusive, the research approach we outline should pave the road to a more scientific account of elucidating paranormal belief.


Transmissible mink encephalopathy: infectivity of corneal epithelium.
Corneal epithelium from hamsters dying of transmissible mink encephalopathy contained a virus titer of 10-4.8 times the 50 percent lethal dose (10-4.8 LD50) per 0.05 milliliter when assayed as a cell suspension derived directly from the infected animal. After one passage in tissue culture, an equivalent concentration of cells contained only 10-0.8 LD50 per 0.05 milliliter.. It is concluded that corneal tissues are infectious; the infectivity may be mainly associated with free nerve endings. However, the most important immediate inference is that corneas from human beings affected with Creuzfeldt-Jakob disease are likely to be lethal if transplanted to healthy recipients.


Identification of 4-Hydroxycumyl Alcohol As the Major MnO2-Mediated Bisphenol A Transformation Product and Evaluation of Its Environmental Fate.
Bisphenol A (BPA), an environmental contaminant with weak estrogenic activity, resists microbial degradation under anoxic conditions but is susceptible to abiotic transformation by manganese dioxide (MnO2). BPA degradation followed pseudo-first-order kinetics with a rate constant of 0.96 (±0.03) min(-1) in the presence of 2 mM MnO2 (0.017% w/w) at pH 7.2. 4-hydroxycumyl alcohol (HCA) was the major transformation product, and, on a molar basis, up to 64% of the initial amount of BPA was recovered as HCA. MnO2 was also reactive toward HCA, albeit at 5-fold lower rates, and CO2 evolution (i.e., mineralization) occurred. In microcosms established with freshwater sediment, HCA was rapidly biodegraded under oxic, but not anoxic conditions. With a measured octanol-water partition coefficient (Log K(ow)) of 0.76 and an aqueous solubility of 2.65 g L(-1), HCA is more mobile in saturated media than BPA (Log K(ow) = 2.76; aqueous solubility = 0.31 g L(-1)), and therefore more likely to encounter oxic zones and undergo aerobic biodegradation. These findings corroborate that BPA is not inert under anoxic conditions and suggest that MnO2-mediated coupled abiotic-biotic processes may be relevant for controlling the fate and longevity of BPA in sediments and aquifers.


Comprehensive gene expression atlas for the Arabidopsis MAP kinase signalling pathways.
* Mitogen activated protein kinase (MAPK) pathways are signal transduction modules with layers of protein kinases having c. 120 genes in Arabidopsis, but only a few have been linked experimentally to functions. * We analysed microarray expression data for 114 MAPK signalling genes represented on the ATH1 Affymetrix arrays; determined their expression patterns during development, and in a wide range of time-course microarray experiments for their signal-dependent transcriptional regulation and their coregulation with other signalling components and transcription factors. * Global expression correlation of the MAPK genes with each of the represented 21 692 Arabidopsis genes was determined by calculating Pearson correlation coefficients. To group MAPK signalling genes based on similarities in global regulation, we performed hierarchical clustering on the pairwise correlation values. This should allow inferring functional information from well-studied MAPK components to functionally uncharacterized ones. Statistical overrepresentation of specific gene ontology (GO) categories in the gene lists showing high expression correlation values with each of the MAPK components predicted biological themes for the gene functions. * The combination of these methods provides functional information for many uncharacterized MAPK genes, and a framework for complementary future experimental dissection of the function of this complex family.


Effect of the assignment of ancestral CpG state on the estimation of nucleotide substitution rates in mammals.
Molecular evolutionary studies in mammals often estimate nucleotide substitution rates within and outside CpG dinucleotides separately. Frequently, in alignments of two sequences, the division of sites into CpG and non-CpG classes is based simply on the presence or absence of a CpG dinucleotide in either sequence, a procedure that we refer to as CpG/non-CpG assignment. Although it likely that this procedure is biased, it is generally assumed that the bias is negligible if species are very closely related. Using simulations of DNA sequence evolution we show that assignment of the ancestral CpG state based on the simple presence/absence of the CpG dinucleotide can seriously bias estimates of the substitution rate, because many true non-CpG changes are misassigned as CpG. Paradoxically, this bias is most severe between closely related species, because a minimum of two substitutions are required to misassign a true ancestral CpG site as non-CpG whereas only a single substitution is required to misassign a true ancestral non-CpG site as CpG in a two branch tree. We also show that CpG misassignment bias differentially affects fourfold degenerate and noncoding sites due to differences in base composition such that fourfold degenerate sites can appear to be evolving more slowly than noncoding sites. We demonstrate that the effects predicted by our simulations occur in a real evolutionary setting by comparing substitution rates estimated from human-chimp coding and intronic sequence using CpG/non-CpG assignment with estimates derived from a method that is largely free from bias. Our study demonstrates that a common method of assigning sites into CpG and non CpG classes in pairwise alignments is seriously biased and recommends against the adoption of ad hoc methods of ancestral state assignment.


The role of spatial and temporal information in learning interval time-place tasks.
In time-place learning (TPL) paradigms animals are thought to form tripartite memory codes consisting of the spatiotemporal characteristics of biologically significant events. In Phase I, rats were trained on a modified TPL task in which either the spatial or temporal component was constant, while the other component varied randomly. If the memory codes are tripartite then when one aspect of the code is random the rats should have difficulty learning the constant aspect of the code. However, rats that were trained with a fixed spatial sequence of food availability and a random duration did in fact learn the task. Rats that were trained with a fixed duration and a random sequence did not learn the task. In Phase II all rats were placed on a TPL task in which food availability was contingent upon both spatial and temporal information. According to the tripartite theory, prior knowledge of either aspect of the code should have little effect on the acquisition of the task. The rats that received fixed spatial training learned the task relatively more quickly. The use of bipartite, rather than tripartite codes, is better able to explain the results of the current study.


Spontaneously disappearing lumbar disc protrusion.
Spontaneous disappearance of a herniated lumbar disc is known to occur. This case study describes a 45-year-old patient whose symptoms of lumbar radiculopathy resolved and follow-up imaging showed complete disappearance of the disc prolapse. This phenomenon strengthens the role of conservative treatment in the management of lumbar disc protrusions.


Medihoney: a complete wound bed preparation product.
In recent years, honey has emerged as a versatile product that can be applied to many different types of wound to achieve a variety of outcomes, depending on the requirements of the clinician and patient. However, there is still some confusion about how specific honeys work, their antibacterial potency, and what effects this has on wounds treated with honey products. This article reviews the need for ongoing use of honey in wound care. It focuses on Medihoney, a medically certified honey licensed for professional wound care, and presents an update of the clinical data supporting its use.


The inhibition of anti-DNA binding to DNA by nucleic acid binding polymers.
Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE) and can mediate disease pathogenesis by the formation of immune complexes. Since blocking immune complex formation can attenuate disease manifestations, the effects of nucleic acid binding polymers (NABPs) on anti-DNA binding in vitro were investigated. The compounds tested included polyamidoamine dendrimer, 1,4-diaminobutane core, generation 3.0 (PAMAM-G3), hexadimethrine bromide, and a β-cylodextrin-containing polycation. As shown with plasma from patients with SLE, NABPs can inhibit anti-DNA antibody binding in ELISA assays. The inhibition was specific since the NABPs did not affect binding to tetanus toxoid or the Sm protein, another lupus autoantigen. Furthermore, the polymers could displace antibody from preformed complexes. Together, these results indicate that NABPs can inhibit the formation of immune complexes and may represent a new approach to treatment.


Laser ablation isotope ratio mass spectrometry for enhanced sensitivity and spatial resolution in stable isotope analysis.
Stable isotope analysis permits the tracking of physical, chemical, and biological reactions and source materials at a wide variety of spatial scales. We present a laser ablation isotope ratio mass spectrometry (LA-IRMS) method that enables δ(13)C measurement of solid samples at 50 µm spatial resolution. The method does not require sample pre-treatment to physically separate spatial zones. We use laser ablation of solid samples followed by quantitative combustion of the ablated particulates to convert sample carbon into CO(2). Cryofocusing of the resulting CO(2) coupled with modulation in the carrier flow rate permits coherent peak introduction into an isotope ratio mass spectrometer, with only 65 ng carbon required per measurement. We conclusively demonstrate that the measured CO(2) is produced by combustion of laser-ablated aerosols from the sample surface. We measured δ(13)C for a series of solid compounds using laser ablation and traditional solid sample analysis techniques. Both techniques produced consistent isotopic results but the laser ablation method required over two orders of magnitude less sample. We demonstrated that LA-IRMS sensitivity coupled with its 50 µm spatial resolution could be used to measure δ(13) C values along a length of hair, making multiple sample measurements over distances corresponding to a single day's growth. This method will be highly valuable in cases where the δ(13)C analysis of small samples over prescribed spatial distances is required. Suitable applications include forensic analysis of hair samples, investigations of tightly woven microbial systems, and cases of surface analysis where there is a sharp delineation between different components of a sample.


