Managing Carious Lesions: Consensus Recommendations on Carious Tissue Removal.
The International Caries Consensus Collaboration undertook a consensus process and here presents clinical recommendations for carious tissue removal and managing cavitated carious lesions, including restoration, based on texture of demineralized dentine. Dentists should manage the disease dental caries and control activity of existing cavitated lesions to preserve hard tissues and retain teeth long-term. Entering the restorative cycle should be avoided as far as possible. Controlling the disease in cavitated carious lesions should be attempted using methods which are aimed at biofilm removal or control first. Only when cavitated carious lesions either are noncleansable or can no longer be sealed are restorative interventions indicated. When a restoration is indicated, the priorities are as follows: preserving healthy and remineralizable tissue, achieving a restorative seal, maintaining pulpal health, and maximizing restoration success. Carious tissue is removed purely to create conditions for long-lasting restorations. Bacterially contaminated or demineralized tissues close to the pulp do not need to be removed. In deeper lesions in teeth with sensible (vital) pulps, preserving pulpal health should be prioritized, while in shallow or moderately deep lesions, restoration longevity becomes more important. For teeth with shallow or moderately deep cavitated lesions, carious tissue removal is performed according toselective removal to firm dentine.In deep cavitated lesions in primary or permanent teeth,selective removal to soft dentineshould be performed, although in permanent teeth,stepwise removalis an option. The evidence and, therefore, these recommendations support less invasive carious lesion management, delaying entry to, and slowing down, the restorative cycle by preserving tooth tissue and retaining teeth long-term.


Leptospira infection and shedding in cats in Thailand.
In Thailand, leptospirosis is considered an emerging disease in humans and animals. Many species can shed pathogenic Leptospira, including domestic cats (felis catus), which might be able to pose a risk to humans. There are no studies on Leptospira infections in cats in Thailand, but in other countries, it was demonstrated that cats can shed pathogenic Leptospira with high prevalences. The aims of this study were to evaluate whether outdoor cats in Thailand shed pathogenic Leptospira in their urine, and to determine antibody prevalence and risk factors associated with Leptospira infection. Two hundred and sixty outdoor cats were prospectively recruited. Urine samples were tested by real-time PCR targeting the lipL32 gene of pathogenic Leptospira. Urine was additionally cultured for 6 months in Ellinghausen-McCullough-Johnson-Harris medium to grow Leptospira. Antibodies against 24 serovars (Anhoa, Australis, Autumnalis, Ballum, Bataviae, Bratislava, Broomi, Canicola, Celledoni, Copenhageni, Coxi, Cynopteri, Djasiman, Grippotyphosa, Haemolytica, Icterohaemorrhagiae, Khorat, Paidja, Patoc, Pomona, Pyrogenes, Rachmati, Saxkoebing, Sejroe) belonging to 16 serogroups were determined using microscopic agglutination tests. Risk factors were analysed by Fisher's exact test. Urine samples of 2/260 cats (0.8%; 95% confidence interval (CI): 0.1%-2.8%) were PCR-positive, but none of the 260 urine samples were culture positive. Leptospira antibodies were detected in 14/260 cats (5.4%; 95% CI: 3.0%-8.6%) with titers ranging from 1:20 to 1:160 (serovars: Anhoa, Autumnalis, Celledoni, Copenhageni, Djasiman, Icterohaemorrhagiae, Patoc). Cats aged ≥4 years were significantly more often infected with Leptospira than younger cats. No other significant risk factors were found. In conclusion, outdoor cats in Thailand can shed DNA and, possibly, viable, pathogenic Leptospira in their urine, although at a much lower prevalence than expected when compared to countries with similar climate. Thus, cats can be a potential source of infection for people. Further studies are needed to determine the role of cats in transmitting this zoonotic disease in Thailand.


Double-wall carbon nanotube-porphyrin supramolecular hybrid: synthesis and photophysical studies.
Double-wall carbon nanotubes (DWCNTs) with pyridyl units covalently attached to the external wall through isoxazolino linkers and carboxylic groups that have been esterified by pentyl chains are synthesized. The properties of these modified DWCNTs are then compared with an analogous sample based on single-wall carbon nanotubes (SWCNTs). Raman spectroscopy shows the presence of characteristic radial breathing mode vibrations, confirming that the samples partly retain the integrity of the nanotubes in the case of DWCNTs, including the internal and external nanotubes. Quantification of the pyridyl content for both samples (DWCNT and SWCNT derivatives) is based on X-ray photoelectron spectroscopy and thermogravimetric profiles, showing very similar substituent load. Both pyridyl-containing nanotubes (DWCNTs and SWCNTs) form a complex with zinc porphyrin (ZnP), as evidenced by the presence of two isosbestic points in the absorption spectra of the porphyrin upon addition of the pyridyl-functionalized nanotubes. Supramolecular complexes based on pyridyl-substituted DWCNTs and SWCNTs quench the emission and the triplet excited state identically, through an energy-transfer mechanism based on pre-assembly of the ground state. Thus, the presence of the intact inner wall in DWCNTs does not influence the quenching behavior, with respect to SWCNTs, for energy-transfer quenching with excited ZnP. These results sharply contrast with previous ones referring to electron-transfer quenching, in which the double-wall morphology of the nanotubes has been shown to considerably reduce the lifetime of charge separation, owing to faster electron mobility in DWCNTs compared to SWCNTs.


Novel similarity measures in spherical fuzzy environment and their applications.
Spherical fuzzy sets (SFSs) have gained great attention from researchers in various fields. The spherical fuzzy set is characterized by three membership functions expressing the degrees of membership, non-membership and the indeterminacy to provide a larger preference domain. It was proposed as a generalization of picture fuzzy sets and Pythagorean fuzzy sets in order to deal with uncertainty and vagueness information. The similarity measure is one of the essential and advantageous tools to determine the degree of similarity between items. Several studies on similarity measures have been developed due to the importance of similarity measure and application in decision making, data mining, medical diagnosis, and pattern recognition in the literature. The contribution of this study is to present some novel spherical fuzzy similarity measures. We develop the Jaccard, exponential, and square root cosine similarity measures under spherical fuzzy environment. Each of these similarity measures is analyzed with respect to decision-makers' optimistic or pessimistic point of views. Then, we apply these similarity measures to medical diagnose and green supplier selection problems. These similarity measures can be computed easily and they can express the dependability similarity relation apparently.


Perfluorochemicals as oxygen transport vehicles.
Perfluorochemical liquids (PFC's) are good solvents for gases and as such, have significant relevance to the field of biology. Approximately 40 ml of oxygen will dissolve in 100 ml of most PFC's, and carbon dioxide is at least twice as soluble. This makes these compounds attractive as vehicles for these and other gases in-vivo and in-vitro. Although many have low viscosities and surface tensions, it is necessary to emulsify them for intravenous use and organ perfusion. The emulsion particles must be very fine, usually about 150 nanometers in diameter, and stable in the presence of blood and other biological fluids. Presently the two most used emulsifying agents are Pluronic F68 and phospholipids. Emulsions made with the former are now known to cause complement activation with accompanying transient decreases in circulating leukocytes and oxygen tension. This phenomenon is reversible and usually not severe. Phospholipid-stabilized PFC emulsions do not activate complement and should therefore, be advantageous. Areas of current research utilizing PFC emulsions are in tumor therapy, by increasing the oxygenation of otherwise hypoxic cells, in ischemic heart treatment, and in alleviating the effects of cerebral ischemia. Many other applications of PFC's are being pursued, and even more research activity in this field is likely.


Rh(III)-catalyzed oxidative [4+2] annulation of 2-arylquinoxalines and 2-aryl-2H-indazoles with allyl alcohols.
Synthesis of functionalized benzo[a]phenazines and indazolo[2,3-a]quinolines has been developed through Rh(III)-catalyzed oxidative annulation of 2-arylquinoxalines and 2-aryl-2H-indazoles with allyl alcohols, respectively. The method features a broad substrate scope, excellent functional group tolerance, good to high yields of annulated products, and scaled-up synthesis capability. Based on a preliminary mechanistic investigation, a tentative mechanism of annulation reaction has been proposed.


Integrin-linked kinase is overexpressed in laryngeal squamous cell carcinoma and correlates with tumor proliferation, migration and invasion.
To investigate the role of integrin-linked kinase (ILK) in invasion and metastasis of the laryngeal squamous cell carcinomas (LSCC) and to evaluate the effects of antisense oligonucleotide sequence (ASONs) targeting the ILK gene on the proliferation, epithelial-mesenchymal transition (EMT), migration and invasion of LSCC. 116 patients who had previously undergone complete resection of the tumor for LSCC were studied retrospectively. The ILK expression level in tumor tissues and adjacent normal tissues were determined by immunohistochemistry. The changes of ILK expression from each group were assessed and correlated to the clinical parameters of the patients. Secondly, ILK antisense oligonucleotide (ILK-ASONS) was used to silence the ILK gene of LSCC cell from Hep-2 cell line. The expression of ILK, epithelial marker E-cadherin and mesenchymal marker Vimentin were evaluated by Western blotting. The proliferation of cells after transfection was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The apoptosis was detected by flow cytometry. The migration and invasion activity of Hep-2 cells was detected by Matrigel invasion and cell migration assays. The expression of the ILK protein was significantly associated with tumor differentiation (p=0.046), lymph node metastasis (p=0.020) and pTNM stage (p=0.019). ILK ASONS-transfected cells showed a significant decrease in cell proliferation, cell migration and invasive activity compared to mock-transfected cells. ILK ASONS-transfected cells increased the expression of E-cadherin, whereas the expression of ILK and Vimentin decreased, compared with mock-transfected cells. The expression of ILK was significantly correlated with differentiation and metastasis of the laryngeal carcinomas. The inhibition of the ILK gene could downregulate the proliferation, migration and invasion of Hep-2 cells. These findings suggest that the ILK gene could be a potential target for the treatment of laryngeal cancer.


