Anticooperative ligand binding properties of recombinant ferric Vitreoscilla homodimeric hemoglobin: a thermodynamic, kinetic and X-ray crystallographic study.
Thermodynamics and kinetics for cyanide, azide, thiocyanate and imidazole binding to recombinant ferric Vitreoscilla sp. homodimeric hemoglobin (Vitreoscilla Hb) have been determined at pH 6.4 and 7.0, and 20.0 degrees C, in solution and in the crystalline state. Moreover, the three-dimensional structures of the diligated thiocyanate and imidazole derivatives of recombinant ferric Vitreoscilla Hb have been determined by X-ray crystallography at 1.8 A (Rfactor=19.9%) and 2.1 A (Rfactor=23.8%) resolution, respectively. Ferric Vitreoscilla Hb displays an anticooperative ligand binding behaviour in solution. This very unusual feature can only be accounted for by assuming ligand-linked conformational changes in the monoligated species, which lead to the observed 300-fold decrease in the affinity of cyanide, azide, thiocyanate and imidazole for the monoligated ferric Vitreoscilla Hb with respect to that of the fully unligated homodimer. In the crystalline state, thermodynamics for azide and imidazole binding to ferric Vitreoscilla Hb may be described as a simple process with an overall ligand affinity for the homodimer corresponding to that for diligation in solution. These data suggest that the ligand-free homodimer, observed in the crystalline state, is constrained in a low affinity conformation whose ligand binding properties closely resemble those of the monoligated species in solution. From the kinetic viewpoint, anticooperativity is reflected by the 300-fold decrease of the second-order rate constant for cyanide and imidazole binding to the monoligated ferric Vitreoscilla Hb with respect to that for ligand association to the ligand-free homodimer in solution. On the other hand, values of the first-order rate constant for cyanide and imidazole dissociation from the diligated and monoligated derivatives of ferric Vitreoscilla Hb in solution are closely similar. As a whole, ligand binding and structural properties of ferric Vitreoscilla Hb appear to be unique among all Hbs investigated to date.


Randomised clinical trial: sustained response to PPI treatment of symptoms resembling functional dyspepsia and irritable bowel syndrome in patients suffering from an overlap with erosive gastro-oesophageal reflux disease.
Gastro-oesophageal reflux disease (GERD), functional dyspepsia (FD) and irritable bowel syndrome (IBS) are highly prevalent gastrointestinal conditions with accumulating evidence of overlap in patients. Despite availability of a vast body of research related to individual disorders, major pharmacological breakthrough in treatment of the overlap condition is still lacking. To assess sustainability of GERD healing and whether known beneficial effects of proton pump inhibitor treatment on GERD also extend to symptoms suggestive of FD and IBS. A total of 626 patients with reflux oesophagitis were treated with pantoprazole for up to 16 weeks depending on healing of GERD, followed by an observational phase of up to 6 months without treatment. Rates of patients suffering from GERD, FD or IBS were assessed at baseline, and at last visits of treatment and observational phase. Rates of patients with reflux oesophagitis and concomitantly with reflux symptoms, FD or IBS were each significantly lower after pantoprazole treatment (P < 0.0001). While rates of patients with reflux signs or symptoms increased again during observational phase, rates of FD and IBS were maintained at the low level after cessation of medication (P < 0.0001). Pantoprazole is efficacious in the treatment of patients suffering from signs and symptoms suggesting an overlap of GERD, FD and/or IBS, providing a sustained response post-treatment in FD and IBS symptom categories. Mechanisms underlying the beneficial effects of improvement in reflux oesophagitis on symptoms suggestive of FD or IBS still need to be determined.


Shape "break-and-repair" strategy and its application to automated medical image segmentation.
In three-dimensional medical imaging, segmentation of specific anatomy structure is often a preprocessing step for computer-aided detection/diagnosis (CAD) purposes, and its performance has a significant impact on diagnosis of diseases as well as objective quantitative assessment of therapeutic efficacy. However, the existence of various diseases, image noise or artifacts, and individual anatomical variety generally impose a challenge for accurate segmentation of specific structures. To address these problems, a shape analysis strategy termed "break-and-repair" is presented in this study to facilitate automated medical image segmentation. Similar to surface approximation using a limited number of control points, the basic idea is to remove problematic regions and then estimate a smooth and complete surface shape by representing the remaining regions with high fidelity as an implicit function. The innovation of this shape analysis strategy is the capability of solving challenging medical image segmentation problems in a unified framework, regardless of the variability of anatomical structures in question. In our implementation, principal curvature analysis is used to identify and remove the problematic regions and radial basis function (RBF) based implicit surface fitting is used to achieve a closed (or complete) surface boundary. The feasibility and performance of this strategy are demonstrated by applying it to automated segmentation of two completely different anatomical structures depicted on CT examinations, namely human lungs and pulmonary nodules. Our quantitative experiments on a large number of clinical CT examinations collected from different sources demonstrate the accuracy, robustness, and generality of the shape "break-and-repair" strategy in medical image segmentation.


An evaluation of the impact of apheresis platelets used in the setting of massively transfused trauma patients.
Trauma is a major cause of morbidity and mortality worldwide. Of patients arriving to trauma centers, patients requiring massive transfusion (MT, >or=10 units in 24 hours) are a small patient subset but are at the highest risk of mortality. Transfusion of appropriate ratios of blood products to such patients has recently been an area of interest to both the civilian and military medical community. Plasma is increasingly recognized as a critical component, though less is known about appropriate ratios of platelets. Combat casualties managed at the busiest combat hospital in Iraq provided an opportunity to examine this question. In-patient records for 8,618 trauma casualties treated at the military hospital in Baghdad more than a 3-year interval between January 2004 and December 2006 were retrospectively reviewed and patients requiring MT (n = 694) were identified. Patients who required MT in the first 24 hours and did not receive fresh whole blood were divided into study groups defined by source of platelets: (1) patient receiving a low ratio of platelets (<1:16 apheresis platelets per stored red cell unit, aPLT:RBC) (n = 214), (2) patients receiving a medium ratio of platelets (1:16 to <1:8 aPLT:RBC) (n = 154), and (3) patients receiving a high ratio of platelets (>or=1:8 aPLT:RBC) (n = 96). The primary endpoint was survival at 24 hours and at 30 days. At 24 hours, patients receiving a high ratio of platelets had higher survival (95%) as compared with patients receiving a medium ratio (87%) and patients receiving the lowest ratio of platelets (64%) (log-rank p = 0.04 and p < 0.001, respectively). The survival benefit for the high and medium ratio groups remained at 30 days as compared with those receiving the lowest ratio of platelets (75% and 60% vs. 43%, p < 0.001 for both comparisons). On multivariate regression, plasma:RBC ratios and aPLT:RBC were both independently associated with improved survival at 24 hours and at 30 days. Transfusion of a ratio of >or=1:8 aPLT:RBC is associated with improved survival at 24 hours and at 30 days in combat casualties requiring a MT within 24 hours of injury. Although prospective study is needed to confirm this finding, MT protocols outside of investigational research should consider incorporation of appropriate ratios of both plasma and platelets.


Effects of a short-term aquatic exercise intervention on symptoms and exercise capacity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a pilot study.
This pilot pre-and post-intervention study investigated the effects of a short-term aquatic exercise programme on physiological outcomes, symptoms and exercise capacity in women with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Eleven women (54.8 ± 12.4 year) volunteered for the 5-week program; an initial 20-min aquatic exercise session then two self-paced 20-min sessions per week for 4 weeks. Pre- and post-intervention outcomes were physiological measures, 6 min Walk Test (6MWT), perceived exertion (RPE), hand grip strength, Sit-to-Stand, Sit-Reach test, Apley's shoulder test, FACIT questionnaire, and 24-h post-test tiredness and pain scores (0-10 visual analogue scale). Heart rates, RPE, 24- and 48-h post-session tiredness/pain scores were recorded each session. 6MWT distance increased by 60.8 m (p = 0.006), left hand grip strength by 6 kg (p = 0.038), Sit-Reach test by 4.0 cm (p = 0.017), right shoulder flexibility by 2.9 cm (p = 0.026), FACIT scores by 8.2 (p = 0.041); 24-h post-test tiredness and pain decreased by 1.5 and 1.6, respectively (p = 0.002). There were significant post-intervention increases in exercising heart rates (6MWT 4- and 6-min time points), oxygen saturation at 2-min, and reduced RPE at 4-min. Weekly resting and exercising heart rates increased significantly during the study but RPE decreased; immediately post- and 24-h post-session tiredness decreased significantly. There were no reports of symptom exacerbation. Five weeks of low-moderate intensity aquatic exercise significantly improved exercise capacity, RPE and fatigue. This exercise mode exercise may potentially be a manageable and safe physical activity for CFS/ME patients.


Hieranoid: hierarchical orthology inference.
An accurate inference of orthologs is essential in many research fields such as comparative genomics, molecular evolution, and genome annotation. Existing methods for genome-scale orthology inference are mostly based on all-versus-all similarity searches that scale quadratically with the number of species. This limits their application to the increasing number of available large-scale datasets. Here, we present Hieranoid, a new orthology inference method using a hierarchical approach. Hieranoid performs pairwise orthology analysis using InParanoid at each node in a guide tree as it progresses from its leaves to the root. This concept reduces the total runtime complexity from a quadratic to a linear function of the number of species. The tree hierarchy provides a natural structure in multi-species ortholog groups, and the aggregation of multiple sequences allows for multiple alignment similarity searching techniques, which can yield more accurate ortholog groups. Using the recently published orthobench benchmark, Hieranoid showed the overall best performance. Our progressive approach presents a new way to infer orthologs that combines efficient graph-based methodology with aspects of compute-intensive tree-based methods. The linear scaling with the number of species is a major advantage for large-scale applications and makes Hieranoid well suited to cope with vast amounts of sequenced genomes in the future. Hieranoid is an open source and can be downloaded at Hieranoid.sbc.su.se.