Plastic and Human Health: A Micro Issue?
Microplastics are a pollutant of environmental concern. Their presence in food destined for human consumption and in air samples has been reported. Thus, microplastic exposure via diet or inhalation could occur, the human health effects of which are unknown. The current review article draws upon cross-disciplinary scientific literature to discuss and evaluate the potential human health impacts of microplastics and outlines urgent areas for future research. Key literature up to September 2016 relating to accumulation, particle toxicity, and chemical and microbial contaminants was critically examined. Although microplastics and human health is an emerging field, complementary existing fields indicate potential particle, chemical and microbial hazards. If inhaled or ingested, microplastics may accumulate and exert localized particle toxicity by inducing or enhancing an immune response. Chemical toxicity could occur due to the localized leaching of component monomers, endogenous additives, and adsorbed environmental pollutants. Chronic exposure is anticipated to be of greater concern due to the accumulative effect that could occur. This is expected to be dose-dependent, and a robust evidence-base of exposure levels is currently lacking. Although there is potential for microplastics to impact human health, assessing current exposure levels and burdens is key. This information will guide future research into the potential mechanisms of toxicity and hence therein possible health effects.


Weak crossability barrier but strong juvenile selection supports ecological speciation of the hybrid pine Pinus densata on the Tibetan plateau.
Determining how a new hybrid lineage can achieve reproductive isolation is a key to understanding the process and mechanisms of homoploid hybrid speciation. Here, we evaluated the degree and nature of reproductive isolation between the ecologically successful hybrid species Pinus densata and its parental species P. tabuliformis and P. yunnanensis. We performed interspecific crosses among the three species to assess their crossability. We then conducted reciprocal transplantation experiments to evaluate their fitness differentiation, and to examine how natural populations representing different directions of introgression differ in adaptation. The crossing experiments revealed weak genetic barriers among the species. The transplantation trials showed manifest evidence of local adaptation as the three species all performed best in their native habitats. Pinus densata populations from the western edge of its distribution have evolved a strong local adaptation to the specific habitat in that range; populations representing different directions of introgressants with the two parental species all showed fitness disadvantages in this P. densata habitat. These observations illustrate that premating isolation through selection against immigrants from other habitat types or postzygotic isolation through selection against backcrosses between the three species is strong. Thus, ecological selection in combination with endogenous components and geographic isolation has likely played a significant role in the speciation of P. densata.


Double photonic bandgaps dynamically induced in a tripod system of cold atoms.
A tripod atomic system driven by two standing-wave fields (a coupling and a driving) is explored to generate tunable double photonic bandgaps in the regime of electromagnetically induced transparency. Both photonic bandgaps depend critically on frequency detunings, spatial periodicities, and initial phases of the two standing-wave fields. When the coupling and driving detunings are very close, a small fluctuation of one standing-wave field may demolish both photonic bandgaps. If the two detunings are greatly different, however, each standing-wave field determines only one photonic bandgap in a less sensitive way. Dynamic generation and elimination of a pair of photonic bandgaps shown here may be exploited toward the end of simultaneous manipulation of two weak light signals even at the single-photon level.


Personal control decreases narcissistic but increases non-narcissistic in-group positivity.
We examined the effects of control motivation on in-group positivity. Past research suggests that people compensate for low personal control by increasing support for social in-groups. We predicted that the effect of personal control on in-group positivity would depend on the type of in-group positivity. Low personal control should increase compensatory, narcissistic in-group positivity, whereas high personal control should increase secure, non-narcissistic in-group positivity. These hypotheses were tested in a cross-sectional survey (Study 1 N = 1,083, 54% female, Mage = 47.68), two experiments (Study 2 N = 105, 50% female, Mage = 32.05; Study 3 N = 154, 40% female, Mage = 29.93), and a longitudinal survey (Study 4 N = 398, 51% female, Mage = 32.05). In all studies, personal control was negatively associated with narcissistic in-group positivity but positively associated with non-narcissistic in-group positivity. The longitudinal survey additionally showed that the positive relationship between personal control and non-narcissistic in-group positivity was reciprocal. Moreover, both types of in-group positivity differentially mediated between personal control and out-group attitudes: Narcissistic in-group positivity predicted negative attitudes, and non-narcissistic positivity predicted positive attitudes. These findings highlight the role of individual motivation in fostering different types of in-group positivity and intergroup outcomes.


Antioxidant Activity and In Vitro Antiglycation of the Fruit of Spondias purpurea.
Hyperglycemia in diabetes mellitus causes irreversible life-threatening micro- and macrovascular complications. There is evidence that the glycation reaction leads to a chemical modification of the proteins contributing to the complications of diabetes. It is known that advanced glycation end products (AGEs) are formed by glycation and oxidation reactions called glycoxidation. CML, a nonfluorescent AGE, has become a biomarker of glycoxidative damage; other AGEs appear to induce oxidative stress, which results in cytotoxicity. To determine antioxidant activity, the FRAP, DPPH, and TEAC tests were used, as well as the polyphenols content using Folin-Ciocalteu's method. To evaluate the antiglycation activity, the BSA/glucose system was used, and the fructosamine concentration, protein carbonyl content, thiol, and CML groups were determined. The results obtained show that the hexane extract of the fruit of Spondias purpurea (CFH) effectively inhibits the glycation reaction, in addition to increasing the thiol groups and decreasing levels of fructosamine, protein carbonyl, and CML. In addition, CFH presented significant antioxidant activity. CFH inhibits the glycation reaction; therefore, it can help prevent complications related to AGEs in diabetes mellitus; it also reduces oxidative stress and is effective in protecting proteins from oxidative damage.


Effects of brief cognitive behavioral therapy on mental health in substance-related disorder: a randomized controlled trial.
Population and aging are major contributing factors influencing the increase in substance use disorder (SUD), which in itself affects mental health, particularly anxiety and depression. Cognitive behavioral therapy (CBT) and pharmacotherapy co-treatment are considered the gold standard for the treatment of SUD. Thus, the present study has been carried out to investigate the efficacy of brief CBT on the general health of opioid users. A randomized controlled trial (RCT) was conducted with forty opioid users whose addiction was dully confirmed by a psychiatrist at the drop-in center of the Ahvaz Jundishapur University of Medical Sciences. The patients were then randomly divided into two equal groups (n = 20). The control group was treated solely using methadone maintenance therapy (MMT); however, the intervention group underwent four sessions of CBT in addition to MMT. The general health questionnaire (GHQ) consisting of 28 items (Goldberg, 1979) was applied to both groups at the beginning and end of the study. The collected data was analyzed using IBM SPSS ver. 26, and data analysis was carried out using chi-square, t-test, Mann-Whitney, and Poisson regression model. P < 0.05 was statistically significant for all the aforementioned tests. The mean age for the control and intervention groups were 37.95 ± 7.64 and 43.85 ± 9.92, respectively (p = 0.042). There was no statistically significant difference in terms of gender and levels of education (p = 0.311 and p = 0.540). Both groups differed statistically regarding marital status and occupation (p = 0.025 and 0.002). There was no significant statistical difference in all subclasses and the total scores of GHQ-28 for both groups, except for anxiety and insomnia in the intervention group (p = 0.038). After applying a Likert scale with a 23-point cut-off score, there was no statistically significant difference in terms of psychosis after intervention in the intervention group (p = 0.077). The results of the current study show that brief CBT is effective on psychiatric health, especially anxiety and sleep disorders, whereas brief CBT fails to affect the patient's depression, somatic symptoms, and social dysfunction. The Iranian Registry of Clinical Trials (IRCT) approved the study design (IRCT registration number: IRCT20190929044917N1, registration date: 13/01/2020).


Neurotransmission and neuromodulation in the chemosensory carotid body.
The mammalian carotid body is a small chemosensory organ that helps maintain the chemical composition of arterial blood via reflex control of ventilation. Thus, in response to decreased PO2 (hypoxia), increased PCO2 (hypercapnia), or decreased pH (acidity), chemoreceptor glomus or type I cells become stimulated and release neuroactive agents that excite apposed sensory terminals of the carotid sinus nerve. The resulting increase in afferent discharge ultimately leads to corrective changes in ventilation so as to maintain blood gas and pH homeostasis. Recent evidence that the organ can also sense low glucose further emphasizes its role as a polymodal sensor of blood-borne stimuli. The chemoreceptors occur in organized cell clusters that receive sensory innervation from petrosal afferents and are intimately associated with the blood supply. Additionally, synaptic specializations between neighboring receptor cells allow for autocrine and paracrine regulation of the sensory output. Though not without controversy, significant progress has been made in elucidating the various chemotransductive pathways, as well as the neurotransmitter and neuromodulatory mechanisms that translate the receptor potential into an afferent sensory discharge. Progress in the latter has been hampered by the presence of a wide variety of endogenous ligands, and an even broader spectrum of receptor subtypes, that apparently help shape the chemoreceptor output and afferent discharge. This review will highlight recent advances in understanding the role of these neuroactive ligands in carotid body function.


