An early stage in T4-induced hyperthyroidism is related to systemic oxidative stress but does not influence the pentose cycle in erythrocytes and systemic inflammatory status.
Hyperthyroidism causes many injuries in its target organs and the consequences are reflected systemically. As systemic alterations in hyperthyroidism at earlier stages have received partial attention, this study aimed to investigate systemic redox and inflammatory status at an early stage of T4-induced hyperthyroidism. Male Wistar rats were assigned to control and hyperthyroid groups (n = 7/group). The hyperthyroid group received L-thyroxine (12 mg/L) in their drinking water for 14 days whereas control group received only the vehicle. Body weight was measured on the 1st and 14th day of the protocol. On the 14th day, animals were anaesthetized. Blood was then collected from the retro-orbital venous plexus and then the animals were euthanised. The blood was separated into plasma and erythrocytes. Plasma was used to measure ROS levels, sulfhydryl compounds, IL-10, TNF-α and LDH levels; erythrocytes were used for the analysis of thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes (total G6PD, G6PD and 6PGD). Hyperthyroid animals presented body weight gain and final body weight reduction, which was associated with increased ROS levels and decreased sulfhydryl content in plasma. Thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes levels in erythrocytes, as well as IL-10, TNF-α and LDH plasma levels were unaltered. Taken together, our results suggest an impairment in corporal mass associated with systemic oxidative stress at this stage of hyperthyroidism. Meanwhile, the pentose cycle was not influenced and systemic inflammation and tissue damage seem to be absent at this stage of hyperthyroidism.


Intersession interval affects performance in the Morris Water Maze.
We have recently reported an effect that shows a sexually dimorphic difference in cognitive style rather than ability. The preparation for potentially producing this proximal perceptual style effect is one where rats are first given 4-trial daily acquisition sessions for 12 days with the platform always in the same position, but sometimes visible (perceptual, "look-out" condition) and sometimes hidden (conceptual, "navigational" condition). On the first, probe trial of the 13th day, the platform's position is shifted to a point very close (proximal) to the rat's starting position, and made visible. The proximal perceptual style (PPS) effect has emerged sexually dimorphically in that only females swam straight to the newly positioned proximal platform. Other studies have shown that the PPS effect is eliminated (with females behaving like males) by nicotine and prepubertal ovariectomy, and does not occur in prepubertal females. Also, as no sex-related effects emerged during acquisition during these studies, the PPS effect appears to be a function of cognitive style rather than ability. The present study varied age, and, in an effort to economize on time, shortened acquisition to 6 days by having morning and afternoon sessions each day. To our surprise, this relatively subtle psychological manipulation eliminated the PPS effect, and also yielded some sex- and age-related effects during acquisition: A male advantage was observed and prepubertal rats had longer escape latencies; there was no significant interaction between sex and age.


Rewilding Apex Predators Has Effects on Lower Trophic Levels: Cheetahs and Ungulates in a Woodland Savanna.
The restoration of ecosystems through trophic rewilding has become increasingly common worldwide, but the effects on predator-prey and ecosystem dynamics remain poorly understood. For example, predation pressure may impose spatiotemporal behavioural adjustments in prey individuals, affecting herbivory and predation success, and therefore potentially impinging on the long-term success of trophic rewilding through apex predator reintroduction. Predation risk might have detrimental effects on prey through displacement from water or other vital resources. We investigated how five species of African ungulates responded behaviourally to changes in predation risk, following cheetah releases in the system. We grouped ungulates by body size to represent preferred prey weight ranges of the cheetah and examined changes in visitation rates, duration of stay, and activity patterns at waterholes with and without cheetah presence. During cheetah presence, visitation rates of ungulates were low for medium-sized species but high for large-sized species, suggesting that the species within the cheetah's preferred prey weight range adjusted behaviourally to minimize waterhole visits. Visits to waterholes were longer for small- and large-sized ungulates with cheetah presence, possibly indicating increased vigilance, or a strategy to maximize water intake per visit while minimizing visits. We did not detect significant differences in circadian or seasonal activity in waterhole visits, which may be attributable to the need of ungulates to access water year-round in our semi-arid study system and where migration was impeded due to physical barriers (fencing). We recommend further research into the long-term behavioural consequences of trophic rewilding on prey populations and trophic cascades to assist the success of recovery programs and to minimize potential detrimental effects at target sites.


Extracellular DNA promotes colorectal tumor cell survival after cytotoxic chemotherapy.
Inflammation promotes the growth and survival of malignant cells. Inflammation within the tumor microenvironment is a result of damage-associated molecular patterns released by dead or dying cells that provide survival signals to the surrounding cells. It has been proposed that extracellular DNA can act as a damage-associated molecular pattern given the association between circulating DNA and autoimmune diseases. Herein, we demonstrate a novel role for genomic extracellular DNA binding to the Toll-like receptor (TLR)-9 on tumor cells in response to cytotoxic insult. The colorectal tumor cell line HCCT116 was used to study the role of DNA in tumor cell response to chemotherapy. Cell viability was assessed using CCK-8 assay. Cell death mechanisms were assessed by YOYO-1 and lactate dehydrogenase staining for necrosis and TUNEL staining for apoptosis. Autophagy was measured by LC3 punctate formation. TLR9-short hairpin RNA was used to knockdown TLR-9 and determine its role in tumor cell response to DNA. DNA is released from necrotic tumor cells after chemotherapy. Survival after cytotoxic insult is enhanced by the presence of extracellular DNA as a result of inhibition of apoptosis and enhanced autophagy. Knockdown of TLR-9 enhanced apoptosis, diminished autophagy, and decreased survival after cytotoxic insult in the presence or absence of extracellular DNA. DNA in the tumor microenvironment promotes survival through induction of autophagy via TLR-9 signaling. This work has important implications for targeting extracellular DNA, TLR-9, and autophagy during treatment with chemotherapy and enhances our understanding of the role of extracellular DNA in the tumor microenvironment.


D-ribose aids advanced ischemic heart failure patients.
Patients with advanced heart failure are exercise intolerant. Low cellular energy levels in the failing heart have been proposed. Energy enhancing substrates have revealed mixed results. Ribose, a pentose monosaccharide, has shown to replenish low myocardial energy levels, improving cardiac dysfunction following ischemia, and improving ventilation efficiency in patients with heart failure. As current pharmaceuticals do not address cellular energy levels, this study was designed to investigate the role of ribose on ventilation at anaerobic threshold in congestive heart failure patients. d-ribose (5 gms/dose, tid) was assessed in 16 NYHA class III-IV, heart failure patients with VO(2), tidal volume/VCO(2), heart rate/tidal volume evaluated at 8 weeks. All patients had a significant improvement in ventilatory parameters at anaerobic threshold, along with a 44% Weber class improvement. Ribose improved the ventilatory exercise status in advanced heart failure patients.


A Convergent Study of Genetic Variants Associated With Crohn's Disease: Evidence From GWAS, Gene Expression, Methylation, eQTL and TWAS.
Crohn's Disease (CD) is one of the predominant forms of inflammatory bowel disease (IBD). A combination of genetic and non-genetic risk factors have been reported to contribute to the development of CD. Many high-throughput omics studies have been conducted to identify disease associated risk variants that might contribute to CD, such as genome-wide association studies (GWAS) and next generation sequencing studies. A pressing need remains to prioritize and characterize candidate genes that underlie the etiology of CD. In this study, we collected a comprehensive multi-dimensional data from GWAS, gene expression, and methylation studies and generated transcriptome-wide association study (TWAS) data to further interpret the GWAS association results. We applied our previously developed method called mega-analysis of Odds Ratio (MegaOR) to prioritize CD candidate genes (CDgenes). As a result, we identified consensus sets of CDgenes (62-235 genes) based on the evidence matrix. We demonstrated that these CDgenes were significantly more frequently interact with each other than randomly expected. Functional annotation of these genes highlighted critical immune-related processes such as immune response, MHC class II receptor activity, and immunological disorders. In particular, the constitutive photomorphogenesis 9 (COP9) signalosome related genes were found to be significantly enriched in CDgenes, implying a potential role of COP9 signalosome involved in the pathogenesis of CD. Finally, we found some of the CDgenes shared biological functions with known drug targets of CD, such as the regulation of inflammatory response and the leukocyte adhesion to vascular endothelial cell. In summary, we identified highly confident CDgenes from multi-dimensional evidence, providing insights for the understanding of CD etiology.


Medicare Part C: tossing another cost cap into the ring.
Rejecting the Clinton Administration's call for mandatory health alliances, a key congressional panel recently passed a bill that expands the Medicare program to cover low-income and uninsured Americans. While some have criticized the bill's cost-containment provisions, the panel agreed that universal coverage cannot be achieved without a national health budget.


Long-term seizure and social outcomes following temporal lobe surgery for intractable epilepsy during childhood.
Studies of adults who underwent temporal lobectomy for intractable temporal lobe epilepsy (TLE) demonstrated declining seizure free rates over time. Using seizure and social parameters, we followed patients who had temporal lobe surgery (TLS) in childhood to determine long-term outcomes. We identified 42 patients who underwent TLS for medically intractable epilepsy during childhood. Follow-up data were collected from 10 to 20 years after surgery (median, 12 years). We studied histopathology, seizure outcome, employment, school enrolment, and driver's licensing. Patients or parents graded their satisfaction with TLS. Number of Engel class I patients was 34 (81%) after 6 months; 32 (76%) after 1 year; 30 (71%) after 5 years; and 28 (67%) at last >or=10 years follow-up. Nineteen (79%) of 24 children with tumors or cavernous angioma achieved class I outcomes in contrast to 9 (50%) of 18 children with other pathologies (p<0.05). Ten (56%) of 18 recurrent seizure patients experienced seizures within the first year; 4 required reoperation for seizure freedom. More seizure free patients (24, 86%) than residual seizure patients (8, 57%) were employed or in school (p=0.05). Twelve (63%) of 19 eligible patients obtained driver's licenses. Twenty-three (82%) of 28 seizure free patients discontinued anticonvulsants. Surgery grading averaged "satisfied." Class I patients reported greater satisfaction than class III/IV patients (p<0.001). Two-thirds of children who underwent TLS achieved seizure freedom at >or=10 year follow-up. Children with tumors or cavernous angiomas achieved better long-term outcomes than those with other histopathologies. Long-term seizure free patients were most often satisfied with surgery and employed or in school.


