Effect of antibiotic prescribing in primary care on meticillin-resistant Staphylococcus aureus carriage in community-resident adults: a controlled observational study.
The objectives of this study were to investigate the relationship between primary care antibiotics prescribed within 2 months and 12 months and the carriage of meticillin-resistant Staphylococcus aureus (MRSA) in nasal flora from a large representative sample of community-resident adults. S. aureus isolates were obtained from nasal samples submitted by UK resident adults aged ≥ 16 years registered with 12 general practices in the former Avon and Gloucestershire health authority areas. Individual-level antibiotic exposure data during the 12 months prior to providing the samples were collected from the primary care electronic records. MRSA status was determined by measuring resistance to cefoxitin. In total, 6937 adults were invited to take part, of whom 5917 returned a nasal sample. S. aureus was identified in 946 samples and a total of 761 participants consented to primary care record review and had complete data for the analyses. There was no evidence of an association between any antibiotic in the previous 2 months and MRSA isolation, with an adjusted odds ratio (aOR) of 1.33 [95% confidence interval (CI) 0.12-15; P=0.8]. There was a suggestion of an association between any antibiotic use in the previous 12 months and MRSA, with an aOR of 2.45 (95% CI 0.95-6.3; P=0.06). In conclusion, there is a suggestion that antibiotics prescribed within 12 months is associated with the carriage of MRSA, but not within 2 months, although the 2-month analysis had fewer data subjects and was therefore underpowered to detect this association. A larger study would be able to clarify these associations further.


Conjugated oligoelectrolytes increase power generation in E. coli microbial fuel cells.
A series of conjugated oligoelectrolytes with structural variations is used to stain E. coli. By taking advantage of a high-throughput screening platform that incorporates gold anodes, it is found that MFCs with COE-modified E. coli generate significantly higher power densities, relative to unmodified E. coli. These findings highlight the potential of using water-soluble molecules inspired by the work on organic semiconductors to improve electrode/microbe interfaces.


Acetaminophen and diphenhydramine premedication for allergic and febrile nonhemolytic transfusion reactions: good prophylaxis or bad practice?
Febrile nonhemolytic and allergic reactions are the most common transfusion reactions, but usually do not cause significant morbidity. In an attempt to prevent these reactions, US physicians prescribe acetaminophen or diphenhydramine premedication before more than 50% of blood component transfusions. Acetaminophen and diphenhydramine are effective therapies for fever and allergy, respectively, so their use in transfusion has some biologic rationale. However, these medications also have potential toxicity, particularly in ill patients, and in the studies performed to date, they have failed to prevent transfusion reactions. Whether the benefits of routine prophylaxis with acetaminophen and diphenhydramine outweigh their risks and cost requires reexamination, particularly in light of the low reaction rates reported at many institutions even when premedication is not prescribed.


Characterization of CS4 and CS6 antigenic components of PCF8775, a putative colonization factor complex from enterotoxigenic Escherichia coli E8775.
PCF8775 is a putative colonization factor complex present on the surface of 10 to 20% of enterotoxigenic Escherichia coli strains and has been reported to be composed of antigen CS6 (morphology undefined) expressed alone or together with either of the rigid fimbrial antigens CS4 and CS5. To better define the individual components of this complex and the determinants of their expression, we prepared antiserum to the PCF8775 complex as it was expressed on prototype strain E8775 and then used the antiserum to identify the subunit structure of the antigens, to study their morphology, and to detect expression of individual components of the complex after transfer of plasmids into laboratory strain HB101. CS4 was purified from strain E8775, confirmed to be fimbrial by electron microscopy, and found to be composed of a 22-kilodalton protein subunit whose N-terminal amino acid sequence (1 to 20) was similar to that of colonization factor antigen I. Transconjugants that express CS6 but not CS4 were obtained by mating prototype strain E8775 with HB101. CS6 expression was mediated by a 61-megadalton plasmid. Expression of CS6 in the transconjugants correlates with expression of a 16-kilodalton cell surface protein. The CS6 antigen was confirmed to be present on the cell surface by immunogold labeling, but its morphology was beyond the limits of resolution by electron microscopy.


Exploring QSARs for inhibitory activity of non-peptide HIV-1 protease inhibitors by GA-PLS and GA-SVM.
The support vector machine (SVM) and partial least square (PLS) methods were used to develop quantitative structure activity relationship (QSAR) models to predict the inhibitory activity of non-peptide HIV-1 protease inhibitors. Genetic algorithm (GA) was employed to select variables that lead to the best-fitted models. A comparison between the obtained results using SVM with those of PLS revealed that the SVM model is much better than that of PLS. The root mean square errors of the training set and the test set for SVM model were calculated to be 0.2027, 0.2751, and the coefficients of determination (R(2)) are 0.9800, 0.9355 respectively. Furthermore, the obtained statistical parameter of leave-one-out cross-validation test (Q(2)) on SVM model was 0.9672, which proves the reliability of this model. The results suggest that TE2, Ui, GATS5e, Mor13e, ATS7m, Ss, Mor27e, and RDF035e are the main independent factors contributing to the inhibitory activities of the studied compounds.


Developmental endothelial locus-1 is a homeostatic factor in the central nervous system limiting neuroinflammation and demyelination.
Inflammation in the central nervous system (CNS) and disruption of its immune privilege are major contributors to the pathogenesis of multiple sclerosis (MS) and of its rodent counterpart, experimental autoimmune encephalomyelitis (EAE). We have previously identified developmental endothelial locus-1 (Del-1) as an endogenous anti-inflammatory factor, which inhibits integrin-dependent leukocyte adhesion. Here we show that Del-1 contributes to the immune privilege status of the CNS. Intriguingly, Del-1 expression decreased in chronic-active MS lesions and in the inflamed CNS in the course of EAE. Del-1-deficiency was associated with increased EAE severity, accompanied by increased demyelination and axonal loss. As compared with control mice, Del-1(-/-) mice displayed enhanced disruption of the blood-brain barrier and increased infiltration of neutrophil granulocytes in the spinal cord in the course of EAE, accompanied by elevated levels of inflammatory cytokines, including interleukin-17 (IL-17). The augmented levels of IL-17 in Del-1-deficiency derived predominantly from infiltrated CD8(+) T cells. Increased EAE severity and neutrophil infiltration because of Del-1-deficiency was reversed in mice lacking both Del-1 and IL-17 receptor, indicating a crucial role for the IL-17/neutrophil inflammatory axis in EAE pathogenesis in Del-1(-/-) mice. Strikingly, systemic administration of Del-1-Fc ameliorated clinical relapse in relapsing-remitting EAE. Therefore, Del-1 is an endogenous homeostatic factor in the CNS protecting from neuroinflammation and demyelination. Our findings provide mechanistic underpinnings for the previous implication of Del-1 as a candidate MS susceptibility gene and suggest that Del-1-centered therapeutic approaches may be beneficial in neuroinflammatory and demyelinating disorders.


The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.
Inflammation is a self-defense response to protect individuals from infection and tissue damage, but excessive or persistent inflammation can have adverse effects on cell survival. Many individuals become especially susceptible to chronic-inflammation-induced sensorineural hearing loss as they age, but the intrinsic molecular mechanism behind aging individuals' increased risk of hearing loss remains unclear. FoxG1 (forkhead box transcription factor G1) is a key transcription factor that plays important roles in hair cell survival through the regulation of mitochondrial function, but how the function of FoxG1 changes during aging and under inflammatory conditions is unknown. In this study, we first found that FoxG1 expression and autophagy both increased gradually in the low concentration lipopolysaccharide (LPS)-induced inflammation model, while after high concentration of LPS treatment both FoxG1 expression and autophagy levels decreased as the concentration of LPS increased. We then used siRNA to downregulate Foxg1 expression in hair cell-like OC-1 cells and found that cell death and apoptosis were significantly increased after LPS injury. Furthermore, we used d-galactose (D-gal) to create an aging model with hair cell-like OC-1 cells and cochlear explant cultures in vitro and found that the expression of Foxg1 and the level of autophagy were both decreased after D-gal and LPS co-treatment. Lastly, we knocked down the expression of Foxg1 under aged inflammation conditions and found increased numbers of dead and apoptotic cells. Together these results suggest that FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.


Validation of a Mathematical Model for Road Cycling Power.
This investigation sought to determine if cycling power could be accurately modeled. A mathematical model of cycling power was derived, and values for each model parameter were determined. A bicycle-mounted power measurement system was validated by comparison with a laboratory ergometer. Power was measured during road cycling, and the measured values were compared with the values predicted by the model. The measured values for power were highly correlated (R2 = .97) with, and were not different than, the modeled values. The standard error between the modeled and measured power (2.7 W) was very small. The model was also used to estimate the effects of changes in several model parameters on cycling velocity. Over the range of parameter values evaluated, velocity varied linearly (R2 > .99). The results demonstrated that cycling power can be accurately predicted by a mathematical model.


Risk Factors for Acquired Rifamycin and Isoniazid Resistance: A Systematic Review and Meta-Analysis.
Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies. Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1) HIV and 2) baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies. Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I2 58%, 95% CI 26 to 76%). Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11); there was considerable heterogeneity amongst these studies (I2 81%, 95% CI 64 to 90%). Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST) was 0.1% (5th to 95th percentile 0.07 to 3.2%). Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely to contribute to the outcome of ADR. The multifactorial aetiology of ADR in a programmatic setting should be further evaluated via appropriately designed studies.


