Proteomic Analysis of Desiccation Tolerance and Its Re-Establishment in Different Embryo Axis Tissues of Germinated Pea Seeds.
The model of loss and re-establishment of desiccation tolerance (DT) in germinated seeds has been well developed to explore the mechanisms associated with DT, but little attention has been paid to the tissue variation in this model. Herein, we investigated DT in different embryo axis tissues of germinated pea seeds and its re-establishment by poly(ethylene glycol) (PEG) treatment and then employed an iTRAQ-based proteomic method to explore the underlying mechanisms. DT varied among the four embryo axis parts of germinated seeds: epicotyl > hypocotyl-E (hypocotyl part attached to the epicotyl) > hypocotyl-R (hypocotyl part attached to the radicle) > radicle. Meanwhile, PEG treatment of germinated seeds resulted in a differential extent of DT re-establishment in these tissues. Proteins involved in detoxification and stress response were enriched in desiccation-tolerant hypocotyls-E and epicotyls of germinated seeds, respectively. Upon rehydration, proteome change during dehydration was recovered in the hypocotyls-E but not in the radicles. PEG treatment of germinated seeds led to numerous changes in proteins, in abundance in desiccation-sensitive radicles and hypocotyls-R, of which many accumulated in the hypocotyls-E and epicotyls before the treatment. We hypothesized that accumulation of groups 1 and 5 LEA proteins and proteins related to detoxification, ABA, ethylene, and calcium signaling contributed mainly to the variation of DT in different tissues and its re-establishment.


Thinking about multiple identities boosts children's flexible thinking.
Studies of children's developing social identification often focus on individual forms of identity. Yet, everyone has multiple potential identities. Here we investigated whether making children aware of their multifaceted identities-effectively seeing themselves from multiple angles-would promote their flexible thinking. In Experiment 1, 6- to 7-year-old children (N = 48) were assigned to either a Multiple-Identities condition where they were led to consider their multiple identities (e.g. friend, neighbor) or to a Physical-Traits condition where they considered their multiple physical attributes (e.g. legs, arms). Children in the Multiple-Identity condition subsequently expressed greater flexibility at problem-solving and categorization than children in the Physical-Traits condition. Experiment 2 (N = 72) replicated these findings with a new sample of 6- to 7-year-old children and demonstrated that a Multiple-Identity mindset must be self-relevant. Children who were led to think about another child's multiple identities did not express as much subsequent creative thinking as did children who thought about their own multiple identities. Experiment 3 (N = 76) showed that a Mmultiple-Identity framework may be particularly effective when the identities are presented via generic language suggesting that they are enduring traits (in this case, identities depicted as noun phrases rather than verbal phrases). These findings illustrate that something as simple as thinking about one's identity from multiple angles could serve as a tool to help reduce rigid thinking, which might increase open-mindedness in a society that is becoming increasingly diverse.


The effects of intracortical endothelin-1 injections on skilled forelimb use: implications for modelling recovery of function after stroke.
Different methods of inducing experimental brain lesions can result in distinct neuropathological sequelae. This could be of consequence in attempts to establish animal models of recovery of function following stroke, as differences in the progression of experimental lesion pathology may have an impact on the magnitude and rate of recovery of function observable with any particular lesioning method. In the present study, a novel method of producing a focal ischaemic lesion by intracortical microinjection of endothelin-1 (ET-1) was compared with excitotoxic (microinjection of quinolinic acid) and mechanical (aspiration) lesioning procedures. Lesions were unilateral and were targeted at the forelimb representation zone in sensorimotor cortex. It was found that all three types of lesion had an essentially identical effect with regard to reaching accuracy in a paw-reaching task. All lesioned animals displayed a similar, significant long-term deficit in reaching accuracy and limited degree of recovery relative to sham animals. Off-line analysis of the performance of animals during post-lesion week 9 indicated that animals in each lesion group also displayed a similar deficit. The current results suggest that the spontaneous behavioural consequences of a unilateral lesion of FL in the rat appear to be independent of the nature of lesion production. However, the increased face validity of an ET-1-induced lesion, coupled with the ease of control of lesion placement and extent offered by this technique make for a potentially important animal model for research into drug effects on recovery of function following stroke.


How has Advanced Practice Nursing Influenced the Nursing Profession in Canada?
The Special Focus on Advanced Practice Nursing in Canada, published in the Canadian Journal of Nursing Leadership (http://www.longwoods.com/publications/nursing-leadership/24885), highlights the unique contributions that advanced practice nurses (APNs) have added to meet the demands of the evolving Canadian healthcare system. Drs. Martin-Misener and Bryant-Lukosius should be commended for their vision as editors of this Special Issue of CJNL, and profiling some excellent work that has occurred across the country in this field of research. In light of this Special Issue, this commentary is written to offer some reflections upon how APNs (i.e., nurse practitioners, clinical nurse specialists) have influenced the nursing profession more broadly within the Canadian context.


Is There Value in Molecular Profiling of Soft-Tissue Sarcoma?
Soft-tissue sarcomas represent a heterogeneous group of diseases accounting for up to 1% of cancer in adults and 15% of cancer in children. Introduction of next-generation sequencing (NGS) technologies has allowed to gain additional insight into the genetic diversity and complexity of sarcomas, including the potential therapeutic implications of some genetic alterations.Two large studies have investigated the role of targeted NGS to identify actionable mutations in patients with soft-tissue sarcomas. In these two studies, actionable alterations were identified in up to 50% of patients. Retrospective data suggest that genomically guided treatments may be associated with substantial clinical benefit in sarcoma patients with advanced disease. However, prospective data are lacking. The MULTISARC is a randomized phase 3 investigating the potential of NGS implementation to improve outcome of metastatic sarcoma patients.Overall, a significant proportion of soft-tissue sarcoma bears potential targetable genomic alteration that can be identified through NGS. There is still a lack of evidence to support routine implementation of NGS for the management of sarcoma patient. The MULTISARC randomized trial which randomized patients to tumor genetic profiling or not might confirm the role of NGS to improve outcome of metastatic sarcoma patients through the identification of additional genomically guided lines of treatment.


Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives.
Chrysin, a naturally occurring flavone, abundantly found in numerous plant extracts including propolis and in honey is one of the most widely used herbal medicine in Asian countries. Nowadays, chrysin has become the foremost candidate exhibiting health benefits, owing to its multiple bioactivities such as antioxidant, anti-inflammatory, anti-allergic, anti-diabetic, anti-estrogenic, antibacterial and antitumor activities. Anticancer activity is most promising among the multiple pharmacological effects displayed by chrysin. In vitro and in vivo models have shown that chrysin inhibits cancer growth through induction of apoptosis, alteration of cell cycle and inhibition of angiogenesis, invasion and metastasis without causing any toxicity and undesirable side effects to normal cells. Chrysin displays these effects through selective modulation of multiple cell signaling pathways which are linked to inflammation, survival, growth, angiogenesis, invasion and metastasis of cancer cells. This broad spectrum of antitumor activity in conjunction with low toxicity underscores the translational value of chrysin in cancer therapy. The present review highlights the chemopreventive and therapeutic effects, molecular targets and antineoplastic mechanisms that contribute to the observed anticancer activity of chrysin.


Designs of devices: the vacuum aspirator and American abortion technology.
In 1965, 71% of legal abortions in the United States were performed using the surgical procedure of dilation and curettage. By 1972, a mere seven years later, approximately the same percentage (72.6%) of legal abortions in the United States were performed using a completely new abortion technology: the electrical vacuum aspirator. This article examines why, in less than a decade, electric vacuum suction became American physicians' abortion technology of choice. It focuses on factors such as political and professional feasibility (the technology was able to complement the decriminalization of abortion in the US, and the interests, abilities, commitments, and personal beliefs of physicians); clinical compatibility (it met physician/patient criteria such as safety, simplicity and effectiveness); and economic viability (it was able to adapt to market factors such as production, cost, supply/demand, availability, and distribution).


Shearing interferometers for testing corner cubes and right angle prisms.
A wavefront reversing interferometer and an inverting interferometer are described for use in testing corner cubes and right angle prisms. Both the interferometers are stable, easy to adjust, and require comparatively simple setup. They have adequate sensitivity for measuring the divergence of the reflected wavefronts, but do not give directly the symmetrical errors of the prisms. With the inverting interferometer, the latter can be determined by changing the shear. Methods are suggested for testing the prisms during manufacture and correcting their defects by use of these interferometers.


Non-allergic eosinophilic inflammation.
Much is known about the eosinophilic processes associated with antigens, tumors, and infection, yet data on other causes of eosinophilic inflammation are scarce. This paper investigates the locations and causes of other nonrespiratory eosinophilic inflammation. Although eosinophilic inflammation can involve locomotor, urinary, cardiovascular, nervous, gastrointestinal, and other mucosal surfaces, such inflammation also can accompany tissue trauma, foreign-body reactions, and necrotic or granulomatous processes. Despite their cytolytic/histolytic effects, eosinophil leukocytes are a component of tissue remodeling, can be antigen-presenting cells, and have a role in the reproductive system and in blood coagulation. The study of various types of eosinophilic inflammation may increase our understanding of the biological responses of eosinophil leukocytes to different inflammatory stimuli.