Circumvention of over-excitation of PSII by maintaining electron transport rate in leaves of four cotton genotypes developed under long-term drought.
We investigated the patterns of response to a long-term drought in the field in cotton cultivars (genotypes) with known differences in their drought tolerance. Four cotton genotypes with varying physiological and morphological traits, suited to different cropping conditions, were grown in the field and subjected to a long-term moderate drought. In general, cotton leaves developed under drought had significantly higher area-based leaf nitrogen content (N (area)) than those under well irrigation. Droughted plants showed a lower light-saturated net photosynthetic rate (A (sat)) with lower stomatal conductance (g (s)) and intercellular CO (2) concentration (C (i)) than irrigated ones. Based on the responses of A (sat) to g (s) and C (i), there was no decreasing trend in A (sat) at a given g (s) and C (i) in droughted leaves, suggesting that the decline in A (sat) in field-grown cotton plants under a long-term drought can be attributed mainly to stomatal closure, but not to nonstomatal limitations. There was little evidence of an increase in thermal energy dissipation as indicated by the lack of a decrease in the photochemical efficiency of open PSII (F (v)'/F (m)') in droughted plants. On the basis of electron transport (ETR) and photochemical quenching (q (P)), however, we found evidence indicating that droughted cotton plants can circumvent the risk of excessive excitation energy in photosystem (PS) II by maintaining higher electron transport rates associated with higher N (area), even while photosynthetic rates were reduced by stomatal closure.


Measurement of corneal epithelial permeability to fluorescein. A repeatability study.
Permeability (Pdc) to sodium fluorescein (F) is a characteristic of the barrier function of the corneal epithelium. The repeatability of several in vivo fluorophotometric methods used to measure permeability in humans remains largely undocumented. This study examines the repeatability of a method based on topical instillation of a single drop of F for the quantitative assessment of Pdc. Nine healthy subjects with no history of ocular disease provided 1 (n = 1), 2 (n = 1), or 3 (n = 7) repeated measurements of each eye at successive visits. After making 3 baseline fluorescence scans centrally through the tear film and cornea, 2 microliters of 0.35% F were instilled and 10 fluorescence scans were obtained at approximately 2-minute intervals immediately after instillation. Subsequently, the eyes were rinsed three times with nonpreserved saline and four additional scans were performed. Pdc was calculated by dividing the baseline-corrected postrinse stromal fluorescence by the time integral of the tear film fluorescence calculated over the 20-minute exposure period. After applying a logarithmic transformation to the Pdc estimates, a mixed-model analysis was used to assess measurement repeatability. On the Pdc scale, there is an estimated 95% chance that a second measurement could be as much as 2.88 times higher or 0.35 times lower than a first measurement. This substantial variability between repeated measurements indicates that the single-drop procedure is unreliable for monitoring individual patient changes. However, with careful sample size planning, this technique can be used in population-based research to compare differences in treatment effects between groups of subjects.


Literature review: decision-making regarding slow resuscitation.
Applying ethical principles as a framework, a review of the literature will be presented regarding the decision-making process of slow codes. Slow codes are cardiopulmonary resuscitative efforts intentionally conducted too slowly for resuscitation to occur. While some authors argue that a slow code is a non-maleficent and beneficent act towards the hopelessly ill patient, others believe that this practice is harmful and deceptive, that it disregards patient and surrogate autonomy and deprives the patient of a peaceful death. Literature review. Decision-making surrounding cardiopulmonary resuscitation receives considerable attention in the literature. However, data relating to the decision-making process in slow codes is sparse. One ethnographic study described the practice of slow codes as doing good and preventing harm to the patient. It was evident from the literature review that slow codes, even in the most limited form, are invasive and undignified and that they prolong death and suffering. Further research is needed to examine why slow codes happen despite the availability of a do-not-resuscitate order. Decision-making regarding cardiopulmonary resuscitation is increasingly problematic in Ireland. The literature review suggests that clinical guidelines regarding decision-making and cardiopulmonary resuscitation should be introduced to reduce the likelihood of slow codes occurring, but also that nurses and doctors endeavour to communicate more effectively with patients and family.


Urinary tract infection in adult women: morbidity without mortality.
This condensed paper deals with that relatively common malady, urinary tract infection in the adult female, from a practical point of view. It serves to emphasise that the great majority of these infections cause distressing morbidity, but little serious renal impairment or mortality. It indicates how the natural history of these infections may be studied to select the minority with serious infection. It stresses the aetiology of urinary tract infection, and thereby indicates a practical management.


The changing presentations of diabetic ketoacidosis during pregnancy.
The purpose of the present study was to examine the presentation and outcomes associated with diabetic ketoacidosis (DKA) in pregnancies complicated by diabetes. Eleven episodes (2%) of DKA were diagnosed during the 10-year study period. All patients were under close observation by the Diabetes-in-Pregnancy Service. Plasma glucose levels of less than 200 mg/dL were present in 4 of the 11 patients (36%), 10 (90%) of whom presented with nausea, vomiting, and decreased caloric intake. Two subsequently had fetal distress necessitating cesarean section. One fetal death occurred in a patient treated with subcutaneous insulin. Despite contemporary methods of diabetes care, near-normal plasma glucose levels are not enough to preclude diabetic ketoacidosis. Nausea, vomiting, and decreased caloric intake in an otherwise normal pregnant, diabetic woman requires evaluation to exclude ketosis.


A linear matrix inequality (LMI) approach to robust H/sub 2/ sampled-data control for linear uncertain systems.
In this paper, we consider the H/sub 2/ sampled-data control for uncertain linear systems by the impulse response interpretation of the H/sub 2/ norm. Two H/sub 2/ measures for sampled-data systems are considered. The robust optimal control procedures subject to these two H/sub 2/ criteria are proposed. The development is primarily concerned with a multirate treatment in which a periodic time-varying robust optimal control for uncertain linear systems is presented. To facilitate multirate control design, a new result of stability of hybrid system is established. Moreover, the single-rate case is also obtained as a special case. The sampling period is explicitly involved in the result which is superior to traditional methods. The solution procedures proposed in this paper are formulated as an optimization problem subject to linear matrix inequalities. Finally, we present a numerical example to demonstrate the proposed techniques.


Smartphone-Based, Rapid, Wide-Field Fundus Photography for Diagnosis of Pediatric Retinal Diseases.
An important, unmet clinical need is for cost-effective, reliable, easy-to-use, and portable retinal photography to evaluate preventable causes of vision loss in children. This study presents the feasibility of a novel smartphone-based retinal imaging device tailored to imaging the pediatric fundus. Several modifications for children were made to our previous device, including a child-friendly 3D printed housing of animals, attention-grabbing targets, enhanced image stitching, and video-recording capabilities. Retinal photographs were obtained in children undergoing routine dilated eye examination. Experienced masked retina-specialist graders determined photograph quality and made diagnoses based on the images, which were compared to the treating clinician's diagnosis. Dilated fundus photographs were acquired in 43 patients with a mean age of 6.7 years. The diagnoses included retinoblastoma, Coats' disease, commotio retinae, and optic nerve hypoplasia, among others. Mean time to acquire five standard photographs totaling 90-degree field of vision was 2.3 ± 1.1 minutes. Patients rated their experience of image acquisition favorably, with a Likert score of 4.6 ± 0.8 out of 5. There was 96% agreement between image-based diagnosis and the treating clinician's diagnosis. We report a handheld smartphone-based device with modifications tailored for wide-field fundus photography in pediatric patients that can rapidly acquire fundus photos while being well-tolerated. Advances in handheld smartphone-based fundus photography devices decrease the technical barrier for image acquisition in children and may potentially increase access to ophthalmic care in communities with limited resources.


Versatility of Pyridoxal Phosphate as a Coating of Iron Oxide Nanoparticles.
Pyridoxal 5'-phosphate (PLP) is the most important cofactor of vitamin B₆-dependent enzymes, which catalyses a wide range of essential body functions (e.g., metabolism) that could be exploited to specifically target highly metabolic cells, such as tumour metastatic cells. However, the use of PLP as a simultaneous coating and targeting molecule, which at once provides colloidal stability and specific biological effects has not been exploited so far. Therefore, in this work iron oxide nanoparticles (IONPs) were coated by PLP at two different pH values to tune PLP bonding (e.g., orientation) at the IONP surface. The surface study, as well as calculations, confirmed different PLP bonding to the IONP surface at these two pH values. Moreover, the obtained PLP-IONPs showed different zeta potential, hydrodynamic radius and agglomeration state, and consequently different uptake by two metastatic-prostate-cancer cell lines (LnCaP and PC3). In LnCaP cells, PLP modified the morphology of IONP-containing intracellular vesicles, while in PC3 cells PLP impacted the amount of IONPs taken up by cells. Moreover, PLP-IONPs displayed high magnetic resonance imaging (MRI) r₂ relaxivity and were not toxic for the two studied cell lines, rendering PLP promising for biomedical applications. We here report the use of PLP simultaneously as a coating and targeting molecule, directly bound to the IONP surface, with the additional high potential for MRI detection.