Sugar starvation-regulated MYBS2 and 14-3-3 protein interactions enhance plant growth, stress tolerance, and grain weight in rice.
Autotrophic plants have evolved distinctive mechanisms for maintaining a range of homeostatic states for sugars. The on/off switch of reversible gene expression by sugar starvation/provision represents one of the major mechanisms by which sugar levels are maintained, but the details remain unclear. α-Amylase (αAmy) is the key enzyme for hydrolyzing starch into sugars for plant growth, and it is induced by sugar starvation and repressed by sugar provision. αAmy can also be induced by various other stresses, but the physiological significance is unclear. Here, we reveal that the on/off switch of αAmy expression is regulated by 2 MYB transcription factors competing for the same promoter element. MYBS1 promotes αAmy expression under sugar starvation, whereas MYBS2 represses it. Sugar starvation promotes nuclear import of MYBS1 and nuclear export of MYBS2, whereas sugar provision has the opposite effects. Phosphorylation of MYBS2 at distinct serine residues plays important roles in regulating its sugar-dependent nucleocytoplasmic shuttling and maintenance in cytoplasm by 14-3-3 proteins. Moreover, dehydration, heat, and osmotic stress repress MYBS2 expression, thereby inducing αAmy3 Importantly, activation of αAmy3 and suppression of MYBS2 enhances plant growth, stress tolerance, and total grain weight per plant in rice. Our findings reveal insights into a unique regulatory mechanism for an on/off switch of reversible gene expression in maintaining sugar homeostatic states, which tightly regulates plant growth and development, and also highlight MYBS2 and αAmy3 as potential targets for crop improvement.


[The reaction of the individual to an uncontrollable exposure depends on the behavioral strategy].
An inescapable electrical shock (IS) induced failures to escape, diminished a locomotor activity and anxiety in Koltushi High-Avoidance rat strains (KHA) as opposed to Koltushi Low-Avoidance (KLA) rat strains. An escapable shock did not affect the KHA rats in behavioural and endocrine experiments, whereas it produced the same effects as the IS in the KLA rats.


Association of positive fluid balance and cardiovascular complications after thoracotomy for noncancer lesions.
The purpose of this study was to explore the influence of positive fluid balance on cardiovascular complications after thoracotomy for noncancer lesions. After approval from an institutional review board, a retrospective cohort study was conducted. All consecutive patients undergoing thoracotomy between January 1, 2005 and December 31, 2011 in a single medical center were recruited. The primary outcome of the study was the incidence of cardiovascular complications, which were defined as cardiac arrhythmia, cardiac arrest, heart failure, myocardial ischemia, and pulmonary embolism. Univariable and multivariable risk regression analyses were used to evaluate the association between positive fluid balance and cardiovascular complications. A total of 720 patients were included in this study. The incidence of cardiovascular complications after thoracotomy for noncancer lesions was 6.7% (48 of 720). Patients with positive fluid balance >2,000 mL had a significantly higher incidence of cardiovascular complications than those with positive fluid balance ≤2,000 mL (22.2% versus 7.0%, P=0.005). Cardiac arrhythmias were the most common complication. Univariable risk regression showed that positive fluid balance >2,000 mL was a significant risk factor (risk ratio =3.15, 95% confident interval [CI] =1.44-6.90, P-value =0.004). After adjustment for all potential confounding variables during multivariable risk regression analysis, positive fluid balance >2,000 mL remained a strong risk factor for cardiovascular complications (risk ratio =2.18, 95% CI =1.36-3.51, P-value =0.001). Causes of positive fluid balance >2,000 mL included excessive hemorrhage (48%), hypotension without excessive hemorrhage (29.6%), and liberal fluid administration (22.4%). Positive fluid balance was a significant risk factor for cardiovascular complications. Strategies to minimize positive fluid balance during surgery for patients at high risk of cardiovascular complications include preparing adequate blood and blood products, considering appropriate hemoglobin level as a transfusion trigger, and adjusting the optimal dose of local anesthetic for intraoperative thoracic epidural analgesia.


Active site loop conformation regulates promiscuous activity in a lactonase from Geobacillus kaustophilus HTA426.
Enzyme promiscuity is a prerequisite for fast divergent evolution of biocatalysts. A phosphotriesterase-like lactonase (PLL) from Geobacillus kaustophilus HTA426 (GkaP) exhibits main lactonase and promiscuous phosphotriesterase activities. To understand its catalytic and evolutionary mechanisms, we investigated a "hot spot" in the active site by saturation mutagenesis as well as X-ray crystallographic analyses. We found that position 99 in the active site was involved in substrate discrimination. One mutant, Y99L, exhibited 11-fold improvement over wild-type in reactivity (kcat/Km) toward the phosphotriesterase substrate ethyl-paraoxon, but showed 15-fold decrease toward the lactonase substrate δ-decanolactone, resulting in a 157-fold inversion of the substrate specificity. Structural analysis of Y99L revealed that the mutation causes a ∼6.6 Å outward shift of adjacent loop 7, which may cause increased flexibility of the active site and facilitate accommodation and/or catalysis of organophosphate substrate. This study provides for the PLL family an example of how the evolutionary route from promiscuity to specificity can derive from very few mutations, which promotes alteration in the conformational adjustment of the active site loops, in turn draws the capacity of substrate binding and activity.


How protein materials balance strength, robustness, and adaptability.
Proteins form the basis of a wide range of biological materials such as hair, skin, bone, spider silk, or cells, which play an important role in providing key functions to biological systems. The focus of this article is to discuss how protein materials are capable of balancing multiple, seemingly incompatible properties such as strength, robustness, and adaptability. To illustrate this, we review bottom-up materiomics studies focused on the mechanical behavior of protein materials at multiple scales, from nano to macro. We focus on alpha-helix based intermediate filament proteins as a model system to explain why the utilization of hierarchical structural features is vital to their ability to combine strength, robustness, and adaptability. Experimental studies demonstrating the activation of angiogenesis, the growth of new blood vessels, are presented as an example of how adaptability of structure in biological tissue is achieved through changes in gene expression that result in an altered material structure. We analyze the concepts in light of the universality and diversity of the structural makeup of protein materials and discuss the findings in the context of potential fundamental evolutionary principles that control their nanoscale structure. We conclude with a discussion of multiscale science in biology and de novo materials design.


Directional reflectance of vegetation measured by a calibrated digital camera.
Obtaining directional reflectance information for vegetation canopies is often an expensive and time-consuming process. We present here a simple approach based on the use of an inexpensive digital camera equipped with a wide-angle lens. By the imaging of a large homogeneous area, a single image captures multiple views of a vegetation canopy. This gives a directional reflectance distribution fully sampled for view direction and free of variations in Sun elevation and azimuth. We determined the radiometric response of the camera sensor CCD's at the focal point and then extended this calibration to the full CCD array by using averaged images of clear blue sky. We evaluated the utility of the system by obtaining directional reflectance distributions of two vegetation targets, grass (Lolium spp) and pine forest (Pinus radiata), for red visible light. The precision of the derived biangular pattern of reflectance was +/-7%.


Hypothermia differentially increases extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun terminal kinase activation in the hippocampus during reperfusion after asphyxial cardiac arrest.
Mitogen-activated protein kinases are signal transduction mediators that have been implicated in cell survival and cell death. This study characterized the activation of pathways in the hippocampus during reperfusion after global cerebral ischemia, as well as the influence of a regimen of hypothermia that reduces ischemic cell death in the hippocampus. Circulatory arrest was induced in rats by 8 min of asphyxia. Relative levels of phosphorylated and total extracellular signal-regulated kinase, stress-activated protein kinase/c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were measured in the hippocampus after 6, 12 or 24h of reperfusion using immunoblotting. Asphyxia induced a progressive increase in phosphorylated extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase, but no change in phosphorylated p38 mitogen-activated protein kinase. Induction of mild hypothermia (33 degrees C) during reperfusion increased extracellular signal-regulated kinase phosphorylation and produced a smaller increase in stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation at 24h. Hypothermia did not alter extracellular signal-regulated kinase activation in rats not subjected to ischemia. Extracellular signal-regulated kinase activation was associated with an increase in phosphorylation of the mitogen-activated protein kinase kinase 1/2, and was inhibited by administration of the specific mitogen-activated protein kinase kinase 1/2 inhibitor SL327. Immunohistochemical staining showed an increase in active extracellular signal-regulated kinase in the CA1, CA2, CA3 and dentate gyrus regions of the hippocampus after ischemia and reperfusion. In contrast, active stress-activated protein kinase/c-Jun N-terminal kinase immunoreactivity was most intense in the CA3 and dentate gyrus regions. These data demonstrate that both extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase pathways are activated during the first 24h of reperfusion after global cerebral ischemia, and that hypothermia increases the activation of extracellular signal-regulated kinase relative to stress-activated protein kinase/c-Jun N-terminal kinase. Thus, an increase in extracellular signal-regulated kinase activation may be associated with improved neuronal survival after ischemic injury.


Proton-Assisted Reduction of CO2 by Cobalt Aminopyridine Macrocycles.
We report here the efficient reduction of CO2 to CO by cobalt aminopyridine macrocycles. The effect of the pendant amines on catalysis was investigated. Several cobalt complexes based on the azacalix[4](2,6)pyridine framework with different substitutions on the pendant amine groups have been synthesized (R = H (1), Me (2), and allyl (3)), and their electrocatalytic properties were explored. Under an atmosphere of CO2 and in the presence of weak Brønsted acids, large catalytic currents are observed for 1, corresponding to the reduction of CO2 to CO with excellent Faradaic efficiency (98 ± 2%). In comparison, complexes 2 and 3 generate CO with TONs at least 300 times lower than 1, suggesting that the presence of the pendant NH moiety of the secondary amine is crucial for catalysis. Moreover, the presence of NH groups leads to a positive shift in the reduction potential of the Co(I/0) couple, therefore decreasing the overpotential for CO2 reduction.


