Search

We explore the complementarity of direct detection (DD) and spallation source (SS) experiments for the study of sterile neutrino physics. We focus on the sterile baryonic neutrino model: an extension of the Standard Model that introduces a massive sterile neutrino with couplings to the quark sector via a new gauge boson. In this scenario, the inelastic scattering of an active neutrino with the target material in both DD and SS experiments gives rise to a characteristic nuclear recoil energy spectrum that can allow for the reconstruction of the neutrino mass in the event of a positive detection. We first derive new bounds on this model based on the data from the COHERENT collaboration on CsI and LAr targets, which we find do not yet probe new areas of the parameter space. We then assess how well future SS experiments will be able to measure the sterile neutrino mass and mixings, showing that masses in the range ~15 − 50 MeV can be reconstructed. We show that there is a degeneracy in the measurement of the sterile neutrino mixing that substantially affects the reconstruction of parameters for masses of the order of 40 MeV. Thanks to their lower energy threshold and sensitivity to the solar tau neutrino flux, DD experiments allow us to partially lift the degeneracy in the sterile neutrino mixings and considerably improve its mass reconstruction down to 9 MeV. Our results demonstrate the excellent complementarity between DD and SS experiments in measuring the sterile neutrino mass and highlight the power of DD experiments in searching for new physics in the neutrino sector. [ABSTRACT FROM AUTHOR]

Reduced graphene oxide (RGO) nanosheets wrapped around samarium oxide (Sm2O3) nanotubes were successfully synthesized using a facile and environmentally friendly hydrothermal method in this paper. X-ray diffraction, SEM, TEM, high resolution TEM, and X-ray photoelectron spectroscopy were used to characterize all of the prepared nanostructures. The purity of the material synthesized, which is made up of Sm2O3 nanotubes in a single cubic crystalline phase with a mean length of about 450 nm and a diameter of about 50 nm, were verified by additional tests. The synthesized samples were used to fabricate resistive sensors, which were then tested for NO2 and CO2 sensing properties at different concentrations (5–1000 ppm). In comparison to pure RGO and Sm2O3, the experimental results showed that the composite-based Sm2O3/RGO sensor has good sensing properties in terms of response (98.3%), fast response (15 s)/recovery time (12 s), and excellent response repeatability. The formations of p–p heterojunction in the Sm2O3/RGO composite were attributed for the improved sensing performance. [ABSTRACT FROM AUTHOR]

The objective was, therefore, to evaluate the impact on organic carbon and the formation of soil aggregates in areas of natural vegetation converted into pastures in southern Amazonas. The research was carried out in seven areas in the municipality of Humaitá, Amazonas, Brazil, five of which were pastureland, one native forest, and one natural field. Soil samples were collected at depths of 0–10 and 10–20 cm in the seven study areas and analyzed for aggregate stability, soil density, soil organic carbon, and the calculated soil organic carbon stock. Univariate, bivariate, and multivariate analyses were then carried out. Conversion from forest to pasture had a negative impact on percentage of aggregates >2 mm, soil density, concentration and stock of soil organic carbon. Organic carbon correlates positively with percentage of aggregates >2 mm, geometric mean diameter and weighted mean diameter, and negatively with soil density. Aggregate stability influences carbon sequestration in the pasture and forest areas studied, but has no influence in the natural grassland environment. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to systematically identify and characterize existing digital health tools for pain monitoring in children with cancer, and to assess common barriers and facilitators of implementation. Methods: A comprehensive literature search (PubMed, Cochrane, Embase, and PsycINFO) was carried out to identify published research on mobile apps and wearable devices focusing on acute and/or chronic pain in children (0–18 years) with cancer (all diagnoses) during active treatment. Tools had to at least include a monitoring feature for one or more pain characteristic(s) (e.g., presence, severity, perceived cause interference with daily life). Project leaders of identified tools were invited for an interview on barriers and facilitators. Results: Of 121 potential publications, 33 met inclusion criteria, describing 14 tools. Two methods of delivery were used: apps (n=13), and a wearable wristband (n=1). Most publications focused on feasibility and acceptability. Results of interviews with project leaders (100% response rate), reveal that most barriers to implementation were identified in the organizational context (47% of barriers), with financial resources and insufficient time available mentioned most often. Most factors that facilitated implementation related to end users (56% of facilitators), with end-user cooperation and end-user satisfaction mentioned most often. Conclusions: Existing digital tools for pain in children with cancer were mostly apps directed at pain severity monitoring and little is still known about their effectiveness. Paying attention to common barriers and facilitators, especially taking into account realistic funding expectations and involving end users during early stages of new projects, might prevent evidence based interventions from ending up unused. [ABSTRACT FROM AUTHOR]