Endoscopic variceal pressure measurements: response to isosorbide dinitrate.
An endoscopic pressure sensor has been evaluated in the measurement of oesophageal variceal pressure and its response to drug ingestion. The variceal pressure showed a highly significant correlation with the splenic pulp pressure (r = 0.97) in six patients with liver disease of diverse aetiology and with hepatic venous wedge pressure (r = 0.92) in eight alcoholic cirrhotic men. Intraduodenal infusion of isosorbide dinitrate in the cirrhotics produced no change in wedge pressure or endoscopic variceal pressure despite profound falls in arterial systolic pressure. Thus isosorbide dinitrate appears to be of no value in treating portal hypertension. This study establishes the endoscopic pressure sensor as a valuable tool in screening drugs in this condition.


Assessing the presence and motivations of orthorexia nervosa among athletes and adults with eating disorders: a cross-sectional study.
Orthorexia nervosa involves restricting diet based on quality rather than quantity. Although orthorexia is well reported in many at-risk populations, limited data addresses its presence in individuals with eating disorder history (EDs) or athletes. We aimed to identify the presence and potential drivers of orthorexia in adults with EDs and endurance athletes, compared to control subjects. Participants ≥ 18y included: people with a diagnosed eating disorder (ED as per DSM-5); endurance athletes (training/competing ≥ 5 h/week); or control subjects. Participants (n = 197) completed an online survey assessing orthorexia (eating habits questionnaire, EHQ), eating motivations (TEMS-B) and compulsive exercise (CET). ED had the highest orthorexia symptom severity (92.0 ± 3.02, n = 32), followed by athletes (76.2 ± 2.74, n = 54) and controls (71.0 ± 1.80, n = 111) (F (2) = 18.2, p < 0.001). A strong positive correlation existed between weight control motives and higher orthorexia symptom severity (r = 0.54, 95% CI [1.35, 2.36], p < 0.001), while a weak negative association existed between Hunger and Pleasure motives and higher orthorexia symptom severity (r = 0.23, 95% CI [- 2.24, - 0.34], p = 0.008; r = 0.26, 95% CI [- 2.11, - 0.47], p = 0.002, respectively). A moderate positive relationship was found between CET and orthorexia symptom severity (95% CI [1.52, 3.12], p < 0.001). Adults with ED history and endurance athletes have greater orthorexia symptom severity compared to control. Clinicians working with at-risk populations should screen patients and be aware of red-flags of orthorexic traits, desire to control weight, and compulsive exercise behavior. III: Evidence obtained from cohort studies.


Multiscale low-dimensional motor cortical state dynamics predict naturalistic reach-and-grasp behavior.
Motor function depends on neural dynamics spanning multiple spatiotemporal scales of population activity, from spiking of neurons to larger-scale local field potentials (LFP). How multiple scales of low-dimensional population dynamics are related in control of movements remains unknown. Multiscale neural dynamics are especially important to study in naturalistic reach-and-grasp movements, which are relatively under-explored. We learn novel multiscale dynamical models for spike-LFP network activity in monkeys performing naturalistic reach-and-grasps. We show low-dimensional dynamics of spiking and LFP activity exhibited several principal modes, each with a unique decay-frequency characteristic. One principal mode dominantly predicted movements. Despite distinct principal modes existing at the two scales, this predictive mode was multiscale and shared between scales, and was shared across sessions and monkeys, yet did not simply replicate behavioral modes. Further, this multiscale mode's decay-frequency explained behavior. We propose that multiscale, low-dimensional motor cortical state dynamics reflect the neural control of naturalistic reach-and-grasp behaviors.


Measuring heterogeneities in soil-transmitted helminth transmission and control.
The global effort over the past decade to control soil-transmitted helminths (STH) has resulted in communities with endemic infection reaching low prevalence levels suitable for the validation of elimination as a public health problem (EPHP), defined by the World Health Organisation (WHO) as <2% of infections classified as moderate or heavy intensity. The spatial scale in which this is validated is currently undefined. As the burden of STH infection decreases, the degree of aggregation of infection within individuals in a population increases. Identifying these remaining pockets of infection requires fine-scale monitoring and evaluation (M&E) programmes that are rarely implemented within current national neglected tropical disease (NTD) control. This review examines various heterogeneities that characterise the epidemiology of STH infections, and discusses their impact on control policy formulation.


Effects of a Behavioral Weight Loss Intervention and Metformin Treatment on Serum Urate: Results from a Randomized Clinical Trial.
Background: Lower body mass index (BMI) has been associated with lower serum urate (SU), but only in observational studies. We sought to determine the effects of behavioral weight loss and metformin treatment on SU in a randomized trial. Methods and Findings: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a parallel three-arm randomized controlled trial of overweight/obese adult cancer survivors without gout at a single center in Maryland, United States. Participants were randomized to: (1) coach-directed weight loss (behavioral telephonic coaching), (2) metformin (up to 2000 mg daily), or (3) self-directed weight loss (informational brochures; reference group). SU and BMI were assessed at baseline and at 3, 6, and 12 months post-randomization. The 121 participants had a mean ± standard deviation (SD) age of 60 ± 9 years, 79% were female, and 45% were Black. At baseline, BMI was 35 ± 5 kg/m2, and SU was 5.6 ± 1.3 mg/dL. Compared to the self-directed group, at 12 months, the coach-directed group reduced BMI by 0.9 kg/m2 (95% confidence interval (CI): -1.5, -0.4) and metformin reduced BMI by 0.6 kg/m2 (95% CI: -1.1, -0.1). However, compared to the self-directed group, the coach-directed group unexpectedly increased SU by 0.3 mg/dL (95% CI: 0.05, 0.6), and metformin non-significantly increased SU by 0.2 mg/dL (95% CI: -0.04, 0.5); these effects were attenuated when analyses included change in estimated glomerular filtration rate (eGFR). Conclusions: In this randomized trial of cancer survivors without gout, reductions in BMI either increased or did not change SU, potentially due to effects on eGFR. These results do not support a focus on BMI reduction for SU reduction; however, long-term studies are needed. ClinicalTrials.gov Registration: NCT02431676.


Individuals with posttraumatic stress disorder show a selective deficit in generalization of associative learning.
Drawing on two different populations, Israeli police and Hungarian civilians, the present study assessed the ability of individuals with posttraumatic stress disorder (PTSD) to generalize previous learning to novel situations. Past neuroimaging studies have demonstrated diminished medial temporal lobe (MTL) activation and/or reduced hippocampal volume in individuals with PTSD. Our earlier computational models of cortico-hippocampal function and subsequent experimental tests of these models in MTL-impaired clinical populations argue that even mild hippocampal dysfunction may result in subtle impairments in generalization. Therefore, we predicted that individuals with PTSD would show impaired generalization. We compared the performance of five groups from two countries, including 19 Israeli police with PTSD and 22 trauma-exposed police without PTSD, and 22 Hungarian civilians with PTSD, 25 trauma-exposed civilians without PTSD, and 25 individuals without PTSD unexposed to the same trauma. Participants were tested on a two-phase learning paradigm, the Acquired Equivalence Task, which measures the ability to generalize past learning to novel situations. We found that both PTSD and non-PTSD participants were capable of learning the initial stimulus-outcome associations, F(4, 108) = 1.79, p = .14. However, as predicted, only individuals with PTSD showed a selective deficit in generalization of this learning to novel situations (F(4, 108) = 8.35, p < .001, Partial η2 = 0.26). Individuals with PTSD show a selective impairment in generalization of past learning similar to other clinical populations with MTL/hippocampal dysfunction. This is consistent with an emerging view of PTSD as being not only an anxiety disorder but also a learning disorder.


Living life for others and/or oneself: The social development of life orientations.
A range of social science research suggests Americans are becoming more self-oriented over time, and that this focus comes at a cost to general concern with community. Examining data from a large-scale national study of college students, we explore this influential hypothesis on two fronts. First, we empirically investigate whether people who are especially concerned with personal achievement are necessarily less concerned about contributing to their community. Contrary to most iterations of the individualism thesis, we find that significant numbers of individuals are concerned with both personal success and political/social involvement. To explore further, we expand this supposed single dimension into a fourfold typology, showing that many people are 'idealists' (concerned with both self and others) and 'apathists' (relatively unconcerned with either). After broadening the taken-for-granted egoist/altruist continuum, we explore antecedent social structural, aspirational, and social psychological factors that predict membership in these value preference groups. The findings from our preliminary model suggest that these broad orientations are shaped by a complex array of factors across multiple domains.