Maternal immune activation mediated prenatal chronic stress induces Th17/Treg cell imbalance may relate to the PI3K/Akt/NF-κB signaling pathway in offspring rats.
Maternal immune activation (MIA), defined as elevated levels of inflammatory markers beyond the normal range, can occur due to psychological stress, infection, and other disruptions during pregnancy. MIA affects the immune system development in offspring and increases the risk of immune-related disorders. Limited studies have investigated the effects of prenatal stress on offspring's immune system. In this study, pregnant rats were exposed to chronic unpredictable mild stress (CUMS) during pregnancy, involving seven different stressors. We examined the impact of prenatal stress stimuli on the offspring's immune system and observed activation of the PI3K/Akt/NF-κB signaling pathway, resulting in an imbalance of Th17/Treg cells in the offspring's spleen. Our findings revealed increased plasma levels of corticosterone, IL-1β, and IL-6 in female rats exposed to prenatal stress, as well as elevated serum levels of IL-6 and TNF-α in the offspring. Furthermore, we identified a correlation between cytokine levels in female rats and their offspring. Transcriptome sequencing and qPCR experiments indicated differentially expressed mRNAs in offspring exposed to prenatal stress, which may contribute to the imbalance of Th17/Treg cells through the activation of the Gng3-related PI3K/Akt/NF-κB pathway.


The retrodural space of Okada.
The retrodural space of Okada is a potential space that can act as a conduit for the spread of inflammatory or infectious processes, connecting ipsilateral adjacent facet joints, contralateral adjacent facet joints, adjacent neural foramen, paraspinal musculature, and spinous process adventitial bursa (i.e., Baastrup disease). Awareness of these potential retrodural communications during diagnostic imaging interpretation and interventional spine injection procedures can play an important role in patient care and management.


A decade of evolution in Indonesian orthopedic publication: A bibliographic report.
During the past decade, there was an increasing interest in orthopedic research in Indonesia. Therefore we aimed to investigate the profile of Indonesian orthopedic trend publication from 2010 to 2019. Systematic research was conducted to identify all orthopedic articles authored by Indonesian orthopedic surgeons. Article details (number of authors, authors' affiliation, publishing journal), type of author's affiliation, affiliate collaboration, study field, type, and level of evidence (LOE) were recorded and evaluated. Publishing journal metric and author h-index were also recorded. Descriptive statistics were used to summarize the data. Two hundred and twenty articles were included in our study. Clinical studies were the most common article type, followed by case reports and basic science. Among clinical articles, therapeutic studies were found significantly more frequent. On the other hand, economic studies were not found in this study period. The most popular field was oncology, followed by knee and spine. The average number of authors per article was 5.23 with a total of 205 individuals who had contributed during this decade. University hospital was the most common affiliation found and single-center study was the most common affiliate collaboration. The most common level of evidence was level V (case reports). Eighty-seven specific publishing journals were identified. More than 42% of the articles were published in journals with SJR between 0.25 and 0.50. The average author h-index was 3.56 (0-7). Although there was an increasing trend and quantity of publications among Indonesian authors, most articles had level 5 evidence (case reports) and the quality of publishing journals was mostly Q3 with a low-moderate SJR. Improvement of the article's quality and institutional collaboration will be needed for future contribution in global orthopedic society.


Compartmentalized morphogenesis in epithelia: from cell to tissue shape.
During development, embryonic tissues are shaped in a species-specific manner. Yet, across species, general classes of tissue remodeling events occur, such as tissue infolding and tissue elongation. The spatiotemporal control of these morphogenetic processes is responsible for the organization of different body plans, as well as for organogenesis. Cell morphogenesis in a mesenchyme contributes to the shaping of embryonic tissues. Epithelial cells, despite that they need to maintain an apicobasal organization, play an equally important role during morphogenesis. Moving from apical to basal, we review compartmentalized cellular rearrangements underlying tissue remodeling in Drosophila and compare them with those found in other organisms. Contractile activity at the apical surface triggers tissue folding and invagination. The regulation of adhesion at adherens junctions controls polarized neighbor exchange during intercalation and tissue elongation. Basolateral protrusive activity underlies other cases of intercalation. These localized cell shape changes are spatially regulated by developmental signals. Some signals define a local change in cell behavior (e.g., apical constriction), others orient a dynamic process in the plane of the tissue (e.g., junction remodeling).


Development of optically pure pyrethroid-like fluorescent substrates for carboxylesterases.
Pyrethroids are now the world's most extensively used insecticides. One of the common metabolic routes of pyrethroid insecticides in living systems is hydrolysis by carboxylesterases, and this hydrolysis may be stereospecific since most pyrethroid insecticides have chiral centers. In previous studies, pyrethroid-like fluorescent substrates have been shown to be hydrolyzed in a fashion similar to actual pyrethroids. It is important to synthesize the stereoisomers of pyrethroid-like fluorescent substrates to study the stereointeraction between carboxylesterases and these substrates. In this study, an effective synthetic method for preparing optically enriched (R)- and (S)-alpha-2-hydroxy-2-(6-methoxy-2-naphthyl)acetonitrile was developed. With this alcohol, an efficient synthetic route for preparation of optically pure cypermethrin and fenvalerate analogues was provided. Identification of these stereoisomers was determined based on GC, HPLC, 1H NMR, and X-ray crystallography. In addition, stereointeraction between carboxylesterases and chiral fluorescent substrates indicated that (i) stereospecificity of recombinant mouse liver carboxylesterases (NCBI accession nos. BAC36707 and NM_133960) varied significantly (up to 300-fold difference) with different stereoisomers of cypermethrin and fenvalerate analogues; (ii) on the basis of Vmax, the sensitivity of this analytical method, using a single stereoisomer of cypermethrin analogues instead of a mixture of eight stereosiomers, could be enhanced by 4-6 times for detection of these carboxylesterases; and (iii) possible usage of these carboxylesterases for chiral synthesis is discussed.


A comparison between the effects of hydrophobic and hydrophilic statins on osteoclast function in vitro and ovariectomy-induced bone loss in vivo.
Statins potently inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase, blocking downstream biosynthesis of isoprenoid lipids and causing inhibition of protein prenylation. Prenylated signaling molecules are essential for osteoclast function, consistent with our previous observation that mevastatin can inhibit osteoclast activity in vitro. Several reports suggest that statins may also have an anabolic effect on bone and stimulate osteoblast differentiation. This study sought to determine the effects of both hydrophobic and hydrophilic statins, particularly rosuvastatin (RSV), on osteoclast function in vitro and in vivo. All statins tested (RSV, pravastatin [PRA], cerivastatin [CER], and simvastatin [SIM]) caused accumulation of unprenylated Rap-1A in rabbit osteoclast-like cells and J774 macrophages in vitro and inhibited osteoclast-mediated resorption. The order of potency for inhibiting prenylation in vitro (at concentrations of 0.01-50 muM) was CER>SIM>RSV>PRA. The most potent hydrophilic statin (CER, 0.05 and 0.3 mg/kg) inhibited prenylation in rabbit osteoclasts 24 hours after a single subcutaneous (s.c.) injection more effectively than the most potent hydrophobic statin (RSV, 20 mg/kg). However, in a mouse model of osteoporosis, s.c. 0.05 mg/kg/day CER and 2 or 20 mg/kg/day RSV for 3 weeks only mildly prevented loss of cortical and trabecular bone induced by ovariectomy. No increase in bone formation rate was observed with statin treatment, suggesting that this effect was due to inhibition of osteoclast-mediated resorption rather than increased bone formation.


How computational models contribute to our understanding of the germ line.
Computational models are an invaluable tool in modern biology. They provide a framework within which to summarize existing knowledge, enable competing hypotheses to be compared qualitatively and quantitatively, and to facilitate the interpretation of complex data. Moreover, models allow questions to be investigated that are difficult to approach experimentally. Theories can be tested in context, identifying the gaps in our understanding and potentially leading to new hypotheses. Models can be developed on a variety of scales and with different levels of mechanistic detail, depending on the available data, the biological questions of interest, and the available mathematical and computational tools. The goal of this review is to provide a broad picture of how modeling has been applied to reproductive biology. Specifically, we look at four uses of modeling: (i) comparing hypotheses; (ii) interpreting data; (iii) exploring experimentally challenging questions; and (iv) hypothesis evaluation and generation. We present examples of each of these applications in reproductive biology, drawing from a range of organisms-including Drosophila, Caenorhabditis elegans, mouse, and humans. We aim to describe the data and techniques used to construct each model, and to highlight the benefits of modeling to the field, as complementary to experimental work. Mol. Reprod. Dev. 83: 944-957, 2016 © 2016 Wiley Periodicals, Inc.


Chelation of neurotoxic zinc levels does not improve neurobehavioral outcome after traumatic brain injury.
Increases of synaptically released zinc and intracellular accumulation of zinc in hippocampal neurons after traumatic or ischemic brain injury is neurotoxic and chelation of zinc has been shown to reduce neurodegeneration. Although our previous studies showed that zinc chelation in traumatically brain-injured rats correlated with an increase in whole-brain expression of several neuroprotective genes and reduced numbers of apoptotic neurons, the effect on functional outcome has not been determined, and the question of whether this treatment may actually be clinically relevant has not been answered. In the present study, we show that treatment of TBI rats with the zinc chelator calcium EDTA reduces the numbers of injured, Fluoro-Jade-positive neurons in the rat hippocampus 24 h after injury but does not improve neurobehavioral outcome (spatial memory deficits) 2 weeks post-injury. Our data suggest that zinc chelation, despite providing short-term histological neuroprotection, fails to improve long-term functional outcome, perhaps because long-term disruptions in homeostatic levels of zinc adversely influence hippocampus-dependent spatial memory.


Will Using a Foreign Language Attenuate the Neophobia?
In two experiments, we tested whether using a foreign language attenuates neophobia at the lexical (Experiment 1) and discoursal (Experiment 2) levels in comparison to using a native language. A total of 687 native Chinese speakers participated in Experiment 1, and 693 in Experiment 2. All of them learned English as a foreign language. They performed paper-and-pencil tasks for measuring their neophobia toward innovative products described in either Chinese or English at the lexical and discoursal levels. Our results suggest that using a foreign language at the discoursal levels can obviously attenuate the neophobia toward innovative products. Moreover, Dual-process Model could explain the mechanisms of neophobic attenuation induced by foreign language use.