Acoustic divergence in the communication of cryptic species of nocturnal primates (Microcebus ssp.).
A central question in evolutionary biology is how cryptic species maintain species cohesiveness in an area of sympatry. The coexistence of sympatrically living cryptic species requires the evolution of species-specific signalling and recognition systems. In nocturnal, dispersed living species, specific vocalisations have been suggested to act as an ideal premating isolation mechanism. We studied the structure and perception of male advertisement calls of three nocturnal, dispersed living mouse lemur species, the grey mouse lemur (Microcebus murinus), the golden brown mouse lemur (M. ravelobensis) and the Goodman's mouse lemur (M. lehilahytsara). The first two species occur sympatrically, the latter lives allopatrically to them. A multi-parameter sound analysis revealed prominent differences in the frequency contour and in the duration of advertisement calls. To test whether mouse lemurs respond specifically to calls of the different species, we conducted a playback experiment with M. murinus from the field using advertisement calls and alarm whistle calls of all three species. Individuals responded significantly stronger to conspecific than to heterospecific advertisement calls but there were no differences in response behaviour towards statistically similar whistle calls of the three species. Furthermore, sympatric calls evoked weaker interest than allopatric advertisement calls. Our results provide the first evidence for a specific relevance of social calls for speciation in cryptic primates. They furthermore support that specific differences in signalling and recognition systems represent an efficient premating isolation mechanism contributing to species cohesiveness in sympatrically living species.


Mechanisms of the vascular effect of pressor hormones.
There exists a considerable gap between the recognition of the effects of pressor hormones and the understanding of their mechanisms. Studies are necessary to provide a more accurate basis for potential therapeutic interventions on the hormonal mechanisms of hyper- and hypotensive states. From recent and previous experimental results, a modified model of vascular smooth muscle cell activation is emerging. In this model, contraction is a complex process involving Ca2+ release, protein kinase C and ionic channel activation and modification in pH and energy metabolism. The combined action of these processes is necessary for the full expression of the contractile response.


Monitoring the mode of action of antibiotics using Raman spectroscopy: investigating subinhibitory effects of amikacin on Pseudomonas aeruginosa.
During the last 20 years the rate at which new antimicrobial agents are produced has decreased dramatically, with concomitant increase in the number of pathogens that are becoming multidrug resistant. Together these have created a patient healthcare risk and this is of great concern. A crucial aspect for the discovery of new antibiotics is the development of new techniques that allow rapid and accurate characterization of the mode of action of the pharmacophore. In this work UV resonance Raman (UVRR) spectroscopy has been developed to monitor the concentration effect of antibiotics on bacterial cells. UVRR was conducted at 244 nm and spectra were collected in typically 60 s. Supervised multivariate analysis and 2D correlation spectroscopy were used to evaluate whether the UVRR spectra contained valuable information that could be used to study the mode of action of antibiotics. The clustering pattern in the discriminant factors space correlated directly to the concentration of amikacin, and partial least squares (PLS) regression analysis of the UVRR spectra was able to predict the concentration of amikacin to which bacterial cells had been exposed. 2D correlation spectroscopy contour maps indicated that spectral changes due to the presence of amikacin in the growth media occur according to the known mode of action of the studied antibiotic. Therefore, we conclude that UVRR spectroscopy, when coupled with chemometrics and 2D correlation spectroscopy, constitutes a powerful approach for the development and screening of new antibiotics.


MILITARY RESEARCH: Researchers Target Flaws in Ballistic Missile Defense Plan.
More than three dozen scientists journeyed to Washington, D.C., this week to warn lawmakers that a proposed $60 billion U.S. missile defense system, designed to knock incoming warheads out of the sky, is technically flawed because it can't pick out real warheads from decoys. Pentagon officials heatedly deny a new report by one scientist that contractors have rigged trials to hide the problem, although they admit that some tests were simplified to save time. In the wake of these events, a leading Democrat is urging President Bill Clinton to delay a pending decision on building the system.


The 6-O'clock Anchor Increases Labral Repair Strength in a Biomechanical Shoulder Instability Model.
To characterize the additive effect of a 6-o'clock anchor in the stabilization of a Bankart lesion. Twelve cadaveric shoulders were tested on a 6-df robotic musculoskeletal simulator to measure the peak resistance force due to anterior displacement of 1 cm. The rotator cuff muscles were loaded dynamically. The test conditions consisted of the intact shoulder, Bankart lesion, Bankart repair (3-, 4-, and 5-o'clock anchors), and Bankart repair with the addition of a 6-o'clock anchor. A 13% anterior bone defect was then created, and all conditions were repeated. Repeated-measures analysis of variance was performed. In the group with no bone loss, the addition of a 6-o'clock anchor yielded the highest peak resistance force (52.8 N; standard deviation [SD], 4.5 N), and its peak force was significantly greater than that of the standard Bankart repair by 15.8% (7.2 N, P = .003). With subcritical glenoid bone loss, the repair with the addition of a 6-o'clock anchor (peak force, 52.6 N; SD, 6.1 N; P = .006) had a significantly higher peak resistance force than the group with bone loss with a Bankart lesion (35.2 N; SD, 5.8 N). Although the 6-o'clock anchor did increase the strength of the standard repair by 6.7%, this was not statistically significant (P = .9) in the bone loss model. The addition of a 6-o'clock suture anchor to a 3-anchor Bankart repair increases the peak resistance force to displacement in a biomechanical model, although this effect is lost with subcritical bone loss. This study provides surgeons with essential biomechanical data to aid in the selection of the repair configuration.


Constitutive overexpression of CDC25A in primary human mammary epithelial cells results in both defective DNA damage response and chromosomal breaks at fragile sites.
CDC25A phosphatase, an essential component of the cell cycle machinery, is also a key player in integrating the specific signals of checkpoint control in response to DNA damage. There are several lines of evidence that indicate a role for CDC25A in cancer development, consistent with the fact that its overexpression is detected in human cancers. In particular we previously reported that CDC25A is overexpressed also in early breast carcinoma. Recent data suggest that oncogene activation during early stages of tumor development causes DNA replication stress resulting in the induction of DNA damage response (DDR) and that the selection of cells defecting in their DDR could lead to malignant progression. To address how CDC25A overexpression contributes to breast cancer development we established a cell model in which CDC25A was constitutively overexpressed in hTERT-immortalized primary human mammary epithelial cells. At the earliest passages following CDC25A transduction we observed DDR signs associated with unscheduled DNA replication origins. In the latest passages DDR was significantly impaired and, even after ionizing radiation exposition, cells failed to induce G1 and G2 checkpoints; moreover DNA replication stress conditions, such as aphidicolin treatment, highlighted increased fragile site breakages and destabilized chromosomes just in these latest passages cells. Our data suggest that CDC25A overexpression, pushing the cell through the cell cycle transitions, induces DDR alterations that might enhance genomic instability.


Substance flow analysis of parabens in Denmark complemented with a survey of presence and frequency in various commodities.
Parabens are commonly used as preservatives due to anti-bactericidal and anti-fungicidal properties and they are ubiquitously present in personal care products, pharmaceuticals, food, industrial and domestic commodities. They are suspected of causing endocrine disrupting effects to aquatic organisms and adverse effects in humans and, thus, it is highly relevant to identify and quantify their sources and transportation pathways in the urban environment. Here a substance flow analysis (SFA) was performed in order to map and comprehend the substances' flow on a national basis. Many household commodities were found to contain parabens; cleaning detergents, slimy toys, and water-based paint. The presence and concentration of parabens are regulated in cosmetics and food. Use of parabens in pharmaceuticals as excipients is documented in Denmark. The import of parabens is increasing; although the number of industrial parabens containing commodities is decreasing and manufacturer reports phase-out of parabens. The vast majority of the paraben containing commodities has a durability of 18-30 months, thus the average lifetime of the paraben stock is perceived to be limited. The inflow was ca. 154 tonnes via pure chemicals and 7.2-73 tonnes via commodities in 2004. This corresponds to an average wastewater concentration of 640-900 microg/L, when excluding discharge to solid waste, soil, biodegradation and metabolism. This is in the same order of magnitudes as can be found in industrial wastewater but higher than that seen in domestic wastewater. The data needed for the SFA is sparse, dispersed, and difficult to access and associated with a great deal of uncertainty.


Urea dependence of thiol-disulfide equilibria in thioredoxin: confirmation of the linkage relationship and a sensitive assay for structure.
Thioredoxin contains a single disulfide bond that can be reduced without perturbing significantly the structure of the enzyme. Upon reduction of the disulfide, protein stability decreases. We have experimentally tested the expected linkage relationship between disulfide bond formation and protein stability for thioredoxin. In order to do this, it is necessary to measure the equilibrium constant for disulfide bond formation in both the folded and unfolded states of the protein. Using glutathione as a reference species, we have measured the equilibrium constant for forming the disulfide bond (effective concentration) in thioredoxin as a function of urea concentration. As a control, we show that urea per se does not interfere with our measurements of thiol-disulfide equilibrium constants. Comparison of the values obtained for disulfide bond formation in the folded and unfolded states with the free energies for unfolding oxidized and reduced thioredoxin using circular dichroism confirms the expected linkage relationship. The urea dependence of thiol-disulfide equilibria provides a sensitive assay for folded structure in peptides or proteins. The method should also be useful to evaluate the stabilizing or destabilizing effect of natural or genetically engineered disulfides in proteins. In future work, the effects of amino acid substitutions on disulfide bond formation could be evaluated individually in the native and unfolded states of a protein.


Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of the Leishmania Inositol Phosphorylceramide Synthase.
Current chemotherapeutics for leishmaniasis have multiple deficiencies, and there is a need for new safe, efficacious, and affordable medicines. This study describes a successful drug repurposing approach that identifies the over-the-counter antihistamine, clemastine fumarate, as a potential antileishmanial drug candidate. The screening for inhibitors of the sphingolipid synthase (inositol phosphorylceramide synthase, IPCS) afforded, following secondary screening against Leishmania major (Lmj) promastigotes, 16 active compounds. Further refinement through the dose response against LmjIPCS and intramacrophage L. major amastigotes identified clemastine fumarate with good activity and selectivity with respect to the host macrophage. On target engagement was supported by diminished sensitivity in a sphingolipid-deficient L. major mutant (ΔLmjLCB2) and altered phospholipid and sphingolipid profiles upon treatment with clemastine fumarate. The drug also induced an enhanced host cell response to infection indicative of polypharmacology. The activity was sustained across a panel of Old and New World Leishmania species, displaying an in vivo activity equivalent to the currently used drug, glucantime, in a mouse model of L. amazonensis infection. Overall, these data validate IPCS as an antileishmanial drug target and indicate that clemastine fumarate is a candidate for repurposing for the treatment of leishmaniasis.


Recycling Endosomes and Viral Infection.
Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral-host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition.


Psychometric Assessment of the Child Surgery Worries Questionnaire Among Portuguese Children.
Worries are common in surgical patients, especially in children. The present study analyzed the factor structure and the psychometric properties of a Portuguese version of the Child Surgery Worries Questionnaire (CSWQ-P) in a Portuguese sample of 490 children. Exploratory factor analysis, conducted via principal axis factoring with oblimin rotation, provided evidence for a four-factor structure of the 21 item questionnaire. A confirmatory factor analysis was also conducted, showing the good fit of this solution. The CSWQ-P proved to have one more subscale than the original Spanish version CSWQ. Correlations with the children's trait anxiety provided evidence of convergent validity for the CSWQ-P. Females also scored higher on worries than males on all subscales. Psychometric properties of this revised version of the CSWQ provided support for use with young children, and indicate the CSWQ-P has value for use in healthcare practice and in clinical research.


Successful implantation of an intracardiac defibrillator in an infant with long QT syndrome and isolated noncompaction of the ventricular myocardium.
Congenital long QT syndrome (LQTS) is an inherited disorder characterized by QT prolongation and polymorphic ventricular tachycardia known as torsade de pointes. The underlying cellular mechanism is prolonged ventricular repolarization caused by mutations in genes encoding cardiac ion channels or membrane adaptors. The disease can be diagnosed at any age and, very rarely, it can be diagnosed prenatally or in the neonatal period. Isolated noncompaction of the ventricular myocardium (INCVM) is defined as the presence of prominent ventricular trabeculations and deep intertrabecular recesses within the endomyocardium. This report describes a newborn baby presenting with polymorphic ventricular tachycardia whose diagnosis was LQTS and INCVM. Ventricular tachycardia did not respond to medical treatment, and a transient epicardial pacemaker was inserted surgically on his 30th day of life for atrioventricular block and bradycardia. The transient epicardial pacemaker was upgraded to an epicardial intracardiac defibrillator on his 40th day. The concomitant occurrence of INCVM, LQTS, and atrioventricular block needs to be evaluated further.


Prevalence and Impact of Treatment Crossover in Cardiac Surgery Randomized Trials: A Meta-Epidemiologic Study.
Background Crossover dilutes treatment effect and reduces statistical power of intention-to-treat analysis. We examined incidence and impact on cardiac surgery randomized controlled trial (RCT) outcomes of crossover from experimental to control interventions, or vice versa. Methods and Results MEDLINE, EMBASE, and Cochrane Library were searched, and RCTs (≥100 patients) comparing ≥2 adult cardiac surgical interventions were included. Crossover from the initial treatment assignment and relative risks (RRs) for each trial's primary end point and mortality at longest available follow-up were extracted. All RRs were calculated as >1 favored control group and <1 favored experimental arm. Primary outcome was the effect estimate for primary end point of each RCT, and secondary outcome was all-cause mortality; both were appraised as RR at the longest follow-up available. Sixty articles reporting on 47 RCTs (25 440 patients) were identified. Median crossover rate from experimental to control group was 7.0% (first quartile, 2.0%; third quartile, 9.7%), whereas from control to experimental group, the rate was 1.3% (first quartile, 0%; third quartile, 3.6%). RRs for primary end point and mortality were higher in RCTs with higher crossover rate from experimental to control group (RR, 1.01 [95% CI, 0.94-1.07] versus RR, 0.80 [95% CI, 0.66-0.97] and RR, 1.02 [95% CI, 0.95-1.11] versus RR, 0.94 [95% CI, 0.82-1.07], respectively). Crossover from control to experimental group did not alter effect estimates for primary end point or mortality (RR, 0.82 [95% CI, 0.63-1.05] versus RR, 0.95 [95% CI, 0.86-1.04] and RR, 0.88 [95% CI, 0.73-1.07] versus RR, 1.02 [95% CI, 0.95-1.09], respectively). Conclusions Crossover from experimental to control group is associated with outcomes of cardiac surgery RCTs. Crossover should be minimized at designing stage and carefully appraised after study completion.


[Progestins and hemostasis].
Progesterone and the progestins do not lead to significant changes of the hemostatic system, which could have a decisive action on hemostasis disturbances. This is true for oral and parenteral application as well. In the oncological high dose therapy with progestins remarkable negative effects on the parameters of the hemostatic system, which is already activated in cancer patients, could not be demonstrated.


Can the sustainable development goals reduce the burden of nutrition-related non-communicable diseases without truly addressing major food system reforms?
While the Millennium Development Goals (MDGs; 2000-2015) focused primarily on poverty reduction, hunger and infectious diseases, the proposed Sustainable Development Goals (SDGs) and targets pay more attention to nutrition and non-communicable diseases (NCDs). One of the 169 proposed targets of the SDGs is to reduce premature deaths from NCDs by one third; another is to end malnutrition in all its forms. Nutrition-related NCDs (NR-NCDs) stand at the intersection between malnutrition and NCDs. Driven in large part by remarkable transformations of food systems, they are rapidly increasing in most low and middle income countries (LMICs). The transformation to modern food systems began in the period following World War II with policies designed to meet a very different set of nutritional and food needs, and continued with globalization in the 1990s onwards. Another type of food systems transformation will be needed to shift towards a healthier and more sustainable diet--as will meeting many of the other SDGs. The process will be complex but is necessary. Communities concerned with NCDs and with malnutrition need to work more closely together to demand food systems change.


[Genetic nature of atrophic rhinitis in swine. II. Cytogenetic research].
This work is concerned with the problem of the nature of the atrophic rhinitis in swine. Our study demonstrates that the filter-passers when injecting intranasal provoke catarrhal rhinitis in sucking-pigs and rabbits and the disease lasts 10-12 days. Guinea-pigs and white mice show no disease symptoms after injection. After four passages of filter-passers through sucking-pigs, the pathogenic properties do not restore. The sucking-pigs and laboratory animals show no changes in organs and in nasal cavity. The findings of cytogenetic and allergic investigations indicate genetic aspects of this disease. To eliminate atrophic rhinitis, it is necessary to reveal heterozygotes, carry out experimental matings and analysis of hybrids. To date, a recessive gene is considered to mediate the disease. To obtain healthy offspring, animals heterozygous for this gene should be bred.


Root hydraulic conductance: diurnal aquaporin expression and the effects of nutrient stress.
It has been shown that N-, P- and S-deficiencies result in major reductions of root hydraulic conductivity (Lpr) which may lead to lowered stomatal conductance, but the relationship between the two conductance changes is not understood. In a variety of species, Lpr decreases in the early stages of NO3-, H2PO4(2-) and SO4(2-) deprivation. These effects can be reversed in 4-24 h after the deficient nutrient is re-supplied. Diurnal fluctuations of root Lpr have also been found in some species, and an example of this is given for Lotus japonicus. In nutrient-sufficient wheat plants, root Lpr is extremely sensitive to brief treatments with HgCl2; these effects are completely reversible when Hg is removed. The low values of Lpr in N- or P-deprived roots of wheat are not affected by Hg treatments. The properties of plasma membrane (PM) vesicles from wheat roots are also affected by NO3(-)-deprivation of the intact plants. The osmotic permeability of vesicles from N-deprived roots is much lower than that of roots adequately supplied with NO3-, and is insensitive to Hg treatment. In roots of L. japonicus, gene transcripts are found which have a strong homology to those encoding the PIP1 and PIP2 aquaporins of Arabidopsis. There is a very marked diurnal cycle in the abundance of mRNAs of aquaporin gene homologues in roots of L. japonicus. The maxima and minima appear to anticipate the diurnal fluctuations in Lpr by 2-4 h. The temporal similarity between the cycles of the abundance of the mRNAs and root Lpr is most striking. The aquaporin encoded by AtPIP1 is known to have its water permeation blocked by Hg binding. The lack of Hg-sensitivity in roots and PMs from N-deprived roots provides circumstantial evidence that lowered root Lpr may be due to a decrease in either the activity of water channels or their density in the PM. It is concluded that roots are capable, by means completely unknown, of monitoring the nutrient content of the solution in the root apoplasm and of initiating responses that anticipate by hours or days any metabolic disturbances caused by nutrient deficiencies. It is the incoming nutrient supply that is registered as deficient, not the plant's nutrient status. At some point, close to the initiation of these responses, changes in water channel activity may be involved, but the manner in which monitoring of nutrient stress is transduced into an hydraulic response is also unknown.