Intraoperative hypotension, new onset atrial fibrillation, and adverse outcome after carotid endarterectomy.
Information regarding predisposing factors, frequency, and prognostic implications of new onset atrial fibrillation (NOAF) after carotid endarterectomy (CEA) is scarce. We assessed the frequency, risk factors, and the prognostic impact of NOAF after CEA. We assessed every patient undergoing CEA (n = 186) at our academic hospital between 2006 and 2009. Patients underwent continuous electrocardiographic monitoring during surgery and during the rest of hospital stay. We performed univariate and multivariate analyses for identifying variables associated with NOAF and for individualizing variables related to four perioperative adverse outcome measures: a) ischemic stroke; b) ischemic stroke and myocardial infarction, c) ischemic stroke and death, and d) ischemic stroke, myocardial infarction, and death. The study cohort comprised 186 patients. Overall, NOAF was detected in 7 cases (3.8%). The only variable associated with NOAF was intraoperative hypotension (OR 9.6, 95% CI 1.9-47.4, P = .006). There were no perioperative deaths. NOAF was associated with perioperative ischemic stroke and with the combined outcome of ischemic stroke and myocardial infarction. We found a low frequency of NOAF after CEA. Intraoperative hypotension was associated to a higher risk of NOAF. In turn, NOAF was related to adverse postoperative outcome. Further research is needed to clarify the pathophysiological relation between intraoperative hypotension, NOAF, and adverse CEA outcome.


Monoclonal antibodies targeting the epidermal growth factor receptor.
The epidermal growth factor receptor (EGFR, HER1) autocrine pathway contributes to a number of highly relevant processes in cancer development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis and metastatic spread. The crucial role that EGFR plays in human cancers has led to an extensive search for selective inhibitors of its signaling pathway. The results of a large body of preclinical studies and clinical trials thus far conducted suggest that targeting the EGFR could bring a significant contribution to cancer therapy. A variety of different approaches are currently being used to target the EGFR. The most promising strategies in clinical development include monoclonal antibodies, to prevent ligand binding, and small molecules inhibitors of the tyrosine kinase enzymatic activity, that inhibit autophosphorylation and downstream intracellular signaling. Several blocking monoclonal antibodies against the EGFR have been developed. Among these, IMC-225 is a chimeric human-mouse monoclonal IgG1 antibody that has been the first anti-EGFR targeted therapy to enter clinical evaluation in cancer patients in Phase II and III studies, alone or in combination with conventional radiotherapy and chemotherapy. However, other antibodies against EGFR have demonstrated antitumor activity in several preclinical models of human cancer and are currently under investigation in the clinical setting, such as ICR62, ABX-EGF and EMD72000. This review will focus on all the preclinical data available on monoclonal antibodies engineered against the EGF receptor.


[Dentigerous cyst in a pediatric patient with acute lymphoblastic leukemia type 1].
To report medical and surgical treatment in a patient with acute lymphoblastic leukemia type 1 who developed a dangerous cyst. A male of 8 years with acute lymphoblastic leukemia type 1, whose treatment was in induction. In one month, the patient presented a facial asymmetry due to mandibular growth and acute pain, hyperthermia and malaise. In the examination, we identified lip parestesia, a second temporal molar treated with chromium steel and expansion involving the cortical of the lateral permanent incisive until the first permanent molar was identified. Since we suspected of bone metastasis, we performed an orthopantomography. We established the diagnosis of dentigerous cyst. Enucleation, curettage, and extraction of decay teeth were done in order to avoid and prevent infectious sources. The most frequent clinical manifestations of acute lymphoblastic leukemia are anemia, leukopenia, and thrombocytopenia. This leukemia may be manifested also as infiltration of the jaw bone. In this case, the results showed no presence of bone metastasis. As a first step before to begin treatment, the physician ought to make sure that the patient is free of infectious processes anywhere that may influence the clinical development of leukemia. Due to the surgical intervention and to a successful bone marrow transplant, the patient is on remission.


Alcohol misuse: a risk factor for putaminal damage by ischemic brain infarct?
The relationship between alcohol consumption and the risk of ischemic stroke has been widely studied, whereas the effect of alcohol use on stroke features is not well established. This study compared the clinical and stroke features of ischemic stroke in two groups of patients with ischemic stroke: those with a history of alcohol misuse and those with a history of more social drinking. DSM-IV criteria were used to diagnose alcohol use disorder (dependency or abuse) in 275 of 486 consecutive patients aged 55-85 years, 3-4 months after ischemic stroke. Magnetic resonance imaging of the head was performed 3 months after stroke. Alcohol use disorder was diagnosed in 37/275 (13.5%) of ischemic stroke patients. These patients had more frequently (70.3 vs. 34.5%; OR 4.5; 95% CI 2.2-9.1; p < 0.000) an infarct affecting the putamen compared with patients who indulged in more social drinking. Another predisposed area was the superior anterior cerebral artery area. The stroke due to large- artery atherosclerosis was more common in patients with alcohol use disorder. The misuse of alcohol seemed to be associated with cerebral infarct localization in the putamen and superior anterior cerebral artery area. Prospective studies are needed to verify our preliminary finding.


[Prevention of periarticular ossification--with results of a randomized, double-blind study comparing acemetacin versus indomethacin].
We examined the effect of NSAR in the prophylaxis of heterotopic ossifications after hip arthroplasty. During a randomized doubleblind study 59 patients took Indometacin and 60 patients Acemetacin for three weeks after the operation. All of them got a thrombosis prophylaxis with Heparin and a short term antibiotic prophylaxis. The range of ossifications was checked three months after the operation according to Arcq. The proportion of patients with no clinical symptoms (grade 0 or 1) was 92.3% in the indometacin group and 98.2% in the acemetacin group. Because of side effects (mainly gastrointestinal) 7 patients (11.9%) in the indometacin group and 5 patients (8.3%) in the acemetacin group stopped the study. In a previous study we had examined the effect of thrombosis prophylaxis by Heparin on the heterotopic ossifications. These results could now be taken for comparison. According to these results the examined NSAR Indometacin and Acemetacin raised the group of low grade heterotopic ossifications. The higher grades (2 degrees and 3 degrees according to Arcq) were only be seen in less than 5%. That is why we recommend the NSAR (Acemetacin or Indometacin) generally after hip arthroplasty as prophylaxis of heterotopic ossifications.


Enhancement of jump performance after a 5-RM squat is associated with postactivation potentiation.
Weight lifting exercise may induce postactivation potentiation (PAP), thereby enhancing performance of a subsequent biomechanically similar "explosive" movement. However, it has not been shown that weight lifting induces PAP, indicated as potentiation of muscle twitch force. Therefore, the present study tested whether a five repetition maximum squat (5-RM squat) both induced PAP and increased the height of subsequently performed counter-movement jumps (CMJs). Eleven male athletes completed four laboratory sessions on separate days. Two sessions determined whether the 5-RM squat induced PAP: in one, a quadriceps maximal twitch was evoked immediately before and 8 min after a set of five CMJs (control); in the other, a twitch was evoked before a CMJ set, which was followed by a 4-min rest, a 5-RM squat, a 4-min rest, and a second twitch. Another two sessions tested the effect of the 5-RM squat on jump performance: in one session, two sets of five CMJs were performed with an 8-min rest between the sets (control); in the second, a 5-RM squat was performed 4 min after the first set of CMJs, and then after another 4 min the second set of CMJs was performed. Neither twitch torque nor CMJ height changed in the control sessions (P > 0.05). In contrast, interpolation of the 5-RM squat increased (P < 0.05) both twitch torque (49.5 ± 7.8 to 54.8 ± 11.9 N m; i.e., PAP = 10.7%) and CMJ height (48.1 ± 5.6 to 49.5 ± 5.9 cm; 2.9%). Since PAP was present at the time when CMJ height increased, it was concluded that PAP may have contributed to the increased CMJ height after a 5-RM squat.


High accuracy label-free classification of single-cell kinetic states from holographic cytometry of human melanoma cells.
Digital holographic cytometry (DHC) permits label-free visualization of adherent cells. Dozens of cellular features can be derived from segmentation of hologram-derived images. However, the accuracy of single cell classification by these features remains limited for most applications, and lack of standardization metrics has hindered independent experimental comparison and validation. Here we identify twenty-six DHC-derived features that provide biologically independent information across a variety of mammalian cell state transitions. When trained on these features, machine-learning algorithms achieve blind single cell classification with up to 95% accuracy. Using classification accuracy to guide platform optimization, we develop methods to standardize holograms for the purpose of kinetic single cell cytometry. Applying our approach to human melanoma cells treated with a panel of cancer therapeutics, we track dynamic changes in cellular behavior and cell state over time. We provide the methods and computational tools for optimizing DHC for kinetic single adherent cell classification.