Characterization of a 125K glycoprotein associated with bovine epithelial desmosomes.
An analysis of the concanavalinA binding polypeptide components of bovine tongue epithelial desmosomes reveals that in addition to the known desmosomal glycoproteins of 100/115K (the 'desmocollins'), 140K and 160/165K ('desmoglein 1') there is an uncharacterized glycoprotein of 125K (K = Mr x 10(-3). This latter polypeptide is immunologically distinct from known desmosomal glycoproteins, as determined by Western immunoblotting, but is recognized by an antibody preparation directed against the epithelial cell adhesion molecule E-cadherin. Moreover, the cadherin antibodies recognize a polypeptide present in bovine muzzle desmosomes that co-migrates with the 125K glycoprotein component of bovine tongue epithelial desmosomes. Upon treatment of bovine tongue desmosomes with a solution containing 9.5 M-urea, the 125K polypeptide becomes enriched in a urea-insoluble, membrane-enriched pelletable desmosomal fraction. Cadherin antibodies and antibodies directed against the 100/115K and 160/165K desmosomal glycoproteins generate similar immunofluorescence staining patterns in cryostat sections of bovine tongue epithelium. However, immunoelectron microscopic analysis of bovine tongue epithelium reveals that cadherin antibodies recognize components located both along the intercellular region of the desmosome and along nondesmosomal cell surfaces whereas antibodies directed against the 100/115K and the 160/165K desmosomal glycoproteins bind specifically to desmosomes. These results suggest that a cadherin-like glycoprotein component may play a role in the adhesive properties of the desmosomes of stratified squamous epithelia.


Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population.
This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance.


Posttraumatic stress without trauma in children.
It remains unclear to what degree children show signs of posttraumatic stress disorder (PTSD) after experiencing low-magnitude stressors, or stressors milder than those required for the DSM-IV extreme stressor criterion. A representative community sample of 1,420 children, ages 9, 11, and 13 at intake, was followed annually through age 16. Low-magnitude and extreme stressors as well as subsequent posttraumatic stress symptoms were assessed with the Child and Adolescent Psychiatric Assessment. Two measures of posttraumatic stress symptoms were used: having painful recall, hyperarousal, and avoidance symptoms (subclinical PTSD) and having painful recall only. During any 3-month period, low-magnitude stressors occurred four times as often as extreme stressors (24.0% compared with 5.9%). Extreme stressors elicited painful recall in 8.7% of participants and subclinical PTSD in 3.1%, compared with 4.2% and 0.7%, respectively, for low-magnitude stressors. Because of their higher prevalence, however, low-magnitude stressors accounted for two-thirds of cases of painful recall and half of cases of subclinical PTSD. Moreover, exposure to low-magnitude stressors predicted symptoms even among youths with no prior lifetime exposure to an extreme stressor. Relative to low-magnitude stressors, extreme stressors place children at greater risk for posttraumatic stress symptoms. Nevertheless, a sizable proportion of children manifesting posttraumatic stress symptoms experienced only a low-magnitude stressor.


Piezo electric sensor for endocrine-disrupting chemicals using receptor-co-factor interaction.
In vitro screening assays are useful techniques for the determination of receptor-mediated activities in environmental samples. In order to define whether environmental chemicals act as an agonist or antagonist to the human estrogen receptor (hER), we have constructed a biosensor based on ligand-inducible interactions between hER and relative proteins on a quartz crystal microbalance (QCM). The his-tagged proteins, which were expressed in E. coli by recombinant DNA technology, were immobilized on an Au-electrode with Ni(II)-mediated chemisorption using the histidine tag and thiol-modified iminodiacetic acid. The resonance-frequency change of the protein-modified electrode was caused by association or dissociation with the hER relative proteins on the surface in the presence of estrogen. These results suggest that this sensor is applicable as a large-scale screening tool for estrogenic compounds.


Itch in Special Skin Locations Management.
Itch management can be particularly complicated in some small areas like the scalp or the anogenital region for many reasons: the frequently poor diagnosis of the causes of itch in these areas, the dense innervation of these areas, and the symbolic value of these areas for the human psyche. The diagnosis of itchy scalp is easier than that of anogenital pruritus. Clinical examination and a careful inventory of all diseases of the patient and of the local environment are necessary. Localized treatments are frequently used at both sites, whereas specific pharmaceutical formulations are necessary for the pilose or the mucous environment. Nonetheless, systemic treatments or psychological interventions can be very useful.


Challenges Coexist with Opportunities: Spatial Heterogeneity Expression of PD-L1 in Cancer Therapy.
Cancer immunotherapy using anti-programmed death-ligand 1 (PD-L1) antibodies has been used in various clinical applications and achieved certain results. However, such limitations as autoimmunity, tumor hyperprogression, and overall low patient response rate impede its further clinical application. Mounting evidence has revealed that PD-L1 is not only present in tumor cell membrane but also in cytoplasm, exosome, or even nucleus. Among these, the dynamic and spatial heterogeneous expression of PD-L1 in tumors is mainly responsible for the unsatisfactory efficacy of PD-L1 antibodies. Hence, numerous studies focus on inhibiting or degrading PD-L1 to improve immune response, while a comprehensive understanding of the molecular mechanisms underlying spatial heterogeneity of PD-L1 can fundamentally transform the current status of PD-L1 antibodies in clinical development. Herein, the concept of spatial heterogeneous expression of PD-L1 is creatively introduced, encompassing the structure and biological functions of various kinds of PD-L1 (including mPD-L1, cPD-L1, nPD-L1, and exoPD-L1). Then an in-depth analysis of the regulatory mechanisms and potential therapeutic targets of PD-L1 is provided, seeking to offer a solid basis for future investigation. Moreover, the current status of agents is summarized, especially small molecular modulators development directed at these new targets, offering a novel perspective on potential PD-L1 therapeutics strategies.


Two distinct pathways for inhibiting pds1 ubiquitination in response to DNA damage.
The presence of DNA damage activates a conserved cellular response known as the DNA damage checkpoint pathway. This pathway induces a cell cycle arrest that persists until the damage is repaired. Consequently, the failure to arrest in response to DNA damage is associated with genomic instability. In budding yeast, activation of the DNA damage checkpoint pathway leads to a mitotic cell cycle arrest. Following the detection of DNA damage, the checkpoint signal is transduced via the Mec1 kinase, which in turn activates two kinases, Rad53 and Chk1 that act in parallel pathways to bring about the cell cycle arrest. The downstream target of Rad53 is unknown. The target of Chk1 is Pds1, an inhibitor of anaphase initiation whose degradation is a prerequisite for mitotic progression. Pds1 degradation is dependent on its ubiquitination by the anaphase-promoting complex/cyclosome ubiquitin ligase, acting in conjunction with the Cdc20 protein (APC/CCdc20). Previous studies showed that the Rad53 and Chk1 pathways independently lead to Pds1 stabilization but the mechanism for this was unknown. In the present study we show that both the Chk1 and the Rad53 pathways inhibit the APC/CCdc20-dependent ubiquitination of Pds1 but they affect different steps of the process: the Rad53 pathway inhibits the Pds1-Cdc20 interaction whereas Chk1-dependent phosphorylation of Pds1 inhibits the ubiquitination reaction itself. Finally, we show that once the DNA damage is repaired, Pds1 dephosphorylation is involved in the recovery from the checkpoint induced cell cycle arrest.


diffReps: detecting differential chromatin modification sites from ChIP-seq data with biological replicates.
ChIP-seq is increasingly being used for genome-wide profiling of histone modification marks. It is of particular importance to compare ChIP-seq data of two different conditions, such as disease vs. control, and identify regions that show differences in ChIP enrichment. We have developed a powerful and easy to use program, called diffReps, to detect those differential sites from ChIP-seq data, with or without biological replicates. In addition, we have developed two useful tools for ChIP-seq analysis in the diffReps package: one for the annotation of the differential sites and the other for finding chromatin modification "hotspots". diffReps is developed in PERL programming language and runs on all platforms as a command line script. We tested diffReps on two different datasets. One is the comparison of H3K4me3 between two human cell lines from the ENCODE project. The other is the comparison of H3K9me3 in a discrete region of mouse brain between cocaine- and saline-treated conditions. The results indicated that diffReps is a highly sensitive program in detecting differential sites from ChIP-seq data.


The pattern of rheumatoid arthritis in West Africa and comparison with a cohort of British patients.
Inadequate information is available on the care burden and severity of rheumatological diseases such as rheumatoid arthritis in West Africa. We therefore studied patients with rheumatoid arthritis presenting to a rheumatology unit in Nigeria and compared these with patients presenting to a British rheumatology unit. The West African patients were younger at onset of disease, less frequently had a family history, showed fewer extra-articular features and erosions and were less commonly rheumatoid factor positive. The overall mildness of the disease in the West Africans was striking.


Health of Spanish centenarians: a cross-sectional study based on electronic health records.
With the number of centenarians increasing exponentially in Spain, a deeper knowledge of their socio-demographic, clinical, and healthcare use characteristics is important to better understand the health profile of the very elderly. We conducted a retrospective, cross-sectional observational study in the EpiChron Cohort (Aragón, Spain) aimed at analyzing the socio-demographic, clinical, drug use and healthcare use characteristics of 1680 centenarians during 2011-2015, using data from electronic health records and clinical-administrative databases. Spanish centenarians (79.1% women) had 101.6 years on average. Approximately 80% of centenarians suffered from multimorbidity, with an average of 4.0 chronic conditions; 50% were exposed to polypharmacy, with an average of 4.8 medications; only 6% of centenarians were free of chronic diseases and only 7% were not on medication. Centenarians presented a cardio-cerebrovascular pattern in which hypertension, heart failure, cerebrovascular disease and dementia were the most frequent conditions. Primary care was the most frequently visited healthcare level (79% of them), followed by medical specialist consultations (23%), hospitalizations (13%), and emergency service use (9%). Multimorbidity is the rule rather than the exception in Spanish centenarians. Addressing medical care in the very elderly from a holistic geriatric view is critical in order to preserve their health, and avoid the negative effects of polypharmacy.