How Accurately Can Extended X-ray Absorption Spectra Be Predicted from First Principles? Implications for Modeling the Oxygen-Evolving Complex in Photosystem II.
First principle calculations of extended X-ray absorption fine structure (EXAFS) data have seen widespread use in bioinorganic chemistry, perhaps most notably for modeling the Mn4Ca site in the oxygen evolving complex (OEC) of photosystem II (PSII). The logic implied by the calculations rests on the assumption that it is possible to a priori predict an accurate EXAFS spectrum provided that the underlying geometric structure is correct. The present study investigates the extent to which this is possible using state of the art EXAFS theory. The FEFF program is used to evaluate the ability of a multiple scattering-based approach to directly calculate the EXAFS spectrum of crystallographically defined model complexes. The results of these parameter free predictions are compared with the more traditional approach of fitting FEFF calculated spectra to experimental data. A series of seven crystallographically characterized Mn monomers and dimers is used as a test set. The largest deviations between the FEFF calculated EXAFS spectra and the experimental EXAFS spectra arise from the amplitudes. The amplitude errors result from a combination of errors in calculated S0(2) and Debye-Waller values as well as uncertainties in background subtraction. Additional errors may be attributed to structural parameters, particularly in cases where reliable high-resolution crystal structures are not available. Based on these investigations, the strengths and weaknesses of using first-principle EXAFS calculations as a predictive tool are discussed. We demonstrate that a range of DFT optimized structures of the OEC may all be considered consistent with experimental EXAFS data and that caution must be exercised when using EXAFS data to obtain topological arrangements of complex clusters.


Dehydrogenation of formic acid by Ir-bisMETAMORPhos complexes: experimental and computational insight into the role of a cooperative ligand.
The synthesis and tautomeric nature of three xanthene-based bisMETAMORPhos ligands (La-Lc) is reported. Coordination of these bis(sulfonamidophosphines) to Ir(acac)(cod) initially leads to the formation of IrI(LH) species (1a), which convert via formal oxidative addition of the ligand to IrIII(L) monohydride complexes 2a-c. The rate for this step strongly depends on the ligand employed. IrIII complexes 2a-c were applied in the base-free dehydrogenation of formic acid, reaching turnover frequencies of 3090, 877 and 1791 h-1, respectively. The dual role of the ligand in the mechanism of the dehydrogenation reaction was studied by 1H and 31P NMR spectroscopy and DFT calculations. Besides functioning as an internal base, bisMETAMORPhos also assists in the pre-assembly of formic acid within the Ir-coordination sphere and aids in stabilizing the rate-determining transition state through hydrogen-bonding.


Comparative Genomics of Staphylococcus Reveals Determinants of Speciation and Diversification of Antimicrobial Defense.
The bacterial genus Staphylococcus comprises diverse species with most being described as colonizers of human and animal skin. A relational analysis of features that discriminate its species and contribute to niche adaptation and survival remains to be fully described. In this study, an interspecies, whole-genome comparative analysis of 21 Staphylococcus species was performed based on their orthologues. Three well-defined multi-species groups were identified: group A (including aureus/epidermidis); group B (including saprophyticus/xylosus) and group C (including pseudintermedius/delphini). The machine learning algorithm Random Forest was applied to prioritize orthologs that drive formation of the Staphylococcus species groups A-C. Orthologues driving staphylococcal intrageneric diversity comprised regulatory, metabolic and antimicrobial resistance proteins. Notably, the BraSR (NsaRS) two-component system (TCS) and its associated BraDE transporters that regulate antimicrobial resistance showed limited distribution in the genus and their presence was most closely associated with a subset of Staphylococcus species dominated by those that colonize human skin. Divergence of BraSR and GraSR antimicrobial peptide survival TCS and their associated transporters was observed across the staphylococci, likely reflecting niche specific evolution of these TCS/transporters and their specificities for AMPs. Experimental evolution, with selection for resistance to the lantibiotic nisin, revealed multiple routes to resistance and differences in the selection outcomes of the BraSR-positive species S. hominis and S. aureus. Selection supported a role for GraSR in nisin survival responses of the BraSR-negative species S. saprophyticus. Our study reveals diversification of antimicrobial-sensing TCS across the staphylococci and hints at differential relationships between GraSR and BraSR in those species positive for both TCS.


DNA Barcoding a Complete Matrix of Stereoisomeric Small Molecules.
It is challenging to incorporate stereochemical diversity and topographic complexity into DNA-encoded libraries (DELs) because DEL syntheses cannot fully exploit the capabilities of modern synthetic organic chemistry. Here, we describe the design, construction, and validation of DOS-DEL-1, a library of 107 616 DNA-barcoded chiral 2,3-disubsituted azetidines and pyrrolidines. We used stereospecific C-H arylation chemistry to furnish complex scaffolds primed for DEL synthesis, and we developed an improved on-DNA Suzuki reaction to maximize library quality. We then studied both the structural diversity of the library and the physicochemical properties of individual compounds using Tanimoto multifusion similarity analysis, among other techniques. These analyses revealed not only that most DOS-DEL-1 members have "drug-like" properties, but also that the library more closely resembles compound collections derived from diversity synthesis than those from other sources (e.g., commercial vendors). Finally, we performed validation screens against horseradish peroxidase and carbonic anhydrase IX, and we developed a novel, Poisson-based statistical framework to analyze the results. A set of assay positives were successfully translated into potent carbonic anhydrase inhibitors (IC50 = 20.1-68.7 nM), which confirmed the success of the synthesis and screening procedures. These results establish a strategy to synthesize DELs with scaffold-based stereochemical diversity and complexity that does not require the development of novel DNA-compatible chemistry.


Reducing temperature dependence of the output energy of a quasi-continuous wave diode-pumped Nd:YAG laser.
It is demonstrated by numerical modeling that spectrally dispersed compound pumping diodes and low-loss pumping chamber reduced the temperature dependence of the output energy of quasi-continuous wave diode-pumped Nd:YAG lasers considerably. Several compound diodes with different spectral profiles were tested for pumping. The laser energy was calculated as a function of diode temperature from -30°C to 60°C. When a compound diode with a flat-top spectrum was used for pumping, the mean laser energy was 83% of the maximum energy of a Nd:YAG laser pumped by a diode with a narrow bandwidth. In addition, a compound diode with three emission lines was tested for pumping. When the wavelength gap between the adjacent emission lines of the pumping diode was in the range of 3-10 nm, the mean energy of the Nd:YAG laser became similar to that of a Nd:YAG laser pumped by a diode with a flat-top spectrum.


Using natural language processing and machine learning to identify gout flares from electronic clinical notes.
Gout flares are not well documented by diagnosis codes, making it difficult to conduct accurate database studies. We implemented a computer-based method to automatically identify gout flares using natural language processing (NLP) and machine learning (ML) from electronic clinical notes. Of 16,519 patients, 1,264 and 1,192 clinical notes from 2 separate sets of 100 patients were selected as the training and evaluation data sets, respectively, which were reviewed by rheumatologists. We created separate NLP searches to capture different aspects of gout flares. For each note, the NLP search outputs became the ML system inputs, which provided the final classification decisions. The note-level classifications were grouped into patient-level gout flares. Our NLP+ML results were validated using a gold standard data set and compared with the claims-based method used by prior literatures. For 16,519 patients with a diagnosis of gout and a prescription for a urate-lowering therapy, we identified 18,869 clinical notes as gout flare positive (sensitivity 82.1%, specificity 91.5%): 1,402 patients with ≥3 flares (sensitivity 93.5%, specificity 84.6%), 5,954 with 1 or 2 flares, and 9,163 with no flare (sensitivity 98.5%, specificity 96.4%). Our method identified more flare cases (18,869 versus 7,861) and patients with ≥3 flares (1,402 versus 516) when compared to the claims-based method. We developed a computer-based method (NLP and ML) to identify gout flares from the clinical notes. Our method was validated as an accurate tool for identifying gout flares with higher sensitivity and specificity compared to previous studies.


Cerebellar synaptic protein expression in schizophrenia.
A cortico-subcortico-cerebellar neural circuit has been postulated to be important in the pathophysiology of schizophrenia. This study investigated whether there are synaptic changes in the cerebellum to accompany its putative involvement in the disorder. We measured the expression of three synaptic proteins (synaptophysin, complexin I and complexin II) in the cerebellar cortex of 16 subjects with schizophrenia and 16 controls using in situ hybridisation histochemistry and immunoautoradiography. Complexin I and II are expressed predominantly by inhibitory and excitatory neurones respectively. In schizophrenia, synaptophysin mRNA was decreased, as was complexin II and its mRNA. Complexin I mRNA and protein levels were unaltered. Expression of the mRNAs in the rat cerebellum was unaffected by 2 weeks administration of antipsychotic drugs (haloperidol, chlorpromazine, risperidone, olanzapine or clozapine). We conclude that there is synaptic pathology in the cerebellum in schizophrenia. By disrupting neural circuits, the alterations may contribute to the cerebellar dysfunction thought to occur in the disorder.


