Evaluation of attic retraction pockets by microendoscopy.
Attic retraction pockets (RPs) are one of the important sequelae of otitis media with effusion and are classified on the basis of the findings of otoscopy or otomicroscopy. It is unclear when and how RPs turn into cholesteatomas. We compared the findings of RPs obtained with the use of a microendoscope with those from an otomicroscope to determine the extension of RPs. Comparative study. Twenty-seven attic RPs (Tos type III or IV) and 10 precholesteatomas previously classified under an otomicroscope were reexamined. A high-resolution, fine, rigid microendoscope with an outer diameter of 1.0 mm was used to observe the extension of a retraction. In addition, to confirm the extent of the RP, computed tomography (CT) scans using water as the contrast media were performed in representative cases. Endoscopy with the microendoscope revealed that in 59%, the RP was deeper than indicated by the initial otomicroscopic estimation, suggesting that the extension of the RP was underestimated. The findings of water-enhanced CT scans were comparable with the endoscopic findings. The bottom was observable with the microendoscope and the otomicroscope in 20 (74%) and 11 (41%) of 27 RPs, respectively. Seven ears had a deeper RP, which extended beyond the incudomallear joint. Of the 10 precholesteatoma cases, in which the bottoms were not visible with an otomicroscope or conventional endoscopes, the microendoscope revealed the bottom in 5 (50%). On the basis of the observations of our study, we suggest that reexamination of cases of RP classified as Tos type III or IV, preferably with a microendoscope, if available, and assessment of the depth of the RP using water-enhanced CT, would be useful and that careful follow-up is necessary for deep RPs because of a potential risk of development into cholesteatoma.


A New Functional Classification of Glucuronoyl Esterases by Peptide Pattern Recognition.
Glucuronoyl esterases are a novel type of enzymes believed to catalyze the hydrolysis of ester linkages between lignin and glucuronoxylan in lignocellulosic biomass, linkages known as lignin carbohydrate complexes. These complexes contribute to the recalcitrance of lignocellulose. Glucuronoyl esterases are a part of the microbial machinery for lignocellulose degradation and coupling their role to the occurrence of lignin carbohydrate complexes in biomass is a desired research goal. Glucuronoyl esterases have been assigned to CAZymes family 15 of carbohydrate esterases, but only few examples of characterized enzymes exist and the exact activity is still uncertain. Here peptide pattern recognition is used as a bioinformatic tool to identify and group new CE15 proteins that are likely to have glucuronoyl esterase activity. 1024 CE15-like sequences were drawn from GenBank and grouped into 24 groups. Phylogenetic analysis of these groups made it possible to pinpoint groups of putative fungal and bacterial glucuronoyl esterases and their sequence variation. Moreover, a number of groups included previously undescribed CE15-like sequences that are distinct from the glucuronoyl esterases and may possibly have different esterase activity. Hence, the CE15 family is likely to comprise other enzyme functions than glucuronoyl esterase alone. Gene annotation in a variety of fungal and bacterial microorganisms showed that coprophilic fungi are rich and diverse sources of CE15 proteins. Combined with the lifestyle and habitat of coprophilic fungi, they are predicted to be excellent candidates for finding new glucuronoyl esterase genes.


MR angiography of the thoracic, abdominal, and extremity venous system.
MR angiography is a useful clinical tool for noninvasive evaluation of the abdominal, thoracic, and peripheral venous system. A variety of MR techniques are available, although two-dimensional time-of-flight is used most commonly. MR imaging of the venous system is less hindered by technical limitations and artifacts commonly encountered with imaging of the arterial system. This article reviews the most commonly used techniques and their clinical application.


Detectable signals of episodic risk effects on acute HIV transmission: strategies for analyzing transmission systems using genetic data.
Episodic high-risk sexual behavior is common and can have a profound effect on HIV transmission. In a model of HIV transmission among men who have sex with men (MSM), changing the frequency, duration and contact rates of high-risk episodes can take endemic prevalence from zero to 50% and more than double transmissions during acute HIV infection (AHI). Undirected test and treat could be inefficient in the presence of strong episodic risk effects. Partner services approaches that use a variety of control options will be likely to have better effects under these conditions, but the question remains: What data will reveal if a population is experiencing episodic risk effects? HIV sequence data from Montreal reveals genetic clusters whose size distribution stabilizes over time and reflects the size distribution of acute infection outbreaks (AIOs). Surveillance provides complementary behavioral data. In order to use both types of data efficiently, it is essential to examine aspects of models that affect both the episodic risk effects and the shape of transmission trees. As a demonstration, we use a deterministic compartmental model of episodic risk to explore the determinants of the fraction of transmissions during acute HIV infection (AHI) at the endemic equilibrium. We use a corresponding individual-based model to observe AIO size distributions and patterns of transmission within AIO. Episodic risk parameters determining whether AHI transmission trees had longer chains, more clustered transmissions from single individuals, or different mixes of these were explored. Encouragingly for parameter estimation, AIO size distributions reflected the frequency of transmissions from acute infection across divergent parameter sets. Our results show that episodic risk dynamics influence both the size and duration of acute infection outbreaks, thus providing a possible link between genetic cluster size distributions and episodic risk dynamics.


Smad3 deficiency attenuates renal fibrosis, inflammation,and apoptosis after unilateral ureteral obstruction.
Transforming growth factor-beta (TGF-beta) has been implicated in the development of renal fibrosis induced by unilateral ureteral obstruction (UUO). However, there is little information on signaling pathways mediating TGF-beta activity involved in molecular and cellular events leading to renal fibrosis induced by UUO. In this study, we sought to determine whether Smad3, a major signaling component of TGF-beta, mediated renal fibrosis induced by UUO. Renal fibrosis, inflammation, and apoptosis induced by UUO were macroscopically and histologically compared between wild-type mice and Smad3 null mice. Gross appearance of the kidney after UUO showed relatively intact kidney in Smad3 null mice [Smad3(-/-) mice] when compared with that of wild-type mice [Smad3(+/+) mice]. Renal interstitial fibrosis based on the interstitial area stained with Aniline-blue or Sirius red solution was significantly attenuated in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice. Deposition of type I and type III collagens were also significantly reduced in the obstructed kidney of Smad3(-/-) mice. In addition, the numbers of myofibroblasts, macrophages, and CD4/CD8 T cells infiltrated into the kidney after UUO were significantly attenuated in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice. Furthermore, terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) staining after UUO showed significantly reduced number of tubular apoptotic cells in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice. Endogenous Smad pathway was activated in the obstructed kidney after UUO in wild-type mice as judged by the increase of phosphorylated Smad2 or phosphorylated Smad2/3-positive cells in renal interstitial area. Smad3 deficiency attenuated renal fibrosis, inflammation, and apoptosis after UUO, suggesting that Smad3 was a key molecule mediating TGF-beta activity leading to real fibrosis after UUO.


Long-Term Safety and Efficacy of Tacrolimus in Myasthenia Gravis.
Myasthenia gravis (MG) is a lifelong autoimmune disorder that affects neuromuscular transmission. The long-term treatment plan should include immunotherapy. We investigated the long-term safety and efficacy of tacrolimus for the treatment of MG in real-world clinical practice. We retrospectively reviewed 160 MG patients treated with tacrolimus from 2005 to 2015. Myasthenia Gravis Foundation of America (MGFA) clinical classification, MGFA post-intervention status, myasthenic functional score, and dose of oral prednisolone were investigated. Adverse events occurred in 68 patients (42.5%), most of which were minor and well-managed. Clinical severity scales improved after administration of tacrolimus, compared to the baseline. Compared to 6 months before administration of tacrolimus, prednisolone dose significantly decreased at 12 months after treatment (2.85±0.92 mg/day, p=0.002), 18 months after treatment (3.36±0.99 mg/day, p=0.001), and 24 months after treatment (3.71±0.93 mg/day, p<0.001). Tacrolimus may be effective in reducing the severity of MG and may permit a reduction in the steroid dose prescribed to the patients. Adverse events due to tacrolimus treatment were not serious.


[Studies on cerebral scavenger cells (fluorescent granular perithelial cells) - especially uptake and digestion of incorporated fat].
Small cerebral vessels including capillaries are provided with the specific barrier (blood brain barrier) for a transport of substances from blood to cerebral tissue. However, it is also established that fat soluble substances are easily permeable in this barrier. Along cerebral small vessels, the cells having intracellular fluorescent granules are distributed and named "fluorescent granular perithelia (F.G.P.)" by the authors. They are potent in the uptake capacity for exogenous substances as reported in the previous papers. In this study, 24 male Wistar rats aged 8 months and 2.5 years old were employed. They were fed with a fat rich chow (Oriental Co.) containing 10% lard, 2% cholesterol and methylthiouracil for one day and fifteen days. Half of them was subcutaneously injected with 5 mg/kg of elastase (Eisai Co.) dissolved in physiological saline once a day. To clarify the effect of elastase on fat incorporated by F.G.P., 4 rats aged 2.5 years were fed with a fat rich chow for 2 days. After then, they were fed with ordinal rat chow for 3 days with or without elastase injection. After decapitation, cerebral cortex of rats was removed in cold physiological saline and sliced with a blade. Half of the sliced specimens was prepared by the authors' method (Mato and Ookawara, 1979) and stained with hematoxylin eosin, periodic acid Schiff reaction and sudan black B for a light microscopical observation. The other half of the specimens was immersed in a mixture containing 2% paraformaldehyde and 2.5% glutaraldehyde buffered with 0.1M phosphate solution (pH 7.4) for 10 h. The specimens were then postfixed with osmium tetroxide buffered with the same solution for 2h. The other procedures for embedding and cutting were the same as in a routine method. Following findings were obtained at the light and electron microscopical levels; when they were fed with a fat rich chow, fat in blood passed through vascular walls and was taken up by F.G.P.. The quantity of fatty deposits in F.G.P. was different depending on age of rats employed for the experiment. The deposits in F.G.P. increased with advancing of age. That is, in old rats a lot of deposits were chiefly distributed in inclusion bodies at one and fifteen days after the administration. The difference in quantity of deposits between young and old rats was not only based on the permeability of vessels, but on the digestion capacity of F.G.P. for fat. On the other hand, Elastase, a specific enzyme for lysis and synthesis of elastic components, prepared by Eisai Co., made a suppressive effect to the permeability of cerebral small vessels and facilitated markedly the digestion capacity of F.G.P. for fat, although the mechanism remained unsettled. From this standpoint, F.G.P. are also designated as "cerebral scavenger cells".


