Accelerated care versus standard care among patients with hip fracture: the HIP ATTACK pilot trial.
A hip fracture causes bleeding, pain and immobility, and initiates inflammatory, hypercoagulable, catabolic and stress states. Accelerated surgery may improve outcomes by reducing the duration of these states and immobility. We undertook a pilot trial to determine the feasibility of a trial comparing accelerated care (i.e., rapid medical clearance and surgery) and standard care among patients with a hip fracture. Patients aged 45 years or older who, during weekday, daytime working hours, received a diagnosis of a hip fracture requiring surgery were randomly assigned to receive accelerated or standard care. Our feasibility outcomes included the proportion of eligible patients randomly assigned, completeness of follow-up and timelines of accelerated surgery. The main clinical outcome, assessed by data collectors and adjudicators who were unaware of study group allocations, was a major perioperative complication (i.e., a composite of death, preoperative myocardial infarction, myocardial injury after noncardiac surgery, pulmonary embolism, pneumonia, stroke, and life-threatening or major bleeding) within 30 days of randomization. Of patients eligible for inclusion, 80% consented and were randomly assigned to groups (30 to accelerated care and 30 to standard care) at 2 centres in Canada and 1 centre in India. All patients completed 30-day follow-up. The median time from diagnosis to surgery was 6.0 hours in the accelerated care group and 24.2 hours in the standard care group (p < 0.001). A major perioperative complication occurred in 9 (30%) of the patients in the accelerated care group and 14 (47%) of the patients in the standard care group (hazard ratio 0.60, 95% confidence interval 0.26-1.39). These results show the feasibility of a trial comparing accelerated and standard care among patients with hip fracture and support a definitive trial. ClinicalTrials.gov, no. NCT01344343.


Deforming glassy polystyrene: Influence of pressure, thermal history, and deformation mode on yielding and hardening.
The toughness of a polymer glass is determined by the interplay of yielding, strain softening, and strain hardening. Molecular-dynamics simulations of a typical polymer glass, atactic polystyrene, under the influence of active deformation have been carried out to enlighten these processes. It is observed that the dominant interaction for the yield peak is of interchain nature and for the strain hardening of intrachain nature. A connection is made with the microscopic cage-to-cage motion. It is found that the deformation does not lead to complete erasure of the thermal history but that differences persist at large length scales. Also we find that the strain-hardening modulus increases with increasing external pressure. This new observation cannot be explained by current theories such as the one based on the entanglement picture and the inclusion of this effect will lead to an improvement in constitutive modeling.


Importance of classical morphology in the diagnosis of myelodysplastic syndrome.
Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders characterized by dysplastic, ineffective, clonal and neoplastic hematopoiesis. MDS represent a complex hematological problem: differences in disease presentation, progression and outcome have necessitated the use of classification systems to improve diagnosis, prognostication, and treatment selection. However, since a single biological or genetic reliable diagnostic marker has not yet been discovered for MDS, quantitative and qualitative dysplastic morphological alterations of bone marrow precursors and peripheral blood cells are still fundamental for diagnostic classification. In this paper, World Health Organization (WHO) classification refinements and current minimal diagnostic criteria proposed by expert panels are highlighted, and related problematic issues are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies. Although, in the future, morphology should be supplemented with new molecular techniques, the morphological approach, at least for the moment, is still the cornerstone for the diagnosis and classification of these disorders.


Next-generation DNA sequencing techniques.
Next-generation high-throughput DNA sequencing techniques are opening fascinating opportunities in the life sciences. Novel fields and applications in biology and medicine are becoming a reality, beyond the genomic sequencing which was original development goal and application. Serving as examples are: personal genomics with detailed analysis of individual genome stretches; precise analysis of RNA transcripts for gene expression, surpassing and replacing in several respects analysis by various microarray platforms, for instance in reliable and precise quantification of transcripts and as a tool for identification and analysis of DNA regions interacting with regulatory proteins in functional regulation of gene expression. The next-generation sequencing technologies offer novel and rapid ways for genome-wide characterisation and profiling of mRNAs, small RNAs, transcription factor regions, structure of chromatin and DNA methylation patterns, microbiology and metagenomics. In this article, development of commercial sequencing devices is reviewed and some European contributions to the field are mentioned. Presently commercially available very high-throughput DNA sequencing platforms, as well as techniques under development, are described and their applications in bio-medical fields discussed.


Aberrant prostaglandin synthase 2 expression defines an antigen-presenting cell defect for insulin-dependent diabetes mellitus.
Prostaglandins (PGs) are lipid molecules that profoundly affect cellular processes including inflammation and immune response. Pathways contributing to PG output are highly regulated in antigen-presenting cells such as macrophages and monocytes, which produce large quantities of these molecules upon activation. In this report, we demonstrate aberrant constitutive expression of the normally inducible cyclooxygenase PG synthase 2 (PGS(2)/ COX-2) in nonactivated monocytes of humans with insulin-dependent diabetes mellitus (IDDM) and those with islet autoantibodies at increased risk of developing this disease. Constitutive PGS(2) appears to characterize a high risk for diabetes as it correlates with and predicts a low first-phase insulin response in autoantibody-positive subjects. Abnormal PGS(2) expression in at-risk subjects affected immune response in vitro, as the presence of a specific PGS(2) inhibitor, NS398, significantly increased IL-2 receptor alpha-chain (CD25) expression on phytohemagglutinin-stimulated T cells. The effect of PGS(2) on CD25 expression was most profound in subjects expressing both DR04 and DQbeta0302 high-risk alleles, suggesting that this cyclooxygenase interacts with diabetes-associated MHC class II antigens to limit T-cell activation. These results indicate that constitutive PGS(2) expression in monocytes defines an antigen-presenting cell defect affecting immune response, and that this expression is a novel cell-associated risk marker for IDDM.


Prevalence of dentine hypersensitivity among adult patients attending a dental hospital clinic in Turkey.
The aim of this study is to determine the prevalence of dentine hypersensitivity (DH) and to examine some associated factors such as the initiating stimuli among adult patients attending the Restorative Clinic of the Kirikkale University Dental Faculty, Turkey. Questionnaires for 1169 patients, 678 men and 491 women, were completed and necessary clinical examinations performed during a one-year period and patients who were diagnosed with DH were questioned further about their occupation and smoking habits. Patients with at least two different quadrants which had sensitive teeth with sound exposed cervical dentine on the facial surface, were included in the study. The amount of cervical lesions, buccal gingival recession and initiating factors associated with the sensitive teeth were also recorded. Of the 1169 patients examined, 89 were diagnosed as having dentine hypersensitivity, giving a prevalence of 7.6%. The commonest teeth affected were the upper premolars and the commonest initiating factor was cold drinks. The prevalence of dentine hypersensitivity in a postgraduate clinic in Turkey was 7.6%. The commonest teeth affected were the upper premolar and the commonest initiating factor was cold drinks.


Evaluation of the safety of recent surgical microscopes equipped with xenon light sources.
Although recent surgical microscopes for neurosurgery are equipped with xenon light sources to obtain bright fields of vision, the safety of a xenon beam, which has strong energy intensity in a long ultraviolet light, for cortical neurons has not been evaluated. Cranial windows were made in the parietal bones of gerbils. The skull of each gerbil was covered with warmed saline (0.5 mm in depth) to maintain the brain temperature. Ultraviolet irradiation (365-nm) was performed for 30 minutes at energy levels of 9.6, 4.4, 1.3, and 0.3 mwatts/cm(2), and neuronal damage was observed in 90 +/- 4%, 42 +/- 23%, 9 +/- 6%, and 0 +/- 0% of pyramidal cells in the parietal cortex 24 hours later. With the use of a logistic regression curve, the energy level causing 50% of neuronal damage was estimated to be 5.4 mwatts/cm(2). By increasing the thickness of the saline layer over the skull surface (1 mm and 2 mm), neuronal damages were significantly attenuated (21 +/- 18% and 10 +/- 8%, respectively, 4.4 mwatts/cm(2). Because the highest energy levels of 365-nm ultraviolet rays emitted from surgical microscopes measured in the present study (0.379 mwatts/cm (2)) were much closer to the dose causing 0% damage than to the dose causing 9% damage, the risk of neuronal injury occurring during microsurgery could be negligible. However, care should be taken in patients who take medicine classified as photosensitizing agents, such as diphenylhydantoin, which are thought to concentrate ultraviolet energy. The use of saline over the cortical surface may be beneficial for reducing the detrimental effects of 365-nm ultraviolet light.


Nursing work and sensory experiences of hospital design: A before and after qualitative study following a move to all-single room inpatient accommodation.
The embodied experience of nursing practice is rarely studied. Drawing on data from an internationally relevant larger study conducted in 2013-14, here we explore the sensory dimension of the embodied experiences of nursing staff working on two acute NHS hospital wards before and after a move to all-single room inpatient accommodation. We undertook a secondary analysis of 25 interviews with nursing staff (12 before and 13 after the move with half [13/25] using photographs taken by participants) from a mixed-method before-and-after study. This analysis focused on the sensory dimensions of nursing staff's experiences of their working practices and the effect of the built environment upon these. Drawing on Pallasmaa's theoretocal insights, we report how the all-single room ward design prioritises 'focused vision' and hinders peripheral perception, whilst the open ward environment is rich in contextual and preconscious information. We suggest all-single room accommodation may offer staff an impoverished experience of caring for patients and of working with each other.