Black blood imaging of intracranial vessel walls.
Traditional vascular imaging focuses on non-invasive cross-sectional imaging to assess luminal morphology; however, the vessel wall itself may be specifically involved in many diseases. Newer pulse sequences, and particularly black blood MRI of intracranial vessels, have brought a paradigm shift in understanding the pathophysiology of many vasculopathies. Black blood MRI of intracranial vessel walls can help in a range of pathologies with differing pathophysiology, including intracranial atherosclerosis, aneurysms, vasculitis and vasculopathy, moyamoya disease, dissection and vertebrobasilar hypoplasia. This review highlights how vessel wall imaging can contribute to the clinical diagnosis and management of patients with intracranial vascular pathology.


On-road driving impairments in Huntington disease.
To determine the driving skill impairments and underlying visual, motor, and cognitive deficits that lead to failure on road testing in manifest Huntington disease (HD). Certified driving assessment experts scored performance on 13 specific on-road driving skills in 30 persons with HD and 30 controls and issued a pass/fail decision based on their overall impression. These on-road skill items were mapped onto an existing theoretical framework that categorized driving skills into operational, tactical, visuo-integrative, and mixed clusters. The HD group additionally completed a detailed off-road battery of motor, visual, and neuropsychological tests. The HD group performed worse on all on-road items. Fourteen drivers with HD (47%) failed the road test compared with none of the controls. Scores on the Total Functional Capacity scale discriminated significantly between pass and fail groups. Total on-road score and performance in operational, tactical, and visuo-integrative clusters correlated strongly (Spearman ρ >0.50) with the pass/fail decision. The off-road tests showed variable strengths of association depending on the level of driving skill. Selective attention was strongly associated (Spearman ρ >0.50) with the total on-road score and all driving clusters. HD affects driving at many levels due to motor and cognitive deficits and leads to unsafe road performance even in mild stages. The high failure rate on the road test and difficulties in all aspects of on-road driving suggest that monitoring of fitness to drive should be initiated in the early course of HD.


Validity of the K-10 in detecting DSM-IV-defined depression and anxiety disorders among HIV-infected individuals.
It has been suggested that an HIV diagnosis may increase the likelihood of mental disorders among infected individuals and that the progression of HIV may be hastened by mental disorders like anxiety and depression. Therefore, a brief screening measure, with good sensitivity/specificity for psychiatric diagnoses that could be given to HIV-infected individuals would be useful. We assessed the validity of the K-10, using the MINI International Neuropsychiatric Interview as the gold standard, in a sample of 429 HIV-infected adults enrolled in HIV care and treatment services near Cape Town, South Africa. There was significant agreement between the K-10 and the MINI-defined depressive and anxiety disorders. A receiver operating characteristic (ROC) curve analysis indicated that the K-10 showed agreeable sensitivity and specificity in detecting depression (area under the ROC curve, 0.77), generalized anxiety disorder (0.78), and posttraumatic stress disorder (PTSD) (0.77). The K-10 may be a useful screening measure for detecting mood and anxiety disorders, including PTSD, in patients with HIV/AIDS.


Frugivores bias seed-adult tree associations through nonrandom seed dispersal: a phylogenetic approach.
Frugivores are the main seed dispersers in many ecosystems, such that behaviorally driven, nonrandom patterns of seed dispersal are a common process; but patterns are poorly understood. Characterizing these patterns may be essential for understanding spatial organization of fruiting trees and drivers of seed-dispersal limitation in biodiverse forests. To address this, we studied resulting spatial associations between dispersed seeds and adult tree neighbors in a diverse rainforest in Madagascar, using a temporal and phylogenetic approach. Data show that by using fruiting trees as seed-dispersal foci, frugivores bias seed dispersal under conspecific adults and under heterospecific trees that share dispersers and fruiting time with the dispersed species. Frugivore-mediated seed dispersal also resulted in nonrandom phylogenetic associations of dispersed seeds with their nearest adult neighbors, in nine out of the 16 months of our study. However, these nonrandom phylogenetic associations fluctuated unpredictably over time, ranging from clustered to overdispersed. The spatial and phylogenetic template of seed dispersal did not translate to similar patterns of association in adult tree neighborhoods, suggesting the importance of post-dispersal processes in structuring plant communities. Results suggest that frugivore-mediated seed dispersal is important for structuring early stages of plant-plant associations, setting the template for post-dispersal processes that influence ultimate patterns of plant recruitment. Importantly, if biased patterns of dispersal are common in other systems, frugivores may promote tree coexistence in biodiverse forests by limiting the frequency and diversity of heterospecific interactions of seeds they disperse.


[Long-term seroprotection against Japanese encephalitis using an inactivated vaccine (Jevax)].
Japanese encephalitis vaccine (Jevax) is an inactivated vaccine using the Nakayama viral strain. Until 2007, Jevax was the only Japanese encephalitis vaccine available in France but the duration of seroprotection after vaccination and exact timing of booster injections was unclear for travelers from non-endemic areas. The purpose of this report is to describe the results of a retrospective study in which neutralizing antibody levels were measured in 71 subjects previously vaccinated with Jevax. All subjects underwent testing at the Pasteur Institute Medical Center as part of preparation for humanitarian missions to endemic Japanese encephalitis areas in 2005-2006. A neutralizing antibody level greater than or equal to 20 was considered as protective. Findings showed that 49 of the 71 subjects (69%) still had protective antibody levels at a median of 4 years after the last Jevax immunization. In multivariate analysis, the only factor correlated with long-term seroprotection was the total number of vaccinations received. Based on these findings, it was concluded that long-term seroprotection after Jevax vaccination requires repeated booster injections even in subjects frequently exposed to the virus. No correlation was found between seroprotection and the interval between the booster injections.


Childhood Prevalence of Involvement with the Child Protection System in Quebec: A Longitudinal Study.
The goal of this study, the first of its kind in Canada, was to estimate the child lifetime prevalence of child protection involvement in Quebec. Using administrative and population data spanning 17 years, we performed a survival analysis of initial incidents of child protection reports, confirmed reports, confirmation of a child's security or development being compromised, and placement outside the home for one day or more. We found that before reaching the age of 18 years, over 18% of children were reported to child protection at least once, one in every ten children (10.1%) in the province had a report that led to the finding of their security or development being compromised, and over 5% were placed outside the home. We found that neglect was a primary concern in close to half (47.6%) of cases. By using a full population dataset, we obtained a more accurate prevalence estimate than studies using synthetic cohort life tables. These findings only captured initial incidents of involvement with child protection, meaning this study does not show the extent of recurrent involvement for some children. The findings reflect prior results showing that neglect is common in initial child protection involvement but less pervasive than has been shown in incidence studies, suggesting that recurrent child protection involvement is more driven by neglect than initial incidents are.


Missing contact probing of DNA-protein interactions.
We have examined the positions of contact between lambda phage repressor protein and operator OR1 DNA by scanning populations of lightly depurinated or depyrimidated DNA for bases essential to or irrelevant to repressor binding. This global scanning technique delineates the apparent contact region between lambda repressor and operator and shows bases previously demonstrated or predicted to be contacted plus some additional bases. A mutant repressor, previously shown to contact DNA as wild-type repressor does with the exception of a missing contact to guanosine G4' [Hochschild, A. & Ptashne, M. (1986) Cell 44, 925-933], similarly failed to contact G4' when assayed by this method. Coupled with altering a test residue of a DNA-contacting protein to glycine or alanine so as to eliminate a specific contact, the method appears to provide an efficient means of scanning for specific residue-base contacts.


GATA transcription factors and cardiac development.
Three members of the GATA family of transcription factors, GATA-4, -5, and -6, are expressed in the developing heart. One family member, GATA-5, is restricted to the endocardium while the other two, GATA-4 and -6, are present in the myocardium where they apparently fulfil distinct functions. The mechanisms underlying GATA factor specificity are not fully understood but may involve interaction with other tissue-restricted or ubiquitous co-factors. Thus, combinatorial interaction among GATA factors or between GATA factors and other co-factors may differentially control various stages of cardiogenesis.


III-V Compounds and Alloys: An Update.
The III-V compounds and alloys have been studied for three decades. Until recently, these materials have been commercialized for only a few specialized optoelectronic devices and microwave devices. Advances in thin-film epitaxy techniques, such as liquid phase epitaxy and chemical vapor deposition, are now providing the ability to form good quality lattice-matched heterojunctions with III-V materials. New optoelectronic devices, such as room-temperature continuous-wave injection lasers, have already resulted. This newfound ability may also affect the field of highspeed integrated circuits.


Role of echocardiography for takotsubo cardiomyopathy: clinical and prognostic implications.
Takotsubo cardiomyopathy (TTC) is newly-described secondary cardiomyopathy characterized by transient left ventricular (LV) dysfunction, which is increasingly recognized in the field of cardiology. TTC occurs in approximately 2% of the patients with acute coronary syndrome. Its onset is rare; however, its specific features play a crucial role in diagnosing the chest pain in clinical practice. TTC has generally favorable outcome with rapid recovery of LV function; however, an increasing evidence suggests that it should be regarded as a more serious acute cardiac disorder with a variety of complications. Owing to its widespread availability, even in emergency settings, transthoracic echocardiography plays a key role in the diagnostic assessment of TTC and contributes to an increased number of disease detection and incidence reports in contemporary clinical practice. This review focuses on the role of echocardiography in understanding the clinical prognostic implications in patients with TTC.