Early-Onset Friedreich's Ataxia With Oculomotor Apraxia.
Friedreich's ataxia (FRDA) is a rare autosomal recessive spinocerebellar ataxia which in the majority of cases is associated with a GAA-trinucleotide repeat expansion in the first intron of Frataxin gene located on chromosome 9. The clinical features include progressive gait and limb ataxia, cerebellar dysarthria, neuropathy, optic atrophy, and loss of vibration and proprioception. Ataxia with ocular motor apraxia type 1 (AOA1) is another autosomal recessive cerebellar ataxia which is associated with oculomotor apraxia, hypoalbuminaemia, and hypercholesterolemia. Here we describe two siblings (13- and 10-year-old) display overlapping clinical features of both early-onset FRDA and AOA1. Almost all of laboratory test (including urinary analysis/culture, biochemistry, peripheral blood smear, C-reactive protein level, erythrocyte sedimentation rate-1h) results were within the normal range for both patients. Due to the normal laboratory test results; we concluded that the diagnosis was more likely to be FRDA than AOA1. Therefore, neurologists should bear in mind that clinical presentations of FRDA may vary widely from the classical phenotype of gait and limb ataxia to atypical manifestations such as oculomotor apraxia.


Controlled synthesis of gold nanostructures by a thermal approach.
Shape-controlled gold nanostructures were successfully synthesized in an aqueous solution by a one-step, non-templated thermal reduction method through heating of a poly(vinylpyrrolidone)/HAuCl4 aqueous solution. Poly(vinylpyrrolidone) (PVP) serves as both the stabilizing surfactant and reducing agent for the controlled synthesis of gold nanostructures with different shapes. Upon adjusting the chain-length and the concentration of the PVP, decahedral, icosahedral and platelike gold nanostructures with dominating distribution were fabricated, respectively, with the ratio of terminating OH groups at the polymer to Au ions as an important experimental parameter. The results suggest that the morphology of the gold nanostructures could be tuned by this method. The successful preparation of gold nanostructures exemplifies a very facile, effective, and generic strategy for fabrication of gold nanoparticles with various shapes.


Leaf Photosynthetic Parameters Related to Biomass Accumulation in a Global Rice Diversity Survey.
Mining natural variations is a major approach to identify new options to improve crop light use efficiency. So far, successes in identifying photosynthetic parameters positively related to crop biomass accumulation through this approach are scarce, possibly due to the earlier emphasis on properties related to leaf instead of canopy photosynthetic efficiency. This study aims to uncover rice (Oryza sativa) natural variations to identify leaf physiological parameters that are highly correlated with biomass accumulation, a surrogate of canopy photosynthesis. To do this, we systematically investigated 14 photosynthetic parameters and four morphological traits in a rice population, which consists of 204 U.S. Department of Agriculture-curated minicore accessions collected globally and 11 elite Chinese rice cultivars in both Beijing and Shanghai. To identify key components responsible for the variance of biomass accumulation, we applied a stepwise feature-selection approach based on linear regression models. Although there are large variations in photosynthetic parameters measured in different environments, we observed that photosynthetic rate under low light (Alow) was highly related to biomass accumulation and also exhibited high genomic inheritability in both environments, suggesting its great potential to be used as a target for future rice breeding programs. Large variations in Alow among modern rice cultivars further suggest the great potential of using this parameter in contemporary rice breeding for the improvement of biomass and, hence, yield potential.


Development of accessible peptidic tool compounds to study the phosphatase PTP1B in intact cells.
Protein tyrosine phosphatases (PTPs) play crucial roles in health and disease. Chemical modulators of their activity are vital tools to study their function. An important aspect is the accessibility of these tools, which is usually limited or not existent due to the required, often complex synthesis of the molecules. We describe here a strategy for the development of cellular active inhibitors and in-cell detection tools for PTP1B as a model PTP, which plays important roles in diabetes, obesity, and cancer. The tool compounds are based on a peptide sequence from PTP1B's substrate Src, and the resulting compounds are commercially accessible through standard peptide synthesis. The peptide inhibitor is remarkably selective against a panel of PTPs. We provide the co-crystal structure of PTP1B with the sequence from Src and the optimized peptide inhibitor, showing the molecular basis of the interaction of PTP1B with part of its natural substrate and explaining the crucial interactions to enhance binding affinity, which are made possible by simple optimization of the sequence. Our approach enables the broad accessibility of PTP1B tools to researchers and has the potential for the systematic development of accessible PTP modulators to enable the study of PTPs.


Laboratory tests for allergy diagnosis.
The introduction of highly purified natural and recombinant single allergenic molecules represented an important improvement in the diagnosis of IgE sensitization. The identification of specific IgE against cross-reacting molecules such as profilin, lipid transfer proteins, calcium binding proteins or against "genuine molecules", represents an added value and allows to distinguish between true and false polysensitization. In vitro tests add information to recognize patients with sensitization to genuine molecules that cause allergic diseases and to evaluate in childhood the spreading of sensitization for each molecule in order to choose the best treatment and to identify the ideal patient for allergen immunotherapy. Also, in order to detect patients with sensitization to pan-allergens it is important to manage the risk of anaphylaxis for patients allergic to latex and to identify IgE to particular molecules involved in occupational allergy. In patients with negative skin prick tests (SPT), that results in a lower sensitivity compared with in vitro tests, the negative test may be caused by the lack of some important allergenic molecules in the extract used for SPT.


Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Buyang Huanwu Decoction in the Treatment of Ischemic Stroke.
The bioactive components and potential targets of BHD were screened by TCMSP, BATMAN-TCM, ETCM, and SymMap databases. Besides, compounds that failed to find the targets from the above databases were predicted through STITCH, SwissTargetPrediction, and SEA. Moreover, six databases were searched to mine targets of IS. The intersection targets were obtained and analyzed by GO and KEGG enrichment. Furthermore, BHD-IS PPI network, compound-target network, and herb-target-pathway network were constructed by Cytoscape 3.6.0. Finally, AutoDock was used for molecular docking verification. A total of 235 putative targets were obtained from 59 active compounds in BHD. Among them, 62 targets were related to IS. PPI network showed that the top ten key targets were IL6, TNF, VEGFA, AKT1, etc. The enrichment analysis demonstrated candidate BHD targets were more frequently involved in TNF, PI3K-Akt, and NF-kappa B signaling pathway. Network topology analysis showed that Radix Astragali was the main herb in BHD, and the key components were quercetin, beta-sitosterol, kaempferol, stigmasterol, etc. The results of molecular docking showed the active components in BHD had a good binding ability with the key targets. Our study demonstrated that BHD exerted the effect of treating IS by regulating multitargets and multichannels with multicomponents through the method of network pharmacology and molecular docking.


A 100 kV, 50 Hz repetitive high-voltage pulse lifetime test platform.
The pulse lifetime characteristics of solid materials have been widely concerned in the field of pulse power technology. In this paper, a repetitive high-voltage pulse lifetime test platform for the pulse lifetime test of insulation materials is set up. The platform contains a closed magnetic-core transformer and a sample cavity. The transformer insulated by transformer oil was stably operated at the 100 kV/50 Hz mode with maximum rise time of 45 µs. The sample cavity insulated by SF6 gas includes a gas switch with an amplitude jitter less than 3% at the 50 Hz mode. The platform has advantages of high efficiency and reliability. First, it can generate three kinds of different pulses simultaneously, which satisfied the insulation test requirements under different pulse conditions. The first kind of the generated pulse is a sinusoidal pulse with an amplitude of 100 kV when the gas switch keeps open. The second one is a unipolar microsecond pulse when the gas switch closes. The last one is a nanosecond pulse generated by secondary capacitor discharge. Second, long-time operation of the platform including the pulse transformer is realized. The platform was stably operated for more than 20 × 106 pulses at the 50 Hz/100 kV mode for pulse lifetime tests of solid pulse forming lines and other solid materials.


Wiki use in mental health practice: recognizing potential use of collaborative technology.
Web 2.0, the second-generation of the World Wide Web, differs to earlier versions of Web development and design in that it facilitates more user-friendly, interactive information sharing and mechanisms for greater collaboration between users. Examples of Web 2.0 include Web-based communities, hosted services, social networking sites, video sharing sites, blogs, mashups, and wikis. Users are able to interact with others across the world or to add to or change website content. This paper examines examples of wiki use in the Australian mental health sector. A wiki can be described as an online collaborative and interactive database that can be easily edited by users. They are accessed via a standard Web browser which has an interface similar to traditional Web pages, thus do not require special application or software for the user. Although there is a paucity of literature describing wiki use in mental health, other industries have developed uses, including a repository of knowledge, a platform for collaborative writing, a project management tool, and an alternative to traditional Web pages or Intranets. This paper discusses the application of wikis in other industries and offers suggestions by way of examples of how this technology could be used in the mental health sector.


The Src family kinase Fgr is critical for activation of mast cells and IgE-mediated anaphylaxis in mice.
Mast cells are critical for various allergic disorders. Mast cells express Src family kinases, which relay positive and negative regulatory signals by Ag. Lyn, for example, initiates activating signaling events, but it also induces inhibitory signals. Fyn and Hck are reported to be positive regulators, but little is known about the roles of other Src kinases, including Fgr, in mast cells. In this study, we define the role of Fgr. Endogenous Fgr associates with FcεRI and promotes phosphorylation of Syk, Syk substrates, which include linkers for activation of T cells, SLP76, and Gab2, and downstream targets such as Akt and the MAPKs in Ag-stimulated mast cells. As a consequence, Fgr positively regulates degranulation, production of eicosanoids, and cytokines. Fgr and Fyn appeared to act in concert, as phosphorylation of Syk and degranulation are enhanced by overexpression of Fgr and further augmented by overexpression of Fyn but are suppressed by overexpression of Lyn. Moreover, knockdown of Fgr by small interfering RNAs (siRNAs) further suppressed degranulation in Fyn-deficient bone marrow-derived mast cells. Overexpression of Fyn or Fgr restored phosphorylation of Syk and partially restored degranulation in Fyn-deficient cells. Additionally, knockdown of Fgr by siRNAs inhibited association of Syk with FcεRIγ as well as the tyrosine phosphorylation of FcεRIγ. Of note, the injection of Fgr siRNAs diminished the protein level of Fgr in mice and simultaneously inhibited IgE-mediated anaphylaxis. In conclusion, Fgr positively regulates mast cell through activation of Syk. These findings help clarify the interplay among Src family kinases and identify Fgr as a potential therapeutic target for allergic diseases.