Geographical variation of human gut microbial composition.
Although we know there is considerable variation in gut microbial composition within host species, little is known about how this variation is shaped and why such variation exists. In humans, obesity is associated with the relative abundance of two dominant bacterial phyla: an increase in the proportion of Firmicutes and a decrease in the proportion of Bacteroidetes. As there is evidence that humans have adapted to colder climates by increasing their body mass (e.g. Bergmann's rule), we tested whether Firmicutes increase and Bacteroidetes decrease with latitude, using 1020 healthy individuals drawn from 23 populations and six published studies. We found a positive correlation between Firmicutes and latitude and a negative correlation between Bacteroidetes and latitude. The overall pattern appears robust to sex, age and bacterial detection methods. Comparisons between African Americans and native Africans and between European Americans and native Europeans suggest no evidence of host genotype explaining the observed patterns. The variation of gut microbial composition described here is consistent with the pattern expected by Bergmann's rule. This surprising link between large-scale geography and human gut microbial composition merits further investigation.


RNAi as a Tool to Study Virulence in the Pathogenic Yeast Candida glabrata.
The yeast Candida glabrata is a major opportunistic pathogen causing mucosal and systemic infections in humans. Systemic infections caused by this yeast have high mortality rates and are difficult to treat due to this yeast's intrinsic and frequently adapting antifungal resistance. To understand and treat C. glabrata infections, it is essential to investigate the molecular basis of C. glabrata virulence and resistance. We established an RNA interference (RNAi) system in C. glabrata by expressing the Dicer and Argonaute genes from Saccharomyces castellii (a budding yeast with natural RNAi). Our experiments with reporter genes and putative virulence genes showed that the introduction of RNAi resulted in 30 and 70% gene-knockdown for the construct-types antisense and hairpin, respectively. The resulting C. glabrata RNAi strain was used for the screening of a gene library for new virulence-related genes. Phenotypic profiling with a high-resolution quantification of growth identified genes involved in the maintenance of cell integrity, antifungal drugs, and ROS resistance. The genes identified by this approach are promising targets for the treatment of C. glabrata infections.


Evaluation of moisturizing effect of methanolic extract of five medicinal plants incorporated into cream bases using impedance and extensiometry methods.
Skin moisturizing is an important issue due to its impact on skin function. Adverse reactions to herbal extracts have been rarely reported and can be used in moisturizers. This study was conduct to evaluate moisturizing effect of a methanolic extract of five medicinal plants incorporated into cream bases. Methanolic extract of five medicinal plants including olive, burdock, licorice, mallow and marsh horsetail was prepared. The extracts were dissolved in distilled water completely and freeze-dried to a dry powder. These extracts were added separately to the cream based formulation that has been suggested to be appropriate for adding herbal extracts. Moisturizing effects of these creams with herbal extracts were assessed using the impedance method on 12 rats equally divided into six groups (one control and five cases), as well as the extensiometry method on 25 mice divided into five groups (in each group one cream with herbal extract and control cream were tested concurrently). Obtained results were compared with the control cream based. The maximum moisturizing effect was observed with the marsh horsetail. Other creams with herbal extracts, except the one with the licorice, also exerted significantly higher moisturizing effect compared to the controls (P<0.05). Regarding the force for skin tearing, the differences were statistically significant in all groups when compared to the control group (P<0.05) and the highest difference was seen in the marsh horsetail group (2.0832 ± 0.6811 kgN). The highest moisturizing activity was observed using marsh horsetail extract that can be explained by flavonoids content of marsh horsetail.


Abdominal synthetic CT reconstruction with intensity projection prior for MRI-only adaptive radiotherapy.
Objective. Owing to the superior soft tissue contrast of MRI, MRI-guided adaptive radiotherapy (ART) is well-suited to managing interfractional changes in anatomy. An MRI-only workflow is desirable, but producing synthetic CT (sCT) data through paired data-driven deep learning (DL) for abdominal dose calculations remains a challenge due to the highly variable presence of intestinal gas. We present the preliminary dosimetric evaluation of our novel approach to sCT reconstruction that is well suited to handling intestinal gas in abdominal MRI-only ART.Approach. We utilize a paired data DL approach enabled by the intensity projection prior, in which well-matching training pairs are created by propagating air from MRI to corresponding CT scans. Evaluations focus on two classes: patients with (1) little involvement of intestinal gas, and (2) notable differences in intestinal gas presence between corresponding scans. Comparisons between sCT-based plans and CT-based clinical plans for both classes are made at the first treatment fraction to highlight the dosimetric impact of the variable presence of intestinal gas.Main results. Class 1 patients (n= 13) demonstrate differences in prescribed dose coverage of the PTV of 1.3 ± 2.1% between clinical plans and sCT-based plans. Mean DVH differences in all structures for Class 1 patients are found to be statistically insignificant. In Class 2 (n= 20), target coverage is 13.3 ± 11.0% higher in the clinical plans and mean DVH differences are found to be statistically significant.Significance. Significant deviations in calculated doses arising from the variable presence of intestinal gas in corresponding CT and MRI scans result in uncertainty in high-dose regions that may limit the effectiveness of adaptive dose escalation efforts. We have proposed a paired data-driven DL approach to sCT reconstruction for accurate dose calculations in abdominal ART enabled by the creation of a clinically unavailable training data set with well-matching representations of intestinal gas.


Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair).
Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair.


Preparation and in-vitro Evaluation of an Antisense-containing Cationic Liposome against Non-small Cell Lung Cancer: a Comparative Preparation Study.
The current methods for treatment of cancers are inadequate and more specific methods such as gene therapy are in progress. Among different vehicles, cationic liposomes are frequently used for delivery of genetic material. This investigation aims to prepare and optimize DOTAP cationic liposomes containing an antisense oligonuclotide (AsODN) against protein kinase C alpha in non-small cells lung cancer (NSCLC). To perform this investigation, two different methods of ethanol injection and thin film hydration were used to prepare AsODN-loaded DOTAP liposomes. The formulated liposomes were then evaluated for their morphology, particle size, zeta potential and encapsulation efficiency, and the best formulation was chosen. In-vitro growth inhibitory effect of encapsulated ODN on A549 cells were evaluated by MTT and colonogenic assay. The physical and serum stability of liposomal ODN were also evaluated. Thin film hydration method resulted in large liposomes that required downsizing by extrusion with an encapsulation efficiency of 13%. Ethanol injection, in a single step gave liposomes with a small size of 115 nm and an encapsulation efficiency of around 90% which were physically stable for 6 months. The optimized liposome could protect oligonucleotides from degradation by nuclease. Cell studies showed a 20% sequence-specific inhibition of cell growth in MTT assay and revealed an LC50 of 103 nM in colonogenic studies. In conclusion, ethanol injection was able to provide suitable liposomes from the permanently charged DOTAP. Also the resulted liposomes were able to inhibit the growth of lung cancer cells.


Fractal flame structure due to the hydrodynamic Darrieus-Landau instability.
By using large scale numerical simulations, we obtain fractal structure, which develops at originally planar flame fronts due to the hydrodynamic Darrieus-Landau (DL) instability bending the fronts. We clarify some important issues regarding the DL fractal flames, which have been debated for a long time. We demonstrate an increase of the flame propagation speed with the hypothetic channel width, which controls the length scale of the instability development. We show that this increase may be fitted by a power law indicating the mean fractal properties of the flame front structure. The power exponent in this law is found to be not a universal constant, rather it depends on the flame properties-on the density drop at the front. Using box counting on the simulated flame front shapes we show the fractal flame dimension at the intermediate scale is smaller than the one given by the power law, but it has a similar dependency on the density drop. We also obtain a formation of pockets at the DL fractal flame fronts, which previously has been associated only with turbulent burning.


Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation.
Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL) cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remain undetected and current treatment is often suboptimal. To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment and management of FH in adults and children, and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of non-cholesterol risk factors, and safe and effective use of LDL lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed. This international guidance acknowledges evidence gaps, but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be employed to inform clinical judgement and be adjusted for country-specific and local health care needs and resources.


Impulsivity or comorbidity in bulimia nervosa. A controlled study of deliberate self-harm and alcohol and drug misuse in a community sample.
Studies showing high rates of alcohol and drug misuse and deliberate self-harm in bulimia nervosa have led some authors to call for a distinct diagnostic subgroup, sometimes termed "multi-impulsive bulimia". However, these studies have been uncontrolled and of clinic samples and may be subject to sampling bias. One hundred and two women with DSM-III-R bulimia nervosa were compared with 204 normal controls and 102 controls with other psychiatric disorders, all recruited from the same community sample. Interview measures were used for diagnosis and for the assessment of alcohol and drug misuse and deliberate self-harm. Bulimia nervosa cases did not differ from either of the control groups in terms of current alcohol consumption. Bulimia nervosa cases used more illicit drugs than either control group, but loss of control over drug use was very uncommon. Bulimia nervosa cases had a higher rate of deliberate self-harm than the controls. Only six (6%) bulimia nervosa cases had two or more of these behaviours concurrently. Sampling bias is present in clinic-based studies of comorbidity in bulimia nervosa. Those with comorbid substance misuse and deliberate self-harm are probably heterogeneous in character, and their classification as a subgroup would therefore be premature.