Antibody response over time correlated with treatment outcome in 30 dogs naturally infected with Brucella canis (2017-2022).
Brucella canis is a zoonotic bacterial pathogen of dogs that is notoriously difficult to diagnose and treat. Humans can become infected with B canis when an infected pet dog is brought into their home. Our objectives were to describe the clinical presentation and outcomes in dogs treated for B canis and evaluate the performance of the quantitative serologic canine Brucella multiplex (CBM) assay for monitoring treatment response. Diagnostic records from the Animal Health Diagnostic Center at Cornell University were retrospectively reviewed (2017-2022) for dogs that underwent repeat B canis serologic testing. Medical records were requested to compare the clinical presentations and outcomes for dogs that underwent treatment for B canis. Changes in CBM antibody values were compared between dogs with and without resolution of clinical signs. While treatment protocols varied in the 30 treated dogs meeting the inclusion criteria, poly-antimicrobial therapy was prescribed in 97% (29/30) of cases. Gait abnormalities, spinal pain, and discospondylitis were the most common clinical abnormalities. A difference (P value = .0075) in the percent decrease in CBM assay PO1 antibody values was found in dogs with resolved clinical signs. Young dogs presenting with recurring lameness or back pain should be screened for B canis infection. A 40% decline in CBM assay values 2 to 6 months posttreatment can be supportive of response to treatment. Further prospective studies are needed to determine the ideal B canis treatment regimen and the magnitude of public health risks associated with maintaining neutered B canis-infected animals as pets.


Reducing Wildlife Damage with Cost-Effective Management Programmes.
Limiting the impact of wildlife damage in a cost effective manner requires an understanding of how control inputs change the occurrence of damage through their effect on animal density. Despite this, there are few studies linking wildlife management (control), with changes in animal abundance and prevailing levels of wildlife damage. We use the impact and management of wild pigs as a case study to demonstrate this linkage. Ground disturbance by wild pigs has become a conservation issue of global concern because of its potential effects on successional changes in vegetation structure and composition, habitat for other species, and functional soil properties. In this study, we used a 3-year pig control programme (ground hunting) undertaken in a temperate rainforest area of northern New Zealand to evaluate effects on pig abundance, and patterns and rates of ground disturbance and ground disturbance recovery and the cost effectiveness of differing control strategies. Control reduced pig densities by over a third of the estimated carrying capacity, but more than halved average prevailing ground disturbance. Rates of new ground disturbance accelerated with increasing pig density, while rates of ground disturbance recovery were not related to prevailing pig density. Stochastic simulation models based on the measured relationships between control, pig density and rate of ground disturbance and recovery indicated that control could reduce ground disturbance substantially. However, the rate at which prevailing ground disturbance was reduced diminished rapidly as more intense, and hence expensive, pig control regimes were simulated. The model produced in this study provides a framework that links conservation of indigenous ecological communities to control inputs through the reduction of wildlife damage and suggests that managers should consider carefully the marginal cost of higher investment in wildlife damage control, relative to its marginal conservation return.


A comparative study of techniques for differential expression analysis on RNA-Seq data.
Recent advances in next-generation sequencing technology allow high-throughput cDNA sequencing (RNA-Seq) to be widely applied in transcriptomic studies, in particular for detecting differentially expressed genes between groups. Many software packages have been developed for the identification of differentially expressed genes (DEGs) between treatment groups based on RNA-Seq data. However, there is a lack of consensus on how to approach an optimal study design and choice of suitable software for the analysis. In this comparative study we evaluate the performance of three of the most frequently used software tools: Cufflinks-Cuffdiff2, DESeq and edgeR. A number of important parameters of RNA-Seq technology were taken into consideration, including the number of replicates, sequencing depth, and balanced vs. unbalanced sequencing depth within and between groups. We benchmarked results relative to sets of DEGs identified through either quantitative RT-PCR or microarray. We observed that edgeR performs slightly better than DESeq and Cuffdiff2 in terms of the ability to uncover true positives. Overall, DESeq or taking the intersection of DEGs from two or more tools is recommended if the number of false positives is a major concern in the study. In other circumstances, edgeR is slightly preferable for differential expression analysis at the expense of potentially introducing more false positives.


The contribution of health technology assessment, health needs assessment, and health impact assessment to the assessment and translation of technologies in the field of public health genomics.
The European Union has named genomics as one of the promising research fields for the development of new health technologies. Major concerns with regard to these fields are, on the one hand, the rather slow and limited translation of new knowledge and, on the other hand, missing insights into the impact on public health and health care practice of those technologies that are actually introduced. This paper aims to give an overview of the major assessment instruments in public health [health technology assessment (HTA), health needs assessment (HNA) and health impact assessment (HIA)] which could contribute to the systematic translation and assessment of genomic health applications by focussing at population level and on public health policy making. It is shown to what extent HTA, HNA and HIA contribute to translational research by using the continuum of translational research (T1-T4) in genomic medicine as an analytic framework. The selected assessment methodologies predominantly cover 2 to 4 phases within the T1-T4 system. HTA delivers the most complete set of methodologies when assessing health applications. HNA can be used to prioritize areas where genomic health applications are needed or to identify infrastructural needs. HIA delivers information on the impact of technologies in a wider scope and promotes informed decision making. HTA, HNA and HIA provide a partly overlapping and partly unique set of methodologies and infrastructure for the translation and assessment of genomic health applications. They are broad in scope and go beyond the continuum of T1-T4 translational research regarding policy translation.


Diagnosis of abdominal masses with percutaneous biopsy guided by ultrasound.
To assess the accuracy and safety of percutaneous biopsy of abdominal masses guided by ultrasound. Prospective study. Combined gastroenterology service, Scarborough Hospital. 108 Consecutive patients identified as having a discrete mass on diagnostic ultrasound examination of the abdomen. A sample of tissue was obtained with an aseptic technique under local anaesthesia: an 18 steel wire gauge needle (Tru-Cut) was mounted in a spring loaded firing device (Biopty gun) that was advanced under simultaneous ultrasound scanning, permitting precise localisation of the target organ. Results of histological examination of tissue specimens. Biopsy failed in four patients. Adequate histological specimens were obtained in 104 patients with masses in the liver (31), pancreas (37), kidney (10), and adrenal glands (six) and in 20 undiagnosed abdominal and retroperitoneal masses. Follow up was until death or confirmation of the diagnosis. Three complications but no deaths occurred. Malignancy was suspected in 84 patients before biopsy. This was confirmed in 70 patients, in 26 of whom confirmation of dissemination obviated the need for further investigation. In 10 patients biopsy indicated a previously unsuspected primary tumour, and in 12 it showed only a benign lesion. Among 24 patients considered to have benign disease biopsy showed an unsuspected neoplasm in seven. Use of biopsy thus had a major effect on clinical management in 55 patients. Four false negative but no false positive diagnoses resulted from the procedure. Percutaneous biopsy of abdominal and retroperitoneal masses under ultrasound guidance is a safe and accurate method of obtaining a histological diagnosis. The results obtained have a considerable effect on clinical management.


Programmable patterns in a DNA-based reaction-diffusion system.
Biology offers compelling proof that macroscopic "living materials" can emerge from reactions between diffusing biomolecules. Here, we show that molecular self-organization could be a similarly powerful approach for engineering functional synthetic materials. We introduce a programmable DNA embedded hydrogel that produces tunable patterns at the centimeter length scale. We generate these patterns by implementing chemical reaction networks through synthetic DNA complexes, embedding the complexes in the hydrogel, and triggering with locally applied input DNA strands. We first demonstrate ring pattern formation around a circular input cavity and show that the ring width and intensity can be predictably tuned. Then, we create patterns of increasing complexity, including concentric rings and non-isotropic patterns. Finally, we show "destructive" and "constructive" interference patterns, by combining several ring-forming modules in the gel and triggering them from multiple sources. We further show that computer simulations based on the reaction-diffusion model can predict and inform the programming of target patterns.


Differential Functional Connectivity along the Long Axis of the Hippocampus Aligns with Differential Role in Memory Specificity and Generalization.
The hippocampus contributes to both remembering specific events and generalization across events. Recent work suggests that information may be represented along the longitudinal axis of the hippocampus at varied levels of specificity: detailed representations in the posterior hippocampus and generalized representations in the anterior hippocampus. Similar distinctions are thought to exist within neocortex, with lateral prefrontal and lateral parietal regions supporting memory specificity and ventromedial prefrontal and lateral temporal cortices supporting generalized memory. Here, we tested whether functional connectivity of anterior and posterior hippocampus with cortical memory regions is consistent with these proposed dissociations. We predicted greater connectivity of anterior hippocampus with putative generalization regions and posterior hippocampus with putative memory specificity regions. Furthermore, we tested whether differences in connectivity are stable under varying levels of task engagement. Participants learned to categorize a set of stimuli outside the scanner, followed by an fMRI session that included a rest scan, passive viewing runs, and category generalization task runs. Analyses revealed stronger connectivity of ventromedial pFC to anterior hippocampus and of angular gyrus and inferior frontal gyrus to posterior hippocampus. These differences remained relatively stable across the three phases (rest, passive viewing, category generalization). Whole-brain analyses further revealed widespread cortical connectivity with both anterior and posterior hippocampus, with relatively little overlap. These results contribute to our understanding of functional organization along the long axis of the hippocampus and suggest that distinct hippocampal-cortical connections are one mechanism by which the hippocampus represents both individual experiences and generalized knowledge.