ΜicroRNA‑421 promotes the progression of non‑small cell lung cancer by targeting HOPX and regulating the Wnt/β‑catenin signaling pathway.
MicroRNAs (miRNAs) function as key regulators of numerous types of cancers. miRNA (miR)‑421 expression is dysregulated in a variety of tumors; however, its role in non‑small cell lung cancer (NSCLC) remains unclear. In the present study, the role and molecular mechanism of miR‑421 in NSCLC was investigated. In this study, miRNA (miR)‑421 was upregulated in NSCLC tissues and cell lines used the reverse transcriptase quantitative polymerase chain reaction. Ectopic expression of miR‑421 significantly promoted cell proliferation in vitro and tumor growth in vivo by promoting cell cycle progression via CCK-8, colony formation, EdU assay, xenograft model and cell cycle assay. In addition, miR‑421 inhibited NSCLC cell apoptosis by flow cytometry apoptosis assay, as evidenced by anti‑apoptosis gene Bcl‑2 and apoptosis gene cleaved caspase‑3 and cleaved PARP using western blot assay. Furthermore, miR‑421 promoted cell migration and invasion through EMT process using Transwell and western blot assay. It was also demonstrated that miR‑421 can directly target HOPX by the EGFP reporter assay and western blot assay. MiR‑421 overexpression promoted the protein expression levels of β‑catenin, cyclin D1 and c‑myc by western blot assay, which are the downstream genes of Wnt pathway. These data indicated that miR‑421 may act as an oncogene through the effects of HOPX on the Wnt/β‑catenin signaling pathway and may provide insight into the mechanisms underlying carcinogenesis and the identification of potential biomarkers associated with NSCLC.


Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries.
To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. Population based cohort study. European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P<0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P<0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P<0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.


Detection of Gardnerella vaginalis in vaginal specimens by direct immunofluorescence.
The preparation of a fluorescein-labeled Gardnerella vaginalis polyclonal antibody is described, and its usefulness is assessed for the detection of this microorganism in vaginal samples obtained from 263 women attending the gynecological department of a general hospital, 66 of whom harbored an intrauterine device. The direct immunofluorescence technique was positive for G. vaginalis in 21% of the specimens, whereas only 12.5% of the total bacteriological cultures were positive. The frequency was higher in patients harboring intrauterine devices since 34.8% exhibited positive immunofluorescence and 30.3% exhibited positive cultures.


Reconstruction of MR images from data acquired on a general nonregular grid by pseudoinverse calculation.
A minimum-norm least-squares image-reconstruction method for the reconstruction of magnetic resonance images from non-Cartesian sampled data is proposed. The method is based on a general formalism for continuous-to-discrete mapping and pseudoinverse calculation. It does not involve any regridding or interpolation of the data and therefore the methodology differs fundamentally from existing regridding-based methods. Moreover, the method uses a continuous representation of objects in the image domain instead of a discretized representation. Simulations and experiments show the possibilities of the method in both radial and spiral imaging. Simulations revealed that minimum-norm least-squares image reconstruction can result in a drastic decrease of artifacts compared with regridding-based reconstruction. Besides, both in vivo and phantom experiments showed that minimum-norm least-squares image reconstruction leads to contrast improvement and increased signal-to-noise ratio compared with image reconstruction based on regridding. As an appendix, an analytical calculation of the raw data corresponding to the well-known Shepp and Logan software head phantom is presented.


Isolation of halimedatrial: chemical defense adaptation in the calcareous reef-building alga halimeda.
Halimedatrial, a structurally unprecedented diterpenoid trialdehyde, has been identified as the major secondary metabolite in six species of the calcareous reef-building alga Halimeda. In laboratory bioassays, halimedatrial is toxic toward reef fishes, significantly reduces feeding in herbivorous fishes, and has cytotoxic and antimicrobial activities. The widespread occurrence of halimedatrial and its potent biological activities suggest that this metabolite represents a chemical defense adaptation in this pantropical marine alga.


Reporting standards in cardiac MRI, CT, and SPECT diagnostic accuracy studies: analysis of the impact of STARD criteria.
Diagnostic accuracy studies determine the clinical value of non-invasive cardiac imaging tests. The 'STAndards for the Reporting of Diagnostic accuracy studies' (STARD) were published in 2003 to improve the quality of study reporting. We aimed to assess the reporting quality of cardiac computed tomography (CCT), single positron emission computed tomography (SPECT), and cardiac magnetic resonance (CMR) diagnostic accuracy studies; to evaluate the impact of STARD; and to investigate the relationships between reporting quality, journal impact factor, and study citation index. We randomly generated six groups of 50 diagnostic accuracy studies: 'CMR 1995-2002', 'CMR 2004-11', 'CCT 1995-2002', 'CCT 2004-11', 'SPECT 1995-2002', and 'SPECT 2004-11'. The 300 studies were double-read by two blinded reviewers and reporting quality determined by % adherence to the 25 STARD criteria. Reporting quality increased from 65.3% before STARD to 74.1% after (P = 0.003) in CMR studies and from 61.6 to 79.0% (P < 0.001) in CCT studies. SPECT studies showed no significant change: 71.9% before and 71.5% after STARD (P = 0.92). Journals advising authors to refer to STARD had significantly higher impact factors than those that did not (P = 0.03), and journals with above-median impact factors published studies of significantly higher reporting quality (P < 0.001). Since STARD, citation index has not significantly increased (P = 0.14), but, after adjustment for impact factor, reporting quality continues to increase by ∼1.5% each year. Reporting standards for diagnostic accuracy studies of non-invasive cardiac imaging are at most satisfactory and have improved since the introduction of STARD. Adherence to STARD should be mandatory for authors of diagnostic accuracy studies.


Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells.
Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.


Characterization of [3H]ABT-418: a novel cholinergic channel ligand.
ABT-418 [(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole] is a potent and selective agonist at neuronal nicotinic acetylcholine receptors (nAChRs) with cognitive enhancing and anxiolytic activities. [3H]ABT-418 was found to bind with high affinity (KD = 2.85 +/- 0.14 nM) to membranes prepared from rat brain. Binding of [3H]ABT-418 was characterized by rapid association (T1/2 = 1.4 +/- 0.3 min) and dissociation (T1/2 = 2.9 +/- 0.4 min) half-times. The pharmacology of [3H]ABT-418 binding was consistent with an interaction with the putative alpha 4 beta 2 nAChR subtype. The nAChR agonists, (-)-nicotine, (-)-cytisine and (+/-)-epibatidine, displayed a high affinity (Ki = 0.8 +/- 0.1, 0.2 +/- 0.1 and 0.05 +/- 0.01 nM, respectively) for [3H]ABT-418 binding sites, whereas among nAChR antagonists examined, only dihydro-beta-erythroidine competed with high affinity (Ki = 32 +/- 1.5 nM). Although autoradiography studies indicate that the binding distribution of [3H]ABT-418 and (-)-[3H]cytisine are largely identical, there are some brain regions including the striatum, olivary pretectal nucleus and the superior colliculus, in which [3H]ABT-418 demonstrates significantly (P < .05) less binding. The data in the present study demonstrate that [3H]ABT-418 binds with high affinity to a population of binding sites in the rat brain that have the pharmacological characteristics of neuronal nAChRs. [3H]ABT-418 may, therefore, serve as a useful radioligand to further probe the observed differences in pharmacological properties between ABT-418 and other nicotinic agonists in vivo.


Foot orthoses for the prevention of lower limb overuse injuries in naval recruits: study protocol for a randomised controlled trial.
Foot orthoses are frequently used for the prevention of lower limb overuse injuries but evidence for their effectiveness is limited. The primary aim of this study is to determine if prefabricated foot orthoses reduce the incidence of lower limb overuse injuries in naval recruits undertaking 11 weeks of basic training. This study is a participant and assessor blinded, parallel-group, randomised controlled trial. The trial will recruit participants undertaking 11 weeks of basic training at the Royal Australian Navy Recruit School, Cerberus, Victoria, Australia. Participants will be randomised to a control group (flat insole) or an intervention group (prefabricated foot orthosis). Over the 11 weeks of basic training, participants will document the presence and location of pain in weekly self-report diaries. The end-point for each participant will be the completion of 11 weeks of basic training. The primary outcome measure will be the combined incidence of four lower limb injuries (medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy, and plantar fasciitis/plantar heel pain) which are common among defence members. Secondary outcome measures include: (i) overall incidence of lower limb pain, (ii) severity of lower limb pain, (iii) time to injury, (iv) time to drop-out due to injury, (v) adverse events, (vi) number of lost training days, (vii) shoe comfort, and (viii) general health status. Data will be analysed using the intention-to-treat principle. This randomised controlled trial will evaluate the effectiveness of prefabricated foot orthoses for the prevention of common lower limb overuse injuries in naval recruits. Australian New Zealand Clinical Trials Registry: ACTRN12615000024549.


Coreceptor utilization by human immunodeficiency virus type 1 is not a primary determinant of neutralization sensitivity.
We have examined the relationship between coreceptor utilization and sensitivity to neutralization in a primary isolate of human immunodeficiency virus type 1 and its T-cell line-adapted (TCLA) derivative. We determined that adaptation of the primary-isolate (PI) virus 168P results in the loss of the unique capacity of PI viruses to utilize the CCR5 coreceptor and in the acquisition by the TCLA 168C virus of sensitivity to neutralization by V3-directed monoclonal antibodies (MAbs). In experiments wherein infection by 168P is directed via either the CCR5 or the CXCR4 pathway, we demonstrate that the virus, as well as pseudotyped virions bearing a molecularly cloned 168P envelope protein, remains refractory to neutralization by MAbs 257-D, 268-D, and 50.1 regardless of the coreceptor utilized. This study suggests that coreceptor utilization is not a primary determinant of differential neutralization sensitivity in PI and TCLA viruses.