Patient and cycle characteristics predicting high pregnancy rates with single-embryo transfer: an analysis of the Society for Assisted Reproductive Technology outcomes between 2004 and 2013.
To analyze factors associated with high live birth rate and low multiple birth rate in fresh and frozen-thawed assisted reproductive technology (ART) cycles. Retrospective cohort analysis. Not applicable. The study population included 181,523 women undergoing in vitro fertilization with autologous fresh first cycles, 27,033 with fresh first oocyte donor cycles, 37,658 with fresh second cycles, and 35,446 with frozen-thawed second cycles. None. Live birth rate and multiple birth rate after single-embryo transfer (SET) and double embryo transfer (DET) were measured, in addition to cycle characteristics. In patients with favorable prognostic factors, including younger maternal age, transfer of a blastocyst, and additional embryos cryopreserved, the gain in the live birth rate from SET to DET was approximately 10%-15%; however, the multiple birth rate increased from approximately 2% to greater than 49% in both autologous and donor fresh and frozen-thawed transfer cycles. This study reports a 10%-15% reduction in live birth rate and a 47% decrement in multiple birth rate with SET compared with DET in the setting of favorable patient prognostic factors. Our findings present an opportunity to increase the rate of SET across the United States and thereby reduce the multiple birth rate and its associated poor perinatal outcomes with assisted reproductive technology pregnancies.


Effects of endotoxin on iron uptake by the hepatocyte.
Administration of endotoxins is often followed within 12-24 h by marked hypoferremia. Because the hepatocyte is the major site of both iron storage and transferrin synthesis, we have investigated the effects of an Escherichia coli endotoxin (lipopolysaccharide, LPS) on these parameters on isolated hepatocytes from normal Wistar rats (ND), rats previously treated intraperitoneally with 2.5 mg/kg (LD) or 25 mg/kg (HD) LPS, and control rats injected intraperitoneally with sterile saline (CD). No effects were observed on iron uptake from transferrin by ND cells incubated in vitro with up to 350 micrograms LPS/10(7) hepatocytes. There was also no significant difference in iron uptake between CD, HD, and LD hepatocytes 1 h after LPS injection. However, hepatocytes isolated 24 h after LPS administration took up iron significantly faster than controls. The uptake of non-transferrin-bound iron was also increased in HD and LD hepatocytes at 24 h but only in HD cells at 1 h. Transferrin binding was not altered in LPS-treated cells from ND rats but was depressed in cells from LPS-treated rats both at 1 h and at 24 h after injection. Transferrin receptor recycling was significantly increased at 24 h in cells from both LD and HD rats. Transferrin and total protein synthesis were also depressed at 1 h in LPS-treated rats, returning to normal values at 24 h. Direct preincubation of ND cells, however, failed to increase synthesis except at the highest concentrations of LPS. We conclude that LPS has an immediate (although indirect) effect on protein synthesis by the hepatocyte but not on iron uptake.(ABSTRACT TRUNCATED AT 250 WORDS)


Cross-reactivity of antibodies in human infections by the kinetoplastid protozoa Trypanosoma cruzi, Leishmania chagasi and Leishmania (viannia) braziliensis.
We have detected antibodies, in the sera of Chagas disease, Kala-azar and Mucocutaneous leishmaniasis patients, that bind multiple antigens shared between the three causative agents. The Chagas disease sera showed 98 to 100% positive results by ELISA when the Leishmania braziliensis and Leishmania chagasi antigens were used, respectively. The Kala-azar sera showed 100% positive results with Trypanosoma cruzi or L. braziliensis antigens by immunofluorescence assays. The antibodies in the sera of Mucocutaneous leishmaniasis patients showed 100% positive results by ELISA assays with T. cruzi or L. chagasi antigens. Furthermore, the direct agglutination of L. chagasi promastigotes showed that 95% of Kala-azar and 35% of Mucocutaneous leishmaniasis sera agglutinated the parasite in dilutions above 1:512. In contrast, 15% of Chagas sera agglutinated the parasite in dilutions 1:16 and below. Western blot analysis showed that the Chagas sera that formed at least 24 bands with the T. cruzi also formed 13 bands with the L. chagasi and 17 bands with the L. braziliensis. The Kala-azar sera that recognized at least 29 bands with the homologous antigen also formed 14 bands with the T. cruzi and 10 bands with the L. braziliensis antigens. Finally, the Mucocutaneous leishmaniasis sera that formed at least 17 bands with the homologous antigen also formed 10 bands with the T. cruzi and four bands with the L. chagasi antigens. These results indicate the presence of common antigenic determinants in several protozoal proteins and, therefore, explain the serologic cross-reactions reported here.


Evaluation of the aerosol models for SeaWiFS and MODIS by AERONET data over open oceans.
The operational atmospheric correction algorithm for Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) and Moderate Resolution Imaging Spectroradiometer (MODIS) uses the predefined aerosol models to retrieve aerosol optical properties, and their accuracy depends on how well the aerosol models can represent the real aerosol optical properties. In this paper, we developed a method to evaluate the aerosol models (combined with the model selection methodology) by simulating the aerosol retrieval using the Aerosol Robotic Network (AERONET) data. Our method can evaluate the ability of aerosol models themselves, independent of the sensor performance. Two types of aerosol models for SeaWiFS and MODIS operational atmospheric correction algorithms are evaluated over global open oceans, namely the GW1994 models and Ahmad2010 models. The results show that GW1994 models significantly overestimate the aerosol optical thicknesses and underestimate the Ångström exponent, which is caused by the underestimation of the scattering phase function. However, Ahmad2010 models can significantly reduce the overestimation of the aerosol optical thickness and the underestimation of the Ångström exponent as a whole, but this improvement depends on the backscattering angle. Ahmad2010 models have a significant improvement in the retrieval of the aerosol optical thickness at a backscattering angle less than 140°. For a backscattering angle larger than 140°, GW1994 models are better at retrieving the aerosol optical thickness than the Ahmad2010 models.


BioTorrents: a file sharing service for scientific data.
The transfer of scientific data has emerged as a significant challenge, as datasets continue to grow in size and demand for open access sharing increases. Current methods for file transfer do not scale well for large files and can cause long transfer times. In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. BioTorrents allows files to be transferred rapidly due to the sharing of bandwidth across multiple institutions and provides more reliable file transfers due to the built-in error checking of the file sharing technology. BioTorrents contains multiple features, including keyword searching, category browsing, RSS feeds, torrent comments, and a discussion forum. BioTorrents is available at http://www.biotorrents.net.


Phantom Shocks Associated With a Wearable Cardioverter Defibrillator.
Wearable cardioverter defibrillators (WCDs) are external devices capable of continuous cardiac rhythm monitoring as well as automatic detection and defibrillation of potentially life-threatening arrhythmias such as ventricular tachycardia (VT) and ventricular fibrillation (VF). They are an alternative approach for patients when an implantable cardioverter defibrillator (ICD) is not appropriate. Although treatment with ICD is considered highly effective for the primary and secondary prevention of sudden cardiac death (SCD) in high-risk patients susceptible to VT and VF, patients may still experience psychological difficulties such as fear of shock, avoidance of normal behaviors and reduced quality of life. One of these phenomena is phantom shock (PS), which is defined as a perception of having received a shock with no evidence of recorded defibrillation upon device interrogation. While PS has been reported in the ICD literature, to the best of our knowledge, we present the first known case of WCD-related PS. We also present a review of the current literature to explore the prevalence of PS, the factors associated with its pathogenesis and interventional studies aimed at reducing its occurrence. We highlight this case because PS is considered a phenomenon that few recognize, which should be discriminated from real device shocks before clinicians initiate treatment, device reprogramming or device discontinuation. We describe the psychosocial factors associated with PS to emphasize the importance of managing any associated psychiatric disorders and psychosocial factors both before and after initiation of device treatment.


Preparation and wettability examinations of transparent SiO2 binder-added MgF2 nanoparticle coatings covered with fluoro-alkyl silane self-assembled monolayer.
SiO2-added MgF2 nanoparticle coatings with various surface roughness properties were formed on fused silica-glass substrates from autoclaved sols prepared at 100-180 °C. To give it hydrophobicity, we treated the samples with fluoro-alkyl silane (FAS) vapor to form self-assembled monolayers on the nanoparticle coating and we examined the wettability of the samples. The samples preserved good transparency even after the FAS treatment. The wettability examination revealed that higher autoclave temperatures produced a larger average MgF2 nanoparticle particle size, a larger surface roughness, and a higher contact angle and the roll-off angle.


Stability of a flow down an incline with respect to two-dimensional and three-dimensional disturbances for Newtonian and non-Newtonian fluids.
Squire's theorem, which states that the two-dimensional instabilities are more dangerous than the three-dimensional instabilities, is revisited here for a flow down an incline, making use of numerical stability analysis and Squire relationships when available. For flows down inclined planes, one of these Squire relationships involves the slopes of the inclines. This means that the Reynolds number associated with a two-dimensional wave can be shown to be smaller than that for an oblique wave, but this oblique wave being obtained for a larger slope. Physically speaking, this prevents the possibility to directly compare the thresholds at a given slope. The goal of the paper is then to reach a conclusion about the predominance or not of two-dimensional instabilities at a given slope, which is of practical interest for industrial or environmental applications. For a Newtonian fluid, it is shown that, for a given slope, oblique wave instabilities are never the dominant instabilities. Both the Squire relationships and the particular variations of the two-dimensional wave critical curve with regard to the inclination angle are involved in the proof of this result. For a generalized Newtonian fluid, a similar result can only be obtained for a reduced stability problem where some term connected to the perturbation of viscosity is neglected. For the general stability problem, however, no Squire relationships can be derived and the numerical stability results show that the thresholds for oblique waves can be smaller than the thresholds for two-dimensional waves at a given slope, particularly for large obliquity angles and strong shear-thinning behaviors. The conclusion is then completely different in that case: the dominant instability for a generalized Newtonian fluid flowing down an inclined plane with a given slope can be three dimensional.