Involvement of intermediate sulfur species in biological reduction of elemental sulfur under acidic, hydrothermal conditions.
The thermoacidophile and obligate elemental sulfur (S(8)(0))-reducing anaerobe Acidilobus sulfurireducens 18D70 does not associate with bulk solid-phase sulfur during S(8)(0)-dependent batch culture growth. Cyclic voltammetry indicated the production of hydrogen sulfide (H(2)S) as well as polysulfides after 1 day of batch growth of the organism at pH 3.0 and 81°C. The production of polysulfide is likely due to the abiotic reaction between S(8)(0) and the biologically produced H(2)S, as evinced by a rapid cessation of polysulfide formation when the growth temperature was decreased, inhibiting the biological production of sulfide. After an additional 5 days of growth, nanoparticulate S(8)(0) was detected in the cultivation medium, a result of the hydrolysis of polysulfides in acidic medium. To examine whether soluble polysulfides and/or nanoparticulate S(8)(0) can serve as terminal electron acceptors (TEA) supporting the growth of A. sulfurireducens, total sulfide concentration and cell density were monitored in batch cultures with S(8)(0) provided as a solid phase in the medium or with S(8)(0) sequestered in dialysis tubing. The rates of sulfide production in 7-day-old cultures with S(8)(0) sequestered in dialysis tubing with pore sizes of 12 to 14 kDa and 6 to 8 kDa were 55% and 22%, respectively, of that of cultures with S(8)(0) provided as a solid phase in the medium. These results indicate that the TEA existed in a range of particle sizes that affected its ability to diffuse through dialysis tubing of different pore sizes. Dynamic light scattering revealed that S(8)(0) particles generated through polysulfide rapidly grew in size, a rate which was influenced by the pH of the medium and the presence of organic carbon. Thus, S(8)(0) particles formed through abiological hydrolysis of polysulfide under acidic conditions appeared to serve as a growth-promoting TEA for A. sulfurireducens.


Determination of intraparticulate mass transfer coefficients via permeation measurements: theory and experimental validation.
A mathematical model of mass transfer through a heterogeneous, multiphase barrier has been developed where the dispersed phase is capable of uptake of the diffusant according to a linear relationship. The model was used to describe the penetration of drugs through dispersions of permeable globules in media of known diffusional properties. Water-in-oil-in-water (W/O/W) multiple emulsions have been studied by this method. When used to analyze data obtained with a simple diffusion cell, the model allows the calculation of the mass transfer coefficient which characterizes the diffusional mass transfer across oil-water interfaces within the emulsions. The mass transfer coefficient is directly related to the drug release rate from the internal phases of multiple emulsions. Those cases where instantaneous equilibria are established or where impermeable globules are present can be treated as special limiting cases. Differential equations which express diffusant concentrations as functions of time, space, and dispersion system parameters have been solved by Laplace transformation without recourse to numerical methods. The values of the mass transfer coefficient are shown to reflect the physical characteristics of multiple emulsion systems.


[A risk analysis by a measles exportation model concerning the FIFA World Cup 2002].
Risk of measles exportation from Japan is of concern regarding the FIFA World Cup 2002 (WC 2002), which will be held in Korea and Japan in June, 2002. During January 1999 through June 2001. the number of reported exportation cases from Japan was 7 to Australia and 22 to the United States. During the same time, a total of 2.13 million and 14.69 million people traveled between Japan-Australia and Japan-US, respectively. Based on an estimated number for travelers during the WC 2002 (420,000-432,000) announced by the Japanese Ministry of Transportation, we estimated the number of travelers for Japan-Australia and Japan-US would be 16,000 and 109,000 respectively. We analyzed the risk of measles exportation to Australia (PAU) and the United States (PUS) regarding travel for the WC2002 by assumption that measles exposure and transmission would be similar with the usual setting: P = 1 - [1 - (reported exported measles/number of travelers)]estimated number of travelers. The risk was estimated as PAU = 0.051 and PUS = 0.15, however, the results could be higher, because the peak of measles usually lies during May through June and exposure of the virus among young population during the soccer watch would be denser. Through immunization to one-year-old Japanese children is highly needed, as well as strengthening of international measles surveillance especially after the WC2002.


An alternative approach for repair of supracardiac and infracardiac total anomalous pulmonary venous drainage in neonates and infants: superior approach with caval transection.
Recently, the superior approach with transaction of the superior vena cava was introduced for the repair of supracardiac anomalies in adults. We developed a bidirectional right-angle venous cannula and placed it within the innominate vein to make the modified superior approach with the superior caval transection suitable for neonates and tiny infants. We applied this modified superior approach for the repair of infracardiac forms of total anomalous pulmonary venous drainage.


The invasion of urban forest by dengue vectors in Rio de Janeiro.
The invasion of a secondary forest within the city of Rio de Janeiro by Aedes aegypti and Ae. albopictus was evaluated from July 1997 to June 1998 through collections of immature stages in ovitraps set at 1 m, 10 m, 100 m, 500 m, and 1,000 m into the forest from houses on the periphery. Both mosquito species were much more abundant close to houses (1-10 m). Aedes aegypti was not collected beyond 100 m, while Ae. albopictus was the most abundant species overall and in ovitraps at all distances from houses. Abundances of Ae. albopictus were significantly correlated with time-lagged rainfall and with abundances of Ae. aegypti. Co-occurrences of Ae. albopictus in traps with Ae. aegypti and Limatus durhami, but not with Culex dolosus, were more likely close to houses. The results suggest that the urban forest is a refuge for both Aedes species, but especially for Ae. albopictus, whose abundance both near houses and in the forest raises concern that this invader may transmit arboviruses to humans that are presently restricted to the sylvan environment.


Sexual Consent Capacity Assessment with Older Adults.
Many healthcare providers have a limited knowledge of sexual and intimate expression in later life, often due to attitudinal and informational limitations. Further, the likelihood of an older adult experiencing cognitive decline increases in a long-term care (LTC) setting, complicating the ability of the providers to know if the older adult can make his or her own sexual decisions, or has sexual consent capacity. Thus, the team is left to question if and how to support intimacy and/or sexuality among residents with intimacy needs. Psychologists working with LTC need to be aware and knowledgeable about sexual consent capacity in older adulthood to be prepared to conduct evaluations and participate in planning care. Limited research is available to consult for best practices in sexual consent capacity assessment; however, models of assessment have been developed based on the best available evidence, clinical judgment, and practice. Existing models will be discussed and an integrated model will be illustrated via a case study.


DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor MEIS1 in acute myeloid leukemia.
Close to half of de novo acute myeloid leukemia (AML) cases do not exhibit any cytogenetic aberrations. In this regard, distortion of the DNA methylation setting and the presence of mutations in epigenetic modifier genes can also be molecular drivers of the disease. In recent years, somatic missense mutations of the DNA methyltransferase 3A (DNMT3A) have been reported in ~20% of AML patients; however, no obvious critical downstream gene has been identified that could explain the role of DNMT3A in the natural history of AML. Herein, using whole-genome bisulfite sequencing and DNA methylation microarrays, we have identified a key gene undergoing promoter hypomethylation-associated transcriptional reactivation in DNMT3 mutant patients, the leukemogenic HOX cofactor MEIS1. Our results indicate that, in the absence of mixed lineage leukemia fusions, an alternative pathway for engaging an oncogenic MEIS1-dependent transcriptional program can be mediated by DNMT3A mutations.


Association of Fellow Eye With Study Eye Disease Trajectories and Need for Fellow Eye Treatment in Collaborative Initial Glaucoma Treatment Study (CIGTS) Participants.
Clinicians would benefit from knowing the association of glaucomatous change in 2 eyes of the same patient. To estimate the time between initial glaucoma treatment of the study eye (SE) and the need for treatment of the fellow eye (FE) and to ascertain the concordance between rates of progression in SEs and FEs. In this post hoc analysis of participants from the Collaborative Initial Glaucoma Treatment Study, 607 participants with newly diagnosed open-angle glaucoma in 1 or both eyes were followed up for up to 11 years. An SE was designated at baseline and randomized to medical or surgical treatment. By protocol, FEs were treated when eligible or at physician discretion. Survival analysis methods were used to estimate the probability of FE treatment over time and to test baseline and time-dependent predictors of treatment. Disease trajectory was calculated with linear regression as the patient eye-specific slopes of mean deviation (MD) and intraocular pressure (IOP) over time, and correlations between SE and FE trajectories were calculated. Data were collected from October 1993 to December 2004. Data were analyzed from September 2012 to May 2018. Time to FE treatment and slopes over time of MD and IOP in SEs and FEs. Of the 607 included patients, 334 (55.0%) were male and 337 (55.5%) were white, and the mean (SD) age was 58.0 (10.9) years. A total of 291 FEs (47.9%) were treated at baseline, 123 (20.3%) were eventually treated, and 193 (31.8%) never received treatment. The probability of FE treatment for open-angle glaucoma was 0.57 at 1 year and 0.68 at 7 years after randomization. Characteristics significantly associated with an increased hazard of FE treatment included older age (hazard ratio [HR], 1.33; 95% CI, 1.08-1.64; P = .007), hypertension (HR, 1.76; 95% CI, 1.16-2.67; P = .008), higher IOP (HR, 1.24; 95% CI, 1.20-1.29; P < .001), large cup-disc ratio (HR, 1.40; 95% CI, 1.23-1.58; P < .001), and worse MD. Correlations in MD slopes between SEs and FEs initially, eventually, and never treated were 0.73, 0.71, and 0.34, respectively. Comparable correlations in IOP slopes were 0.57, 0.24, and 0, respectively. Among patients with newly diagnosed open-angle glaucoma, almost half had initial treatment of both eyes. After 7 years, approximately two-thirds of patients had bilateral treatment. Of the variables predictive of FE treatment, modifiable factors included hypertension and IOP. Slopes of MD were similar between SEs and treated FEs. This implies that SE change is a harbinger of FE change and therefore warrants close surveillance.