The enhanced effect of activated sludge attached to the roots of Pistia stratiotes on nutrient removal for secondary effluent.
Aquatic plants are widely used for treating wastewater treatment plant secondary effluent. During this process, some residual activated sludge in the secondary effluent is intercepted and attaches to the plant roots. However, the effect of the attached activated sludge on nutrient removal in secondary effluent has up to now been unknown. Aiming at this problem, this investigation was conducted to compare the nutrient removal rates in secondary effluent by washed Pistia stratiotes (washed batch) and Pistia stratiotes with activated sludge attached to the roots (study batch). Extracellular polymeric substances (EPS) from the activated sludge attached to the roots were extracted and characterized by three-dimensional excitation emission matrix (3D-EEM) fluorescence spectroscopy. The results showed that the nutrient removal rates in the study batch were better than that in the washed batch. The 3D-EEM results showed that the protein content of EPS increased during the experiment, indicating the growth of microorganisms in the attached activated sludge. Our work demonstrated the enhanced effect of activated sludge attached to the roots of Pistia stratiotes on the removal of pollutants in secondary effluent, which is useful to guide the practical engineering of secondary effluent treatment.


Treatment of pressure ulcers: a clinical practice guideline from the American College of Physicians.
The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations based on the comparative effectiveness of treatments of pressure ulcers. This guideline is based on published literature on this topic that was identified by using MEDLINE, EMBASE, CINAHL, EBM Reviews, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and the Health Technology Assessment database through February 2014. Searches were limited to English-language publications. The outcomes evaluated for this guideline include complete wound healing, wound size (surface area, volume, and depth) reduction, pain, prevention of sepsis, prevention of osteomyelitis, recurrence rate, and harms of treatment (including but not limited to pain, dermatologic complications, bleeding, and infection). This guideline grades the quality of evidence and strength of recommendations by using ACP's clinical practice guidelines grading system. The target audience for this guideline includes all clinicians, and the target patient population is patients with pressure ulcers. ACP recommends that clinicians use protein or amino acid supplementation in patients with pressure ulcers to reduce wound size. (Grade: weak recommendation, low-quality evidence). ACP recommends that clinicians use hydrocolloid or foam dressings in patients with pressure ulcers to reduce wound size. (Grade: weak recommendation, low-quality evidence). ACP recommends that clinicians use electrical stimulation as adjunctive therapy in patients with pressure ulcers to accelerate wound healing. (Grade: weak recommendation, moderate-quality evidence).


Effect of mastication on lipid bioaccessibility of almonds in a randomized human study and its implications for digestion kinetics, metabolizable energy, and postprandial lipemia.
The particle size and structure of masticated almonds have a significant impact on nutrient release (bioaccessibility) and digestion kinetics. The goals of this study were to quantify the effects of mastication on the bioaccessibility of intracellular lipid of almond tissue and examine microstructural characteristics of masticated almonds. In a randomized, subject-blind, crossover trial, 17 healthy subjects chewed natural almonds (NAs) or roasted almonds (RAs) in 4 separate mastication sessions. Particle size distributions (PSDs) of the expectorated boluses were measured by using mechanical sieving and laser diffraction (primary outcome). The microstructure of masticated almonds, including the structural integrity of the cell walls (i.e., dietary fiber), was examined with microscopy. Lipid bioaccessibility was predicted by using a theoretical model, based on almond particle size and cell dimensions, and then compared with empirically derived release data. Intersubject variations (n = 15; 2 subjects withdrew) in PSDs of both NA and RA samples were small (e.g., laser diffraction; CV: 12% and 9%, respectively). Significant differences in PSDs were found between these 2 almond forms (P < 0.05). A small proportion of lipid was released from ruptured cells on fractured surfaces of masticated particles, as predicted by using the mathematical model (8.5% and 11.3% for NAs and RAs, respectively). This low percentage of lipid bioaccessibility is attributable to the high proportion (35-40%) of large particles (>500 μm) in masticated almonds. Microstructural examination of the almonds indicated that most intracellular lipid remained undisturbed in intact cells after mastication. No adverse events were recorded. Following mastication, most of the almond cells remained intact with lipid encapsulated by cell walls. Thus, most of the lipid in masticated almonds is not immediately bioaccessible and remains unavailable for early stages of digestion. The lipid encapsulation mechanism provides a convincing explanation for why almonds have a low metabolizable energy content and an attenuated impact on postprandial lipemia.


A Mixed-Method Design Evaluation of the SAFE Obstetric Anaesthesia Course at 4 and 12-18 Months After Training in the Republic of Congo and Madagascar.
Maternal mortality in low- and middle-income countries (LMICs) is higher than in high-income countries (HICs), and poor anesthesia care is a contributing factor. Many anesthesia complications are considered preventable with adequate training. The Safer Anaesthesia From Education Obstetric Anaesthesia (SAFE-OB) course was designed as a refresher course to upgrade the skills of anesthesia providers in low-income countries, but little is known about the long-term impact of the course on changes in practice. We report changes in practice at 4 and 12-18 months after SAFE-OB courses in Madagascar and the Republic of Congo. We used a concurrent embedded mixed-methods design based on the Kirkpatrick model for evaluating educational training courses. The primary outcome was qualitative determination of personal and organizational change at 4 months and 12-18 months. Secondary outcomes were quantitative evaluations of knowledge and skill retention over time. From 2014 to 2016, 213 participants participated in 5 SAFE-OB courses in 2 countries. Semistructured interviews were conducted at 4 and 12-18 months using purposive sampling and analyzed using thematic content analysis. Participants underwent baseline knowledge and skill assessment, with 1 cohort reevaluated using repeat knowledge and skills tests at 4 months and another at 12-18 months. At 4 months, 2 themes of practice change (Kirkpatrick level 3) emerged that were not present at 12-18 months: neonatal resuscitation and airway management. At 12-18 months, 4 themes emerged: management of obstetric hemorrhage, management of eclampsia, using a structured approach to assessing a pregnant woman, and management of spinal anesthesia. With respect to organizational culture change (Kirkpatrick level 4), the same 3 themes emerged at both 4 and 12-18 months: improved teamwork, communication, and preparation. Resistance from peers, lack of senior support, and lack of resources were cited as barriers to change at 4 months, but at 12-18 months, very few interviewees mentioned lack of resources. Identified catalysts for change were self-motivation, credibility, peer support, and senior support. Knowledge and skills tests both showed an immediate improvement after the course that was sustained. This supports the qualitative responses suggesting personal and organizational change. Participation at a SAFE-OB course in the Republic of Congo and in Madagascar was associated with personal and organizational changes in practice and sustained improvements in knowledge and skill at 12-18 months.


TFmapper: A Tool for Searching Putative Factors Regulating Gene Expression Using ChIP-seq Data.
Background: Next-generation sequencing coupled to chromatin immunoprecipitation (ChIP-seq), DNase I hypersensitivity (DNase-seq) and the transposase-accessible chromatin assay (ATAC-seq) has generated enormous amounts of data, markedly improved our understanding of the transcriptional and epigenetic control of gene expression. To take advantage of the availability of such datasets and provide clues on what factors, including transcription factors, epigenetic regulators and histone modifications, potentially regulates the expression of a gene of interest, a tool for simultaneous queries of multiple datasets using symbols or genomic coordinates as search terms is needed. Results: In this study, we annotated the peaks of thousands of ChIP-seq datasets generated by ENCODE project, or ChIP-seq/DNase-seq/ATAC-seq datasets deposited in Gene Expression Omnibus (GEO) and curated by Cistrome project; We built a MySQL database called TFmapper containing the annotations and associated metadata, allowing users without bioinformatics expertise to search across thousands of datasets to identify factors targeting a genomic region/gene of interest in a specified sample through a web interface. Users can also visualize multiple peaks in genome browsers and download the corresponding sequences. Conclusion: TFmapper will help users explore the vast amount of publicly available ChIP-seq/DNase-seq/ATAC-seq data and perform integrative analyses to understand the regulation of a gene of interest. The web server is freely accessible at http://www.tfmapper.org/.


Do employer-sponsored health insurance schemes affect the utilisation of medically trained providers and out-of-pocket payments among ready-made garment workers? A case-control study in Bangladesh.
We estimated the effect of an employer-sponsored health insurance (ESHI) scheme on healthcare utilisation of medically trained providers and reduction of out-of-pocket (OOP) expenditure among ready-made garment (RMG) workers. We used a case-control study design with cross-sectional preintervention and postintervention surveys. The study was conducted among workers of seven purposively selected RMG factories in Shafipur, Gazipur in Bangladesh. In total, 1924 RMG workers (480 from the insured and 482 from the uninsured, in each period) were surveyed from insured and uninsured RMG factories, respectively, in the preintervention (October 2013) and postintervention (April 2015) period. We tested the effect of a pilot ESHI scheme which was implemented for 1 year. The outcome measures were utilisation of medically trained providers and reduction of OOP expenditure among RMG workers. We estimated difference-in-difference (DiD) and applied two-part regression model to measure the association between healthcare utilisation, OOP payments and ESHI scheme membership while controlling for the socioeconomic characteristics of workers. The ESHI scheme increased healthcare utilisation of medically trained providers by 26.1% (DiD=26.1; p<0.01) among insured workers compared with uninsured workers. While accounting for covariates, the effect on utilisation significantly reduced to 18.4% (p<0.05). The DiD estimate showed that OOP expenditure among insured workers decreased by -3700 Bangladeshi taka and -1100 Bangladeshi taka compared with uninsured workers when using healthcare services from medically trained providers or all provider respectively, although not significant. The multiple two-part models also reported similar results. The ESHI scheme significantly increased utilisation of medically trained providers among RMG workers. However, it has no significant effect on OOP expenditure. It can be recommended that an educational intervention be provided to RMG workers to improve their healthcare-seeking behaviours and increase their utilisation of ESHI-designated healthcare providers while keeping OOP payments low.


Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer.
To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small-cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m(2)) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m(2)) after CPT-11 administration on day 1. Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1-year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32. 7% ) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to < or = 40 mg/m(2) in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies. CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.


Myocarditis and the military patient.
Myocarditis, simply defined as inflammation of the heart muscle, is a commonly encountered cardiac disease in primary and secondary care, both in the UK and on Operational deployments. In the UK Armed Forces, myocarditis results in deaths as well as the premature termination of military careers on medical grounds. The aetiology is usually the result of a number of infectious aetiologies with viruses being the most common pathogens in the vast majority of cases. However, it may also be the result of autoimmune activation, chemical or pharmacological toxins, environmental insult or hypersensitivity reactions. Particular aetiologies that are more likely to be seen in a military population are discussed and include certain infections, smallpox vaccine, and hyperthermia and hypothermia. The clinical features can be highly variable ranging from an asymptomatic infection to fulminant heart failure. Features pertinent to the military doctor, including the natural history, investigative modalities and management strategies, with a particular emphasis on the occupational impact of myocarditis in the UK Armed Forces are reviewed.


Physiological responses to prolonged bed rest and fluid immersion in humans.
Rest in bed and immersion in water have been used for centuries by physicians and healers in treating injury and disease. The qualitative similarity of acute and chronic responses to bed rest, immersion, and weightlessness has sparked renewed interest in and a resultant greater understanding of the mechanisms of disuse deconditioning. Some combination of changes in hydrostatic pressure, reduced total metabolism (exercise), compression force on weight-bearing bones, as well as psychological factors associated with prolonged confinement in a new environment probably comprise the major input stimuli for the adaptive responses. Virtually every physiological system is affected. Early responses involve the fluid, electrolyte, and blood pressure control systems with significant muscular atrophy and decreases in bone density occurring over weeks and months. Much effort has been expended to describe the various responses to bed rest and immersion with understandably less effort devoted to research during weightlessness. Future research should be directed mainly toward an understanding of the mechanisms of these adaptive responses. Additional work is especially needed to elucidate the effects of deconditioning on drug metabolism, functioning of the immune system, carbohydrate metabolism, protein and peptide metabolism in muscle, and calcium metabolism as it affects integrity of bone.


LcrQ blocks the role of LcrF in regulating the Ysc-Yop type III secretion genes in Yersinia pseudotuberculosis.
Pathogenic Yersinia species employ the Ysc-Yop type III secretion system (T3SS) encoded by a highly conserved pYV virulence plasmid to export the virulence effectors into host cells. The Ysc-Yop T3SS is tightly regulated by multiple contributing proteins that function at different levels. However, systematic transcriptional regulation analysis of Ysc-Yop T3SS is lacking and the detailed mechanism under this regulation process is still elusive. Aimed at systematically characterizing transcriptional regulations of all T3SS genes in Y. pseudotuberculosis, we amplified 97 non-coding fragments from the pYV plasmid and analyzed transcriptional responses of the T3SS genes under different growth conditions. Transcriptions of T3SS genes were induced at 37°C and genes encoding T3SS effectors were highly induced by further depletion of Ca2+. The temperature induced gene transcription process is mediated by modules encoded on the chromosome, while the Ca2+ depletion-induced process is controlled by the positive regulatory protein LcrF as well as the negative regulatory protein LcrQ. In this process, LcrQ shares the same targets with LcrF and the effect of LcrQ is dependent on the presence of LcrF. Furthermore, over-expression of LcrF showed the same phenotype as that of the lcrQ mutant strain and intracellular amount balance of LcrQ and LcrF is important in T3SS regulation. When the expression level of LcrF exceeds LcrQ, expression of the Ysc-Yop T3SS genes is activated and vice versa. Together, these data support a model in which LcrQ blocks the activation role of LcrF in regulating the transcription of T3SS genes in Yersinia.


The relationship between sleep disorders and testosterone in men.
Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone (LH) secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3 h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin (SHBG), or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea (OSA) appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure (CPAP) does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture.


Lygus spp. (Heteroptera: Miridae) host-plant interactions with Lesquerella fendleri (Brassicaceae), a new crop in the arid southwest.
Lesquerella fendleri is a new crop being cultivated in the arid Southwest for the hydroxy fatty acids found in its seed oils; however, little is know about the agricultural pests that will affect the seed production of this crop or the role the crop may have as a possible source or sink for current agricultural pests in the Arizona landscape. In the early spring, lygus bugs, some of our most important agricultural pests, are normally found in relatively small numbers on weeds; however, as lesquerella production increases, it may serve as an important early-season host for lygus. Here we present results from olfactometer bioassays that showed a significant attraction by Lygus hesperus females to volatiles associated with flowering lesquerella. Headspace volatiles of flowering lesquerella were collected and identified by gas chromatography-mass spectrometry, and phenylacetaldehyde (PAA) was found to be the major component, followed by benzaldehyde and Z-3- hexenyl acetate. In the field, we examined the Lygus spp. complex, as well as the prevalence of other herbivores and select predators, and monitored their responses to unbaited sticky traps of various colors and PAA-baited green and blue sticky traps. Green, blue, and clear sticky traps captured significantly more Lygus spp. (L. elisus in particular) than opaque yellow and red traps, but PAA-baited blue and green traps did not capture more lygus than unbaited traps. Collops spp., however, were collected in higher numbers on PAA-baited traps, suggesting that this compound might provide a means of recruiting and/or retaining this particular natural enemy.


The role of the endogenous cannabinoid system in peripheral analgesia.
The therapeutic potential of cannabinoids has been studied and investigated through centuries, although many interesting discoveries have emerged from this field in the past decades. Indeed, peripheral analgesic effects of cannabinoids are a new avenue of treatment since they are avoiding the deleterious central side effects of systemic administration. Recently, it has been demonstrated that cannabinoid receptors (more specifically CB(1) and CB(2) receptors) and their endogenous ligands are present at the peripheral level, especially in different layers of skin, and mostly, in the epidermis and dermis. Those findings are reinforcing and confirming the efficacy of peripheral administration of cannabinoids used to alleviate pain in many different animal models. However, many studies have shown that the endocannabinoid system interacts with other receptors and pathways to modulate pain at the peripheral level. Thereof, the main goal of this review is to explain, in a better way, the different interactions regarding the cannabinoid system with other cellular components of its environment, its involvement in the modulation of pain at the peripheral level and, more precisely, in different layers of the skin.


First person account: finding myself and loving it.
The article that follows is part of the Schizophrenia Bulletin's ongoing First Person Accounts series. We hope that mental health professionals--the Bulletin's primary audience--will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex-patients, or family members. Our major editorial requirement is that such contributions be clearly written and organized and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients, with experiences they believe should be shared, might encourage these patients to submit their articles to First Person Accounts, Center for Studies of Schizophrenia, NIMH, 5600 Fishers Lane, Rm. 10C-18, Rockville, MD 20857.


Up-regulation of NOTCH4 gene expression in bipolar disorder.
Immunopathogenic mechanisms have been implicated in schizophrenia and bipolar disorder, and genome-wide association studies (GWAS) point to the major histocompatibility complex, a region that contains many immune-related genes. One of the strongest candidate risk genes for schizophrenia and bipolar disorder is the NOTCH4 gene within the major histocompatibility complex. The authors investigated the NOTCH4 gene expression in individuals with bipolar disorder and schizophrenia relative to healthy comparison subjects and identified putative expression quantitative trait loci in and around the NOTCH4 gene. The authors measured and compared NOTCH4 mRNA in whole blood in 690 individuals (479 patients and 211 healthy comparison subjects) and adjusted for a range of confounders. The authors also genotyped 20 single-nucleotide polymorphisms (SNPs) and investigated possible associations between expression quantitative trait loci and NOTCH4 expression. The authors found a strong association between NOTCH4 expression and bipolar disorder after adjusting for a range of confounders and multiple testing. In addition, seven SNPs within the NOTCH4 gene region were associated with enhanced NOTCH4 mRNA levels. Three of these expression quantitative trait loci were independent (not in linkage disequilibrium). The results indicate that the association between NOTCH4 DNA markers and bipolar disorder is related to altered function at the mRNA level, supporting the notion that NOTCH4 pathways are involved in the pathophysiology of bipolar disorder.


