Post-stroke depression therapy: where are we now?
Post-stroke depression is an important psychological consequence of ischemic stroke, and affects around one third of stroke patients at any time post-stroke. It has a negative impact on patient morbidity and mortality, and as such development of effective post-stroke recognition and treatment strategies are very important. There are several therapeutic strategies for post-stroke depression, including both pharmacological and non-pharmacological approaches. In this review, we present evidence regarding the underlying biology of post-stroke depression, commonalities between post-stroke depression and Major Depressive Disorder and explore several treatment approaches, including antidepressant therapy, psychotherapy, surgical therapy, electroconvulsive therapy, acupuncture, music therapy and natural products. Further experimental and clinical studies are required, particularly in emerging fields such as the role of nutraceuticals in the treatment of stroke.


A cloud-based approach to medical NLP.
Natural Language Processing (NLP) enables access to deep content embedded in medical texts. To date, NLP has not fulfilled its promise of enabling robust clinical encoding, clinical use, quality improvement, and research. We submit that this is in part due to poor accessibility, scalability, and flexibility of NLP systems. We describe here an approach and system which leverages cloud-based approaches such as virtual machines and Representational State Transfer (REST) to extract, process, synthesize, mine, compare/contrast, explore, and manage medical text data in a flexibly secure and scalable architecture. Available architectures in which our Smntx (pronounced as semantics) system can be deployed include: virtual machines in a HIPAA-protected hospital environment, brought up to run analysis over bulk data and destroyed in a local cloud; a commercial cloud for a large complex multi-institutional trial; and within other architectures such as caGrid, i2b2, or NHIN.


The effect of baduanjin on promoting the physical fitness and health of adults.
The purpose of study was to assess the efficacy of a 16-week Baduanjin qigong training intervention in promoting physical fitness and health for adults. An experimental design was adopted, and subjects were assigned randomly into an experimental group (n = 55) and a control group (n = 55). In the intervention group comprised of adults, there were no significant variations in blood glucose, blood lipid, blood pressure, heart rate variability, and vital capacity indices. The body weight and body mass index (BMI) dropped in the intervention group. Compared with the control group, the skinfold thicknesses decreased at lower corner of scapula, triceps brachii, and abdomen, with a statistical significance (P < 0.001; P = 0.005; P = 0.003). By comparing the physical fitness indices, it was found that the increase of the results of sit-and-reach test in the intervention group had statistical significance (P = 0.001). In conclusion, it was found by our trial that Baduanjin exercise could significantly improve the physical flexibility and subcutaneous adipose accumulation in the healthy adults.


Implementation strategies for digital mental health interventions in health care settings.
U.S. health care systems are tasked with alleviating the burden of mental health, but are frequently underprepared and lack workforce and resource capacity to deliver services to all in need. Digital mental health interventions (DMHIs) can increase access to evidence-based mental health care. However, DMHIs commonly do not fit into the day-to-day activities of the people who engage with them, resulting in a research-to-practice gap for DMHI implementation. For health care settings, differences between digital and traditional mental health services make alignment and integration challenging. Specialized attention is needed to improve the implementation of DMHIs in health care settings so that these services yield high uptake, engagement, and sustainment. The purpose of this article is to enhance efforts to integrate DMHIs in health care settings by proposing implementation strategies, selected and operationalized based on the discrete strategies established in the Expert Recommendations for Implementing Change project, that align to DMHI-specific barriers in these settings. Guidance is offered in how these strategies can be applied to DMHI implementation across four phases commonly distinguished in implementation science using the Exploration, Preparation, Implementation, Sustainment Framework. Next steps to advance research in this area and improve the research-to-practice gap for implementing DMHIs are recommended. Applying implementation strategies to DMHI implementation will enable psychologists to systematically evaluate this process, which can yield an enhanced understanding of the factors that facilitate implementation success and improve the translation of DMHIs from controlled trials to real-world settings. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


The amino acid sequences of erabutoxins, neurotoxic proteins of sea-snake (Laticauda semifasciata) venom.
1. Erabutoxin b was reduced, S-carboxymethylated and hydrolysed with trypsin. Seven tryptic fragments were isolated by column chromatography and paper electrophoresis. Some of the fragments were further hydrolysed with alpha-chymotrypsin, pepsin, Nagarse, Proctase A or Proctase B. The amino acid sequences of the fragment peptides were determined by subtractive Edman degradation. 2. From the tryptic digest of reduced, S-carboxymethylated and trifluoroacetylated erabutoxin b two fragments were isolated. From the amino acid composition of the fragments and from the terminal sequence studies on the reduced and S-carboxymethylated erabutoxin b, the sequence of the above seven tryptic fragments was elucidated. 3. The tryptic digestion of reduced and S-carboxymethylated erabutoxin a gave fragments, only one of which was different from the corresponding fragment from erabutoxin b. The amino acid sequence analysis of the fragment peptide showed that the only difference between erabutoxins a and b was that the former had asparagine and the latter had histidine at position 26.


Progress and opportunities for tissue-engineered skin.
Tissue-engineered skin is now a reality. For patients with extensive full-thickness burns, laboratory expansion of skin cells to achieve barrier function can make the difference between life and death, and it was this acute need that drove the initiation of tissue engineering in the 1980s. A much larger group of patients have ulcers resistant to conventional healing, and treatments using cultured skin cells have been devised to restart the wound-healing process. In the laboratory, the use of tissue-engineered skin provides insight into the behaviour of skin cells in healthy skin and in diseases such as vitiligo, melanoma, psoriasis and blistering disorders.


Preparation of imprinted bacterial cellulose aerogel with intelligent modulation of thermal response stimulation for selective adsorption of Gd(III) from wastewater.
Research on recycling of used rare earth elements has been of great interest. Adsorption is one of the advantageous methods to recover gadolinium with high value. In the process of adsorption and separation of gadolinium from materials, the selectivity of materials for gadolinium can be significantly improved by using ion imprinting technique. However, gadolinium elution process is a traditional pickling process, which may affect the construction of imprinting sites. In this study, bacterial cellulose with three-dimensional spatial structure was used as the base material of aerogel material, and functional materials containing a large number of carboxyl groups were introduced by chemical grafting method. In combination with ion imprinting technology and N-polyacrylamide as intelligent temperature control valve, intelligent imprinting aerogel (PNBC-IIPS) with specific selectivity to gadolinium was prepared. The properties of aerogel materials were analyzed by SEM, FT-IR, and BET characterization. The experimental analysis shows that the desorption of gadolinium can be achieved by controlling the temperature change. The adsorption experiments show that PNBC-IIPS can selectively adsorb gadolinium ions from aqueous solution. The maximum adsorption capacity reached 95.51 mg g-1. Compared with unimprinted aerogel, the maximum adsorption capacity of gadolinium ion is significantly increased, which proves that the introduced ion imprinting technique plays a key role in the adsorption process. Cyclic experiments show that the adsorption capacity of PNBC-IIPS can still maintain 88% of the original adsorption capacity after 5 times of adsorption and desorption. In conclusion, PNBC-IIPS is a green adsorbent for selective recovery of gadolinium ions.


Cross-sectional risk models using quantitative fecal hemoglobin in colorectal cancer screening: a systematic review.
Fecal Immunochemical Testing (FIT) is a central tool in colorectal cancer (CRC) screening. To improve the selection of individuals for colonoscopy, risk models combining FIT with additional CRC risk factors have been developed. This systematic review aims to provide an overview of the current noninvasive FIT-based risk models for CRC screening to facilitate future implementation. We performed a systematic literature search for risk models that combined quantitative fecal hemoglobin with clinical data or noninvasive biomarkers and that were intended for CRC screening. Risk of bias was assessed using the PROBAST tool. Twenty risk models reported across 29 publications were included. The overall risk of bias was high. In studies that compared risk models to FIT, 11/12 (92%) risk models had a significantly higher c-statistic than FIT only. 16/20 risk models (80%) had not been externally validated and only one model has been implemented so far. FIT-based risk models have the potential to improve the yield of CRC screening. Unfortunately, all included publications had a high risk of bias and most risk models have not yet been externally validated. The prospect of improved CRC screening with risk models should encourage more rigorous evaluation in existing screening programs.


Islands of cartilage and bone at the margin of the carotid bodies of rats.
Islands of mature cartilage or bone were observed in 6 respectively 7 out of 1395 carotid bodies of rats studied. They were found only in spontaneously hypertensive rats of the Okamoto-Aoki stain and situated regularly at the margin of the carotid bodies. The bone islands were bigger than those of cartilage. The presence of such tissue components in the carotid bodies of rats is discussed in connection with the embryology of this peripheral arterial chemoreceptor, especially its mesodermal origin.


In vitro effects of antibiotics on Brugia malayi worm survival and reproduction.
Recent studies have suggested that intracellular Wolbachia spp. endobacteria are necessary for the reproduction and survival of filarial nematodes. The effects of antibiotics that are active against related bacteria on adult worms and microfilariae (Mf) of Brugia malayi in vitro were investigated. Antibiotics tested were doxycycline (Doxy), tetracycline (Tet), rifampicin (Rif), azithromycin (Azith), and chloramphenicol (Chlor). Doxy, Tet, Rif, and Azith reduced release of Mf by adult female worms. The minimum effective concentrations that reduced Mf release by 50% were 5 microg/ml for Doxy, 20 microg/ml for Tet, 40 microg/ml for Rif, and 100 microg/ml for Azith. The same drugs (at higher concentrations) killed adult worms and Mf. Embryograms showed that Tets blocked embryogenesis in female worms. Electron microscopy (EM) showed that the Tets, Rif, and Azith cleared Wolbachia spp. from adult worms and damaged developing embryos. These studies show that antibiotics active against Rickettsiaceae affect adult B. malayi worms and Mf in vitro. Additional studies will be needed to elucidate the mechanisms of action of these antibiotics on Wolbachia and filarial worms.