Exposure to nature has been suggested to promote immigrants' health and facilitate adaptation. This review summarizes previous research focusing on the relationship between nature and immigrants' integration, wellbeing and physical activity. A search strategy was developed and adapted to seven databases. After removing duplicates, 4861 records were screened, 81 met inclusion criteria. Community gardens and urban parks were the most studied environments. In these settings, embodied experiences (the interactive processes of sensing and cognition) can foster new memories that facilitate adaptation and attachment to new natural environments. Social interaction and reconnecting with pre-migration experiences through specific use patterns can promote cultural continuation, sense of belonging and wellbeing. Other health benefits such as physical activity, disease management and improved nutrition were less frequently studied. Barriers to participation and recommendations for research and practice were also identified. Use of stronger study designs and greater inclusion of immigrant groups in research, design and evaluation of nature-based initiatives is needed. [ABSTRACT FROM AUTHOR]

Mosquitoes are globally distributed and adapted to a broad range of environmental conditions. As obligatory hosts of many infectious pathogens, mosquito abundance and distribution are primarily determined by the presence and quality of larval habitats. To understand the dynamics and productivity of larval habitats in changing island environments, we conducted a four-month mosquito survey across ten inhabited islands in the Lakshadweep archipelago. Using fine-resolution larval habitat mapping, we recorded 7890 mosquitoes representing 13 species and 7 genera. Of these, four species comprised 95% of the total collections—Aedes albopictus (Stegomyia) was the dominant species followed by Armigeres subalbatus, Culex quinquefasciatus and Malaya genurostris. We found larval species richness was positively associated with the island area and mosquito larval richness (Chao1 estimator) was higher in artificial habitats than in natural habitats. Furthermore, mosquito species composition did not deteriorate with distance between islands. Mosquito abundance by species was associated with microclimatic variables—pH and temperature. We detected co-existence of multiple species at a micro-habitat level with no evidence of interactions like competition or predation. Our study analyzed and identified the most productive larval habitats –discarded plastic container and plastic drums contributing to high larval indices predicting dengue epidemic across the Lakshadweep islands. Our data highlight the need to devise vector control strategies by removal of human-induced plastic pollution (household waste) which is a critical driver of disease risk. [ABSTRACT FROM AUTHOR]

Mosquitoes are globally distributed and adapted to a broad range of environmental conditions. As obligatory hosts of many infectious pathogens, mosquito abundance and distribution are primarily determined by the presence and quality of larval habitats. To understand the dynamics and productivity of larval habitats in changing island environments, we conducted a four-month mosquito survey across ten inhabited islands in the Lakshadweep archipelago. Using fine-resolution larval habitat mapping, we recorded 7890 mosquitoes representing 13 species and 7 genera. Of these, four species comprised 95% of the total collections—Aedes albopictus (Stegomyia) was the dominant species followed by Armigeres subalbatus, Culex quinquefasciatus and Malaya genurostris. We found larval species richness was positively associated with the island area and mosquito larval richness (Chao1 estimator) was higher in artificial habitats than in natural habitats. Furthermore, mosquito species composition did not deteriorate with distance between islands. Mosquito abundance by species was associated with microclimatic variables—pH and temperature. We detected co-existence of multiple species at a micro-habitat level with no evidence of interactions like competition or predation. Our study analyzed and identified the most productive larval habitats –discarded plastic container and plastic drums contributing to high larval indices predicting dengue epidemic across the Lakshadweep islands. Our data highlight the need to devise vector control strategies by removal of human-induced plastic pollution (household waste) which is a critical driver of disease risk. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed adherence to, feasibility of, and barriers and facilitators of implementation of an app developed to monitor and follow-up with pain in children with cancer at home. Methods: Children (8–18 years) receiving cancer treatment (all diagnoses) or their parents (of children aged 0–7 years) used the KLIK Pain Monitor app for 3 weeks. Pain was assessed twice daily using an 11-point numeric rating scale (NRS-11) (ranging from 0 to 10). Healthcare professionals (HCP's) from the hospital's Pediatric Pain Service were instructed to follow-up with clinically significant pain scores (≥ 4) within 120 min (scores 4–6) or 30 min (scores 7–10). Adherence, feasibility, and implementation outcomes were assessed using questionnaires, app log data, and interviews. Results: Twenty-seven children (M age = 7.3 years, 51.8% male) and six HCP's participated. Sixty-three percent (N = 17) of families used the app on a daily basis during three weeks, and 18.5% (N = 5) reported pain scores twice daily during that time (family adherence). Twelve out of 27 children (44.4%) reported a clinically significant pain score at least once. In 70% (14/20) of clinically significant pain scores, HCP's followed-up with families within the set timeframe (HCP adherence). Outcomes reveal feasibility for the majority of app functions (i.e., positive evaluation by ≥ 70% families/HCP's), and non-feasible aspects could be resolved. Identified barriers and facilitators were used to improve future implementation efforts. Conclusion: Use of the KLIK Pain Monitor app seems feasible. Future research will determine its effectiveness in reducing pain in children with cancer at home. [ABSTRACT FROM AUTHOR]

