Physiology of the IGF system.
The insulin-like growth factors (IGFs) comprise a complex regulation system with two growth factors, cell-surface receptors, 6 specific high affinity IGF binding proteins (IGFBP1-6), IGFBP-proteases, as well as other IGFBP-interacting molecules. Although the IGFs and their signalling receptor closely resemble the peptide hormone (after which they were named) and its cell receptor; their modus operandi is very different from that of traditional peptide hormones. The IGFs are not stored within cells of a specific tissue but are present at very high levels throughout the body. They circulate at total concentrations approximately 1000 times higher than that of most peptide hormones and although tissue levels are somewhat lower, they are still present in vast excess compared to that required for maximal cellular stimulation. These high levels are maintained due to their association with the IGFBPs, which dramatically slow their clearance. The IGFBPs bind the IGFs with greater affinity than their cell surface receptors, enabling them to tightly control tissue activity. The IGFBP proteases modify the IGFBPs, lowering the affinity with which they bind IGFs. In the tissues the IGFs are important regulators of cell survival, growth, metabolism and differentiated function; the complex system confers specificity on these actions.


The novel catabolic pathway of 3,6-anhydro-L-galactose, the main component of red macroalgae, in a marine bacterium.
The catabolic fate of the major monomeric sugar of red macroalgae, 3,6-anhydro-L-galactose (AHG), is completely unknown in any organisms. AHG is not catabolized by ordinary fermentative microorganisms, and it hampers the utilization of red macroalgae as renewable biomass for biofuel and chemical production. In this study, metabolite and transcriptomic analyses of Vibrio sp., a marine bacterium capable of catabolizing AHG as a sole carbon source, revealed two key metabolic intermediates of AHG, 3,6-anhydrogalactonate (AHGA) and 2-keto-3-deoxy-galactonate; the corresponding genes were verified in vitro enzymatic reactions using their recombinant proteins. Oxidation by an NADP(+) -dependent AHG dehydrogenase and isomerization by an AHGA cycloisomerase are the two key AHG metabolic processes. This newly discovered metabolic route was verified in vivo by demonstrating the growth of Escherichia coli harbouring the genes of these two enzymes on AHG as a sole carbon source. Also, the introduction of only these two enzymes into an ethanologenic E. coli strain increased the ethanol production in E. coli by fermenting both AHG and galactose in an agarose hydrolysate. These findings provide not only insights for the evolutionary adaptation of a central metabolic pathway to utilize uncommon substrates in microbes, but also a metabolic design principle for bioconversion of red macroalgal biomass into biofuels or industrial chemicals.


An investigation of the toxicity of gadolinium based MRI contrast agents using neutron activation analysis.
The toxicity of gadolinium (Gd) based MRI contrast agents, is based upon the amount of Gd that dissociates from its chelate and deposits in tissues. In this study, the toxicities of two contrast agents were tested using different injection strategies in two animal models. Following a bolus injection of 0.2 mmol/kg of Gd-DTPA in a pilot study with a single canine, Gd levels were as high as 2.05 +/- 0.17 ppm and 0.47 +/- 0.11 ppm 2 weeks post injection in the kidney and liver tissues, respectively. To evaluate the role that the injection strategy plays in toxicity, 0.8 mmol/kg of Gd-(HP-DO3A) was injected into rats, in a second study, via bolus and constant infusion techniques. Gd was only detected in the kidney in the bolus injected rats but in the lung as well in the constant infusion injected rats. Concentrations detected in the kidney for both strategies, were comparable within error: 1.37 +/- 0.46 ppm for the bolus and 1.24 +/- 0.39 ppm for the bolus/constant infusion strategy and 0.16 +/- 0.14 ppm in the lung for the constant infusion technique. The contrast infusion technique does not appear to present an increased risk of toxicity over the bolus technique except perhaps to a small degree in the lung.


Internal stabilization of a flexion-distraction injury of the upper cervical spine of a toddler: a new technique and literature review.
A case report and literature review. To present a new and simple technique of fixation without fusion of a rare unstable Salter-Harris type I injury in the upper cervical spine of a 23-month-old toddler. Surgical treatment of unstable pediatric cervical spine injuries most commonly involves posterior fusion with internal fixation, usually posterior wiring. Detailed description of the surgical procedure carried out for fixating an unstable flexion-distraction injury in a 23-month-old toddler, with severe head injury and pneumothorax, is presented. A rare unstable flexion-distraction injury in the upper cervical spine of a toddler was successfully treated with a posterior Number 2 Vicryl (polyglactin 910; ETHICON Division of Johnson & Johnson) suture fixation, with good healing of the ligaments and end plates, without fusion. Preservation of motion was achieved without obvious instability at 28 months postsurgery. In selected cases of cervical spine injuries in the young pediatric population, simple stabilization of the spine using degradable Number 2 Vicryl (polyglactin 910) sutures with minimal exposure can provide sufficient stability until healing occurs. Advantages are that fusion is avoided and motion preserved.


When do phylogenetic mixture models mimic other phylogenetic models?
Phylogenetic mixture models, in which the sites in sequences undergo different substitution processes along the same or different trees, allow the description of heterogeneous evolutionary processes. As data sets consisting of longer sequences become available, it is important to understand such models, for both theoretical insights and use in statistical analyses. Some recent articles have highlighted disturbing "mimicking" behavior in which a distribution from a mixture model is identical to one arising on a different tree or trees. Other works have indicated such problems are unlikely to occur in practice, as they require very special parameter choices. After surveying some of these works on mixture models, we give several new results. In general, if the number of components in a generating mixture is not too large and we disallow zero or infinite branch lengths, then it cannot mimic the behavior of a nonmixture on a different tree. On the other hand, if the mixture model is locally overparameterized, it is possible for a phylogenetic mixture model to mimic distributions of another tree model. Although theoretical questions remain, these sorts of results can serve as a guide to when the use of mixture models in either maximum likelihood or Bayesian frameworks is likely to lead to statistically consistent inference, and when mimicking due to heterogeneity should be considered a realistic possibility. [Phylogenetic mixture models; parameter identifiability; heterogeneous sequence evolution.].


Multiple Tobacco Product Use among Adolescents with Asthma in Korea.
Few studies have examined the use of multiple tobacco products among adolescents with asthma. The purpose of this study was to examine multiple tobacco product use and smoking behaviors. In this study, data from the Korea Youth Risk Behavior Web-based Survey (KYRBWS) were used, and 57,303 samples from 400 middle schools and 400 high schools in Korea were classified as study participants. Statistical analysis was performed with a complex sample design, using frequency analysis, chi-square test, and multiple logistic regression analysis. Adolescents with asthma had a higher current smoking rate for combustible cigarettes (CC), e-cigarettes (EC), and heated tobacco products (HTPs) than those without asthma (p < 0.001). The rates of dual use (using two types of tobacco; CC + EC or CC + HTPs or EC + HTPs; OR = 2.62, 95% CI: 1.626−4.240, R2 = 26.8%) and triple use (using three types of tobacco; CC + EC + HTPs; OR = 2.61, 95% CI: 1.678−4.065, R2 = 34.9%) were higher in adolescents with asthma than those without asthma, after adjusting for confounders. The smoking rate of new types of tobacco among adolescents with asthma is on the rise. Therefore, the calculation of basic data related to new tobacco smoking among adolescents is essential for establishing a continuous monitoring system to alleviate the burden of disease on national health.


Identifying generalised segmental acceleration patterns that contribute to ground reaction force features across different running tasks.
To support future developments of field-based biomechanical load monitoring tools, this study aimed to identify generalised segmental acceleration patterns and their contribution to ground reaction forces (GRFs) across different running tasks. Exploratory experimental design. A multivariate principal component analysis (PCA) was applied to a combination of segmental acceleration data from all body segments for 15 team-sport athletes performing accelerated, decelerated and constant low-, moderate- and high-speed running, and 90° cutting trials. Segmental acceleration profiles were then reconstructed from each principal component (PC) and used to calculate their specific GRF contributions. The first PC explained 48.57% of the acceleration variability for all body segments and was primarily related to the between-task differences in the overall magnitude of the GRF impulse. Magnitude and timing of high-frequency acceleration and GRF features (i.e. impact related characteristics) were primarily explained by the second PC (12.43%) and also revealed important between-task differences. The most important GRF characteristics were explained by the first five PCs, while PCs beyond that primarily contained small contributions to the overall GRF impulse. These findings show that a multivariate PCA approach can reveal generalised acceleration patterns and specific segmental contributions to GRF features, but their relative importance for different running activities are task dependent. Using segmental acceleration to assess whole-body biomechanical loading generically across various movements may thus require task identification algorithms and/or advanced sensor or data fusion approaches.


Management of secondary lymphoedema.
Lymphoedema is a chronic, progressive condition. There is no cure but it is most easily managed with early recognition and therapy; those who do not have treatment tend to worsen rapidly and advanced disease is more difficult to treat than early disease. Surgery for lymphoedema is often regarded as a last resort but traditional excisional techniques that have been slightly modified for modern practice have shown good results, whilst newer microsurgical reconstruction techniques show promise although long-term results are lacking. This report provides an update on the therapy of lymphoedema.


Beating cancer-related fatigue with the Untire mobile app: Results from a waiting-list randomized controlled trial.
This waiting-list randomized controlled trial examined the effectiveness of a self-management mHealth app in improving fatigue and quality of life (QoL) in cancer patients and survivors. Persons with cancer-related fatigue (CRF) were recruited across four English speaking countries, via social media, and randomized into intervention (n = 519) and control (n = 280) groups. Whereas the intervention group received immediate access to the Untire app, the control group received access only after 12-weeks. Primary outcomes fatigue severity and interference, and secondary outcome QoL were assessed at baseline, 4, 8, and 12-weeks. We ran generalized linear mixed models for all outcomes to determine the effects of app access (yes/no), over 12-weeks, following the intention-to-treat principle. Compared with the control group, the intervention group showed significantly larger improvements in fatigue severity (d = 0.40), fatigue interference (d = 0.35), and overall QoL on average (d = 0.32) (P's < .01), but not for overall QoL in the past week (P = .07). Sensitivity analyses indicated that participants with medium or high app use benefited most when compared with nonusers and control participants (P's ≤ .02). The intervention effect on fatigue interference was slightly stronger in younger participants (≤56 vs. >56). Effects did not depend on education and cancer status. Reliable change analyses indicated that significantly more people showed full recovery for fatigue in the intervention vs the control group (P's = .02). The Untire app can be an effective mHealth solution for cancer patients and survivors with moderate to severe CRF.