Disruption of structure-function coupling in the schizophrenia connectome.
Neuroimaging studies have demonstrated that the phenomenology of schizophrenia maps onto diffuse alterations in large-scale functional and structural brain networks. However, the relationship between structural and functional deficits remains unclear. To answer this question, patients with established schizophrenia and matched healthy controls underwent resting-state functional and diffusion weighted imaging. The network-based statistic was used to characterize between-group differences in whole-brain functional connectivity. Indices of white matter integrity were then estimated to assess the structural correlates of the functional alterations observed in patients. Finally, group differences in the relationship between indices of functional and structural brain connectivity were determined. Compared to controls, patients with schizophrenia showed decreased functional connectivity and impaired white matter integrity in a distributed network encompassing frontal, temporal, thalamic, and striatal regions. In controls, strong interregional coupling in neural activity was associated with well-myelinated white matter pathways in this network. This correspondence between structure and function appeared to be absent in patients with schizophrenia. In two additional disrupted functional networks, encompassing parietal, occipital, and temporal cortices, the relationship between function and structure was not affected. Overall, results from this study highlight the importance of considering not only the separable impact of functional and structural connectivity deficits on the pathoaetiology of schizophrenia, but also the implications of the complex nature of their interaction. More specifically, our findings support the core nature of fronto-striatal, fronto-thalamic, and fronto-temporal abnormalities in the schizophrenia connectome.


Computer assisted echocardiographic assessment of left ventricular function before and after anatomical correction of transposition of the great arteries.
Left ventricular function before and after anatomical correction of transposition of the great arteries was assessed by computer assisted analysis of 78 echocardiographs from 27 patients obtained one year before to five years after operation. Sixteen patients had simple transposition, and 11 had complex transposition with additional large ventricular septal defect. Immediately after correction mean shortening fraction fell from 46(9)% to 33(8)%. There was a corresponding drop in normalised peak shortening rate from 5.4(3.7) to 3.3(1.1) s-1 and normal septal motion was usually absent. Systolic shortening fraction increased with time after correction and left ventricular end diastolic diameter increased appropriately for age. The preoperative rate of free wall thickening was significantly higher in simple (5.6(2.8) s-1) and complex transposition (4.5(1.8) s-1) than in controls (2.9(0.8) s-1). After operation these values remained high in both the short and long term. Thus, computer assisted analysis of left ventricular dimensions and their rates of change before and after anatomical correction showed only slight postoperative changes which tended to become normal with time. Septal motion was commonly absent after operation. This was associated with an increase in the rate of posterior wall thickening that suggested normal ventricular function associated with an altered contraction pattern. Computer assisted echocardiographic analysis may be helpful in the long term assessment of ventricular function after operation for various heart abnormalities.


Scheduled second-look endoscopy is not recommended after endoscopic submucosal dissection for gastric neoplasms (the SAFE trial): a multicentre prospective randomised controlled non-inferiority trial.
To clarify the effectiveness of second-look endoscopy (SLE) at preventing bleeding after gastric endoscopic submucosal dissection (ESD). A multicentre prospective randomised controlled non-inferiority trial was conducted at five referral institutions across Japan. Patients with a solitary gastric neoplasm were enrolled. Exclusion criteria were previous oesophagogastric surgery or radiation therapy; perforation and the administration of antithrombotics, steroids or non-steroidal anti-inflammatory drugs. Patients were assigned to the SLE group or the non-SLE group by a computer-generated random sequence after ESD and were treated perioperatively with a proton pump inhibitor. SLE was performed one day after ESD. The primary endpoint was post-ESD bleeding, defined as an endoscopically proven haemorrhage. The trial had the power to detect a non-inferiority criterion of 7% between the groups. From February 2012 to February 2013, 130 and 132 patients were assigned to the SLE and the non-SLE groups, respectively. All patients were included in the intention-to-treat analysis of the primary endpoint. Post-ESD bleeding occurred in seven patients with (5.4%) SLE and five patients with (3.8%) non-SLE (risk difference--1.6% (95% CI -6.7 to 3.5); pnon-inferiority<0.001), meeting the non-inferiority criterion. All 12 patients with post-ESD bleeding and one patient with a delayed perforation were successfully managed with conservative treatment. SLE after gastric ESD is not routinely recommended because it does not contribute to the prevention of post-ESD bleeding for patients with an average bleeding risk. UMIN-CTR000007170.


Self-directed learning: faculty and student perceptions.
This article reports the results of a qualitative study that explored faculty and student perceptions of self-directed learning (SDL) and investigated factors that facilitate or impede it. This study was conducted at McMaster University with faculty and students in a 4-year undergraduate nursing program. Data were collected from 47 faculty and 17 students by means of focus groups that were audiotaped and transcribed. Content analysis was conducted to identify common themes in faculty and student transcripts. The themes that emerged provide insight into the educational strategy of self-directed learning and can be summarized by the following major points: (1) commitment to SDL requires students and faculty to understand the value of empowering learners to take increased responsibility for decisions related to learning; (2) students engaged in self-directed learning undergo a transformation that begins with negative feelings (i.e., confusion, frustration, and dissatisfaction) and ends with confidence and skills for lifelong learning; and (3) faculty development is important to ensure high levels of competency in facilitating self-directed learning.


[Endovascular treatment of descending thoracic aorta aneurysm].
The natural history of aneurysms ends in rupture and death. In 1990 the first endovascular exclusion of an aneurysm, using an endoluminal graft implanted through the femoral arteries was performed. More recently, the same procedure has been used for aneurysms of the thoracic aorta. To report our experience with endovascular treatment of thoracic aorta aneurysms. Analysis of 14 patients (nine male), aged 30 to 79 years, treated between May 2001 and August 2002. The mean diameter of the aneurysms was 6.9 cm. The etiology was atherosclerotic in nine patients. The Excluder device (Gore) was preferentially used. There was no operative mortality or paraplegia. One patient had a transient leg monoparesis that reverted completely. No patient had type I endoleaks. Two patients had type II endoleaks on discharge, that sealed spontaneously. In a follow up, ranging from 2 to 17 months, one patient died of a bronchopneumonia and no aneurysm rupture has been detected. The short term results of endoluminal treatment of thoracic aorta aneurysms are excellent. This treatment is less invasive and has less complications than conventional surgery.


Kaposi sarcoma-associated herpesvirus (KSHV) seroprevalence in population-based samples of African children: evidence for at least 2 patterns of KSHV transmission.
Kaposi sarcoma-associated herpesvirus (KSHV) infection is endemic among adult populations in Africa. A prevailing view is that childhood transmission is primarily responsible for the high seroprevalence of KSHV among adults that is observed throughout the continent. However, few studies have directly examined children, particularly in locations where KS is not commonly endemic. Participants were children aged 1.5-8.9 years, including 427 children from a population-based sample in South Africa, 422 from a population-based sample in Uganda, and 567 from a clinic-based sample in Uganda. All serum specimens were tested by the same laboratory for KSHV antibodies with use of 2 enzyme immunoassays (against K8.1 and ORF65) and 1 immunofluorescence assay. KSHV seroprevalence was 7.5%-9.0% among South African children and was not associated with age. In contrast, in the Ugandan population-based sample, KSHV seroprevalence increased from 10% among 2-year-old children to 30.6% among 8-year-old children (P(trend) < .001). In the Ugandan clinic-based sample, seroprevalence increased from 9.3% among 2-year-old children to 36.4% among 8-year-old children (P(trend) < .001). Two distinct relationships between age and KSHV infection among children imply that KSHV transmission among children is not uniform throughout Africa and is therefore not always responsible for the high seroprevalence observed in adults. There are at least 2 patterns of KSHV transmission in Africa.


A vertical jump force test for assessing bilateral strength asymmetry in athletes.
To establish the validity and reliability of a new vertical jump force test (VJFT) for the assessment of bilateral strength asymmetry in a total of 451 athletes. The VJFT consists of countermovement jumps with both legs simultaneously: one on a single force platform, the other on a leveled wooden platform. Jumps with the right or the left leg on the force platform were alternated. Bilateral strength asymmetry was calculated as [(stronger leg - weaker leg)/stronger leg] x 100. A positive sign indicates a stronger right leg; a negative sign indicates a stronger left leg. Studies 1 (N = 59) and 2 (N = 41) examined the correlation between the VJFT and other tests of lower-limb bilateral strength asymmetry in male athletes. In study 3, VJFT reliability was assessed in 60 male athletes. In study 4, the effect of rehabilitation on bilateral strength asymmetry was examined in seven male and female athletes 8-12 wk after unilateral knee surgery. In study 5, normative data were determined in 313 male soccer players. Significant correlations were found between VJFT and both the isokinetic leg extension test (r = 0.48; 95% confidence interval, 0.26-0.66) and the isometric leg press test (r = 0.83; 0.70-0.91). VJFT test-retest intraclass correlation coefficient was 0.91 (0.85-0.94), and typical error was 2.4%. The change in mean [-0.40% (-1.25 to 0.46%)] was not substantial. Rehabilitation decreased bilateral strength asymmetry (mean +/- SD) of the athletes recovering from unilateral knee surgery from 23 +/- 3 to 10 +/- 4% (P < 0.01). The range of normal bilateral strength asymmetry (2.5th to 97.5th percentiles) was -15 to 15%. The assessment of bilateral strength asymmetry with the VJFT is valid and reliable, and it may be useful in sports medicine.


A fast autofocus unit for fluorescence microscopy.
In this paper a fast autofocus unit is introduced for fluorescence microscopy based on image content information. The module, an electronic board with several differentiators and integrators, is designed for high-speed autofocusing and is directly coupled to the output of the video camera. A Leitz MPV II fluorescence microscope with x, y, z stepping motors was used as basic equipment. The microscope images were focused by using an intensified target camera with a following analogue-digital converter and a PC. Thus one obtains a focus value for the current image within one video cycle. Furthermore, it is possible to process three different focus functions (weighted intensity, first derivative and second derivative) simultaneously. The flexibility to select a certain focus function or a combination of these functions allows the use of the analogue detector for various cell types and fluorescent dyes. In order to test the experimental set-up we use three different kinds of biological specimen (lymphocytes, fibroblasts and comet cells) which are distinguished by large differences in their morphological structure. Successful focusing is carried out in more than 95% of cases (investigation of several hundred different cells). The focusing procedure is almost finished after 1-2 s.