The recent measurement of the muon anomalous magnetic moment by the Fermilab E989 experiment, when combined with the previous result at BNL, has confirmed the tension with the SM prediction at 4.2 σ CL, strengthening the motivation for new physics in the leptonic sector. Among the different particle physics models that could account for such an excess, a gauged U (1) L μ - L τ stands out for its simplicity. In this article, we explore how the combination of data from different future probes can help identify the nature of the new physics behind the muon anomalous magnetic moment. In particular, we contrast U (1) L μ - L τ with an effective U (1) L μ -type model. We first show that muon fixed target experiments (such as NA64 μ ) will be able to measure the coupling of the hidden photon to the muon sector in the region compatible with (g - 2) μ , and will have some sensitivity to the hidden photon's mass. We then study how experiments looking for coherent elastic neutrino-nucleus scattering (CE ν NS) at spallation sources will provide crucial additional information on the kinetic mixing of the hidden photon. When combined with NA64 μ results, the exclusion limits (or reconstructed regions) of future CE ν NS detectors will also allow for a better measurement of the mediator mass. Finally, the observation of nuclear recoils from solar neutrinos in dark matter direct detection experiments will provide unique information about the coupling of the hidden photon to the tau sector. The signal expected for U (1) L μ - L τ is larger than for U (1) L μ with the same kinetic mixing, and future multi-ton liquid xenon proposals (such as DARWIN) have the potential to confirm the former over the latter. We determine the necessary exposure and energy threshold for a potential 5 σ discovery of a U (1) L μ - L τ boson, and we conclude that the future DARWIN observatory will be able to carry out this measurement if the experimental threshold is lowered to 1 keV nr . [ABSTRACT FROM AUTHOR]

Models of gauged U 1 L μ − L τ can provide a solution to the long-standing discrepancy between the theoretical prediction for the muon anomalous magnetic moment and its measured value. The extra contribution is due to a new light vector mediator, which also helps to alleviate an existing tension in the determination of the Hubble parameter. In this article, we explore ways to probe this solution via the scattering of solar neutrinos with electrons and nuclei in a range of experiments and considering high and low solar metallicity scenarios. In particular, we reevaluate Borexino constraints on neutrino-electron scattering, finding them to be more stringent than previously reported, and already excluding a part of the (g − 2)μ explanation with mediator masses smaller than 2 × 10−2 GeV. We then show that future direct dark matter detectors will be able to probe most of the remaining solution. Due to its large exposure, LUX-ZEPLIN will explore regions with mediator masses up to 5 × 10−2 GeV and DARWIN will be able to extend the search beyond 10−1 GeV, thereby covering most of the area compatible with (g − 2)μ. For completeness, we have also computed the constraints derived from the recent XENON1T electron recoil search and from the CENNS-10 LAr detector, showing that none of them excludes new areas of the parameter space. Should the excess in the muon anomalous magnetic moment be confirmed, our work suggests that direct detection experiments could provide crucial information with which to test the U 1 L μ − L τ solution, complementary to efforts in neutrino experiments and accelerators. [ABSTRACT FROM AUTHOR]

The article presents the discussion on correction "The Relationship Between Nature and Immigrants' Integration, Wellbeing and Physical Activity: A Scoping Review."