Relations between nursing data collection, diagnoses and prescriptions for adult patients at an intensive care unit.
This descriptive, retrospective study aimed to analyze the relation between nursing data collection, diagnoses and prescriptions for 26 adult patients who were hospitalized at the intense care unit of a large teaching hospital for at least 24 hours. Through the analysis of medical records, 135 diagnoses and 421 nursing prescriptions were established, and 24 different diagnosis categories and 20 different items for prescriptions were identified. The most frequent diagnosis risk was that for infection, present in the medical records of 22 (84.60%) patients, with 175 prescriptions (42%) related to this diagnosis. The data the nurses collected were sufficient to establish the nursing diagnoses, and the majority of prescriptions (87.9%) were related to the diagnoses.


Host-Cell-Dependent Roles of E-Cadherin in Serratia Invasion.
Bacteria use cell surface proteins to mediate host-pathogen interactions. Proteins responsible for cell adhesion, including E-cadherin, serve as receptors for entry into the host cell. We have previously shown that an increase in eukaryotic cell sensitivity to Serratia grimesii correlates with an increase in E-cadherin expression. On the other hand, Serratia proteamaculans invasion involves the EGFR, which can interact with E-cadherin on the surface of host cells. Therefore, we investigated the role of E-cadherin in Serratia invasion into M-HeLa and Caco-2 cells. Bacterial infection increased E-cadherin expression in both cell lines. Moreover, E-cadherin was detected in the Caco-2 cells in a full-length form and in the M-HeLa cells in only a truncated form in response to incubation with bacteria. Transfection with siRNA targeting E-cadherin inhibited S. proteamaculans invasion only into the Caco-2 cells. Thus, only full-length E-cadherin is involved in S. proteamaculans invasion. On the other hand, transfection with siRNA targeting E-cadherin inhibited S. grimesii invasion into both cell lines. Thus, not only may full-length E-cadherin but also truncated E-cadherin be involved in S. grimesii invasion. Truncated E-cadherin can be formed as a result of cleavage by bacterial proteases or the Ca2+-activated cellular protease ADAM10. The rate of Ca2+ accumulation in the host cells depends on the number of bacteria per cell upon infection. During incubation, Ca2+ accumulates only when more than 500 S. grimesii bacteria are infected per eukaryotic cell, and only under these conditions does the ADAM10 inhibitor reduce the sensitivity of the cells to bacteria. An EGFR inhibitor has the same quantitative effect on S. grimesii invasion. Apparently, as a result of infection with S. grimesii, Ca2+ accumulates in the host cells and may activate the ADAM10 sheddase, which can promote invasion by cleaving E-cadherin and, as a result, triggering EGFR signaling. Thus, the invasion of S. proteamaculans can only be promoted by full-length E-cadherin, and S. grimesii invasion can be promoted by both full-length and truncated E-cadherin.


Arginine Deprivation Inhibits the Warburg Effect and Upregulates Glutamine Anaplerosis and Serine Biosynthesis in ASS1-Deficient Cancers.
Targeting defects in metabolism is an underutilized strategy for the treatment of cancer. Arginine auxotrophy resulting from the silencing of argininosuccinate synthetase 1 (ASS1) is a common metabolic alteration reported in a broad range of aggressive cancers. To assess the metabolic effects that arise from acute and chronic arginine starvation in ASS1-deficient cell lines, we performed metabolite profiling. We found that pharmacologically induced arginine depletion causes increased serine biosynthesis, glutamine anaplerosis, oxidative phosphorylation, and decreased aerobic glycolysis, effectively inhibiting the Warburg effect. The reduction of glycolysis in cells otherwise dependent on aerobic glycolysis is correlated with reduced PKM2 expression and phosphorylation and upregulation of PHGDH. Concurrent arginine deprivation and glutaminase inhibition was found to be synthetic lethal across a spectrum of ASS1-deficient tumor cell lines and is sufficient to cause in vivo tumor regression in mice. These results identify two synthetic lethal therapeutic strategies exploiting metabolic vulnerabilities of ASS1-negative cancers.


Does the tutors' academic background influence the learning objectives in problem-based learning?
Background: Problem-based learning (PBL) is an essential element of the curriculum of the Medical University of Vienna (MUV) and is performed in an eight steps model with: clarifying, defining, analysing, shifting & sorting, identifying learning objectives, going to learn and coming back to talk and feedback. With an annual intake of up to 740 students the MUV has to recruit PBL tutors from various academic backgrounds including undergraduate near-peer students. Therefore, we were interested to see whether a tutor's academic background had an influence on the resulting PBL sessions as reflected by the percentage of learning objectives (LOs) which were actually achieved in relation to the intended LOs. Methods: For each PBL session "intended learning objectives" (ILOs) were defined. ILOs were communicated to all tutors by means of PBL session guides in order to provide homogenous learning opportunities to all students. However, it was not mandatory to reach all ILOs. The PBL coordination regarded a range of two thirds to three quarters of ILOs as a desirable goal. For analysis we retrieved data concerning ILOs, characteristics of tutors and PBL groups from the institution's PBL quality assurance system. Results: From 2012-2014, 216 PBL groups were facilitated by 106 tutors with different academic backgrounds. On average, 70.8% (95% CI: 69.2-72.5%) of the ILOs were achieved; MUV clinicians reached 74.3% (70.8-77.8%), MUV non-clinicians 74.2% (71.7-76.6%), external faculty (clinicians and non-clinicians) 68.6% (64.4-72.8%), and near-peer students 64.7% (61.8-67.7%). Statistically significant differences were found between near-peer students and MUV clinicians (p<.001) as well as MUV non-clinicians (p<.001). Conclusions: ILOs were reached within a satisfactory range. However, groups taught by near-peer students reached significantly fewer ILOs than groups taught by MUV faculty tutors. This finding raises the question whether tutor training for near-peer students should be intensified. Also, further research is needed to explore the group dynamics of student-led PBL groups.


[Osteoarticular paleopathology in a Chinchorro body: report of one case].
We report a severe osteo-arthropathy in a body of a Chinchorro adult mole exhumed from the pre-Hispanic site of Playa Miller 8, located in the city of Arica, on the northern coast of Chile. The advanced state of joint disease shows that the individual was cared by his social group, to be able to survive. This care was perpetuated in the postmortem treatment, applying red color to the body. Particular self-care social dynamics of Chinchorro society are inferred.


Exploring the effects of ownership and choice on self-memory biases.
Objects encoded in the context of temporary ownership by self enjoy a memorial advantage over objects owned by other people. This memory effect has been linked to self-referential encoding processes. The current inquiry explored the extent to which the effects of ownership are influenced by the degree of personal choice involved in assigning ownership. In three experiments pairs of participants chose objects to keep for ownership by self, and rejected objects that were given to the other participant to own. Recognition memory for the objects was then assessed. Experiment 1 showed that participants recognised more items encoded as "self-owned" than "other-owned", but only when they had been chosen by self. Experiment 2 replicated this pattern when participants' sense of choice was illusory. A source memory test in Experiment 3 showed that self-chosen items were most likely to be correctly attributed to ownership by self. These findings are discussed with reference to the link between owned objects and the self, and the routes through which self-referential operations can impact on cognition.


A multilead scheme based on periodic component analysis for T-wave alternans analysis in the ECG.
T-wave alternans (TWA) is a cardiac phenomenon that appears in the electrocardiogram (ECG) and is associated with the mechanisms leading to sudden cardiac death (SCD). In this study, we propose the use of a multilead TWA analysis scheme that combines the Laplacian likelihood ratio (LLR) method and periodic component analysis (piCA), an eigenvalue decomposition technique whose aim is to extract the most periodic sources of the signal. The proposed scheme is evaluated in different scenarios--from synthetic signals to stress test ECGs--and is compared to other reported schemes based on the LLR method. Results demonstrate that the piCA-based scheme provides a superior ability to detect TWA than previously reported schemes, and has the potential to improve the prognostic value of testing for TWA.


TOR kinase pathway and 14-3-3 proteins regulate glucose-induced expression of HXT1, a yeast low-affinity glucose transporter.
Expression of HXT1, a gene encoding a Saccharomyces cerevisiae low-affinity glucose transporter, is regulated by glucose availability, being activated in the presence of glucose and inhibited when the levels of the sugar are scarce. In this study we show that 14-3-3 proteins are involved in the regulation of the expression of HXT1 by glucose. We also demonstrate that 14-3-3 proteins, in complex with Reg1, a regulatory subunit of Glc7 protein phosphatase, interact physically with Grr1 (a component of the SCF-Grr1 ubiquitination complex), a key player in the process of HXT1 induction by glucose. In addition, we show that the TOR kinase pathway participates actively in the induction of HXT1 expression by glucose. Inhibition of the TOR kinase pathway by rapamycin treatment abolishes HXT1 glucose induction. A possible involvement of PP2A protein phosphatase complex, through the Cdc55 B-subunit, in the glucose induction of HXT1 is also discussed.


Prediction of the active-site structure and NAD(+) binding in SQD1, a protein essential for sulfolipid biosynthesis in Arabidopsis.
Sulfolipids of photosynthetic bacteria and plants are characterized by their unique sulfoquinovose headgroup, a derivative of glucose in which the 6-hydroxyl group is replaced by a sulfonate group. These sulfolipids have been discussed as promising anti-tumor and anti-HIV therapeutics based on their inhibition of DNA polymerase and reverse transcriptase. To study sulfolipid biosynthesis, in particular the formation of UDP-sulfoquinovose, we have combined computational modeling with biochemical methods. A database search was performed employing the derived amino acid sequence from SQD1, a gene involved in sulfolipid biosynthesis of Arabidopsis thaliana. This sequence shows high similarity to other sulfolipid biosynthetic proteins of different organisms and also to sugar nucleotide modifying enzymes, including UDP-glucose epimerase and dTDP-glucose dehydratase. Additional biochemical data on the purified SQD1 protein suggest that it is involved in the formation of UDP-sulfoquinovose, the first step of sulfolipid biosynthesis. To understand which aspects of epimerase catalysis may be shared by SQD1, we built a three-dimensional model of SQD1 using the 1.8 A crystallographic structure of UDP-glucose 4-epimerase as a template. This model predicted an NAD(+) binding site, and the binding of NAD(+) was subsequently confirmed by enzymatic assay and mass spectrometry. The active-site interactions together with biochemical data provide the basis for proposing a reaction mechanism for UDP-sulfoquinovose formation.