Relationship between academic achievement and COMLEX-USA Level 1 performance: a multisite study.
The purpose of this study was to examine the relationship of performance on the Comprehensive Osteopathic Medical Licensing Examination (COMLEX-USA) Level 1 with academic performance at colleges accredited by the American Osteopathic Association (AOA). Eighteen (95%) of 19 AOA-accredited colleges and 2146 students (91% of those taking the June 1999 examination) met criteria and participated. Students were classified by school representatives on the basis of academic performance in the first 2 years of the curriculum. The relationships of Level 1 performance with assigned classifications and grade point averages (GPAs) were studied. Of students classified in the highest 20% academically, the Level 1 pass rate was 100%, with a mean score of 599. Of students classified in the lowest 5%, the pass rate was 63.5%, with a mean of 416.3. For 16 schools that provided GPAs, the within-school correlations between Level 1 scores and GPAs ranged from r = 0.76 to r = 0.85, with a mean correlation of r = 0.79. School representatives were also asked to indicate, for each student, whether they expected the student to pass the examination. Pass rate for students in the "sure pass" category was 98.9%; "borderline," 82.5%; and "concerns," 61.5%. Academic performance in the first 2 years of osteopathic medical school was strongly associated with performance on COMPLEX-USA Level 1. The national pass rate for this examination was similar to those in previous years, and it remains unclear why school representatives overpredicted the number of failures. Further research is needed.


Soluble ST2 testing in the general population.
ST2 is a member of the interleukin (IL)-1 receptor family biomarker, and circulating soluble ST2 concentrations are believed to reflect cardiovascular stress. Recent studies have demonstrated soluble ST2 to be a strong predictor of cardiovascular outcomes in community-based populations free of cardiovascular disease. This report reviews the role of soluble ST2 in relation to cardiovascular risk factors and clinical outcomes in the general population. Furthermore, the recommendations regarding the role of soluble ST2 in general population-based testing, as formulated by the International ST2 Consensus Panel, are presented. There may be a role for soluble ST2 in improving current risk-stratification strategies for the prediction of cardiovascular outcomes, potentially in combination with other biomarkers in a multimarker strategy. However, the role of soluble ST2 testing in the general population has not yet been conclusively established. Future studies investigating the clinical utility of soluble ST2 screening in the general population are warranted.


Polyphenic trait promotes liver cancer in a model of epigenetic instability in mice.
Hepatocellular carcinoma (HCC) represents the fifth-most common form of cancer worldwide and carries a high mortality rate attributed to lack of effective treatment. Males are 8 times more likely to develop HCC than females, an effect largely driven by sex hormones, albeit through still poorly understood mechanisms. We previously identified TRIM28 (tripartite protein 28), a scaffold protein capable of recruiting a number of chromatin modifiers, as a crucial mediator of sexual dimorphism in the liver. Trim28hep-/- mice display sex-specific transcriptional deregulation of a wide range of bile and steroid metabolism genes and development of liver adenomas in males. We now demonstrate that obesity and aging precipitate alterations of TRIM28-dependent transcriptional dynamics, leading to a metabolic infection state responsible for highly penetrant male-restricted hepatic carcinogenesis. Molecular analyses implicate aberrant androgen receptor stimulation, biliary acid disturbances, and altered responses to gut microbiota in the pathogenesis of Trim28hep-/- -associated HCC. Correspondingly, androgen deprivation markedly attenuates the frequency and severity of tumors, and raising animals under axenic conditions completely abrogates their abnormal phenotype, even upon high-fat diet challenge. This work underpins how discrete polyphenic traits in epigenetically metastable conditions can contribute to a cancer-prone state and more broadly provides new evidence linking hormonal imbalances, metabolic disturbances, gut microbiota, and cancer. (Hepatology 2017;66:235-251).


Somitic positional information guides self-organized patterning of snake scales.
Two influential concepts in tissue patterning are Wolpert's positional information and Turing's self-organized reaction-diffusion (RD). The latter establishes the patterning of hair and feathers. Here, our morphological, genetic, and functional-by CRISPR-Cas9-mediated gene disruption-characterization of wild-type versus "scaleless" snakes reveals that the near-perfect hexagonal pattern of snake scales is established through interactions between RD in the skin and somitic positional information. First, we show that ventral scale development is guided by hypaxial somites and, second, that ventral scales and epaxial somites guide the sequential RD patterning of the dorsolateral scales. The RD intrinsic length scale evolved to match somite periodicity, ensuring the alignment of ribs and scales, both of which play a critical role in snake locomotion.


Cytologic features of pulmonary hamartoma. Report of a case diagnosed by fine needle aspiration cytology.
Pulmonary hamartoma (PH) is the most common benign tumor of the lung. It is usually composed of cartilage, fat, smooth muscle and respiratory epithelium. Its diagnosis is based on imaging methods (radiography, computed tomography) and cytohistomorphologic study by means of fine needle aspiration cytology (FNAC). A 59-year-old female had a productive cough and lung mass on chest radiography. Fine needle aspiration of the nodule showed a fusiform tumor cell, which was diagnosed as consistent with PH. The patient underwent surgery for the tumor. Histopathologic study confirmed the diagnosis of PH. The fluoroscopically guided FNAC specimen was adequate in achieving a diagnosis. Cytologic features consisted of a serosanguineous background in which scant cellular elements of spindle and stellate cells, as well as fibromyxoid material, enabled us to make a definitive diagnosis. Since this technique is relatively noninvasive, it is very useful in diagnosing PH before a preoperative biopsy.


An immunohistochemical study of ras oncoprotein expression in gastric carcinoma.
Previous studies have shown that ras oncoprotein is overexpressed in gastric carcinoma. It is unsettled whether there is differential expression of this oncoprotein in the two major subtypes of gastric carcinoma--intestinal type and diffuse type. Forty-four cases of gastric carcinomas (24 intestinal type, 18 diffuse type, and 2 mixed according to the Lauren classification) were analyzed for ras oncoprotein expression using commercially available antibodies in routinely formaldehyde-fixed, paraffin-embedded tissue sections. Altogether, 13 cases stained unequivocally, and these appeared as granular cytoplasmic staining in tumor cells. Only five were intestinal-type carcinomas; the remaining eight were diffuse type and included two intramucosal carcinomas. When the comparison between the two subtypes was limited only to the poorly differentiated carcinomas, the difference was statistically significant (P < 0.05). ras Oncoprotein also was strongly expressed in normal duodenal mucosa as well as areas of gastric intestinal metaplasia. These results suggest that the strong expression of ras oncoprotein in gastric intestinal metaplasia may be merely a reflection of metaplastic change to an intestinal epithelial phenotype. The differential expression of ras oncoprotein between diffuse-type and poorly differentiated intestinal-type gastric carcinoma implies that these are two distinct subtypes of gastric carcinoma.


Acute cerebral compression caused by an epidural hematoma associated with cryptococcosis in a dog.
To describe acute cerebral compression caused by an epidural hematoma (EDH) in a dog with cryptococcal infection. An 18-month-old neutered male Neapolitan Mastiff was found comatose with no preceding clinical signs apart from a mild forelimb lameness. A CT scan of the head revealed a lesion within the right caudal nasal cavity that traversed the cribriform plate in addition to a right epidural lesion resulting in compression of the right cerebrum. Assessment of brain death was made based on the presence of coma, apnea, and absence of brain stem reflexes and included assessment of the vestibulo-ocular reflex. Postmortem identified a large EDH causing marked compression of the right frontal lobe. A nasal biopsy cultured Cryptococcus gattii. EDH formation in a dog secondary to cryptococcosis has not been previously reported. This is also the first time a caloric vestibulo-ocular reflex assessment has been reported in a dog.


Di-n-butyl phthalate causes antiestrogenic effects in female Murray rainbowfish (Melanotaenia fluviatilis).
Di-n-butyl phthalate (DnBP) is an industrial pollutant with antiandrogenic effects reported in male mammals and fish. Little research has been done on the endocrine effects of DnBP in female fish. The present study investigated the changes in ovarian histology and serum vitellogenin concentrations in adult Murray rainbowfish (Melanotaenia fluviatilis) after exposure to 125 µg/L, 250 µg/L, 500 µg/L, and 1000 µg/L DnBP for 7 d. Treatment at 125 µg/L to 1000 µg/L DnBP for 7 d had no significant effect on the survival, condition factor, gonadosomatic index, hepatosomatic index, and developmental stage of the fish. Based on the histological investigation, the sizes of the previtellogenic oocytes in the fish treated at 250 µg/L to 1000 µg/L were found to be significantly higher than in the corresponding control fish (p ≤ 0.05). The early vitellogenic oocytes in the fish treated at 1000 µg/L were significantly smaller relative to those in the unexposed fish (p ≤ 0.05). Histological changes like chorion folding, shrunken ooplasm, impaired yolk production, granulomatous inflammation, and interstitial fibrosis were observed in the ovaries of the fish treated with DnBP. The circulating levels of plasma vitellogenin were significantly lower in the fish exposed to 500 µg/L and 1000 µg/L DnBP (p ≤ 0.05). These data show that a continuous exposure to subacute concentrations of DnBP for 7 d can cause antiestrogenicity in female adult Murray rainbowfish.