Molecular characterisation of Haemoglobin Constant Spring and Haemoglobin Quong Sze with a Combine-Amplification Refractory Mutation System.
The interaction of the non-deletional α(+)-thalassaemia mutations Haemoglobin Constant Spring and Haemoglobin Quong Sze with the Southeast Asian double α-globin gene deletion results in non-deletional Haemoglobin H disease. Accurate detection of non-deletional Haemoglobin H disease, which is associated with severe phenotypes, is necessary as these mutations have been confirmed in the Malaysian population. DNA from two families with Haemoglobin H disease was extracted from EDTA-anticoagulated whole blood and subjected to molecular analysis for α-thalassaemia. A duplex polymerase chain reaction was used to detect the Southeast Asian α-globin gene deletion. Polymerase chain reaction-restriction fragment length polymorphism analysis was then carried out to determine the presence of Haemoglobin Constant Spring and Haemoglobin Quong Sze. A combine-amplification refractory mutation system protocol was optimised and implemented for the rapid and specific molecular characterisation of Haemoglobin Constant Spring and Haemoglobin Quong Sze in a single polymerase chain reaction. The combine-amplification refractory mutation system for Haemoglobin Constant Spring and Haemoglobin Quong Sze, together with the duplex polymerase chain reaction, provides accurate pre- and postnatal diagnosis of non-deletional Haemoglobin H disease and allows detailed genotype analyses using minimal quantities of DNA.


An improved limit on the charge of antihydrogen from stochastic acceleration.
Antimatter continues to intrigue physicists because of its apparent absence in the observable Universe. Current theory requires that matter and antimatter appeared in equal quantities after the Big Bang, but the Standard Model of particle physics offers no quantitative explanation for the apparent disappearance of half the Universe. It has recently become possible to study trapped atoms of antihydrogen to search for possible, as yet unobserved, differences in the physical behaviour of matter and antimatter. Here we consider the charge neutrality of the antihydrogen atom. By applying stochastic acceleration to trapped antihydrogen atoms, we determine an experimental bound on the antihydrogen charge, Qe, of |Q| < 0.71 parts per billion (one standard deviation), in which e is the elementary charge. This bound is a factor of 20 less than that determined from the best previous measurement of the antihydrogen charge. The electrical charge of atoms and molecules of normal matter is known to be no greater than about 10(-21)e for a diverse range of species including H2, He and SF6. Charge-parity-time symmetry and quantum anomaly cancellation demand that the charge of antihydrogen be similarly small. Thus, our measurement constitutes an improved limit and a test of fundamental aspects of the Standard Model. If we assume charge superposition and use the best measured value of the antiproton charge, then we can place a new limit on the positron charge anomaly (the relative difference between the positron and elementary charge) of about one part per billion (one standard deviation), a 25-fold reduction compared to the current best measurement.


Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study.
High intake of folate may reduce risk for colon cancer, but the dosage and duration relations and the impact of dietary compared with supplementary sources are not well understood. To evaluate the relation between folate intake and incidence of colon cancer. Prospective cohort study. 88,756 women from the Nurses' Health Study who were free of cancer in 1980 and provided updated assessments of diet, including multivitamin supplement use, from 1980 to 1994. 442 women with new cases of colon cancer. Multivariate relative risk (RR) and 95% CIs for colon cancer in relation to energy-adjusted folate intake. Higher energy-adjusted folate intake in 1980 was related to a lower risk for colon cancer (RR, 0.69 [95% CI, 0.52 to 0.93] for intake > 400 microg/d compared with intake < or = 200 microg/d) after controlling for age; family history of colorectal cancer; aspirin use; smoking; body mass; physical activity; and intakes of red meat, alcohol, methionine, and fiber. When intake of vitamins A, C, D, and E and intake of calcium were also controlled for, results were similar. Women who used multivitamins containing folic acid had no benefit with respect to colon cancer after 4 years of use (RR, 1.02) and had only nonsignificant risk reductions after 5 to 9 (RR, 0.83) or 10 to 14 years of use (RR, 0.80). After 15 years of use, however, risk was markedly lower (RR, 0.25 [CI, 0.13 to 0.51]), representing 15 instead of 68 new cases of colon cancer per 10,000 women 55 to 69 years of age. Folate from dietary sources alone was related to a modest reduction in risk for colon cancer, and the benefit of long-term multivitamin use was present across all levels of dietary intakes. Long-term use of multivitamins may substantially reduce risk for colon cancer. This effect may be related to the folic acid contained in multivitamins.


Glucosylation of (Z)-3-hexenol informs intraspecies interactions in plants: A case study in Camellia sinensis.
Plants emit a variety of volatiles in response to herbivore attack, and (Z)-3-hexenol and its glycosides have been shown to function as defence compounds. Although the ability to incorporate and convert (Z)-3-hexenol to glycosides is widely conserved in plants, the enzymes responsible for the glycosylation of (Z)-3-hexenol remained unknown until today. In this study, uridine-diphosphate-dependent glycosyltransferase (UGT) candidate genes were selected by correlation analysis and their response to airborne (Z)-3-hexenol, which has been shown to be taken up by the tea plant. The allelic proteins UGT85A53-1 and UGT85A53-2 showed the highest activity towards (Z)-3-hexenol and are distinct from UGT85A53-3, which displayed a similar catalytic efficiency for (Z)-3-hexenol and nerol. A single amino acid exchange E59D enhanced the activity towards (Z)-3-hexenol, whereas a L445M mutation reduced the catalytic activity towards all substrates tested. Transient overexpression of CsUGT85A53-1 in tobacco significantly increased the level of (Z)-3-hexenyl glucoside. The functional characterization of CsUGT85A53 as a (Z)-3-hexenol UGT not only provides the foundation for the biotechnological production of (Z)-3-hexenyl glucoside but also delivers insights for the development of novel insect pest control strategies in tea plant and might be generally applicable to other plants.


Water relations of native and introduced C4 grasses in a neotropical savanna.
Introduced African grasses are invading Neotropical savannas and displacing the native herbaceous community. This work, which is part of a program to understand the success of the African grasses, specifically investigates whether introduced and native grasses differ in their water relations. The water relations of the native Trachypogon plumosus and the successful invader Hyparrhenia rufa were studied in the field during two consecutive years in the seasonal savannas of Venezuela. The two C4 grasses differed clearly in their responses to water stress. H. rufa consistently had higher stomatal conductance, transpiration rate, leaf water and osmotic potential and osmotic adjustment than the native T. plumosus. Also, leaf senescence occurred much earlier during the dry season in H. rufa. Both grasses showed a combination of water stress evasion and tolerance mechanisms such as stomatal sensitivity to atmospheric or soil water stress, decreased transpiring area and osmotic adjustment. Evasion mechanisms are more conspicuous in H. rufa whereas T. plumosus is more drought tolerant and uses water more "conservatively". The evasion mechanisms and oportunistic use of water by H. rufa, characteristic of invading species, contribute to, but only partially explain, the success of this grass in the Neotropical savannas where it displaces native plants from sites with better water and nutrient status. Conversely, the higher water stress tolerance of t. plumosus is consistent with its capacity to resist invasion by alien grasses on shallow soils and sites with poorer nutrient and water status.


Factors affecting the prescribing patterns of antibiotics and injections.
There are serious problems concerning the inadequate prescription of antibiotics and overuse of injections in primary care. However, the determinants of prescription patterns in Korea are not well-documented. To examine the area characteristics affecting the prescription of antibiotics and injections in primary care practices in the treatment of respiratory tract infections (RTIs), a nationwide cross-sectional study was performed in all 250 administrative districts of Korea. The outcome was modeled as a binary variable: over-prescription or not compared with the nation-wide average. Over-prescription of antibiotics was associated with the ratio of specialists to general physicians and over-prescription in previous years in the area (adjusted odds ratio [aOR], 4.8; 95% confidence interval [CI] 1.5-14.8; and aOR, 12.0; 95% CI 5.5-25.9, respectively). Over-use of injections was associated with younger population, urban living and the number of hospital beds in the area (aOR, 0.2; 95% CI 0.1-0.4; aOR, 0.3; 95% CI 0.1-0.8; and aOR, 0.4, 95% CI 0.2-0.9; respectively). There were differences in the prescribing patterns in different districts; prescription patterns were affected more by supply factors than by demand factors. Highly competitive medical environment associated with supply factors is a significant determinant of prescription patterns in Korea.


Improving Sprint Performance in Soccer: Effectiveness of Jump Squat and Olympic Push Press Exercises.
Training at the optimum power load (OPL) is an effective way to improve neuromuscular abilities of highly trained athletes. The purpose of this study was to test the effects of training using the jump squat (JS) or Olympic push-press (OPP) exercises at the OPL during a short-term preseason on speed-power related abilities in high-level under-20 soccer players. The players were divided into two training groups: JS group (JSG) and OPP group (OPPG). Both groups undertook 12 power-oriented sessions, using solely JS or OPP exercises. Pre- and post-6 weeks of training, athletes performed squat jump (SJ), countermovement jump (CMJ), sprinting speed (5, 10, 20 and 30 m), change of direction (COD) and speed tests. To calculate the transfer effect coefficient (TEC) between JS and MPP OPP and the speed in 5, 10, 20, and 30 m, the ratio between the result gain (effect size [ES]) in the untrained exercise and result gain in the trained exercise was calculated. Magnitude based inference and ES were used to test the meaningful effects. The TEC between JS and VEL 5, 10, 20, and 30 m ranged from 0.77 to 1.29, while the only TEC which could be calculated between OPP and VEL 5 was rather low (0.2). In addition, the training effects of JS on jumping and speed related abilities were superior (ES ranging from small to large) to those caused by OPP (trivial ES). To conclude, the JS exercise is superior to the OPP for improving speed-power abilities in elite young soccer players.