First Report of Dollar Spot Caused by Sclerotinia homoeocarpa on Agrostis stolonifera in Argentina.
During the summer of 2000, circular, yellow-to-brown, blighted, 2- to 4-cm-diameter patches were observed on creeping bentgrass (Agrostis stolonifera) putting greens (cv. Pennlinks) maintained at a 4- to 5-mm height on a golf course in Pilar (Buenos Aires, Argentina). Symptomatic leaves had transverse chlorotic bands that sometimes extended to the tip with brown lesions inside the bands. A fungus was isolated from symptomatic tissue after surface sterilization with 2% bleach for 1 min and plating on 2% potato dextrose agar (PDA). The mycelium was fluffy and white. The culture turned olive to brown and developed black stromata on the lower side of the plate base after 2 weeks. Pathogenicity tests were performed on 2-month-old healthy plants of A. stolonifera (cv. Crenshaw) grown in sterilized sand. Recently cut, 14-mm-diameter plugs of A. stolonifera were placed in 22- × 17-cm plastic trays filled with a sterilized mixture of 50:50 soil/sand (vol/vol). Plants were maintained at a 7-mm height. Two sources of inoculum were prepared; one was cultured on PDA at 22 to 25°C for 10 days and the other was prepared by incubating in sterilized soil at room temperature for 14 days. Twenty pieces of 1-cm-diameter agar blocks containing mycelium were placed in each plug at the base of the plants. In the infested soil inoculation, 25 g of soil were distributed among the plants on the substrate surface. Control plants were treated with either sterile PDA pieces or noninfested soil. The trays were irrigated with sterilized distilled water, covered with polyethylene bags, and kept in a controlled environment chamber at 25°C with 12 h per day of fluorescent light for 30 days. Leaf chlorosis appeared 7 and 10 days after inoculation for the agar-plug and infested-soil methods, respectively. Leaf necrosis was observed at day 23. Controls remained asymptomatic. The inoculated fungus was reisolated from symptomatic leaf tissue. The pathogen was identified as Sclerotinia homoeocarpa (1,2). To our knowledge, this is the first report of Sclerotinia homoeocarpa causing dollar spot disease on Agrostis stolonifera in Argentina and the first report of a disease on golf courses in our country. References: (1) J. E. M. Mordue. Sclerotinia homoeocarpa. No. 618 in: Descriptions of Pathogenic Fungi and Bacteria. CMI, Kew, Surrey, UK, 1979. (2) R. W. Smiley. Dollar Spot. Pages 14-16 in: Compendium of Turfgrass Diseases. The American Phytopathological Society, St. Paul, MN, 1983.


Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor.
A novel microfluidic device that can selectively and specifically isolate exceedingly small numbers of circulating tumor cells (CTCs) through a monoclonal antibody (mAB) mediated process by sampling large input volumes (>/=1 mL) of whole blood directly in short time periods (<37 min) was demonstrated. The CTCs were concentrated into small volumes (190 nL), and the number of cells captured was read without labeling using an integrated conductivity sensor following release from the capture surface. The microfluidic device contained a series (51) of high-aspect ratio microchannels (35 mum width x 150 mum depth) that were replicated in poly(methyl methacrylate), PMMA, from a metal mold master. The microchannel walls were covalently decorated with mABs directed against breast cancer cells overexpressing the epithelial cell adhesion molecule (EpCAM). This microfluidic device could accept inputs of whole blood, and its CTC capture efficiency was made highly quantitative (>97%) by designing capture channels with the appropriate widths and heights. The isolated CTCs were readily released from the mAB capturing surface using trypsin. The released CTCs were then enumerated on-device using a novel, label-free solution conductivity route capable of detecting single tumor cells traveling through the detection electrodes. The conductivity readout provided near 100% detection efficiency and exquisite specificity for CTCs due to scaling factors and the nonoptimal electrical properties of potential interferences (erythrocytes or leukocytes). The simplicity in manufacturing the device and its ease of operation make it attractive for clinical applications requiring one-time use operation.


Oral Hygiene Facilitators and Barriers in Greek 10 Years Old Schoolchildren.
The aim of this study was to determine the oral hygiene facilitators and barriers for 10 years old Greek children, via a questionnaire and clinical examination. This was a cross-sectional study of 266, 10 years old, children recruited from schools in 3 locations in Greece. Data were collected via questionnaires and clinical examination. Questionnaires referred to Children's oral hygiene knowledge, behavior and attitude as well as parents' oral hygiene behavior and educational level. Children were clinically examined by two calibrated pediatric dentists using a WHO probe and artificial light to assess dental plaque (hygiene index-HI), gingivitis (simplified gingival index-GIs) and dental caries (DMFT-BASCD criteria). Regarding oral hygiene knowledge, although 80% of the children were literate of the proper means of oral hygiene, only 58.64% brushed their teeth twice daily and 36.84% used dental floss. Children's oral hygiene knowledge was positively correlated with both parental brushing frequency (ρ = 0.175, p < 0.05) and educational level (ρ = -0.216, p < 0.05). Toothpaste use was reported by 92.11% of the children. Regarding Children's attitude, 62.28% were concerned whether their teeth were clean, with girls showing greater concern than boys (p < 0.001). Their reported beliefs regarding brushing avoidance were boredom (84.06%), low oral health literacy (73.91%) and forgetfulness (56.52%). Oral hygiene facilitators were found to be the concern about how clean were their teeth, oral health literacy of both children and parents and toothpaste appeal to children. Oral hygiene barriers were Children's boredom, low oral health literacy, forgetfulness and low socioeconomic level. How to cite this article: Angelopoulou M, Kavvadia K, Oulis C, Reppa C. Oral Hygiene Facilitators and Barriers in Greek 10 Years Old Schoolchildren. Int J Clin Pediatr Dent 2015;8(2):87-93.


Phenol derivatives accelerate inactivation kinetics in one inactivation-deficient mutant human skeletal muscle Na(+) channel.
Altered inactivation kinetics in skeletal muscle Na(+) channels due to mutations in the encoding gene are causal for the alterations in muscle excitability in nondystrophic myotonia. Na(+) channel blockers like lidocaine and mexiletine, suggested for therapy of myotonia, do not reconstitute inactivation in channels with defective inactivation in vitro. We examined the effects of four methylated and/or halogenated phenol derivatives on one heterologously expressed inactivation-deficient Paramyotonia congenita-mutant (R1448H) muscle Na(+) channel in vitro. All these compounds accelerated delayed inactivation of R1448H-whole-cell currents during a depolarization and delayed accelerated recovery from inactivation. The potency of these effects paralleled the potency of the drugs to block the peak current amplitude. We conclude that the investigated phenol derivatives affect inactivation-deficient Na(+) channels more specifically than lidocaine and mexiletine. However, for all compounds, the effect on inactivation was accompanied by a substantial block of the peak current amplitude.


Potential role of estradiol and progesterone in insulin resistance through constitutive androstane receptor.
Normal pregnancy is characterized by insulin resistance, which contributes to the development of gestational diabetes mellitus and preeclampsia by incompletely understood mechanisms. The constitutive androstane receptor (CAR) may participate in insulin resistance in pregnancy, and sex steroids, estradiol (E(2)) and progesterone, may also be involved. We applied glucose and insulin tolerance tests and measured the expression of gluconeogenic and lipogenic genes in the livers of oophorectomized mice treated with E(2) and progesterone with or without CAR ligands. We also investigated how E(2) and progesterone affected CAR-mediated signaling and the activity of transcription factors in gluconeogenesis in vitro. Mice with the concentrations of E(2) and progesterone within normal physiological range during pregnancy exhibited increased insulin resistance along with increased expression of gluconeogenic and lipogenic genes, and CAR activation rescued the abnormal glucose metabolism. In HepG2 cells, CAR ligands suppressed the gluconeogenic and lipogenic gene expression in the presence of E(2) and/or progesterone. DNA affinity immunoblotting and chromatin immunoprecipitation assay revealed that CAR ligand enhanced the recruitment of the gluconeogenic transcription factors, forkhead box O1 (FOXO1) and hepatocyte nuclear factor 4α (HNF4α), but sex steroids suppressed these recruitments on the CAR responsive element. Moreover, CAR ligand suppressed the recruitment of FOXO1 and HNF4α on their responsive element in gluconeogenic gene promoters and E(2) and progesterone augmented these recruitments on their responsive element. Taken together, these findings suggest that the activation of CAR-mediated signaling may ameliorate insulin resistance under relatively high concentrations of E(2) and progesterone, which were compatible with pregnancy via decreased activities of transcription factors in gluconeogenesis in combination with CAR.