Atypical Meningiomas: Recurrence, Reoperation, and Radiotherapy.
Atypical meningiomas (World Health Organization [WHO] grade II) represent a therapeutic challenge given their high recurrence rate and greater mortality compared with WHO grade I meningiomas. Traditionally, treatment has entailed attempts at gross total resection with radiation therapy reserved for residual disease or recurrences. We retrospectively reviewed our patient database of atypical meningioma (AM) patients over the past 10 years to assess surgical and radiotherapeutic treatments administered, treatment-related complications, radiographic-clinical progression after treatment, and mortality. We identified 45 patients with AMs and excluded 2 patients with incomplete hospital records. The average age of our patients was 59.7 years. Forty-three AM patients underwent a total of 62 surgeries. Thirty patients underwent one initial surgical resection; 8 patients underwent a second resection for recurrence; 4 patients underwent 3 resections; and 1 patient underwent 4 resections for recurrences. The rate of postoperative complication was 12.9% (8/62). Five patients had postoperative wound infections requiring treatment, and 1 patient had a postoperative hematoma requiring surgical evacuation. There was 1 case of wound breakdown in a patient with a previously irradiated scalp and 1 case of lower-extremity venous thrombosis. Clinical follow-up ranged from 11-120 months with average follow-up of 43 months and median follow-up of 65 months. Nineteen patients (44%) developed clinical-radiographic evidence of recurrence at an average of 32.4 months after surgical resection. Of the recurrences, 12 were treated with repeat surgery and radiation therapy, 3 were treated with radiation therapy alone, and 2 with surgery alone. Radiation therapy included Gamma Knife (GK), CyberKnife (CK), intensity-modulated radiation therapy (IMRT), or some combination of these. There was one case of symptomatic radiation necrosis (1/15 or 6.6%). The survival rate at last follow-up of our patient cohort was 95.3%. Given their high rates of recurrence, AMs require close clinical follow-up and an individualized treatment strategy. Reoperation, radiotherapy, or combination therapy can be effective strategies at managing disease progression while minimizing treatment-related morbidity. Treatment planning that attempts to anticipate future therapies in the form of further surgery or radiotherapy may improve clinical outcomes in these patients. Seventeen patients underwent adjuvant radiation therapy: 7 patients with intensity-modulated radiation therapy (IMRT), 4 patients with Gamma Knife (GK), and 2 with CyberKnife (CK). Four patients underwent multiple treatments.


Zataria multiflora, broiler health and performance: a review.
Zataria multiflora Boiss. (ZM) from Lamiaceae family, is an herb native to Iran, Pakistan, and Afghanistan with a history of use both as a condiment and a traditional medicine. The herb and/or its preparations have also shown promising effects in modern pharmacological studies. With regard to the importance of reducing synthetic drug administration both as growth promoters and therapeutic agents in poultry industry, this review is a short account of current knowledge about the beneficial effects of this herb on broiler health and performance parameters based on published materials in different databases such as Google Scholar, PubMed, ScienceDirect, Scientific Information Database, Scopus, etc. It seems that ZM, possibly due to the presence of thymol and carvacrol as its main constituents, can affect broiler's health especially with regard to its antioxidant effects, immunomodulatory properties and proper effects on gut bacterial pathogens and/or microbiota. It should be kept in mind that although major constituents of ZM essential oil (as the most studied preparation of the herb) are relatively similar, their relative content may show a broad range that can subsequently affect the outcome of ZM essential oil administration to broilers. Overall, ZM is a pluripotent herb and its effect on broilers should be more clarified in future studies.


Magneto-optical tracking of flexible laparoscopic ultrasound: model-based online detection and correction of magnetic tracking errors.
Electromagnetic tracking is currently one of the most promising means of localizing flexible endoscopic instruments such as flexible laparoscopic ultrasound transducers. However, electromagnetic tracking is also susceptible to interference from ferromagnetic material, which distorts the magnetic field and leads to tracking errors. This paper presents new methods for real-time online detection and reduction of dynamic electromagnetic tracking errors when localizing a flexible laparoscopic ultrasound transducer. We use a hybrid tracking setup to combine optical tracking of the transducer shaft and electromagnetic tracking of the flexible transducer tip. A novel approach of modeling the poses of the transducer tip in relation to the transducer shaft allows us to reliably detect and significantly reduce electromagnetic tracking errors. For detecting errors of more than 5 mm, we achieved a sensitivity and specificity of 91% and 93%, respectively. Initial 3-D rms error of 6.91 mm were reduced to 3.15 mm.


[Role of adrenergic mechanisms in the regulation of aspartate aminotransferase isoenzyme activity in the liver of white rats].
Cytoplasmic (c) and mitochondrial (m) isozymes of aspartate aminotransferase (AAT) (EC 18.104.22.168) were isolated from white rat liver tissue by means of electrophoresis in agar gel. For the enzymes Km values, pH optima were estimated and conditions, suitable for the reaction, were studied. On the basis of activating effectiveness on c-AAT the catecholamines were arranged in decreasing order as follows: adrenaline, isadrine, noradrenaline. Towards the m-AAT the series was: noradrenaline, isadrine, adrenaline. Obsidane decreased the action of adrenaline more effectively than it did isadrine. Phentholamine did not alter the effect of noradrenalin on c-AAT, but distinctly decreased the m-AAT activity. Beta-adrenergic receptor, but not alpha-receptor, participated in regulation of the AAT isozymes activity. Adrenaline promoted and isadrine inhibited the penetration of m-AAT into cytoplasma. Obsidane increased the effect of these catecholamines. After administration of phentholamine an increase in the AAT activity was caused by an increase in content of catecholamines in the organism.


Influence of Roux-en-Y gastric bypass on plasma bile acid profiles: a comparative study between rats, pigs and humans.
Roux-en-Y gastric bypass (RYGBP) is the most widely used bariatric surgery procedure, which induces profound metabolic and physiological effects, such as substantial improvements in obesity, type 2 diabetes and their comorbidities. Increasing evidence identifies bile acids (BAs) as signaling molecules that contribute to the metabolic improvement after RYGBP. However, how and to what extent BAs mediate the metabolic effects of RYGBP still remains unclear and requires mechanism of action studies using preclinical models. In this study, we compared plasma BA profiles before and after RYGBP in two animal models, rats and pigs, with humans to evaluate their translational potential. Plasma BAs were profiled in rats, pigs and humans by liquid chromatography coupled with tandem mass spectrometry before and after RYGBP. RYGBP increased baseline plasma total BA concentrations in humans and in the two animal models to a similar extent (∼3-fold increase), despite differences in presurgery BA levels and profiles between the models. However, qualitatively, RYGBP differently affected individual plasma BA species, with similar increases in some free species (cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)), different increases in glyco-conjugated species depending on the model and globally no increase in tauro-conjugated species whatever the model. The tested animal models share similar quantitative RYGBP-induced increases in peripheral blood BAs as humans, which render them useful for mechanistic studies. However, they also present qualitative differences in BA profiles, which may result in different signaling responses. Such differences need to be taken into account when translating results to humans.


Differences in nuclear gene expression between cells containing monomer and dimer mitochondrial genomes.
It is known that point mutations and rearrangements (deletions and duplications) of mammalian mitochondrial DNA (mtDNA) can result in mitochondrial dysfunction and human disease. Very little attention has been paid to mtDNA circular dimers (a complex form consisting of two genomes joined head-to-tail) despite their close association with human neoplasia. MtDNA dimers are frequently found in human leukemia, but the clinical relevance of their presence remains unknown. To begin to investigate the role of circular dimer mtDNA in the tumorigenic phenotype, we have created isogenic cell lines containing monomer and dimer mitochondrial genomes and compared the respective nuclear mRNA expression using Affymetrix gene array analysis. Surprisingly, a large number of nuclear gene changes were observed, with one of the largest category of genes being associated with remodeling of the cell surface and extracellular matrix. Since cell growth, migration, apoptosis, and many other cellular processes are influenced by signals initiating from the cell surface, the changes associated with the presence of mtDNA dimers could lead to significant alterations in tumorigenic potential and/or progression.


Self-cleaving ribozymes of hepatitis delta virus RNA.
Hepatitis delta virus (HDV) is a small single-stranded RNA satellite of hepatitis B virus. Although it is a human pathogen, it shares a number of features with a subset of the small plant satellite RNA viruses, including self-cleaving sequences in the genomic and antigenomic sequences of the viral RNA. The self-cleaving sequence is critical to viral replication and is thought to function as a ribozyme in vivo to process the products of rolling-circle replication to unit-length molecules. A divalent cation is required for cleavage and while a structural role is implicated for metal ions, a more direct role for a metal ion in catalysis has not yet been proven. A minimal natural ribozyme sequence with proficient in vitro self-cleavage activity is about 85 nucleotides long and adopts a secondary structure with four paired regions (P1-P4). The two pairings that define the 5' and 3' boundaries of the ribozyme, P1 and P2, form an atypical pseudoknot arrangement. This secondary structure places a number of constraints on the possible tertiary folding of the sequence, which together with chemical probing, photo-cross-linking, mutagenesis and computer-assisted modeling provides clues to the three-dimensional structure. The data are consistent with a model in which the cleavage site, located at the 5' end of P1, is in close proximity to three single-stranded regions, consisting of a hairpin loop at the end of P3 and two sequences joining P1 to P4 and P4 to P2. While the natural forms of the HDV ribozymes appear to be prone to misfolding, biochemical and mutagenesis studies from a number of laboratories has allowed the production of trans-acting ribozymes and smaller more active cis-acting ribozymes, both of which will aid in further mechanistic and structural studies of this RNA.