Sensory Input-Dependent Changes in Glutamatergic Neurotransmission- Related Genes and Proteins in the Adult Rat Trigeminal Ganglion.
Experience-dependent plasticity induces lasting changes in the structure of synapses, dendrites, and axons at both molecular and anatomical levels. Whilst relatively well studied in the cortex, little is known about the molecular changes underlying experience-dependent plasticity at peripheral levels of the sensory pathways. Given the importance of glutamatergic neurotransmission in the somatosensory system and its involvement in plasticity, in the present study, we investigated gene and protein expression of glutamate receptor subunits and associated molecules in the trigeminal ganglion (TG) of young adult rats. Microarray analysis of naïve rat TG revealed significant differences in the expression of genes, coding for various glutamate receptor subunits and proteins involved in clustering and stabilization of AMPA receptors, between left and right ganglion. Long-term exposure to sensory-enriched environment increased this left-right asymmetry in gene expression. Conversely, unilateral whisker trimming on the right side almost eliminated the mentioned asymmetries. The above manipulations also induced side-specific changes in the protein levels of glutamate receptor subunits. Our results show that sustained changes in sensory input induce modifications in glutamatergic transmission-related gene expression in the TG, thus supporting a role for this early sensory-processing node in experience-dependent plasticity.


Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease.
Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development.


Risk factors for hospital-acquired non-catheter-associated urinary tract infection.
Nosocomial urinary tract infection in patients with no Foley catheter [non-catheter-associated urinary tract infection (non-CAUTI)] has been a serious health issue that is associated with an increase in the cost of care, morbidity, and mortality. Identifying the risk factors of non-CAUTI would help determine patients at high risk and prevent complications. This study aims to identify the risk factors of non-CAUTI. This study was conducted in four hospitals in three Middle Eastern countries: Jordan, Qatar, and Saudi Arabia. A convenience sample of 189 participants was recruited, of which 83 had non-CAUTI. Case-control design was used. Patients who had non-CAUTI while hospitalized were compared with others who did not. A questionnaire was developed based on the non-CAUTI diagnostic criteria from the Centers for Disease Control and Prevention. The questionnaire contained two parts: part one included participants' characteristics and part two assessed the symptoms of non-CAUTI. Comorbidity is associated with a higher risk of having nosocomial non-CAUTI among hospitalized patients. This study showed that the diagnosis and management of comorbidity is important in lowering the risk of non-CAUTI in hospitalized patients. Age and antibiotic administration were statistically significant; however, their effects were small and were unlikely to have any clinical significance. Identifying patients at high risk is imperative to prevent the development of non-CAUTI. Nurse practitioners may implement an early intervention for patients with comorbidity to counteract its effect on patients' health.


Ocular defects in photosensitive epilepsy.
Patients with photosensitive epilepsy are susceptible to seizures due to photoparoxysmal response (PPR). This response adversely precipitates factors that modify the functional status of the visual system. Such factors may or may not be evident superficially, but may lead to ocular defects due to trauma, hormonal imbalance, abnormal intraocular pressure (IOP), or any other reflex-inducing stimuli. The extent to which photosensitive epileptic patients suffer from PPR-related ocular defects has not been documented fully. In this investigation, ocular defects in patients with photosensitive epilepsy are studied using visual-evoked response (VER). A total of 212 photosensitive epileptic patients were studied to ascertain the magnitude and distribution of ocular defects using the changes in EEG and visual-evoked potential (VEP); 51% of the patients were female, the age range was 1-46 years. The major ocular defects and complications found were visual field defects, optic nerve abnormalities, nystagmus, cataracts, amblyopia, and migraine. These findings were analyzed according to age and sex. The relationship between the ocular abnormalities and the interpretations of the changes in the characteristics of the VEP indicated that optic-related atrophies, visual defects, optic neuritis, chiasmal compression, nystagmus, migraine headache, cataracts, and amblyopia were prevalent in photosensitive epileptic patients at varying degrees. The results showed that although ocular defects in photosensitive epilepsy may not be obvious differentially, VEP can be used in their diagnosis, contrary to earlier studies reporting that VEP is not of much value in epilepsy diagnosis.


Effect of whey protein isolate on rehydration after exercise.
Studies have examined adding protein to carbohydrate-electrolyte rehydration drinks, but the effects of protein in isolation remain unknown. Ten subjects completed two trials in which they were dehydrated (~2 % of pre-exercise body mass) by intermittent cycling in the heat. Subjects then rehydrated (150 % total mass loss) over 1 h with mineral water (W) or mineral water plus 20 g L(-1) whey protein isolate (WP) and remained in the laboratory for a further 4 h. Blood and urine samples were provided pre-exercise, post-exercise, post-rehydration and every hour thereafter. From blood samples, serum osmolality, change in plasma volume and plasma albumin content was determined, whilst the volume and osmolality of urine samples were determined. There was no difference between trials for total urine volume [W: 1,234 (358) mL; WP: 1,306 (268) mL; P = 0.409], drink retention [W: 40 (14) %; WP: 37 (14) %; P = 0.322] or net fluid balance [W: -605 (318) mL; WP: -660 (274) mL; P = 0.792] 4-h post-rehydration. Plasma volume was greater 3 and 4 h post-drinking during WP, and plasma albumin content relative to pre-exercise was increased 1-4 h post-drinking in WP only. These results suggest that addition of 20 g L(-1) whey protein isolate neither enhances nor inhibits post-exercise rehydration, when a volume equivalent to 150 % of sweat losses is ingested in 1 h. As post-exercise nutritional requirements are multifactorial (rehydration, glycogen resynthesis, myofibrillar/mitochondrial protein synthesis), these data demonstrate that when post-exercise protein intake might benefit recovery or adaptation, this can be achieved without compromising rehydration.


Peaceful play yoga: serenity and balance for children with cancer and their parents.
Children with a cancer diagnosis experience symptom distress, including anxiety, because of the disease and its treatment. Parents experience stress and anxiety because of the uncertainty of the disease as well as the suffering of their children. Yoga is a complementary intervention that has physiological and psychological benefits in healthy children and healthy and chronically ill adults. On an inpatient hematology/oncology unit, 11 children aged 6 to 12 years, 5 adolescents aged 13 to 18 years, and 33 parents participated in a single yoga session tailored to the needs and abilities of the patients and parents. Sense of well-being pre- and postclass was measured with the Spielberger State Anxiety Scale. Children had normal anxiety scores preclass that did not change. Adolescents and parents experienced significant decreases in anxiety scores, and all cohorts gave positive feedback about the experience. The authors conclude that yoga is a feasible intervention for this population and is beneficial to adolescents and parents.


Coupling aging immunity with a sedentary lifestyle: has the damage already been done?--a mini-review.
The elderly population is at an unprecedented risk of infectious diseases and malignancy due to apparently inevitable age-related declines in immunity. The 'immune risk profile' (IRP) is an array of biomarkers that has been used to predict morbidity and mortality in older adults. As it is generally accepted that middle-aged and elderly individuals who habitually participate in moderate-intensity exercise are less likely to incur an infection than their sedentary counterparts, this review addresses current knowledge on the effects of regular exercise on aspects of adaptive immunity as they relate to the IRP. Findings from cross-sectional studies mostly show enhanced immunity in physically active compared to sedentary older adults. These include greater T-cell responsiveness to mitogens in vitro, a reduced frequency of antigen-experienced and senescent T-cells (i.e. CD45RO+/KLRG1+/CD57+/CD28-), enhanced IL-2 production and T-lymphocyte expression of the IL-2 receptor, longer chromosome telomere lengths in blood leukocytes and in vivo immune responses to vaccines and recall antigens. In contrast, the evidence from the available longitudinal studies that have used an exercise training intervention in previously sedentary elderly to improve similar immune responses is less compelling. Although this might indicate that exercise has limited immune restorative properties in previously sedentary elderly, there are still relatively few studies that have addressed specific IRP criteria and the large variation in experimental design among the longitudinal studies complicates the juxtaposition of these results. It is clear that a more substantial and focused research approach is required before physical exercise can be used in earnest as an effective immune restorative strategy in the elderly. This mini-review summarizes the major findings of these studies and proposes future avenues of research to investigate the effects of regular exercise on aspects of adaptive immunity in the elderly as they relate to the IRP.


Energy transport in linear dielectrics.
We examine the energy exchanged between an electromagnetic pulse and a linear dielectric medium in which it propagates. While group velocity indicates the presence of field energy (the locus of which can move with arbitrary speed), the velocity of energy transport maintains strict luminality. This indicates that the medium treats the leading and trailing portions of the pulse differently. The principle of causality requires the medium to respond to the instantaneous spectrum, the spectrum of the pulse truncated at each new instant as a given locale in the medium experiences the pulse.


System effectiveness of a targeted free mass distribution of long lasting insecticidal nets in Zanzibar, Tanzania.
Insecticide-treated nets (ITN) and long-lasting insecticidal treated nets (LLIN) are important means of malaria prevention. Although there is consensus regarding their importance, there is uncertainty as to which delivery strategies are optimal for dispensing these life saving interventions. A targeted mass distribution of free LLINs to children under five and pregnant women was implemented in Zanzibar between August 2005 and January 2006. The outcomes of this distribution among children under five were evaluated, four to nine months after implementation. Two cross-sectional surveys were conducted in May 2006 in two districts of Zanzibar: Micheweni (MI) on Pemba Island and North A (NA) on Unguja Island. Household interviews were conducted with 509 caretakers of under-five children, who were surveyed for socio-economic status, the net distribution process, perceptions and use of bed nets. Each step in the distribution process was assessed in all children one to five years of age for unconditional and conditional proportion of success. System effectiveness (the accumulated proportion of success) and equity effectiveness were calculated, and predictors for LLIN use were identified. The overall proportion of children under five sleeping under any type of treated net was 83.7% (318/380) in MI and 91.8% (357/389) in NA. The LLIN usage was 56.8% (216/380) in MI and 86.9% (338/389) in NA. Overall system effectiveness was 49% in MI and 87% in NA, and equity was found in the distribution scale-up in NA. In both districts, the predicting factor of a child sleeping under an LLIN was caretakers thinking that LLINs are better than conventional nets (OR = 2.8, p = 0.005 in MI and 2.5, p = 0.041 in NA), in addition to receiving an LLIN (OR = 4.9, p < 0.001 in MI and in OR = 30.1, p = 0.001 in NA). Targeted free mass distribution of LLINs can result in high and equitable bed net coverage among children under five. However, in order to sustain high effective coverage, there is need for complimentary distribution strategies between mass distribution campaigns. Considering the community's preferences prior to a mass distribution and addressing the communities concerns through information, education and communication, may improve the LLIN usage.


Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial.
Cognitive behaviour therapy (CBT) added to specialist medical care (SMC), or graded exercise therapy (GET) added to SMC, are more effective in reducing fatigue and improving physical function than both adaptive pacing therapy (APT) plus SMC and SMC alone for chronic fatigue syndrome. We investigate putative treatment mechanisms. We did a planned secondary mediation analysis of the PACE trial comparing SMC alone or SMC plus APT with SMC plus CBT and SMC plus GET for patients with chronic fatigue syndrome. 641 participants were recruited from six specialist chronic fatigue syndrome clinics in the UK National Health Service between March 18, 2005, and Nov 28, 2008. We assessed mediation using the product of coefficients method with the 12 week measure of the mediators and the 52 week measure of the outcomes. The primary outcomes were fatigue measured by the Chalder fatigue scale and physical function measured by the physical function subscale of the SF-36. We included confounder covariates and used treatment by mediator interaction terms to examine differences in mediator-outcome relations by treatment group. The largest mediated effect for both CBT and GET and both primary outcomes was through fear avoidance beliefs with an effect of larger magnitude for GET (standardised effects ×10, CBT vs APT, fatigue -1.22, 95% CI -0.52 to -1.97, physical function 1.54, 0.86 to 2.31; GET vs APT, fatigue -1.86, -0.80 to -2.89, physical function 2.35, 1.35 to 3.39). Increase in exercise tolerance (6 min walk distance) was a potent mediator of the effect of GET (vs APT, fatigue -1.37, 95% CI -0.76 to -2.21, physical function 1.90, 1.10 to 2.91), but not CBT. Our main finding was that fear avoidance beliefs were the strongest mediator for both CBT and GET. Changes in both beliefs and behaviour mediated the effects of both CBT and GET, but more so for GET. The results support a treatment model in which both beliefs and behaviour play a part in perpetuating fatigue and disability in chronic fatigue syndrome. UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions, National Institute for Health Research (NIHR), NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust, and Institute of Psychiatry, Psychology, and Neuroscience, King's College London.


Spousal veto over family planning services.
In many countries a spouse, usually the husband, can veto a partner's use of family planning services. Where spousal veto acts as a barrier to family planning services it represents a serious threat to the lives and health of women and children. Removal of spousal authorization requirements has been shown to increase the use of family planning services. The Family Guidance Association of Ethiopia, for example, removed their requirement in 1982 and clinic utilization increased by 26 per cent within a few months. Courts of several countries have held that spousal veto practices violate principles of personal privacy and autonomy and the right to health care. The effect of such judgements has been to reinforce rights to sexual nondiscrimination found, for example, in national constitutions and the Convention on the Elimination of All Forms of Discrimination against Women. This article discusses the nature and application of spousal veto practices, explains how such requirements can violate certain human rights, and explores possible remedies to this problem, including ministerial, legislative, and judicial initiatives.


Medical professionalism: an experimental look at physicians' Facebook profiles.
Use of social networking services (SNS) is on the rise. While many users sign in for personal purposes, it is not uncommon for professionals to connect over SNSs with clients, students, and patients. The present study used an experimental approach to examine how medical doctors' SNS profiles impacted potential patients' impressions of professionalism. Participants (N=250 students) were randomly assigned to view one of six Facebook profiles. Profiles were populated with 1) solely professional material, 2) personal material that was strictly healthy, or 3) personal material that included unhealthy behavior. Profiles portrayed a male or female physician resulting in a total of six experimental conditions. Medical professionalism was measured with the First Impressions of Medical Professionalism (FIMP) scale, specifically developed for this study. There was a large and statistically significant main effect for profile type, F(2, 250)=54.77, p<0.001, ηp(2)=0.31. Post hoc tests indicated that personal profiles that contained healthy behavior were rated as most professional followed by profiles with strictly professional content. Personal unhealthy profiles were rated as least professional. Additionally, female profiles consistently received higher professionalism ratings across all three profile types [F(1, 250)=5.04, p=0.026, ηp(2)=0.02]. Our results suggest that a physician's SNS profile affects a patient's perception of that physician's medical professionalism. A personal, healthy profile may augment a patient's perception of that physician's character virtues if the profile content upholds the decorum of the medical field.


Family history, waist circumference and risk of ischemic stroke: A prospective cohort study among Chinese adults.
The associations between genetic factors and waist circumference (WC) with stroke risk have been evaluated in Western studies. However, evidence of this association has rarely been reported in the Chinese population. This study aimed to evaluate the association between WC and family history of stroke (FHS) with ischemic stroke (IS) risk among Chinese adults and to further explore the potential interaction of these associations. The China Kadoorie Biobank (CKB) study recruited 35,508 participants aged 30-79 years from the Qingdao urban area during 2004-2008. A total of 33,355 participants were included in study. Cox regression analysis was used to estimate the multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the independent and interactional associations between FHS and WC and IS risk. Participants with FHS had a 29% (HR = 1.29, 95% CI: 1.12-1.50) higher IS risk than those without FHS. Participants with excessive WC (85 cm for males and 80 cm for females) had a 78% (HR = 1.78, 95% CI: 1.51-2.10) higher IS risk than those with normal WC. The combined effect of FHS and excessive WC on IS was statistically significant (HR = 2.29, 95% CI: 1.84-2.86). The present study further found statistically significant multiplicative interactions of FHS and WC with IS risk (Pinteraction < 0.001). The present study indicated that FHS and WC were significantly associated with an increased risk of IS. The association between FHS and IS was associated with excessive WC.


Evaluating data capture methods for the establishment of diagnostic reference levels in CT scanning.
Concerns about the radiation dose associated with CT scanning have led to a call for establishment of diagnostic reference levels. Self-complete surveys have been used extensively to gather this information, however, departmental Radiological Information System's/Picture Archive Communication Systems (RIS/PACS) also hold this information. We compared dosimetry derived from survey with that using RIS/PACSs. Technical data were collected from a large metropolitan tertiary hospital in WA using both data collection methods for a range of adult CT scanning examinations. Radiation dose was calculated from both datasets and the results evaluated for several indexes of inter-rater agreement. Radiation dose calculated using self-report survey data differed both systematically and proportionally from that calculated using RIS/PACS data. Differences were not consistent across CT examination type and thus not amenable to simple correction. The disparity was greater and more variable for organ dose than effective dose due to reliance of survey data on "generic" anatomical start and stop limits compared with actual data available on RIS/PACS. The bias observed in our study indicates that care should be taken when interpreting the results of studies measuring radiation dose using self-complete surveys. The availability of electronic databases that include information required for the evaluation and monitoring of CT radiation dose provides the opportunity to capture better quality data in a cost-effective manner. We recommend that national and local databases are established that routinely capture these data so as to facilitate the development and monitoring of radiation dose associated with CT scanning.


Decreased Serum Epinephrine in Children With Positive Skin Prick Test.
To evaluate the association between catecholamine levels and skin prick test results among children. Two hundred eight first grade children from one elementary school were invited to participate in this study. Skin prick test (SPT) for six allergens (2 house dust mites, cat, dog, mugwort, and pollen mixture) was performed, and patient demographic information was recorded. The parents were surveyed using questionnaires about rhinitis-related symptoms. Finally, venous blood sampling was done to measure catecholamine levels (epinephrine, norepinephrine, and dopamine) by high-performance liquid chromatography. Out of 208 children, 174 (106 boys and 68 girls) enrolled in this study. Ninety-six of the children (55%) had negative SPT (nonsensitization group), while 78 (45%) had a positive SPT to at least one of six allergens (sensitization group). The diagnosis of chronic rhinitis was more prevalent in the sensitization group (35.9%) than nonsensitization group (26.0%), however the finding was not significant (P=0.186). Epinephrine levels were decreased between the sensitization group compared to the nonsensitization group (P=0.004). There was no difference in norepinephrine and dopamine levels (P>0.05). Epinephrine levels are lower in children with positive SPT compared to controls, however, the level of the catecholamine was not associated with the presence or absence of rhinitis symptoms.


Smartphone as a simple device for visual and on-site detection of fluoride in groundwater.
Developing a portable device for visual and on-site detection of fluoride in groundwater is highly anticipated. In this paper, 2-(tert-butyl-diphenylsilanyloxy)-5-nitro-1H-benzoimidazole (1) has been rationally designed via a silanization reaction for self-calibration detection of fluoride, and the detection limit was calculated as 0.11 μM. The contact of 1 with fluoride would induce the cleavage of Si-O bond and trigger the emergence of excited state intramolecular proton transfer (ESIPT) process, and then the enol-like emission at 437 nm decreased accompanying with the increase of keto-like tautomerism emission at 550 nm. More importantly, considering the demand of field detection for fluoride in groundwater and combining the function of smartphone to obtain the chroma of photos. The chroma value of the fluorescence color changes from blue to yellow could be conveniently determined through a color recognizer application installed in smartphone. The device can accurately reflect the concentration of fluoride by analyzing the chroma value. The test in actual water samples confirmed that the simple device based on smartphone could be used efficiently for visual, on-site and accurate detection of fluoride in groundwater.