The best possible child.
Julian Savulescu argues for two principles of reproductive ethics: reproductive autonomy and procreative beneficence, where the principle of procreative beneficence is conceptualised in terms of a duty to have the child, of the possible children that could be had, who will have the best opportunity of the best life. Were it to be accepted, this principle would have significant implications for the ethics of reproductive choice and, in particular, for the use of prenatal testing and other reproductive technologies for the avoidance of disability, and for enhancement. In this paper, it is argued that this principle should be rejected, and it is concluded that while potential parents do have important obligations in relation to the foreseeable lives of their future children, these obligations are not best captured in terms of a duty to have the child with the best opportunity of the best life.


Postexposure treatment with a Src-PTK inhibitor in combination with N-l-acetyl cysteine to reduce noise-induced hearing loss.
Both the antioxidant, N-l-acetyl cysteine (NAC), and the Src inhibitor, KX1-004, have been used to protect the cochlea from hazardous noise. In order to extend our previous work on KX1-004 with noise exposure, the current studies were undertaken with two goals: (1) to test the effectiveness of NAC and KX1-004 in combination with one another when given in a protection paradigm, and (2) to test the NAC+KX1-004 combination in a postexposure rescue paradigm. The noise exposure for the first experiment consisted of a 4-kHz octave band of noise at 107 dB SPL for 2 hours. The combination of NAC and KX1-004 were administered either prior to the noise exposure or post exposure (rescue). The second experiment was undertaken to extend the findings of the first experiment's rescue paradigm. The 4 kHz octave band noise was delivered at 112 dB SPL for 1 hour, with the experimental drugs delivered only in a rescue paradigm. In Experiment 1, animals treated before the 2-hour noise exposure with the combination of NAC and KX1-004 had from 12 to 17 dB less permanent threshold shift when compared to control saline treated animals. Treatment in the rescue paradigm did not produce any reductions in threshold shift from the 2-hour exposure. In the second experiment, with the 1-hour noise, rescue with KX1-004 or KX1-004 plus NAC yielded small, but significant, reductions in threshold shift. There was no additional benefit from the combination of NAC and KX1-004 over KX1-004 by itself.


Several empirical studies have investigated Job Burnout and its predictors, underlining the role of situational and organizational factors. The Perceptions of Context construct (PoC) has yet to be studied in healthcare contexts. The aim of the study is to broaden the knowledge of the Job Burnout determinants focusing on the dimensions of the context and to integrate research in this field with a construct that emphasizes the relational dimension, the Interpersonal Strain. 105 health-care workers of an Italian organization have completed a self-report questionnaire including the following scales: Perceptions of Context - Perceptions of the social component (colleagues, teamwork, supervisor, management, collaboration of patients and family members, collaboration between wards) and Perceptions of the task (workload and time pressure); MBI-GS (Exhaustion and Cynicism); ISW Scale (Interpersonal Strain). The results confirm the association between the PoC and Job Burnout and show the cross-sectional role played by Perception of Time Pressure on all three dimensions of Job Burnout. An interesting result is the role played by the perceptions of the social component, in particular the role of Supervisor Perceptions in predicting Exhaustion and Cynicism, and the role of Teamwork Perceptions in predicting Interpersonal Strain. Significant differences between the PoCs and the membership ward emerged. Based on our results, it is possible to plan focused prevention and intervention actions.


The relationship between employment status and self-rated health among wage workers in South Korea: the moderating role of household income.
The purpose of the study reported in this article was to investigate the relationship between employment status and self-rated health (SRH) and the moderating effect of household income among wage workers in South Korea. This research analyzed the Korean Labor and Income Panel Study, 2005 to 2008. Of the 10,494 respondents participating in the survey during the period, a total of 1,548 people whose employment status had remained either precarious or nonprecarious were selected. A moderated multiple regression model was used to examine the main effect of employment status on SRH and the moderating effect of total household income on the relationship between employment status and SRH. Among 343 precarious workers and 1,205 nonprecarious workers, after controlling for gender, age, education, smoking, and drinking, employment status was associated with SRH of wage workers, and household income was found to have a moderating effect on SRH in that higher income buffers the link between unstable employment status and low SRH. Unstable employment, combined with low income, was significantly related to precarious wage workers' perceived health. To promote public health, efforts may be needed to secure not only people's employment, but also their income.


Exploring barriers to and facilitators of malaria prevention practices: a photovoice study with rural communities at risk to Plasmodium knowlesi malaria in Sabah, Malaysia.
The control of Plasmodium knowlesi malaria remains challenging due to the presence of macaque monkeys and predominantly outdoor-biting Anopheles mosquitoes around human settlements. This study aims to explore the barriers and facilitators related to prevention of mosquito bites among rural communities living in Sabah, Malaysia using the participatory visual method, photovoice. From January through June 2022, 26 participants were recruited from four villages in Kudat, Sabah, using purposive sampling. Participants were male and female villagers, aged > 18 years old. After photovoice training in the villages, participants documented facilitators of and barriers related to avoiding mosquito bites using their own smartphone cameras, and provided narratives for their photos. Twelve Focus Group Discussions (FGDs) sessions in three rounds were held to share and discuss the photos, and to address challenges to the avoidance of mosquito bites. All discussions were conducted in the Sabah Malay dialect, and were video and audio recorded, transcribed, and analyzed using reflexive thematic analysis. The Ideation Model, a meta-theoretical model of behaviour change, underpinned this study. The most common types of barriers identified by participants included (I) intrapersonal factors such as low perceived threat of malaria, (II) livelihood and lifestyle activities consisting of the local economy and socio-cultural activities, and (III) physical and social environment. The facilitators were categorized into (I) intrapersonal reasons, including having the opportunity to stay indoors, especially women who are housewives, (II) social support by the households, neaighbours and healthcare workers, and (III) support from healthcare services and malaria awareness program. Participants emphasized the importance of stakeholder's support in implementing feasible and affordable approaches to P. knowlesi malaria control. Results provided insights regarding the challenges to preventing P. knowlesi malaria in rural Kudat, Sabah. The participation of communities in research was valuable in expanding knowledge of local challenges and highlighting possible ways to overcome barriers. These findings may be used to improve strategies for zoonotic malaria control, which is critical for advancing social change and minimizing health disparities in malaria prevention.


Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice.
Hepatitis B virus (HBV) infection is a global health issue. With over 350 million people affected worldwide, HBV infection remains the leading cause of liver cancer. This is a major concern, especially in developing countries. Failure of the immune system to mount an effective response against HBV leads to chronic infection. Although HBV vaccine is present and novel antiviral medicines are being created, eradication of virus-reservoir cells remains a major health topic. Described here is a method for the generation of viral antigen (Ag) -specific CD8+ cytotoxic T lymphocytes (CTLs) derived from induced pluripotent stem cells (iPSCs) (i.e., iPSC-CTLs), which have the ability to suppress HBV replication. HBV replication is efficiently induced in mice through hydrodynamic injection of an HBV expression plasmid, pAAV/HBV1.2, into the liver. Then, HBV surface Ag-specific mouse iPSC-CTLs are adoptively transferred, which greatly suppresses HBV replication in the liver and blood as well as prevents HBV surface Ag expression in hepatocytes. This method demonstrates HBV replication in mice after hydrodynamic injection and that stem cell-derived viral Ag-specific CTLs can suppress HBV replication. This protocol provides a useful method for HBV immunotherapy.


Computational model explains high activity and rapid cycling of Rho GTPases within protein complexes.
Formation of multiprotein complexes on cellular membranes is critically dependent on the cyclic activation of small GTPases. FRAP-based analyses demonstrate that within protein complexes, some small GTPases cycle nearly three orders of magnitude faster than they would spontaneously cycle in vitro. At the same time, experiments report concomitant excess of the activated, GTP-bound form of GTPases over their inactive form. Intuitively, high activity and rapid turnover are contradictory requirements. How the cells manage to maximize both remains poorly understood. Here, using GTPases of the Rab and Rho families as a prototype, we introduce a computational model of the GTPase cycle. We quantitatively investigate several plausible layouts of the cycling control module that consist of GEFs, GAPs, and GTPase effectors. We explain the existing experimental data and predict how the cycling of GTPases is controlled by the regulatory proteins in vivo. Our model explains distinct and separable roles that the activating GEFs and deactivating GAPs play in the GTPase cycling control. While the activity of GTPase is mainly defined by GEF, the turnover rate is a sole function of GAP. Maximization of the GTPase activity and turnover rate places conflicting requirements on the concentration of GAP. Therefore, to achieve a high activity and turnover rate at once, cells must carefully maintain concentrations of GEFs and GAPs within the optimal range. The values of these optimal concentrations indicate that efficient cycling can be achieved only within dense protein complexes typically assembled on the membrane surfaces. We show that the concentration requirement for GEF can be dramatically reduced by a GEF-activating GTPase effector that can also significantly boost the cycling efficiency. Interestingly, we find that the cycling regimes are only weakly dependent on the concentration of GTPase itself.