Requirement of interventional treatment in a patient being conservatively managed for persistent pneumothorax over a prolonged period.
An 85-year-old ex-smoker being managed conservatively over 2 years for a small right apical pneumothorax presented to the respiratory clinic with suddenly worsening shortness of breath and chest pain. A chest radiograph demonstrated sudden deterioration in the size of his pneumothorax. Previous CT scans had found emphysematous cystic changes within the lungs, and his new presentation warranted definitive surgical intervention with a right bullectomy and talc pleurodesis through a video-assisted thoracoscopic surgery procedure. The patient made a good recovery and was discharged from clinic a year later. This case demonstrates the importance of follow-up in patients with unresolved pneumothoraces due to the potential for sudden deterioration, and highlights the significance of respecting patient involvement and autonomy in the decision-making process.


Molecular Basis for the Final Oxidative Rearrangement Steps in Chartreusin Biosynthesis.
Oxidative rearrangements play key roles in introducing structural complexity and biological activities of natural products biosynthesized by type II polyketide synthases (PKSs). Chartreusin (1) is a potent antitumor polyketide that contains a unique rearranged pentacyclic aromatic bilactone aglycone derived from a type II PKS. Herein, we report an unprecedented dioxygenase, ChaP, that catalyzes the final α-pyrone ring formation in 1 biosynthesis using flavin-activated oxygen as an oxidant. The X-ray crystal structures of ChaP and two homologues, docking studies, and site-directed mutagenesis provided insights into the molecular basis of the oxidative rearrangement that involves two successive C-C bond cleavage steps followed by lactonization. ChaP is the first example of a dioxygenase that requires a flavin-activated oxygen as a substrate despite lacking flavin binding sites, and represents a new class in the vicinal oxygen chelate enzyme superfamily.


Eyes of Things.
Embedded systems control and monitor a great deal of our reality. While some "classic" features are intrinsically necessary, such as low power consumption, rugged operating ranges, fast response and low cost, these systems have evolved in the last few years to emphasize connectivity functions, thus contributing to the Internet of Things paradigm. A myriad of sensing/computing devices are being attached to everyday objects, each able to send and receive data and to act as a unique node in the Internet. Apart from the obvious necessity to process at least some data at the edge (to increase security and reduce power consumption and latency), a major breakthrough will arguably come when such devices are endowed with some level of autonomous "intelligence". Intelligent computing aims to solve problems for which no efficient exact algorithm can exist or for which we cannot conceive an exact algorithm. Central to such intelligence is Computer Vision (CV), i.e., extracting meaning from images and video. While not everything needs CV, visual information is the richest source of information about the real world: people, places and things. The possibilities of embedded CV are endless if we consider new applications and technologies, such as deep learning, drones, home robotics, intelligent surveillance, intelligent toys, wearable cameras, etc. This paper describes the Eyes of Things (EoT) platform, a versatile computer vision platform tackling those challenges and opportunities.


Applying community ecological theory to maximize productivity of cultivated biocrusts.
Degraded rangelands around the world may benefit from the reestablishment of lost biological soil crusts (biocrusts, soil surface cryptogamic-microbial communities). Cultivation of biocrust organisms is the first step in this process, and may benefit from harnessing species interactions. Species interactions are a dominant force structuring ecological communities. One key element of community structure, species richness, is itself important because it can promote the productivity of the entire community. Here, we use biological soil crusts as a model to test the effects of species interactions on production of biocrust materials for use in ecosystem rehabilitation. We screened eight different moss and lichen species from semiarid rangelands of Montana, USA, for growth potential under two watering regimes. Mosses generally grew well, but we were unable to cultivate the selected lichen species. We produced a >400% increase in the biomass of one species (Ceratodon purpureus). We tested whether a parasite-host relationship between two lichens could be used to enhance productivity of the parasite species, but this also resulted in no net gain of lichen productivity. Finally, we constructed all possible community combinations from a pool of five moss species to test for overyielding (community productivity exceeding that expected from the growth of community members in monoculture), and to determine both if, and the mode in which, species richness increases productivity. Polycultures yielded more than would be expected based upon the production of community constituents in monoculture. Using structural equation models, we determined that there was a modest effect of species richness on community productivity (r = 0.24-0.25), which was independent of a stronger effect of the identity of species in the community (r = 0.41-0.50). These results will contribute to the optimization of biocrust cultivation, promoting the development of this emerging ecological rehabilitation technology.


Asthma-related school absenteeism and school concentration of low-income students in California.
Asthma is one of the leading causes of school absenteeism. Previous studies have shown that school absenteeism is related to family income of individual students. However, there is little research examining whether school absenteeism is related to school-level concentration of low-income students, independent of family income. The objective of this study was to examine whether the proportion of low-income students at a school was related to school absenteeism due to asthma. Using data from the 2007 California Health Interview Survey, a population-based survey of California households, we examined the association between attending schools with high concentrations of low-income students and missing school because of asthma, adjusting for demographic characteristics, asthma severity, and health insurance status. Schools with high concentrations of low-income students were identified on the basis of the percentage of students participating in the free and reduced-price meal program, data publicly available from the California Department of Education. Students attending schools with the highest concentrations of low-income students were more likely to miss school because of asthma. Students from low-income families, younger students, those with more frequent asthma symptoms, or those taking prescription asthma medications also were more likely to miss school because of asthma. The use of school-level interventions to decrease school absenteeism due to asthma should be explored, especially in schools with high concentrations of low-income students. Potential interventions could include school-based asthma education and disease management or indoor and outdoor air pollution control.


Spontaneous Rapid Odor Source Localization Behavior Requires Interhemispheric Communication.
Navigation, finding food sources, and avoiding danger critically depend on the identification and spatial localization of airborne chemicals. When monitoring the olfactory environment, rodents spontaneously engage in active olfactory sampling behavior, also referred to as exploratory sniffing [1]. Exploratory sniffing is characterized by stereotypical high-frequency respiration, which is also reliably evoked by novel odorant stimuli [2, 3]. To study novelty-induced exploratory sniffing, we developed a novel, non-contact method for measuring respiration by infrared (IR) thermography in a behavioral paradigm in which novel and familiar stimuli are presented to head-restrained mice. We validated the method by simultaneously performing nasal pressure measurements, a commonly used invasive approach [2, 4], and confirmed highly reliable detection of inhalation onsets. We further discovered that mice actively orient their nostrils toward novel, previously unexperienced, smells. In line with the remarkable speed of olfactory processing reported previously [3, 5, 6], we find that mice initiate their response already within the first sniff after odor onset. Moreover, transecting the anterior commissure (AC) disrupted orienting, indicating that the orienting response requires interhemispheric transfer of information. This suggests that mice compare odorant information obtained from the two bilaterally symmetric nostrils to locate the source of the novel odorant. We further demonstrate that asymmetric activation of the anterior olfactory nucleus (AON) is both necessary and sufficient for eliciting orienting responses. These findings support the view that the AON plays an important role in the internostril difference comparison underlying rapid odor source localization.


Preservation of human cell bioassay device for the on-site evaluation of environmental waters.
We have already developed a novel disposable bioassay device based on the low-density lipoprotein (LDL) uptaking activity of human hepatoblastoma Hep G2 cells in our previous work. However, this device is not readily applicable to evaluate river water toxicity on-site because it cannot be preserved for more than one week. In this work, we developed the method for preservation of the device to enable it to be preserved for at least one month. The device can be supplied to individual environmental sites without any facilities for cell culture. We can evaluate river water toxicity by 2 hours of exposure after thawing. Therefore, this kind of device could be a promising tool for daily water quality management.


Assessment of Surgical Treatment Strategies for Moderate to Severe Cervical Spinal Deformity Reveals Marked Variation in Approaches, Osteotomies, and Fusion Levels.
Although previous reports suggest that surgery can improve the pain and disability of cervical spinal deformity (CSD), techniques are not standardized. Our objective was to assess for consensus on recommended surgical plans for CSD treatment. Eighteen CSD cases were assembled, including a clinical vignette, cervical imaging (radiography, computed tomography/magnetic resonance imaging), and full-length standing radiography. Fourteen deformity surgeons (10 orthopedic, 4 neurosurgery) were queried regarding recommended surgical plans. There was marked variation in treatment plans across all deformity types. Even for the least complex deformities (moderate midcervical apex kyphosis), there was lack of agreement on approach (50% combined anterior-posterior, 25% anterior only, 25% posterior only), number of anterior (range, 2-6) and posterior (range, 4-16) fusion levels, and types of osteotomies. As the kyphosis apex moved caudally (cervical-thoracic junction/upper thoracic spine) and for cases with chin-on-chest kyphosis, >80% of surgeons agreed on a posterior-only approach and >70% recommended a pedicle subtraction osteotomy or vertebral column resection, but the range in number of anterior (4-8) and posterior (4-27) fusion levels was exceptionally broad. Cases of cervical/cervical-thoracic scoliosis had the least agreement for approach (48% posterior only, 33% combined anterior-posterior, 17% anterior-posterior-anterior or posterior-anterior-posterior, 2% anterior only) and had broad variation in the number of anterior (2-5) and posterior (6-19) fusion levels, and recommended osteotomies (41% pedicle subtraction osteotomy/vertebral column resection). Among a panel of deformity surgeons, there was marked lack of consensus on recommended surgical approach, osteotomies, and fusion levels for CSD. Further study is warranted to assess whether specific surgical treatment approaches are associated with better outcomes.