[Parathyroid hypofunction after total thyroidectomy for differentiated thyroid carcinoma--perspectives after long term observation and treatment].
Hypoparathyroidism remains a serious complication of total thyroidectomy for differentiated thyroid carcinoma (DTC). In Brachytherapy Department 952 patients affected with DTC were followed up in the years 1996-2000. Radical total thyroidectomy was performed in 235 (24.6%) of cases, while the other 717 patients underwent complete rethyroidectomy. The incidence of hypoparathyroidism following radical operation and after complete rethyroidectomy was 15.74% and 23.43%, respectively. In patients operated in our institution, blood for calcium was analyzed daily for five days following the surgery. If calcium level was normal the next measurement was performed 4-5 weeks thereafter. Hypoparathyroidism was diagnosed later in postoperative period in many patients operated elsewhere. Asymptomatic hypocalcemia during the first week after the operation requires oral administration of calcium. If hypocalcemia requiring intravenous calcium supplementation does not resolve in a few days, vitamin 1(OH)D3 is introduced. Vitamin 1(OH)D3 and calcium carbonate play the main role in management of persistent hypocalcemia. In case of marked hypercalciuria thiazid diuretics are instituted. Low-phosphate diet is recommended. The aim of treatment of hypoparathyroidism is to restore normal serum calcium level with calciuria not exceeding 5 mg/kg/24 h, so to avoid hypocalcemic complications as well as vitamin D intoxication.


Radiofrequency Exposures of Workers on Low-Power FM Radio Transmitters.
Low-power radio transmitters are one of the most common radio frequency sources and the exposure limit values (ELVs) for occupational exposure may be exceeded close to them. Therefore, a detailed analysis and assessment of occupational exposure in their vicinity is presented in the paper. For 20 different exposure scenarios, electric field strength and specific absorption rate (SAR) values were computed to determine whether the action levels (ALs) and ELVs of the European directive 2013/35/EU are exceeded for different 500 W radio transmitters. The results show that the ALs are very conservative for such exposure situations. Even when the ALs are greatly exceeded, the SAR values are not necessarily above the limit. However, in some situations, the ELVs were also exceeded. The local 10 g averaged value of the SAR can be exceeded if the worker is grounded (in direct contact with the steel structure), while the whole body ELVs can be exceeded for exposures at distances of <1 m from the transmitting dipole array antennas.


Indications of penetrating keratoplasty in northern India.
To identify the indications for penetrating keratoplasty in northern India. All the eye bank records of penetrating keratoplasties performed during the period from June 1997 to November 2003 at Rajendra Prasad Center for Ophthalmic Sciences were reviewed. During this period, 2022 penetrating keratoplasties were performed. The leading indications for penetrating keratoplasty were corneal scarring (38.03%) followed by acute infectious keratitis (28.38%), regrafting (11.5%), aphakic bullous keratopathy (7.27%), pseudophakic bullous keratopathy (6.18%), and corneal dystrophy (3.85%). Healed infectious keratitis (19.83%) was the most common subcategory among the eyes with corneal scarring followed by traumatic corneal scars (16.71%). Healed (19.83%) and active keratitis (28.38%) together accounted for the majority of keratoplasties (48.21%). In cataract-related corneal edema (13.45%), aphakic bullous keratopathy (7.27%) was almost as frequent as compared with pseudophakic bullous keratopathy (6.18%). Corneal infections either active or healed are the most common indication for keratoplasty in northern India.


Effectiveness of tomotherapy vs linear accelerator image-guided intensity-modulated radiotherapy for localized pharyngeal cancer treated with definitive concurrent chemoradiotherapy: a Taiwanese population-based propensity score-matched analysis.
This study used a population-based propensity score (PS)-matched analysis to compare the effectiveness of tomotherapy-based image-guided intensity-modulated radiotherapy (referred to as T-IMRT) with that of linear accelerator based (referred to as L-IMRT) for clinically localized pharyngeal cancer (LPC, divided into nasopharyngeal cancer and non-nasopharyngeal cancer) with definitive concurrent chemoradiotherapy (CCRT). Eligible LPC patients diagnosed between 2007 and 2014 were identified among all citizens in Taiwan from the Health and Welfare Data Science Center database. A PS-matched sample based on the PS estimated from the covariables of interest was constructed to compare the effectiveness of T-IMRT with L-IMRT. In the primary analysis, overall survival (OS) was compared for assessment of effectiveness. We also evaluated freedom from local regional recurrence and pharyngeal cancer-specific survival and performed supplementary analyses. The study population included 960 patients equally divided into two groups. OS did not differ significantly between the T-IMRT and L-IMRT groups (hazard ratio for death: 0.82, p = 0.15, 5-year OS rate: 79 and 74% for T-IMRT and L-IMRT, respectively), and there were no significant differences in the other endpoints or supplementary analyses. For LPC patients treated with definitive CCRT, we found no significant difference in disease control or survival between the T-IMRT and L-IMRT groups. However, further studies, especially randomized trials or studies focusing on other dimensions, such as quality of life, are needed. Advances in knowledge: We provide the first population-based study, as well as the largest study, on the clinical effectiveness of T-IMRT compared with L-IMRT in conjunction with CCRT in LPC patients.


Posterior Vertebral Pedicular Tethering for the Treatment of Idiopathic Adolescent Scoliosis.
Over the last decade, there has been a new wave of interest in non-fusion techniques for the treatment of adolescent idiopathic scoliosis. These are not new techniques, as they were first published and presented in the late 1950s, using compression of the convexity or distraction of the concavity of the main curvature. More recently, anterior vertebral body tethering has raised great interest, as although it is a major procedure through the child's chest, it seems appropriate for the thoracic curves. The main objective of this article is to describe Posterior Vertebral Pedicular Tethering (PVPT) as a "new" technique performed as a less invasive spinal procedure for the treatment of certain thoracolumbar and lumbar scoliosis in growing adolescents. It is an alternative growth modulation technique appropriate for thoracolumbar and lumbar curvatures where we observe reduction of the three plane deformity of idiopathic scoliosis in adolescents.


Systemic Administration of Polyelectrolyte Microcapsules: Where Do They Accumulate and When? In Vivo and Ex Vivo Study.
Multilayer capsules of 4 microns in size made of biodegradable polymers and iron oxide magnetite nanoparticles have been injected intravenously into rats. The time-dependent microcapsule distribution in organs was investigated in vivo by magnetic resonance imaging (MRI) and ex vivo by histological examination (HE), atomic absorption spectroscopy (AAS) and electron spin resonance (ESR), as these methods provide information at different stages of microcapsule degradation. The following organs were collected: Kidney, liver, lung, and spleen through 15 min, 1 h, 4 h, 24 h, 14 days, and 30 days after intravenous injections (IVIs) of microcapsules in a saline buffer at a dosage of 2.5 × 10⁸ capsule per kg. The IVI of microcapsules resulted in reversible morphological changes in most of the examined inner organs (kidney, heart, liver, and spleen). The capsules lost their integrity due to degradation over 24 h, and some traces of iron oxide nanoparticles were seen at 7 days in spleen and liver structure. The morphological structure of the tissues was completely restored one month after IVI of microcapsules. Comprehensive analysis of the biodistribution and degradation of entire capsules and magnetite nanoparticles as their components gave us grounds to recommend these composite microcapsules as useful and safe tools for drug delivery applications.


[Impact of exercise on cardiac hemodynamic parameters in students].
Functional changes were studied in first-year students performing exercises. Analyzing the findings indicated that a 500-m race caused unidirectional varying changes in young women and young men. The functional systems of the first-year students responded to strenuous exercises due to the tension of cardiac rhythm regulatory mechanisms, which manifested itself as almost 4.5-fold increase in the activity of the sympathetic regulatory circuit. Excessive tension that was a result of long-term inactivity may be further a cause of disproportionally developed cardiac chambers, leading to myocardial hypertrophy, cardiac arrhythmia, weakened valvular apparatus.


TSC2/Rheb signaling mediates ERK-dependent regulation of mTORC1 activity in C2C12 myoblasts.
The enhanced rate of protein synthesis in skeletal muscle cells results in a net increase in total protein content that leads to skeletal muscle growth/hypertrophy. The mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent regulation of the activity of mechanistic target of rapamycin (mTOR) and subsequent protein synthesis has been suggested as a regulatory mechanism; however, the exact molecular processes underlying such a regulation are poorly defined. The purpose of this study was to investigate regulatory mechanisms involved in the MEK/ERK-dependent pathway leading to mTORC1 activation in skeletal muscle cells. Treatment with phorbol-12-myristate-13-acetate (PMA), a potent agonist of protein kinase C (PKC) and its downstream effector in the MEK/ERK-dependent pathway, resulted in the activation of mTORC1 signaling and phosphorylation of the upstream regulator tuberous sclerosis 2 (TSC2) in C2C12 myoblasts. PMA-induced activation of mTORC1 signaling was partially prevented by treatment with U0126 (a selective inhibitor of MEK1/2) or BIX-02189 (a selective inhibitor of MEK5) and completely blocked with BIM-I (a selective inhibitor of upstream PKC). TSC2 phosphorylation at Ser664 (an ERK-dependent phosphorylation site) was prevented with U0126, and BIM-I treatment blocked PMA-induced phosphorylation of TSC2 at multiple residues (Ser664, Ser939, and Thr1462). Overexpression of Ras homolog enriched in brain (Rheb), a downstream target of TSC2, and an mTORC1 activator, was sufficient to activate mTORC1 signaling. We also identified that PMA-induced activation of mTORC1 signaling was significantly inhibited in the absence of Rheb with siRNA knockdown. These observations demonstrate that the PKC/MEK/ERK-dependent activation of mTORC1 is mediated through TSC2 phosphorylation and its downstream target Rheb in C2C12 myoblasts.