Genomic Signatures of North American Soybean Improvement Inform Diversity Enrichment Strategies and Clarify the Impact of Hybridization.
Crop improvement represents a long-running experiment in artificial selection on a complex trait, namely yield. How such selection relates to natural populations is unclear, but the analysis of domesticated populations could offer insights into the relative role of selection, drift, and recombination in all species facing major shifts in selective regimes. Because of the extreme autogamy exhibited by soybean (Glycine max), many "immortalized" genotypes of elite varieties spanning the last century have been preserved and characterized using ∼50,000 single nucleotide polymorphic (SNP) markers. Also due to autogamy, the history of North American soybean breeding can be roughly divided into pre- and posthybridization eras, allowing for direct interrogation of the role of recombination in improvement and selection. Here, we report on genome-wide characterization of the structure and history of North American soybean populations and the signature of selection in these populations. Supporting previous work, we find that maturity defines population structure. Though the diversity of North American ancestors is comparable to available landraces, prehybridization line selections resulted in a clonal structure that dominated early breeding and explains many of the reductions in diversity found in the initial generations of soybean hybridization. The rate of allele frequency change does not deviate sharply from neutral expectation, yet some regions bare hallmarks of strong selection, suggesting a highly variable range of selection strengths biased toward weak effects. We also discuss the importance of haplotypes as units of analysis when complex traits fall under novel selection regimes.


Design of Thiol- and Light-sensitive Degradable Hydrogels using Michael-type Addition Reactions.
Injectable depots that respond to exogenous and endogenous stimuli present an attractive strategy for tunable, patient-specific drug delivery. Here, the design of injectable and multimodal degradable hydrogels that respond to externally applied light and physiological stimuli, specifically aqueous and reducing microenvironments, is reported. Rapid hydrogel formation was achieved using a thiol-maleimide click reaction between multifunctional poly(ethylene glycol) macromers. Hydrogel degradation kinetics in response to externally applied cytocompatible light, reducing conditions, and hydrolysis were characterized, and degradation of the gel was controlled over multiple time scales from seconds to days. Further, tailored release of an encapsulated model cargo, fluorescent nanobeads, was demonstrated.


Dispersion of Air Bubbles in Isotropic Turbulence.
Bubbles play an important role in the transport of chemicals and nutrients in many natural and industrial flows. Their dispersion is crucial to understanding the mixing processes in these flows. Here we report on the dispersion of millimetric air bubbles in a homogeneous and isotropic turbulent flow with a Taylor Reynolds number from 110 to 310. We find that the mean squared displacement (MSD) of the bubbles far exceeds that of fluid tracers in turbulence. The MSD shows two regimes. At short times, it grows ballistically (∝τ^{2}), while at larger times, it approaches the diffusive regime where the MSD∝τ. Strikingly, for the bubbles, the ballistic-to-diffusive transition occurs one decade earlier than for the fluid. We reveal that both the enhanced dispersion and the early transition to the diffusive regime can be traced back to the unsteady wake-induced motion of the bubbles. Further, the diffusion transition for bubbles is not set by the integral timescale of the turbulence (as it is for fluid tracers and microbubbles), but instead, by a timescale of eddy crossing of the rising bubbles. The present findings provide a Lagrangian perspective towards understanding mixing in turbulent bubbly flows.


Effects of cannabidiol in animal models predictive of antipsychotic activity.
The effects of cannabidiol (CBD) were compared to those produced by haloperidol in rats submitted to experimental models predictive of antipsychotic activity. Several doses of CBD (15-480 mg/kg) and haloperidol (0.062-1.0 mg/kg) were tested in each model. First, CBD increased the effective doses 50% (or) ED50 of apomorphine for induction of the sniffing and biting stereotyped behaviors. In addition, both CBD and haloperidol reduced the occurrence of stereotyped biting induced by apomorphine (6.4 mg/kg), increased plasma prolactin levels and produced palpebral ptosis, as compared to control solutions. However, CBD did not induce catalepsy even at the highest doses, in contrast to haloperidol. Such a pharmacological profile is compatible with that of an "atypical" antipsychotic agent, though the mechanism of action is uncertain and may not be identical to that of the dopamine antagonists.


The course of non-malignant chronic pain: a 12-year follow-up of a cohort from the general population.
The high prevalence of chronic pain (duration >3 months) reported from different populations indicates a public health problem. Knowledge of the long-term course of chronic non-malignant pain is incomplete and scarce. This paper describes a follow-up of a cohort recruited from a survey in the general population. The cohort (n=214) consisted initially of individuals with widespread or located (neck-shoulder) pain or without chronic pain. The individuals were initially examined and replied to questionnaires on pain, social factors, lifestyle, medication and health care after two and 12 years. The deaths during the period were obtained from the population register. Complete data exist for 77% of the eligible individuals. After 12 years one-third of the individuals initially without pain reported chronic pain, and among those with initial chronic pain 85% still reported chronic pain. The number of painful areas was the strongest predictor of chronic pain 12 years later (OR 15.8; >3 locations vs. 0) whereas a social factor (having a close friend) decreased the risk (OR 0.44). The onset of chronic pain during the same period was related to the physical workload (work with bent positions; OR 5.31; yes vs. no). Mortality was significantly higher in the group initially reporting widespread pain compared with the other groups. The chronicity of widespread chronic pain supports early and intense intervention among individuals with located pain. The association between chronic widespread pain and increased mortality needs further investigation but may deepen the view of chronic pain as a public health problem.


Doctors Have no Right to Refuse Medical Assistance in Dying, Abortion or Contraception.
In an article in this journal, Christopher Cowley argues that we have 'misunderstood the special nature of medicine, and have misunderstood the motivations of the conscientious objectors'. We have not. It is Cowley who has misunderstood the role of personal values in the profession of medicine. We argue that there should be better protections for patients from doctors' personal values and there should be more severe restrictions on the right to conscientious objection, particularly in relation to assisted dying. We argue that eligible patients could be guaranteed access to medical services that are subject to conscientious objections by: (1) removing a right to conscientious objection; (2) selecting candidates into relevant medical specialities or general practice who do not have objections; (3) demonopolizing the provision of these services away from the medical profession.


Telomere length and pulse pressure in newly diagnosed, antipsychotic-naive patients with nonaffective psychosis.
Recent studies suggest that in addition to factors such as treatment side effects, suicide, and poor health habits, people with schizophrenia may have an increased risk of diabetes prior to antipsychotic treatment. Diabetes is associated with an increased pulse pressure (PP) and a shortened telomere. We tested the hypothesis that prior to antipsychotic treatment, schizophrenia and related disorders are associated with a shortened telomere, as well as an increased PP. Telomere content (which is highly correlated with telomere length) and PP were measured in newly diagnosed, antipsychotic-naive patients with schizophrenia and related disorders on first clinical contact and in matched control subjects. Both groups were also administered an oral glucose tolerance test. Compared with control subjects, the patients with psychosis had decreased telomere content and an increased PP. As previously reported, they also had increased glucose concentrations at 2 hours. These differences could not be attributed to differences in age, ethnicity, smoking, gender, body mass index, neighborhood of residence, socioeconomic status, aerobic conditioning, or an increased cortisol concentration in the psychotic subjects. These results suggest that prior to antipsychotic use, nonaffective psychosis is associated with reduced telomere content and increased PP, indices that have been linked to an increased risk of diabetes and hypertension.


Newborn humans manifest autoantibodies to defined self molecules detected by antigen microarray informatics.
Autoimmune diseases are often marked by autoantibodies binding to self antigens. However, many healthy persons also manifest autoantibodies that bind to self antigens, known as natural autoantibodies. In order to characterize natural autoantibodies present at birth, we used an antigen microarray (antigen chip) to analyze informatically (with clustering algorithms and correlation mapping) the natural IgM, IgA, and IgG autoantibody repertoires present in 10 pairs of sera from healthy mothers and the cords of their newborn babies. These autoantibodies were found to bind to 305 different, mostly self, molecules. We report that in utero, humans develop IgM and IgA autoantibodies to relatively uniform sets of self molecules. The global patterns of maternal IgM autoantibodies significantly diverged from those at birth, although certain reactivities remained common to both maternal and cord samples. Because maternal IgG antibodies (unlike IgM and IgA) cross the placenta, maternal and cord IgG autoantibodies showed essentially identical reactivities. We found that some self antigens that bind cord autoantibodies were among the target self antigens associated with autoimmune diseases later in life. Thus, the obviously benign autoimmunity prevalent at birth may provide the basis for the emergence of some autoimmune diseases relatively prevalent later in life.


Underweight, overweight and obesity among zaboli adolescents: a comparison between international and iranians' national criteria.
Obesity and overweight are the major health problems in Iran. The aim of this study was to determine the prevalence of overweight and obesity among adolescents living in Zabol settled in Sistan va Baluchistan, one of economically underprivileged provinces in South Eastern of Iran, based on four different definitions. This cross-sectional study was accomplished among a sample of 837 Zaboli adolescents (483 males; 354 females) aged 11-15 years. Anthropometric measurements including weight and height were measured and body mass index (BMI) was calculated. Sex-specific BMI-for-age reference data of the Iranian national data, Centers for Disease Control data (CDC 2000), International Obesity Task Force data (IOTF) and recent World Health Organization (WHO) data was used to define overweight and obesity. Mean age of the studied population was 13.14 year. Underweight was prevalent among almost 18.7% and 18.4% of adolescents by the use of WHO 2007 and CDC 2000 cut-off points. The prevalence rates reached 25.8% and 27.2% by IOTF and Iranian national criteria, respectively. The highest prevalence of overweight was obtained by IOTF cut-points (10.8%) followed by CDC 2000 criteria (9.4%), WHO 2007 (8.8%) while national Iranian cut-points resulted in the lowest prevalence (2.4%). 7.5% of the studied population were found to be obese by WHO 2007 definition, while this rate was 2.2%, 3.4% and 1.5% by IOTF, CDC 2000 and national Iranian cut-points. Almost all definitions revealed coexistence of underweight, overweight, and obesity among Zaboli adolescents. Huge differences exist between different criteria. To understand the best appropriate criteria for Iranian adolescents, future studies should focus on the predictability of obesity-related co-morbidities by these criteria.