Fourier-based spatial mapping of oscillatory phenomena in fungi.
Microorganisms display a range of oscillatory phenomena that operate over different temporal scales. Fourier analysis provides a compact description of such oscillations in terms of their frequency, magnitude and phase. However, in the majority of studies there is no explicit consideration of the spatial organisation of the oscillation. Here we describe procedures and a software package to map oscillatory phenomena in microorganisms in both the time and frequency domains. Key parameters of interest, such as frequency, phase or magnitude of the oscillations, are presented as pseudo-colour coded maps. This maintains the spatial information in the image and greatly facilitates understanding of potentially complex propagating waves or development of oscillatory domains with distinct behaviour. We illustrate the utility of this system with reference to spatial analysis of the pulsatile component to amino acid transport in mycelial systems of Phanerochaete velutina and Coniophora puteana, and actin-myosin based contractions in Physarum polycephalum.


The emergence of tropical medicine in Portugal: the School of Tropical Medicine and the Colonial Hospital of Lisbon (1902-1935).
The School of Tropical Medicine was founded in 1902 along with the Colonial Hospital of Lisbon. The Portuguese government recognized the importance of colonising the tropics and therefore supported the creation of a specific locus of medical training that would prove to be crucial to the clinical and experimental study of tropical diseases. This paper examines the importance of such institutions for the emergence of a new scientific area of research while also functioning as a consolidation factor for the Third Portuguese Colonial Empire. The creation of a new concept of medical practice with respect to tropical diseases characterizes a specific aspect of colonization: it underlies and drives the discourse of colonization itself. Consultation of data collected by the Portuguese Tropical School and the Colonial Hospital during the period between 1902 and 1935, the starting point of the present study, seeks to shed light on the ongoing debate concerning the history of tropical medicine within European colonial discourse.


Evaluation of rodent control to fight Lassa fever based on field data and mathematical modelling.
The Natal multimammate mouse (Mastomys natalensis) is the reservoir host of Lassa virus, an arenavirus that causes Lassa haemorrhagic fever in humans in West Africa. Because no vaccine exists and therapeutic options are limited, preventing infection through rodent control and human behavioural measures is currently considered to be the only option. In order to assess the efficacy of rodent control, we performed a 4-year field experiment in rural Upper Guinea and developed a mathematical model to simulate different control strategies (annual density control, continuous density control, and rodent vaccination). For the field study, rodenticide baits were placed each year in three rural villages, while three other villages were used as controls. Rodents were trapped before and after every treatment and their antibody status and age were determined. Data from the field study were used to parameterize the mathematical model. In the field study, we found a significant negative effect of rodent control on seroprevalence, but this effect was small especially given the effort. Furthermore, the rodent populations recovered rapidly after rodenticide application, leading us to conclude that an annual control strategy is unlikely to significantly reduce Lassa virus spillover to humans. In agreement with this finding, the mathematical model suggests that the use of continuous control or rodent vaccination is the only strategy that could lead to Lassa virus elimination. These field and model results can serve as a guide for determining how long and frequent rodent control should be done in order to eliminate Lassa virus in rural villages.


The porA alleles are identical in subgroup III serogroup A Neisseria meningitidis strains isolated in China in the 1960s and 1980s.
The porA genes from serogroup A, subgroup III strains isolated in the People's Republic of China in 1966 and in 1984 and 1985 were amplified by PCR at an annealing temperature of 75 degrees C. The DNA sequences (5 strains) and the restriction patterns generated by MspI (14 strains) were identical, unlike the results reported by Peixuan et al. (Z. Peixuan, H. Xujing, and X. Li, J. Clin. Microbiol. 33:458-462, 1995). Furthermore, PCR products which were amplified at an annealing temperature of 60 degrees C, as described by Peixuan et al., were heterogeneous in our study.


Changes in the axon terminals of primary afferents from a single vibrissa in the rat trigeminal nuclei after active touch deprivation or exposure to an enriched environment.
Lasting modifications of sensory input induce structural and functional changes in the brain, but the involvement of primary sensory neurons in this plasticity has been practically ignored. Here, we examine qualitatively and quantitatively the central axonal terminations of a population of trigeminal ganglion neurons, whose peripheral axons innervate a single mystacial vibrissa. Vibrissa follicles are heavily innervated by myelinated and unmyelinated fibers that exit the follicle mainly through a single deep vibrissal nerve. We made intraneural injections of a mixture of cholera-toxin B (CTB) and isolectin B4, tracers for myelinated and unmyelinated fibers, respectively, in three groups of young adult rats: controls, animals subjected to chronic haptic touch deprivation by unilateral whisker trimming, and rats exposed for 2 months to environmental enrichment. The regional and laminar pattern of terminal arborizations in the trigeminal nuclei of the brain stem did not show gross changes after sensory input modification. However, there were significant and widespread increases in the number and size of CTB-labeled varicosities in the enriched condition, and a prominent expansion in both parameters in laminae III-IV of the caudal division of the spinal nucleus in the whisker trimming condition. No obvious changes were detected in IB4-labeled terminals in laminae I-II. These results show that a prolonged exposure to changes in sensory input without any neural damage is capable of inducing structural changes in terminals of primary afferents in mature animals, and highlight the importance of peripheral structures as the presumed earliest players in sensory experience-dependent plasticity.


MULTIDETECTOR-ROW COMPUTED TOMOGRAPHIC CHARACTERISTICS OF PRESUMED PREURETERAL VENA CAVA IN CATS.
Preureteral vena cava (circumcaval ureter, retrocaval ureter) occurs in a third of the feline population and has been associated with ureteral strictures in humans. The aim of this retrospective cross-sectional study was to describe the contrast-enhanced multidetector row computed tomographic (MDCT) characteristics of presumed preureteral vena cava in a group of cats. Medical records from two institutions located in different continents were searched from 2010-2013 for cases with complete contrast-enhanced MDCT examinations of the abdomen (i.e. included the entire course of the ureters and prerenal and renal segments of the caudal vena cava) and a diagnosis of preureteral caudal vena cava. For cases meeting inclusion criteria, CT scan data were retrieved and characteristics of the preureteral caudal vena cava were recorded. Presence of concomitant renal or ureteral diseases was also recorded. A total of 272 cats had contrast-enhanced abdominal CT scans during the study period and of these, 68 cats (22.43 ± 4.96%) had a diagnosis of presumed preureteral vena cava. In all affected cats, a "reverse-J ureter" was observed, i.e. a ureter running medially at the level of L4-5, passing dorsally to the caudal vena cava and then exiting ventrally between the caudal vena cava and aorta returning to its normal position. Having a preureteral vena cava resulted in an increased risk for concurrent urinary signs (OR = 3.00; CI: 95%; 1.28-6.99; P = 0.01). Findings supported the use of contrast-enhanced MDCT for characterizing morphology of preureteral vena cava and its relation with ureters in cats.


Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria.
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria. Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured. Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria. These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.


A realistic appraisal of boron neutron capture therapy as a cancer treatment modality.
Boron neutron capture therapy (BNCT) is a binary therapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope boron-10 is irradiated with neutrons to produce high-energy alpha particles and recoiling lithium-7 nuclei. In this Commentary we will focus on a number of papers that were presented at a Symposium entitled "Current Clinical Status of Boron Neutron Capture Therapy and Paths to the Future", which was held in September 2017 at the China National Convention Center in Beijing. Results were presented by clinicians from Japan, Finland, the United States, the China mainland and Taiwan, China who have been working in the multiple disciplines that are required for carrying out clinical BNCT. The main focus was on the treatment of patients with malignant brain tumors, recurrent tumors of the head and neck region, and cutaneous melanomas. The results obtained in treating these patients were reported in detail and, although most of the patients with brain tumors and head and neck cancer were not cured, there was evidence of some clinical efficacy. Although there are a number of problems that must be addressed, further clinical studies to evaluate the efficacy of BNCT are warranted. First, despite considerable effort by numerous investigators over the past 40 years, there still are only two boron-containing drugs in clinical use, L-boronophenylalanine (BPA) and sodium borocaptate (BSH). Therefore, until new and more effective boron delivery agents are developed, efforts should be directed to improving the dosing and delivery of BPA and BSH. Second, due to a variety of reasons, nuclear reactor-based BNCT has ended except for its use in the China mainland and Taiwan. Therefore, the future of BNCT depends upon the results of the ongoing Phase II clinical trials that are being carried out in Japan and the soon to be initiated trials that will be carried out in Finland. If the results obtained from these clinical trials are sufficiently promising, then BNCT will have a clear path to the future, especially for patients with the therapeutically challenging malignancies that in the past have been treated with reactor-based BNCT.


A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle.
Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing sarcomeres. To study sarcomerogenesis, we have generated a transcriptomics resource of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, most sarcomeric components group in two clusters, which are strongly induced after all myofibrils have been assembled, indicating a transcriptional transition during myofibrillogenesis. Following myofibril assembly, many short sarcomeres are added to each myofibril. Subsequently, all sarcomeres mature, reaching 1.5 µm diameter and 3.2 µm length and acquiring stretch-sensitivity. The efficient induction of the transcriptional transition during myofibrillogenesis, including the transcriptional boost of sarcomeric components, requires in part the transcriptional regulator Spalt major. As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, this defines an ordered sarcomere morphogenesis process under precise transcriptional control - a concept that may also apply to vertebrate muscle or heart development.