Contraceptive prescriptions for US servicewomen, 2008-2013.
To determine the proportion and characteristics of US servicewomen who were prescribed contraception between 2008 and 2013 and to estimate the prevalence of contraceptive utilization among women who deployed during the surveillance period. This is a descriptive study of all servicewomen of child-bearing potential serving in the active component of the US armed forces at any time between 2008 and 2013. We estimated contraceptive utilization status using pharmacy, procedural and diagnostic codes as recorded in the Defense Medical Surveillance System and Pharmacy Data Transaction Service. Estimates of contraceptive utilization were compared by demographic and military variables, including deployment status. Poisson regression with robust error variance was used to estimate adjusted prevalence ratios and 95% confidence intervals. Among eligible servicewomen (N=375,847), 68.7% received at least one form of contraception during the surveillance period. Contraceptive methods included short acting only (55.6%), long-acting (11.9%), permanent (1.0%) and barrier methods (0.2%). An additional 8.2% received counseling services only without an associated procedure or prescription. After adjusting by several demographic variables, receipt of contraception was highest among women aged 25-29 years and lowest among those aged 17-19 and 45-49 years. Receipt of any contraception was similar across racial/ethnic groups, although Hispanic and black, non-Hispanic women were more likely to receive long-acting reversible contraception. Of those who deployed (N=131,597), 53.6% received contraception before or during their deployment, with 7.9% using long-acting contraception. US servicewomen utilize contraception at high levels, with few demographic disparities. Gaps still exist, especially among the youngest women and around the time of deployment. US servicewomen are prescribed contraception at high levels, but utilization is lower in the youngest servicewomen and around the time of deployment. Such data provide opportunities for development and evaluation of interventions designed to improve access to contraceptive services for all servicewomen and to reduce the rate of unintended pregnancy.


Pattern of intraocular pressure in epidemic dropsy in India.
This study was conducted to report on the intraocular pressure (IOP) pattern in patients with epidemic dropsy. Two hundred and thirty proven cases of epidemic dropsy were sent for ocular examination. We measured IOP by applanation tonometry at different intervals. Patients were followed up until 24 weeks. Intraocular pressure of more than 22 mm of Hg was detected in 10.86% patients at the start of the study. However, at 12 weeks only 0.43% patients needed medication for control of IOP. None required medication for IOP control after 20 weeks. The rise of IOP in this case series of epidemic dropsy appeared to be a transient phenomenon and drugs needed to be titrated on a weekly basis.


'HIV has a woman's face': vaginal microbicides and a case of ambiguous failure.
The case is a primary unit of knowledge production in the field of HIV research, yet the work that is done to construct cases often goes unremarked. In this paper, the case takes centre stage in an analysis of a set of apparent failures in HIV prevention research, namely a series of clinical trials to test vaginal microbicides. Returning to the genesis of the microbicide concept in the early 1990s, I examine how the discourse of women's empowerment was linked to HIV prevention in a way that mobilized a particular vision of the case, which was both politically and scientifically expedient. Drawing on an in-depth empirical study of one particular trial, I show the success of the case in mobilizing funds and interest in the research, as well its success in accounting for the failure of the pharmaceutical technology. Drawing in alternative scientific accounts of the failure of microbicides, however, a different version of events is indicated, in which what can ultimately be said to have failed is not the technology itself, but the act of casing upon which its testing was founded.


A new class of binuclear gallium hydrides: synthesis and properties of [{GaCl(hpp)H}2] (hpp=1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidate).
Herein we report on the synthesis and characterization of the first representative of a new class of gallium hydrides, namely [{GaCl(hpp)H}2] (hpp=1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidate). Our X-ray diffraction data suggest the presence of weak H--H contacts between adjacent [{GaCl(hpp)H}2] molecules in the crystal. With the aid of quantum-chemical calculations, the pathway of its formation starting with the adduct H2ClGaNMe3 and the pyrimidine hppH were analyzed. [{GaCl(hpp)H}2] slowly decomposes at 25 degrees C, a process which presumably leads under H2 elimination to [{GaCl(hpp)}2]. Although we were not yet able to characterize [{GaCl(hpp)}2] experimentally, DFT calculations provide information about its likely structure. According to these calculations, the molecule features a Ga--Ga single bond.


Assessment of the association between genetic factors regulating thyroid function and microvascular complications in diabetes: A two-sample Mendelian randomization study in the European population.
Observational studies have identified a possible link between thyroid function and diabetic microangiopathy, specifically in diabetic kidney disease (DKD) and diabetic retinopathy (DR). However, it is unclear whether this association reflects a causal relationship. To assess the potential direct effect of thyroid characteristics on DKD and DR based on Mendelian randomization (MR). We conducted an MR study using genetic variants as an instrument associated with thyroid function to examine the causal effects on DKD and DR. The study included the analysis of 4 exposure factors associated with thyroid hormone regulation and 5 outcomes. Genomewide significant variants were used as instruments for standardized freethyroxine (FT4) and thyroid-stimulating hormone (TSH) levels within the reference range, standardized free triiodothyronine (FT3):FT4 ratio, and standardized thyroid peroxidase antibody (TPOAB) levels. The primary outcomes were DKD and DR events, and secondary outcomes were estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR) in diabetes, and proliferative diabetic retinopathy (PDR). Satisfying the 3 MR core assumptions, the inverse-variance weighted technique was used as the primary analysis, and sensitivity analysis was performed using MR-Egger, weighted median, and MR pleiotropy residual sum and outlier techniques. All outcome and exposure instruments were selected from publicly available GWAS data conducted in European populations. In inverse-variance weighted random-effects MR, gene-based TSH with in the reference range was associated with DKD (OR 1.44; 95%CI 1.04, 2.41; P = 0.033) and eGFR (β: -0.031; 95%CI: -0.063, -0.001; P = 0.047). Gene-based increased FT3:FT4 ratio, decreased FT4 with in the reference range were associated with increased ACR with inverse-variance weighted random-effects β of 0.178 (95%CI: 0.004, 0.353; P = 0.046) and -0.078 (95%CI: -0.142, -0.014; P = 0.017), respectively, and robust to tests of horizontal pleiotropy. However, all thyroid hormone instruments were not associated with DR and PDR at the genetic level. In diabetic patients, an elevated TSH within the reference range was linked to a greater risk of DKD and decreased eGFR. Similarly, decreased FT4 and an increased FT3:FT4 ratio within the reference range were associated with increased ACR in diabetic patients. However, gene-based thyroid hormones were not associated with DR, indicating a possible pathway involving the thyroid-islet-renal axis. However, larger population studies are needed to further validate this conclusion.


Remarkable effect of the preparation technique on the state of cobalt ions in BEA zeolites evidenced by FTIR spectroscopy of adsorbed CO and NO, TPR and XRD.
The state of cobalt in two BEA zeolites was studied by XRD, TPR, and FTIR spectroscopy using CO and NO as probe molecules. One of the samples, CoAlBEA (0.4 wt % of Co), was prepared by conventional ion exchange and the other, CoSiBEA (0.7 wt % Co), by a two-step postsynthesis method involving dealuminated SiBEA zeolite. The introduction of Co into SiBEA leads to an increase of unit cell parameters of the BEA structure and to the consumption of silanol groups in vacant T-sites of the dealuminated zeolite. In contrast, no structural changes are observed after incorporation of cobalt into AlBEA by ion-exchange. The reduction temperature of cobalt in CoSiBEA zeolite (1130 K), is much higher than for CoAlBEA and indicates a strong interaction of cobalt ions with SiBEA. Low-temperature CO adsorption on CoAlBEA results in (i) H-bonded CO, (ii) Co(3+)-CO adducts (2,208 cm(-1)) and (iii) a small amount of Co(2+)-CO complexes (2,188 cm(-1)). In agreement with these results, NO adsorption leads to the appearance of (i) NO(+) (2,133 cm(-1), formed with the participation of the zeolite acidic hydroxyls), (ii) Co(3+)-NO (1932 cm(-1)), and (iii) a small amount of Co(2+)(NO)(2) dinitrosyls (nu(s) = 1,898 and nu(as) = 1,814 cm(-1)). Low-temperature CO adsorption on CoSiBEA leads to formation of two kinds of Co(2+)-CO adducts (2,185 and 2,178 cm(-1)). No Co(3+) cations are detected. In line with these results, adsorption of NO reveals the existence of two kinds of Co(2+)(NO)(2) dinitrosyls (nu(s) = 1,888 and nu(as) = 1,808 cm(-1) and nu(s) = 1,878 and nu(as) = 1,799 cm(-1), respectively).


Median arcuate ligament syndrome: evaluation with CT angiography.
The median arcuate ligament is a fibrous arch that unites the diaphragmatic crura on either side of the aortic hiatus. The ligament usually passes superior to the origin of the celiac axis. However, in some people, the ligament inserts low and thus crosses the proximal portion of the celiac axis, causing compression and sometimes resulting in abdominal pain. The diagnosis of clinically significant celiac axis compression, referred to as median arcuate ligament syndrome, is traditionally made with conventional angiography; however, the condition can now be diagnosed with three-dimensional computed tomographic (CT) angiography. In patients with median arcuate ligament syndrome, CT angiograms demonstrate a characteristic focal narrowing in the proximal celiac axis. The focal narrowing has a characteristic hooked appearance, which can help distinguish this condition from other causes of celiac artery narrowing, such as atherosclerotic disease. Once the disorder has been diagnosed, surgery can be performed to relieve the compression. In some patients, the ligamentous constriction of the celiac axis causes vascular damage, which may require vascular reconstruction. CT angiography can play a role in the diagnosis of median arcuate ligament syndrome by demonstrating the characteristic focal narrowing of the celiac artery in patients presenting with the appropriate clinical symptoms.


Candidaemia in Sweden: a nationwide prospective observational survey.
A prospective observational nationwide investigation was performed from September 2005 to August 2006 to study the epidemiology of candidaemia in Sweden. From 385 patients, 403 isolates were recovered, yielding an incidence of 4.2 cases per 100 000 inhabitants. Candida albicans was the most common species (61%), followed by Candida glabrata (20%) and Candida parapsilosis (9%). The rates of resistance to fluconazole were ≤ 1% in C. albicans and 6-29% in non-albicans species other than C. glabrata and Candida krusei. Resistance to voriconazole was rare, except for C. glabrata and C. krusei. Only three isolates had reduced susceptibility to amphotericin B, and one had reduced susceptibility to caspofungin.