Waterborne Diseases and Wastewater Treatment in Iraq.
Iraq is a desert country with access to large river resources and an extensive aquifer, but these have already been overdrawn for domestic, industry and agriculture use. The diminished flow of the Tigris and Euphrates rivers has allowed seawater intrusion from the Persian Gulf 110 km up as far as Basra, the county's third largest city. In addition, water distribution systems are overloaded and wastewater treatment plants (WWTP) need upgrading, and fresh water sources polluted by lack of sanitation, agricultural runoff, household and industrial waste, and including the irrigation of vegetables with sewage water, have led to episodes of bacterial, viral and parasitic diseases. Also, there have been increases in many types of cancer since the early 1990s, and based on clinical and epidemiological data, these increases could be attributable to exposure to depleted uranium in the environment arising from conflict in Iraq and particularly during the Iraqi War started 20 years ago. The population affected would like government action to reduce their health concerns, and policies that have been proposed for improving water availability and quality, as well as but have not been followed up sufficiently to tackle these, including increasing the capacity and efficiency of WWTP; promoting the most efficient irrigation techniques for the local growing conditions; reducing the use of chemical fertilizers and pesticides that can decrease the water quality; reducing saline intrusion challenges; building compact desalination units; constructing water storage facilities to address water scarcity challenges; and establishing public education plans for consumers to reduce the water demand during the hot season. Whether the government rises to the task remains to be seen. Also, do those countries that used the DU have a responsibility to remove or otherwise dispose of the fragments that remain?


Properties of "creep currents" in single frog atrial cells.
Changes in membrane current in response to an elevation of [Na]i were studied in enzymatically dispersed frog atrial cells. Na loading by either intracellular dialysis or exposure to the Na ionophore monensin produces changes in membrane current that resemble the "creep currents" originally observed in cardiac Purkinje fibers during exposure to low-K solutions. Na loading induces a transient outward current during depolarizing voltage-clamp pulses, followed by an inward current in response to repolarization back to the holding potential. In contrast to cardiac Purkinje fibers, Na loading of frog atrial cells induces creep currents without accompanying transient inward currents. Creep currents induced by Na loading are insensitive to K channel antagonists like Cs and 4-aminopyridine; they are not influenced by doses of Ca channel antagonists that abolish iCa, but are sensitive to changes in [Ca]o or [Na]o. A comparison of the time course of development of inward creep currents are not tail currents associated with iCa. Inward creep currents can also be induced by experimental interventions that increase the iCa amplitude. Exposure to isoproterenol enhances the iCa amplitude and induces inward creep currents; both can be attenuated by Ca channel antagonists. Both inward and outward creep currents are blocked by low doses of La, independently of La's ability to block iCa. It is concluded that (a) creep currents are not mediated by voltage-gated Na, Ca, or K channels or by an electrogenic Na,K pump; (b) inward creep currents induced either by Na loading or in response to an increase in the amplitude of iCa are triggered by an elevation of [Ca]i; and (c) creep currents may be generated by either an electrogenic Na/Ca exchange mechanism or by a nonselective cation channel activated by [Ca]i.


Surgical management of juvenile amputation overgrowth with a synthetic cap.
Seventeen amputations (in 14 children) with established overgrowth were treated by capping of the residual limb with a polytetrafluoroethylene (PTFE) felt pad. Average age at the time of the procedure was 7 years 10 months. Mean follow-up was 4 years 9 months. Statistical comparisons were made to historical controls, treated by resection revision or biologic capping, from a prior overgrowth study from the authors' institution. Revision surgery was necessary in 86% of resection revisions, 29% of biologic caps, and 29% of PTFE caps. Kaplan-Meier analysis estimated survival times of 3 years 3 months for resection revision, 6 years 1 month for biologic caps, and 7 years 2 months for PTFE caps. PTFE and biologic caps were both statistically better than resection revision with regard to need for subsequent operation and survivorship, but were not statistically different from each other. Complications associated with PTFE capping and biologic capping were distinct.


Bcl-2 attenuation of oxidative cell death is associated with up-regulation of gamma-glutamylcysteine ligase via constitutive NF-kappaB activation.
Oxidative stress induced by reactive oxygen intermediates often causes cell death via apoptosis, which is regulated by many functional genes and their protein products. The evolutionarily conserved protein Bcl-2 blocks apoptosis induced by a wide array of death signals. Despite extensive research, the molecular milieu that characterizes the anti-apoptotic function of Bcl-2 has not been fully clarified. In this work, we have investigated the role of bcl-2 in protecting against oxidative death induced by H(2)O(2) in cultured rat pheochromocytoma PC12 cells. Transfection with the bcl-2 gene rescued PC12 cells from apoptotic death caused by H(2)O(2). Addition of NF-kappaB inhibitors such as pyrrolidine dithiocarbamate and N-tosyl-l-phenylalanine chloromethyl ketone to the medium aggravated oxidative cell death. PC12 cells overexpressing bcl-2 exhibited relatively high constitutive DNA binding and transcriptional activities of NF-kappaB compared with vector-transfected control cells. Western blot analysis and immunocytochemistry revealed that bcl-2-transfected PC12 cells retained a higher level of p65 (the functionally active subunit of NF-kappaB) in the nucleus compared with vector-transfected controls. In addition, sustained activation of ERK1/2 (upstream of NF-kappaB) was observed in bcl-2-overexpressing cells. In contrast, the cytoplasmic inhibitor IkappaBalpha was present in lower amounts in cells overexpressing bcl-2. The ectopic expression of bcl-2 increased the cellular glutathione level and gamma-glutamylcysteine ligase expression, which were attenuated by NF-kappaB inhibitors. These results suggest that NF-kappaB plays a role in bcl-2-mediated protection against H(2)O(2)-induced apoptosis in PC12 cells through augmentation of antioxidant capacity.


On the surface lattice of microtubules: helix starts, protofilament number, seam, and handedness.
The tubulin monomers of brain microtubules reassembled in vitro are arranged on a 3-start helix, irrespective of whether the number of protofilaments is 13 or 14. The dimer packing is that of the B-lattice described for flagellar microtubules. This implies that the tubulin core of microtubules contains at least one helical discontinuity. Neither 5-start nor 8-start helices have a physical significance and thus cannot be implicated in models of microtubule elongation, but the structure is compatible with elongation of protofilaments by dimers or protofilamentous oligomers. The inner and outer surfaces of the microtubule wall can be visualized by propane jet freezing, freeze fracturing, and metal replication, at a resolution of at least 4 nm. The 3-start helix is left-handed, in contrast to a previous study based on negative staining and shadowing. The reasons for this discrepancy are discussed.


Detection of in Situ Early Corrosion on Polymer-Coated Metal Substrates.
Protective coating systems (PCS) are a common and facile method to protect metal substrates from corrosion. The corrosion control performance of polymer-coated metal substrates is still predominantly evaluated by visual assessment. Unfortunately, for many decades, PCS material development and performance testing has basically been a complicated process of waiting to determine which coating, in relative terms, allows corrosion to occur first from an intentionally created breach through the coating. This type of testing provides only relative ratings between PCS performance. Electrochemical methods, such as electrochemical impedance spectroscopy, each have caveats and pitfalls for qualifying or quantifying polymer-coated metal substrates. When these data are studied carefully, these measurements result in many false positive and false negative results compared with real environmental testing and the paths to failure vary dramatically. The critical issue is that these methods do not result in a scientific basis for understanding either the pathway(s) or progressive milestones toward diminished PCS performance, failure, and the loss of substrate structural integrity for coated substrates. Data supports that ultimately all PCS fail to provide the necessary substrate protection. However, to make substantive gains, scientists and engineers require a rational basis to design, engineer, test, quantify, and/or estimate service life and remaining service life and repair future generations of PCS. Our research goal was to establish a quantifiable characterization protocol (CP) that directly detected, monitored, and ideally quantified the pathway(s) and important milestones of PCS corrosion spatially and temporally, with or without defects which related with testing and assessment variables regardless of environmental severity (real, laboratory, or accelerated). We report herein the CP and the results from an embedded pH-sensitive "turn-on" fluorescent probe blended with a simplified thermoplastic model PCS. The results support that the average-localized macroscopic pH is detected and tracked, and these "molecular titrations" result in values consistent with literature pH citations for premacroscopic corrosion processes, that is, before delamination and a detectable breach. The CP results are an improvement over visual corrosion detection and yet proportional to the steel substrate corrosion. The CP results deliver extreme early detection (within minutes), spatial and temporal tracking, and potentially quantifiable performance differences for the pathways and milestones toward failure of coated substrates with validated sensitivity to variables such as defect versus defect-free films, blending solvent type(s) influence, differences from varied degrees of annealing relative to Tg (thermoplastic films), substrate topography, and preparation differences. The CP utilizes small sample areas (25 mm spheres) and gathers data in a manner designed to improve statistical relevancy, provide results within short timeframes using real-time testing, diminish materials-testing timelines, and connect results with laboratory, accelerated, and real environmental severity differences. The results support that the CP directly measured the earliest possible in situ corrosion processes using defect and defect-free simplified model PCS.


Determine neighboring region spatial effect on dengue cases using ensemble ARIMA models.
The state of Selangor, in Malaysia consist of urban and peri-urban centres with good transportation system, and suitable temperature levels with high precipitations and humidity which make the state ideal for high number of dengue cases, annually. This study investigates if districts within the Selangor state do influence each other in determining pattern of dengue cases. Study compares two different models; the Autoregressive Integrated Moving Average (ARIMA) and Ensemble ARIMA models, using the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) measurement to gauge their performance tools. ARIMA model is developed using the epidemiological data of dengue cases, whereas ensemble ARIMA incorporates the neighbouring regions' dengue models as the exogenous variable (X), into traditional ARIMA model. Ensemble ARIMA models have better model fit compared to the basic ARIMA models by incorporating neighbuoring effects of seven districts which made of state of Selangor. The AIC and BIC values of ensemble ARIMA models to be smaller compared to traditional ARIMA counterpart models. Thus, study concludes that pattern of dengue cases for a district is subject to spatial effects of its neighbouring districts and number of dengue cases in the surrounding areas.


Blood levels of a pteridine-binding alpha 1-acid glycoprotein in cancer patients.
A variant of alpha 1-acid glycoprotein was found previously in blood of malignant cases. It had been characterized as a pteridine-binding alpha 1-acid glycoprotein (P-AGPM). P-AGPM as well as the corresponding fraction of control origin were selectively enriched in the supernatant (Fraction b), obtained after digitonin extraction and subsequent alcohol and trichloroacetic acid fractionation of whole blood. In Fraction b, alpha 1-acid glycoprotein from control subjects + P-AGPM comprised 90 to 95% of total protein; it was quantitated by colorimetric determination of the protein-bound tyrosine and calibrated with the isolated compound. During a screening of malignant and nonmalignant cases, P-AGPM proved to be an acute-phase reactant to some extent. Marked increases during extended cancer and especially during leukemias corroborated the view that P-AGPM may be identical with abnormal orosomucoid. Longitudinal sections during leukemias suggested that the biopterin of leukemic cells may be metabolically related to the pteridine moiety of P-AGPM. Biopterin determinations by means of Crithidia assay in the blood of 136 cases of solid tumors showed that, due to its high rate of renal clearance, blood biopterin is not a reliable and persistent marker for proliferative activity, unless it is contained in the immature blood cells themselves, as is the case during leukemias.