Impact of polymorphisms in WFS1 on prediabetic phenotypes in a population-based sample of middle-aged people with normal and abnormal glucose regulation.
Recently, variants in WFS1 have been shown to be associated with type 2 diabetes. We aimed to examine metabolic risk phenotypes of WFS1 variants in glucose-tolerant people and in individuals with abnormal glucose regulation. The type 2 diabetes-associated WFS1 variant rs734312 (His611Arg) was studied in the population-based Inter99 cohort involving 4,568 glucose-tolerant individuals and 1,471 individuals with treatment-naive abnormal glucose regulation, and in an additional 3,733 treated type 2 diabetes patients. The WFS1 rs734312 showed a borderline significant association with type 2 diabetes with directions and relative risks consistent with previous reports. In individuals with abnormal glucose regulation, the diabetogenic risk A allele of rs734312 was associated in an allele-dependent manner with a decrease in insulinogenic index (p = 0.025) and decreased 30-min serum insulin levels (p = 0.047) after an oral glucose load. In glucose-tolerant individuals the same allele was associated with increased fasting serum insulin concentration (p = 0.019) and homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.026). To study the complex interaction of WFS1 rs734312 on insulin release and insulin resistance we introduced Hotelling's T (2) test. Assuming bivariate normal distribution, we constructed standard error ellipses of the insulinogenic index and HOMA-IR when stratified according to glucose tolerance status around the means of each WFS1 rs734312 genotype level. The interaction term between individuals with normal glucose tolerance and abnormal glucose regulation on the insulinogenic index and HOMA-IR was significantly associated with the traits (p = 0.0017). Type 2 diabetes-associated risk alleles of WFS1 are associated with estimates of a decreased pancreatic beta cell function among middle-aged individuals with abnormal glucose regulation.


Distributive justice in Medicaid capitation: the evidence from Colorado.
In 1995, the state of Colorado began a new funding program for the provision of mental health services to Medicaid recipients. Medicaid funding was restructured from a fee-for-service system into a capitated managed care system. The restructuring altered the way in which mental health resources were allocated within Colorado's mental health system. This article explores the ethical principles inherent in the allocation of mental health resources within Colorado. The allocation system before and after the capitation pilot is analyzed according to three models of distributive justice. Under capitation, access to care corresponds to egalitarian ideals, while service delivery and outcomes follow a more utilitarian philosophy. Results from several empirical studies of the Colorado Medicaid system are used to support this ethical analysis. The analysis leads to the suggestion that the fair-opportunity rule may be a useful principle for developing just distribution systems in other states in the future.


Cytometric characterization of circulating tumor cells captured by microfiltration and their correlation to the CellSearch(®) CTC test.
Recent studies reporting hundreds, to thousands, of circulating tumor cells (CTCs) in the blood of cancer patients have raised questions regarding the prevalence of CTCs, as enumerated by the CellSearch(®) CTC Test. Although CellSearch has been shown to consistently detect clinically relevant CTCs; the ability to only capture EpCAM positive cells has led to speculation that it captures limited subsets of CTCs. In contrast, alternative approaches to CTC isolation are often cited as capturing large numbers of CTCs from patient blood. Not surprisingly the number of cells isolated by alternative approaches show poor correlations when compared to CellSearch, even when accounting for EpCAM presence or absence. In an effort to address this discrepancy, we ran an exploratory method comparison study to characterize and compare the CTC subgroups captured from duplicate blood samples from 30 breast and prostate cancer patients using a microfiltration system (CellSieve™) and CellSearch. We then categorized the CellSieve Cytokeratin(CK)+/CD45-/DAPI+ cells into five morphologically distinct subpopulations for correlative analysis. Like other filtration techniques, CellSieve isolated greater numbers of CK+/CD45- cells than CellSearch. Furthermore, analysis showed low correlation between the total CK+/CD45- cells captured by these two assays, regardless of EpCAM presence. However, subgrouping of CK+/CD45-/DAPI+ cells based on distinct cytokeratin staining patterns and nuclear morphologies elucidated a subpopulation correlative to CellSearch. Using method comparison analyses, we identified a specific CTC morphology which is highly correlative between two distinct capture methods. These data suggests that although various morphologic CTCs with similar phenotypic expressions are present in the blood of cancer patients, the clinically relevant cells isolated by CellSearch can potentially be identified using non-EpCAM dependent isolation. © 2014 The Authors. Published by Wiley Periodicals, Inc.


Peroxisome enzyme modification and oxidative stress in rat by hypolipidemic and antiinflammatory drugs.
Changes in the activities of two peroxisomal enzymes (catalase and thiolase), some parameters related to oxidative situations, such as conjugated dienes, zinc, iron, copper and superoxide dismutase after the administration of two known peroxisome proliferators (clofibrate and acetylsalicylic acid), and two drugs pharmacologically related to the former (probucol and diflunisal) have been studied in male Wistar rats. Administration of the drugs was made by p.o. for 15 days. After the treatment the rats were killed, their livers and brains were taken out, and their blood was collected. Peroxisomes were purified by differential centrifugation followed by ultracentrifugation. Total RNA was also extracted and the acyl CoA oxidase mRNA expression was studied. Clofibrate was inactive on both enzymes studied in liver and diflunisal in brain. However, the acyl CoA oxidase mRNA expression increased by clofibrate treatment. Results are justified by the liposolubility and protein-binding properties of the drugs. Otherwise, the present results show the existence of an increased lipid peroxidation, lower value of superoxide dismutase, and variable results for zinc, copper and iron trace elements. These data evidence an oxidative stress situation in plasma of rats treated with these drugs, probably as a consequence of an increase in some beta-oxidation enzymes, which brings about an overproduction of H2O2.


Consolidating emerging evidence surrounding HIVST and HIVSS: a rapid systematic mapping protocol.
HIV self-testing (HIVST) is becoming popular with policy makers and commissioners globally, with a key aim of expanding access through reducing barriers to testing for individuals at risk of HIV infection. HIV self-sampling (HIVSS) was available previously to self-testing but was confined mainly to the USA and the UK. It remains to be seen whether the momentum behind HIVST will also energise efforts to expand HIVSS. Recent years have seen a rapid growth in the type of evidence related to these interventions as well as several systematic reviews. The vast majority of this evidence relates to acceptability as well as values and preferences, although new types of evidence are emerging. This systematic map aims to consolidate all emerging evidence related to HIVST and HIVSS to respond to this rapidly changing area. We will systematically search databases and the abstracts of five conferences from 2006 to the present date, with monthly-automated database searches. Searches will combine key terms relating to HIV (e.g. HIV, AIDS, human immune-deficiency syndrome) with terms related to self-testing (e.g. home-test, self-test, mail-test, home dried blood spot test). Abstracts will be reviewed against inclusion criteria in duplicate. Data will be manually extracted through a standard form and then entered to an open access relational map (HIVST.org). When new and sufficient evidence emerges which addresses existing knowledge gaps, we will complete a review on a relevant topic. This innovative approach will allow rapid cataloguing, documenting and dissemination of new evidence and key findings as they emerge into the public domain. This protocol has not been registered with PROSPERO as they do not register systematic maps.


Comparing thoracic and intra-nasal pressure transients to monitor active odor sampling during odor-guided decision making in the mouse.
Recording of physiological parameters in behaving mice has seen an immense increase over recent years driven by, for example, increased miniaturization of recording devices. One parameter particularly important for odorant-driven behaviors is the breathing frequency, since the latter dictates the rate of odorant delivery to the nasal cavity and the olfactory receptor neurons located therein. Typically, breathing patterns are monitored by either measuring the breathing-induced temperature or pressure changes in the nasal cavity. Both require the implantation of a nasal cannula and tethering of the mouse to either a cable or tubing. To avoid these limitations we used an implanted pressure sensor which reads the thoracic pressure and transmits the data telemetrically, thus making it suitable for experiments which require a freely moving animal. Mice performed a Go/NoGo odorant-driven behavioral task with the implanted pressure sensor, which proved to work reliably to allow recording of breathing signals over several weeks from a given animal. We simultaneously recorded the thoracic and nasal pressure changes and found that measuring the thoracic pressure change yielded similar results compared to measurements of nasal pressure changes. Telemetrically recorded breathing signals are a feasible method to monitor odorant-guided behavioral changes in breathing rates. Its advantages are most significant when recording from a freely moving animal over several weeks. The advantages and disadvantages of different methods to record breathing patterns are discussed.