Multilevel Modelling with Spatial Interaction Effects with Application to an Emerging Land Market in Beijing, China.
This paper develops a methodology for extending multilevel modelling to incorporate spatial interaction effects. The motivation is that classic multilevel models are not specifically spatial. Lower level units may be nested into higher level ones based on a geographical hierarchy (or a membership structure--for example, census zones into regions) but the actual locations of the units and the distances between them are not directly considered: what matters is the groupings but not how close together any two units are within those groupings. As a consequence, spatial interaction effects are neither modelled nor measured, confounding group effects (understood as some sort of contextual effect that acts 'top down' upon members of a group) with proximity effects (some sort of joint dependency that emerges between neighbours). To deal with this, we incorporate spatial simultaneous autoregressive processes into both the outcome variable and the higher level residuals. To assess the performance of the proposed method and the classic multilevel model, a series of Monte Carlo simulations are conducted. The results show that the proposed method performs well in retrieving the true model parameters whereas the classic multilevel model provides biased and inefficient parameter estimation in the presence of spatial interactions. An important implication of the study is to be cautious of an apparent neighbourhood effect in terms of both its magnitude and statistical significance if spatial interaction effects at a lower level are suspected. Applying the new approach to a two-level land price data set for Beijing, China, we find significant spatial interactions at both the land parcel and district levels.


Employment of MELD score for the prediction of survival after liver transplantation.
To assess the overall accuracy of the preoperative MELD score for predicting survival after liver transplantation (LT) and appraise medium-term (24 months) predictors of survival. We conducted a cross-sectional study including patients transplanted by the Department of General Surgery and Liver Transplantation of the Oswaldo Cruz University Hospital, University of Pernambuco, between July 15th, 2003 and July 14th, 2009. We used analysis of area under ROC (receiver operating characteristic) as a summary measure of the performance of the MELD score and assessed predictors of medium-term survival using univariate and multivariate analysis. The cumulative survival of three, six, 12 and 24 months of the 208 patients studied was 85.1%, 79.3%, 74.5% and 71.1%, respectively. The preoperative MELD score showed a low discriminatory power for predicting survival after TH. By univariate analysis, we identified intraoperative transfusion of red blood cells (p <0.001) and platelets (p = 0.004) and type of venous hepatocaval anastomosis (p = 0.008) as significantly related to medium-term survival of the patients studied. However, by multivariate analysis only red blood cell transfusion was a significant independent predictor of outcome. The MELD score showed low overall accuracy for predicting post-transplant survival of patients studied, among which only intraoperative transfusion of red blood cells was identified as an independent predictor of survival in the medium term after TH.


Nanoconfinement and Crowding Enhanced Single-Molecule Detection of Small Molecules with Nanopipettes.
Glass nanopipettes have gained widespread use as a versatile single-entity detector in chemical and biological sensing, analysis, and imaging. Its advantages include low cost, easy accessibility, simplicity of use, and high versatility. However, conventional nanopipettes based on the volume exclusion mechanism have limitations in detecting small biomolecules due to their small volume and high mobility in aqueous solution. To overcome this challenge, we have employed a novel approach by capitalizing on the strong nanoconfinement effect of nanopipettes. This is achieved by utilizing both the hard confinement provided by the long taper nanopipette tip at the cis side and the soft confinement offered by the hydrogel at the trans side. Through this approach, we have effectively slowed down the exit motion of small molecules, allowing us to enrich and jam them at the nanopipette tip. Consequently, we have achieved high throughput detection of small biomolecules with sizes as small as 1 nm, including nucleoside triphosphates, short peptides, and small proteins with excellent signal-to-noise ratios. Furthermore, molecular complex formation through specific intermolecular interactions, such as hydrogen bonding between closely spaced nucleotides in the jam-packed nanopipette tip, has been detected based on the unique ionic current changes.


Comparison of blood pressure measurements using an automated blood pressure device in community pharmacies and family physicians' offices: a randomized controlled trial.
Accurate measurement of blood pressure is the foundation of appropriate diagnosis, treatment and ongoing management of hypertension. The use of automated blood pressure devices in community settings such as pharmacies provide opportunities for additional blood pressure measurement; however, it is important to ensure that these measurements are comparable to those taken in physicians' offices using the same devices. We conducted a randomized controlled trial to assess whether blood pressure readings assessed by use of an automated device differed according to the setting, specifically in community pharmacies and family physicians' offices. We included adults aged 65 years and older who did not live in long-term care facilities or in hospital. The trial was administered by volunteer peer health educators, family physicians and pharmacists in 2 midsized communities in Ontario from April to September 2010. The 5 participating family physicians mailed invitations to their eligible patients. Those who gave informed consent were randomly allocated to 1 of 2 assessment sequences: group A had their blood pressure measured at their physician's office, then at a pharmacy, then again at their physician's office; those in group B had their blood pressure measured at a pharmacy, then at their physician's office, then again at a pharmacy. An automated blood pressure device (BpTRU) was used in both settings. We calculated the differences in mean systolic and diastolic blood pressure, and we compared the readings at both settings and by sequence of assessment. In total, 275 adults completed the trial (mean age 75.9 yr, 49.5% male, 46.9% with a self-reported diagnosis of hypertension). There were no statistically significant differences in systolic or diastolic blood pressure measurements associated with the sequence of assessment or the setting. There was a significant difference in the overall mean systolic blood pressure between the 2 assessment sequences (group A 122.0 v. group B 127.8 mm Hg, p < 0.001). Automated devices used in pharmacies to measure blood pressure provide accurate and valid information that can be used in the diagnosis and management of hypertension among older adults in the community. www.controlled-trials.com, no. ISRCTN91799042.


The prevalence and severity of dry skin and related skin care in older adult residents in institutional long-term care: A cross-sectional study.
To identify possible factors associated with different severities of xerosis cutis and to describe possible associations between (skin) care dependency and application of moisturizers. Cross-sectional study using baseline data from a cluster-randomized controlled trial. Demographic and health characteristics, skin physiological measurements, functional abilities and application of moisturizers were compared between the participants with mild and severe dry skin. Frequency of moisturization were also compared based on the participants' skin care dependency. The more distal the body area, the more severe xerosis were observed. There were no or minor differences between the groups, except for the stratum corneum hydration and skin surface pH. Participants with severe xerosis received moisturizers less often. Skin care dependent residents received moisturizers frequently. There is under-application regarding xerosis cutis treatment in long-term care. Skin care provided by nurses, in adequate frequencies, might be helpful compared to skin care performed by the residents themselves.


Whole-body vibration training improves balance control and sit-to-stand performance among middle-aged and older adults: a pilot randomized controlled trial.
Aging is associated with decreased balance, which increases falling risk. The objective of the current study was to determine the feasibility and effects of whole-body vibration (WBV) training on knee extensor muscle power, limits of stability, and sit-to-stand performance among community-dwelling middle-aged and older adults in the United States. A randomized pilot study with participant blinding was conducted. Feasibility outcomes included recruitment and compliance rate. Twenty-nine community-dwelling older adults were randomly assigned to perform body-weight exercises with either an individualized vibration frequency and amplitude, a fixed vibration frequency and amplitude, or no vibration. Isokinetic knee extensor power, limits of stability, and sit-to-stand tests were conducted before beginning the exercises (baseline) and after 8 weeks of training. With a favorable recruitment rate (58%) and compliance rates (attrition 9%; adherence 85%), the intervention was deemed feasible. The limits of stability endpoint excursion score for the individualized frequency-amplitude group was increased by 8.8 (12.9%; P = 0.025) after training, and that group's maximum excursion score was increased by 9.2 (11.5%; P = 0.006) after training. The average weight transfer time score was significantly decreased by 0.2 s in the fixed group. The participants in the individualized group demonstrated a significant increase (3.2%) in weight rising index score after 8 weeks of WBV training. WBV training is feasible for use with elderly people, and this study achieved good recruitment and compliance. The present paper suggests that 8 weeks of WBV training improves limits of stability and sit-to-stand performance. Future studies must determine whether WBV training improves other factors that affect posture control. This study was registered at the Texas Woman's University Institutional Review Board [TWU IRB 17632] on the 3rd of November 2014.