Superhydrophobic conducting polymers based on hydrocarbon poly(3,4-ethylenedioxyselenophene).
We report the first studied example of wettability of conducting polymers based on poly(3,4-ethylenedioxyselenophene). Hydrocarbon 3,4-ethylenedioxyselenophene (C2H5 to C12H25) derivatives are synthesized and electropolymerized in propylene carbonate using lithium tetrafluoroborate (LiBF4) and lithium bistrifluoromethanesulfonimidate (LiTf2N) as electrolyte. Highly structured films are obtained from a C8H17 chain independent of the electrolyte used. Superhydrophobic properties with high adhesion are specifically reached if using a C12H25 chain and LiBF4. The surface morphology is porous and highly structured as the films consist of assemblies of nanofibrils.


Clinical isolates of GB virus type C vary in their ability to persist and replicate in peripheral blood mononuclear cell cultures.
GB virus C/hepatitis G virus (GBV-C) replication in vitro is inefficient and inconsistent. In this study, clinical isolates of GBV-C were evaluated using peripheral blood mononuclear cell (PBMC) based culture methods. Isolates varied consistently in their ability to persistently replicate, and yield increased in cells grown without PHA/IL-2 stimulation. The deduced polyprotein sequence of an isolate that replicated well was determined (GenBank AY196904) and compared to 20 full-length GBV-C sequences. Fourteen of the 16 unique amino acid polymorphisms identified were in the coding regions for nonstructural proteins associated with interferon resistance and RNA replication. These data indicate that clinical GBV-C isolates vary in their ability to persist in culture, do not require PHA/IL-2 stimulation, and that sequence variability in key regulatory regions may affect growth in PBMC cultures. Since GBV-C appears to inhibit HIV replication in a coinfection model, these studies should facilitate determination of the mechanism of this interaction.


Relationships between plasma leptin and insulin concentrations, but not insulin resistance, in non-insulin-dependent (type 2) diabetes mellitus.
In non-diabetic subjects, insulin concentrations and insulin resistance are clearly connected, and both correlate with leptin levels, making interpretations about mechanisms difficult. In non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), however, insulin concentrations and insulin resistance are less closely associated. Therefore, we examined the relationship of plasma leptin concentrations within insulin resistance and insulin levels in 32 subjects with NIDDM, who underwent measurement of insulin resistance with an insulin sensitivity test. Plasma leptin was measured with an in-house monoclonal immunoradiometric assay. Fasting leptin level correlated with BMI (r = 0.78; p < 0.001), metabolic clearance rate of glucose (= -0.44; p = 0.015), and fasting specific insulin (r = 0.58; p = 0.001), but not with age, cholesterol, triglycerides or blood pressure (r = -0.26 to 0.21; p = NS). In linear regression analysis, after adjustment for BMI and gender, leptin concentrations correlated with those of insulin (partial r = 0.42; p = 0.025), but not insulin resistance (partial r = -0.10; p = NS). We conclude that in NIDDM, concentrations of plasma leptin are closely related to those of insulin per se and to obesity, but not to insulin resistance. Insulin may be an important regulator of leptin concentration in NIDDM.


Intake of foods and nutrients and cancer of the exocrine pancreas: a population-based case-control study in The Netherlands.
During 1984-88 a population-based case-control study was carried out in the Netherlands in collaboration with the International Agency for Research on Cancer in order to investigate the role of diet in exocrine pancreatic carcinoma. A semi-quantitative food-frequency questionnaire was used to comprehensively assess usual diet about 1 year prior to diagnosis of 164 cases or interview of 480 controls. More than half of the cases were directly interviewed. After controlling for age, gender, response status, life-time cigarette consumption and dietary intake of total energy, monotonic, significantly inverse dose-response effects with estimates of daily consumption of vegetables were found. The significant inverse effect of total cooked vegetables was primarily concentrated in cruciferous vegetables. Consumption of fresh vegetables was also significantly and inversely related to risk. A monotonic, positive dose-response gradient was seen for the consumption of eggs, while consumption of fish was significantly related to risk as well. Among direct respondents, significantly inverse relationships were found for the consumption of legumes, tomatoes, cheese and fermented milk products. Inverse associations with consumption of (subgroups of) fruits were observed in women only. The monotonic, significantly inverse relationship for consumption of low-fibre vegetables and the somewhat weaker, inverse association for high-fibre vegetables in directly interviewed subjects only, may point to protective agents other than vegetable fibre. Although intake of dietary fibre and beta-carotene were both inversely related to risk, simultaneous estimation suggested that beta-carotene or other as yet unknown correlated constituents, rather than dietary fibre, might explain the inverse relationships. A significant protective effect of vitamin C was demonstrated in women but not in men. Our study suggests that, independent of smoking and dietary intake of total energy, low consumption of specific vegetables and possibly fermented milk products and high consumption of eggs and fish may have influenced the development of exocrine pancreatic cancer.


Turtle anoxia tolerance: Biochemistry and gene regulation.
While oxygen limitation can be extremely damaging for many animals, some vertebrates have perfected anaerobic survival. Freshwater turtles belonging to the Trachemys and Chrysemys genera, for example, can survive many weeks without oxygen, and as such are commonly used as model animals for vertebrate anoxia tolerance. In the present review we discuss the recent advances made in understanding the biochemical and molecular nature of natural anoxia tolerance of freshwater turtles. Research in recent years has shown that activation of several important pathways occurs in response to anoxia in turtles, including those that function in the stress response, cell cycle arrest, inhibition of gene expression and metabolism. These likely contribute to anoxia tolerance in turtle tissues by minimizing cell damage in response to anoxia, as well as facilitating metabolic rate depression. The research discussed in the present review contributes to the understanding of how freshwater turtles can survive without oxygen for prolonged periods of time. This could also improve understanding of the molecular nature of hypoxic/ischemic injuries in mammalian tissues and suggest potential ways to avoid these.


Functional equivalence of monomeric and dimeric forms of purified acetylcholine receptors from Torpedo californica in reconstituted lipid vesicles.
Acetylcholine receptors from Torpedo californica electric organ were solubilized and purified under conditions which prevent inactivation of the agonist-regulated cation channels. The dimer form of the receptors was preserved during purification. Treatment with reducing agents converted dimers into monomers. Receptor monomers and dimers were separately reconstituted into soybean lipid vesicles by the cholate dialysis technique. Reconstituted monomers and dimers were functionally equivalent with respect to their carbamylcholine-induced dose-dependent uptake of 22Na+, the total flux of 22Na+ per receptor during the permeability response, and the occurrence of desensitization. Evidence against non-covalent association of monomers to produce dimeric functional units was obtained using glutaraldehyde as a crosslinking agent. These results show that both the acetylcholine-binding sites and the agonist-regulated cation-specific channel are contained within the alpha 2 beta gamma delta subunit structure of the acetylcholine receptor monomer.


Interacting effects of cold snaps, rain, and agriculture on the fledging success of a declining aerial insectivore.
Climate change predicts the increased frequency, duration, and intensity of inclement weather periods such as unseasonably low temperatures (i.e., cold snaps) and prolonged precipitation. Many migratory species have advanced the phenology of important life history stages and, as a result, are likely to be exposed to these periods of inclement spring weather more often, therefore risking reduced fitness and population growth. For declining avian species, including aerial insectivores, anthropogenic landscape changes such as agricultural intensification are another driver of population declines. These landscape changes may affect the foraging ability of food provisioning parents and reduce the survival of nestlings exposed to inclement weather through, for example, pesticide exposure impairing thermoregulation and punctual anorexia. Breeding in agro-intensive landscapes may therefore exacerbate the negative effects of inclement weather under climate change. We observed that a significant reduction in the availability of insect prey occurred when daily maximum temperatures fell below 18.3°C, and thereby defined any day when the maximum temperature fell below this value as a day witnessing a cold snap. We then combined daily information on the occurrence of cold snaps and measures of precipitation to assess their impact on the fledging success of Tree Swallows (Tachycineta bicolor) occupying a nest box system placed across a gradient of agricultural intensification. Estimated fledging success of this declining aerial insectivore was 36.2% lower for broods experiencing 4 cold-snap days during the 12 days post-hatching period versus broods experiencing none, and this relationship was worsened when facing more precipitation. We further found that the overall negative effects of a brood experiencing periods of inclement weather was exacerbated in more agro-intensive landscapes. Our results indicate that two of the primary hypothesized drivers of many avian population declines may interact to further increase the rate of declines in certain landscape contexts.


Promoting and developing a trail network across suburban, rural, and urban communities.
The Wyoming Valley Wellness Trails Partnership received an Active Living by Design grant late in 2003 for a project centered on a growing trail network linking urban, suburban, and rural communities in northeast Pennsylvania, a former coal region, in order to increase physical activity among residents. The partnership conducted research, collected information, created promotional documents, worked with partners on events and programs, and participated in trail planning. Local trail organizations continued planning and construction toward developing a trail network. Other partners spearheaded policy change in schools and worksites and worked toward downtown revitalization. The partnership assisted these efforts by providing a forum in which organizations could meet. The partnership became a central resource for information about local parks, trails, and outdoor recreational activities. The partnership increased awareness and use of recreational facilities. Trail partners constructed 22 miles of walking and biking trails. The partnership took advantage of an allied effort that created organizational capacity for wellness in schools and worksites. Messages promoting social and entertainment benefits of physical activity were more successful than those promoting health benefits. The existence of multiple small, independent trail organizations can help advance trail development through concurrent development efforts. Urban, suburban, and rural residents' conceptions of walkability may differ. Trails provide options for recreational and transportation-related physical activity across urban, suburban, and rural landscapes that are supported by all constituents. Trail builders can be strong allies in bringing active living to suburban and rural places.