Lycopene improves autophagy and attenuates carbon tetrachloride-induced hepatic fibrosis in rats.
To evaluate the effect of lycopene on carbon tetrachloride (CCl4)-induced hepatic fibrosis and elucidate the underlying mechanism. Male rats were randomly assigned to the control group, CCl4 group, and lycopene group. The CCl4 group was intraperitoneally injected with CCl4 twice per week for 12 weeks to induce hepatic fibrosis. The control group was intraperitoneally injected with olive oil. Lycopene was orally administered during CCl4 treatment. Body weight and liver weight were recorded. Liver function was assessed. Biomarkers of oxidative stress and inflammatory factors were measured. Histological changes and collagen expression were evaluated. The expression of TGF-β1, α-SMA, HO-1, SIRT 1, REDD1, SHP2, P62, and LC3 in the liver was determined, as well as the levels of phosphorylated NF-κB and IκB α. Lycopene significantly reduced the liver/body weight ratio, and AST (P=0.001) and ALT levels (P=0.009). It also significantly increased CAT and SOD activities (P<0.001) and decreased MDA content (P<0.001), IL-6 (P<0.001), and TNF-α (P=0.001). Histological analysis demonstrated that lycopene improved lobular architecture and decreased collagen expression. It also decreased the expression of TGF-β1, α-SMA, P62, and SHP2, and increased the ratio of LC3 II/I, as well as Beclin 1 and REDD1 expression. In addition, it reduced NF-κB and IκB-α phosphorylation, and elevated the levels of HO-1, SIRT 1, and PGC 1α. Lycopene attenuates CCl4-induced hepatic fibrosis because of its effect on autophagy by reducing oxidative stress and inflammation.


The human genome project and the Catholic Church (1)
The Cathlic Church has not made any formal statements about the Human Genome Project as such. But the present Pope, John Paul II, has commented, albeit very briefly, on various aspects of genetic manipulation. Genetic interventions which are therapeutic (e.g. gene therapy), namely, directed to the correction or amelioration of a disorder are acceptable, in principle, provided they promote the personal well being of the individual being so treated. Genetic interventions which are not therapeutic for the specific individual involved but are experimental and directed primarily to improving humans as biological entities are of dubious moral probity, but are not necessarily to be totally rejected out of hand. To be morally acceptable such genetic intervention should meet certain conditions which include due respect for the given psychological nature of each individual human being. In addition, no harm should be inflicted on the process of human generation, and its fundamental design should not be altered. Any genetic manipulation which results in, or tends to, the creation of groups with different qualities such that there would result a fresh marginalization of these people must be avoided. It has been also suggested by a few that because the Son of God took on a human nature in Jesus Christ, one may not so alter the human genome that a new distinct species would be created....


A multiobjective evolutionary algorithm based on similarity for community detection from signed social networks.
Various types of social relationships, such as friends and foes, can be represented as signed social networks (SNs) that contain both positive and negative links. Although many community detection (CD) algorithms have been proposed, most of them were designed primarily for networks containing only positive links. Thus, it is important to design CD algorithms which can handle large-scale SNs. To this purpose, we first extend the original similarity to the signed similarity based on the social balance theory. Then, based on the signed similarity and the natural contradiction between positive and negative links, two objective functions are designed to model the problem of detecting communities in SNs as a multiobjective problem. Afterward, we propose a multiobjective evolutionary algorithm, called MEAs-SN. In MEAs-SN, to overcome the defects of direct and indirect representations for communities, a direct and indirect combined representation is designed. Attributing to this representation, MEAs-SN can switch between different representations during the evolutionary process. As a result, MEAs-SN can benefit from both representations. Moreover, owing to this representation, MEAs-SN can also detect overlapping communities directly. In the experiments, both benchmark problems and large-scale synthetic networks generated by various parameter settings are used to validate the performance of MEAs-SN. The experimental results show the effectiveness and efficacy of MEAs-SN on networks with 1000, 5000, and 10,000 nodes and also in various noisy situations. A thorough comparison is also made between MEAs-SN and three existing algorithms, and the results show that MEAs-SN outperforms other algorithms.


Gender roles, family relationships, and household food and nutrition security in Ohafia matrilineal society in Nigeria.
This study examined gender roles, family relationships, food security, and nutritional status of households in Ohafia: a matrilineal society in Nigeria. A cross-sectional descriptive study was conducted. Multistage sampling technique was used to select 287 households from three villages: Akanu, Amangwu, and Elu. Qualitative and quantitative data collection methods were adopted, namely, focus group discussions and questionnaires. Anthropometric measurements (height and weight for mothers and children and Mid-Upper Arm Circumference for young children) were taken using standard techniques. The body mass index of women was calculated. All nutritional indices were compared with reference standards. Food insecurity was assessed using the Household Hunger Scale and Dietary Diversity Score, then analysed using the Statistical Product for Service Solution version 21. Data analysis used descriptive statistics. Most (91.2%) of the respondents were female. The matrilineal system known as ikwu nne or iri ala a nne (inheritance through mothers' lineage) is still in place but is changing. One important benefit of the system is the access to land by women. Whereas women participated actively in agriculture, food preparation, and care of family, the men were moving to off-farm activities. High prevalence of household food insecurity (66%) and signs of malnutrition including moderate to severe stunting (48.4%) and wasting (31.7%) in children, household hunger (34.5%), and overweight (27.5%) and obesity (19.2%) among mothers were observed. These communities urgently need gender sensitive food and nutrition interventions.


Tumor-targeting and microenvironment-responsive smart nanoparticles for combination therapy of antiangiogenesis and apoptosis.
Tumor microenvironment, such as the lowered tumor extracellular pH (pHe) and matrix metalloproteinase 2 (MMP2), has been extensively explored, which promotes the development of the microenvironment-responsive drug delivery system. Utilizing these unique features, an activatable cell-penetrating peptide (designated as dtACPP) that is dual-triggered by the lowered pHe and MMP2 has been constructed, and a smart nanoparticle system decorating with dtACPP has been successfully developed, which could dual-load gene drug and chemotherapeutics simultaneously. After systemic administration, dtACPP-modified nanoparticles possess passive tumor targetability via the enhanced permeability and retention effect. Then dtACPP would be activated to expose cell-penetrating peptide to drive the nanoparticles' internalization into the intratumoral cells. As angiogenesis and tumor cells might be mutually improved in tumor growth, so combining antiangiogenesis and apoptosis is meaningful for oncotherapy. Vascular endothelial growth factor (VEGF) is significant in angiogenesis, and anti-VEGF therapy could decrease blood vessel density and delay tumor growth obviously. Chemotherapy using doxorubicin (DOX) could kill off tumor cells efficiently. Here, utilizing dtACPP-modified nanoparticles to co-deliver plasmid expressing interfering RNA targeting VEGF (shVEGF) and DOX (designated as dtACPPD/shVEGF-DOX) results in effective shutdown of blood vessels and cell apoptosis within the tumor. On the premise of effective drug delivery, dtACPPD/shVEGF-DOX has demonstrated good tumor targetability, little side effects after systemic administration, and ideal antitumor efficacy.


Development and validation of the Perceived Food Environment Questionnaire in a French-Canadian population.
The present study aimed to develop and validate a questionnaire assessing perceived food environment in a French-Canadian population. A questionnaire, the Perceived Food Environment Questionnaire, was developed assessing perceived accessibility to healthy (nine items) and unhealthy foods (three items). A pre-test sample was recruited for a pilot testing of the questionnaire. For the validation study, another sample was recruited and completed the questionnaire twice. Exploratory factor analysis was performed on the items to assess the number of factors (subscales). Cronbach's α was used to measure internal consistency reliability. Test-retest reliability was assessed with Pearson correlations. Online survey. Men and women from the Québec City area (n 31 in the pre-test sample; n 150 in the validation study sample). The pilot testing did not lead to any change in the questionnaire. The exploratory factor analysis revealed a two-subscale structure. The first subscale is composed of six items assessing accessibility to healthy foods and the second includes three items related to accessibility to unhealthy foods. Three items were removed from the questionnaire due to low loading on the two subscales. The subscales demonstrated adequate internal consistency (Cronbach's α=0·77 for healthy foods and 0·62 for unhealthy foods) and test-retest reliability (r=0·59 and 0·60, respectively; both P<0·0001). The Perceived Food Environment Questionnaire was developed for a French-Canadian population and demonstrated good psychometric properties. Further validation is recommended if the questionnaire is to be used in other populations.


Synthesis of Lamellarin D Trimethyl Ether and Lamellarin H via 6π-Electrocyclization.
An electrocyclic ring closure of a 2-azapentadienyl anion generated in situ from a chalcone and glycine ester is the key step of an efficient synthesis of the pyrrole core of the lamellarin alkaloids. A recently developed scalable one-pot procedure provides multigram quantities of a 3,5-diaryl-4-iodopyrrole-2-carboxylate intermediate which is transformed in four further high-yielding operations including a one-pot Pomeranz-Fritsch alkylation/cyclization and an Ullmann-type lactone ring closure into the pentacyclic lamellarin skeleton.


Intergenomic interactions between mitochondrial and Y-linked genes shape male mating patterns and fertility in Drosophila melanogaster.
Under maternal inheritance, mitochondrial genomes are prone to accumulate mutations that exhibit male-biased effects. Such mutations should, however, place selection on the nuclear genome for modifier adaptations that mitigate mitochondrial-incurred male harm. One gene region that might harbor such modifiers is the Y-chromosome, given the abundance of Y-linked variation for male fertility, and because Y-linked modifiers would not exert antagonistic effects in females because they would be found only in males. Recent studies in Drosophila revealed a set of nuclear genes whose expression is sensitive to allelic variation among mtDNA- and Y-haplotypes, suggesting these genes might be entwined in evolutionary conflict between mtDNA and Y. Here, we test whether genetic variation across mtDNA and Y haplotypes, sourced from three disjunct populations, interacts to affect male mating patterns and fertility across 10 days of early life in D. melanogaster. We also investigate whether coevolved mito-Y combinations outperform their evolutionarily novel counterparts, as predicted if the interacting Y-linked variance is comprised of modifier adaptations. Although we found no evidence that coevolved mito-Y combinations outperformed their novel counterparts, interactions between mtDNA and Y-chromosomes affected male mating patterns. These interactions were dependent on male age; thus male reproductive success was shaped by G × G × E interactions.