The father-daughter dance: the relationship between father-daughter relationship quality and daughters' stress response.
The goal of the study was to determine whether father-daughter relationship quality is related to activity of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol) and autonomic nervous system (salivary alpha-amylase, sAA) in late adolescence-emerging adulthood during peer interactions. In the 1st study, reported father-daughter relationships characterized by rejection, chaos, and coercion had lower morning cortisol levels and were temperamentally more sensitive to emotional changes. In the 2nd study, young women who reported father-daughter relationships characterized by warmth, autonomy, support, and structure had lower pretask cortisol levels, and they had attenuated cortisol responses to problem discussion with a friend. In contrast, those who reported father-daughter relationships characterized by rejection, chaos, and coercion had higher pretask cortisol levels, had elevated cortisol in response to problem discussion with a friend, and were more likely to self-disclose about psychosocial stressors. No differences were observed between reported father-daughter relationship quality and sAA levels or task-related reactivity. The findings suggest that father-daughter interactions potentially influence both social cognition and HPA reactivity to developmentally salient stressors in young women.


Argonaute-2 is associated to brown adipose tissue activation.
MicroRNAs (miRNAs) are important modulators of thermogenic brown adipose tissue (BAT). They have been involved in its differentiation and hence its functioning. While different regulators of the miRNA machinery have been shown to be essential for BAT differentiation, little is known about their implication in BAT activation. The aim of this work was to evaluate the role of AGO2, the chief miRNA mediator, in BAT activation. We took advantage of two non-genetic models of BAT activation to analyze the miRNA machinery and miRNA expression in BAT. We used principal component analysis (PCA) to obtain an overview of miRNA expression according to the BAT activation state. In vitro, we examined AGO2 expression during brown adipocyte differentiation and activation. Finally, we downregulated AGO2 to reveal its potential role in the thermogenic function of brown adipocytes. PCA analysis allowed to cluster animals on their miRNA signature in active BAT. Moreover, hierarchical clustering showed a positive correlation between global upregulation of miRNA expression and active BAT. Consistently, the miRNA machinery, particularly AGO2, was upregulated in vivo in active BAT and in vitro in mature brown adipocytes. Finally, the partial loss-of-function of AGO2 in mature brown adipocytes is sufficient to lead to a diminished expression of UCP1 associated to a decreased uncoupled respiration. Therefore, our study shows the potential contribution of AGO2 in BAT activation. Since BAT is a calorie-burning tissue these data have a translational potential in terms of therapeutic target in the field of altered fuel homeostasis associated to obesity and diabetes.


How do disturbances and climate effects on carbon and water fluxes differ between multi-aged and even-aged coniferous forests?
Disturbances and climatic changes significantly affect forest ecosystem productivity, water use efficiency (WUE) and carbon (C) flux dynamics. A deep understanding of terrestrial feedbacks to such effects and recovery mechanisms in forests across contrasting climatic regimes is essential to predict future regional/global C and water budgets, which are also closely related to the potential forest management decisions. However, the resilience of multi-aged and even-aged forests to disturbances has been debated for >60years because of technical measurement constraints. Here we evaluated 62site-years of eddy covariance measurements of net ecosystem production (NEP), evapotranspiration (ET), the estimates of gross primary productivity (GPP), ecosystem respiration (Re) and ecosystem-level WUE, as well as the relationships with environmental controls in three chronosequences of multi- and even-aged coniferous forests covering the Mediterranean, temperate and boreal regions. Age-specific dynamics in multi-year mean annual NEP and WUE revealed that forest age is a key variable that determines the sign and magnitude of recovering forest C source-sink strength from disturbances. However, the trends of annual NEP and WUE across succession stages between two stand structures differed substantially. The successional patterns of NEP exhibited an inverted-U trend with age at the two even-aged chronosequences, whereas NEP of the multi-aged chronosequence increased steadily through time. Meanwhile, site-level WUE of even-aged forests decreased gradually from young to mature, whereas an apparent increase occurred for the same forest age in multi-aged stands. Compared with even-aged forests, multi-aged forests sequestered more CO2 with forest age and maintained a relatively higher WUE in the later succession periods. With regard to the available flux measurements in this study, these behaviors are independent of tree species, stand ages and climate conditions. We also found that distinctly different environmental factors controlled forest C and water fluxes under three climatic regimes. Typical weather events such as temperature anomalies or drying-wetting cycles severely affected forest functions. Particularly, a summer drought in the boreal forest resulted in an increased NEP owing to a considerable decrease in Re, but at the cost of greater water loss from deeper groundwater resources. These findings will provide important implications for forest management strategies to mitigate global climate change.


Protective Effects of Nucleobinding-2 After Cerebral Ischemia Via Modulating Bcl-2/Bax Ratio and Reducing Glial Fibrillary Acid Protein Expression.
Nucleobinding-2 (NUCB2) or nesfatin-1, a newly identified anorexigenic peptide, has antioxidant, anti-inflammatory, and anti-apoptotic properties. Brain ischemiareperfusion induces irreversible damages, especially in the hippocampus area. However, the therapeutic effects of NUCB2 have not been well investigated in cerebral ischemia. This study was designed for the first time to investigate the protective effects of NUCB2/Nesfatin-1 on the expression of apoptosis-related proteins and reactive astrogliosis level in the CA1 area of hippocampus in an experimental model of transient global cerebral ischemia. The male Wistar rats were randomly allocated into 4 groups (sham, NUCB2, ischemia-reperfusion, and ischemia-reperfusion+NUCB21) (n =7). The model of cerebral ischemia was prepared by common carotid arteries occlusion for 20 minutes. Nesfatin-1 (20 μg/kg) and saline (as a vehicle) were injected (intraperitoneally) at the beginning of the reperfusion period. The assessment of the protein expression levels was performed by immunofluorescence and immunohistochemical staining. NUCB2 significantly reduced the Bax and GFAP protein levels in the CA1 area after ischemia (P<0.05). Also, NUCB2 increased Bcl-2 protein level (P<0.05). NUCB2 exerted protective effects against ischemic injury by the inhibition of astrocytes activation as an inflammatory response and decreased neuronal cell apoptosis. The present study provides the possible neuroprotective view of nesfatin-1 in the treatment of ischemia injury model in rat hippocampus.


Identification and Expression Analyses of Olfactory Gene Families in the Rice Grasshopper, Oxya chinensis, From Antennal Transcriptomes.
The rice grasshopper Oxya chinensis is an important agricultural pest of rice and other gramineous plants. Chemosensory genes are crucial factors in direct interactions with odorants in the olfactory process. Here we identified genes encoding 18 odorant-binding proteins (OBPs), 13 chemosensory proteins (CSPs), 94 olfactory receptors (ORs), 12 ionotropic receptors (IRs), and two sensory neuron membrane proteins (SNMPs) from O. chinensis using an transcriptomic approach. Semi-quantitative RT-PCR assays revealed that six OBP-encoding genes (OchiOBP4, 5, 8, 9, 10, and 14), one CSP gene (OchiOBP10) and two IR genes (OchiIR28 and 29) were exclusively expressed in antennae, suggesting their roles in olfaction. Real-time quantitative PCR analyses revealed that genes expressed exclusively or predominantly in antennae also displayed significant differences in expression levels between males and females. Among the differentially expressed genes, 17 OR-encoding genes, one CSP- and one SNMP-gene showed female-biased expression, suggesting that they may be involved in some female-specific behaviors such as seeking oviposition site; whereas the three remaining OR-encoding genes showed male-biased expression, indicating their possible roles in sensing female sex pheromones. Our results laid a solid foundation for future studies to reveal olfactory mechanisms as well as designing strategies for controlling this rice pest.


Lymphocytic ganglioneuritis secondary to intervertebral disc extrusion in a dog.
This study presents a case of lymphocytic ganglioneuritis in a dog secondary to intervertebral disc extrusion that mimicked a peripheral nerve sheath tumour on magnetic resonance imaging. A four-year-old spayed female dachshund with lumbar pain was imaged via magnetic resonance. A tubular, space-occupying, contrast-enhancing lesion was noted in the right intervertebral foramen at L6 to L7. This was presumed to represent focal enlargement of the right sixth lumbar spinal nerve. A right-sided haemilaminectomy was performed at L6 to L7 and material that grossly resembled extruded nucleus pulposus was removed. The right L6 dorsal root ganglion, dorsal nerve root and proximal spinal nerve were severely enlarged and a partial thickness biopsy was collected from the dorsal root ganglion. Results of histopathological examination of the submitted tissue samples were consistent with extruded disc material and lymphocytic ganglioneuritis. To the author's knowledge, this is the first published report of lymphocytic ganglioneuritis secondary to intervertebral disc disease in a dog.


STAT1-induced upregulation of lncRNA LINP1 promotes cell proliferation and inhibits apoptosis via AMPK signaling pathway in papillary thyroid cancer.
The purpose of this study was to detect the relative expression of long non-coding ribonucleic acid (lncRNA) in non-homologous end joining pathway 1 (LINP1) in papillary thyroid cancer (PTC) tissues and cells, and to investigate the molecular mechanisms of abnormal expression and biological function of LINP1. The relative expression of LINP1 in PTC tissues and cells was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the impact of small interfering (si)-LINP1 on the proliferative capacity of PTC cells was studied using Cell Counting Kit-8 (CCK-8) and colony formation assays. After the expression of LINP1 in PTC cells was interfered, flow cytometry was applied to determine the changes in cell cycle distribution and apoptosis rate. The transcription factors binding to the promoter region of LINP1 were predicted by bioinformatics. Next, qRT-PCR assay was adopted to measure the changes in LINP1 expression after interference in the expression of signal transducer and activator of transcription 1 (STAT1). Finally, the changes in the expressions of molecular markers of the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway were examined via Western blotting assay after the expressions of STAT1 and LINP1 were interfered. It was shown in qRT-PCR results that LINP1 expression was upregulated in 42 out of 53 cases of PTC tissues and in all PTC cells. After interference in the expression of LINP1 in PTC cells, the results of CCK-8 and colony formation assays indicated that the proliferative capacity of the cells was repressed. According to the results of flow cytometry, the cell cycle was arrested at the G1/G0 phase, and the apoptosis rate was increased. In addition, the bioinformatics predicted that STAT1 could bind to the promoter region of LINP1, and the results of qRT-PCR indicated that the expression of LINP1 declined after STAT1 expression was interfered. Moreover, it was indicated in the Western blotting assay after interference in the expressions of STAT1 and LINP1 that the expression of molecular marker (Phosphorylation AMPK, p-AMPK) of the AMPK signaling pathway was altered but the expression of total AMPK did not change. The transcription factor STAT1 promotes the expression of LINP1 in PTC, and highly expressed LINP1 facilitates the proliferation and inhibits the apoptosis of PTC by suppressing the AMPK signaling pathway.