PDCA cycle management combined with detailed management of postoperative deep vein thrombosis in patients undergoing hip replacement surgery.
This study aimed to analyze and explore the effect of Plan-Do-Check-Act (PDCA) cycle management combined with detailed management on postoperative deep venous thrombosis in patients undergoing hip replacement surgery. Patients who underwent hip replacement surgery in our hospital between November 2021 and April 2023 were recruited for the study. After screening, patients who met all the inclusion criteria were assessed for eligibility. Finally, 80 adults were enrolled. All patients were assigned into observation and control groups (1:1) according to the sequence of admission, i.e., patients admitted between November 2021 and August 2022 were the control group, and patients admitted between September 2022 and April 2023 were the observation group. The intraoperative blood loss and hospital stay in the observation group were significantly less than those in the control group (p<0.05). After the intervention, the levels of plasma prothrombin time (PT), thrombin time (TT), and thromboplastin time (APTT) in the observation group were higher than those in the control group, and the DD level was lower than that in the control group (p<0.05). There was one patient in the observation group who developed deep venous thrombosis after the operation, and the incidence was 2.50%. The rate was significantly lower than that of the control group (p<0.05). The hip joint function score of the observation group was higher than that of the control group, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale score was lower than that of the control group (p<0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group (p<0.05). PDCA cycle management plus detailed management in patients with hip replacement surgery yields a favorable clinical outcome, which can effectively prevent postoperative deep vein thrombosis, and improve surgical indicators and postoperative coagulation function. Also, it reduces the incidence of adverse reactions in patients and facilitates recovery. It has a beneficial impact on the prognosis of patients and deserves promotion.


Establishing a pediatric cardiac intensive care unit - Special considerations in a limited resources environment.
Pediatric cardiac intensive care has evolved as a distinct discipline in well-established pediatric cardiac programs in developed nations. With increasing demand for pediatric heart surgery in emerging economies, a number of new programs are being established. The development of robust pediatric cardiac intensive care units (PCICU) is critical to the success of these programs. Because of substantial resource limitations existing models of PCICU care cannot be applied in their existing forms and structure. A number of challenges need to be addressed to deliver pediatric cardiac intensive care in the developing world. Limitations in infrastructure, human, and material resources call for a number of innovations and adaptations. Additionally, a variety of strategies are required to minimize costs of care to the individual patient. This review provides a framework for the establishment of a new PCICU program in face of resource limitations typically encountered in the developing world and emerging economies.


Is this a chemical bond? A theoretical study of Ng2@C60 (Ng=He, Ne, Ar, Kr, Xe).
Quantum-chemical calculations using DFT (BP86) and ab initio methods (MP2, SCS-MP2) have been carried out for the endohedral fullerenes Ng2@C60 (Ng=He-Xe). The nature of the interactions has been analyzed with charge- and energy-partitioning methods and with the topological analysis of the electron density (Atoms-in-Molecules (AIM)). The calculations predict that the equilibrium geometries of Ng2@C60 have D3d symmetry when Ng=Ne, Ar, Kr, while the energy-minimum structure of Xe2@C60 has D5d symmetry. The precession movement of He2 in He2@C60 has practically no barrier. The Ng--Ng distances in Ng2@C60 are much shorter than in free Ng2. All compounds Ng2@C60 are thermodynamically unstable towards loss of the noble gas atoms. The heavier species Ar2@C60, Kr2@C60, and Xe2@C60 are high energy compounds which are at the BSSE corrected SCS-MP2/TZVPP level in the range 96.7-305.5 kcal mol(-1) less stable than free C60+2 Ng. The AIM method reveals that there is always an Ng--Ng bond path in Ng2@C60. There are six Ng--C bond paths in (D3d) Ar2@C60, Kr2@C60, and Xe2@C60, whereas the lighter D3d homologues He2@C60 and Ne2@C60 have only three Ng--C2 paths. The calculated charge distribution and the orbital analysis clearly show that the bonding situation in Xe2@C60 significantly differs from those of the lighter homologues. The atomic partial charge of the [Xe2] moiety is +1.06, whereas the charges of the lighter dimers [Ng2] are close to zero. The a2u HOMO of (D3d) Xe2@C60 in the 1A1g state shows a large mixing of the highest lying occupied sigma* orbital of [Xe2] and the orbitals of the C60 cage. There is only a small gap between the a2u HOMO of Xe2@C60 and the eu LUMO and the a2u LUMO+1. The calculations show that there are several triplet states which are close in energy to each other and to the 1A1g state. The bonding analysis suggests that the interacting species in Xe2@C60 are the charged species Xe2q+ and C60q-, where 1<q<2. The calculated Xe--Xe distance in the endohedral fullerene (2.494 A) is even shorter than the calculated value for free Xe2(2+) (2.746 A). Thus, the Xe--C and Xe--Xe interactions in Xe2@C60 should be considered as genuine chemical bonds which are enforced by the compression energy. The Ng--Ng and Ng--C interactions in the lighter homologues Ar2@C60 and Kr2@C60 may also be considered as chemical bonds because the theoretically predicted properties of the endohedral fullerenes are significantly different from the free C60 and noble gas atoms. According to the bonding analysis, He2@C60 and Ne2@C60 are weakly bonded van der Waals complexes.


MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against diabetic nephropathy in rats through facilitating M2 macrophage polarization.
Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and a common cause of end-stage renal disease (ESRD). Mesenchymal stem cells (MSCs) possess potent anti-inflammatory and immunomodulatory properties, which render them an attractive therapeutic tool for tissue damage and inflammation. This study was designed to determine the protective effects and underlying mechanisms of human umbilical cord-derived MSCs (UC-MSCs) on streptozotocin-induced DN. Renal function and histological staining were used to evaluate kidney damage. RNA high-throughput sequencing on rat kidney and UCMSC-derived exosomes was used to identify the critical miRNAs. Co-cultivation of macrophage cell lines and UC-MSCs-derived conditional medium were used to assess the involvement of macrophage polarization signaling. UC-MSC administration significantly improved renal function, reduced the local and systemic inflammatory cytokine levels, and attenuated inflammatory cell infiltration into the kidney tissue in DN rats. Moreover, UC-MSCs shifted macrophage polarization from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. Mechanistically, miR-146a-5p was significantly downregulated and negatively correlated with renal injury in DN rats as determined through high-throughput RNA sequencing. Importantly, UC-MSCs-derived miR-146a-5p promoted M2 macrophage polarization by inhibiting tumor necrosis factor receptor-associated factor-6 (TRAF6)/signal transducer and activator of transcription (STAT1) signaling pathway. Furthermore, miR-146a-5p modification in UC-MSCs enhanced the efficacy of anti-inflammation and renal function improvement. Collectively, our findings demonstrate that UC-MSCs-derived miR-146a-5p have the potential to restore renal function in DN rats through facilitating M2 macrophage polarization by targeting TRAF6. This would pave the way for the use of miRNA-modified cell therapy for kidney diseases.


The regulation of hydroxysteroid 17β-dehydrogenase type 1 and 2 gene expression in breast cancer cell lines by estradiol, dihydrotestosterone, microRNAs, and genes related to breast cancer.
To investigate the influence of estrogen, androgen, microRNAs, and genes implicated in breast cancer on the expression of HSD17B1 and HSD17B2. Breast cancer cell lines ZR-75-1, MCF7, T47D, SK-BR-3, and the immortalized epithelial cell line MCF10A were used. Cells were treated either with estradiol or dihydrotestosterone for 6, 24, 48 hours, or 7 days or treated with miRNAs or siRNAs predicted to influence HSD17B expression Results and discussion. Estradiol treatment decreased HSD17B1 expression and had a time-dependent effect on HSD17B2 expression. This effect was lost in estrogen receptor-α down-regulated or negative cell lines. Dihydrotestosterone treatment increased HSD17B2 expression, with limited effect on HSD17B1 expression. No effect was seen in cells without AR or in combination with the AR inhibitor hydroxyflutamide. The miRNA-17 up-regulated HSD17B1, while miRNA-210 and miRNA-7-5p had up- and down-regulatory effect and miRNA-1304-3p reduced HSD17B1 expression. The miRNA-204-5p, 498, 205-3p and 579-3p reduced HSD17B2 expression. Downregulation of CX3CL1, EPHB6, and TP63 increased HSD17B1 and HSD17B2 expression, while GREB1 downregulation suppressed HSD17B1 and promoted HSD17B2 expression. We show that HSD17B1 and HSD17B2 are controlled by estradiol, dihydrotestosterone, and miRNAs, as well as modulated by several breast cancer-related genes, which could have future clinical applications.