Blue Excitement: The Lanthanide(III) Chloride Oxidomolybdates(VI) Ln3Cl3[MoO6] (Ln = La, Pr, and Nd) and Their Spectroscopic Properties.
The lanthanide(III) chloride oxidomolybdates(VI) with the empirical formula Ln3Cl3[MoO6] (Ln = La, Pr, and Nd) were synthesized by solid-state reactions utilizing the respective lanthanide trichloride, lanthanide sesquioxide (where available), and molybdenum trioxide together with lithium chloride as a fluxing agent. The title compounds crystallize in hexagonal space group P63/ m ( a = 942-926 pm, c = 542-533 pm, Z = 2). Besides tetracapped trigonal prismatically coordinated Ln3+ cations, noncondensed trigonal prismatic [MoO6]6- entities are found in the crystal structure. In addition to X-ray diffraction, the title compounds were also characterized by single-crystal Raman and infrared spectroscopy as well as measurements to determine their magnetic susceptibility and behavior at low temperatures. The most outstanding properties of the Ln3Cl3[MoO6] representatives (Ln = La, Pr, and Nd), however, are of an optical nature, because their band gaps, determined by diffuse reflectance spectroscopy, show a significant shift toward lower energies compared to those of other rare-earth metal chloride molybdates with a different polyhedral arrangement. This culminates in La3Cl3[MoO6]:Eu3+ exhibiting luminescence, which can be excited in the visible range of the electromagnetic spectrum by a blue light-emitting diode.


p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats.
Phosphorylated cAMP-responsive element binding protein-1 (p-CREB-1) is an important transcription factor which has been reported to be implicated in fibrogenesis. However, the association between p-CREB-1 and transforming growth factor-β1 (TGF-β1)-mediated liver fibrogenesis remains poorly understood. In the present study, exogenous TGF-β1 recombinant protein was used to activate hepatic stellate cells (HSCs), and we established a rat model of tetrachloromethane (CCl4)‑induced liver fibrosis. Loss- and gain-of-function studies were performed to examine the role of p-CREB-1 in liver fibrogenesis, and the detailed mechanism responsible for these effects was further explored using chromatin immunoprecipitation and luciferase reporter gene assays. We found that p-CREB-1 expression was significantly upregulated in a rat model of hepatic fibrosis. We also demonstrated that p-CREB-1 increased TGF-β1 expression and auto‑induction in HSCs, through directly binding to the CRE site within the TGF-β1 promoter in order to enhance its transcriptional activity. Moreover, lentivirus-mediated CREB-1 overexpression promoted hepatic fibrogenesis in rats. These findings suggest that p-CREB-1 may function as a potent profibrogenic factor through the transactivation of TGF-β1 expression in liver fibrosis.


Sex under Influence of Drugs: A Nationwide Survey among Iranian Female Sex Workers.
Due to the high level of sexual relationships, prostitute women are faced with many dangers, including acquired immune deficiency syndrome (AIDS), sexually transmitted infections (STIs), fertility problems, drug use, etc. In this regard, addict prostitute women are exposed to more risks because drug use is considered as an outstanding factor in those associated with transmission of AIDS and being in an insecure sexual relationship. The purpose of this study was to find out the variables influential on the level of drug use, before or during sexual relationship. In 2010, 625 prostitute women were selected by multistage sampling from 21 centers out of 12 provinces. Then, we used a standard questionnaire for gathering data by a face-to-face interview. The multilevel ordinal logistic regression in survey model was used to find out the relationship between variables and the level of drug use before or during sexual relationship. The number of monetary customers at the last working day [adjusted odds ratio (AOR): 1.87, 95% confidence interval (CI): 1.50-2.32] and having sexual relationship during the past month with monetary customers (AOR: 4.77, 95% CI: 2.61-8.70) were significantly related to the level of drug use before or during sexual relationship in the past month. Since the level of drug use before or during sexual relationship was higher in women who had more daily sexual relationships, these women are exposed to the consequences of drug use; thus, identifying the status of this group of women is important to plan for future injuries.


Purification, subunit structure and properties of a high-molecular-mass protein phosphatase capable of dephosphorylating mRNP of the brine shrimp Artemia sp.
A phosphoprotein phosphatase active towards casein, phosphorylase a and mRNP proteins has been detected in the cytosol of cryptobiotic gastrulae of Artemia sp. This phosphatase has a relative molecular mass (Mr) of 225,000 as measured by gel filtration on Sephadex G-200 and has been purified to near homogeneity by ion-exchange chromatography on different DEAE-substituted matrices, affinity chromatography on polylysine-agarose, histone-Sepharose 4B and protamine-agarose, hydrophobic chromatography on phenyl-Sepharose 4B and gel filtration on Sephadex G-200. Sodium dodecyl sulphate gel electrophoresis of the final purification step revealed that the enzyme contains two types of subunits, alpha and beta, with Mr of 40,000 and 75,000, respectively. These values, in conjunction with the native Mr and the molar ratios of the subunits estimated by densitometric analysis of the gel, suggested that the subunit composition of the enzyme is alpha 2 beta 2. When treated with 1.7% (v/v) 2-mercaptoethanol at -20 degrees C or with ethanol, the enzyme released the catalytic alpha subunit of Mr 40,000. The protein phosphatase was activated by basic proteins e.g. protamine (A 0.5 = 1 microM), histone H1 (A 0.5 = 1.6 microM) and polylysine (A 0.5 = 0.2 microM) and inhibited by ATP (I 0.5 = 12 microM), NaF (I 0.5 = 3.1 mM) and pyrophosphate (I 0.5 = 0.6 mM). The enzyme is a polycation-stimulated protein phosphatase. Purified mRNP proteins, phosphorylated by the mRNP-associated casein kinase type II, are among the substrates used by the enzyme. The function of reversible phosphorylation-dephosphorylation of mRNP as a regulatory mechanism in mRNP metabolism is discussed.


A Bax/Bak-independent mitochondrial death pathway triggered by Drosophila Grim GH3 domain in mammalian cells.
Grim encodes a protein required for programmed cell death in Drosophila, whose proapoptotic activity is conserved in mammalian cells. Two proapoptotic domains are relevant for Grim killing function; the N-terminal region, which induces apoptosis by disrupting inhibitor of apoptosis protein (IAP) blockage of caspase activity, and the internal GH3 domain, which triggers a mitochondrial pathway. We explored the role of these two domains in heterologous killing of mammalian cells by Grim. The GH3 domain is essential for Grim proapoptotic activity in mouse cells, whereas the N-terminal domain is dispensable. The GH3 domain is required and sufficient for Grim targeting to mitochondria and for cytochrome c release in a caspase- and N-terminal-independent, IAP-insensitive manner. These Grim GH3 activities do not require Bax or Bak function, revealing GH3 activity as the first proapoptotic stimulus able to trigger the mitochondrial death pathway in mammalian cells in the absence of multidomain proapoptotic Bcl-2 proteins.


Description of Micropygomyia (Micropygomyia) ancashensis sp. nov. and the female of Lutzomyia (Helcocyrtomyia) chavinensis Pérez & Ogusuku (Diptera, Psychodidae, Phlebotominae) from Ancash department, Peru.
A male of a new species Micropygomyia (Micropygomyia) ancashensis sp. nov. and a female of the Lutzomyia (Helcocyrtomyia) chavinensis Pérez & Ogusuku, 1999 captured in the Antonio Raymondi province, department of Ancash, Peru are described and illustrated. The new species belongs to the cayennensis series, being closest to Mi. lewisi (Feliciangeli Ordoñez & Férnandez) though presenting highly sclerotized pseudotracheae on the labella that seem to constitute an autapomorphy among American Phlebotominae, and a clypeus almost completely covered with setae, as in Warileya. The female of Lu. chavinensis is close to those of Lu. blancasi Galati & Cáceres 1990, Lu. noguchii (Shannon, 1929), and Lu. pallidithorax Galati & Cáceres 1994.


Acid-base transport in the collecting duct.
The collecting duct is responsible for the final secretion or reabsorption of protons and bicarbonate, respectively. Approximately 2% of the total filtered bicarbonate is reabsorbed in this segment. At least two different types of cells are involved in the transport of protons and bicarbonate, namely, type A and B intercalated cells. Their relative abundance differs in zonal distribution in the collecting duct. A variety of transport proteins and enzymes take part in the transcellular movement of protons and bicarbonate, some of them identified on a molecular level. These proteins are tightly regulated by hormones such as angiotensin II, aldosterone or endothelin or by the metabolic status of the organism. Alterations in acid-base intake or electrolyte status have profound effects on the collecting duct. Moreover, drugs interacting with renal electrolyte or bicarbonate handling (i.e. diuretics, glucocorticoids) also often affect acid-base transport in the collecting duct. For some of the identified proteins mutations have been found in various genetic diseases and syndromes of distal renal tubular acidosis leading to metabolic acidosis and an increased risk of nephrocalcinosis or -lithiasis.


Involvement of the Hippocampus in Binge Ethanol-Induced Spleen Atrophy in Adolescent Rats.
Ethanol (EtOH) affects the immune system. Binge drinking of hard liquor initiates a stress response. This form of drinking is popular during adolescence, which involves maturation of the immune system. The spleen is a key immune organ, and spleen atrophy is associated with immunosuppression. While the hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the initial stress response, the hippocampus may be involved in stress beyond the HPA axis. Blood ethanol concentration (BEC), blood endotoxin levels, and plasma corticosterone levels were measured following binge EtOH treatment. Absolute and relative spleen sizes were analyzed, and stress-related gene expression was compared in the hypothalamus and hippocampus. Polymerase chain reaction array was performed to analyze the expression profile of EtOH metabolism and immune regulation-related genes in the spleen. Relationships among variables were analyzed using the Pearson correlation. At 24 hours following a 3-day EtOH treatment, no significant difference in BEC was detected between EtOH-treated and control rats. Average plasma endotoxin levels in EtOH-treated animals were significantly higher than in controls, and spleen size was significantly lower. Spleen size did not correlate with plasma endotoxin levels; however, it did significantly negatively correlate with plasma corticosterone levels. Spleen size significantly negatively correlated with hippocampal CRH expression and significantly positively correlated with hippocampal MR expression. No correlation was observed in the hypothalamus. Significantly higher hippocampal CRH and significantly lower MR expression was seen in low spleen/body weight (sp-wt) ratio rats. No gene was found to decrease expression ≥1.5-fold (p < 0.05) in the spleen of high sp-wt group, whereas expression of several genes, including Gabra1, Gabra5, Ifnb1, Irf9, Il12b, and Cx3cr1, decreased significantly in the low sp-wt group. Our findings suggest that binge EtOH exposure causes lower spleen size in adolescents and that the hippocampus and stress may be associated with alterations in spleen structure and gene expression.