Anthropometric and biochemical parameters in adolescents and their relationship with eating habits and household food availability.
To evaluate the per capita availability of energy and macronutrients in the home and frequency of food consumption by adolescents and to relate them with anthropometric and biochemical variables, as well as verify if the eating habits of parents are associated to the children. We evaluated the weight, height, body fat (%BF), glucose, insulin, triglycerides, total cholesterol (TC) and fractions of 120 adolescents. We evaluated also the eating habits of adolescents and their parents. Adolescents with more than 35% of available lipids had 9.1-fold higher chances of presenting alterations in TC. Those who replaced the main meals for snacks had 3.66, 4.66 and 2.82 higher chances of presenting alterationsin %BF, insulin and triglycerides, respectively. The daily consumption of fruit was considered as a protective factor in relation to hyperinsulinemia. There was a similar feeding behavior among adolescents and their mothers. The results suggest the importance of specific attention to adolescent health, focused on family education.


Encryption Based Image Watermarking Algorithm in 2DWT-DCT Domains.
This paper proposes an encryption-based image watermarking scheme using a combination of second-level discrete wavelet transform (2DWT) and discrete cosine transform (DCT) with an auto extraction feature. The 2DWT has been selected based on the analysis of the trade-off between imperceptibility of the watermark and embedding capacity at various levels of decomposition. DCT operation is applied to the selected area to gather the image coefficients into a single vector using a zig-zig operation. We have utilized the same random bit sequence as the watermark and seed for the embedding zone coefficient. The quality of the reconstructed image was measured according to bit correction rate, peak signal-to-noise ratio (PSNR), and similarity index. Experimental results demonstrated that the proposed scheme is highly robust under different types of image-processing attacks. Several image attacks, e.g., JPEG compression, filtering, noise addition, cropping, sharpening, and bit-plane removal, were examined on watermarked images, and the results of our proposed method outstripped existing methods, especially in terms of the bit correction ratio (100%), which is a measure of bit restoration. The results were also highly satisfactory in terms of the quality of the reconstructed image, which demonstrated high imperceptibility in terms of peak signal-to-noise ratio (PSNR ≥ 40 dB) and structural similarity (SSIM ≥ 0.9) under different image attacks.


Nurses' and physicians' narratives about long-term non-malignant pain among men.
The aim of this study was to illuminate the meaning of skilled nurses' and physicians' lived experiences in their encounters with men suffering from long-term, non-malignant pain of at least 6 months duration. Seventeen nurses and four physicians participated in the study. A phenomenological-hermeneutic method was used. In the analysis three themes, 'needing to be manly', 'struggling for relief from pain' and 'needing human support' emerged. The phenomenon 'confirmation' was especially important in all three themes. This study indicates that confirmation of the theme 'needing to be manly' means that nurses' and physicians' must have such a relationship with these men that they really feel respected. Confirmation of the theme 'struggling for relief from pain' means that the care givers must convince these men that they really believe each unique individual's narratives. Confirmation of the theme 'needing human support' means that nurses and physicians have to behave in such a way that these men are convinced that the caregivers really care about them. When the men felt confirmation they dared to disclose their pain experiences more honestly. This is a preliminary prerequisite for nurses' and physicians' potential to help these men.


Health effects of subchronic inhalation exposure to gasoline engine exhaust.
Gasoline engine emissions are a ubiquitous source of exposure to complex mixtures of particulate matter (PM) and non-PM pollutants; yet their health hazards have received little study in comparison with those of diesel emissions. As a component of the National Environmental Respiratory Center (NERC) multipollutant research program, F344 and SHR rats and A/J, C57BL/6, and BALBc mice were exposed 6 h/day, 7 days/week for 1 week to 6 months to exhaust from 1996 General Motors 4.3-L engines burning national average fuel on a simulated urban operating cycle. Exposure groups included whole exhaust diluted 1:10, 1:15, or 1:90, filtered exhaust at the 1:10 dilution, or clean air controls. Evaluations included organ weight, histopathology, hematology, serum chemistry, bronchoalveolar lavage, cardiac electrophysiology, micronuclei in circulating cells, DNA methylation and oxidative injury, clearance of Pseudomonas aeruginosa from the lung, and development of respiratory allergic responses to ovalbumin. Among the 120 outcome variables, only 20 demonstrated significant exposure effects. Several statistically significant effects appeared isolated and were not supported by related variables. The most coherent and consistent effects were those related to increased red blood cells, interpreted as likely to have resulted from exposure to 13-107 ppm carbon monoxide. Other effects supported by multiple variables included mild lung irritation and depression of oxidant production by alveolar macrophages. The lowest exposure level caused no significant effects. Because only 6 of the 20 significant effects appeared to be substantially reversed by PM filtration, the majority of effects were apparently caused by non-PM components of exhaust.


Stress, Coping, and Lived Experiences among Caregivers of Cancer Patients on Palliative Care: A Mixed Method Research.
The aim of this study is to assess stress and coping among caregivers of cancer patients on palliative care and to acquire a deeper understanding of their lived experiences. A mixed method study was conducted among caregivers of cancer patients on palliative care using mixed method approach and triangulation design. Data were gathered using self-administered stress rating scale, brief COPE inventory, and structured interview schedule. Nested sampling technique was adopted. The sample size for quantitative approach was eighty and qualitative approach was eight. The results showed that 74% of the participants were females and 30% of them belong to the age group between 51 and 60 years. Fifty-four percent of them belong to Hindu religion and 40% were unemployed. Sixty-two percent of the patients were dependent on caregivers for all activities of daily living. Assessment of stress revealed that 82% of the participants had moderate stress and 18% had severe stress. Participants adopted both negative and positive coping. There was a significant negative correlation (r = -0.722, P = 0.001) between stress and coping. Similar findings were also observed in the phenomenological approach. The theme evolved was "caring companionship to palliative care." Palliative caregiving is stressfull, challenging and can impact the caregiver's physical, emotional, psychological, and social well-being. Understanding lived experiences of caregivers of cancer patients on palliative care is important for the health professionals to improve the support, guidance, and education given to the caregivers of cancer patients on palliative care.


Histologic study of the normal human adult soft palate.
Detailed information about the tissue components of the soft palate is needed to construct biomechanical models that are functionally useful. Soft palates were removed from 10 adult cadavers, four males and six females. One-half of each palate was further divided into 10 blocks of equal anterior-to-posterior thickness. The face of each block was sectioned and stained using three different stains, thus providing a sample of 300 histologic slides. Each slide was carefully examined and major anatomic characteristics were noted and recorded. The results indicate that a typical adult soft palate consists of several major tissue layers including: (1) the oral aspect, which is glandular with a zone of adipose tissue located somewhat laterally; (2) the two middle layers are muscular with the more inferior layer consisting mainly of transverse levator veli palatini fibers and the overlying longitudinal layer of musculus uvulae fibers; (3) a superoanterior layer consisting of the tensor veli palatini tendon; and (4) a posteroinferior layer consisting of a mixture of tissue that is primarily glandular. The oral mucosa consists of stratified squamous epithelium with a basement membrane that is reinforced with a dense meshwork of elastic fibers. The nasal mucosa consists of pseudostratified ciliated columnar epithelium anteriorly and stratified squamous epithelium posteroinferiorly. The functional implications of these findings are discussed.


Methodology for the Evaluation of Double-Layered Microcapsule Formability Zone in Compound Nozzle Jetting Based on Growth Rate Ratio.
Double-layered microcapsules, which usually consist of a core (polymeric) matrix surrounded by a (polymeric) shell, have been used in many industrial and scientific applications, such as microencapsulation of drugs and living cells. Concentric compound nozzle-based jetting has been favored due to its efficiency and precise control of the core-shell compound structure. Thus far, little is known about the underlying formation mechanism of double-layered microcapsules in compound nozzle jetting. This study aims to understand the formability of double-layered microcapsules in compound nozzle jetting by combining a theoretical analysis and numerical simulations. A linear temporal instability analysis is used to define the perturbation growth rates of stretching and squeezing modes and a growth ratio as a function of the wave number, and a computational fluid dynamics (CFD) method is implemented to model the microcapsule formation process in order to determine the good microcapsule forming range based on the growth ratio curve. Using a pseudobisection method, the lower and upper bounds of the good formability range have been determined for a given materials-nozzle system. The proposed formability prediction methodology has been implemented to model a water-poly (lactide-co-glycolide) (PLGA)-air compound jetting system.


Aggressive behavior of papillary microcarcinoma in a patient with Graves' disease initially presenting as cystic neck mass.
Prognosis of papillary carcinoma of the thyroid associated with Graves' disease is controversial; nevertheless, tumors smaller than 1 cm (microcarcinoma) are usually considered to render a good prognosis. We describe a patient with Graves' disease who developed a lateral cystic neck mass that was later confirmed to be a metastatic lymph node from papillary thyroid microcarcinoma. Contrary to having a good prognosis with a microcarcinoma, our patient developed bilateral lung metastases. The possible role of thyroid stimulating immunoglobulins in the aggressive course of the tumor is discussed.