Mycobacterial immune reconstitution inflammatory syndrome in HIV-1 infection after antiretroviral therapy is associated with deregulated specific T-cell responses: beneficial effect of IL-2 and GM-CSF immunotherapy.
With the advent of antiretroviral therapy (ART) cases of immune reconstitution inflammatory syndrome (IRIS) have increasingly been reported. IRIS usually occurs in individuals with a rapidly rising CD4 T-cell count or percentage upon initiation of ART, who develop a deregulated immune response to infection with or without reactivation of opportunistic organisms. Here, we evaluated rises in absolute CD4 T-cells, and specific CD4 T-cell responses in 4 HIV-1+ individuals presenting with mycobacterial associated IRIS who received in conjunction with ART, IL-2 plus GM-CSF immunotherapy. We assessed CD4 T-cell counts, HIV-1 RNA loads, phenotype for naïve and activation markers, and in vitro proliferative responses. Results were compared with those observed in 11 matched, successfully treated asymptomatic clinical progressors (CP) with no evidence of opportunistic infections, and uninfected controls. Median CD4 T-cell counts in IRIS patients rose from 22 cells/microl before initiation of ART, to 70 cells/microl after 8 months of therapy (median 6.5 fold increase). This coincided with IRIS diagnosis, lower levels of naïve CD4 T-cells, increased expression of immune activation markers, and weak CD4 T-cell responses. In contrast, CP had a median CD4 T-cell counts of 76 cells/microl at baseline, which rose to 249 cells/microl 6 months post ART, when strong T-cell responses were seen in > 80% of patients. Higher levels of expression of immune activation markers were seen in IRIS patients compared to CP and UC (IRIS > CP > UC). Immunotherapy with IL-2 and GM-CSF paralleled clinical recovery. These data suggest that mycobacterial IRIS is associated with inadequate immune reconstitution rather than vigorous specific T-cell responses, and concomitant administration of IL-2 and GM-CSF immunotherapy with effective ART may correct/augment T-cell immunity in such setting resulting in clinical benefit.


Redox Chemistry and the Role of Trapped Molecular O2 in Li-Rich Disordered Rocksalt Oxyfluoride Cathodes.
In the search for high energy density cathodes for next-generation lithium-ion batteries, the disordered rocksalt oxyfluorides are receiving significant attention due to their high capacity and lower voltage hysteresis compared with ordered Li-rich layered compounds. However, a deep understanding of these phenomena and their redox chemistry remains incomplete. Using the archetypal oxyfluoride, Li2MnO2F, we show that the oxygen redox process in such materials involves the formation of molecular O2 trapped in the bulk structure of the charged cathode, which is reduced on discharge. The molecular O2 is trapped rigidly within vacancy clusters and exhibits minimal mobility unlike free gaseous O2, making it more characteristic of a solid-like environment. The Mn redox process occurs between octahedral Mn3+ and Mn4+ with no evidence of tetrahedral Mn5+ or Mn7+. We furthermore derive the relationship between local coordination environment and redox potential; this gives rise to the observed overlap in Mn and O redox couples and reveals that the onset potential of oxide ion oxidation is determined by the degree of ionicity around oxygen, which extends models based on linear Li-O-Li configurations. This study advances our fundamental understanding of redox mechanisms in disordered rocksalt oxyfluorides, highlighting their promise as high capacity cathodes.


Hereditary angioneurotic oedema.
Three families with hereditary angioneurotic oedema (HANE) are described. Serum CI-INH and C4 immunochemical determinations were performed on 23 members of the families: in 6 persons low CI-INH and C4 levels were found with typical symptoms of HANE, and in one asymptomatic subject. Normal ranges of both proteins for adults, children and newborns are given for comparative purposes. The importance of the early diagnosis and treatment is emphasized.


A systems-based approach to the environmental risk assessment of multiple stressors in honey bees.
The European Parliament requested EFSA to develop a holistic risk assessment of multiple stressors in honey bees. To this end, a systems-based approach that is composed of two core components: a monitoring system and a modelling system are put forward with honey bees taken as a showcase. Key developments in the current scientific opinion (including systematic data collection from sentinel beehives and an agent-based simulation) have the potential to substantially contribute to future development of environmental risk assessments of multiple stressors at larger spatial and temporal scales. For the monitoring, sentinel hives would be placed across representative climatic zones and landscapes in the EU and connected to a platform for data storage and analysis. Data on bee health status, chemical residues and the immediate or broader landscape around the hives would be collected in a harmonised and standardised manner, and would be used to inform stakeholders, and the modelling system, ApisRAM, which simulates as accurately as possible a honey bee colony. ApisRAM would be calibrated and continuously updated with incoming monitoring data and emerging scientific knowledge from research. It will be a supportive tool for beekeeping, farming, research, risk assessment and risk management, and it will benefit the wider society. A societal outlook on the proposed approach is included and this was conducted with targeted social science research with 64 beekeepers from eight EU Member States and with members of the EU Bee Partnership. Gaps and opportunities are identified to further implement the approach. Conclusions and recommendations are made on a way forward, both for the application of the approach and its use in a broader context.


Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple-negative breast cancer.
Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition MET, are crucial in several stages of cancer metastasis. Epithelial-mesenchymal transition allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processes are dynamic, mesenchymal cancer cells are likely to undergo MET transiently and subsequently re-undergo EMT to restart the metastatic process. Therefore, spatiotemporally coordinated mutual regulation between EMT and MET could occur during metastasis. To elucidate such regulation, we chose HCC38, a human triple-negative breast cancer cell line, because HCC38 is composed of epithelial and mesenchymal populations at a fixed ratio even though mesenchymal cells proliferate significantly more slowly than epithelial cells. We purified epithelial and mesenchymal cells from Venus-labeled and unlabeled HCC38 cells and mixed them at various ratios to follow EMT and MET. Using this system, we found that the efficiency of EMT is approximately an order of magnitude higher than that of MET and that the two populations significantly enhance the transition of cells from the other population to their own. In addition, knockdown of Zinc finger E-box-binding homeobox 1 (ZEB1) or Zinc finger protein SNAI2 (SLUG) significantly suppressed EMT but promoted partial MET, indicating that ZEB1 and SLUG are crucial to EMT and MET. We also show that primary breast cancer cells underwent EMT that correlated with changes in expression profiles of genes determining EMT status and breast cancer subtype. These changes were very similar to those observed in EMT in HCC38 cells. Consequently, we propose HCC38 as a suitable model to analyze EMT-MET dynamics that could affect the development of triple-negative breast cancer.


Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal.
Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy). Epidemiological data suggest that CAG is associated with two different types of tumors: Intestinal-type gastric cancer (GC) and type I gastric carcinoid (TIGC). The pathophysiological mechanisms which lead to the development of these gastric tumors are different. It is accepted that a multistep process initiating from Helicobacter pylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The TIGC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of TIGC. Thus, several events occur in the gastric mucosa before the development of intestinal-type GC and/or TIGC and these take several years. Knowledge of CAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.


Helical twist controls the thickness of F-actin bundles.
In the presence of condensing agents such as nonadsorbing polymer, multivalent counter ions, and specific bundling proteins, chiral biopolymers typically form bundles with a finite thickness, rather than phase-separating into a polymer-rich phase. Although short-range repulsive interactions or geometrical frustrations are thought to force the equilibrium bundle size to be limited, the precise mechanism is yet to be resolved. The importance of the tight control of biopolymer bundle size is illustrated by the ubiquitous cytoskeletal actin filament bundles that are crucial for the proper functioning of cells. Using an in vitro model system, we show that size control relies on a mismatch between the helical structure of individual actin filaments and the geometric packing constraints within bundles. Small rigid actin-binding proteins change the twist of filamentous actin (F-actin) in a concentration-dependent manner, resulting in small, well defined bundle thickness up to approximately 20 filaments, comparable to those found in filopodia. Other F-actin cross-linking proteins can subsequently link these small, well organized bundles into larger structures of several hundred filaments, comparable to those found in, for example, Drosophila bristles. The energetic tradeoff between filament twisting and cross-linker binding within a bundle is suggested as a fundamental mechanism by which cells can precisely adjust bundle size and strength.


Predicting posttraumatic distress in hospitalized trauma survivors with acute injuries.
Each year approximately 2.5 million Americans are hospitalized after sustaining traumatic physical injuries. Few investigations have comprehensively screened for posttraumatic symptomatic distress or identified predictors of posttraumatic stress disorder (PTSD) in representative samples of surgical inpatients. The subjects were 101 randomly selected survivors of motor vehicle crashes or assaults who were interviewed while hospitalized and 1, 4, and 12 months after injury. In the surgical ward, inpatients were screened for PTSD, depressive, and dissociative symptoms, for prior trauma, for pre-event functioning, and for alcohol and drug intoxication. Patient demographic and injury characteristics were also recorded. Random coefficient regression models were used to assess the association between these clinical, injury, and demographic characteristics and PTSD symptom levels over the year after the injury. Of the 101 surgical inpatients, 73% screened positive for high levels of symptomatic distress and/or substance intoxication. At 1, 4, and 12 months after the injury, 30%-40% reported symptoms consistent with a diagnosis of PTSD. High ward PTSD symptom levels were the strongest and most parsimonious predictor of persistent symptoms over the course of the year. Greater prior trauma, stimulant intoxication, and female gender were also associated with higher symptom levels. Increasing injury severity, however, was not associated with higher PTSD symptom levels. Clinical and demographic characteristics readily identifiable at the time of surgical inpatient hospitalization predict PTSD symptoms over the year after injury. Effectiveness trials that test screening and intervention procedures for at-risk inpatients should be developed.


Right to sexual and reproductive health in new population policies of Iran.
Sexual and reproductive health services in Iran are influenced by population policies. Willingness of Iranian policy makers to control the population's growth rate resulted in the provision of countrywide family planning services and contraceptives from 1990 to 2013. Now policy makers favour population growth because of a statistically significant decline in the fertility rate and ageing of the population. New population policies contain incentives for higher fertility and limitations on family planning services. Some elements of these policies contradict standards of international human rights treaties including prohibition against retrogressive measures and limitations on sexual and reproductive health services. These policies may jeopardize individual and public health. Iran should immediately revoke these laws and policies and progressively improve people's enjoyment of their right to sexual and reproductive health. The country's population policies should focus on encouraging people to have higher fertility by providing financial and social support to parents and future children.