Biallelic variants in MAATS1 encoding CFAP91, a calmodulin-associated and spoke-associated complex protein, cause severe astheno-teratozoospermia and male infertility.
Multiple morphological abnormalities of the flagella (MMAF) consistently lead to male infertility due to a reduced or absent sperm motility defined as asthenozoospermia. Despite numerous genes recently described to be recurrently associated with MMAF, more than half of the cases analysed remain unresolved, suggesting that many yet uncharacterised gene defects account for this phenotype METHODS: Exome sequencing was performed on 167 infertile men with an MMAF phenotype. Immunostaining and transmission electron microscopy (TEM) in sperm cells from affected individuals were performed to characterise the ultrastructural sperm defects. Gene inactivation using RNA interference (RNAi) was subsequently performed in Trypanosoma. We identified six unrelated affected patients carrying a homozygous deleterious variants in MAATS1, a gene encoding CFAP91, a calmodulin-associated and spoke-associated complex (CSC) protein. TEM and immunostaining experiments in sperm cells showed severe central pair complex (CPC) and radial spokes defects. Moreover, we confirmed that the WDR66 protein is a physical and functional partner of CFAP91 into the CSC. Study of Trypanosoma MAATS1's orthologue (TbCFAP91) highlighted high sequence and structural analogies with the human protein and confirmed the axonemal localisation of the protein. Knockdown of TbCFAP91 using RNAi impaired flagellar movement led to CPC defects in Trypanosoma as observed in humans. We showed that CFAP91 is essential for normal sperm flagellum structure and function in human and Trypanosoma and that biallelic variants in this gene lead to severe flagellum malformations resulting in astheno-teratozoospermia and primary male infertility.


Racial and ethnic disparities in sexual risk behaviors and STDs during young men's transition to adulthood.
Racial and ethnic health disparities are an important issue in the United States. The extent to which racial and ethnic differences in STDs among youth are related to differences in socioeconomic characteristics and risky sexual behaviors requires investigation. Data from three waves of the National Survey of Adolescent Males (1988, 1990-1991 and 1995) were used to examine 1,880 young men's history of STDs and their patterns and trajectories of sexual risk behavior during adolescence and early adulthood. Multinomial and logistic regression analyses were conducted to test whether racial and ethnic differences in STDs are due to the lower socioeconomic status and higher levels of risky sexual behavior among minority groups. Young black men reported the highest rates of sexual risk and STDs at each wave and across waves. Compared with white men, black and Latino men had higher odds of maintaining high sexual risk and increasing sexual risk over time (odds ratios, 1.7-1.9). In multivariate analyses controlling for socioeconomic characteristics, black men were more likely than white men to have a history of STDs (3.2-5.0); disparities persisted in analyses controlling for level of risky sexual behavior. Race and ethnicity continue to differentiate young black and Latino men from their white peers in terms of STDs. Prevention programs that target different racial and ethnic subgroups of adolescent men and address both individual- and contextual-level factors are needed to curb STD incidence.


Impact of the expanded criteria donor allocation system on the use of expanded criteria donor kidneys.
The U.S. Organ Procurement and Transplantation Network recently implemented a policy allocating expanded criteria donor (ECD) kidneys by waiting time alone. ECD kidneys were defined as having a risk of graft failure > or = 1.7 times that of ideal donors. ECDs include any donor > or = 60 years old and donors 50 to 59 years old with at least two of the following: terminal creatinine >1.5 mg/dL, history of hypertension, or death by cerebrovascular accident. The impact of this policy on use of ECD kidneys is assessed. The authors compared use of ECD kidneys recovered in the 18 months immediately before and after policy implementation. Differences were tested using t test and chi2 analyses. There was an 18.3% increase in ECD kidney recoveries and a 15.0% increase in ECD kidney transplants in the first 18 months after policy implementation. ECD kidneys made up 22.1% of all recovered kidneys and 16.8% of all transplants, compared with 18.8% (P<0.001) and 14.5% (P<0.001), respectively, in the prior period. The discard rate was unchanged. The median relative risk (RR) for graft failure for transplanted ECD kidneys was 2.07 versus 1.99 in the prepolicy period (P=not significant); the median RR for procured ECD kidneys was unchanged at 2.16. The percentage of transplanted ECD kidneys with cold ischemia times (CIT) <12 hr increased significantly; the corresponding percentage for CIT > or = 24 hr decreased significantly. The recent increase in ECD kidney recoveries and transplants appears to be related to implementation of the ECD allocation system.


Impact of Baseline Hemodynamics on the Effects of a Transcatheter Interatrial Shunt Device in Heart Failure With Preserved Ejection Fraction.
Background Interatrial shunt device (IASD) effects have been described in patients with heart failure and ejection fractions (EFs) ≥40%. However, baseline characteristics that correlate with greatest hemodynamic effects are unknown. On the basis of fundamental principles, we hypothesized that larger pressure gradients between left and right atria would yield greater shunt flow and greater hemodynamic effects. Methods and Results REDUCE LAP-HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a multicenter study that investigated IASD safety and performance. Sixty-four patients with EF ≥40% underwent device implantation followed by hemodynamic assessments at rest and exercise, including pulmonary capillary wedge pressure (PCWP, surrogate for left atrial pressure) and central venous pressure (CVP). At 6 months, IASD resulted in an average pulmonary-to-systemic blood flow ratio of 1.27 and increased exercise tolerance. The PCWP-CVP gradient (ie, the driving pressure for shunt flow) decreased at peak exercise from 16.8±6.9 to 11.4±5.5 mm Hg, because of increased CVP (17.5±5.4 to 20.3±7.9 mm Hg; P=0.04) and decreased PCWP (34.1±7.6 to 31.6±8.0 mm Hg; P=0.025). Baseline PCWP-CVP gradient during exercise correlated with changes of both PCWP-CVP and PCWP: Δ(PCWP-CVP)=10.0-0.89·(PCWP-CVP)baseline ( r2=0.56) and ΔPCWP=7.54-0.60·(PCWP-CVP)baseline ( P=0.001). Hemodynamics of patients with EF ≥50% and those with EF <50% responded similarly to IASD. Conclusions In heart failure patients with EF ≥40%, IASD significantly reduced PCWP and PCWP-CVP at peak exercise. Patients with higher baseline PCWP-CVP gradient had greater reductions in both parameters at follow-up. Results were sustained through 12 months and were independent of whether EF was ≥50% or between 40% and 49%. Additional studies will help further define the baseline hemodynamic predictors of exercise, hemodynamic, and clinical efficacy of the IASD. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01913613.


Experience-related reductions of myelin and axon diameter in adulthood.
The production of new myelin has been highlighted as an underappreciated mechanism of brain plasticity, but whether plastic decreases in myelin also happen in the adult brain has been largely unexplored. Recently, Sinclair et al. (Sinclair JS, Fischl MJ, Alexandrova O, Heß M, Grothe B, Leibold C, and Kopp-Scheinpflug C. J Neurosci 37: 8239-8255, 2017) have shown that auditory deprivation can lead to decrease in myelination and axon caliber even in healthy adulthood. These findings show that activity-regulated myelination is more complex than previously thought and expand our knowledge of how adult brain plasticity could operate on a cellular level.


Formation of transient dimers by a retroviral protease.
Retroviral proteases have been shown previously to be only active as homodimers. They are essential to form the separate and active proteins from the viral precursors. Spumaretroviruses produce separate precursors for Gag and Pol, rather than a Gag and a Gag-Pol precursor. Nevertheless, processing of Pol into a PR (protease)-RT (reverse transcriptase) and integrase is essential in order to obtain infectious viral particles. We showed recently that the PR-RT from a simian foamy virus, as well as the separate PRshort (protease) domain, exhibit proteolytic activities, although only monomeric forms could be detected. In the present study, we demonstrate that PRshort and PR-RT can be inhibited by the putative dimerization inhibitor cholic acid. Various other inhibitors, including darunavir and tipranavir, known to prevent HIV-1 PR dimerization in cells, had no effect on foamy virus protease in vitro. 1H-15N HSQC (heteronuclear single quantum coherence) NMR analysis of PRshort indicates that cholic acid binds in the proposed PRshort dimerization interface and appears to impair formation of the correct dimer. NMR analysis by paramagnetic relaxation enhancement resulted in elevated transverse relaxation rates of those amino acids predicted to participate in dimer formation. Our results suggest transient PRshort homodimers are formed under native conditions but are only present as a minor transient species, which is not detectable by traditional methods.


Long-term regular exercise and intraocular pressure: the Hisayama Study.
To investigate the association between long-term regular exercise (exercise frequency and exercise time) and 5-year changes in intraocular pressure in a general Japanese population. This population-based, cohort study was conducted in 2007. A total of 3119 Japanese community dwellers aged ≥ 40 years underwent eye examinations including intraocular pressure measurement with a noncontact tonometer. Of these, 1871 subjects (801 men and 1070 women) who underwent intraocular pressure measurement in 2012 participated. We assessed the associations of exercise frequency and exercise time with intraocular pressure using a linear regression model, adjusted for age and possible risk factors that can affect intraocular pressure. The mean 5-year intraocular pressure change ± standard deviation was - 0.84 ± 1.9 mmHg. After adjustment for age, sex, systolic blood pressure, diabetes, total cholesterol, high-density lipoprotein cholesterol, body mass index, waist circumference, smoking habit, alcohol intake, work intensity levels, and intraocular pressure at baseline, we observed that increased exercise frequency (times/week) and increased exercise time (min/week) were both significantly associated with reduced intraocular pressure (p < 0.05 each). In the subgroup analyses based on the presence/absence of possible confounding risk factors, there was no evidence of heterogeneity among all subgroups (p for heterogeneity > 0.2). Increased exercise frequency levels and increased exercise time are both independently associated with reduced intraocular pressure levels after adjustment for confounding factors.