Effect of reboxetine on depression in Parkinson's disease patients.
Depression occurs frequently in patients with Parkinson's disease and appears to be associated with increased disability and reduced quality of life. Pharmacologic treatment with tricyclic antidepressants or serotonin reuptake inhibitors may produce adverse effects on cognition or motor functions in Parkinson's disease patients. The efficacy of reboxetine, a novel norepinephrine reuptake inhibitor, has been shown in major depressive disorder, with specific effects on motivation and negligible effects on psychomotor and cognitive function. The effects of reboxetine on depression were investigated in 16 patients with idiopathic Parkinson's disease in an open, prospective study. Prior antidepressant medication was stopped because of lack of efficacy or intolerable side effects. Severity of depressive symptoms was assessed by the Hamilton Rating Scale for Depression, the Self-Rating Depression Scale, the Snaith-Hamilton Pleasure Scale, and the Social Adaptation Self-Evaluation Scale during the study period of 4 weeks. A significant improvement in depression scores was observed after 4 weeks (z = -3.31, p < .008). In 1 subject, reboxetine treatment was discontinued because of psychotic symptoms. Seven patients experienced transient side effects, including restlessness, insomnia, and increased sweating. There were no significant changes in parkinsonian motor symptoms or dosage of levodopa. Reboxetine appears to be effective and well tolerated in Parkinson's disease patients receiving 4 weeks of treatment of moderate-to-severe depression. There are good theoretical and clinical reasons, including pharmacologic specificity of effects and low incidence of side effects, to consider reboxetine for treatment of depression in Parkinson's disease.


Roles of Rap1 signaling in tumor cell migration and invasion.
Ras-associated protein-1 (Rap1), a small GTPase in the Ras-related protein family, is an important regulator of basic cellular functions (e.g., formation and control of cell adhesions and junctions), cellular migration, and polarization. Through its interaction with other proteins, Rap1 plays many roles during cell invasion and metastasis in different cancers. The basic function of Rap1 is straightforward; it acts as a switch during cellular signaling transduction and regulated by its binding to either guanosine triphosphate (GTP) or guanosine diphosphate (GDP). However, its remarkably diverse function is rendered by its interplay with a large number of distinct Rap guanine nucleotide exchange factors and Rap GTPase activating proteins. This review summarizes the mechanisms by which Rap1 signaling can regulate cell invasion and metastasis, focusing on its roles in integrin and cadherin regulation, Rho GTPase control, and matrix metalloproteinase expression.


TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis.
Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. We found lncRNA GHRLOS was decreased in NSCLC cell lines and tissues which correlated with poor prognosis of NSCLC patients. However, the role and underlying mechanisms of lncRNA GHRLOS in NSCLC progression remains elusive. The expression of lncRNA GHRLOS was examined in NSCLC cell lines and biopsy specimens of patients with NSCLC by quantitative real time polymerase chain reaction (qRT-PCR). The effects of GHRLOS on proliferation, invasion and apoptosis of NSCLC cells were determined by both in vitro and in vivo experiments. The interaction between GHRLOS and TP53 was determined by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) combined with qRT-PCR analysis. RNA immunoprecipitation (RIP) was conducted to validate the binding between GHRLOS and microRNA-346 (miR-346). Dual-luciferase reporter assays were also carried out to reveal the interaction between miR-346 and the 3' untranslated region (3'UTR) of adenomatous polyposis coli (APC) mRNA.Our data demonstrated that overexpression of lncRNA GHRLOS suppressed cancer cell proliferation and invasion as well as promoted cell apoptosis by regulating the expression of CDK2, PCNA, E-cadherin, N-cadherin, Bax, and Bcl-2 in NSCLC cells. Moreover, lncRNA GHRLOS was upregulated by the binding of TP53 to the GHRLOS promoter. The binding target of lncRNA GHRLOS was identified to be miR-346. Impressively, overexpression of miR-346 promoted cell proliferation and invasion, as well as inhibited cell apoptosis, however, these effects can be blocked by overexpression of lncRNA GHRLOS both in vitro and in vivo. In summary, this study reveals lncRNA GHRLOS, upregulated by TP53, acts as a molecule sponge of miR-346 to cooperatively modulates expression of APC, a miR-346 target, and potentially inhibits NSCLC progression via TP53/lncRNA GHRLOS/miR-346/APC axis, which represents a novel pathway that could be useful in targeted therapy against NSCLC.


New Generation Cardiac Contractility Modulation Device-Filling the Gap in Heart Failure Treatment.
(1) Background: Heart failure (HF) is a major cause of morbidity and mortality throughout the world. Despite substantial progress in its prevention and treatment, mortality rates remain high. Device therapy for HF mainly includes cardiac resynchronization therapy (CRT) and the use of an implantable cardioverter-defibrillator (ICD). Recently, however, a new device therapy-cardiac contractility modulation (CCM)-became available. (2) Aim: The purpose of this study is to present a first case-series of patients with different clinical patterns of HF with a reduced ejection fraction (HFrEF), supported with the newest generation of CCM devices. (3) Methods and results: Five patients with a left ventricular ejection fraction (LVEF) ≤ 35% and a New York Heart Association (NYHA) class ≥ III were supported with CCM OPTIMIZER® SMART IPGCCMX10 at our clinic. The patients had a median age of 67 ± 8.03 years (47-80) and were all males-four with ischemic etiology dilated cardiomyopathy. In two cases, CCM was added on top of CRT (non-responders), and, in one patient, CCM was delivered during persistent atrial fibrillation (AF). After 6 months of follow-up, the LVEF increased from 25.4 ± 6.8% to 27 ± 9%, and the six-minute walk distance increased from 310 ± 65.1 m to 466 ± 23.6 m. One patient died 47 days after device implantation. (4) Conclusion: CCM therapy provided with the new model OPTIMIZER® SMART IPG CCMX10 is safe, feasible, and applicable to a wide range of patients with HF.


Disability in people affected by leprosy: the role of impairment, activity, social participation, stigma and discrimination.
Leprosy-related disability is a challenge to public health, and social and rehabilitation services in endemic countries. Disability is more than a mere physical dysfunction, and includes activity limitations, stigma, discrimination, and social participation restrictions. We assessed the extent of disability and its determinants among persons with leprosy-related disabilities after release from multi drug treatment. We conducted a survey on disability among persons affected by leprosy in Indonesia, using a Rapid Disability Appraisal toolkit based on the International Classification of Functioning, Disability and Health. The toolkit included the Screening of Activity Limitation and Safety Awareness (SALSA) scale, Participation Scale, Jacoby Stigma Scale (anticipated stigma), Explanatory Model Interview Catalogue (EMIC) stigma scale and Discrimination assessment. Community members were interviewed using a community version of the stigma scale. Multivariate linear regression was done to identify factors associated with social participation. Overall 1,358 persons with leprosy-related disability (PLD) and 931 community members were included. Seventy-seven percent of PLD had physical impairments. Impairment status deteriorated significantly after release from treatment (from 59% to 77%). Around 60% of people reported activity limitations and participation restrictions and 36% anticipated stigma. As for participation restrictions and stigma, shame, problems related to marriage and difficulties in employment were the most frequently reported problems. Major determinants of participation were severity of impairment and level of education, activity and stigma. Reported severity of community stigma correlated with severity of participation restrictions in the same districts. The majority of respondents reported problems in all components of disability. The reported physical impairment after release from treatment justifies ongoing monitoring to facilitate early prevention. Stigma was a major determinant of social participation, and therefore disability. Stigma reduction activities and socio-economic rehabilitation are urgently needed in addition to strategies to reduce the development of further physical impairment after release from treatment.


Thioredoxin is transcriptionally induced upon activation of heat shock factor 2.
Heat shock gene expression is differentially regulated in cells exposed to stress stimuli and in cells undergoing processes of differentiation and development. Regulation of the classical heat shock response is mediated by heat shock factor 1 (HSF1), whereas heat shock factor 2 (HSF2) is activated in certain differentiating cells, for example during hemin-mediated differentiation of human K562 erythroleukemia cells. Hence, the signaling pathways leading to induction of heat shock gene expression upon different stimuli are likely to be distinct. We have used RNA arbitrarily primed polymerase chain reaction to identify genes that are differentially regulated upon activation of HSF1 and HSF2. In this study, we report that thioredoxin (TRX) expression is induced in K562 cells in response to hemin in an HSF2-dependent manner. Increased TRX expression was primarily detected on the transcriptional level, subsequently leading to elevated TRX mRNA and protein levels. Hemin treatment caused no reduction in cellular glutathione concentrations, indicating that the increased TRX expression was not due to oxidative stress. Studies using cell lines where overexpression of the HSF2-beta isoform represses HSF2 activation implied that active HSF2 is required for transcriptional induction of TRX. Unlike HSF2, activation of HSF1 did not induce TRX expression. Taken together, our results suggest that HSF1 and HSF2 may regulate distinct target genes, and activation of HSF2 could be involved in the regulation of TRX expression during hemin-mediated differentiation of K562 cells.


RP-UPLC method development and validation for the simultaneous estimation of ibuprofen and famotidine in pharmaceutical dosage form.
A stability-indicating LC method was developed for the simultaneous determination of Ibuprofen and Famotidine in pharmaceutical dosage forms. The chromatographic separation was achieved on Acquity UPLC BEH C-18,50 mm × 2.1 mm and 1.7 μm column with gradient elution. The mobile phase A contains a mixture of 50 mM sodium acetate buffer (pH 5.5): methanol (85:15, v/v), and the mobile phase B contains a mixture of 50 mM sodium acetate buffer (pH 5.5): methanol (25:75, v/v). The flow rate was 0.3 mL min(-1), and the detection wavelength was 260 nm. The limit of detection for Ibuprofen and Famotidine was 1.6 and 1.2 μg mL(-1), respectively. The limit of quantification (LOQ) for Ibuprofen and Famotidine was 5.1 and 4.3 μg mL(-1), respectively. This method was validated for accuracy, precision, and linearity. The method was also found to be stability indicating.


Atmospheric turbulence effects on the performance of a free space optical link employing orbital angular momentum multiplexing.
We experimentally investigate the performance of an orbital angular momentum (OAM) multiplexed free space optical (FSO) communication link through emulated atmospheric turbulence. The turbulence effects on the crosstalk and system power penalty of the FSO link are characterized. The experimental results show that the power of the transmitted OAM mode will tend to spread uniformly onto the neighboring mode in medium-to-strong turbulence, resulting in severe crosstalk at the receiver. The power penalty is found to exceed 10 dB in a weak-to-medium turbulence condition due to the turbulence-induced crosstalk and power fluctuation of the received signal.