Adult size and timing of reproduction in five species of Asobara parasitoid wasps.
The majority of adult parasitoid wasps are unable to synthesize lipids and therefore face a trade-off between the investment of lipids in eggs or in the maintenance of soma. It has been shown that resource allocation should depend on body size in parasitoids. Given that smaller females have shorter expected life times, they should concentrate their reproductive effort into early life. To test this prediction, we investigated the relationship between body size and the timing of egg production in parasitoids. We measured body size, lipid reserves, and reproductive investment (number of eggs, ovigeny index equivalent [OIE] and egg size) at eclosion in five species of Asobara (Hymenoptera: Braconidae) originating from different geographic and climatic environments. Our results show significant interspecific variation in all these traits. A diagnostic test for phylogenetic independence revealed that closely related species did not resemble each other more closely than expected by chance for all traits measured. Lipid reserves scaled positively with body size both between and within species. In agreement with theory, OI correlated negatively with body size both between and within species. Total egg area at eclosion correlated negatively with lipid reserves both between and within species. This indicates the existence of a trade-off between allocation of lipids to current reproduction and survival/future reproduction. With the exception of the most extreme pro-ovigenic species, A. persimilis, we found that pro-ovigeny was compensated for by small egg size. Our results indicate the role of habitats in shaping interspecific variation in resource allocation strategies.


Eltrombopag for the Treatment of Severe Inherited Thrombocytopenia.
Inherited thrombocytopenias correspond to a group of hereditary disorders characterized by a reduced platelet count, platelet dysfunction, and a family history of thrombocytopenia. It is commonly associated with mucocutaneous bleeding. Thrombocytopenia results from mutations in genes involved in megakaryocyte differentiation, platelet formation, and clearance. Here we report on a patient presenting with severe syndromic inherited thrombocytopenia manifesting as spontaneous mucocutaneous bleeds, requiring frequent platelet transfusions. Thrombocytopenia was explained by the presence of 4 mutations in 3 hematopoietic transcription factor genes: FLI1, RUNX1, and ETV6. The patient was successfully treated with high-dose eltrombopag at 150 mg/day, an orally available non-peptide thrombopoietin receptor agonist. Since the start of treatment 23 months ago, the manifestations of bleeding have resolved, and no platelet transfusions or corticosteroids have been required. The patient has no clinical or laboratory evidence of myeloid malignancy so far.


Relationship between Freezing of Gait and Anxiety in Parkinson's Disease Patients: A Systemic Literature Review.
Freezing of gait (FOG) is experienced by a significant number of patients with Parkinson's disease (PD). The pathophysiology of this disabling motor symptom remains unclear, and there are no effective therapies. Anxiety has previously been posited as a contributing factor to gait freezing. There have been few studies directly investigating this topic, and a comprehensive literature review is lacking. The objective of this paper was to systematically review the evidence associating anxiety with the presence, severity, and progression of FOG in PD patients. The PubMed, EMBASE, and PsycINFO databases were searched up to September 19, 2018, for English-language, peer-reviewed articles that explored anxiety and FOG as outcome measures in a PD population base. Review articles, case reports, and articles that assessed gait disorders other than FOG were excluded, yielding a total of 26 articles in the final analysis. Of these 26 studies, 16 had a significant relationship between anxiety outcome measure and either presence or severity of FOG. There was great variability among studies in terms of outcome measures for both FOG and anxiety. Despite this heterogeneity, most studies relate anxiety and FOG. Standardized, high-validity outcome measures of anxiety and FOG are needed. Future exploration should aim to clarify the role of anxiety in FOG as a causal factor, pathophysiological marker, and manifestation of a common pathophysiological process versus a consequence of FOG itself. Clarifying the relationship between anxiety and FOG could reveal anxiety reduction as a therapy for FOG.


[Successful drug therapy in Aspergillus endocarditis].
A 74-year-old man who had a weight loss of 7 kg in three months, with fever up to 38 degrees C and anaemia (Hb 9.4 g/dl) began to have pain and blue discoloration of fingers II-V of the right hand. Echocardiography demonstrated vegetation on the aortic valve cusps and blood culture grew Aspergillus fumigatus, indicating Aspergillus endocarditis. There were no predisposing factors. Valve replacement was contraindicated because of the age of the patient, the presence of peripheral arterial disease, and previous myocardial infarction. Treatment was started with amphotericin B i.v. (dosage increasing to 50 mg daily) and 1.5 g daily of flucytosine by mouth, to a total of 1.1 g amphotericin B and 41.5 g flucytosine in five weeks. During this time there was a gradual decrease in symptoms and the valve vegetations. Nine months later there has been no recurrence.


A238L inhibits NF-ATc2, NF-kappa B, and c-Jun activation through a novel mechanism involving protein kinase C-theta-mediated up-regulation of the amino-terminal transactivation domain of p300.
The transcriptional coactivators CREB-binding protein and p300 regulate inducible transcription in multiple cellular processes and during the establishment of inflammatory and immune response. Several viruses have been shown to interfere with CREB-binding protein/p300 function, modulating their transcriptional activity. In this study, we report that the viral protein A238L interacts with the amino-terminal region of p300, inhibiting the acetylation and transcriptional activation of NF-ATc2, NF-kappaB, and c-Jun in stimulated human T cells. We demonstrate that A238L modulates the autoacetylation of p300 without altering its intrinsic histone acetyl transferase activity. Furthermore, we show that the molecular mechanism of the inhibition executed by the viral protein is conducted through blocking protein kinase C (PKC)-p300 interaction and further acetylation in the amino-terminal transactivation domain of the coactivator, and that Ser(384), within the CH1 domain, is essential for the full transcriptional activation of the coactivator. Moreover, we show that overexpression of an active form of PKC-theta reverts the A238L-mediated inhibition of the transcriptional activity of p300, showing, for the first time, a PKC-theta-mediated up-regulation of the coactivator. These findings provide new strategies to develop therapies potentially useful in the control of disorders related to p300 deregulation.


Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging.
The water extract of Centella asiatica (CAW) improves cognitive and mitochondrial function and activates the nuclear factor erythroid 2-related factor 2 (NRF2) regulated antioxidant response pathway in aged mice. Here we investigate whether NRF2 activation is required for the cognitive and mitochondrial effects of prolonged CAW exposure during aging. Five-month-old NRF2 knockout (NRF2KO) and wild-type mice were treated with CAW for 1, 7, or 13 months. Each cohort underwent cognitive testing and hippocampal mitochondrial analyses. Age-related cognitive decline was accelerated in NRF2KO mice and while CAW treatment improved cognitive performance in wild-type mice, it had no effect on NRF2KO animals. Hippocampal mitochondrial function also declined further with age in NRF2KO mice and greater hippocampal mitochondrial dysfunction was associated with poorer cognitive performance in both genotypes. Long-term CAW treatment did not affect mitochondrial endpoints in animals of either genotype. These data indicate that loss of NRF2 results in accelerated age-related cognitive decline and worsened mitochondrial deficits. NRF2 also appears to be required for the cognitive enhancing effects of CAW during aging.


[Women's body image in three rural areas in Mexico: perception and desire].
To identify how women who live in rural zones perceive their bodies. A group of women between 15 and 60 years of age from three rural zones in Mexico were interviewed and measured. They were questioned as to their body image. There was a decrease in the normality when comparing body mass index (BMI) and self-perception, an increase in terms of malnutrition when comparing BMI and self-perception, and a decrease in perceived overweight among the groups of women from Oaxaca. A desire for being thin was detected among roughly 50%. The issue of body image must be more fully explored in order to incorporate, from another perspective, body issues in food and nutritional studies. Body image is fundamentally a subjective experience and thus must be based on different epistemological and methodological premises.


Functional haematopoietic progenitor cells in the adult human lung.
The bone marrow is classically viewed as the main site of blood cell production in adults, however, rare pools of haematopoietic stem and progenitor cells with self-renewal and differentiation potential have been described in extramedullary organs. The lung is primarily known for its role in gas exchange but has recently been identified as a site of blood (platelet) production in mice. Here, we show that functional haematopoietic precursors reside in the extravascular spaces of the human lung, at a frequency similar to the bone marrow, and are capable of proliferation and engraftment. Comparative transcriptomic profiling of pulmonary and medullary CD34 + haematopoietic progenitor cells revealed organ-specific gene signatures and indicated greater baseline activation of immune, megakaryocyte/platelet and erythroid-related pathways in progenitors from the lung. In the lung, these cells predominately reside in the vascular-rich alveolar interstitium and near macrophages. These results identify the lung as an important niche for uniquely programmed blood stem and progenitor cells with considerable potential to support haematopoiesis in humans.


A laparoscopic radical prostatectomy assisted by the "ZEUS" robotic system: an initial case report.
A 68-year-old man with prostate cancer, T1cN0M0, was treated with laparoscopic radical prostatectomy (LRP) assisted by the ZEUS robotic system. The ZEUS system was utilized only for vesico-urethral anastomosis, one of the most difficult procedures to perform during LRP. We could complete the vesico-urethral anastomosis using the ZEUS system for 100 min without any intraoperative complications. The urethral catheter was removed 7 days after operation. To our knowledge, this is the initial case of robot-assisted radical prostatectomy using the ZEUS system.


Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study.
Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease (AD), and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD. Given this association, we hypothesized that the central nervous system-penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and/or symptomatic therapy for AD, and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid (CSF), neuroimaging, and cognitive biomarkers. Twenty nondiabetic subjects with mild cognitive impairment or mild dementia due to AD were randomized to receive metformin then placebo for 8 weeks each or vice versa. CSF and neuroimaging (Arterial Spin Label MRI) data were collected for biomarker analyses, and cognitive testing was performed. Metformin was found to be safe, well-tolerated, and measureable in CSF at an average steady-state concentration of 95.6 ng/mL. Metformin was associated with improved executive functioning, and trends suggested improvement in learning/memory and attention. No significant changes in cerebral blood flow were observed, though post hoc completer analyses suggested an increase in orbitofrontal cerebral blood flow with metformin exposure. Further study of these findings is warranted.