Evolutionary dynamics of human autoimmune disease genes and malfunctioned immunological genes.
One of the main issues of molecular evolution is to divulge the principles in dictating the evolutionary rate differences among various gene classes. Immunological genes have received considerable attention in evolutionary biology as candidates for local adaptation and for studying functionally important polymorphisms. The normal structure and function of immunological genes will be distorted when they experience mutations leading to immunological dysfunctions. Here, we examined the fundamental differences between the genes which on mutation give rise to autoimmune or other immune system related diseases and the immunological genes that do not cause any disease phenotypes. Although the disease genes examined are analogous to non-disease genes in product, expression, function, and pathway affiliation, a statistically significant decrease in evolutionary rate has been found in autoimmune disease genes relative to all other immune related diseases and non-disease genes. Possible ways of accumulation of mutation in the three steps of the central dogma (DNA-mRNA-Protein) have been studied to trace the mutational effects predisposed to disease consequence and acquiring higher selection pressure. Principal Component Analysis and Multivariate Regression Analysis have established the predominant role of single nucleotide polymorphisms in guiding the evolutionary rate of immunological disease and non-disease genes followed by m-RNA abundance, paralogs number, fraction of phosphorylation residue, alternatively spliced exon, protein residue burial and protein disorder. Our study provides an empirical insight into the etiology of autoimmune disease genes and other immunological diseases. The immediate utility of our study is to help in disease gene identification and may also help in medicinal improvement of immune related disease.


Magnetowetting and sliding motion of a sessile ferrofluid droplet in the presence of a permanent magnet.
Motion of a droplet on a planar surface has applications in droplet-based lab on a chip technology. This paper reports the experimental results of the shape, contact angles, and motion of ferrofluid droplets driven by a permanent magnet on a planar homogeneous surface. The water-based ferrofluid in use is a colloidal suspension of single-domain magnetic nanoparticles. The effect of the magnetic field on the apparent contact angle of the ferrofluid droplet was first investigated. The results show that an increasing magnetic flux decreases the apparent contact angle of a sessile ferrofluid droplet. Next, the dynamic contact angle was investigated by observing the shape and the motion of a sessile ferrofluid droplet. The advancing and receding contact angles of the moving ferrofluid were measured at different moving speeds and magnetic field strengths. The measured contact angles were used to estimate the magnitude of the forces involved in the sliding motion. Scaling analysis was carried out to derive the critical velocity, beyond which the droplet is not able to catch up with the moving magnet.


Oral manganese as an MRI contrast agent for the detection of nociceptive activity.
The ability of divalent manganese to enter neurons via calcium channels makes manganese an excellent MRI contrast agent for the imaging of nociception, the afferent neuronal encoding of pain perception. There is growing evidence that nociceptive neurons possess increased expression and activity of calcium channels, which would allow for the selective accumulation of manganese at these sites. In this study, we show that oral manganese chloride leads to increased enhancement of peripheral nerves involved in nociception on T(1)-weighted MRI. Oral rather than intravenous administration was chosen for its potentially better safety profile, making it a better candidate for clinical translation with important applications, such as pain diagnosis, therapy and research. The spared nerve injury (SNI) model of neuropathic pain was used for the purposes of this study. SNI rats were given, sequentially, increasing amounts of manganese chloride (lowest, 2.29 mg/100 g weight; highest, 20.6 mg/100 g weight) with alanine and vitamin D(3) by oral gavage. Compared with controls, SNI rats demonstrated increased signal-to-background ratios on T(1)-weighted fast spin echo MRI, which was confirmed by and correlated strongly with spectrometry measurements of nerve manganese concentration. We also found the difference between SNI and control rats to be greater at 48 h than at 24 h after dosing, indicating increased manganese retention in addition to increased manganese uptake in nociceptive nerves. This study demonstrates that oral manganese is a viable method for the imaging of nerves associated with increased nociceptive activity.


Tetherin restricts productive HIV-1 cell-to-cell transmission.
The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or DeltaVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of DeltaVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread.


Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida blacktip sharks: guidance for empiric antibiotic therapy.
Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline.


Optical FFT/IFFT circuit realization using arrayed waveguide gratings and the applications in all-optical OFDM system.
Arrayed waveguide gratings (AWG) are widely used as wavelength division multiplexers (MUX) and demultiplexers (DEMUX) in optical networks. Here we propose and demonstrate that conventional AWGs can also be used as integrated spectral filters to realize a Fast Fourier transform (FFT) and its inverse form (IFFT). More specifically, we point out that the wavelength selection conditions of AWGs when used as wavelength MUX/DEMUX also enable them to perform FFT/IFFT functions. Therefore, previous research on AWGs can now be applied to optical FFT/IFFT circuit design. Compared with other FFT/IFFT optical circuits, AWGs have less structural complexity, especially for a large number of inputs and outputs. As an important application, AWGs can be used in optical OFDM systems. We propose an all-optical OFDM system with AWGs and demonstrate the simulation results. Overall, the AWG provides a feasible solution for all-optical OFDM systems, especially with a large number of optical subcarriers.


Spectrum of hypokalaemic periodic paralysis in a tertiary care centre in India.
Acute flaccid paralysis is a common neurological emergency with diverse causes and variable outcome. There is a paucity of reports documenting the spectrum of hypokalaemic paralysis in neurological practice. To report the clinical features, aetiology, and outcome of patients with hypokalaemic paralysis in a tertiary care teaching hospital in India. Consecutive patients with acute flaccid paralysis with hypokalaemia from 2008 to 2010 were included in the study. Patients with Guillain-Barré syndrome, porphyria, polio and non-polio enterovirus infection and myositis were excluded. Detailed clinical examination, urinalysis, renal function tests, arterial blood gas analysis, thyroid hormones, and electrocardiogram were carried out. Patients received intravenous or oral potassium supplementation and their underlying causes were treated. Thirty patients aged 17-52 years, including three females, were included. Secondary causes of hypokalaemic paralysis were present in 13 patients and included thyrotoxic paralysis in five and renal tubular acidosis (RTA) and Gitelman syndrome in four each. All the patients had quadriparesis and 10 had severe weakness (MRC grade <2). Tendon reflexes were reduced in eight and brisk in four patients. Respiratory paralysis was present in six patients and one needed artificial ventilation. Fifteen patients had severe hypokalaemia (<2 mmol/l), four had acidosis, and six had alkalosis. The secondary group had more severe hypokalaemia and needed longer time to recover. 43.3% of patients with hypokalaemic paralysis had a secondary cause for their condition. Patients with severe hypokalaemia with acidosis or alkalosis should be investigated for secondary causes as their management differ.


Directional selection effects on patterns of phenotypic (co)variation in wild populations.
Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient.


Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial.
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).


Spatial patterning of soil microbial communities created by fungus-farming termites.
Spatially overdispersed mounds of fungus-farming termites (Macrotermitinae) are hotspots of nutrient availability and primary productivity in tropical savannas, creating spatial heterogeneity in communities and ecosystem functions. These termites influence the local availability of nutrients in part by redistributing nutrients across the landscape, but the links between termite ecosystem engineering and the soil microbes that are the metabolic agents of nutrient cycling are little understood. We used DNA metabarcoding of soils from Odontotermes montanus mounds to examine the influence of termites on soil microbial communities in a semi-arid Kenyan savanna. We found that bacterial and fungal communities were compositionally distinct in termite-mound topsoils relative to the surrounding savanna, and that bacterial communities were more diverse on mounds. The higher microbial alpha and beta diversity associated with mounds created striking spatial patterning in microbial community composition, and boosted landscape-scale microbial richness and diversity. Selected enzyme assays revealed consistent differences in potential enzymatic activity, suggesting links between termite-induced heterogeneity in microbial community composition and the spatial distribution of ecosystem functions. We conducted a large-scale field experiment in which we attempted to simulate termites' effects on microbes by fertilizing mound-sized patches; this altered both bacterial and fungal communities, but in a different way than natural mounds. Elevated levels of inorganic nitrogen, phosphorus and potassium may help to explain the distinctive fungal communities in termite-mound soils, but cannot account for the distinctive bacterial communities associated with mounds.


Tackling in Youth Football.
American football remains one of the most popular sports for young athletes. The injuries sustained during football, especially those to the head and neck, have been a topic of intense interest recently in both the public media and medical literature. The recognition of these injuries and the potential for long-term sequelae have led some physicians to call for a reduction in the number of contact practices, a postponement of tackling until a certain age, and even a ban on high school football. This statement reviews the literature regarding injuries in football, particularly those of the head and neck, the relationship between tackling and football-related injuries, and the potential effects of limiting or delaying tackling on injury risk.