As known "ecosystem engineers", beavers influence river hydrology, geomorphology, biochemistry, and biological assemblages. However, there is a lack of research regarding the effects of beaver activities on freshwater meiofauna. In this study, we investigated the taxonomic and functional composition of the benthic copepod assemblage of a segment of the Tiber River (Italy) where a beaver dam, created about 7 weeks before our survey, had formed a semi-lentic habitat upstream and a lotic habitat downstream of the dam. We also analyzed the copepod assemblage before and after a flood event that destroyed the beaver dam, providing a unique opportunity to observe changes in a naturally reversing scenario. Our analyses revealed that, while the taxonomic composition and functional traits of the copepod assemblage remained largely unchanged across the recently formed semi-lentic and lotic habitats, substantial differences were evident between the dammed and undammed states. The dammed state showed lower copepod abundances, biomass, and functionality than the undammed one. These results highlight the role of beaver dams in changing the composition and functionality of meiofaunal assemblages offering insights into the dynamic interactions within aquatic ecosystems. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection in children is usually asymptomatic/mild. However, some patients may develop critical forms. We aimed to describe characteristics and evaluate the factors associated to in-hospital mortality of patients with critical COVID-19/MIS-C in the Amazonian region. This multicenter prospective cohort included critically ill children (1 mo–18 years old), with confirmed COVID-19/MIS-C admitted to 3 tertiary Pediatric Intensive Care Units (PICU) in the Brazilian Amazon, between April/2020 and May/2023. The main outcome was in-hospital mortality and were evaluated using a multivariable Cox proportional regression. We adjusted the model for pediatric risk of mortality score version IV (PRISMIV) score and age/comorbidity. 266 patients were assessed with 187 in the severe COVID-19 group, 79 included in the MIS-C group. In the severe COVID-19 group 108 (57.8%) were male, median age was 23 months, 95 (50.8%) were up to 2 years of age. Forty-two (22.5%) patients in this group died during follow-up in a median time of 11 days (IQR, 2–28). In the MIS-C group, 56 (70.9%) were male, median age was 23 months and median follow-up was 162 days (range, 3–202). Death occurred in 17 (21.5%) patients with a median death time of 7 (IQR, 4–13) days. The mortality was associated with higher levels of Vasoactive Inotropic-Score (VIS), presence of acute respiratory distress syndrome (ARDS), higher levels of Erythrocyte Sedimentation Rate, (ESR) and thrombocytopenia. Critically ill patients with severe COVID-19 and MIS-C from the Brazilian Amazon showed a high mortality rate, within 12 days of hospitalization. [ABSTRACT FROM AUTHOR]

Plant growth-promoting bacteria and arbuscular mycorrhizal fungi improve plant tolerance to abiotic stress. Here, we evaluated the growth and nitrogen metabolism parameters of soybean (Glycine max (L.) Merril) plants subjected to waterlogging, followed by reoxygenation. Seeds were inoculated with Bradyrhizobium or co-inoculated with Bradyrhizobium and Azospirillum brasilense and/or Rhizophagus intraradices. Plants were subjected to waterlogging at the V8 stage for eight days, followed by reoxygenation for an additional four days. After both periods, plants were collected for growth analyses and quantification of amino acid and ureide content and glutamine synthetase (GS) and glutamate synthase (NADH-GOGAT) activity. Plants co-inoculated with A. brasilense and R. intraradices had increased levels of amino acids and ureides when exposed to waterlogging and reoxygenation. Similarly, co-inoculation increased GS and NADH-GOGAT activity during both conditions and mitigated the decreases in plant growth caused by waterlogging. Our results indicate that co-inoculation with Bradyrhizobium, A. brasilense, and R. intraradices alleviates the nitrogen deficit and improves the biomass accumulation of soybean plants exposed to waterlogging stress. However, A. brasilense showed the best performance in dealing with waterlogging conditions and recovering from them. [ABSTRACT FROM AUTHOR]