Characterisation of senescence-induced changes in light harvesting complex II and photosystem I complex of thylakoids of Cucumis sativus cotyledons: age induced association of LHCII with photosystem I.
Structure and function of chloroplasts are known to after during senescence. The senescence-induced specific changes in light harvesting antenna of photosystem II (PSII) and photosystem I (PSI) were investigated in Cucumis cotyledons. Purified light harvesting complex II (LHCII) and photosystem I complex were isolated from 6-day non-senescing and 27-day senescing Cucumis cotyledons. The chlorophyll a/b ratio of LHCII obtained from 6-day-old control cotyledons and their absorption, chlorophyll a fluorescence emission and the circular dichroism (CD) spectral properties were comparable to the LHCII preparations from other plants such as pea and spinach. The purified LHCII obtained from 27-day senescing cotyledons had a Chl a/b ratio of 1.25 instead of 1.2 as with 6-day LHCII and also exhibited significant changes in the visible CD spectrum compared to that of 6-day LHCII, indicating some specific alterations in the organisation of chlorophylls of LHCII. The light harvesting antenna of photosystems are likely to be altered due to aging. The room temperature absorption spectrum of LHCII obtained from 27-day senescing cotyledons showed changes in the peak positions. Similarly, comparison of 77K chlorophyll a fluorescence emission characteristics of LHCII preparation from senescing cotyledons with that of control showed a small shift in the peak position and the alteration in the emission profile, which is suggestive of possible changes in energy transfer within LHCII chlorophylls. Further, the salt induced aggregation of LHCII samples was lower, resulting in lower yields of LHCII from 27-day cotyledons than from normal cotyledons. Moreover, the PSI preparations of 6-day cotyledons showed Chl a/b ratios of 5 to 5.5, where as the PSI sample of 27-day cotyledons had a Chl a/b ratio of 2.9 suggesting LHCII association with PSI. The absorption, fluorescence emission and visible CD spectral measurements as well as the polypeptide profiles of 27-day cotyledon-PSI complexes indicated age-induced association of LHCII of PSII with PSI obtained from 27-day cotyledons. We modified our isolation protocols by increasing the duration of detergent Triton X-100 treatment for preparing the PSI and LHCII complexes from 27-day cotyledons. However, the PSI complexes isolated from senescing samples invariably proved to have significantly low Chl a/b ratio suggesting an age induced lateral movement and possible association of LHCII with PSI complexes. The analyses of polypeptide compositions of LHCII and PSI holocomplexes isolated from 6-day control and 27-day senescing cotyledons showed distinctive differences in their profiles. The presence of 26-28 kDa polypeptide in PSI complexes from 27-day cotyledons, but not in 6-day control PSI complexes is in agreement with the notion that senescence induced migration of LHCII to stroma lamellae and its possible association with PSI. We suggest that the migration of LHCII to the stroma lamellae region and its possible association with PSI might cause the destacking and flattening of grana structure during senescence of the chloroplasts. Such structural changes in light harvesting antenna are likely to alter energy transfer between two photosystems. The nature of aging induced migration and association of LHCII with PSI and its existence in other senescing systems need to be estimated in the future.


[Prevalence of antiphospholipid syndrome in patients with systemic lupus erythematosus at the University Hospital of Puerto Rico].
This is a retrospective study based on a population of 80 patients with connective tissue diseases from the University Hospital of Puerto Rico. Among the population, 62 (77.5%) of the patients had Systemic Lupus Erythematosus (SLE), whom we were most interested to monitor. The investigation revealed an incidence of 13.8% of anthiophospholipid syndrone within the general population. Among the patients with SLE it was 12.9%, and only 5.5% among the population with other diagnoses. The antibody found with the highest frequency within the systemic lupus erythematosus population was the anticardiolipin IgG (30.6%) and lupus anticoagulant (17.7%). The antibody frequency among patients with other diagnoses was only 5.5% for lupus anticoagulant and 5.5% for anticardiolipin IgM (the only one found). Among SLE's clinical manifestations, the most frequently found were thrombocitopenia and pregnancy complications.


Cannabis for the treatment of ulcerative colitis.
Cannabis and cannabinoids are often promoted as treatment for many illnesses and are widely used among patients with ulcerative colitis (UC). Few studies have evaluated the use of these agents in UC. Further, cannabis has potential for adverse events and the long-term consequences of cannabis and cannabinoid use in UC are unknown. To assess the efficacy and safety of cannabis and cannabinoids for the treatment of patients with UC. We searched MEDLINE, Embase, WHO ICTRP, AMED, PsychINFO, the Cochrane IBD Group Specialized Register, CENTRAL, ClinicalTrials.Gov and the European Clinical Trials Register from inception to 2 January 2018. Conference abstracts and references were searched to identify additional studies. Randomized controlled trials (RCTs) comparing any form or dose of cannabis or its cannabinoid derivatives (natural or synthetic) to placebo or an active therapy for adults (> 18 years) with UC were included. Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. The primary outcomes were clinical remission and relapse (as defined by the primary studies). Secondary outcomes included clinical response, endoscopic remission, endoscopic response, histological response, quality of life, C-reactive protein (CRP) and fecal calprotectin measurements, symptom improvement, adverse events, serious adverse events, withdrawal due to adverse events, psychotropic adverse events, and cannabis dependence and withdrawal effects. We calculated the risk ratio (RR) and corresponding 95% confidence interval for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) and corresponding 95% CI. Data were pooled for analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). Data were analyzed on an intention-to-treat basis. GRADE was used to evaluate the overall certainty of evidence. Two RCTs (92 participants) met the inclusion criteria. One study (N = 60) compared 10 weeks of cannabidiol capsules with up to 4.7% D9-tetrahydrocannabinol (THC) with placebo capsules in participants with mild to moderate UC. The starting dose of cannabidiol was 50 mg twice daily increasing to 250 mg twice daily if tolerated. Another study (N = 32) compared 8 weeks of therapy with two cannabis cigarettes per day containing 0.5 g of cannabis, corresponding to 23 mg THC/day to placebo cigarettes in participants with UC who did not respond to conventional medical treatment. No studies were identified that assessed cannabis therapy in quiescent UC. The first study was rated as low risk of bias and the second study (published as an abstract) was rated as high risk of bias for blinding of participants and personnel. The studies were not pooled due to differences in the interventional drug.The effect of cannabidiol capsules (100 mg to 500 mg daily) compared to placebo on clinical remission and response is uncertain. Clinical remission at 10 weeks was achieved by 24% (7/29) of the cannabidiol group compared to 26% (8/31) in the placebo group (RR 0.94, 95% CI 0.39 to 2.25; low certainty evidence). Clinical response at 10 weeks was achieved in 31% (9/29) of cannabidiol participants compared to 22% (7/31) of placebo patients (RR 1.37, 95% CI 0.59 to 3.21; low certainty evidence). Serum CRP levels were similar in both groups after 10 weeks of therapy. The mean CRP in the cannabidiol group was 9.428 mg/L compared to 7.638 mg/L in the placebo group (MD 1.79, 95% CI -5.67 to 9.25; moderate certainty evidence). There may be a clinically meaningful improvement in quality of life at 10 weeks, measured with the IBDQ scale (MD 17.4, 95% CI -3.45 to 38.25; moderate certainty evidence). Adverse events were more frequent in cannabidiol participants compared to placebo. One hundred per cent (29/29) of cannabidiol participants had an adverse event, compared to 77% (24/31) of placebo participants (RR 1.28, 95% CI 1.05 to1.56; moderate certainty evidence). However, these adverse events were considered to be mild or moderate in severity. Common adverse events included dizziness, disturbance in attention, headache, nausea and fatigue. None (0/29) of the cannabidiol participants had a serious adverse event compared to 13% (4/31) of placebo participants (RR 0.12, 95% CI 0.01 to 2.11; low certainty evidence). Serious adverse events in the placebo group included worsening of UC and one complicated pregnancy. These serious adverse events were thought to be unrelated to the study drug. More participants in the cannabidiol group withdrew due to an adverse event than placebo participants. Thirty-four per cent (10/29) of cannabidiol participants withdrew due to an adverse event compared to 16% (5/31) of placebo participants (RR 2.14, 95% CI 0.83 to 5.51; low certainty evidence). Withdrawls in the cannabidiol group were mostly due to dizziness. Withdrawals in the placebo group were due to worsening UC.The effect of cannabis cigarettes (23 mg THC/day) compared to placebo on mean disease activity, CRP levels and mean fecal calprotectin levels is uncertain. After 8 weeks, the mean disease activity index score in cannabis participants was 4 compared with 8 in placebo participants (MD -4.00, 95% CI -5.98 to -2.02). After 8 weeks, the mean change in CRP levels was similar in both groups (MD -0.30, 95% CI -1.35 to 0.75; low certainty evidence). The mean fecal calprotectin level in cannabis participants was 115 mg/dl compared to 229 mg/dl in placebo participants (MD -114.00, 95% CI -246.01 to 18.01). No serious adverse events were observed. This study did not report on clinical remission, clinical response, quality of life, adverse events or withdrawal due to adverse events. The effects of cannabis and cannabidiol on UC are uncertain, thus no firm conclusions regarding the efficacy and safety of cannabis or cannabidiol in adults with active UC can be drawn.There is no evidence for cannabis or cannabinoid use for maintenance of remission in UC. Further studies with a larger number of patients are required to assess the effects of cannabis in UC patients with active and quiescent disease. Different doses of cannabis and routes of administration should be investigated. Lastly, follow-up is needed to assess the long term safety outcomes of frequent cannabis use.


Optimizing nutrient management for farm systems.
Increasing the inputs of nutrients has played a major role in increasing the supply of food to a continually growing world population. However, focusing attention on the most important nutrients, such as nitrogen (N), has in some cases led to nutrient imbalances, some excess applications especially of N, inefficient use and large losses to the environment with impacts on air and water quality, biodiversity and human health. In contrast, food exports from the developing to the developed world are depleting soils of nutrients in some countries. Better management of all essential nutrients is required that delivers sustainable agriculture and maintains the necessary increases in food production while minimizing waste, economic loss and environmental impacts. More extensive production systems typified by 'organic farming' may prove to be sustainable. However, for most of the developed world, and in the developing world where an ever-growing population demands more food, it will be essential to increase the efficiency of nutrient use in conventional systems. Nutrient management on farms is under the control of the land manger, the most effective of whom will already use various decision supports for calculating rates of application to achieve various production targets. Increasingly, land managers will need to conform to good practice to achieve production targets and to conform to environmental targets as well.


Detection of cyclin messenger RNAs by nonradioactive ribonuclease protection assay: a comparison of four detection methods.
Stable, nonradioactive riboprobes were used in ribonuclease protection assays to monitor the changes in cyclin mRNA expression during cell cycle progression in human mammary epithelial cells. Probes labeled with biotin demonstrated sufficient sensitivity (comparable to 32P) to detect these low-abundance mRNAs and thus offer a safe and easy alternative to traditional radioactive assays. Three detection systems based on chemiluminescence generated by horseradish peroxidase or alkaline phosphatase were compared for sensitivity, background and ease of use.