Efficacy and tolerability of pegylated interferon-α-2a in chronic hepatitis B: a multicenter clinical experience.
Pegylated interferon-α (PEG-IFN) provides potential advantages over nucleos(t)ide analogues in the treatment of chronic hepatitis B (CHB) given its finite course, durability and lack of drug resistance. Much of the evidence is derived from controlled studies and it is unclear whether these results can be replicated in an everyday, non-controlled setting. The aim of this study was to examine the efficacy and tolerability of PEG-IFN-α2A in CHB patients in a clinical setting. Chronic hepatitis B patients treated with PEG-IFN-α2A (180µg/week, 48 weeks) at five tertiary hospitals were retrospectively identified. Baseline demographic and clinical data, on-treatment virological and serological responses and adverse events (AE) were recorded. Treatment outcomes were defined as alanine aminotransferase (ALT) normalization, hepatitis B virus DNA <351 IU/mL and hepatitis B e antigen (HBeAg) seroconversion. Sixty three HBeAg positive patients were identified (65% male, 80% born in Asia, 84% with viral loads > 6log IU/mL, 9.5% advanced fibrosis). Six months after therapy 46% achieved normalization of ALT, 16% had viral loads < 351 IU/mL and 32% achieved HBeAg seroconversion. 29 HBeAg negative patients were treated (75% male, 86% born in Asia, 48% had viral loads > 6log IU/mL, 24% advanced fibrosis). Six months post-treatment, 55% and 36% maintained a normalized ALT and HBV DNA < 351 IU/mL, respectively. Optimal viral suppression was maintained in 50-75% of patients over 2 years of follow up. 6.5% of all patients discontinued therapy due to AEs. In everyday clinical practice PEG-IFN therapy in CHB is well tolerated and can achieve a similar efficacy to that seen in large controlled trials.


Plasmodium chabaudi limits early Nippostrongylus brasiliensis-induced pulmonary immune activation and Th2 polarization in co-infected mice.
Larvae of several common species of parasitic nematodes obligately migrate through, and often damage, host lungs. The larvae induce strong pulmonary Type 2 immune responses, including T-helper (Th)2 cells as well as alternatively activated macrophages (AAMphi) and associated chitinase and Fizz/resistin family members (ChaFFs), which are thought to promote tissue repair processes. Given the prevalence of systemic or lung-resident Type 1-inducing pathogens in geographical areas in which nematodes are endemic, we wished to investigate the impact of concurrent Type 1 responses on the development of these Type 2 responses to nematode larval migration. We therefore infected BALB/c mice with the nematode Nippostrongylus brasiliensis, in the presence or absence of Plasmodium chabaudi chabaudi malaria parasites. Co-infected animals received both infections on the same day, and disease was assessed daily before immunological measurements were taken at 3, 5, 7 or 20 days post-infection. We observed that the nematodes themselves caused transient loss of body mass and red blood cell density, but co-infection then slightly ameliorated the severity of malarial anaemia. We also tracked the development of immune responses in the lung and thoracic lymph node. By the time of onset of the adaptive immune response around 7 days post-infection, malaria co-infection had reduced pulmonary expression of ChaFFs. Assessment of the T cell response demonstrated that the Th2 response to the nematode was also significantly impaired by malaria co-infection. P. c. chabaudi co-infection altered both local and lymph node Type 2 immune activation due to migration of N. brasiliensis larvae. Given recent work from other laboratories showing that N. brasiliensis-induced ChaFFs correlate to the extent of long-term lung damage, our results raise the possibility that co-infection with malaria might alter pulmonary repair processes following nematode migration. Further experimentation in the co-infection model developed here will reveal the longer-term consequences of the presence of both malaria and helminths in the lung.


Structure-based inhibitor discovery against adenylyl cyclase toxins from pathogenic bacteria that cause anthrax and whooping cough.
Edema factor (EF) and CyaA are adenylyl cyclase toxins secreted by pathogenic bacteria that cause anthrax and whooping cough, respectively. Using the structure of the catalytic site of EF, we screened a data base of commercially available, small molecular weight chemicals for those that could specifically inhibit adenylyl cyclase activity of EF. From 24 compounds tested, we have identified one quinazoline compound, ethyl 5-aminopyrazolo[1,5-a]quinazoline-3-carboxylate, that specifically inhibits adenylyl cyclase activity of EF and CyaA with approximately 20 microm Ki. This compound neither affects the activity of host resident adenylyl cyclases type I, II, and V nor exhibits promiscuous inhibition. The compound is a competitive inhibitor, consistent with the prediction that it binds to the adenine portion of the ATP binding site on EF. EF is activated by the host calcium sensor, calmodulin. Surface plasmon resonance spectroscopic analysis shows that this compound does not affect the binding of calmodulin to EF. This compound is dissimilar from a previously described, non-nucleoside inhibitor of host adenylyl cyclase. It may serve as a lead to design antitoxins to address the role of adenylyl cyclase toxins in bacterial pathogenesis and to fight against anthrax and whooping cough.


Family background of children with Down's syndrome and of children with a similar degree of mental retardation.
The families of Down's Syndrome children and another group with a similar degree of retardation were compared using data collected at interview. Differences in social class distribution were explained by the maternal age effect in the Down's group. Divorce was more common in the control group but the quality of marriage in those parents still together and the health of parents were similar. No close associations were found between behaviour disorders in the children and family factors, except that behaviour disorders were likely to be associated with similar disturbance in siblings next in age and to be more common in the less happy marriages.


Plant-aphid interactions with a focus on legumes.
Sap-sucking insects such as aphids cause substantial yield losses in agriculture by draining plant nutrients as well as vectoring viruses. The main method of control in agriculture is through the application of insecticides. However, aphids rapidly evolve mechanisms to detoxify these, so there is a need to develop durable plant resistance to these damaging insect pests. The focus of this review is on aphid interactions with legumes, but work on aphid interactions with other plants, particularly Arabidopsis and tomato is also discussed. This review covers advances on the plant side of the interaction, including the identification of major resistance genes and quantitative trait loci conferring aphid resistance in legumes, basal and resistance gene mediated defence signalling following aphid infestation and the role of specialised metabolites. On the aphid side of the interaction, this review covers what is known about aphid effector proteins and aphid detoxification enzymes. Recent advances in these areas have provided insight into mechanisms underlying resistance to aphids and the strategies used by aphids for successful infestations and have significant impacts for the delivery of durable resistance to aphids in legume crops.


Established thymic epithelial progenitor/stem cell-like cell lines differentiate into mature thymic epithelial cells and support T cell development.
Common thymic epithelial progenitor/stem cells (TEPCs) differentiate into cortical and medullary thymic epithelial cells (TECs), which are required for the development and selection of thymocytes. Mature TEC lines have been widely established. However, the establishment of TEPC lines is rarely reported. Here we describe the establishment of thymic epithelial stomal cell lines, named TSCs, from fetal thymus. TSCs express some of the markers present on tissue progenitor/stem cells such as Sca-1. Gene expression profiling verifies the thymic identity of TSCs. RANK stimulation of these cells induces expression of autoimmune regulator (Aire) and Aire-dependent tissue-restricted antigens (TRAs) in TSCs in vitro. TSCs could be differentiated into medullary thymic epithelial cell-like cells with exogenously expressed NF-κB subunits RelB and p52. Importantly, upon transplantation under the kidney capsules of nude mice, TSCs are able to differentiate into mature TEC-like cells that can support some limited development of T cells in vivo. These findings suggest that the TSC lines we established bear some characteristics of TEPC cells and are able to differentiate into functional TEC-like cells in vitro and in vivo. The cloned TEPC-like cell lines may provide useful tools to study the differentiation of mature TEC cells from precursors.


Seasonal variation in life history traits in two Drosophila species.
Seasonal environmental heterogeneity is cyclic, persistent and geographically widespread. In species that reproduce multiple times annually, environmental changes across seasonal time may create different selection regimes that may shape the population ecology and life history adaptation in these species. Here, we investigate how two closely related species of Drosophila in a temperate orchard respond to environmental changes across seasonal time. Natural populations of Drosophila melanogaster and Drosophila simulans were sampled at four timepoints from June through November to assess seasonal change in fundamental aspects of population dynamics as well as life history traits. D. melanogaster exhibit pronounced change across seasonal time: early in the season, the population is inferred to be uniformly young and potentially represents the early generation following overwintering survivorship. D. melanogaster isofemale lines derived from the early population and reared in a common garden are characterized by high tolerance to a variety of stressors as well as a fast rate of development in the laboratory environment that declines across seasonal time. In contrast, wild D. simulans populations were inferred to be consistently heterogeneous in age distribution across seasonal collections; only starvation tolerance changed predictably over seasonal time in a parallel manner as in D. melanogaster. These results suggest fundamental differences in population and evolutionary dynamics between these two taxa associated with seasonal heterogeneity in environmental parameters and associated selection pressures.


Predicting Participant Compliance With Fitness Tracker Wearing and Ecological Momentary Assessment Protocols in Information Workers: Observational Study.
Studies that use ecological momentary assessments (EMAs) or wearable sensors to track numerous attributes, such as physical activity, sleep, and heart rate, can benefit from reductions in missing data. Maximizing compliance is one method of reducing missing data to increase the return on the heavy investment of time and money into large-scale studies. This paper aims to identify the extent to which compliance can be prospectively predicted from individual attributes and initial compliance. We instrumented 757 information workers with fitness trackers for 1 year and conducted EMAs in the first 56 days of study participation as part of an observational study. Their compliance with the EMA and fitness tracker wearing protocols was analyzed. Overall, 31 individual characteristics (eg, demographics and personalities) and behavioral variables (eg, early compliance and study portal use) were considered, and 14 variables were selected to create beta regression models for predicting compliance with EMAs 56 days out and wearable compliance 1 year out. We surveyed study participation and correlated the results with compliance. Our modeling indicates that 16% and 25% of the variance in EMA compliance and wearable compliance, respectively, could be explained through a survey of demographics and personality in a held-out sample. The likelihood of higher EMA and wearable compliance was associated with being older (EMA: odds ratio [OR] 1.02, 95% CI 1.00-1.03; wearable: OR 1.02, 95% CI 1.01-1.04), speaking English as a first language (EMA: OR 1.38, 95% CI 1.05-1.80; wearable: OR 1.39, 95% CI 1.05-1.85), having had a wearable before joining the study (EMA: OR 1.25, 95% CI 1.04-1.51; wearable: OR 1.50, 95% CI 1.23-1.83), and exhibiting conscientiousness (EMA: OR 1.25, 95% CI 1.04-1.51; wearable: OR 1.34, 95% CI 1.14-1.58). Compliance was negatively associated with exhibiting extraversion (EMA: OR 0.74, 95% CI 0.64-0.85; wearable: OR 0.67, 95% CI 0.57-0.78) and having a supervisory role (EMA: OR 0.65, 95% CI 0.54-0.79; wearable: OR 0.66, 95% CI 0.54-0.81). Furthermore, higher wearable compliance was negatively associated with agreeableness (OR 0.68, 95% CI 0.56-0.83) and neuroticism (OR 0.85, 95% CI 0.73-0.98). Compliance in the second week of the study could help explain more variance; 62% and 66% of the variance in EMA compliance and wearable compliance, respectively, was explained. Finally, compliance correlated with participants' self-reflection on the ease of participation, usefulness of our compliance portal, timely resolution of issues, and compensation adequacy, suggesting that these are avenues for improving compliance. We recommend conducting an initial 2-week pilot to measure trait-like compliance and identify participants at risk of long-term noncompliance, performing oversampling based on participants' individual characteristics to avoid introducing bias in the sample when excluding data based on noncompliance, using an issue tracking portal, and providing special care in troubleshooting to help participants maintain compliance.


Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B.
Lamivudine and interferon have been widely used for the treatment of patients with chronic HBV infection. Serum HBV RNA is detected during lamivudine therapy as a consequence of interrupted reverse transcription and because RNA replicative intermediates are unaffected by the drug. In this study, we aimed to determine the detectability of serum HBV RNA during sequential combination therapy of interferon and lamivudine. HBV DNA and RNA in serum samples were quantified by reverse transcription of HBV nucleic acid extract and real-time PCR. Samples were analysed every 2 weeks to 3 months from three groups of patients: 10 male patients treated with nucleoside analogue monotherapy for 44-48 weeks (5 with lamivudine and 5 with entecavir), 6 males on sequential interferon and lamivudine combination therapy, and 3 males on lamivudine monotherapy for 20-24 weeks. HBV RNA was not detectable in any patients before treatment, but became detectable in 15 during antiviral treatment. Among the three groups, pre-treatment HBV DNA (8.1 +/-2.4 versus 7.7 +/-1.4 versus 5.1 +/-0.3 log(10) copies/ml; P=0.06), treatment and follow-up durations (45.5 +/-2.0 versus 49.7 +/-5.6 versus 48.7 +/-6.4 weeks; P=0.32) were comparable. HBV RNA was detectable at the end of treatment or follow-up in all patients with monotherapy, but in none of those with sequential combination therapy (100% versus 0%; P<0.001). Compared with lamivudine therapy with detectable serum HBV RNA in patients with chronic HBV infection, interferon treatment might reduce HBV DNA replication through the inhibition of HBV RNA replicative intermediates, resulting in the loss of serum HBV RNA.


Conducting polyaniline filaments in a mesoporous channel host.
Conducting filaments of polyaniline have been prepared in the 3-nanometer-wide hexagonal channel system of the aluminosilicate MCM-41. Adsorption of aniline vapor into the dehydrated host, followed by reaction with peroxydisulfate, leads to encapsulated polyaniline filaments. Spectroscopic data show that the filaments are in the protonated emeraldine salt form, and chromatography indicates chain lengths of several hundred aniline rings. The filaments have significant conductivity while encapsulated in the channels, as measured by microwave absorption at 2.6 gigahertz. This demonstration of conjugated polymers with mobile charge carriers in nanometer channels represents a step toward the design of nanometer electronic devices.


[Digital subtraction dacryocystography and sialography].
Fourteen examinations of the tear ducts and 21 sialograms were performed using digital subtraction and conventional techniques. In nine of the former and 15 of the latter, digital subtraction produced better results, in the remainder conventional technique was equally good. The advantages of digital subtraction are due to the removal of superimposed structures of the skull. Dose measurements at the level of the lens of the eye showed a greatly reduced radiation dose when using digital subtraction, as compared with conventional dacryocystography. Digital subtraction techniques with pulsed radiation and the ability to perform pixel shift is an optimal method for performing radiological examinations of the tear ducts and salivary glands.


G protein-coupled receptors go extracellular: RhoA integrates the integrins.
The identification of downstream effectors of G protein-coupled receptors (GPCRs) is critical for understanding the interactions between signaling cascades and for developing new pharmacological approaches for controlling GPCR-mediated responses. RhoA is a small G protein that serves as a proximal downstream effector of numerous GPCRs and regulates a variety of basic cell functions, including migration, survival, and proliferation. Intriguingly, GPCR ligands such as thrombin, sphingosine-1-phosphate, and lysophosphatidic acid, which signal through G(12/13) and activate RhoA, have recently been shown to induce the expression of the extracellular matrix protein Cyr61 (i.e., CCN1). Cyr61 is secreted and interacts with cell surface integrins to activate kinase and transcriptional cascades that are also known to contribute to cell migration, survival, and proliferation. The GPCR/RhoA/Cyr61/integrin pathway defines a novel convergence mechanism for integrating GPCR-and integrin-dependent signaling cascades that may contribute to sustained and pathophysiological responses to GPCR activation.


CREB-binding protein modulates repeat instability in a Drosophila model for polyQ disease.
Although expansion of trinucleotide repeats accounts for over 30 human diseases, mechanisms of repeat instability remain poorly understood. We show that a Drosophila model for the CAG/polyglutamine (polyQ) disease spinocerebellar ataxia type 3 recapitulates key features of human CAG-repeat instability, including large repeat changes and strong expansion bias. Instability is dramatically enhanced by transcription and modulated by nuclear excision repair and a regulator of DNA repair adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB)-binding protein-a histone acetyltransferase (HAT) whose decreased activity contributes to polyQ disease. Pharmacological treatment to normalize acetylation suppressed instability. Thus, toxic consequences of pathogenic polyQ protein may include enhancing repeat instability.


Regulatory roles of ACSL5 in the anti-tumor function of palmitic acid (C16:0) via the ERK signaling pathway.
Previous studies have highlighted the susceptibility of cancer to perturbations in lipid metabolism. In particular, C16:0 has emerged as a promising novel treatment for hepatocellular carcinoma. In our study, we investigated the levels of C16:0 in the serum of non-small lung cancer patients were significant downregulation compared to healthy individuals (n=10; p<0.05). Moreover, our in vitro experiments using A549 cells demonstrated that C16:0 effectively inhibited proliferation, apoptosis, migration, and invasion. Despite these promising results, its pathogenesis remains poorly understood. CCK-8 assay, annexin V-FITC/PI double staining assay, wound healing assay and transwell assay were performed to evaluate the effects of C16:0, on proliferation, apoptosis, migration and invasion of A549 cells. RNA sequencing was used to identify essential factors involved in C16:0-growth inhibition in lung cancer. Further, the expression levels of related gene and proteins were detected by quantitative RT-PCR and Western blotting. Mouse NSCLC subcutaneous xenograft tumor model was established, and gastric lavage was given with C16:0. Tumor volume assay and hematoxylin-eosin staining were used to detect tumor growth in vivo. Our analysis revealed a significant upregulation of ACSL5 and its associated proteins in C16:0-treated A549 cells compared to the control group both in vivo and in vitro. Moreover, the knockdown of ACSL5 reversed the anti-tumor effect, resulting in an increased rate of the malignant phenotype mentioned above. Additionally, the expression of phosphorylated ERK protein was significantly inhibited with increasing concentrations of C16:0 in A549 cells. These results reveal for the first time that C16:0, as a novel target, regulates ACLS5 through the ERK signaling pathway, to inhibit the proliferation and apoptosis and inhibits cell migration and invasion of NSCLC. These findings may lead to the development of a novel therapeutic approach for non-small lung cancer.


Impact of Prolonged Anticoagulation with Rivaroxaban on Provoked Venous Thromboembolism Recurrence: IMPROVE-VTE.
We sought to evaluate the real-world effectiveness and safety of prolonged anticoagulation with rivaroxaban following a provoked venous thromboembolism. Using US MarketScan claims from November 2012 to March 2017, we identified adults with ≥1 primary hospitalization or emergency department diagnosis code for venous thromboembolism, a provoking (major or minor, persistent or transient) risk factor, at least 3 months of continuous rivaroxaban treatment, and ≥12 months of continuous insurance benefits prior to their qualifying venous thromboembolism. Patients were categorized as either continuing rivaroxaban or discontinuing anticoagulation (no anticoagulation or nonaspirin antiplatelet agents but may have received aspirin) after the initial 3 months of rivaroxaban treatment (index date). Differences in baseline covariates between cohorts were adjusted for using inverse probability-of-treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Twelve month incidences of recurrent venous thromboembolism or major bleeding were compared between cohorts using Cox regression (according to an intention-to-treat methodology) and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Among patients experiencing a provoked venous thromboembolism and treated with rivaroxaban for the first 3 months (N=4,990), continued rivaroxaban use beyond 3 months (median [25%, 75% range duration of additional rivaroxaban use = 3 [2, 5] months) was associated with a 44% (95% CI of 9%-66%) lower hazard of recurrent venous thromboembolism without altering major bleeding risk [HR of 0.87, 95% CI of 0.51-1.49] versus anticoagulation discontinuation (with or without aspirin use). Our study suggests continuing rivaroxaban after the initial 3 month period was associated with a decreased risk of recurrent venous thromboembolism. The observed reduction in recurrent venous thromboembolism with prolonged rivaroxaban use was not associated with a significant change in major bleeding risk.


Unidirectional edge states in topological honeycomb-lattice membrane photonic crystals.
Photonic analogs of electronic systems with topologically non-trivial behavior such as unidirectional scatter-free propagation has tremendous potential for transforming photonic systems. Like in electronics topological behavior can be observed in photonics for systems either preserving time-reversal (TR) symmetry or explicitly breaking it. TR symmetry breaking requires magneto-optic photonics crystals (PC) or generation of synthetic gauge fields. For on-chip photonics that operate at optical frequencies both are quite challenging because of poor magneto-optic response of materials or substantial nanofabrication challenges in generating synthetic gauge fields. A recent work by Ma, et al. [Phys. Rev. Lett.114, 223901 (2015)] based on preserving pseudo TR symmetry offers a promising design scheme for observing unidirectional edge states in a modified honeycomb photonic crystal (PC) lattice of circular rods that offers encouraging alternatives. Here we propose through bandstructure calculations the inverse system of modified honeycomb PC of circular holes in a dielectric membrane which is more attractive from fabrication standpoint for on-chip applications. We observe trivial and non-trivial bandgaps as well as unidirectional edge states of opposite helicity propagating in opposite directions at the interface of a trivial and non-trivial PC structures. Around 1550nm operating wavelength ~55nm of bandwidth is possible for practicable values of design parameters (lattice constant, hole radii, membrane thickness, scaling factor etc.) and robust to reasonable variations in those parameters.