Variation in Seed Allergen Content From Three Varieties of Soybean Cultivated in Nine Different Locations in Iowa, Illinois, and Indiana.
Soybean (Glycine max) is an important food stock, and also considered an allergenic food with at least eight well characterized allergens. However, it is a less prevalent allergen source than many other foods and is rarely life-threatening. Soybean is incorporated into commonly consumed foods, and therefore, the allergens pose a potential concern for individuals already sensitized. The protein profile of soybean can be affected by several factors including genetic and environmental. To investigate how soybean allergen content may be affected by genetics and/or environment, nine soy allergens were quantified from three commercial soybean varieties grown at nine locations in three states within a single climate zone in North America; Iowa, Illinois, and Indiana, United States. Quantitation was achieved using liquid chromatography-selected reaction monitoring (LC-SRM) tandem mass spectrometry with AQUA peptide standards specific to the nine target allergens. Quantitation of allergen concentration indicated that both genetics and location affected specific allergen content. Seven of the nine allergens were significantly influenced by genetics, with the exceptions of glycinin G4 and KTI 3. The allergens P34, Gly m Bd 28k, glycinin G3, and KTI 1 showed statistically significant impact from location as well, but at a lower threshold of significance compared with genetics (cultivar/variety). This dataset contributes to our understanding of the natural variation of endogenous allergens, as it represents a sampling of soybeans grown in a controlled, distributed plot design under agronomic conditions common for commercial soybean food and feed production. The aim was to build upon our recent understanding of how allergens are expressed as part of the overall soybean proteome.


Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity.
Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects.


[The criterion of cell division synchronization for assessing the stressor exposure of a Salmonella typhi population].
Criterion of the synchronization (CS) of cells division for S. typhi population is proposed. The criterion is based on the assumption of the normal distribution of cells with different generation time in the population after stressor (shock) action. CS is equal to the ratio of the dispersion of the generation time of cells in the population to the average generation time of the whole population and determined from the parameters of the mathematical model. The quantitative values of the parameters of the mathematical model were obtained by the minimization of error between the calculation and experimental data. CS was used for the evaluation and choice of the optimum stressor action in the synchronization of the division of S. typhi.


Evaluations of Structural Interventions for HIV Prevention: A Review of Approaches and Methods.
Structural interventions alter the social, economic, legal, political, and built environments that underlie processes affecting population health. We conducted a systematic review of evaluations of structural interventions for HIV prevention in low- and middle-income countries (LMICs) to better understand methodological and other challenges and identify effective evaluation strategies. We included 27 peer-reviewed articles on interventions related to economic empowerment, education, and substance abuse in LMICs. Twenty-one evaluations included clearly articulated theories of change (TOCs); 14 of these assessed the TOC by measuring intermediary variables in the causal pathway between the intervention and HIV outcomes. Although structural interventions address complex interactions, no evaluation included methods designed to evaluate complex systems. To strengthen evaluations of structural interventions, we recommend clearly articulating a TOC and measuring intermediate variables between the predictor and outcome. We additionally recommend adapting study designs and analytic methods outside traditional epidemiology to better capture complex results, influences external to the intervention, and unintended consequences.


Chondroitinase ABC reduces dopaminergic nigral cell death and striatal terminal loss in a 6-hydroxydopamine partial lesion mouse model of Parkinson's disease.
Parkinson's disease (PD) is characterised by dopaminergic cell loss within the substantia nigra pars compacta (SNc) that leads to reduced striatal dopamine content and resulting motor deficits. Identifying new strategies to protect these cells from degeneration and retain striatal dopaminergic innervation is therefore of great importance. Chondroitin sulphate proteoglycans (CSPGs) are recognised contributors to the inhibitory extracellular milieu known to hinder tissue recovery following CNS damage. Digestion of these molecules by the bacterial lyase chondroitinase ABC (ChABC) has been shown to promote functional recovery in animal models of neurological injury. Although ChABC has been shown to promote sprouting of dopaminergic axons following transection of the nigrostriatal pathway, its ability to protect against nigrostriatal degeneration in a toxin-based module with better construct validity for PD has yet to be explored. Here we examined the neuroprotective efficacy of ChABC treatment in the full and partial 6-hydroxydopamine (6-OHDA) lesion mouse models of PD. In mice bearing a full 6-OHDA lesion, ChABC treatment failed to protect against the loss of either nigral cells or striatal terminals. In contrast, in mice bearing a partial 6-OHDA lesion, ChABC treatment significantly protected cells of the rostral SNc, which remained at more than double the numbers seen in vehicle-treated animals. In the partial lesion model, ChABC treatment also significantly preserved dopaminergic fibres of the rostral dorsal striatum which increased from 15.3 ± 3.5% of the intact hemisphere in saline-treated animals to 36.3 ± 6.5% in the ChABC-treated group. These protective effects of ChABC treatment were not accompanied by improvements in either the cylinder or amphetamine-induced rotations tests of motor function. ChABC treatment provided significant protection against a partial 6-OHDA lesion of the nigrostriatal tract although the degree of protection was not sufficient to improve motor outcomes. These results support further investigations into the benefits of ChABC treatment for providing neuroprotection in PD.


Breaking the passivation--the road to a solvent free borohydride synthesis.
We describe a new method for the solvent-free synthesis of borohydrides at room temperature and demonstrate its feasibility by the synthesis of three of the most discussed borohydrides at present: LiBH(4), Mg(BH(4))(2) and Ca(BH(4))(2). This new gas-solid mechanochemical synthesis method is based on the reaction of metal hydrides with diborane to form the corresponding borohydrides. The synthesis will facilitate the preparation of a wide range of different borohydrides, including mixed borohydride systems, with tuneable sorption properties. We propose that diborane is an intermediate compound for the hydrogen sorption in borohydrides and may be the key for a reversible hydrogen ab- and desorption reaction under moderate conditions.


Single cell optical transfection.
The plasma membrane of a eukaryotic cell is impermeable to most hydrophilic substances, yet the insertion of these materials into cells is an extremely important and universal requirement for the cell biologist. To address this need, many transfection techniques have been developed including viral, lipoplex, polyplex, capillary microinjection, gene gun and electroporation. The current discussion explores a procedure called optical injection, where a laser field transiently increases the membrane permeability to allow species to be internalized. If the internalized substance is a nucleic acid, such as DNA, RNA or small interfering RNA (siRNA), then the process is called optical transfection. This contactless, aseptic, single cell transfection method provides a key nanosurgical tool to the microscopist-the intracellular delivery of reagents and single nanoscopic objects. The experimental possibilities enabled by this technology are only beginning to be realized. A review of optical transfection is presented, along with a forecast of future applications of this rapidly developing and exciting technology.


The integration of higher order form and motion by the human brain.
Our experience with a dynamic environment has tuned our visual system to use form and motion as complementary sources of information for object recognition. To identify the neural systems involved in integrating form and motion information during dynamic object processing, we used an fMRI adaptation paradigm which factorially manipulated form and motion repetition. Observers were sequentially presented with pairs of rotating novel objects in which the form or rotation direction in depth could be repeated. They were required to discriminate either dimension of the second target object, while the first object served as a form and/or motion prime. At the behavioural level, observers were faster to recognize the target or discriminate its direction when primed by the same form. Importantly, this form priming effect was enhanced when prime and target objects rotated in the same direction. At the neural level, the two priming effects (i.e., the main effect of form repetition and the interaction between form and motion repetition) were associated with reduced activations in distinct brain regions. Bilateral lateral occipital regions exhibited reduced activation when form was repeated irrespective of rotation direction. In contrast, bilateral anterior fusiform and posterior middle temporal regions (overlapping with hMT+/V5) regions showed an adaptation effect that depended on both form and motion direction. Thus, the current results reveal a visual processing hierarchy with lateral occipito-temporal cortex representing an object's 3D structure, and anterior fusiform and posterior middle temporal regions being involved in spatio-temporal integration of form and motion during dynamic object processing.


N-formylpeptide and complement C5a receptors are expressed in liver cells and mediate hepatic acute phase gene regulation.
Although the classical chemotactic receptor for complement anaphylatoxin C5a has been associated with polymorphonuclear and mononuclear phagocytes, several recent studies have indicated that this receptor is expressed on nonmyeloid cells including human endothelial cells, vascular smooth muscle cells, bronchial and alveolar epithelial cells, hepatocytes, and in the human hepatoma cell line HepG2. In this study, we examined the possibility that other members of the chemotactic receptor family are expressed in HepG2 cells and human liver, and the possibility that such receptors mediate changes in acute phase gene expression in HepG2 cells. Using polymerase chain reaction (PCR) amplification of HepG2 mRNA with primers based on highly conserved regions of the chemotactic subgroup of the G protein-coupled receptor family, we identified a PCR fragment from the formyl-methionyl-leucyl-phenylalanine (FMLP) receptor, as well as one from the C5a receptor. Immunostaining with antipeptide antisera to FMLPR confirmed the presence of this receptor in HepG2 cells. Receptor binding studies showed specific saturable binding of a radioiodinated FMLP analogue to HepG2 cells (Kd approximately 2.47 nM; R approximately 6 x 10(3) plasma membrane receptors per cell). In situ hybridization analysis showed the presence of FMLPR mRNA in parenchymal cells of the human liver in vivo. Both C5a and FMLP mediated concentration- and time-dependent changes in synthesis of acute phase proteins in HepG2 cells including increases in complement C3, factor B, and alpha 1-antichymotrypsin, as well as concomitant decreases in albumin and transferrin synthesis. The effects of C5a and FMLP on the synthesis of these acute phase proteins was evident at concentrations as low as 1 nM, and they were specifically blocked by antipeptide antisera for the corresponding receptor. In contrast to the effect of other mediators of hepatic acute phase gene regulation, such as interleukin 6, the effects of C5a and FMLP were reversed by increased concentrations well above the saturation point of the respective receptor. These results suggest that acute phase gene regulation by C5a and FMLP is desensitized at high concentrations, a property that is unique among the several known mechanisms for hepatic acute phase gene regulation.