Alternating Hemiplegia of Childhood: Understanding the Genotype-Phenotype Relationship of ATP1A3 Variations.
Alternating hemiplegia of childhood (AHC) is a rare neurological disorder affecting children with an onset before 18 months. Diagnostic clues include transient episodes of hemiplegia alternating in the laterality or quadriparesis, nystagmus and other paroxysmal attacks as tonic and dystonic spells. Epilepsy is also a common feature. In the past, a great effort has been done to understand the genetic basis of the disease leading to the discovery of mutations in the ATP1A3 gene encoding for the alpha3 subunit of Na+/K+ATPase, a protein already related to another disease named Rapid Onset Dystonia Parkinsonism (RDP). ATP1A3 mutations account for more than 70% of cases of AHC. In particular, three hotspot mutations account for about 60% of all cases, and these data have been confirmed in large population studies. Specifically, the p.Asp801Asn variant has been found to cause 30-43% of all cases, p.Glu815Lys is responsible for 16-35% of cases and p.Gly947Arg accounts for 8-15%. These three mutations are associated with different clinical phenotype in terms of symptoms, severity and prognosis. In vitro and in vivo models reveal that a crucial role of Na+/K+ATPase pump activity emerges in maintaining a correct membrane potential, survival and homeostasis of neurons. Herein, we attempt to summarize all clinical, genetic and molecular aspects of AHC considering ATP1A3 as its primary disease-causing determinant.


Development of a rapid titration method for predicting optimal coagulant concentration for filled tofu.
A rapid titration method was developed for predicting the optimal coagulant concentration for making filled tofu. Cooked soymilk (350 mL, 20 degrees C) in a 400 mL beaker was stirred by a magnetic stirrer to form a swirl. The quick-acting coagulant solution (20.0 Brix) was added into the soymilk at 1.0 mL/min. The swirl depth decreased when the soymilk viscosity increased as a result of increasing the concentration of coagulant in the soymilk. At a suitable stirrer speed, the swirl finally disappeared but the soymilk still maintained rotation, and then the swirl reappeared after around 1 min. The critical point of coagulant concentration (CPCC) was calculated on the basis of the volume of coagulant consumed to get the swirl to disappear. The influences of several factors on the CPCC were investigated, including coagulant addition rate, soymilk temperature, soymilk concentration, soymilk volume, stir bar length, and container size. For validation, 33 soybean samples were used to determine their CPCCs and make filled tofus. The results indicated that CPCC was a characteristic parameter of soymilk and could be used as an effective indicator for predicting optimal coagulant concentration.


Experimental study of dye removal from industrial wastewater by membrane technologies of reverse osmosis and nanofiltration.
Currently, biological method has been utilized in the treatment of wastewater -containing synthetic dyes used by textile industries in Iraq. The present work was devoted to study the operating feasibility using reverse osmosis (RO) and nanofiltration (NF) membrane systems as an alternative treatment method of wastewater discharged from Iraqi textile mills. Acid red, reactive black and reactive blue dyes were selected, based on the usage rate in Iraq. Effects of dye concentration, pH of solution, feed temperature, dissolved salts and operating pressure on permeate flux and dye rejection were studied. Results at operating conditions of dye concentration = 65 mg/L, feed temperature = 39°C and pressure = 8 bar showed the final dye removal with RO membrane as 97.2%, 99.58% and 99.9% for acid red, reactive black and reactive blue dyes, respectively. With NF membrane, the final dye removal were as 93.77%, 95.67%, and 97% for red, black and blue dyes, respectively. The presence of salt (particularly NaCl) in the dye solution resulted in a higher color removal with a permeate flux decline. It was confirmed that pH of solution had a positive impact on dye removal while feed temperature showed a different image. A comparison was made between the results of dye removal in biological and membrane methods. The results showed that membrane method had higher removal potential with lower effective cost. The present study indicates that the use of NF membrane in dye removal from the effluent of Iraqi textile mills is promising.


Optimal dosing of angiotensin-converting enzyme inhibitors and β-blockers for acute coronary syndrome: up-titration remains a challenge.
Suboptimal dosing of angiotensin-converting enzyme inhibitors and β-blockers limits the mortality benefit for acute coronary syndrome patients. Recent National Institute for Health and Care Excellence (NICE) guidelines emphasise prompt initiation and up-titration from inpatient to community care to achieve this. The aim of this study was to assess the impact of simple interventions on inpatient and community up-titration of bisoprolol and ramipril for acute coronary syndrome patients admitted to Leeds General Infirmary. An initial prospective audit of 37 acute coronary syndrome patients admitted to Leeds General Infirmary in January 2013 assessed inpatient up-titration of bisoprolol and ramipril, discharge advice and doses at 6 weeks after discharge. Following a collective multidisciplinary effort with education, posters and discharge advice templates, a re-audit of 34 acute coronary syndrome patients admitted from November to December 2014 assessed the impact of these interventions. The independent samples t test was used to compare the mean difference between doses of ramipril and bisoprolol from initiation to discharge to dose at 6 weeks after discharge before and after intervention. There was a statistically significant improvement in the mean difference from initiation to discharge dose for both ramipril and bisoprolol (p=0.012 and p=0.017, respectively). However, there was little difference in community up-titration despite a 68% improvement in discharge advice. Simple multidisciplinary interventions improved inpatient up-titration of ramipril and bisoprolol but continued up-titration to achieve the target doses remains a challenge in primary care. Acute coronary syndrome patients are precluded from maximum mortality benefit due to suboptimal dosing after discharge.


A perspective on the dysplastic nevus controversy.
In 1992 an impartial scientific panel concluded that the term "dysplastic nevus" has created significant confusion and thus has outlived its usefulness. This chapter reviews the evolution of the controversy and offers a basis for understanding the panel's recommendations.


Does intraoperative gallbladder perforation influence the early outcome of laparoscopic cholecystectomy?
Laparoscopic cholecystectomy is rapidly becoming the preferred therapy for symptomatic cholelithiasis. It was our impression that the necessary traction exerted on the gallbladder during this procedure would frequently lead to intraoperative perforation with bile leak. We sought to determine prospectively the incidence of gallbladder perforation during laparoscopic cholecystectomy and to ascertain whether or not intraoperative bile leak resulted in overt complications. Laparoscopic cholecystectomy was performed successfully on 250 patients between November 1989 and December 1990. Gallbladder perforation occurred in 80 patients (32%). Compared with those without a bile leak, there was a larger percentage of men (p < 0.05), and the average weight was greater (p < 0.01) in those developing a bile leak. Operating time was significantly longer in patients with gallbladder perforation (mean +/- SEM, 104 +/- 4 min) than in those without a bile leak (94 +/- 3 min, p < 0.01), presumably because of the increased time spent irrigating the abdomen and retrieving gallstones. There was no difference in postoperative serum liver enzymes, amount or type of analgesia administered, interval to return to work or to full activity, or the development of postoperative infections. A wound infection requiring antibiotic therapy developed in only one patient who had not suffered a bile leak. The incidence of bile leak during the performance of laparoscopic cholecystectomy is therefore appreciable, occurring in approximately a third of our patients. Gallbladder perforation does not lead to any other adverse complications and should not cause the surgeon to convert to an open cholecystectomy.


Fiber-optic Sagnac interferometer for noncontact structural monitoring in power plant applications.
The design of a noncontact fiber-optic sensor is described for the detection of acoustic emission for structural integrity monitoring in high-temperature power plant applications. The sensor is based on a Sagnac interferometer and produces an output proportional to target velocity, without the need for active phase stabilization. It is inherently insensitive to low-frequency perturbations of the instrument or the target and incorporates an environmentally insensitive downlead, which may be of arbitrary length. It is shown that the sensor is capable of meeting the specifications for structural integrity monitoring of high-temperature power plant components based on acoustic emission detection and has a velocity resolution of 50 nm s(-1) Hz(-1/2).


Effect on Body Weight, Quality of Life and Appetite Following Individualized, Nutritional Counselling to Home-Living Elderly after Rehabilitation - An Open Randomized Trial.
We examined if individually-adapted nutritional counselling could prevent > 5% weight loss among elderly patients 3 months after discharge from a rehabilitation institution. In addition we assessed quality of life (QoL) and appetite. An open, randomized trial. Godthaab Health and Rehabilitation Institution in Bærum, Norway. Patients identified as being undernourished or at risk of disease-related malnutrition using the Nutritional Risk Screening tool NRS-2002. Shortly before discharge, patients in the intervention group received an individually-tailored nutrition plan. During the subsequent 3 months these patients were contacted 3 times via telephone calls and they received one visit at their homes, for nutrition counselling. Focus on this counselling was on optimizing meal environment, improving appetite, increasing food intake, advice on food preparation, and motivation and support. In addition to weight, QoL and appetite were assessed using the EQ-5D questionnaire and a modified version of the Disease-Related Appetite Questionnaire, respectively. Among 115 considered eligible for the study, 100 were enrolled (72 women and 28 men), with a mean age of 75 years and a mean body mass index of 20 kg/m2. Two in the intervention group (n = 52) and 5 in the control group (n = 48) lost > 5% of their body weight, giving an odds ratio of 0.34 (95% CI: 0.064 - 1.86; p = 0.22). We did not detect any significant differences in the QoL- or appetite scores between the two study groups after three months. An individually-adapted nutritional counselling did not improve body mass among elderly patients 3 months after discharge from a rehabilitation institution. Neither quality of life nor appetite measures were improved. Possibly, nutritional counselling should be accompanied with nutritional supplementation to be effective in this vulnerable group of elderly. The trial is registered in Clinical Trials (ID: NCT01632072).


Effect of guanabenz and hydrochlorothiazide on blood pressure and plasma renin activity.
Patients with mild to moderate essential hypertension were treated with guanabenz plus placebo (26 patients) or guanabenz plus hydrochlorothiazide (26 patients) for one year. Ambulatory plasma renin activity was determined during placebo treatment, after four weeks and one year of treatment with the study drugs, and one month after discontinuation of guanabenz while continuing the same hydrochlorothiazide dosage. Treatment with guanabenz plus hydrochlorothiazide proved more satisfactory than treatment with guanabenz plus placebo in that fewer patients were treatment failures, a smaller dosage of guanabenz was required, better control of supine blood pressure was achieved, and no increase in guanabenz dosage was needed to maintain chronic blood pressure control. Drowsiness, dry mouth, and dizziness were the side effects noted most commonly. Plasma renin activity was not significantly suppressed by chronic guanabenz therapy. Thus, guanabenz is an effective new antihypertensive that provides optimal blood pressure control when used with a diuretic.