[Facial profile improving interventions using tissue expansion techniques].
If there is a lack of soft tissue in the face, no matter what the cause, the reconstruction should be performed using tissue from neighboring areas because tissue in the same aesthetic and functional area guarantees the best results. Two methods of dilation are described for such skin expansion explained by examples, and substantiated by statistics: (1) dilation with the aid of osteosynthesis plates; and (2) dilation with tissue expansion. To make an objective evaluation, only cases where considered that were finished 3 years ago.


Virtual objects in large scale health information systems.
This paper presents an approach of data integration in Health Virtual Organization (HVO). It targets large scale contexts where high distribution and autonomy of sources produce complex integration scenarios. The principle is to provide a high conceptual level composed of Virtual Data Objects (VDO) that can be queried independently of the data sources that are behind them and without requiring technical skills. The approach uses a mediation architecture improved to be viable in large scale contexts through the concept of query cartography and applying a semantic caching strategy specific for VDOs that reduces network latency.


Acculturation and eating disorders in Asian and Caucasian Australian university students.
This study aimed to compare the attitudes and psychopathology of eating disorders of Asian and Caucasian university students using a survey method. The study also investigated the relationship between acculturation, attitudes and psychopathology of eating disorders in sub-groups of Asian girls. There were 130 Asian and 110 Caucasian adolescent girls, aged 18-24 who were screened using the Eating Attitudes Test (EAT-26), the Eating Disorders Inventory (EDI-2) and an Acculturation Index. The Asian group did not have higher mean EAT score than the Caucasian group, but had higher mean score in some sub-scales of the EDI-2. Eating disordered attitudes and psychopathology was not significantly different in the low compared to the high accultured Asian girls. This study suggests that Asian and Caucasian university students in Western Australia are equally susceptible to eating disorders, and that the level of acculturation does not modify the susceptibility of Asian students for eating disorders.


N-methyl-D-aspartate receptor antagonism has differential effects on alcohol craving and drinking in heavy drinkers.
The objective of this study was to determine the effects of the N-methyl-d-aspartate (NMDA) receptor antagonist, memantine (0, 20, 40 mg/d), upon alcohol drinking and craving in heavy drinkers with or without a family history (FH) of alcoholism, and to explore the modulatory influence of the presence of impulsivity on these outcomes. Ninety-two, nontreatment-seeking, heavy drinkers received memantine or placebo for 8 days. On the eighth day, they received a priming dose of alcohol followed by a 3-hour period of alcohol access. Memantine at a dose of 20 mg reduced alcohol craving but did not influence alcohol drinking. No effects of FH were observed. In participants with higher baseline levels of impulsivity, 40 mg of memantine reduced alcohol craving but increased alcohol drinking and alcohol-induced stimulation. NMDA receptor signaling may play divergent roles in mediating alcohol cue-induced craving and alcohol drinking in heavy drinkers. The potential efficacy of memantine as monotherapy for alcohol use disorders may be limited by its tendency to disinhibit drinking in some individuals.


Indirect immunofluorescence in toxoplasmosis: frequency, nature and specificity of polar staining.
In the indirect immunofluorescence test ant the Remington test for Toxoplasmosis of some sera, a polar fluorescence of the parasite has been observed. This "Polar Factor" is not observed in umbilical cord blood and in sera of children less than 6 months old, but has a relative high frequency in sera of adults. The detection of the factor depends on the nature of the used antigen. With sucrose gradient centrifugation, anti-IgM immunofluorescence, 2-mercaptoethanol-treatment and selective adsorption of sera, we could demonstrate that this factor is a non-specific IgM.


Challenges in Implementing Low-Latency Holographic-Type Communication Systems.
Holographic-type communication (HTC) permits new levels of engagement between remote users. It is anticipated that it will give a very immersive experience while enhancing the sense of spatial co-presence. In addition to the newly revealed advantages, however, stringent system requirements are imposed, such as multi-sensory and multi-dimensional data capture and reproduction, ultra-lightweight processing, ultra-low-latency transmission, realistic avatar embodiment conveying gestures and facial expressions, support for an arbitrary number of participants, etc. In this paper, we review the current limitations to the HTC system implementation and systemize the main challenges into a few major groups. Furthermore, we propose a conceptual framework for the realization of an HTC system that will guarantee the desired low-latency transmission, lightweight processing, and ease of scalability, all accompanied with a higher level of realism in human body appearance and dynamics.


Higher leptin levels in Asian Indians than Creoles and Europids: a potential explanation for increased metabolic risk.
Leptin predicts cardiovascular diseases and type 2 diabetes, diseases to which Asian Indians are highly susceptible. As a risk marker, leptin's intra-individual and seasonal stability is unstudied and only small studies have compared leptin levels in Asian Indians with other populations. The aim of this study was to explore ethnicity related differences in leptin levels and its intra-individual and seasonal stability. Leptin and anthropometric data from the northern Sweden MONICA (3513 Europids) and the Mauritius Non-communicable Disease (2480 Asian Indians and Creoles) studies were used. In both studies men and women, 25- to 74-year old, participated in both an initial population survey and a follow-up after 5-13 years. For the analysis of seasonal leptin variation, a subset of 1780 participants, 30- to 60-year old, in the Västerbotten Intervention Project was used. Asian Indian men and women had higher levels of leptin, leptin per body mass index (BMI) unit (leptin/BMI) or per cm in waist circumference (WC; leptin/waist) than Creoles and Europids when adjusted for BMI (all P<0.0005) or WC (all P<0.005). In men, Creoles had higher leptin, leptin/BMI and leptin/waist than Europids when adjusted for BMI or WC (all P<0.0005). In women, Creoles had higher leptin/BMI and leptin/waist than Europids only when adjusted for WC (P<0.0005). Asian Indian ethnicity in both sexes, and Creole ethnicity in men, was independently associated with high leptin levels. The intra-class correlation for leptin was similar (0.6-0.7), independently of sex, ethnicity or follow-up time. No seasonal variation in leptin levels was seen. Asian Indians have higher levels of leptin, leptin/BMI and leptin/waist than Creoles and Europids. Leptin has a high intra-individual stability and seasonal leptin variation does not appear to explain the ethnic differences observed here.


Scar shape analysis and simulated electrical instabilities in a non-ischemic dilated cardiomyopathy patient cohort.
This paper presents a morphological analysis of fibrotic scarring in non-ischemic dilated cardiomyopathy, and its relationship to electrical instabilities which underlie reentrant arrhythmias. Two dimensional electrophysiological simulation models were constructed from a set of 699 late gadolinium enhanced cardiac magnetic resonance images originating from 157 patients. Areas of late gadolinium enhancement (LGE) in each image were assigned one of 10 possible microstructures, which modelled the details of fibrotic scarring an order of magnitude below the MRI scan resolution. A simulated programmed electrical stimulation protocol tested each model for the possibility of generating either a transmural block or a transmural reentry. The outcomes of the simulations were compared against morphological LGE features extracted from the images. Models which blocked or reentered, grouped by microstructure, were significantly different from one another in myocardial-LGE interface length, number of components and entropy, but not in relative area and transmurality. With an unknown microstructure, transmurality alone was the best predictor of block, whereas a combination of interface length, transmurality and number of components was the best predictor of reentry in linear discriminant analysis.


Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene.
To produce disease, viruses must enter the host, multiply locally in host tissues, spread from the site of entry, and overcome or evade host immune responses. At each stage in this infectious process, specific microbial and host genes determine the ultimate virulence of the virus. Genetic approaches have identified many viral genes that play critical roles in virulence and are presumed to target specific components of the host innate and acquired immune response. However, formal proof that a virulence gene targets a specific protein in a host pathway in vivo has not been obtained. Based on cell culture studies, it has been proposed that the herpes simplex virus type 1 gene ICP34.5 (ICP, infected cell protein) enhances neurovirulence by negating antiviral functions of the IFN-inducible double-stranded RNA-dependent protein kinase R or PKR [Chou, J., Chen, J.J., Gross, M. & Roizman, B. (1995) Proc. Natl. Acad. Sci. USA 92, 10516-10520]. Herein, we show that a virus that has been attenuated by deletion of ICP34.5 exhibits wild-type replication and virulence in a host from which the PKR gene has been deleted. We show that restoration of virulence is specific to ICP34.5 and PKR by using additional host and viral mutants. The use of recombinant viruses to infect animals with null mutations in host defense genes provides a formal genetic test for identifying in vivo mechanisms and targets of microbial virulence genes.


A new multiresponsive drug delivery system using smart nanogels.
This paper addresses the synthesis and characterization of a novel temperature- and pH-responsive nanogel system based on poly(vinylcaprolactam-co-2-dimethylaminoethyl methacrylate) [P(VCL-co-DMAEMA)] by using a surfactant-free emulsion polymerization procedure for the multiresponsive drug delivery of hydrophobic drugs. The effects of solvent, monomer, pH, and temperature were studied to tailor the average particle hydrodynamic diameters and the polydispersity index of the final particles. According to dynamic light-scattering measurements, the obtained nanogels show a narrow particle-size distribution and their hydrodynamic diameters can be varied from 81 to 368 nm. The nanogels display a re-entrant phase-transition state, and the equilibrium volume swelling ratio of the nanogels decreases drastically down to 47 °C and then increases up to 65 °C. In addition, the nanogels show pH-dependent behavior. They exhibit a maximum size at pH 5.0. Rhodamine B (RhB) was chosen as a model compound for drug loading and release studies from P(VCL-co-DMAEMA) on the basis of particles in different phosphate buffer solutions at different temperatures. The temperature/pH-dependent cumulative release and ultrasound-enhanced pulsatile release properties were investigated for RhB-loaded nanogels for long-term and one-shot delivery. The nanogels display efficient delivery for both long-term and one-shot delivery systems. We provide here a proof of concept for the novel use of multiresponsive nanogels having an overall size below 200 nm as a cargo system for hydrophobic drugs and for controlled release mediated by temperature/pH and ultrasound.