This study investigated the importance of applying explainable artificial intelligence (XAI) on different machine learning (ML) models developed to predict the strength characteristics of basalt-fiber reinforced concrete (BFRC). Even though ML is widely adopted in strength prediction in concrete, the black-box nature of predictions hinders the interpretation of results. Among several attempts to overcome this limitation by using explainable AI, researchers have employed only a single explanation method. In this study, we used three tree-based ML models (Decision tree, Gradient Boosting tree, and Light Gradient Boosting Machine) to predict the mechanical strength characteristics (compressive strength, flexural strength, and tensile strength) of basal fiber reinforced concrete (BFRC). For the first time, we employed two explanation methods (Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME)) to provide explanations for all models. These explainable methods reveal the underlying decision-making criteria of complex machine learning models, improving the end user's trust. The comparison highlights that tree-based models obtained good accuracy in predicting strength characteristics yet, their explanations were different either by the magnitude of feature importance or the order of importance. This disagreement pushes towards complicated decision-making based on ML predictions which further stresses (1) extending XAI-based research in concrete strength predictions, and (2) involving domain experts to evaluate XAI results. The study concludes with the development of a "user-friendly computer application" which enables quick strength prediction of basalt fiber reinforced concrete (BFRC). [ABSTRACT FROM AUTHOR]

Patients with systemic mastocytosis (SM) are at high risk of bone deterioration. However, the evaluation of bone microarchitecture in this disease remains unclear. We aimed to assess bone microarchitecture in patients with SM. This was a cross-sectional study of 21 adult patients with SM conducted in a quaternary referral hospital in Sao Paulo, Brazil. A healthy, age-, weight-, and sex-matched cohort of 63 participants was used to provide reference values for bone microarchitecture, assessed by high resolution peripheral quantitative computed tomography (HR-pQCT). Total volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness at the radius were significantly lower in the control group compared with the SM group (all P < 0.001). Patients with aggressive SM had significantly lower trabecular number (Tb.N) (P = 0.035) and estimated failure load (F.load) (P = 0.032) at the tibia compared with those with indolent SM. Handgrip strength was significantly higher in patients who had more Tb.N at the radius (ρ, 0.46; P = 0.036) and tibia (ρ, 0.49; P = 0.002), and lower who had more trabecular separation at the radius (ρ, −0.46; P = 0.035) and tibia (ρ, −0.52; P = 0.016). Strong and positive associations between F.load (ρ, 0.75; P < 0.001) and stiffness (ρ, 0.70; P < 0.001) at the radius, and between F.load at the tibia (ρ, 0.45; P = 0.038) were observed with handgrip strength. In this cross-sectional study, aggressive SM was more susceptible to bone deterioration compared with indolent SM. In addition, the findings demonstrated that handgrip strength was associated with bone microarchitecture and bone strength. [ABSTRACT FROM AUTHOR]

This study investigated the importance of applying explainable artificial intelligence (XAI) on different machine learning (ML) models developed to predict the strength characteristics of basalt-fiber reinforced concrete (BFRC). Even though ML is widely adopted in strength prediction in concrete, the black-box nature of predictions hinders the interpretation of results. Among several attempts to overcome this limitation by using explainable AI, researchers have employed only a single explanation method. In this study, we used three tree-based ML models (Decision tree, Gradient Boosting tree, and Light Gradient Boosting Machine) to predict the mechanical strength characteristics (compressive strength, flexural strength, and tensile strength) of basal fiber reinforced concrete (BFRC). For the first time, we employed two explanation methods (Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME)) to provide explanations for all models. These explainable methods reveal the underlying decision-making criteria of complex machine learning models, improving the end user's trust. The comparison highlights that tree-based models obtained good accuracy in predicting strength characteristics yet, their explanations were different either by the magnitude of feature importance or the order of importance. This disagreement pushes towards complicated decision-making based on ML predictions which further stresses (1) extending XAI-based research in concrete strength predictions, and (2) involving domain experts to evaluate XAI results. The study concludes with the development of a "user-friendly computer application" which enables quick strength prediction of basalt fiber reinforced concrete (BFRC). [ABSTRACT FROM AUTHOR]

Background: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples.Methods: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold>3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample.Results: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC).Conclusions: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression. [ABSTRACT FROM AUTHOR]