Thermodynamic targeting of electrocatalytic CO2 reduction: advantages, limitations, and insights for catalyst design.
Herein is reported the electrocatalytic reduction of CO2 with the complex [Ni(bis-NHC)(dmpe)]2+ (1) (bis-NHC = 1,l':3,3'-bis(1,3-propanediyl)dibenzimidazolin-2,2'-diylidene; dmpe = 1,2-bis(dimethylphosphino)ethane). The hydricity of 1 was previously benchmarked to be , equating to a driving force of a minimum of ∼3.4 kcal mol-1 for hydride transfer to CO2. While hydride transfer to CO2 is thermodynamically favorable, electrocatalytic and infrared spectroelectrochemical (IR-SEC) experiments reveal that hydride transfer is blocked by direct reactivity with CO2 in the reduced, Ni(0) state of the catalyst, yielding CO via reductive disproportionation (2CO2 + 2e- = CO + CO32-) and concomitant catalyst degradation. Although thermodynamic scaling relationships provide guidance in catalyst targeting, the findings herein illustrate the fundamental kinetic challenges in balancing substrate reactivity and selectivity in the design of CO2 reduction electrocatalysts. Advantages and limitations of this scaling relationship as well as approaches by which divergence from it may be achieved are discussed, which provides insight on important parameters for future catalyst design.


The association between reproductive period and handgrip strength in postmenopausal women: a nationwide cross-sectional study.
Menarche and menopause are associated with muscle loss and strength in women. Handgrip strength (HGS) is a reliable measurement method of muscle strength. However, it is unclear whether the entire reproductive period, which encompasses both menarche and menopause, is associated with HGS in postmenopausal women. A total of 2,354 postmenopausal women aged 45-75 years were included for statistical analysis. The reproductive period was divided into tertiles, and HGS was divided into four quartiles. HGS was measured to evaluate muscle strength. Binary logistic regression analysis was used to identify significant predictors with the first quartile HGS, derived from quartile data. Multiple logistic regression analysis was used to assess the relationship between the reproductive period (exposure) and low HGS (outcome). We found that the more extended the reproductive period, the lower the risk of low absolute HGS. This trend persisted even after controlling for other variables. Specifically, the odds ratio for low absolute HGS was 0.752 (95% confidence interval [CI], 0.563-1.000) for the second tertile reproductive period and 0.683 (95% CI, 0.513-0.900) for the third tertile reproductive period, with the first tertile reproductive period as the reference. The odds ratio for low relative HGS was 0.761 (95% CI, 0.551-1.052) for the second tertile reproductive period and 0.732 (95% CI, 0.533-0.972) for the third tertile reproductive period, using first tertile reproductive period as the reference, after covariate adjustment. A longer reproductive period is associated with a decreased risk of low HGS in postmenopausal women.


Controlling dental enamel-cavity ablation depth with optimized stepping parameters along the focal plane normal using a three axis, numerically controlled picosecond laser.
The purpose of this study was to establish a depth-control method in enamel-cavity ablation by optimizing the timing of the focal-plane-normal stepping and the single-step size of a three axis, numerically controlled picosecond laser. Although it has been proposed that picosecond lasers may be used to ablate dental hard tissue, the viability of such a depth-control method in enamel-cavity ablation remains uncertain. Forty-two enamel slices with approximately level surfaces were prepared and subjected to two-dimensional ablation by a picosecond laser. The additive-pulse layer, n, was set to 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70. A three-dimensional microscope was then used to measure the ablation depth, d, to obtain a quantitative function relating n and d. Six enamel slices were then subjected to three dimensional ablation to produce 10 cavities, respectively, with additive-pulse layer and single-step size set to corresponding values. The difference between the theoretical and measured values was calculated for both the cavity depth and the ablation depth of a single step. These were used to determine minimum-difference values for both the additive-pulse layer (n) and single-step size (d). When the additive-pulse layer and the single-step size were set 5 and 45, respectively, the depth error had a minimum of 2.25 μm, and 450 μm deep enamel cavities were produced. When performing three-dimensional ablating of enamel with a picosecond laser, adjusting the timing of the focal-plane-normal stepping and the single-step size allows for the control of ablation-depth error to the order of micrometers.


TEM8 interacts with the cleaved C5 domain of collagen alpha 3(VI).
Tumor endothelial marker (TEM)8 was uncovered as a gene expressed predominantly in tumor endothelium, and its protein product was recently identified as the receptor for anthrax toxin. Here, we demonstrate that TEM8 protein is preferentially expressed in endothelial cells of neoplastic tissue. We used the extracellular domain of TEM8 to search for ligands and identified the alpha 3 subunit of collagen VI as an interacting partner. The TEM8-interacting region on collagen alpha 3(VI) was mapped to its COOH-terminal C5 domain. Remarkably, collagen alpha 3(VI) is also preferentially expressed in tumor endothelium in a pattern concordant with that of TEM8. These results suggest that the TEM8/C5 interaction may play an important biological role in tumor angiogenesis.


Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling.
Patients suffering from neuropathic pain have a higher incidence of mood disorders such as depression. Increased expression of tumor necrosis factor (TNF) has been reported in neuropathic pain and depressive-like conditions and most of the pro-inflammatory effects of TNF are mediated by the TNF receptor 1 (TNFR1). Here we sought to investigate: (1) the occurrence of depressive-like behavior in chronic neuropathic pain and the associated forms of hippocampal plasticity, and (2) the involvement of TNFR1-mediated TNF signaling as a possible regulator of such events. Neuropathic pain was induced by chronic constriction injury of the sciatic nerve in wild-type and TNFR1(-/-) mice. Anhedonia, weight loss and physical state were measured as symptoms of depression. Hippocampal neurogenesis, neuroplasticity, myelin remodeling and TNF/TNFRs expression were analyzed by immunohistochemical analysis and western blot assay. We found that neuropathic pain resulted in the development of depressive symptoms in a time dependent manner and was associated with profound hippocampal alterations such as impaired neurogenesis, reduced expression of neuroplasticity markers and myelin proteins. The onset of depressive-like behavior also coincided with increased hippocampal levels of TNF, and decreased expression of TNF receptor 2 (TNFR2), which were all fully restored after mice spontaneously recovered from pain. Notably, TNFR1(-/-) mice did not develop depressive-like symptoms after injury, nor were there changes in hippocampal neurogenesis and plasticity. Our data show that neuropathic pain induces a cluster of depressive-like symptoms and profound hippocampal plasticity that are dependent on TNF signaling through TNFR1.


'Schizoid' personality in childhood and adult life. III: The childhood picture.
The childhood case records of 32 'schizoid' children and 32 matched controls were analysed. 'Schizoid' children were characterised by solitariness, unusual fantasies, special interests, and specific developmental delays, especially of language-related skills. They were of average or above-average IQ, and half presented with other, common, child psychiatric syndromes. It is important to distinguish 'schizoid' children from children with reactive psychiatric disorders.


Transabdominal contrast-enhanced ultrasound imaging of the prostate.
Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time-intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r(2) = 0.91 (r(2) > 0.75 for 78.6% of all prostate pixels) compared with r(2) = 0.91 (r(2) > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitoring.


Guess who's not coming to dinner? Evaluating online restaurant reservations for disease surveillance.
Alternative data sources are used increasingly to augment traditional public health surveillance systems. Examples include over-the-counter medication sales and school absenteeism. We sought to determine if an increase in restaurant table availabilities was associated with an increase in disease incidence, specifically influenza-like illness (ILI). Restaurant table availability was monitored using OpenTable, an online restaurant table reservation site. A daily search was performed for restaurants with available tables for 2 at the hour and at half past the hour for 22 distinct times: between 11:00 am-3:30 pm for lunch and between 6:00-11:30 PM for dinner. In the United States, we examined table availability for restaurants in Boston, Atlanta, Baltimore, and Miami. For Mexico, we studied table availabilities in Cancun, Mexico City, Puebla, Monterrey, and Guadalajara. Time series of restaurant use was compared with Google Flu Trends and ILI at the state and national levels for the United States and Mexico using the cross-correlation function. Differences in restaurant use were observed across sampling times and regions. We also noted similarities in time series trends between data on influenza activity and restaurant use. In some settings, significant correlations greater than 70% were noted between data on restaurant use and ILI trends. This study introduces and demonstrates the potential value of restaurant use data for event surveillance.


Complete genome sequence of Streptomyces lividans TK24.
Streptomyces lividans TK24 is the standard host for the heterologous expression of a number of different proteins and antibiotic-synthesizing enzymes. As such, it is often used as an experimental microbial cell factory for the production of secreted heterologous proteins including human cytokines and industrial enzymes, and of several antibiotics. It accepts methylated DNA and is an ideal Streptomyces cloning system. Here, we report the complete genome sequence of S. lividans TK24 that includes a plasmid-less genome of 8.345Mbp (72.24% G+C content).


[Drug-induced liver injury caused by a dietary supplement (Kin-toki Shoga(®)) made from ginger].
A 70-year-old woman who took a dietary supplement, Kin-toki Shoga(®) made from ginger for peripheral psychroesthesia and numbness, experienced an epigastric sense of incongruity and appetite loss and passed brown urine for 2 months. Although she had stopped taking the supplement, her symptoms had not improved. She was admitted to our hospital because of jaundice and liver dysfunction. After an investigation of causes, she was diagnosed with drug-induced liver injury caused by Kin-toki Shoga(®). Liver dysfunction gradually improved with conservative treatment. She was discharged on the 25th day of illness. Liver biopsy findings were compatible with drug-induced liver injury.


Son preference, sex selection, and kinship in Vietnam.
This article examines the recent rise in the sex ratio at birth in Vietnam and relates its emergence to kinship systems and ethnic composition using 2009 census micro-data. Presentation of the main socioeconomic and ethnic differentials in birth masculinity is followed by a review of the three intermediate factors leading to increases in the sex ratio at birth: prenatal technology, declining fertility, and gender bias. An indirect measurement of fertility behavior is used to demonstrate the close association between levels of the sex ratio at birth and the intensity of son preference. Data on household composition indicate that Vietnam is characterized by the co-existence of kinship patterns typical of East and Southeast Asia. Son preference in Vietnam is found to be related to the prevalence of more traditional patrilineal systems. The article concludes by considering the implications of the cultural dimensions of prenatal sex selection for policy responses and for the likely future change in the sex ratio at birth.