Propofol inhibits muscarinic acetylcholine receptor-mediated signal transduction in Xenopus Oocytes expressing the rat M1 receptor.
The effects of propofol, 2,6-diisopropylphenol, an intravenous general anesthetic, on signal transduction mediated by the rat M1 muscarinic acetylcholine (ACh) receptor (M1 receptor) were examined in electrophysiological studies by analyzing receptor-stimulated, Ca2+-activated Cl--current responses in the Xenopus oocyte expression system. In oocytes expressing the M1 receptor, ACh induced the Ca2+-activated C1- current, in a dose-dependent manner (EC50= 114 nM). Propofol (5-50 microM) reversibly and dose-dependently inhibited induction of the Ca2+-activated Cl- current by ACh (100 nM) (IC50=5.6 microM). To determine a possible site affected by propofol in this signal transduction, we tested the effects of this anesthetic (10 microM) on the activation of current by injection of CaCl2 and aluminum fluoride (AlF4-). Propofol did not affect activation of the current by the intracellular injected Ca2+, or activation of the current by the intracellular injected AlF4-. These results indicate that propofol does not affect G protein, the inositol phosphate turnover, release of Ca2+ from Ca2+ store or the Ca2+-activated Cl- channel. Propofol apparently inhibits the M1 receptor-mediated signal transduction at the receptor site and/or the site of interaction between the receptor and associated G protein.


Edge fires drive the shape and stability of tropical forests.
In tropical regions, fires propagate readily in grasslands but typically consume only edges of forest patches. Thus, forest patches grow due to tree propagation and shrink by fires in surrounding grasslands. The interplay between these competing edge effects is unknown, but critical in determining the shape and stability of individual forest patches, as well the landscape-level spatial distribution and stability of forests. We analyze high-resolution remote-sensing data from protected Brazilian Cerrado areas and find that forest shapes obey a robust perimeter-area scaling relation across climatic zones. We explain this scaling by introducing a heterogeneous fire propagation model of tropical forest-grassland ecotones. Deviations from this perimeter-area relation determine the stability of individual forest patches. At a larger scale, our model predicts that the relative rates of tree growth due to propagative expansion and long-distance seed dispersal determine whether collapse of regional-scale tree cover is continuous or discontinuous as fire frequency changes.


Hormonal contraceptive use, pregnancy and parity, and the risk of cervical intraepithelial neoplasia 3 among oncogenic HPV DNA-positive women with equivocal or mildly abnormal cytology.
Oral contraceptive (OC) use, hormonal contraceptive use and multiparity are potential risk factors for cervical precancer, cervical intraepithelial neoplasia 3 (CIN3), but a limited number of studies have adequately accounted for possible confounding effect of oncogenic human papillomavirus (HPV) infection. To examine the relationships of these factors with CIN3, we conducted an analysis of women (n = 5,060) with minimally abnormal Pap smears who were enrolled in the ASCUS and LSIL Triage Study (ALTS), a clinical trial to evaluate management strategies. Cervical specimens collected at enrollment were tested for HPV DNA using 2 methods. Multivariate logistics regression models were used to assess associations (odds ratio [OR] with 95% confidence intervals [CI]) of the potential risk factors (e.g., OC use and parity) with testing oncogenic HPV positive among controls (<CIN2) (n = 4,114) and with rigorously reviewed cases of CIN3 identified throughout the study (n = 499) among women with oncogenic HPV (n = 3,126). Only former oral contraceptive use (OR = 1.3, 95% CI = 1.0-1.7) was associated marginally with having an oncogenic HPV infection among controls. Restricted to women with oncogenic HPV, current injectable hormonal contraceptive users were at an elevated risk of CIN3 (OR = 1.6, 95% CI = 1.2-2.1) compared to women who never used them. Similarly, restricted to women with HPV16 infection, current users of injectable contraceptives were at a marginally elevated risk of CIN3 (OR = 1.5, 95% CI = 1.0-2.3) compared to women who never used them. Oral contraceptive use, Norplant (implantable hormonal contraceptive) use, a history of pregnancy, age at first pregnancy, lifetime numbers of pregnancies and lifetime numbers of live births were not associated with CIN3. We conclude that only current injectable hormonal contraceptive use slightly elevated the risk (approximately 50%) of CIN3 in this young and low parity population of women with oncogenic HPV and minimally abnormal Pap smears but further confirmation of this relationship is needed.


Paired octamer rings of retinoschisin suggest a junctional model for cell-cell adhesion in the retina.
Retinoschisin (RS1) is involved in cell-cell junctions in the retina, but is unique among known cell-adhesion proteins in that it is a soluble secreted protein. Loss-of-function mutations in RS1 lead to early vision impairment in young males, called X-linked retinoschisis. The disease is characterized by separation of inner retinal layers and disruption of synaptic signaling. Using cryo-electron microscopy, we report the structure at 4.1 Å, revealing double octamer rings not observed before. Each subunit is composed of a discoidin domain and a small N-terminal (RS1) domain. The RS1 domains occupy the centers of the rings, but are not required for ring formation and are less clearly defined, suggesting mobility. We determined the structure of the discoidin rings, consistent with known intramolecular and intermolecular disulfides. The interfaces internal to and between rings feature residues implicated in X-linked retinoschisis, indicating the importance of correct assembly. Based on this structure, we propose that RS1 couples neighboring membranes together through octamer-octamer contacts, perhaps modulated by interactions with other membrane components.


Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3-3zeta.
Erythrocyte formation occurs throughout life in response to cytokine signaling. We show that microRNA-451 (miR-451) regulates erythropoiesis in vivo. Mice lacking miR-451 display a reduction in hematrocrit, an erythroid differentiation defect, and ineffective erythropoiesis in response to oxidative stress. 14-3-3zeta, an intracellular regulator of cytokine signaling that is repressed by miR-451, is up-regulated in miR-451(-/-) erythroblasts, and inhibition of 14-3-3zeta rescues their differentiation defect. These findings reveal an essential role of 14-3-3zeta as a mediator of the proerythroid differentiation actions of miR-451, and highlight the therapeutic potential of miR-451 inhibitors.


Characteristics of primary care office systems as predictors of mammography utilization.
To evaluate the association between primary care office systems and mammography utilization by women older than 50 years. Cross-sectional. An independent-practice association health maintenance organization (HMO) in Massachusetts. One hundred thirty-two primary care practices, representing 321 physicians and 4378 women with at least 12 months of recent, continuous assignment to a practice participating in the HMO. Practice characteristics and procedures for mammography referral and follow-up were ascertained by interviews of office managers. For each practice, the proportion of women older than 50 years who received a mammogram during their most recent 12-month period of assignment to the practice was calculated. Forty-five percent of eligible women received a mammogram during their most recent year of assignment to an HMO practice. In a regression model, use of one particular urban mammography center, group practice, and low percentage of Medicaid patients in the practice were each associated with 9% to 12% higher mammography utilization; use of flowsheets and the scheduling of mammograms by the patients themselves were associated with 7% to 9% higher utilization. Smaller, nonsignificant increases were associated with the use of reminders to patients (5%) and the presence of only internists on staff (5%). The model accounted for 51% of the variation in mammography utilization among practices. Mammography utilization among women older than 50 years, in a population in which cost was not a barrier, was related to specific office characteristics. Features of the mammography center, the process for scheduling mammograms, the use of flowsheets to prompt physicians, and the use of reminders to patients are important.


Antitumor effect of culinary-medicinal oyster mushroom, Pleurotus ostreatus (Jacq.: Fr.) P. Kumm., derived protein fraction on tumor-bearing mice models.
Previously, we reported the in vitro anticancer and immunomodulatory effect of a protein fraction designated as Cibacron blue affinity purified protein (CBAEP) obtained from the culinary-medicinal oyster mushroom, Pleurotus ostreatus. In the present study, we investigated the in vivo antitumor potential of CBAEP in different tumor-bearing mice models and studied the detailed mechanism of tumor regression in Dalton lymphoma (DL)-bearing mice. The lethal dose (LD50) of CBAEP was found to be 55 mg/kg body weight and sublethal doses (5 mg/kg and 10 mg/kg body weight) showed a prolonged tumor survival time in DL, Sarcoma-180, and B16F0 melanoma tumor-bearing mice. Further, CBAEP reduced about 35.68 and 51.43% DL cell growth in 5 and 10 mg/kg body weight, respectively. The in vivo CBAEP treatment showed an apoptotic feature as demonstrated in morphological study and sub-G0/G1 population in cell cycle and Western blot of DL cells. CBAEP also activated immunosuppression condition in DL tumor-bearing host. It also stimulated immune cells in the presence of nonspecific immunostunulator (LPS and ConA) ex vivo as well as enhanced Th1 response with production of TNF-α, IFN-γ, and IL-2. Moreover, it activated tumor-associated macrophages and NK cells. The present findings revealed the potent antitumor property of CBAEP, which might help in developing a new anticancer drug.