Genetic relationships among turnip (Brassica rapa var. rapa) genotypes.
Turnip (Brassica rapa var. rapa) is one of the main vegetables consumed by people living in Eastern Anatolia in Turkey. In this region, farmers obtain their own seeds for production, which results in considerable morphological variability. We examined the genetic variation and relationships among 11 turnip genotypes sampled from diverse environments of the Erzurum region located in Eastern Anatolia in Turkey. Thirty-two Operon RAPD primers were screened; among them, 20 gave reproducible and clear DNA fragments after amplification. The average polymorphism ratio was 90.4%. The genetic distance between turnip genotypes were found to range from 0.302 to 0.733, indicating high genetic variability. Eleven genotypes were divided into three main clusters in a dendrogram; ETS2 and ETS8 genotypes were the most distant. We conclude that RAPD analysis would be useful for genotyping turnip genotypes.


Multi-polarization passive millimeter-wave imager and outdoor scene imaging analysis for remote sensing applications.
Polarimetric passive millimeter-wave (PMMW) measurements can provide additional information about scenes. We report on the development of a 94GHz Multi-Polarization Scanning Imaging Radiometer (MPSIR) for outdoor imaging applications, and the polarization characteristic analysis of experimentally acquired images. The imager angular resolution is measured to be 0.37°, and the thermal sensitivity is about 0.46K. Multi-polarization measurements are realized by rotating the detector around the observation axis direction. Several outdoor complex scenes are selected to passive image, which include the outdoor parking lot and the dormitory buildings in the woods. Various polarization parameter images are generated to analyze the polarization characteristics. Based on the multi-polarization imaging, eight more polarization parameters are created and they are all have the special distribution properties. The experimental results indicate that the multi-polarization imaging and the modified polarization parameters have the great potential for three-dimensional reconstruction, edge detection and image segmentation.


The effect of acetazolamide and carbonic anhydrase inhibition on erythrocyte 2,3-diphosphoglycerate content and metabolism.
Experiments were designed to test the hypothesis that the change in erythrocyte 2,3-diphosphoglycerate (2,3-DPG) content which occurs when metabolic acidosis is induced by prolonged inhibition of carbonic anhydrase in vivo is the same as that which occurs with the induction of other types of metabolic acidosis states. 1) Thirteen-hour infusions of nondiuretic doses of a potent carbonic anhydrase inhibitor, acetazolamide (Diamox) did not alter erythrocyte 2,3-DPG levels in rats. 2) In vitro incubation of whole blood from rats for 10 days with high concentrations of two carbonic anhydrase inhibitors failed to alter the red cell content of 2,3-DPG. 3) Purified human carbonic anhydrase B had no phosphatase activity on 2,3-DPG and it appears unlikely that the enzyme hydrolyzes other phosphate esters of the erythrocyte which could indirectly alter 2,3-DPG content. 4) Acetazolamide administered in diuretic doses for 8 days to rats induced a metabolic acidosis which was accompanied by a decrease in erythrocyte 2,3-DPG. The change in 2,3-DPG content was similar to that produced by other methods of producing metabolic acidosis, namely NH4Cl treatment and nephrectomy. It appears that changes in 2,3-DPG content associated with effects of carbonic anhydrase inhibition can be ascribed to the metabolic acidosis resulting from the action of these drugs on the kidney.


The effects of melatonin on the antioxidant systems in experimental spinal injury.
Melatonin has been recently shown by various in-vivo and in-vitro studies to exert potent neutralising effects on hydroxyl radicals, stimulate glutathione peroxidase (GSH-Px) activity, and protect catalase (CAT) from the destructive activity of hydroxyl radicals in neural tissue. We aimed to investigate the possible effects of pharmacological dose of melatonin on some of the antioxidant defence systems in an in-vivo study of experimental spinal injury. Seven groups of adult male Sprague Dawley rats were used in the following scheme: Group I: Naive (n = 6), Group II: Lesion (n = 8), Group III: Melatonin (n = 5), Group IV: Melatonin + Lesion (n = 8), Group V: Placebo + Lesion (n = 5), Group VI: Sham operation (n = 5), and Group VII: Placebo (n = 5). Experimental spinal injury was induced at level T7-T8 by 5 sec compression of the total cord with an aneurysm clip on anaesthetised and laminectomized animals. The total 10 mg/kg dose of melatonin (Sigma) dissolved in alcohol-water was administered i.p. four times in 2.5 mg/kg doses, at 20 min pre-, at the time of and at 1 h and 2h post-compression. At 24 +/- 2h post-injury, the rats were euthanized and the lesioned segments of cord were dissected and homogenised with special care taken to distribute equal amount of injured tissue in each sample for analysis of reduced glutathione (GSH), oxidised glutathione (GSSG), superoxide dismutase (SOD), and CAT activity. Compression injury decreased GSH/GSSG ratio significantly (p < .0001). Melatonin, by itself, significantly decreased GSSG content (p < .05) and increased CAT activity (p < .05) in the naïve rats. Melatonin treatment decreased GSSG activity, thus elevating GSH/GSSG ratio, and also increased SOD and CAT activity without reaching statistical significance in the lesioned animals. In conclusion, pharmacological dose of systemically applied melatonin seemed to support some features of the antioxidant defence systems in our hands.


Cardiac outflow tract: a review of some embryogenetic aspects of the conotruncal region of the heart.
A review concerning some embryogenetic aspects of the cardiac outflow tract is presented. Two main topics are discussed: the truncal septation and the secondary heart field. In the context of the septation of the truncus arteriosus, the development of the arterial valves is largely discussed, particularly in reference to the sinuses of Valsalva. Emphasis is also given to the fate of the external myocardial wall of the truncus arteriosus, as this primordial myocardial surface disappears later in the development. Molecular genetics data concerning Sox4 and NF-Atc transcription factors are correlated in the present review with rare forms of truncus malformations encountered in human pathology. The roles exerted by the secondary heart field and the neural crest on the development and growth of the conotruncal musculature are largely discussed. Reported experimental ablations of both secondary heart field and neural crest, showed conotruncal defects such as persistent truncus arteriosus, tetralogy of Fallot, and double-outlet right ventricle, which were considered as the result of a short outflow tract causing, ultimately, a lack of conotruncal rotation. In this regard, some morphologic correlations are carried out, in the present review, between these experimental animal models and human malformations, and it is thought that this sort of conotruncal defects cannot be explained always in terms of conotruncal hypoplasia. Finally, influence of Pitx2c, a left-right laterality signaling gene, on the modulation of the conotruncal rotation, as most recently reported, is emphasized in terms of very likely multifactorial contributions in the embryogenesis of the conotruncal region of the heart.


Effects of heparin catheter-sealing solution for implantable venous access ports on D-dimer levels in older cancer patients.
To investigate the effects of different concentrations of heparin catheter-sealing solution for implantable venous access ports (VAPs) on D-dimers (D-D) in older cancer patients. A total of 208 older cancer patients who received intravenous chemotherapy for the first time were randomly divided into four groups: the normal saline group, the low concentration heparin group (25 U/ml), the medium concentration heparin group (50 U/ml), and the high concentration heparin group (75 U/ml), with 52 patients in each group. VAPs were sealed by the positive pressure technique every day before and after perfusion, as well as at the end of a course of chemotherapy when the butterfly needle was removed. The patients were followed-up for three courses of chemotherapy, and comparisons of the clinical effects were conducted. Before treatment and at the end of follow-up, no significant differences among groups were found in platelet count, prothrombin time, thrombin time, or activated partial thromboplastin time (p>0.05). At the end of follow-up, the high concentration heparin group had reduced fibrinogen (FIB) and increased D-D compared with the other groups, and the differences were statistically significant (p<0.05). The other three groups showed no significant differences in FIB or D-D before treatment or at the end of follow-up (p>0.05). The high concentration heparin group had higher local bleeding rate, while the saline group had higher partial and complete prevalence of blockage compared with the other groups. The differences were statistically significant (p<0.05). 25-50 U/ml heparin catheter-sealing solution had little effect on blood circulation and coagulation. Additionally, it did not increase the risk of local bleeding or thrombotic blockage.


Inventory and assessment of foliar natural enemies of the soybean aphid (Hemiptera: Aphididae) in South Dakota.
Soybean aphid (Aphis glycines Matsumura) (Hemiptera: Aphididae) is a major pest of soybean in northern production regions of North America, and insecticides have been the primary management approach while alternative methods are developed. Knowledge of arthropod natural enemies and their impact on soybean aphid is critical for developing biological control as a management tool. Soybean is a major field crop in South Dakota, but information about its natural enemies and their impact on soybean aphid is lacking. Thus, this study was conducted in field plots in eastern South Dakota during July and August of 2004 and 2005 to characterize foliar-dwelling, arthropod natural enemies of soybean aphid, and it used exclusion techniques to determine impact of natural enemies and ants (Hymenoptera: Formicidae) on soybean aphid densities. In open field plots, weekly soybean aphid densities reached a plateau of several hundred aphids per plant in 2004, and peaked at roughly 400 aphids per plant in 2005. Despite these densities, a relatively high frequency of aphid-infested plants lacked arthropod natural enemies. Lady beetles (Coleoptera: Coccinellidae) were most abundant, peaking at 90 and 52% of all natural enemies sampled in respective years, and Harmonia axyridis Pallas was the most abundant lady beetle. Green lacewings (Neuroptera: Chrysopidae) were abundant in 2005, due mainly to large numbers of their eggs. Abundances of arachnids and coccinellid larvae correlated with soybean aphid densities each year, and chrysopid egg abundance was correlated with aphid density in 2005. Three-week cage treatments of artificially infested soybean plants in 2004 showed that noncaged plants had fewer soybean aphids than caged plants, but abundance of soybean aphid did not differ among open cages and ones that provided partial or total exclusion of natural enemies. In 2005, plants within open cages had fewer soybean aphids than those within cages that excluded natural enemies, and aphid density on open-cage plants did not differ from that on noncaged plants and those accessible by small predators. In a separate 3-yr experiment, exclusion of ants from soybean plants did not lead to differences in soybean aphid density compared with ant-accessible plants. Overall, these results suggest that the soybean aphid natural enemy guild is unsaturated and could be enhanced to improve biological control of soybean aphid in South Dakota.