Renal function in children with congenital neurogenic bladder.
Preservation of renal function in children with congenital neurogenic bladder is an important goal of treatment for the disease. This study analyzed the evolution of renal function in patients with congenital neurogenic bladder. We reviewed the records of 58 pediatric patients with respect to the following attributes: gender, age, etiology of neurogenic bladder, reason for referral, medical/surgical management, episodes of treated urinary tract infections, urodynamics, DMSA scintigraphy, weight, height, blood pressure, glomerular filtration rate, microalbuminuria and metabolic acidosis. Statistical analysis was performed, adopting the 5% significance level. The mean age at presentation was 4.2 ± 3.5 years. Myelomeningocele was the most frequent etiology (71.4%). Recurrent urinary tract infection was the reason for referral in 82.8% of the patients. Recurrent urinary tract infections were diagnosed in 84.5% of the patients initially; 83.7% of those patients experienced improvement during follow-up. The initial mean glomerular filtration rate was 146.7 ± 70.1 mL/1.73 m²/min, and the final mean was 193.6 ± 93.6 mL/1.73 m²/min, p = 0.0004. Microalbuminuria was diagnosed in 54.1% of the patients initially and in 69% in the final evaluation. Metabolic acidosis was present in 19% of the patients initially and in 32.8% in the final assessment. Patient referral to a pediatric nephrologist was late. A reduction in the number of urinary tract infections was observed with adequate treatment, but microalbuminuria and metabolic acidosis occurred frequently despite adequate management.


Genetic diversity confers colony-level benefits due to individual immunity.
Several costs and benefits arise as a consequence of eusociality and group-living. With increasing group size, spread of disease among nest-mates poses selective pressure on both individual immunity and group-level mechanisms of disease resistance (social immunity). Another factor known to influence colony-level expression of disease is intracolony genetic diversity, which in honeybees (Apis mellifera) is a direct function of the number of mates of the queen. Colonies headed by queens with higher mating numbers have less variable infections of decreased intensity, though the underlying mechanisms remain unclear. By pathogen-challenging larvae in vitro, we decoupled larval immune response from mechanisms of social immunity. Our results show that baseline immunity and degree of immune response do not vary with genetic diversity. However, intracolony variance in antimicrobial peptide production after pathogen challenge decreases with increasing genetic diversity. This reduction in variability of the larval immune response could drive the mitigation of disease observed in genetically diverse colonies.


The role of microbes in developmental immunologic programming.
The role of microorganisms in the gastrointestinal tract has undergone significant modification in the past few decades with new observations from clinical, epidemiologic, and basic science research. We now know that the perception of these gut microbes as pathogens or even as commensals is somewhat outdated. It is becoming increasingly clear that the gut microbiome plays an important role in a host of activities including digestion, protection from potentially pathogenic organisms, and the regulation and development of the host immune system. The complex interactions between microbes and host combined with recent clinical observations and epidemiologic trends may point to the convergence of two well-supported (though imperfect) hypotheses: the "hygiene hypothesis" and the "fetal programming hypothesis." We are beginning to understand that exposure to microbes before conception, during gestation, and in the neonatal period have profound effects on the developing immune system. Recent observations from a variety of fields help support the expansion of the "fetal programming hypothesis" to a host-microbe corollary that microbe-host interactions at critical windows influence the future immune phenotype, the maintenance of immune health, and the development of immune-mediated disease.


Non-ischemic cerebral enhancing lesions after intracranial aneurysm endovascular repair: a retrospective French national registry.
Non-ischemic cerebral enhancing (NICE) lesions are exceptionally rare following aneurysm endovascular therapy (EVT). To investigate the presenting features and longitudinal follow-up of patients with NICE lesions following aneurysm EVT. Patients included in a retrospective national multicentre inception cohort were analysed. NICE lesions were defined, using MRI, as delayed onset punctate, nodular or annular foci enhancements with peri-lesion edema, distributed in the vascular territory of the aneurysm EVT, with no other confounding disease. From a pool of 58 815 aneurysm endovascular treatment procedures during the study sampling period (2006-2019), 21/37 centres identified 31 patients with 32 aneurysms of the anterior circulation who developed NICE lesions (mean age 45±10 years). Mean delay to diagnosis was 5±9 months, with onset occurring a month or less after the index EVT procedure in 10 out of 31 patients (32%). NICE lesions were symptomatic at time of onset in 23 of 31 patients (74%). After a mean follow-up of 25±26 months, 25 patients (81%) were asymptomatic or minimally symptomatic without disability (modified Rankin Scale (mRS) score 0-1) at last follow-up while 4 (13%) presented with mild disability (mRS score 2). Clinical follow-up data were unavailable for two patients. Follow-up MRI (available in 27 patients; mean time interval after onset of 22±22 months) demonstrated persistent enhancement in 71% of cases. The clinical spectrum of NICE lesions following aneurysm EVT therapy spans a wide range of neurological symptoms. Clinical course is most commonly benign, although persistent long-term enhancement is frequent.


Anopheline mosquito (Diptera: Culicidae) ecology in relation to malaria transmission in the inner and outer terai of Nepal, 1987-1989.
The ecology of Anopheles mosquitoes in relation to malaria transmission was studied at sprayed and unsprayed villages and two unsprayed cattle sheds in the inner terai of Sindhuli District, Central Region, and at two unsprayed villages and one cattle shed in Kanchanpur, Far Western Region of Nepal, from August 1987 to August 1989. Anopheles maculatus was the most abundant of 26 anopheline species collected in Sindhuli District; however, An. fluviatilis was collected most frequently at human bait and was infected most frequently with malaria sporozoites. Residual house spray controlled the indoor resting abundance of the endophilic resting species and protected the population from malaria during midsummer, but had less effect on exophilic resting species and those abundant after and before spray application during the fall and spring, respectively. Malaria at the unsprayed village was detected predominantly in adults of both sexes, perhaps because young children retired early and frequently slept indoors under bed nets during the early evening period of elevated anopheline host-seeking activity. Malaria transmission was verified by the collection of sporozoite infected An. fluviatilis and An. maculatus during spring at cattle sheds in the forested Churia Hills and during the summer monsoon season within the unsprayed village. An. culicifacies was the most abundant of 12 anopheline species collected in Kanchanpur District. Few females of all species were collected at human bait positioned in or out of houses or had human positive blood meals; none were infected with sporozoites. Malaria incidence was higher in the study village positioned along the forest-rice field ecotone than in the cleared rice growing area.


A prospective randomized double-blind study of gastroesophageal reflux surgery in pediatric-sized developmentally disabled patients: Nissen fundoplication versus Angelchik prosthesis.
In order to compare the standard Nissen fundoplication with the more recent Angelchik antireflux prosthesis, 47 pediatric-sized, developmentally disabled patients were prospectively randomized to receive either of these gastroesophageal antireflux procedures. The two groups were comparable at the time of surgery with regard to age, weight, surface area, emesis, number of chest radiographs, medications, lower esophageal sphincter pressure, and number and duration of reflux episodes during standard acid reflux testing. The Angelchik group required significantly less anesthesia time than the Nissen group: 107.4 +/- 22.6 min (mean +/- SD) versus 156.5 +/- 42.4 min (p less than 0.001). There was no difference in length of postsurgical hospital stay. Six months after surgery, both groups showed improvement. There was no significant difference between the Angelchik and Nissen groups in mean subjective assessment score, increased weight gain, decreases in emesis, numbers of chest radiographs, hospital days, or medications, increased lower esophageal sphincter pressure, or decreased numbers and duration of reflux during acid reflux testing. Long-term follow-up of eight Angelchik and 10 Nissen patients 12-30 months postsurgery (Angelchik 21.6 +/- 6.0 months, Nissen 21.9 +/- 5.0 months) demonstrated no significant difference in the percent of time the distal esophageal pH was below 4.0. Significant complications potentially related to the type of procedure developed in 1/21 patients in the Angelchik group and 1/17 patients in the Nissen group. We conclude that both procedures are usually effective for the surgical treatment of gastroesophageal reflux. Further study is indicated in order to establish the long-term superiority of one procedure.


Synthesis, characterization and in vitro anticancer activity of the biomolecule-based coordination complex nanotubes.
Biomolecule-based coordination complex nanoassemblies are a new type of functional materials that are attracting increasing attention. They could possess functionalities that are not readily attainable with other materials, and represent a promising research area that can be exploited in coordination chemistry and materials science. Using bioactive folic acid molecule as a linker, Ni-folate-hydrazine coordination complex nanotubes (CCNTs) have been effectively constructed using the solvothermal method. This is not only the first example of the CCNTs being formed using a nonpyridyl-based molecule as a linker, but also the first report on biomolecule-based CCNTs (BMB-CCNTs) with anticancer activity. It does not require any post treatment to achieve targeted delivery and biocompatible performance. The BMB-CCNTs are sufficiently stable at normal pH of 7.4 until it enters a tumor cell, subsequently it breaks open to release drug in the tumor cell. Furthermore, it overcomes the major limitations of antibody-drug and folate-drug conjugates and is a potential smart multi-functional nanomedicine system. The results of in vitro cytotoxicity assay reveal that the antitumor ability of BMB-CCNTs is similar to cisplatin (CDDP), while their cytotoxicity for normal cells is lower than the latter. Furthermore, BMB-CCNTs exhibit excellent performance as drug carriers and target agents for delivering drugs into tumor cells. Bio-TEM and confocal laser scanning microscope images trace the uptake process of CDDP-CCNTs by a tumor cell. CDDP-CCNTs exhibit dual anti-cancer effect.