Education and levels of salivary cortisol over the day in US adults.
Dysregulation of the hypothalamic-pituitary-adrenal axis is hypothesized to be an important pathway linking socioeconomic position and chronic disease. This paper tests the association between education and the diurnal rhythm of salivary cortisol. Up to eight measures of cortisol (mean of 5.38 per respondent) over 2 days were obtained from 311 respondents, aged 18-70, drawn from the 2001-2002 Chicago Community Adult Health Study. Multi-level models with linear splines were used to estimate waking level, rates of cortisol decline, and area-under-the-curve over the day, by categories of education. Lower education (0-11 years) was associated with lower waking levels of cortisol, but not the rate of decline of cortisol, resulting in a higher area-under-the-curve for more educated respondents throughout the day. This study found evidence of lower cortisol exposure among individuals with less education and thus does not support the hypothesis that less education is associated with chronic over-exposure to cortisol.


The effect of MElatonin on Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS): study protocol for a randomized controlled trial.
Depression following acute coronary syndrome (ACS) constitutes a serious and debilitating problem. Approximately one in five patients will develop significant depression following ACS and less severe depressive symptoms are even more frequent. Furthermore, anxiety symptoms and sleep-wake disturbances are frequent. The objective of the MEDACIS trial is to investigate whether prophylactic treatment with melatonin has a preventive effect on depression, depressive and anxiety symptoms, sleep, and circadian disturbances following ACS. "The effect of MElatonin and Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome" trial (MEDACIS) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial. A total of 240 patients with ACS and no depressive symptoms will be included in the trial for treatment with either 25 mg melatonin or placebo for a 12-week period. Development and severity of depressive symptoms will be evaluated using Major Depression Inventory every 2 weeks with the purpose of investigating the potential preventive effect of melatonin on depressive symptoms. Previously, only selective serotonin reuptake inhibitors (SSRIs) have been investigated in a primary preventive setup in patients following ACS. However, SSRIs are associated with several side effects. An ideal intervention would constitute the highest degree of prevention of depressive symptoms with the lowest risk of side effects. In this regard, melatonin may have advantages due to its low toxicity as well as its proven anxiolytic and hypnotic effects. ClinicalTrials.gov, Identifier: NCT02451293 . Registered on 12 May 2015. EudraCT nr. 2015-002116-32.


Oral treatment of chickens with Lactobacillus reuteri LM1 reduces Brachyspira pilosicoli-induced pathology.
Avian intestinal spirochaetosis (AIS) results from the colonization of the caeca and colon of poultry by pathogenic Brachyspira, notably Brachyspira pilosicoli. Following the ban on the use of antibiotic growth promoters in the European Union in 2006, the number of cases of AIS has increased, which, alongside emerging antimicrobial resistance in Brachyspira, has driven renewed interest in alternative intervention strategies. Lactobacillus-based probiotics have been shown to protect against infection with common enteric pathogens in livestock. Our previous studies have shown that Lactobacillus reuteri LM1 antagonizes aspects of the pathobiology of Brachyspira in vitro. Here, we showed that L. reuteri LM1 mitigates the clinical symptoms of AIS in chickens experimentally challenged with B. pilosicoli. Two groups of 15 commercial laying hens were challenged experimentally by oral gavage with B. pilosicoli B2904 at 18 weeks of age; one group received unsupplemented drinking water and the other received L. reuteri LM1 in drinking water from 1 week prior to challenge with Brachyspira and thereafter for the duration of the study. This treatment regime was protective. Specifically, B. pilosicoli was detected by culture in fewer birds, bird weights were higher, faecal moisture contents were significantly lower (P<0.05) and egg production as assessed by egg weight and faecal staining score was improved (P<0.05). Also, at post-mortem examination, significantly fewer B. pilosicoli were recovered from treated birds (P<0.05), with only mild-moderate histopathological changes observed. These data suggest that L. reuteri LM1 may be a useful tool in the control of AIS.


First Report of Cylindrocladiella parva as a Grapevine Pathogen in New Zealand.
Isolates morphologically identified as Cylindrocladiella parva were isolated from characteristic black foot symptoms on a grapevine (Vitis vinifera) rooted on 101-14 rootstock from Central Otago in 2005 and 101-14 rootstocks from a nursery in the Auckland Region in 2007 and 2008. On potato dextrose agar, the isolates initially produced cottony, white mycelia that turned grayish cream or golden cream within 10 days, the initially tawny colony undersides becoming dark brown with age. Conidia (0 to 1 septate; 16.4 to 17.0 [16.7] × 2.3 to 2.6 [2.5] μm) and abundant chlamydospores were produced. To confirm identity of the isolates, genomic DNA was extracted and the ribosomal DNA (rDNA) and β-tubulin gene were amplified and sequenced (3,4). Sequences of the PCR products were compared with sequences in GenBank. The rDNA (535 bp) and β-tubulin (297 bp) sequences of the four isolates were 100 and 99% identical, respectively, to reported sequences of C. parva in GenBank (AY793454, grapevine isolate (4)/AY793455 for rDNA; AY793486/AY793488, grapevine isolate (4)/AY793489/HM034822 for β-tubulin). Although C. parva was previously isolated from grapevines in New Zealand (2) and rootstocks of mature grapevines, cuttings, and graft unions of grafted young grapevines in South Africa (4), its role as a pathogen of Vitis spp. has not been confirmed (2,4). However, it has been reported as a pathogen of Eucalyptus spp. (1) and was also isolated from Telopea speciosissima and Macadamia integrifolia in New Zealand (2,4). The C. parva isolates were tested as a mixed inoculum (four isolates) for pathogenicity on roots of 10 grapevine rootstock plants each of cvs. 101-14 and Schwarzmann (Sch). The rootstocks were grown in potting mix for 4 months, after which the root systems of all vines were wounded with an asparagus knife with a sharp, square tip, driven vertically down into the soil at four equidistant locations approximately 8 cm from the trunk. Each plant was inoculated with 50 ml of the mixed-isolate conidial suspension (106/ml), or 50 ml water (controls), followed by 50 ml of water. After 7 months of growth, the plants were harvested. For C. parva-inoculated plants, internal blackening of the stem base tissue was observed. Isolations from surface-sterilized trunk bases recovered C. parva from four and nine plants of 101-14 and Sch, respectively, with C. parva infections in 25 and 48%, respectively, of the four wood pieces taken per plant. Plants inoculated with water had no blackening and no C. parva was isolated from their stem bases. Mean shoot dry weights of inoculated plants (17.9 and 15.0 g for 101-14 and Sch, respectively) were significantly lower (P = 0.035) than noninoculated controls (26.5 and 20.0 g for 101-14 and Sch, respectively). Mean root dry weights were reduced by C. parva inoculation, although not significantly (32.7 and 27.0 g for C. parva inoculated 101-14 and Sch, respectively, and 36.2 and 27.4 g for control 101-14 and Sch, respectively). To our knowledge, this is the first report of C. parva as a pathogen of grapevines (2,4) and suggests that along with Cylindrocarpon spp., C. parva is part of the pathogen complex responsible for black foot of grapevines. References: (1) P. W. Crous et al. Plant Pathol. 42:302, 1993. (2) P. D. Gadgil et al. Fungi on Trees and Shrubs in New Zealand. Fungal Diversity Press, Hong Kong, 2005. (3) N. L. Glass and G. C. Donaldson. Appl. Environ. Microbiol. 61:1323, 1995. (4) G. J. van Coller et al. Australas. Plant Pathol. 34:489, 2005.


Use of pulsed-field gel electrophoresis typing to study an outbreak of infection due to Serratia marcescens in a neonatal intensive care unit.
Serratia marcescens is a well-known cause of nosocomial infections and outbreaks, particularly in critically ill neonates and immunocompromised patients. Numerous methods have been proposed for typing. We used pulsed-field gel electrophoresis (PFGE) typing to analyze an outbreak in a neonatal intensive care unit (NICU). We included 23 patient isolates from an outbreak (March to July 1995), and 10 patient isolates from different wards during the same time period. PFGE of whole-cell DNA digested by SpeI was used as a marker of strain identity. The most common presentation of the infection was sepsis in 18 of 23 (78%) neonates. Only four different biotypes were identified; biotype A8d accounted for 84% of the strains. PFGE typing revealed two clones responsible for two different clonal strain dissemination outbreaks from March to July, with 24 patient isolates being pattern A and 4 patient isolates being pattern E. PFGE typing suggests cross transmission between patients in the NICU and other wards. The isolates from 5 other patients showed distinct PFGE patterns. Extensive investigation and cultures failed to identify any environmental or staff reservoir of S. marcescens. This is one of the first reports applying PFGE to the study of S. marcescens, and this method was a useful marker of strain identity. PFGE typing distinguished strains which appeared to be the same by biotyping.


Water, sulfur dioxide and nitric acid adsorption on calcium carbonate: a transmission and ATR-FTIR study.
Calcium carbonate (CaCO3) is a reactive component of mineral dust aerosol as well as buildings, statues and monuments. In this study, attenuated total reflection (ATR) and transmission Fourier transform infrared spectroscopy (FTIR) have been used to study the uptake of water, sulfur dioxide and nitric acid on CaCO3 particles at 296 K. Under atmospheric conditions, CaCO3 particles are terminated by a Ca(OH)(CO3H) surface layer. In the presence of water vapor between 5 and 95% relative humidity (RH), water molecularly adsorbs on the Ca(OH)(CO3H) surface resulting in the formation of an adsorbed thin water film. The adsorbed water film assists in the enhanced uptake of sulfur dioxide and nitric acid on CaCO3 in several ways. Under dry conditions (near 0% RH), sulfur dioxide and nitric acid react with the Ca(OH)(CO3H) surface to form adsorbed carbonic acid (H2CO3) along with sulfite and nitrate, respectively. Adsorbed carbonic acid is stable on the surface under vacuum conditions. Once the surface saturates with a carbonic acid capping layer, there is no additional uptake of gas-phase sulfur dioxide and nitric acid. However, upon adsorption of water, carbonic acid dissociates to form gaseous carbon dioxide and there is further uptake of sulfur dioxide and nitric acid. In addition, adsorbed water increases the mobility of the ions at the surface and enhances uptake of SO2 and HNO3. In the presence of adsorbed water, CaSO3 forms islands of a crystalline hydrate whereas Ca(NO3)2 forms a deliquescent layer or micropuddles. Thus adsorbed water plays an important and multi-faceted role in the uptake of pollutant gases on CaCO3.