Dissociation of the neural networks recruited during a haptic object-recognition task: complementary results with a tensorial independent component analysis.
The cerebral and cerebellar networks involved in bimanual object recognition were assessed by blood oxygen level-dependent functional MR imaging by using multivariate model-free analysis, because conventional univariate model-based analysis, such as the general linear model (GLM), does not allow investigation of resting, background, and transiently task-related brain activities. Data from 14 healthy right-handed volunteers, scanned while successively performing bilateral finger movements and a bimanual tactile-tactile matching discrimination task were analyzed by using tensor-independent component analysis (TICA), which computes statistically independent spatiotemporal processes (P > .7) thought to reflect specific and distinct anatomofunctional neural networks. These results were compared with the network obtained in a previous study by using the same paradigm based on GLM to evaluate the advantages of TICA. TICA characterized and distinguished the following: 1) resting-state networks such as the default-mode networks, 2) networks transiently synchronized with the beginning and end of the task, such as temporo-pericentral and temporo-pericentral-occipital networks, and 3) task-related networks such as cerebello-fronto-parietal, cerebello-prefrontocingulo-insular, and cerebello-parietal networks. Bimanual tactile-tactile matching discrimination specifically recruits a complex neural network, which can be dissociated into 3 distinct but cooperative neural subnetworks related to sensorimotor function, salience detection, executive control, and, possibly, sensory expectation. This tripartite network involved in bimanual object recognition could not be demonstrated by GLM. Moreover, TICA allowed monitoring of the temporal succession of the networks recruited during the resting phase, audition of the "go" and "stop" signals, and the tactile discrimination task.


Evaluation of extrapancreatic inflammation on abdominal computed tomography as an early predictor of organ failure in acute pancreatitis as defined by the revised Atlanta classification.
The aim of the study was to determine whether extrapancreatic inflammation on computed tomography (EPIC) is helpful in predicting organ failure in the early phase of acute pancreatitis (AP) as defined by the 2012 revised Atlanta classification.Patients (n = 208) who underwent abdominal computed tomography (CT) within 24 hours after AP onset and admission were retrospectively identified. Each patient's EPIC score, Balthazar score, bedside index of severity in acute pancreatitis (BISAP), and systemic inflammatory response syndrome (SIRS) score were obtained. Primary endpoints were organ failure occurrence and death. Scores were evaluated by receiver operator characteristic (ROC) curve and area under the curve (AUC) analysis.Median age was 45 years (range: 18-83 years). Forty-seven patients (22.6%) developed organ failure, and 5 patients (2.4%) developed infection and underwent surgery. Two patients died. The median EPIC score was 2 (range: 0-7). EPIC score accuracy (AUC = 0.724) in predicting organ failure was similar to that of BISAP (0.773) and SIRS (0.801) scores, whereas Balthazar scoring was not significant (P = .293). An EPIC score of 3 or greater had a sensitivity and specificity of 80.65% and 63.16%, respectively. EPIC scores correlated moderately with organ failure severity (Spearman r = 0.321) and number of failed organs (r = 0.343).The EPIC scoring system can be useful in predicting the occurrence of organ failure, but it does not differentiate severity and number of failed organs in early phase AP.


MutT homolog-1 attenuates oxidative DNA damage and delays photoreceptor cell death in inherited retinal degeneration.
Retinitis pigmentosa (RP) is a genetically heterogenous group of inherited retinal degenerative diseases resulting from photoreceptor cell death and affecting >1 million persons globally. Although oxidative stress has been implicated in the pathogenesis of RP, the mechanisms by which oxidative stress mediates photoreceptor cell death are largely unknown. Here, we show that oxidation of nucleic acids is a key component in the initiation of death-signaling pathways in rd10 mice, a model of RP. Accumulation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) increased in photoreceptor cells, and especially within their nuclei, in rd10 mice as well as in Royal College of Surgeons rats, another model of RP caused by different genetic mutations. Vitreous samples from humans with RP contained higher levels of 8-oxo-dG excreted than samples from nondegenerative controls. Transgenic overexpression of human MutT homolog-1, which hydrolyzes oxidized purine nucleoside triphosphates in the nucleotide pool, significantly attenuated 8-oxo-dG accumulation in nuclear DNA and photoreceptor cell death in rd10 mice, in addition to suppressing DNA single-strand break formation, poly(ADP-ribose) polymerase activation, and nuclear translocation of apoptosis-inducing factor. These findings indicate that oxidative DNA damage is an important process for the triggering of photoreceptor cell death in rd10 mice and suggest that stimulation of DNA repair enzymes may be a novel therapeutic approach to attenuate photoreceptor cell loss in RP.


Longitudinal measurements of exhaled nitric oxide in children-what is a significant change in FE(NO) ?
The principle aim of this study was to describe the variability of exhaled nitric oxide (FE(NO)) concentrations over 10 months in children with and without asthma. FE(NO) was measured on six occasions at 2-month intervals in a community-based cohort of children with and without asthma. There were 178 children recruited, 47 had asthma, mean age 9.6 yr. A total of 851 FE(NO) measurements were made. The change in FE(NO) values was positively associated with the initial FE(NO) concentration (p < 0.001) and duration between paired measurements (p = 0.016) but not asthma diagnosis; there was an interaction between initial FE(NO) and duration between measurements. As an approximate rule-of-thumb, a child's FE(NO) may rise by up to 100% of their current FE(NO) over 2 and 4 months, independent of asthma. Both the baseline FE(NO) and interval between repeated FE(NO) measurements are relevant to FE(NO) values, independent of asthma. These findings may be useful to clinical interpretation of FE(NO) results in children.


Assessing the impact of anion-π effects on phenylalanine ion structures using IRMPD spectroscopy.
The gas-phase structures of two halide-bound phenylalanine anions (PheX(-), X = Cl(-) or Br(-)) and five fluorinated derivatives have been identified using infrared multiple photon dissociation (IRMPD) spectroscopy. The addition of electron-withdrawing groups to the aromatic ring creates a π-acidic system that additionally stabilizes the halide above the ring face. Detailed ion structures were determined by comparing the IRMPD spectra with harmonic and anharmonic infrared spectra computed using B3LYP/6-311++G(d,p) as well as with 298 K enthalpies and Gibbs energies determined by the MP2(full)/6-311++G(2d,2p)//B3LYP/6-311++G(d,p) and MP2(full)/aug-cc-pVTZ//B3LYP/6-311++G(d,p) methods. PheX(-) structures were found to be dependent on both the nature of the anion and the extent of ring fluorination. Canonical isomers were established to be the dominant structures in every case, but halide addition significantly narrowed the energy gap with zwitterionic potential energy surfaces. This enabled zwitterions to appear as minor contributors to the gas-phase populations of Phe35F2Cl(-) and PheF5Br(-).


[Integration of plasmid RP1 with the chromosome of Escherichia coli K-12 recA. 2 classes of Hfr strains].
Integration of broad host range RP1 plasmid into the chromosome of Escherichia coli K-12 recA- cells has been studied. Using temperature-sensitive for replication plasmids pVD1 and pVD3, the derivatives of RP1, it has been shown that integration of RP1 into the bacterial chromosome results in formation of two classes of Hfr strains. Properties of these Hfrs have been examined. From the data obtained, it has been concluded that the plasmid integration and formation of one of the Hfrs classes appear to be mediated by transposon Tn1 residing on RP1. The other class of Hfr strains is formed due to a stable integration of RP1. In the course of analysis of R+ transconjugants arising at low frequency in crosses between stable Hfrs and E. coli rec+ recipients, it has been found that the significant part of them contain plasmid-chromosome hybrids (R-prim plasmids). On the basis of the latter results, a new simple method for R' plasmids selection has been proposed. Using restriction endonuclease analysis, the structure of plasmids that were excised from chromosomes of the stable Hfr strains and were comparable in their size to RP1, has been investigated. Probable mechanisms of the stable Hfr strains formation are discussed.


Surgical approach and results of surgery in adenocarcinoma of the gastro-oesophageal junction.
This paper attempts to determine the appropriate surgical procedure in relation to the pathological types of adenocarcinoma of the gastro-oesophageal junction in Singapore. Data on population characteristics, clinical presentation, pathology, surgical procedures and results of treatment were gathered from the case records of a personal series of 32 patients resected for adenocarcinoma of the gastro-oesophageal junction. The 32 patients with adenocarcinoma of the gastro-oesophageal junction (Type I, 9; II, 20 and III, 3), presented at a late stage (Stage I-II, 5; III, 14; IV, 13). In 19 patients with Stages I-III disease, attempted curative surgery was performed--extended total gastrectomy for Types II and III disease (13 patients) and oesophagectomy for Type I (6 patients). There was one operative mortality following curative resection. Palliative resection was performed on 13 patients with Stage IV disease with one operative mortality. The main operative morbidity was anastomotic leakage, occurring in 5 patients; both operative deaths were associated with this complication. The actuarial 5-year survival was 20%. Although gastro-oesophageal cancer presents late, it can be resected safely by extended total gastrectomy for Types II and III disease and oesophagectomy for Type I disease, taking precautions to minimise anastomotic leakage. Although usually palliative, Stages I and II and to a lesser extent Stage III, are curable by these surgical procedures which ensure a tumour free surgical margin and adequate lymphadenectomy.


Predictive factors for the development of brain metastasis in advanced unresectable metastatic melanoma.
Melanoma that metastasizes to distant sites is associated with a grave prognosis. The objectives of the study were (1) to identify predictive factors for the development of brain metastases from the time of diagnosis of stage III/IV disease, (2) to identify predictive factors for the development of central nervous system (CNS) metastases from the time of diagnosis of primary melanoma, and (3) to assess whether the incidence of brain metastasis is more frequent in patients who had no tumor response to systemic therapy for stage III/IV disease compared with those who had partial or complete response. We collected and retrospectively analyzed information of 740 patients with advanced metastatic melanoma treated at MD Anderson Cancer Center over 15 years. Three hundred and twenty-nine patients had CNS metastases. The characteristics of these patients in terms of median age, sex, primary site, Breslow thickness, stage at first visit, baseline serum parameters, and response to systemic therapy were compared with those of patients who did not develop CNS metastasis. Cox proportional hazards models were used to analyze the cause-specific hazard function for CNS metastasis and deaths without CNS metastasis. We identified that M-stage [stage M1b vs. stage III or M1a, hazard ratio (HR)=2.64; stage M1c vs. stage III or M1a, HR=2.13, P<0.0001] and lactic acid dehydrogenase (LDH) (elevated vs. normal LDH, HR=1.51, P<0.001) at diagnosis of unresectable stage III/IV disease can independently predict the risk of developing CNS metastasis from the time of diagnosis of stage III/IV disease. Older age (HR=1.01, P=0.076), chemoresistance (stable disease+progressive disease vs. complete response+partial response HR=2.91, P<0.0001), low level of albumin (vs. normal HR=2.87, P<0.0001), elevated LDH (vs. normal HR=1.55, P=0.0004), and M-stage (M1c disease vs. stage III or M1a HR=1.89, P<0.0001) can independently predict shorter time to death without CNS metastasis from the diagnosis of stage III/IV disease. The location (head and neck vs. limbs HR=1.56, P=0.028; trunk and abdomen vs. limbs HR=1.45, P=0.029; unknown site vs. limbs HR=8.43, P=0.036) and pathology [Clark level (CL)=3 and/or BR2 to 4 mm vs. CL≤2 and/or BR<2 mm HR=1.60, P=0.037; CL>3 and/or BR> 4 mm vs. CL≤2 and/or BR<2 mm HR=2.03, P=0.001) of the primary melanoma can independently predict CNS metastasis-free interval from the time of diagnosis of primaries. Age (HR=1.012, P=0.034) and pathology of the primary melanoma (CL>3 and/or BR>4 mm vs. CL≤2 and/or BR<2 mm HR=1.54, P=0.024) can independently predict time to death without CNS metastasis from primaries. We identified the predictive factors associated with the development of CNS metastasis in patients with unresectable metastatic melanoma.