[Growth of anorexic adolescents].
Growth and puberty were studied in 19 children with anorexia nervosa (15 girls and 4 boys), the onset being before puberty or in its early stages. Growth retardation reached 2.04 +/- 1.39 SD, with important individual changes and for some patients a prolonged interruption of growth. Seventeen of 19 patients presented delayed puberty, and in some, hypogonadism persisted after recovery from anorexia nervosa. Endocrine investigations concerning the pituitary somatotropic (GH) and gonadotropic (FSH, LH) secretions, as well as gonadal steroids showed highly variable changes from one patient to another and even variations in the same patient from one test to another. However, no correlation could be found between the hormonal abnormalities and the degree or length of undernutrition. Some patients recovered normal endocrine function when they reached an adequate weight, others kept a lasting deficiency. The endocrine impairment in anorexia, well known in adults, is probably more severe in adolescents.


Studies on the mechanisms underlying amiloride enhancement of 3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats.
Amiloride and several of its congeners known to block the Na(+)/Ca(2+) and/or Na(+)/H(+) antiporters potentiate methamphetamine-induced neurotoxicity without altering methamphetamine-induced hyperthermia. We now examine whether amiloride also exacerbates 3,4-methylenedioxymethamphetamine (MDMA)-induced long-term serotonin (5-HT) loss in rats. Amiloride (2.5 mg/kg, every 2 h x 3, i.p.) given at ambient temperature 30 min before MDMA (5 mg/kg, every 2 h x 3, i.p.), markedly exacerbated long-term 5-HT loss. However, in contrast to methamphetamine, amiloride also potentiated MDMA-induced hyperthermia. Fluoxetine (10 mg/kg i.p.) completely protected against 5-HT depletion caused by the MDMA/amiloride combination without significantly altering the hyperthermic response. By contrast, the calcium channel antagonists flunarizine or diltiazem did not afford any protection. Findings with MDMA and amiloride were extended to the highly selective Na(+)/H(+) exchange inhibitor dimethylamiloride, suggesting that the potentiating effects of amiloride are probably mediated by the blockade of Na(+)/H(+) exchange. When the MDMA/amiloride combination was administered at 15 degrees C hyperthermia did not develop and brain 5-HT concentrations remained unchanged 7 days later. Intrastriatal perfusion of MDMA (100 microM for 8 h) in combination with systemic amiloride caused a small depletion of striatal 5-HT content in animals made hyperthermic but not in the striatum of normothermic rats. These data suggest that enhancement of MDMA-induced 5-HT loss caused by amiloride or dimethylamiloride depends on their ability to enhance MDMA-induced hyperthermia. We hypothesise that blockade of Na(+)/H(+) exchange could synergize with hyperthermia to render 5-HT terminals more vulnerable to the toxic effects of MDMA.


Toward carbon-nanotube-based theranostic agents for microwave detection and treatment of breast cancer: enhanced dielectric and heating response of tissue-mimicking materials.
The experimental results reported in this paper suggest that single-walled carbon nanotubes (SWCNTs) have the potential to enhance dielectric contrast between malignant and normal tissue for microwave detection of breast cancer and facilitate selective heating of malignant tissue for microwave hyperthermia treatment of breast cancer. In this study, we constructed tissue-mimicking materials with varying concentrations of SWCNTs and characterized their dielectric properties and heating response. At SWCNT concentrations of less than 0.5% by weight, we observed significant increases in the relative permittivity and effective conductivity. In microwave heating experiments, we observed significantly greater temperature increases in mixtures containing SWCNTs. These temperature increases scaled linearly with the effective conductivity of the mixtures. This work is a first step towards the development of functionalized, tumor-targeting SWCNTs as theranostic (integrated therapeutic and diagnostic) agents for microwave breast cancer detection and treatment.


Characterization of a Mesorhizobium loti alpha-type carbonic anhydrase and its role in symbiotic nitrogen fixation.
Carbonic anhydrase (CA) (EC 18.104.22.168) is a widespread enzyme catalyzing the reversible hydration of CO(2) to bicarbonate, a reaction that participates in many biochemical and physiological processes. Mesorhizobium loti, the microsymbiont of the model legume Lotus japonicus, possesses on the symbiosis island a gene (msi040) encoding an alpha-type CA homologue, annotated as CAA1. In the present work, the CAA1 open reading frame from M. loti strain R7A was cloned, expressed, and biochemically characterized, and it was proven to be an active alpha-CA. The biochemical and physiological roles of the CAA1 gene in free-living and symbiotic rhizobia were examined by using an M. loti R7A disruption mutant strain. Our analysis revealed that CAA1 is expressed in both nitrogen-fixing bacteroids and free-living bacteria during growth in batch cultures, where gene expression was induced by increased medium pH. L. japonicus plants inoculated with the CAA1 mutant strain showed no differences in top-plant traits and nutritional status but consistently formed a higher number of nodules exhibiting higher fresh weight, N content, nitrogenase activity, and delta(13)C abundance. Based on these results, we propose that although CAA1 is not essential for nodule development and symbiotic nitrogen fixation, it may participate in an auxiliary mechanism that buffers the bacteroid periplasm, creating an environment favorable for NH(3) protonation, thus facilitating its diffusion and transport to the plant. In addition, changes in the nodule delta(13)C abundance suggest the recycling of at least part of the HCO(3)(-) produced by CAA1.


The formation of a dissociable plasmid cointegrate from the Flac factor and the resident plasmid of Salmonella typhimurium LT2.
The Flac factor showed unstable maintenance in Salmonella typhimurium dnaC MP10LT2. The properties of a more stable lac+ derivate (SD-1) are described. SD-1 was ts and carried the fi+ property and the ability to transfer the lac+ character. It contained a large plasmid of molecular weight about 129 X 10(6) DALTONS. The properties of SD-1 and its derivatives suggested that the large plasmid was a cointegate of Flac and the MP10lt2 plasmid. Lac+ transfer was efficient from SD-1 to M799 MP10LT2 and one lac+ exconjugant contained the intact cointegrate. The cointegrate was not successfully transferred to strains lacking MP10LT2. It dissociated into apparently unaltered Flac and MP10LT2 plasmids, but the deletion of small parts of one or both plasmids during cointegrate formation could not be ruled out. Cointegrate dissociation was more marked in M799 than in SD-1 especially during growth in glucose-Casamino acids minimal medium. In the presence of R1drd19, the cointegrate (like the MP10LT2 plasmid) was stable maintained in the dnaC strain; maintenance of Flac was, however, unstable. It seems likely that replication of the cointegrate was controlled by the MP10LT2 plasmid constitutent.


Digital Health Apps in the Clinical Care of Inflammatory Bowel Disease: Scoping Review.
Digital health is poised to transform health care and redefine personalized health. As Internet and mobile phone usage increases, as technology develops new ways to collect data, and as clinical guidelines change, all areas of medicine face new challenges and opportunities. Inflammatory bowel disease (IBD) is one of many chronic diseases that may benefit from these advances in digital health. This review intends to lay a foundation for clinicians and technologists to understand future directions and opportunities together. This review covers mobile health apps that have been used in IBD, how they have fit into a clinical care framework, and the challenges that clinicians and technologists face in approaching future opportunities. We searched PubMed, Scopus, and ClinicalTrials.gov to identify mobile apps that have been studied and were published in the literature from January 1, 2010, to April 19, 2019. The search terms were ("mobile health" OR "eHealth" OR "digital health" OR "smart phone" OR "mobile app" OR "mobile applications" OR "mHealth" OR "smartphones") AND ("IBD" OR "Inflammatory bowel disease" OR "Crohn's Disease" (CD) OR "Ulcerative Colitis" (UC) OR "UC" OR "CD"), followed by further analysis of citations from the results. We searched the Apple iTunes app store to identify a limited selection of commercial apps to include for discussion. A total of 68 articles met the inclusion criteria. A total of 11 digital health apps were identified in the literature and 4 commercial apps were selected to be described in this review. While most apps have some educational component, the majority of apps focus on eliciting patient-reported outcomes related to disease activity, and a few are for treatment management. Significant benefits have been seen in trials relating to education, quality of life, quality of care, treatment adherence, and medication management. No studies have reported a negative impact on any of the above. There are mixed results in terms of effects on office visits and follow-up. While studies have shown that digital health can fit into, complement, and improve the standard clinical care of patients with IBD, there is a need for further validation and improvement, from both a clinical and patient perspective. Exploring new research methods, like microrandomized trials, may allow for more implementation of technology and rapid advancement of knowledge. New technologies that can objectively and seamlessly capture remote data, as well as complement the clinical shift from symptom-based to inflammation-based care, will help the clinical and health technology communities to understand the full potential of digital health in the care of IBD and other chronic illnesses.