Photosynthesis by inflated pods of a desert shrub, Isomeris arborea.
The photosynthetic capacity and carbon metabolism of the fruits of Isomeris arborea (Capparidaceae), an evergreen shrub endemic to the desert and coastal habitats of Southern California and Baja California, are described. The inflated structure of the pods of I. arborea provides a model system for experimental studies of fruit photosynthesis in native plants since the gas concentration of the internal space can be manipulated and monitored separately from the external pod environment. CO2 released by seed respiration is partially contained in the inner gas space of the pods, resulting in an elevated CO2 environment inside the fruit (500 to 4000 μmol mol-1 depending on the stage of fruit development). A portion of this CO2 is assimilated by the inner layers of the pericarp, but a larger fraction leaks out. The photosynthetic layers of the pericarp use two different sources of CO2: the exocarp fixes exogenous CO2 while the endocarp fixes CO2 released by seed respiration into the pod cavity. Even though the total weight of the fruit increases during development, the combined rates of fixation of externally and internally supplied CO2 remained constant (10-11 μmol CO2 pod-1 h-1). After the pods attain maximum volume, the major change in gas exchange that takes place during fruit growth is a gradual increase in the amount of respiratory CO2 released by the seeds. This shifts the CO2 balance of the fruit from positive, in young fruits, to negative in mature fruits. Pericarp photosynthesis helped support not only the cost of fruit maintenance, but also the cost of fruit growth, particularly during the first stages of fruit development. During later fruiting stages insufficient carbon is fixed to fully supply either respiration or growth.


Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir).
The aim of this work was to develop an individualized score for predicting hepatocellular carcinoma (HCC) in patients with hepatitis C (HCV)-compensated cirrhosis. Among 1,323 patients with HCV cirrhosis enrolled in the French prospective ANRS CO12 CirVir cohort, 720 and 360 were randomly assigned to training and validation sets, respectively. Cox's multivariate model was used to predict HCC, after which a nomogram was computed to assess individualized risk. During follow-up (median, 51.0 months), 103 and 39 patients developed HCC in the training and validation sets, respectively. Five variables were independently associated with occurrence of HCC: age > 50 years (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.16; 3.25; P = 0.012); past excessive alcohol intake (HR, 1.55; 95% CI, 1.02; 2.36; P = 0.041); low platelet count (<100 Giga/mm(3) : HR, 2.70; 95% CI, 1.62; 4.51; P < 0.001; [100; 150] Giga/mm(3) : HR, 1.87; 95% CI, 1.10; 3.18; P = 0.021); gamma-glutamyl transpeptidase above the upper limit of normal (HR, 1.96; 95% CI, 1.11; 3.47; P = 0.021); and absence of a sustained virological response during follow-up (HR, 3.02; 95% CI, 1.67; 5.48; P < 0.001). An 11-point risk score was derived from the training cohort and validated in the validation set. Based on this score, the population was stratified into three groups, in which HCC development gradually increased, from 0% to 30.1% at 5 years for patients with the lowest (≤3) and highest (≥8) scores (P < 0.001). Using this score, a nomogram was built enabling individualized prediction of HCC occurrence at 1, 3, and 5 years. This HCC score can accurately predict HCC at an individual level in French patients with HCV cirrhosis. (Hepatology 2016;64:1136-1147).


Structural and functional characterisation of cardiac fibroblasts.
Cardiac fibroblasts form one of the largest cell populations, in terms of cell numbers, in the heart. They contribute to structural, biochemical, mechanical and electrical properties of the myocardium. Nonetheless, they are often disregarded by in vivo and in vitro studies into cardiac function. This review summarizes our understanding of fibroblast origin and identity, their structural organization and role in myocardial architecture, as well as functional aspects related to cell signalling and electro-mechanical function in the heart.


Improving the retrieval of water inherent optical properties in noisy hyperspectral data through statistical modeling.
The use of the Mahalanobis distance in a lookup table approach to retrieval of in-water Inherent Optical Properties (IOPs) led to significant improvements in the accuracy of the retrieved IOPs, as high as 50% in some cases, with an average improvement of 20% over a wide range of case II waters. Previous studies have shown that inherent noise in hyperspectral data can cause significant errors in the retrieved IOPs. For LUT-based retrievals that rely on spectrum matching, the particular metric used for spectral comparisons has a significant effect on the accuracy of the results, especially in the presence of noise in the data. In this study, we have compared the Euclidean distance and the Mahalanobis distance as metrics for spectral comparison. In addition to providing justification for the preference of the Mahalanobis Distance over the Euclidean Distance, we have also included a statistical description of noisy hyperspectral data.


The putative brain photoperiodic photoreceptors in the vetch aphid, Megoura viciae.
In an attempt to identify the brain photoreceptors that mediate the photoperiodic response of the vetch aphid, Megoura viciae, we utilised immunocytochemical techniques and employed 20 antibodies directed against invertebrate and vertebrate opsins and phototransduction proteins. A sub-set of these antibodies (to Drosophila rhodopsin 1: RH1-1; vertebrate cone opsins: COS-1; CERN-874; CERN-933; vertebrate rod opsin: CERN-901; vertebrate arrestin: AB-Arr; vertebrate transducin+arrestin+rhodopsin kinase+cGMP phosphodiesterase: CERN-911; and vertebrate cellular retinoid binding protein: CRALBP) consistently labelled an anterior ventral neuropile region of the protocerebrum. These anatomical findings, coupled with previous localised illumination and micro-lesion studies, provide strong evidence that this region of the aphid brain houses the photoperiodic photoreceptors. The present study also confirms that the medial (Group I) neurosecretory cells are not the photoperiodic photoreceptors.


Association of arterial stiffness with progression of subclinical brain and cognitive disease.
We tested whether abnormal arterial stiffness and blood pressure would be associated with progression of brain aging measured by brain MRI and neurocognitive testing. Framingham Offspring Cohort participants (n = 1,223, 61 ± 9 years, 56% women) without previous stroke or dementia underwent applanation tonometry, brain MRI, and neurocognitive testing at examination 7 (1998-2001). Follow-up brain MRI and neurocognitive testing was performed at examination 8 (2005-2008, mean interval 6.4 ± 1.3 years). We related examination 7 inverse-transformed carotid-femoral pulse wave velocity (iCFPWV), central pulse pressure (CPP), and mean arterial pressure to changes in the following variables between examinations 7 and 8: total cerebral brain volume, white matter hyperintensity volume, and performance on executive function and abstraction tasks, the Trail Making Test, Parts B and A (ΔTrails B-A), and Similarities tests. Higher baseline iCFPWV and CPP were associated with greater progression of neurocognitive decline (iCFPWV and ΔTrails B-A association: SD unit change in outcome variable per SD change in tonometry variable [β] ± SE = 0.10 ± 0.04, p = 0.019; CPP and ΔSimilarities association: -0.08 ± 0.03, p = 0.013). Higher mean arterial pressure, but not iCFPWV or CPP, was associated with increase in white matter hyperintensity volume ([β ± SE] 0.07 ± 0.03, p = 0.017). No tonometry measures were associated with change in cerebral brain volume. In middle-aged and older adults without evidence of clinical stroke or dementia, elevated arterial stiffness and pressure pulsatility are associated with longitudinal progression of subclinical vascular brain injury and greater neurocognitive decline. Treatments to reduce arterial stiffness may potentially reduce the progression of neurovascular disease and cognitive decline.


Dynamic BRG1 recruitment during T helper differentiation and activation reveals distal regulatory elements.
T helper cell differentiation and activation require specific transcriptional programs accompanied by changes in chromatin structure. However, little is known about the chromatin remodeling enzymes responsible. We performed genome-wide analysis to determine the general principles of BRG1 binding, followed by analysis of specific genes to determine whether these general rules were typical of key T cell genes. We found that binding of the remodeling protein BRG1 was programmed by both lineage and activation signals. BRG1 binding positively correlated with gene activity at protein-coding and microRNA (miRNA) genes. BRG1 binding was found at promoters and distal regions, including both novel and previously validated distal regulatory elements. Distal BRG1 binding correlated with expression, and novel distal sites in the Gata3 locus possessed enhancer-like activity, suggesting a general role for BRG1 in long-distance gene regulation. BRG1 recruitment to distal sites in Gata3 was impaired in cells lacking STAT6, a transcription factor that regulates lineage-specific genes. Together, these findings suggest that BRG1 interprets both differentiation and activation signals and plays a causal role in gene regulation, chromatin structure, and cell fate. Our findings suggest that BRG1 binding is a useful marker for identifying active cis-regulatory regions in protein-coding and miRNA genes.


The Vibrio harveyi quorum-sensing system uses shared regulatory components to discriminate between multiple autoinducers.
The quorum-sensing bacterium Vibrio harveyi produces and responds to three autoinducers (AIs), and this sensory information converges to control the expression of bioluminescence, biofilm formation, type III secretion (TTS), and protease production. The AIs are detected by cognate sensor histidine kinases that all relay phosphate to the shared response regulator LuxO. LuxO indirectly represses the master regulator of quorum sensing, LuxR, through the activation of multiple genes encoding small regulatory RNAs (called qrr genes for Quorum Regulatory RNA). Here we use differential fluorescence induction to identify 50 quorum-sensing-controlled promoters. Some promoters only showed significant responses in the simultaneous presence of all three AIs, while others displayed substantial responses to the individual AIs. A differential response to each AI input state was also observed for qrr and luxR expression and LuxR protein production. Individual cell analyses revealed that, in each case, all the bacteria in the population respond in unison to the various AI inputs. We propose that the V. harveyi quorum-sensing transition is not switch-like but rather operates in a graded manner, and that this signaling arrangement, which uses shared regulatory proteins, nonetheless provides V. harveyi a mechanism to respond uniquely to different AI input states.