Factors Influencing Discharge Readiness After Total Knee Replacement.
Total knee replacement (TKR) surgery has been found to achieve positive outcomes for many patients such as reduced pain and increased function. However, some patients experience suboptimal outcomes including falls, readmission to hospital, and reduced functional performance. Preparation for discharge after TKR surgery is often defined related to pain control, walking, knee function, and ability to climb stairs. These measures may not fully encompass aspects of recovery that impact patients' readiness for discharge after surgery. The purpose of this article is to review discharge readiness following TKR surgery and discuss factors that are known to impact preparedness for discharge.


Validation and Application of a Dried Blood Spot Assay for Biofilm-Active Antibiotics Commonly Used for Treatment of Prosthetic Implant Infections.
Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des-RIF, CIP, and FUS in DBS were 15 μg/liter, 14 μg/liter, 25 μg/liter, and 153 μg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (r > 0.95; P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4°C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections.


Catenane and Rotaxane Synthesis from Cucurbit[6]uril-Mediated Azide-Alkyne Cycloaddition.
The chemistry of mechanically interlocked molecules (MIMs) such as catenane and rotaxane is full of new opportunities for the presence of a mechanical bond, and the efficient synthesis of these molecules is therefore of fundamental importance in realizing their unique properties and functions. While many different types of preorganizing interactions and covalent bond formation strategies have been exploited in MIMs synthesis, the use of cucurbit[6]uril (CB[6]) in simultaneously templating macrocycle interlocking and catalyzing the covalent formation of the interlocked components is particularly advantageous in accessing high-order catenanes and rotaxanes. In this review, catenane and rotaxane obtained from CB[6]-catalyzed azide-alkyne cycloaddition will be discussed, with special emphasis on the synthetic strategies employed for obtaining complex [n]rotaxanes and [n]catenanes, as well as their properties and functions.


Longitudinal assessment of adaptive and maladaptive behaviors in fragile X males: growth, development, and profiles.
As young fully mutated fragile X [fra(X)] males age, cognitive levels (IQ scores) and adaptive behavior levels (DQ scores) decline. Given the variable behavioral profiles reported previously, we wondered whether changes in specific attributes of adaptive behavior are related to declines in composite adaptive behavior levels. We also examined maladaptive behavior to determine if changes are related to age. Therefore, we evaluated three areas of adaptive behavior, as well as maladaptive behavior, in 28 fully mutated fra(X) males, ages 4-14 years. To develop a profile of adaptive behavior, we analyzed nine subscale scores from the Vine-land Adaptive Behavior Scale (VABS). To assess maladaptive behavior, we graded part I of the VABS Maladaptive Behavior Scale. Subjects were sorted into three age cohorts, according to their initial test age: younger than 6 years; 6 to 9 years; older than 9 years. Results indicate that, in all age groups, the communications domain is the most severely impacted compared with either the socialization domain or daily living skills and that, in all age groups, the socialization domain is a relative strength compared with either the communications domain or daily living skills. The youngest cohort manifested significant increases in age-equivalent community living skills. Significant differences in age-equivalent scores between cohorts were observed in written language and play skills. Maladaptive behavior scores were available from cross-sectional data only. Twenty males (74%) showed significantly higher maladaptive scores than expected from other children their age. Our data analysis also revealed a moderate and significant negative correlation between maladaptive behavior levels and age (r = -0.54; P < 0.01). Curiously, adaptive and maladaptive behaviors did not correlate with each other.


Modelling behaviour in intergroup conflicts: a review of microeconomic approaches.
Microeconomic modelling offers a powerful formal toolbox for analysing the complexities of real-world intergroup relations and conflicts. One important class of models scrutinizes individuals' valuations of different group memberships, attitudes towards members of different groups and preferences for resource distribution in group contexts. A second broad class uses game theoretical methods to study strategic interactions within and between groups of individuals in contest and in conflict. After a concise discussion of some essential peculiarities of microeconomic modelling, this review provides an overview of the pertinent literatures in economics, highlights instructive examples of central model types and points out several ways forward. This article is part of the theme issue 'Intergroup conflict across taxa'.


Targeting Chitinase 1 and Chitinase 3-Like 1 as Novel Therapeutic Strategy of Pulmonary Fibrosis.
Chitinase 1 (CHIT1) and chitinase 3-like-1 (CHI3L1), two representative members of 18-Glycosyl hydrolases family, are significantly implicated in the pathogenesis of various human diseases characterized by inflammation and remodeling. Notably, dysregulated expression of CHIT1 and CHI3L1 was noted in the patients with pulmonary fibrosis and their levels were inversely correlated with clinical outcome of the patients. CHIT1 and CHI3L1, mainly expressed in alveolar macrophages, regulate profibrotic macrophage activation, fibroblast proliferation and myofibroblast transformation, and TGF-β signaling and effector function. Although the mechanism or the pathways that CHIT1 and CHI3L1 use to regulate pulmonary fibrosis have not been fully understood yet, these studies identify CHIT1 and CHI3L1 as significant modulators of fibroproliferative responses leading to persistent and progressive pulmonary fibrosis. These studies suggest a possibility that CHIT1 and CHI3L1 could be reasonable therapeutic targets to intervene or reverse established pulmonary fibrosis. In this review, we will discuss specific roles and regulatory mechanisms of CHIT1 and CHI3L1 in profibrotic cell and tissue responses as novel therapeutic targets of pulmonary fibrosis.


Effect of antiviral substances on hepatitis A virus replication in vitro.
The effect of protamine, atropine, selenocystamine, taxifolin, and catechin on the infectivity and antigenicity of the cell culture-adapted hepatitis A virus (HAV) strain CF 53 was studied. The toxicity on uninfected PLC/PRF/5 cells was examined for each antiviral compound by morphological and biochemical methods, in order to determine concentrations without cytotoxic effect. At these concentrations, protamine and taxifolin, added to infected cells for a 15-day period, caused concentration-dependent reductions in the infectivity and antigenicity of HAV. Atropine also caused a concentration-dependent reduction of HAV infectivity but did not affect the antigenicity of the virus. At the highest concentration used, 50 micrograms/ml of protamine, 59 micrograms/ml of taxifolin, and 50 micrograms/ml of atropine, the infectious viral titer reduction was 1.56, 0.77, and 0.68 log10, respectively. Selenocystamine and catechin had no effect on HAV replication.


Applications of combined spectral lifetime microscopy for biology.
Live cell imaging has been greatly advanced by the recent development of new fluorescence microscopy-based methods such as multiphoton laser-scanning microscopy, which can noninvasively image deep into live specimens and generate images of extrinsic and intrinsic signals. Of recent interest has been the development of techniques that can harness properties of fluorescence, other than intensity, such as the emission spectrum and excited state lifetime of a fluorophore. Spectra can be used to discriminate between fluorophores, and lifetime can be used to report on the microenvironment of fluorophores. We describe a novel technique-combined spectral and lifetime imaging-which combines the benefits of multiphoton microscopy, spectral discrimination, and lifetime analysis and allows for the simultaneous collection of all three dimensions of data along with spatial and temporal information.


[The use of opioids by the regional route in the treatment of pain].
The decision to administer regional opioids either by an epidural or a subarachnoid route (intrathecal or intraventricular) necessitates a prior multiparametric analysis. When opiate therapy is definitively indicated regional opiate administration usually relays an insufficient or poorly tolerated oral route. The epidural route seems to be the best way for transient indications; the choice of the opioid drug then depends on the local or disseminated character of pain. For definitive opioid treatment, morphine is the only substance which can be used for long periods of time; the choice of the route depends on the life expectancy; epidural way combined with "open devices or half open devices" chiefly concerns patients with a poor life expectancy and a rather low daily morphine regime: a subarachnoid approach is best indicated in cases with good life expectancy, however, other criteria--intellectual, socioeconomical levels and quality of the "support system"--are important factors for the choice of the route and of the type of administration devices.


Selective degeneration of dopaminergic neurons by MPP(+) and its rescue by D2 autoreceptors in Drosophila primary culture.
Drosophila melanogaster is widely used to study genetic factors causing Parkinson's disease (PD) largely because of the use of sophisticated genetic approaches and the presence of a high conservation of gene sequence/function between Drosophila and mammals. However, in Drosophila, little has been done to study the environmental factors which cause over 90% of PD cases. We used Drosophila primary neuronal culture to study degenerative effects of a well-known PD toxin MPP(+) . Dopaminergic (DA) neurons were selectively degenerated by MPP(+) , whereas cholinergic and GABAergic neurons were not affected. This DA neuronal loss was because of post-mitotic degeneration, not by inhibition of DA neuronal differentiation. We also found that MPP(+) -mediated neurodegeneration was rescued by D2 agonists quinpirole and bromocriptine. This rescue was through activation of Drosophila D2 receptor DD2R, as D2 agonists failed to rescue MPP(+) -toxicity in neuronal cultures prepared from both a DD2R deficiency line and a transgenic line pan-neuronally expressing DD2R RNAi. Furthermore, DD2R autoreceptors in DA neurons played a critical role in the rescue. When DD2R RNAi was expressed only in DA neurons, MPP(+) toxicity was not rescued by D2 agonists. Our study also showed that rescue of DA neurodegeneration by Drosophila DD2R activation was mediated through suppression of action potentials in DA neurons.


Effects of the Mediterranean diet on cardiovascular risk factors in non-alcoholic fatty liver disease patients: A systematic review and meta-analysis.
We aimed to investigate the effect of the Mediterranean diet (MedDiet) on cardiovascular risk factors in patients with non-alcoholic fatty liver disease (NAFLD). A systematic search was performed in Scopus, Web of Science, Cochrane library and PubMed databases to find randomized controlled trials (RCTs) related to the effect of the MedDiet in patients with NAFLD, up to July, 2019. There was no language and time limitation. Meta-analyses were performed using both the random and fixed effects model where appropriate, and I2 index was used to evaluate the heterogeneity. Primary search yielded 467 publications. Five RCTs were eligible. Our meta-analysis indicated that the MedDiet resulted in a significant decrease in serum levels of triglyceride and total cholesterol, and a decrease in body weight and HOMA-IR in comparison to a control diet, in NAFLD patients. Whereas, there were no significant improvement in the MedDiet group compared with the control group regarding other variables such as liver enzymes and blood pressure. This meta-analysis indicated the advantageous effects of the MedDiet on some cardiovascular risks factors, as compared with a control diet. It seems that the MedDiet can be considered as an appropriate strategy to reduce cardiovascular risk factors in NAFLD patients.