Examination of bariatric surgery Facebook support groups: a content analysis.
Support following bariatric surgery is vital to ensure long-term postoperative success. Many individuals undergoing bariatric surgery are turning to online modalities, especially the popular social media platform Facebook, to access support groups and pages. Despite evidence suggesting that the majority of patients considering bariatric surgery are utilizing online groups, little is known about the actual content of these groups. The purpose of the present study was to conduct a content analysis of bariatric surgery support groups and pages on Facebook. Online via Facebook, independent academic medical center, United States. Data from bariatric surgery-related Facebook support groups and pages were extracted over a 1-month period in 2016. Salient content themes (e.g., progress posts, depression content, eating behaviors) were coded reliably (all κ> .70). More than 6,800 posts and replies were coded. Results indicated that seeking recommendations (11%), providing information or recommendations (53%), commenting on changes since surgery (19%), and lending support to other members (32%) were the most common types of posts. Content surrounding anxiety, eating behaviors, depression, body image, weight bias, and alcohol was found less frequently. Online bariatric surgery groups can be used to receive support, celebrate physical and emotional accomplishments, provide anecdotal accounts of the "bariatric lifestyle" for preoperative patients, and comment on challenges with mental health and experiences of weight bias. Providers should become acquainted with the content commonly found in online groups and exercise caution in recommending these platforms to information-seeking patients.


Sleep disturbances and post-traumatic stress disorder in women.
Sleep disturbances are found in a majority of individuals diagnosed with posttraumatic stress disorder (PTSD). The purpose of this literature review is to provide information about PTSD, in addition to assessing sleep quality. Current research observes that the lifetime prevalence of PTSD diagnosis in women is increasing. Although there are several studies that have been conducted to assess PTSD and sleep, there is a gap in the research that pertains to women, PTSD, and sleep quality. The current study will compile information on the subject to aid in decreasing the gender disparity in PTSD research, which is important for treating the entire PTSD population. Using the PubMed and PsycINFO databases, a comprehensive search was conducted to find relevant research about sleep difficulties and PTSD. Sleep disturbances such as insomnia, re-current nightmares, REM sleep dysfunction, and obstructive sleep apnea (OSA) affect sleep quality in PTSD patients. The implications of this study suggest that more research should be conducted pertaining to women and PTSD with sleep difficulties. This research is needed to decrease both PTSD symptoms and sleep-related disorders.


Consensus Update for Systemic Treatment of Atopic Dermatitis.
In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD). We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience. We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations. We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate. We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.


Microarray gene expression: a study of between-platform association of Affymetrix and cDNA arrays.
Microarrays technology has been expanding remarkably since its launch about 15 years ago. With its advancement along with the increase of popularity, the technology affords the luxury that gene expressions can be measured in any of its multiple platforms. However, the generated results from the microarray platforms remain incomparable. In this direction, we earlier developed and tested an approach to address the incomparability of the expression measures of Affymetrix®- and cDNA-platforms. The method was an exploit involving transformation of Affymetrix data, which brought the gene expressions of both cDNA and Affymetrix platforms to a common and comparable level. The encouraging outcome of that investigation has subsequently acted as a motivator to focus attention on examining further in the direction of defining the association between the two platforms. Accordingly, this paper takes on a novel exploration towards determining a precise association using a wide range of statistical and machine learning approaches, specifically the various models are elaborately trailed using-regression (linear, cubic-polynomial, LOESS, bootstrap aggregating) and artificial neural networks (self-organizing maps and feedforward networks). After careful comparison, the existing relationship between the data from the two platforms is found to be non-linear where feedforward neural network captures the best delineation of the association.


Identification of telomerase RNAs from filamentous fungi reveals conservation with vertebrates and yeasts.
Telomeres are the nucleoprotein complexes at eukaryotic chromosomal ends. Telomeric DNA is synthesized by the ribonucleoprotein telomerase, which comprises a telomerase reverse transcriptase (TERT) and a telomerase RNA (TER). TER contains a template for telomeric DNA synthesis. Filamentous fungi possess extremely short and tightly regulated telomeres. Although TERT is well conserved between most organisms, TER is highly divergent and thus difficult to identify. In order to identify the TER sequence, we used the unusually long telomeric repeat sequence of Aspergillus oryzae together with reverse-transcription-PCR and identified a transcribed sequence that contains the potential template within a region predicted to be single stranded. We report the discovery of TERs from twelve other related filamentous fungi using comparative genomic analysis. These TERs exhibited strong conservation with the vertebrate template sequence, and two of these potentially use the identical template as humans. We demonstrate the existence of important processing elements required for the maturation of yeast TERs such as an Sm site, a 5' splice site and a branch point, within the newly identified TER sequences. RNA folding programs applied to the TER sequences show the presence of secondary structures necessary for telomerase activity, such as a yeast-like template boundary, pseudoknot, and a vertebrate-like three-way junction. These telomerase RNAs identified from filamentous fungi display conserved structural elements from both yeast and vertebrate TERs. These findings not only provide insights into the structure and evolution of a complex RNA but also provide molecular tools to further study telomere dynamics in filamentous fungi.


Interaction of hydroxylated collagen IV with the von hippel-lindau tumor suppressor.
The von Hippel-Lindau tumor suppressor (pVHL) targets hydroxylated alpha-subunits of hypoxia-inducible factor (HIF) for ubiquitin-mediated proteasomal destruction through direct interaction with the hydroxyproline binding pocket in its beta-domain. Although disruption of this process may contribute to VHL-associated tumor predisposition by up-regulation of HIF target genes, genetic and biochemical analyses support the existence of additional functions, including a role in the assembly of extracellular matrix. In an attempt to delineate these pathways, we searched for novel pVHL-binding proteins. Here we report a direct, hydroxylation-dependent interaction with alpha-chains of collagen IV. Interaction with pVHL was also observed with fibrillar collagen chains, but not the folded collagen triple helix. The interaction was suppressed by a wide range of tumor-associated mutations, including those that do not disturb the regulation of HIF, supporting a role in HIF-independent tumor suppressor functions.


First principles modeling of eosin-loaded ZnO films: a step toward the understanding of dye-sensitized solar cell performances.
A theoretical investigation of eosin-Y (EY) loaded ZnO thin films, the basic components of a dye-sensitized solar cell (DSSC), is presented. The EY/ZnO wurtzite (10-10) system has been fully described within a periodic approach using density functional theory (DFT) and a hybrid exchange-correlation functional. Reduced systems were also analyzed to simulate an electron transfer from the dye to the substrate. Injection times from dye to the semiconductor were calculated using the Newns-Anderson approach. Finally, the UV-visible spectra of EY/ZnO films were simulated using a time-dependent DFT approach and compared to that of the EY molecule computed in solution. The results obtained highlight that EY strongly adsorbs on the ZnO substrate contributing significantly to the electronic structure of the adsorbed system. The UV-visible spectral signature of the isolated EY molecule is still found when adsorbed on ZnO but the analysis of Gamma-point crystalline orbitals reveals that a direct HOMO-->LUMO excitation cannot lead to a direct electron injection into the semiconductor, the first unoccupied orbital with contributions from the ZnO substrate being the LUMO + 1. As a consequence, a two photon injection mechanism is proposed explaining the low efficiency of the EY/ZnO solar cells. On this basis, possible strategies for enhancing the cell efficiency are presented and discussed.


Nutrition of Honduran mothers/caretakers.
In 1996, the Honduran Ministry of Health conducted a national micronutrient survey of children 12-71 months old, which also included an assessment of the nutrition status of their mothers/caretakers. The 1,126 mothers/caretakers who participated in the survey tended to be short and plump. About 15% of them were at obstetric risk by virtue of their short stature and/or low body weight. About 9% had chronic energy deficiency (CED), but 27% were at least 20% overweight. CED was associated with socioeconomic indicators of poverty. Risk factors for being at least 20% overweight included being over 30 years old, not breast-feeding, having attended no higher than grade 4, 5, or 6 of primary school, coming from a wealthier household, and living in San Pedro Sula or medium-sized cities. Among the women surveyed, 26% of nonpregnant and 32% of pregnant mothers/caretakers were anemic. The likely principal cause of anemia was the low intake of bioavailable iron from food and, in some cases, excessive iron loss associated with intestinal parasites, especially hookworm. Only 50% of the mothers/caretakers participating in this study had received iron during their last pregnancy, and just 13% had received postpartum vitamin A. The results highlight the need to develop and implement an effective program to control iron deficiency anemia in women of reproductive age, including by fortifying such widely consumed foods as processed wheat and maize flour and by routinely administering iron supplements to high-risk groups. Postpartum vitamin A supplementation should be encouraged to protect both the mother and newborn infant against vitamin A deficiency.