BICS01 Mediates Reversible Anti-seizure Effects in Brain Slice Models of Epilepsy.
Drug-resistant epilepsy remains a significant clinical and societal burden, with one third of people with epilepsy continuing to experience seizures despite the availability of around 30 anti-seizure drugs (ASDs). Further, ASDs often have substantial adverse effects, including impacts on learning and memory. Therefore, it is important to develop new ASDs, which may be more potent or better tolerated. Here, we report the preliminary preclinical evaluation of BICS01, a synthetic product based on a natural compound, as a potential ASD. To model seizure-like activity in vitro, we prepared hippocampal slices from adult male Sprague Dawley rats, and elicited epileptiform bursting using high extracellular potassium. BICS01 (200 μM) rapidly and reversibly reduced the frequency of epileptiform bursting but did not change broad measures of network excitability or affect short-term synaptic facilitation. BICS01 was well tolerated following systemic injection at up to 1,000 mg/kg. However, we did not observe any protective effect of systemic BICS01 injection against acute seizures evoked by pentylenetetrazol. These results indicate that BICS01 is able to acutely reduce epileptiform activity in hippocampal networks. Further preclinical development studies to enhance pharmacokinetics and accumulation in the brain, as well as studies to understand the mechanism of action, are now required.


Aromatase and dual aromatase-steroid sulfatase inhibitors from the letrozole and vorozole templates.
Concurrent inhibition of aromatase and steroid sulfatase (STS) may provide a more effective treatment for hormone-dependent breast cancer than monotherapy against individual enzymes, and several dual aromatase-sulfatase inhibitors (DASIs) have been reported. Three aromatase inhibitors with sub-nanomolar potency, better than the benchmark agent letrozole, were designed. To further explore the DASI concept, a new series of letrozole-derived sulfamates and a vorozole-based sulfamate were designed and biologically evaluated in JEG-3 cells to reveal structure-activity relationships. Amongst achiral and racemic compounds, 2-bromo-4-(2-(4-cyanophenyl)-2-(1H-1,2,4-triazol-1-yl)ethyl)phenyl sulfamate is the most potent DASI (aromatase: IC₅₀ =0.87 nM; STS: IC₅₀ =593 nM). The enantiomers of the phenolic precursor to this compound were separated by chiral HPLC and their absolute configuration determined by X-ray crystallography. Following conversion to their corresponding sulfamates, the S-(+)-enantiomer was found to inhibit aromatase and sulfatase most potently (aromatase: IC₅₀ =0.52 nM; STS: IC₅₀ =280 nM). The docking of each enantiomer and other ligands into the aromatase and sulfatase active sites was also investigated.


Sex-Dependent Modulation of Anxiety and Fear by 5-HT1A Receptors in the Bed Nucleus of the Stria Terminalis.
Serotonin (5-hydroxytryptamine; 5-HT) coordinates behavioral responses to stress through a variety of presynaptic and postsynaptic receptors distributed across functionally diverse neuronal networks in the central nervous system. Efferent 5-HT projections from the dorsal raphe nucleus (DRN) to the bed nucleus of the stria terminalis (BNST) are generally thought to enhance anxiety and aversive learning by activating 5-HT2C receptor (5-HT2CR) signaling in the BNST, although an opposing role for postsynaptic 5-HT1A receptors has recently been suggested. In the present study, we sought to delineate a role for postsynaptic 5-HT1A receptors in the BNST in aversive behaviors using a conditional knockdown of the 5-HT1A receptor. Both males and females were tested to dissect out sex-specific effects. We found that male mice have significantly reduced fear memory recall relative to female mice and inactivation of 5-HT1A receptor in the BNST increases contextual fear conditioning in male mice so that they resemble the females. This coincided with an increase in neuronal excitability in males, suggesting that 5-HT1A receptor deletion may enhance contextual fear recall by disinhibiting fear memory circuits in the BNST. Interestingly, 5-HT1A receptor knockdown did not significantly alter anxiety-like behavior in male or female mice, which is in agreement with previous findings that anxiety and fear are modulated by dissociable circuits in the BNST. Overall, these results suggest that BNST 5-HT1A receptors do not significantly alter behavior under basal conditions, but can act as a molecular brake that buffer against excessive activation of aversive circuits in more threatening contexts.


Genomic variation and biogeography of Antarctic haloarchaea.
The genomes of halophilic archaea (haloarchaea) often comprise multiple replicons. Genomic variation in haloarchaea has been linked to viral infection pressure and, in the case of Antarctic communities, can be caused by intergenera gene exchange. To expand understanding of genome variation and biogeography of Antarctic haloarchaea, here we assessed genomic variation between two strains of Halorubrum lacusprofundi that were isolated from Antarctic hypersaline lakes from different regions (Vestfold Hills and Rauer Islands). To assess variation in haloarchaeal populations, including the presence of genomic islands, metagenomes from six hypersaline Antarctic lakes were characterised. The sequence of the largest replicon of each Hrr. lacusprofundi strain (primary replicon) was highly conserved, while each of the strains' two smaller replicons (secondary replicons) were highly variable. Intergenera gene exchange was identified, including the sharing of a type I-B CRISPR system. Evaluation of infectivity of an Antarctic halovirus provided experimental evidence for the differential susceptibility of the strains, bolstering inferences that strain variation is important for modulating interactions with viruses. A relationship was found between genomic structuring and the location of variation within replicons and genomic islands, demonstrating that the way in which haloarchaea accommodate genomic variability relates to replicon structuring. Metagenome read and contig mapping and clustering and scaling analyses demonstrated biogeographical patterning of variation consistent with environment and distance effects. The metagenome data also demonstrated that specific haloarchaeal species dominated the hypersaline systems indicating they are endemic to Antarctica. The study describes how genomic variation manifests in Antarctic-lake haloarchaeal communities and provides the basis for future assessments of Antarctic regional and global biogeography of haloarchaea.


HAase-sensitive dual-targeting irinotecan liposomes enhance the therapeutic efficacy of lung cancer in animals.
Among all cancers, lung cancer is one of the most common and serious types of cancer. It is challenging for site-specific delivery of anticancer therapeutics to tumor cells. Herein, we developed a novel"smart" dual-targeting liposomal platform to respond to the highly expressed hyaluronidase (HAase) in the tumor microenvironment and improve tumor targeting and antitumor efficacy. Methods: In our design, the HA was used as a sensitive linker between a liposomal lipid and long chain PEG block to synthesize three functional conjugates in order to prepare"smart" liposomal platform modified with epidermal growth factor receptor (EGFR) antibody (GE11) and cell-penetrating peptide (TATp). Using irinotecan as a model therapeutic, evaluations were performed on the human lung adenocarcinoma A549 cells as well as the xenografted A549 cancer cells in nude mice. Results: The GE11/HA/TATp-irinotecan liposomes evidently increased the uptake of irinotecan and showed significant antitumor efficacy in the xenografted A549 cancer cells in nude mice by intravenous administration. The mechanisms were defined to be two aspects: GE11 exhibits high affinity for EGFR binding and the degradation of the HA by HAase results in the long-chain PEG removal and exposure of the previously hidden surface-attached TATp to enhance the target cell internalization. Conclusion: Our findings suggest that this functional liposomal platform may provide a novel strategy for treating lung cancers because of effective intracellular delivery.


Frequency calibration in the ArF excimer laser-tuning range using laser-induced fluorescence of NO.
A frequency calibration in the tuning range of the ArF excimer laser near 193 nm was performed. Different electronic spectra of NO were measured by laser-induced fluorescence in a cell and in an oxyacetylene flame. Spectra were measured with a frequency-doubled and Raman-shifted dye laser system and with a tunable ArF excimer laser with a modified configuration. A list of absolute frequencies of the B(2)II(upsilon' = 7) ? X(2)II(upsilon'' = 0) and D(2)Sigma(+)(upsilon' = 0) ? X(2)II(upsilon'' = 1) transitions in this spectral region is given, including a more comprehensive assignment of the latter excitation spectrum.


[Nocebo effects and negative suggestion in anesthesia].
Anesthetists have an impact on patients and healing processes not only through drugs, interventions and therapy but also significantly by their words and personality. A substantial part of observed side effects is caused by nocebo effects and negative suggestion, i.e. by the doctor and the medical surroundings. Every symptom of an illness, side effect or complication can also be induced by the wrong way of talking about it. Patients perceive medical situations, such as an emergency, anesthesia or intensive care as extreme or even as life-threatening. This can induce a natural trance, an altered state of consciousness characterized by increased suggestibility. Suggestions affect mental functions, such as anxiety and pain as well as physical functions. Strong figurative words, ambiguity, misunderstandings, incidental conversations, medical jargon and risk information are prone to generate negative suggestion. Not the informed consent per se but the way it is presented should be under scrutiny. Knowledge about nocebo effects and negative suggestion can help recognize and avoid these more easily. These negative factors depend on the context, i.e. they are strongly influenced by the individual background history and anxieties of the patient and also by the physician-patient relationship. The best protection against harm from informed consent and negative suggestion is a supportive therapeutic relationship.


Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study.
Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in the Netherlands Cohort Study. In 1986, 120,852 Dutch men and women aged 55-69 filled out a questionnaire on diet and other cancer risk factors. After 16.3 years of follow-up, 101 ESCC, 144 EAC, 156 GCA, 460 GNCA cases and 4,035 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Multivariable adjusted incidence rate ratios (RRs) were generally below unity. Total vegetable consumption was nonsignificantly inversely associated with EAC and ESCC risk, but not with GCA and GNCA risk. Significant inverse associations were observed for raw vegetables and EAC risk [RR per 25 g/day: 0.81, 95% confidence interval (CI) 0.68-0.98], and Brassica vegetables and GCA risk (RR per 25 g/day: 0.72, 95% CI 0.54-0.95). Total fruit consumption was associated with a nonsignificantly decreased EAC risk. Citrus fruits were inversely associated with EAC and GCA risk (RRs for highest vs. lowest intake: 0.55, 95% CI 0.31-0.98 and 0.38, 95% CI 0.21-0.69, respectively). Specifically for current smokers, vegetables and possibly also fruits intake was inversely associated with ESCC and EAC risk. Consumption of (specific groups of) vegetables and fruits may protect against subtypes of esophageal and gastric cancer.


Tolterodine extended release is well tolerated in older subjects.
To investigate the tolerability of tolterodine extended release (ER) in older subjects with overactive bladder (OAB). This was a retrospective analysis of pooled data from five large, randomised, double-blind, placebo-controlled trials. Subjects with OAB symptoms, including urinary frequency and urgency (and nocturia in two studies) with or without urgency urinary incontinence, received qd treatment with tolterodine ER (4 mg) or placebo for 8-12 weeks. Data were stratified post hoc by age group: < 65 (n = 2531), 65-74 (n = 1059) and > or = 75 years (n = 573). Tolerability was assessed by evaluating the occurrence of adverse events (AEs). AE occurrences from each study were mapped to the MedDRA coding dictionary of preferred terms. Discontinuation rates were slightly higher among subjects > or = 75 years of age vs. those < 65 years of age; however, this was observed in subjects treated with placebo as well as tolterodine ER. Overall, there were no significant differences in the occurrence of dry mouth, headache, constipation, nausea, urinary tract infection, blurred vision, dry eye, dizziness and micturition disorder in older (65-74 or > or = 75 years) vs. younger (< 65 years) subjects treated with tolterodine ER relative to placebo (treatment x age; all p > 0.1). Dry mouth was the only AE consistently associated with tolterodine ER treatment (< 65 years, 17%; 65-74 years, 16%; > or = 75 years, 15%). The occurrence of all other AEs was < or = 5% in most age and treatment cohorts. Most AEs were mild or moderate in all age and treatment cohorts. The nature and frequency of AEs associated with tolterodine ER treatment were similar across age groups in subjects with OAB, suggesting that tolterodine ER was not associated with an increased risk of AEs in older vs. younger subjects and, thus, is a suitable first-line pharmacotherapy treatment for OAB in this population.


Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016.
The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years. Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests. No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years. Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.


Blockade of senescence-associated microRNA-195 in aged skeletal muscle cells facilitates reprogramming to produce induced pluripotent stem cells.
The low reprogramming efficiency in cells from elderly patients is a challenge that must be overcome. Recently, it has been reported that senescence-associated microRNA (miR)-195 targets Sirtuin 1 (SIRT1) to advance cellular senescence. Thus, we hypothesized that a blockade of miR-195 expression could improve reprogramming efficiency in old skeletal myoblasts (SkMs). We found that miR-195 expression was significantly higher in old SkMs (24 months) isolated from C57BL/6 mice as compared to young SkMs (2 months, 2.3-fold). Expression of SIRT1 and telomerase reverse transcriptase (TERT) was downregulated in old SkMs, and transduction of old SkMs with lentiviral miR-195 inhibitor significantly restored their expression. Furthermore, quantitative in situ hybridization analysis demonstrated significant telomere elongation in old SkMs transduced with anti-miR-195 (1.7-fold increase). It is important to note that blocking miR-195 expression markedly increased the reprogramming efficiency of old SkMs as compared to scramble (2.2-fold increase). Transduction of anti-miR-195 did not alter karyotype or pluripotency marker expression. Induced pluripotent stem cells (iPSCs) from old SkMs transduced with anti-miR-195 successfully formed embryoid bodies that spontaneously differentiated into three germ layers, indicating that deletion of miR-195 does not affect pluripotency in transformed SkMs. In conclusion, this study provided novel evidence that the blockade of age-induced miR-195 is a promising approach for efficient iPSC generation from aging donor subjects, which has the potential for autologous transplantation of iPSCs in elderly patients.


Porous ionic liquids: synthesis and application.
Solidification of fluidic ionic liquids into porous materials yields porous ionic networks that combine the unique characteristics of ionic liquids with the common features of polymers and porous materials. This minireview reports the most recent advances in the design of porous ionic liquids. A summary of the synthesis of ordered and disordered porous ionic liquid-based nanoparticles or membranes with or without templates is provided, together with the new concept of room temperature porous ionic liquids. As a versatile platform for functional materials, porous ionic liquids have shown widespread applications in catalysis, adsorption, sensing, actuation, etc. This new research direction towards ionic liquids chemistry is still in its early stages but has great potential.


Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice.
Recent studies suggest health benefits including protection from cancer after eating fermented foods such as probiotic yogurt, though the mechanisms are not well understood. Here we tested mechanistic hypotheses using two different animal models: the first model studied development of mammary cancer when eating a Westernized diet, and the second studied animals with a genetic predilection to breast cancer. For the first model, outbred Swiss mice were fed a Westernized chow putting them at increased risk for development of mammary tumors. In this Westernized diet model, mammary carcinogenesis was inhibited by routine exposure to Lactobacillus reuteri ATCC-PTA-6475 in drinking water. The second model was FVB strain erbB2 (HER2) mutant mice, genetically susceptible to mammary tumors mimicking breast cancers in humans, being fed a regular (non-Westernized) chow diet. We found that oral supplement with these purified lactic acid bacteria alone was sufficient to inhibit features of mammary neoplasia in both models. The protective mechanism was determined to be microbially-triggered CD4+CD25+ lymphocytes. When isolated and transplanted into other subjects, these L. reuteri-stimulated lymphocytes were sufficient to convey transplantable anti-cancer protection in the cell recipient animals. These data demonstrate that host immune responses to environmental microbes significantly impact and inhibit cancer progression in distal tissues such as mammary glands, even in genetically susceptible mice. This leads us to conclude that consuming fermentative microbes such as L. reuteri may offer a tractable public health approach to help counteract the accumulated dietary and genetic carcinogenic events integral in the Westernized diet and lifestyle.


Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria.
Chloroquine (CQ)-resistant Plasmodium vivax malaria was first reported 12 years ago, nearly 30 years after the recognition of CQ-resistant P. falciparum. Loss of CQ efficacy now poses a severe problem for the prevention and treatment of both diseases. Mutations in a digestive vacuole protein encoded by a 13-exon gene, pfcrt, were shown recently to have a central role in the CQ resistance (CQR) of P. falciparum. Whether mutations in pfcrt orthologues of other Plasmodium species are involved in CQR remains an open question. This report describes pfcrt homologues from P. vivax, P. knowlesi, P. berghei, and Dictyostelium discoideum. Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a survey of patient isolates and monkey-adapted lines has shown no association between in vivo CQR and codon mutations in the P. vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum.


A multi-sample based method for identifying common CNVs in normal human genomic structure using high-resolution aCGH data.
It is difficult to identify copy number variations (CNV) in normal human genomic data due to noise and non-linear relationships between different genomic regions and signal intensity. A high-resolution array comparative genomic hybridization (aCGH) containing 42 million probes, which is very large compared to previous arrays, was recently published. Most existing CNV detection algorithms do not work well because of noise associated with the large amount of input data and because most of the current methods were not designed to analyze normal human samples. Normal human genome analysis often requires a joint approach across multiple samples. However, the majority of existing methods can only identify CNVs from a single sample. We developed a multi-sample-based genomic variations detector (MGVD) that uses segmentation to identify common breakpoints across multiple samples and a k-means-based clustering strategy. Unlike previous methods, MGVD simultaneously considers multiple samples with different genomic intensities and identifies CNVs and CNV zones (CNVZs); CNVZ is a more precise measure of the location of a genomic variant than the CNV region (CNVR). We designed a specialized algorithm to detect common CNVs from extremely high-resolution multi-sample aCGH data. MGVD showed high sensitivity and a low false discovery rate for a simulated data set, and outperformed most current methods when real, high-resolution HapMap datasets were analyzed. MGVD also had the fastest runtime compared to the other algorithms evaluated when actual, high-resolution aCGH data were analyzed. The CNVZs identified by MGVD can be used in association studies for revealing relationships between phenotypes and genomic aberrations. Our algorithm was developed with standard C++ and is available in Linux and MS Windows format in the STL library. It is freely available at: http://embio.yonsei.ac.kr/~Park/mgvd.php.


Low blood pressure and adverse outcomes in acute stroke: HeadPoST study explanations.
As uncertainties exist over underlying causes, we aimed to define the characteristics and prognostic significance of low blood pressure (BP) early after the onset of acute stroke. Post hoc analyzes of the international Head Positioning in acute Stroke Trial (HeadPoST), a pragmatic cluster-crossover randomized trial of lying flat versus sitting up in stroke patients from nine countries during 2015-2016. Associations of baseline BP and death or dependency [modified Rankin scale (mRS) scores 3-6] and serious adverse events (SAEs) at 90 days were assessed in generalized linear mixed models with adjustment for multiple confounders. SBP and DBP was analysed as continuous measures fitted with a cubic spline, and as categorical measures with low (<10th percentile) and high (≥140 and ≥90 mmHg, respectively) levels compared with a normal range (≥10th percentile; 120-139 and 70-89 mmHg, respectively). Among 11 083 patients (mean age 68 years, 39.9% women) with baseline BP values, 7.2 and 11.7% had low SBP (<120 mmHg) and DBP (<70 mmHg), respectively. Patients with low SBP were more likely to have preexisting cardiac and ischemic stroke and functional impairment, and to present earlier with more severe neurological impairment than other patients. Nonlinear 'J-shaped' relationships of BP and poor outcome were apparent: compared with normal SBP, those with low SBP had worse functional outcome (adjusted odds ratio 1.27, 95% confidence interval 1.02-1.58) and more SAEs, particularly cardiac events, with adjustment for potential confounders to minimize reverse causation. The findings were consistent for DBP and were stronger for ischemic rather than hemorrhagic stroke. The prognostic significance of low BP on poor outcomes in acute stroke was not explained by reverse causality from preexisting cardiovascular disease, and propensity towards greater neurological deficits and cardiac events. These findings provide support for the hypothesis that low BP exacerbates cardiac and cerebral ischemia in acute ischemic stroke.