Effect of storage temperature on quality of light and full-fat ice cream.
Ice cream quality is dependent on many factors including storage temperature. Currently, the industry standard for ice cream storage is -28.9 °C. Ice cream production costs may be decreased by increasing the temperature of the storage freezer, thus lowering energy costs. The first objective of this research was to evaluate the effect of 4 storage temperatures on the quality of commercial vanilla-flavored light and full-fat ice cream. Storage temperatures used were -45.6, -26.1, and -23.3 °C for the 3 treatments and -28.9 °C as the control or industry standard. Ice crystal sizes were analyzed by a cold-stage microscope and image analysis at 1, 19.5, and 39 wk of storage. Ice crystal size did not differ among the storage temperatures of light and full-fat ice creams at 19.5 or 39 wk. An increase in ice crystal size was observed between 19.5 and 39 wk for all storage temperatures except -45.6 °C. Coldness intensity, iciness, creaminess, and storage/stale off-flavor of the light and full-fat ice creams were evaluated at 39 wk of storage. Sensory evaluation indicated no difference among the different storage temperatures for light and full-fat ice creams. In a second study, light and full-fat ice creams were heat shocked by storing at -28.9 °C for 35 wk and then alternating between -23.3 and -12.2 °C every 24h for 4 wk. Heat-shocked ice creams were analyzed at 2 and 4 wk of storage for ice crystal size and were evaluated by the sensory panel. A difference in ice crystal size was observed for light and full-fat ice creams during heat-shock storage; however, sensory results indicated no differences. In summary, storage of light or full-fat vanilla-flavored ice creams at the temperatures used within this research did not affect quality of the ice creams. Therefore, ice cream manufacturers could conserve energy by increasing the temperature of freezers from -28.9 to -26.1 °C. Because freezers will typically fluctuate from the set temperature, usage of -26.1 °C allows for a safety factor, even though storage at -23.3 °C did not affect ice cream quality.


Audiovisual aids: guidelines for the use of overhead projector.
The overhead projector is a versatile audio-visual (AV) aid. When used effectively, it can render a presentation very impressive. It is easy to maintain and operate, and offers considerable flexibility of text and image projection. It is the most commonly used AV aid in teaching institutions and an appreciation of its strengths and weaknesses can be useful to teachers and students alike.


Grid-free 3D multiple spot generation with an efficient single-plane FFT-based algorithm.
Algorithms based on the fast Fourier transform (FFT) for the design of spot-generating computer generated holograms (CGHs) typically only make use of a few sample positions in the propagated field. We have developed a new design method that much better utilizes the information-carrying capacity of the sampled propagated field. In this way design tasks which are difficult to accomplish with conventional FFT-based design methods, such as spot positioning at non-sample positions and/or spot positioning in 3D, are solved as easily as any standard design task using a conventional method. The new design method is based on a projection optimization, similar to that in the commonly used Gerchberg-Saxton algorithm, and the vastly improved design freedom comes at virtually no extra computational cost compared to the conventional design. Several different design tasks were demonstrated experimentally with a liquid crystal spatial light modulator, showing highly accurate creation of the desired field distributions.


Establishment of a transgenic tobacco cell suspension culture system for producing murine granulocyte-macrophage colony stimulating factor.
We tested if murine granulocyte-macrophage colony stimulating factor (mGM-CSF) is produced as a biologically active form through plant cell culture. The mGM-CSF gene was cloned into the plant expression vector, pBI121, and Ti-plasmid mediated transformation of tobacco leaves was conducted using Agrobacterium tumefaciens harboring the recombinant mGM-CSF (rmGM-CSF) gene. Cell suspension culture was established from the leaf-derived calli of transgenic tobacco plants. Northern blot analysis indicated the expression of the introduced mGM-CSF gene in both transgenic plant and cell suspension cultures. In addition, the biological activity of rmGM-CSF from plant cell culture was confirmed by measuring the proliferation of GM-CSF dependent FDC-P1 cells.


Design, synthesis, and characterization of novel Xc- transport inhibitors: Inhibition of microglial glutamate release and neurotoxicity.
Neuroinflammation appears to involve some degree of excitotoxicity promulgated by microglia, which release glutamate via the system Xc- cystine-glutamate antiporter. With the aim of mitigating this source of neuronal stress and toxicity, we have developed a panel of inhibitors of the Xc- antiporter. The compounds were based on L-tyrosine, as elements of its structure align with those of glutamate, a primary physiological substrate of the Xc- antiporter. In addition to 3,5-dibromotyrosine, ten compounds were synthesized via amidation of that parent molecule with a selection of acyl halides. These agents were tested for the ability to inhibit release of glutamate from microglia activated with lipopolysaccharide (LPS), an activity exhibited by eight of the compounds. Two of these were further tested for the ability to inhibit death of primary cortical neurons in the presence of activated microglia. While both showed some neuroprotective activity, they were quantitatively distinct with a compound we refer to as "35DBTA7" showing the greatest effi cacy. This agent may hold promise in reducing the neurodegenerative effects of neuroinflammation in conditions such as encephalitis, traumatic brain injury, stroke, or neurodegenerative diseases.


DISSECTING THE PHYSIOLOGICAL RESPONSE TO PHOSPHORUS STRESS IN MARINE SYNECHOCOCCUS ISOLATES (CYANOPHYCEAE)(1).
Marine Synechococcus is ubiquitous in aquatic environments. However, distinct phylogenetic lineages of this genus have a complex ecological distribution that is not fully explained. Here, we undertook a broad study of the phosphorus (P)-related behavior of marine Synechococcus isolates from all previously described ribotypes (sensu Fuller et al. 2003). A wide variability in P-related physiology was noted among members of this genus, particularly in the utilization of organic P sources. However, some characteristics (e.g., cell size change during P limitation and the ability to accumulate polyphosphate) were largely consistent with their phylogenetic lineage and inferred ecology, with clear distinctions between oligotrophic, mesotrophic, and opportunistic lineages. Similarly, the ability to induce protein expression in response to P limitation was consistent with the presence/absence of phoB/R regulatory capacity of the corresponding strain. Taxonomic differences in P uptake, storage, and utilization strategies could explain the ubiquitous distribution of marine Synechococcus throughout the world's oceans and explain the coexistence and/or ecological partitioning of multiple phototrophic taxa in the photic zone of tropical and subtropical oligotrophic oceans.


The timing of antibiotic administration in the management of infant dacryocystitis.
To report (1) the prevalence of bacteremia among infants with dacryocystitis and (2) the influence of timing of antibiotic administration on the need for repeat probing in the management of these patients. A retrospective analysis of the hospital records of 25 infants < or =6 weeks of age treated for acute dacryocystitis was conducted, including analysis of laboratory data and outcomes. Of 22 infants who underwent blood cultures, 5 (22.7%) were bacteremic. Twenty-one of the 25 infants underwent nasolacrimal duct probing. Infants who received preoperative antibiotics were less likely to require a repeat probing than those who did not (6% vs. 80%), and this difference was statistically significant (p = 0.004). The high rate of bacteremia in this series of patients and the significantly lower incidence of repeat probing among infants who received preprocedural antibiotics suggests that blood cultures and subsequent administration of intravenous antibiotics should be considered prior to probing of infants with dacryocystitis.


Refined carbohydrates - a cause of suboptimal nutrient intake.
During the refining of carbohydrate foods there is a sharp drop in the concentration of dietary fiber and of various vitamins and minerals. Estimates were made of the effect of refining on the total diet intake of fiber, selenium, folic acid, vitamins E and B6, choline, chromium, magnesium, zinc, manganese, copper, sodium and potassium. The health implications of this are discussed and it is concluded that the losses are likely to be detrimental.


Pseudo-fivefold diffraction symmetries in tetrahedral packing.
We review the way in which atomic tetrahedra composed of metallic elements pack naturally into fused icosahedra. Orthorhombic, hexagonal, and cubic intermetallic crystals based on this packing are all shown to be united in having pseudo-fivefold rotational diffraction symmetry. A unified geometric model involving the 600-cell is presented: the model accounts for the observed pseudo-fivefold symmetries among the different Bravais lattice types. The model accounts for vertex-, edge-, polygon-, and cell-centered fused-icosahedral clusters. Vertex-centered and edge-centered types correspond to the well-known pseudo-fivefold symmetries in Ih and D5h quasicrystalline approximants. The concept of a tetrahedrally-packed reciprocal space cluster is introduced, the vectors between sites in this cluster corresponding to the principal diffraction peaks of fused-icosahedrally-packed crystals. This reciprocal-space cluster is a direct result of the pseudosymmetry and, just as the real-space clusters, can be rationalized by the 600-cell. The reciprocal space cluster provides insights for the Jones model of metal stability. For tetrahedrally-packed crystals, Jones zone faces prove to be pseudosymmetric with one another. Lower and upper electron per atom bounds calculated for this pseudosymmetry-based Jones model are shown to accord with the observed electron counts for a variety of Group 10-12 tetrahedrally-packed structures, among which are the four known Cu/Cd intermetallic compounds: CdCu2, Cd3Cu4, Cu5Cd8, and Cu3Cd10. The rationale behind the Jones lower and upper bounds is reviewed. The crystal structure of Zn11Au15Cd23, an example of a 1:1 MacKay cubic quasicrystalline approximant based solely on Groups 10-12 elements is presented. This compound crystallizes in Im3 (space group no. 204) with a = 13.842(2) Å. The structure was solved with R1 = 3.53 %, I > 2σ; = 5.33 %, all data with 1282/0/38 data/restraints/parameters.