Alteration of a p53 gene status affects outcome of patients with recurrent ovarian cancer.
The aim of this longitudinal study was to examine whether and how the p53 gene is altered in patients with recurrent ovarian cancer and to determine the significance of p53 mutation in recurrent tumors. The primary and recurrent tumors were examined in 15 patients who had recurrent epithelial ovarian cancer, and whose primary tumor contained a wild-type p53 gene. The interval between cytoreductive surgery and the appearance of recurrence ranged from 5. 2 to 63.6 months (mean 23.4 months). Mutations in the p53 gene were screened by polymerase chain reaction single strand conformation polymorphism analysis and determined by cycle sequencing. Mutation of the p53 gene in the recurrent tumor was found in 7 of the 15 patients (46.7%). Estimated 3- and 5-year survival rates were 57.1 and 0%, respectively, for patients with p53 gene mutation detected in the recurrence tumor, and 75.0% and 37.5% for patients without the mutation (p = 0.0155). The interval between cytoreductive surgery and the appearance of recurrence did not differ between those groups (549.7 +/- 102.2 vs. 832.9 +/- 283.8 days). Mean survival time after recurrence was significantly better in the patients without mutation (438.6 +/- 56.4 vs. 873.0 +/- 157.5 days, p = 0.0125). The present study suggests that p53 gene mutation frequently occurs in recurrent ovarian cancer and that alteration of p53 gene status affects salvage chemotherapy. This phenomenon affects the prognosis of recurrent disease and may predict outcome.


CYP2C19*17 association with higher plasma 4-hydroxy tamoxifen in Pakistani (estrogen-positive) breast cancer patients.
Breast cancer (BC) continues to be the most common cancer in the women worldwide. Since estrogen receptor (ER)-positive BC accounts for the majority of newly diagnosed cases, endocrine therapy is advised to utilize either tamoxifen (Tam) or aromatase inhibitors. The use of Tam as a monotherapy or in conjunction with an aromatase inhibitor following two or three years of endocrine therapy has long been recommended. When used adjuvantly, Tam medication reduces BC mortality and relapses, while it extends survival times in metastatic BC when used in conjunction with other treatments. Unfortunately, the efficiency of Tam varies considerably. This study was conducted to explore the influence of genetic polymorphisms in CYP2C19 gene on Tam's pharmacogenetics and pharmacokinetics in estrogen-positive BC patients. Data from healthy, unrelated individuals (n = 410; control group) and ER-positive BC patients (n = 430) receiving 20 mg of Tam per day were recruited. Steady-state plasma concentrations of Tam and its three metabolites were quantified using the high-performance liquid chromatography in the patients. The CYP2C19 polymorphisms were genotyped using an Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) approach. More than 65% of healthy individuals were extensive metabolizers (*1/*1) for CYP2C19, whereas more than 70% of ER-positive BC patients were rapid and ultrarapid metabolizers (*1/17*, *17/17*). The polymorphism CYP2C19*17 is significantly associated with higher 4-hydroxytamoxifen (4-OH-Tam). Patients with the *17/*17 genotype exhibited 1- to 1.5-fold higher 4-OH-Tam, which was also high in patients with the *1/*2 and *2/*2 genotypes.


The conservation nexus: valuing interdependent water and energy savings in Arizona.
Water and energy resources are intrinsically linked, yet they are managed separately--even in the water-scarce American southwest. This study develops a spatially explicit model of water-energy interdependencies in Arizona and assesses the potential for cobeneficial conservation programs. The interdependent benefits of investments in eight conservation strategies are assessed within the context of legislated renewable energy portfolio and energy efficiency standards. The cobenefits of conservation are found to be significant. Water conservation policies have the potential to reduce statewide electricity demand by 0.82-3.1%, satisfying 4.1-16% of the state's mandated energy-efficiency standard. Adoption of energy-efficiency measures and renewable generation portfolios can reduce nonagricultural water demand by 1.9-15%. These conservation cobenefits are typically not included in conservation plans or benefit-cost analyses. Many cobenefits offer negative costs of saved water and energy, indicating that these measures provide water and energy savings at no net cost. Because ranges of costs and savings for water-energy conservation measures are somewhat uncertain, future studies should investigate the cobenefits of individual conservation strategies in detail. Although this study focuses on Arizona, the analysis can be extended elsewhere as renewable portfolio and energy efficiency standards become more common nationally and internationally.


How to Classify Super-Utilizers: A Methodological Review of Super-Utilizer Criteria Applied to the Utah Medicaid Population, 2016-2017.
A limited number of patients, commonly termed super-utilizers, account for the bulk of health care expenditures. Multiple criteria for identifying super-utilizers exist, but no standard methodology is available for determining which criteria should be used for a specific population. Application is often arbitrary, and poorly aligned super-utilizer criteria might result in misallocation of resources and diminished effects of interventions. This study sought to apply an innovative, data-driven approach to classify super-utilizers among Utah Medicaid beneficiaries. The authors conducted a literature review of research methods to catalogue applied super-utilizer criteria. The most commonly used criteria were applied to Utah Medicaid beneficiaries enrolled during July 1, 2016-June 30, 2017, using their previous 12 months of claims data (N = 309,921). The k-medoids algorithm cluster analysis was used to find groups of beneficiaries with similar characteristic based on criteria from the literature. In all, 180 super-utilizer criteria were identified in the literature, 21 of which met the inclusion criteria. When these criteria were applied to Utah Medicaid data, 5 distinct subpopulation clusters were found: non-super-utilizers (n = 163,118), beneficiaries with multiple chronic or mental health conditions (n = 68,054), beneficiaries with a single chronic health condition (n = 43,939), emergency department super-utilizers with chronic or mental health conditions (n = 7809), and beneficiaries with uncomplicated hospitalizations (n = 27,001). This study demonstrates how cluster analysis can aid in selecting characteristics from the literature that systematically differentiate super-utilizer groups from other beneficiaries. This methodology might be useful to health care systems for identifying super-utilizers within their patient populations.


Effect of serine hydroxamate on the growth of Escherichia coli.
The structural analogue of l-serine, l-serine hydroxamate, inhibited the growth of Escherichia coli K-12. Of the other amino acid hydroxamates tested, only l-lysine hydroxamate reduced the rate of growth. Inhibition of growth by l-serine hydroxamate was rapidly reversed by the addition of l-serine to the bacterial culture or by removal of the analogue by filtration. The reversal of inhibition was specific for l-serine. l-Alanine, glycine, or adenine had no effect on an inhibited culture. No evidence for active transport of the analogue was obtained.


Thumb carpometacarpal arthritis.
Osteoarthritis of the thumb carpometacarpal joint has a reported radiographic prevalence of 7 percent in men and 15 percent in women. Many patients remain minimally symptomatic; however, a subset of patients develop debilitating pain, weakness, and instability that severely limit hand function. Treatment options have focused on removal of the diseased trapezium and stabilization of the metacarpal base. Newer options, including carpometacarpal arthroplasty, may have a role in some patients for improving function. This article explores the anatomy and biomechanics of carpometacarpal arthritis and its present surgical treatment options.


[Modernization of production as criterion for reducing of sanitary protection zone].
The complex hygienic assessment of a large enterprise of chemical profile as a source of the chemical and physical effects on the environment and human health has been given. Modernization of the production with the introduction of modern technologies, effective gas- powered dust collector units was found to permit to reduce emissions by 20%, diminish the levels of atmospheric air pollution to the normative values, health risks--to acceptable. According to the research after the reconstruction of the plant the possibility to move it from 1 to 2 danger class with reduction in size of sanitary protection zones in 2 times (from 1000 to 500 m).


Investigation of the role of CD8+ T cells in bovine tuberculosis in vivo.
Mycobacterium bovis is the causative agent of bovine tuberculosis (TB), and it has the potential to induce disease in humans. CD8(+) T cells (CD8 cells) have been shown to respond to mycobacterial antigens in humans, cattle, and mice. In mice, CD8 cells have been shown to play a role in protection against mycobacterial infection. To determine the role of CD8 cells in bovine TB in vivo, two groups of calves were infected with the virulent M. bovis strain AF2122/97. After infection, one group was injected with a CD8 cell-depleting monoclonal antibody (MAb), and the other group was injected with an isotype control MAb. Immune responses to mycobacterial antigens were measured weekly in vitro. After 8 weeks, the animals were killed, and postmortem examinations were carried out. In vitro proliferation responses were similar in both calf groups, but in vitro gamma interferon (IFN-gamma) production in 24-h whole-blood cultures was significantly higher in control cattle than in CD8 cell-depleted calves. Postmortem examination showed that calves in both groups had developed comparable TB lesions in the lower respiratory tract and associated lymph nodes. Head lymph node lesion scores, on the other hand, were higher in control calves than in CD8 cell-depleted calves. Furthermore, there was significant correlation between the level of IFN-gamma and the head lymph node lesion score. These experiments indicate that CD8 cells play a role in the immune response to M. bovis in cattle by contributing to the IFN-gamma response. However, CD8 cells may also play a deleterious role by contributing to the immunopathology of bovine TB.