Electric vagal nerve stimulation inhibits inflammation and improves early postoperation cognitive dysfunction in aged rats.
This study aimed to evaluate effects of electric vagal nerve stimulation on early postoperation cognitive dysfunction in aged rats. A total of 33 male Sprague Dawley rats were selected and assigned randomly to three groups, control group (C, n = 10), splenectomy group (S, n = 10) and splenectomy+vagal nerve stimulation group (SV, n = 13). Behavior and memory of rats were evaluated by Open Field Test and Morris Water Maze. Levels of TNF-α, IL-6 and IL-10 in serum were measured by ELISA. The level of TNF-α protein in hippocampus was assessed by Western blotting. rt-PCR was used to detect mRNA expression of NF-κB in hippocampus. During anesthesia/operation, vital life signs of rats were stable. In SV group, vagal nerve stimulation decreased heart rate lower than 10% of basic level and kept it at a stable range by regulating stimulation intensity. After stimulation stop, heart rate returned to the basic level again. This indicated that the model of vagal nerve stimulation was successful. Serum levels of TNF-α and IL-6 increased by the operation/anesthesia, but they decreased with vagal nerve stimulation (all P < 0.05). TNF-α protein and mRNA expression of NF-κB in hippocampus were also eliminated by vagal nerve stimulation compared to S group (P < 0.05). Results of Morris Water Maze showed escape latency of postoperation in S group was significantly longer than C group (P < 0.05), and times of crossing platform in S group was lower than that of C group (P < 0.05). Although escape latency of postopration in SV group was shorter than that of S group, there was no significant difference between two groups. Meanwhile there were no significant differences of behavior test in Open Field test between three groups, although vagal nerve stimulation improved partly active explore behavior compared to S group. The inflammation caused by operation and general anesthesia was an important reason of early postoperation cognitive dysfunction, and electric vagal nerve stimulation could inhibit the inflammation. Meanwhile, vagal nerve stimulation could ameliorate early postoperation cognitive dysfunction partly, but its protective effects were not enough and should be studied and improved in future.


Unmasking the Practices of Nurses and Intercultural Health in Sub-Saharan Africa: A Useful Way to Improve Health Care?
In 2001 and 2013, the World Health Organization (WHO) published the WHO Traditional Medicine Strategy 2002-2005 and 2014-2023, respectively, to address policy, ethics, quality, and integration of complementary health therapies (CHT). Despite the adoption of these strategic frameworks, sub-Saharan African (SSA) countries largely run dualistic and inclusive health care system. A recent article published in Complementary Therapies in Clinical Practice analyzed the role of practicing nurses in CHT integration and intercultural health in an SSA country setting. Drawing on the Complementary and Alternative Medicine Health Belief Questionnaire, the study specifically examined nurses' knowledge, practices, and attitudes toward CHT. The study revealed that nurses had low knowledge about CHT, which reflected in their ineptitude to engage in professional practices of CHT. In spite of the knowledge deficit, nurses generally held favorable attitudes toward CHT and the majority supported the need for "safe" and evidence-based integrative model. Efforts to improve CHT-related knowledge of nurses may enhance medical integration in SSA. This commentary proposes novel political will and investment in CHT education and research as well as an inclusion of CHT modules in the nurses' training programs; viabilities to achieve intercultural health and improved care in SSA.


Acupuncture for fibromyalgia--a systematic review of randomized clinical trials.
Acupuncture is often used and frequently advocated for the symptomatic treatment of fibromyalgia. A systematic review has previously demonstrated encouraging findings. As it is now outdated, we wanted to update it. We searched seven electronic databases for relevant randomized clinical trials (RCTs). The data were extracted and validated independently by both authors. As no meta-analysis seemed possible, the results were evaluated in narrative form. Five RCTs met our inclusion criteria, all of which used acupuncture as an adjunct to conventional treatments. Their methodological quality was mixed and frequently low. Three RCTs suggested positive but mostly short-lived effects and two yielded negative results. There was no significant difference between the quality of the negative and the positive RCTs. All positive RCTs used electro-acupunture. The notion that acupuncture is an effective symptomatic treatment for fibromyaligia is not supported by the results from rigorous clinical trials. On the basis of this evidence, acupuncture cannot be recommended for fibromyalgia.


Single-resonance optical pumping spectroscopy and application in dressed-state measurement with atomic vapor cell at room temperature.
By monitoring the transmission of probe laser beam (also served as coupling laser beam) which is locked to a cycling hyperfine transition of cesium D(2) line, while pumping laser is scanned across cesium D(1) or D(2) lines, the single-resonance optical pumping (SROP) spectra are obtained with atomic vapor cell. The SROP spectra indicate the variation of the zero-velocity atoms population of one hyperfine fold of ground state, which is optically pumped into another hyperfine fold of ground state by pumping laser. With the virtue of Doppler-free linewidth, high signal-to-noise ratio (SNR), flat background and elimination of crossover resonance lines (CRLs), the SROP spectra with atomic vapor cell around room temperature can be employed to measure dressed-state splitting of ground state, which is normally detected with laser-cooled atomic sample only, even if the dressed-state splitting is much smaller than the Doppler-broaden linewidth at room temperature.


In vitro and in vivo toxicity evaluation of halloysite nanotubes.
Because of their outstanding properties, increasing numbers of research studies and emerging applications for manufacturing products are currently in progress for halloysite nanotubes (HNTs). Therefore, the impact of HNTs on the environment and human health should be taken into consideration. In order to clearly show the cell uptake of HNTs and the biodistribution of HNTs in zebrafish, HNTs are labeled with fluorescein isothiocyanate (FITC-HNTs). The cytotoxicity assays showed that the cell viabilities of human umbilical vein endothelial cells (HUVECs) and human breast adenocarcinoma (MCF-7) cells were above 60% after being treated with different concentrations of HNTs (2.5-200 μg mL-1) for 72 h. Confocal laser scanning microscopy (CLSM) results showed the uptake of HNTs by HUVECs and MCF-7 cells. The in vivo toxicity of HNTs was then investigated in the early development of zebrafish embryos. The percent survival of zebrafish embryos and larvae showed no significant changes at different developmental stages (24, 48, 72, 96, and 120 hpf) when treated with various concentrations of HNTs (0.25-10 mg mL-1). Besides, HNTs could promote the hatchability of zebrafish embryos and did not affect the morphological development of zebrafish at a concentration of ≤25 mg mL-1. HNTs could also be ingested by zebrafish larvae and accumulated predominantly in the gastrointestinal tract. The fluorescence intensity of FITC-HNTs decreased gradually with time, which suggested that HNTs could be excreted by zebrafish larvae through the gastrointestinal metabolism. Therefore, it can be concluded that HNTs are relatively biocompatible nanomaterials, which can be utilized in many fields.


A unifying mechanism for the biogenesis of membrane proteins co-operatively integrated by the Sec and Tat pathways.
The majority of multi-spanning membrane proteins are co-translationally inserted into the bilayer by the Sec pathway. An important subset of membrane proteins have globular, cofactor-containing extracytoplasmic domains requiring the dual action of the co-translational Sec and post-translational Tat pathways for integration. Here, we identify further unexplored families of membrane proteins that are dual Sec-Tat-targeted. We establish that a predicted heme-molybdenum cofactor-containing protein, and a complex polyferredoxin, each require the concerted action of two translocases for their assembly. We determine that the mechanism of handover from Sec to Tat pathway requires the relatively low hydrophobicity of the Tat-dependent transmembrane domain. This, coupled with the presence of C-terminal positive charges, results in abortive insertion of this transmembrane domain by the Sec pathway and its subsequent release at the cytoplasmic side of the membrane. Together, our data points to a simple unifying mechanism governing the assembly of dual targeted membrane proteins.


Extinction bursts in rats trained to self-administer nicotine or food in 1-h daily sessions.
Extinction bursts are characterized by a temporary increase in responding when drug access is withheld from rats trained to self-administer drugs of abuse. Thus far, one study has examined extinction bursts for nicotine self-administration using a 23-h access paradigm [1]. Here we examined extinction bursts using previously published and unpublished data in which rats were trained to self-administer nicotine (0.03mg/kg/infusion) or food pellets (as a comparator) in 1-h sessions under an FR5 schedule of reinforcement followed by 1-h extinction sessions. Analysis of response rates during nicotine self-administration (NSA) was indicative of a loading phase, as response rates were significantly higher at the beginning of the session, which was not observed for food self-administration. At the start of extinction for both food and nicotine, although sessional response rates did not increase, there was an increase in response rate during the first 5-min of the first extinction session relative to self-administration. This transient extinction burst following nicotine was observed in a minority of subjects and correlated with the number of nicotine infusions obtained during self-administration. This transient extinction burst following food was observed in all subjects. Nicotine and food produce more transient extinction bursts compared to other drugs of abuse and only for a minority of animals in the case of nicotine. This study supports the presence of a loading phase in rats trained to self-administer nicotine in 1-r daily sessions and the presence of a transient extinction burst.