Purpose: Atypical teratoid/rhabdoid tumours (ATRTs) are malignant embryonal tumours of childhood that affect the central nervous system (CNS). We aim to determine which factors, including patient age, extent of resection (EOR), presence of distal metastasis and use of adjuvant therapies, affect overall survival in children with atypical teratoid/rhabdoid tumours (ATRTs) treated at this single centre. Methods: Retrospective cohort review of patients with histological diagnosis of ATRT treated over 21 years (1999–2020) was conducted. Data on demographics, tumour location, presence of metastasis, use of adjuvant therapy, extent of resection (EOR), complications, neurological outcome post-surgery, and overall survival were collected. Kaplan-Meier survival analysis was performed. Results: A total of 45 children (mean age 2 years) underwent 64 operations. 25 patients were <1 year of age. Gross-total resection (GTR) pre-adjuvant therapy was achieved in 15, near-total resection (NTR) in 15, subtotal resection (STR) in 9, and biopsy in 6 children. Most children had good neurological outcomes post-operatively (28/45 with GOS 5). Fourteen patients survived longer than 4 years. Survival analysis showed a significant difference in median survival in favour of GTR and localised disease. There was no significant difference in median survival between patients <1 year vs >1 year of age (p=0.84). Conclusion: We find that presence of metastasis was an important factor in poor survival in patients with ATRT. GTR, where possible, may confer significant survival benefit in ATRT. Children aged <1 year appear to have performed as well as those >1 year and therefore should still be considered for radical surgery. [ABSTRACT FROM AUTHOR]

Background:Isoforms of the PDE4 family of cAMP-specific phosphodiesterases (PDEs) are expressed in a cell type-dependent manner and contribute to underpinning the paradigm of intracellular cAMP signal compartmentalisation. Here we identify the differential regulation of the PDE4D7 isoform during prostate cancer progression and uncover a role in controlling prostate cancer cell proliferation.Methods:PDE4 transcripts from 19 prostate cancer cell lines and xenografts were quantified by qPCR. PDE4D7 expression was further investigated because of its significant downregulation between androgen-sensitive (AS) and androgen-insensitive (AI) samples. Western blot analysis, PDE activity assay, immunofluorescent staining and cAMP responsive FRET assays were used to investigate the sub-plasma membrane localisation of a population of PDE4D7 in VCaP (AS) and PC3 (AI) cell lines. Disruption of this localisation pattern using dominant-negative protein expression and siRNA knockdown showed that PDE4D7 acts in opposition to proliferative signalling as assessed by electrical impedance-based proliferation assays.Results:Here we identify the differential regulation of the PDE4D7 isoform during prostate cancer progression. PDE4D7 is highly expressed in AS cells and starkly downregulated in AI samples. The significance of this downregulation is underscored by our finding that PDE4D7 contributes a major fraction of cAMP degrading PDE activity tethered at the plasma membrane and that displacement of PDE4D7 from this compartment leads to an increase in the proliferation of prostate cancer cells. PDE4D7 mRNA expression is not, however, directly regulated by the androgen receptor signalling axis despite an overlapping genomic structure with the androgen responsive gene PART1. PDE4D7, which locates to the plasma membrane, acts to supress aberrant non-steroidal growth signals within the prostate or AS metastasis.Conclusions:PDE4D7 expression is significantly downregulated between AS and AI cell phenotypes. This change in expression potentially provides a novel androgen-independent biomarker and manipulation of its activity or its expression may provide therapeutic possibilities and insights into contributory aspects of the complex molecular pathology of prostate cancer. [ABSTRACT FROM AUTHOR]

When prevention of dental caries fails, and a child is exposed to the risk of pain and infection, the disease must be managed to reduce this risk. There is growing evidence supporting more 'biological' and fewer 'surgical' approaches to managing dental caries in primary teeth. These biological methods include partial and stepwise caries removal procedures, as well as techniques where no caries is removed. An overview of clinical trials comparing these biological methods to complete caries removal shows that they perform as well as traditional methods and have the advantage of reducing the incidence of iatrogenic pulpal exposures. The Hall Technique is one biological approach to managing caries in primary molars which involves sealing caries beneath preformed metal (stainless steel) crowns. The crown is cemented over the tooth without caries removal, tooth preparation or use of local anaesthesia. The clinical steps for the Hall Technique are straightforward but, as with all dental care provision, appropriate treatment planning for the procedure requires skill. The Hall Technique offers another method of managing early to moderately advanced, active carious lesions in primary molars, with good evidence of effectiveness and acceptability. This evidence aligns with the positive findings of other studies on biological strategies for managing caries in primary teeth. [ABSTRACT FROM AUTHOR]