The World Health Organization - Community Empowerment Model in Addressing Food Insecurity in Low-Income African-American Women: A Review of the Literature.
Numerous researchers have examined the serious consequences of food insecurity and food deserts affecting the nutritional health of poor or low-income African-American women and their families. Food insecurity is defined as having limited or uncertain capacityfor acquiring sufficient, safe, and nutritious food at all times to meet one's dietary needs, while food deserts refer to economically and socially-deprived inner city areas with inadequate food supply that are often inhabited by low-income groups. Researchers have found that despite the capacity of community-level resources such as SNAP (Supplemental Nutrition Assistance Program) and WIC (Women, Infants, and Children) supporting healthy nutrition, food insecurity persists among some recipients of both nutritional resources. Both food insecurity and food deserts had a negative effect on the emotional eating, emotional coping, coping strategies, and depressive symptoms in low-income African-American women. Even more concerning is that food deserts have been linked to decreased physical activity in low-income African-American women. Neighborhoods with fewer food supermarkets in which to purchase fresh produce and other healthy nutritious foods also emphasized junk food displays. Thus, neighborhoods with persons that have powerful influences (e.g., local merchants and community liaisons) must bear responsibility to help eliminate food deserts that were linked to obesity, high BMI measures, and Type 2 diabetes in African-American women. Food inse- curity was viewed from the lens of the World Health Organization - Community Empowerment Model (CEM) that incorporates 5 core processes or barometers for change: community coalitions, critical consciousness raising, exerting public pressure, lobbying, advocacy and mediation, and reframing and reorienting health services. Each of the processes plays a powerful role in assisting communities in taking charge of their health and assuming responsibility for improving access to healthy nutritious foods and eliminating food deserts in low-income communities. The implications of change and community involvement rely on all persons with a vested interest in address- ing the disturbing problem offood insecurity and food deserts affecting the nutritional health and well-being of African-American communities.


[Severe acute respiratory syndrome: the first transmissible disease of the 21st century].
The Severe Acute Respiratory Syndrome (SARS) is the first severe and easily transmissible disease to emerge in the 21st century. It is caused by the infection with a coronavirus, a single strand RNA capsulated virus, recently found in a small mammalian, the masked palm civet. It is likely to represent the source of human infection. The first cases of SARS have been reported in the Chinese province of Guangdong and, since then, probable cases have been reported world wide. The clinical picture is characterized by nonspecific symptoms such as fever, cough or dyspnea in patients affected by air-space opacities (unifocal involvement in the 54.6% of cases) or distress respiratory syndrome and linked to a recent exposure to a SARS case or to a travel/residence in an affected area. The empirical therapy is based on broad-spectrum antibiotics, steroids and ribavirin, but susceptibility testing have failed to demonstrate direct anti-viral activity of ribavirin against SARS-related coronavirus in vitro. The exposure to respiratory droplets and the contact with biologic fluids (respiratory and gastrointestinal secretions) represent the most efficient transmission modality of the SARS-related coronavirus. Hand hygiene is the most simple and cost effective measure of infection control to prevent contagion, and the use of airborne, contact and droplet precaution is strictly recommended to all health care workers taking care of such patients. The spread of SARS, to less developed country with limited resource for public health programs, represent the emerging alarming threat in the new global scenario.


Association between Upper Respiratory Infection and Idiopathic Unilateral Vocal Fold Paralysis.
Unilateral vocal fold paralysis (UVFP) without an identifiable cause is termed idiopathic unilateral vocal fold paralysis (IUVFP). Some authors have postulated that select cases of IUVFP have a viral etiology, but the causality has not been established. We set out to review institutional cases of IUVFP and determine if there is a correlation between upper respiratory infection symptoms and presentation of IUVFP. Cases of IUVFP were reviewed over a 10-year period (2002-2012). The history was investigated to review presenting symptoms. We specifically reviewed for symptoms of upper respiratory infection at the onset of UVFP and tallied the frequency. Symptoms included sore throat, laryngitis, cough, influenza, bronchitis, pneumonia, otalgia, and sinusitis. The seasonal onset (if possible) was determined based on the history provided from the initial consultation. Case series. Overall, 107 patients presented with IUVFP; 35.5% of patients reported symptoms of upper respiratory infection at the onset of UVFP. Among these individuals, pharyngitis/laryngitis was the most common presenting symptom; 34.2% reported cough. In total, 40.0% of patients with IUVFP reported an onset of symptoms between December and February. This study suggests that symptoms of upper respiratory infection frequently occur with the presentation of IUVFP. The onset of symptoms tended to occur between December and February. The mechanism of viral-mediated UVFP has not been established. Future studies to explore this pathophysiology are needed.


The demographics and outcomes in patients with bilateral distal radius fractures.
Although distal radius fractures are quite common, bilateral distal radius fractures seldomly occur. Due to this, treatment is primarily based on surgeon experience with unilateral fractures, however bi- lateral fractures add a level of complexity : loss of functional independence. The purpose of this study was to examine a cohort of patients with bilateral distal radius fractures to identify differences in demographics, mechanism of injury, and outcomes to further our understanding of these rare injuries. 23 patients were identified retrospectively over a 5-year period that met inclusion criteria. The medical records were reviewed with multiple demographic and clinical parameters recorded and analyzed. Males were more likely to sustain high-energy mechanisms (80% vs. 53%). Patients <50 years old were more likely to sustain high-energy mechanisms (90% vs. 46%) and were more likely to be treated operatively (80% vs. 62%). The most commonly associated injury was a head injury (30%). All patients treated non-operatively reported minimal/no pain upon final follow-up where 57% of patients treated operatively noted regular pain. 75% of patients with medical comorbidities had minimal/no pain upon final follow- up. Conclusions : Patients with bilateral fractures were more likely to be younger males who suffered from higher energy mechanisms. Age was a critical factor in determining treatment strategy. Rates of associated head injuries were elevated, which is an important factor for the clinician to keep in mind when treating this population. As we further our understanding of this unique population, we can improve our treatment approaches and subsequently attain better outcomes.


Growth and DNA damage-inducible transcription factor 153 mediates apoptosis in response to fenretinide but not synergy between fenretinide and chemotherapeutic drugs in neuroblastoma.
Fenretinide induces apoptosis of neuroblastoma cells in vitro and interacts synergistically with the chemotherapeutic drugs cisplatin and etoposide. The stress-inducible transcription factor known as growth and DNA damage (GADD)-inducible transcription factor 153 is induced in response to fenretinide and in other cell types modulates apoptosis via pro- and antiapoptotic members of the BCL2 family. Because BCL2-family proteins are important in apoptosis induced by chemotherapeutic drugs, GADD153 may be a key mediator of synergy between fenretinide and chemotherapeutic drugs. To investigate this, GADD153 cDNA in sense and antisense orientations was stably transfected into SH-SY5Y neuroblastoma cells using a tetracycline-inducible vector. Increased expression of GADD153 raised the background level of apoptosis and increased apoptosis induced by fenretinide or the chemotherapeutic drugs cisplatin and etoposide. However, there was no increase in synergy between fenretinide and chemotherapeutic drugs. Conversely, expression of antisense-GADD153 virtually abolished the induction of apoptosis in response to fenretinide but overall had no significant effect on apoptosis induced by chemotherapeutic drugs. The effect of antisense-GADD153 on synergy between chemotherapeutic drugs and fenretinide varied with the drug used: there was no effect on synergy between fenretinide and cisplatin, but the combination of fenretinide with etoposide became antagonistic. These results suggest that mechanisms mediating synergy between fenretinide and chemotherapeutic drugs lie upstream of GADD153.


A chimeric peptide composed of a dermaseptin derivative and an RNA III-inhibiting peptide prevents graft-associated infections by antibiotic-resistant staphylococci.
Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K(4)-S4(1-13)(a) is a 13-residue dermaseptin derivative (DD(13)) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD(13)-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD(13)-RIP and DD(13) were equally effective, and that the chimeric peptide but not DD(13) was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD(13) act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections.


Role of Oxylipins in the Inflammatory-Related Diseases NAFLD, Obesity, and Type 2 Diabetes.
Oxygenated polyunsaturated fatty acids (oxylipins) are bioactive molecules established as important mediators during inflammation. Different classes of oxylipins have been found to have opposite effects, e.g., pro-inflammatory prostaglandins and anti-inflammatory resolvins. Production of the different classes of oxylipins occurs during distinct stages of development and resolution of inflammation. Chronic inflammation is involved in the progression of many pathophysiological conditions and diseases such as non-alcoholic fatty liver disease, insulin resistance, diabetes, and obesity. Determining oxylipin profiles before, during, and after inflammatory-related diseases could provide clues to the onset, development, and prevention of detrimental conditions. This review focusses on recent developments in our understanding of the role of oxylipins in inflammatory disease, and outlines novel technological advancements and approaches to study their action.


Percutaneous cryoablation in early stage hepatocellular carcinoma: analysis of local tumor progression factors.
We aimed to evaluate the effectiveness and safety of percutaneous cryoablation (PC) for early or very early stage hepatocellular carcinoma (HCC) and assess the risk factors for local tumor progression (LTP) after PC. A total of 45 treatment-naïve patients treated with PC for early or very early stage HCCs were included in this retrospective study. The safety of PC was assessed by evaluating procedure-related complications and comparing hepatic function before and after the procedure. The effectiveness was assessed by evaluating technical success, LTP rates, and disease progression (DP) rates. Prognostic factors associated with LTP after PC were also analyzed. Technical success and complete response were achieved in all patients (100%) by 1 month after PC. During a mean of 28.1±15.6 months of follow-up, the incidences of LTP and DP were 11.1% and 37.8%, respectively. The LTP-free and DP-free survival rates were 93.3% and 84.4% at 1 year and 88.9% and 62.2% at 2 years, respectively. Hepatic function was normalized within 3 months after PC. There were no major complications and only one minor complication of small hematoma. On univariate and multivariate analysis, minimal ablative margin <5 mm was the only significant risk factor associated with LTP. PC is a safe and effective therapy for patients with early or very early stage HCC. Minimal ablative margin <5 mm was a significant prognostic factor for LTP.