The Development of Causal Structure without a Language Model.
Across a diverse range of languages, children proceed through similar stages in their production of causal language: their initial verbs lack internal causal structure, followed by a period during which they produce causative overgeneralizations, indicating knowledge of a productive causative rule. We asked in this study whether a child not exposed to structured linguistic input could create linguistic devices for encoding causation and, if so, whether the emergence of this causal language would follow a trajectory similar to the one observed for children learning language from linguistic input. We show that the child in our study did develop causation-encoding morphology, but only after initially using verbs that lacked internal causal structure. These results suggest that the ability to encode causation linguistically can emerge in the absence of a language model, and that exposure to linguistic input is not the only factor guiding children from one stage to the next in their production of causal language.


Iatrogenic vitamin D toxicity in an infant--a case report and review of literature.
Public concern over vitamin D deficiency has led to widespread use of over the counter (OTC) vitamin D (-D3 or -D2) supplements, containing up to 10,000 IU/unit dose (400 IU=10μg). Overzealous use of such supplements can cause hypercalcemia due to vitamin D toxicity. Infants are particularly vulnerable to toxicity associated with vitamin D overdose. OTC supplements are not subject to stringent quality control regulations from FDA and high degree of variability in vitamin D content in OTC pills has been demonstrated. Other etiologies of vitamin D induced hypercalcemia include hyperparathyroidism, granulomatous malignancies like sarcoidosis and mutations in the CYP24A1 gene. The differential diagnosis of hypercalcemia should include iatrogenic and genetic etiologies. C24-hydroxylation and C3-epimerization are two important biochemical pathways via which 25-hydroxyvitamin D3 (25(OH)D3) is converted to its metabolites, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or its C3 epimer, 3-epi-25-OH-D3 respectively. Mutations in the CYP24A1 gene cause reduced serum 24,25(OH)2D3 to 25(OH)D3 ratio (<0.02), elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D3), hypercalcemia, hypercalciuria and nephrolithiasis. Studies in infants have shown that 3-epi-25(OH)D3 can contribute 9-61.1% of the total 25(OH)D3. Therefore, measurements of parathyroid hormone (PTH) and vitamin D metabolites 25(OH)D3, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3 are useful to investigate whether the underlying cause of vitamin D toxicity is iatrogenic versus genetic. Here we report a case of vitamin D3 associated toxicity in a 4-month-old female who was exclusively breast-fed and received an oral liquid vitamin D3 supplement at a dose significantly higher than recommended on the label. The vitamin D3 content of the supplement was threefold higher (6000 IU of D/drop) than listed on the label (2000 IU). Due to overdosing and higher vitamin D3 content, the infant received ∼50,000 IU/day for two months resulting in severe hypercalcemia, hypercalciuria and nephrocalcinosis. We also review the relevant literature on vitamin D3 toxicity in this report.


Prevention of deformity during limb lengthening.
Deformity occurs frequently at the site of distraction during leg lengthening and can add to disability. The elastic and nonelastic displacements have been measured in a model that simulates leg lengthening in the laboratory. Measurements have been made for different fixator systems. The angulation in the vertical plane that occurs during leg lengthening is minimized if the distance between the bone and the fixator bar is kept as small as possible, if three screws are inserted in the proximal and distal bone fragments, and if the peak loads on the fixator are reduced by adjusting the rhythm of distraction. However, even if these precautions are taken, the results show that some fixators designed for leg lengthening will fail and lead to deformity at the osteotomy site. This may occur under the repeated cycles of high loads associated with the rises in soft tissue tension that are known to occur in certain groups of patients. This study suggests that deformity can be prevented by the proper selection of a suitable frame and the adjustment of its configuration to meet the loading requirements.


Difference in Practice Patterns in the Management of Endometrial Cancer: A Survey of the Members of 4 East Asian Gynecologic Oncology Groups.
The aim of this article was to identify current practice patterns of care in the surgical and adjuvant management of endometrial cancer in East Asia (Korea, Japan, China, and Taiwan) METHODS: A validated 20-item questionnaire on surgical and adjuvant procedures for endometrial cancer was sent to active members of the Gynecologic Oncology Group from 4 East Asian countries. Data were collected using an Internet survey database. A total of 376 members from Korea (n = 108), Japan (n = 140), China (n = 51), and Taiwan (n = 77) responded to the survey. With respect to early-stage endometrial cancer, laparotomy (57.7%) was the most preferred mode of surgery in Japan, whereas laparoscopy was the most common in the remaining 3 countries. For patients with presumed stage IA/G1 disease, approximately 65% of respondents favored systematic lymphadenectomy. For patients with presumed stage IB disease, most respondents stated that systematic lymphadenectomy should be performed (92.6% for stage IBG1, 95.8% for stage IBG3). Meanwhile, the extents of lymphadenectomy differed among countries (P < 0.001). Considerable agreement was noted between countries regarding indications for adjuvant therapy for stage IIIA or IIIC1 disease, whereas the preferred options for adjuvant therapy varied according to country (P < 0.001). Specifically, chemotherapy was the most common selection option in Japan, whereas concurrent chemoradiotherapy was preferred in the other countries. Considerable agreement was identified with respect to the necessity for lymphadenectomy for surgical staging and the indications for adjuvant therapy. However, extents of surgery and preferred adjuvant treatment options for endometrial cancer varied widely between countries.


Caregiving and elderly health in Mexico.
Using the National Mexican Health and Aging Study panel dataset, the authors estimate the effect of having informal care on the probability of dying and on the change in elderly health over a two-year period. Three measures of functional health were used: self-reported health, activities of daily living, and instrumental activities of daily living. We develop an empirical strategy that relies on the panel structure of the dataset to sort out the possible correlation between unobservable characteristics that affect both elderly health and an individual's decision to provide informal care. Our findings suggest that informal care provided by daughters reduces the probability of dying. In addition, informal care provided by daughters reduces the probability of having a decline in activities of daily living and instrumental activities of daily living, while it has no effect on the observed changes in self-reported health status. The protective effect of informal care provided by sons is not statistically significant for any health outcomes. A discussion of the policy options to increase elderly health and to improve the role of caregivers is included.


Direct observation of aqueous secondary organic aerosol from biomass-burning emissions.
The mechanisms leading to the formation of secondary organic aerosol (SOA) are an important subject of ongoing research for both air quality and climate. Recent laboratory experiments suggest that reactions taking place in the atmospheric liquid phase represent a potentially significant source of SOA mass. Here, we report direct ambient observations of SOA mass formation from processing of biomass-burning emissions in the aqueous phase. Aqueous SOA (aqSOA) formation is observed both in fog water and in wet aerosol. The aqSOA from biomass burning contributes to the "brown" carbon (BrC) budget and exhibits light absorption wavelength dependence close to the upper bound of the values observed in laboratory experiments for fresh and processed biomass-burning emissions. We estimate that the aqSOA from residential wood combustion can account for up to 0.1-0.5 Tg of organic aerosol (OA) per y in Europe, equivalent to 4-20% of the total OA emissions. Our findings highlight the importance of aqSOA from anthropogenic emissions on air quality and climate.


Pharmacological interventions for sleepiness and sleep disturbances caused by shift work.
Are pharmacological interventions associated with better-quality sleep and alertness in shift workers? Low-quality evidence shows that melatonin is associated with 24 minutes longer daytime sleep after the shift but not with faster falling asleep compared with placebo. There is no association between hypnotics, such as zopiclone, and sleep outcomes, alertness, or harms. The alertness-promoting medications armodafinil and modafinil are associated with improved alertness during shift work but are also associated with headache and nausea.


Successful heparin desensitization after anaphylactic shock due to heparin.
A successful desensitization protocol in a patient with low molecular weight heparin induced anaphylactic reaction is being presented. A 72-years-old patient who was known to have multiple drug allergies and asthma was admitted with acute renal insufficiency. She had an anaphylactic reaction with a low molecular weight heparin during a hemodialysis session. Peritoneal dialysis was not feasible. Anticoagulation with warfarin was not considered appropriate; alternative anticoagulants were not available. Therefore a desensitization protocol was planned and applied, comprising of IV administration of diluted heparin by gradually increasing doses (0.1 to 5000 units), at 15 minute intervals, completing 8 hours before the procedure. By this way, IV heparin could be administered during the subsequent hemodialysis sessions with no reactions. The Naranjo probability scale revealed a probable adverse reaction associated with nadroparin for this patient. Anaphylactic reaction to low molecular weight heparins is reported rarely in the literature. To the best of our knowledge, this is the third case of successful heparin desensitization. When other anticoagulants are not available and anticoagulation is indispensible, heparin desensitization can be an option.


A survey of United States periodontists' knowledge, attitudes, and behaviors related to tobacco-cessation interventions.
Because of the clear causal relationship between smoking and periodontal disease, and the negative effect of smoking on wound healing, it is of great importance to evaluate the tobacco-cessation interventions provided by periodontal practices. The use of tobacco-cessation interventions in clinical practice can be measured by whether the practitioner uses any of the "5 A's" defined by the 2008 United States Public Health Services Clinical Practice Guideline. Surveys were mailed to 1,000 active members of the American Academy of Periodontology. The surveys assessed the periodontists' demographic information, educational and professional background, knowledge and attitudes about tobacco cessation, and use of interventions in the daily practice of periodontics. Data were collected from 231 periodontists via a self-administered survey. Most (92%) believed that tobacco cessation is a responsibility of the dental profession. A pattern of declining levels of involvement was seen as the providers moved through the suggested "5 A's" for promoting tobacco cessation. Providers with formal tobacco-cessation training were more likely to perform interventions. The primary perceived barriers to providing tobacco-cessation interventions were low patient acceptance of treatment, lack of time, and lack of training. The findings of this study indicate that periodontists believe that tobacco-cessation interventions are a responsibility of the dental profession; however, because of several perceived barriers, reported rates of comprehensive tobacco interventions in periodontal practices are low.