Ovarian clear cell carcinomas (OCCCs) account for about 5-13% of all epithelial ovarian carcinomas in Western populations. It is characterised by resistance to conventional platinum-based chemotherapy, and new therapeutic strategies are urgently required. This article will focus on how recent discoveries have enhanced our understanding of the molecular pathogenesis of OCCCs, leading to new therapeutic opportunities. These include mutations in ARID1A, which provides a link to endometriosis, upregulation of the phosphatidylinositol 3-kinase/AKT pathway, particularly through mutations of PIK3CA and inactivation of PTEN, and increased activity of pathways involved in angiogenesis. Targeting HER2, apoptotic escape mechanisms and mismatch repair defects offer additional opportunities for treating this enigmatic tumour subtype. [ABSTRACT FROM AUTHOR]

MLL-rearranged infant acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia characterized by a unique gene-expression profile. We uncovered that the activation of particular (proto-onco)genes is mediated by promoter hypomethylation. In search for therapeutic agents capable of targeting these potential cancer-promoting genes, we applied connectivity mapping on a gene expression signature based on the genes most significantly hypomethylated in t(4;11)-positive infant ALL as compared with healthy bone marrows. This analysis revealed histone deacetylase (HDAC) inhibitors as suitable candidates to reverse the unfavorable gene signature. We show that HDAC inhibitors effectively induce leukemic cell death in t(4;11)-positive primary infant ALL cells, accompanied by downregulation of MYC, SET, RUNX1, RAN as well as the MLL-AF4 fusion product. Furthermore, DNA methylation was restored after HDAC inhibitor exposure. Our data underlines the essential role for epigenetic de-regulation in MLL-rearranged ALL. Furthermore, we show, for the first time, that connectivity mapping can indirectly be applied on DNA methylation patterns, providing a rationale for HDAC inhibition in t(4;11)-positive leukemias. Given the presented potential of HDAC inhibitors to target important proto-oncogenes including the leukemia-specific MLL fusion in vitro, these agents should urgently be tested in in vivo models and subsequent clinical trials. [ABSTRACT FROM AUTHOR]

Cluster headache without headache (CH-H) has been described several times. We add three new CH-H patients and a patient with (probable) paroxysmal hemicrania without headache (PH-H). We searched the literature and found some more cases of CH-H and PH-H. CH-H attacks may have a shorter minimal attack duration than CH attacks. We propose the term trigeminal autonomic cephalalgia without headache (TAC-H) for autonomic attacks and/or extracephalic pain or sensory symptoms with an attack duration and distribution and/or response to therapy suggesting one of the trigeminal autonomic cephalalgias, but without accompanying headache. Secondary TAC-H may develop after treatment for painful TAC attacks. We discuss pathophysiological issues, particularly the central role of the hypothalamus and the suggestion that the superior salivatory nucleus (SSN) might be triggered by the diencephalic pacemaker without nociceptive activation. [ABSTRACT FROM AUTHOR]

MLL-rearranged acute lymphoblastic leukemia (ALL) in infants (<1 year) is the most aggressive type of childhood leukemia. To develop more suitable treatment strategies, a firm understanding of the biology underlying this disease is of utmost importance. MLL-rearranged ALL displays a unique gene expression profile, partly explained by erroneous histone modifications. We recently showed that t(4;11)-positive infant ALL is also characterized by pronounced promoter CpG hypermethylation. In this study, we investigated whether this widespread hypermethylation also affected microRNA (miRNA) expression. We identified 11 miRNAs that were downregulated in t(4;11)-positive infant ALL as a consequence of CpG hypermethylation. Seven of these miRNAs were re-activated after exposure to the de-methylating agent Zebularine. Interestingly, five of these miRNAs are associated either with MLL or MLL fusions, and for miR-152 we found both MLL and DNA methyltransferase 1 (DNMT1) as potential targeted genes. Finally, a high degree of methylation of the miR-152 CpG island was strongly correlated with a poor clinical outcome. Our data suggests that inhibitors of methylation have a potential beyond re-expression of hypermethylated protein-coding genes in t(4;11)-positive infant ALL. In this study, we provide additional evidence that they should be tested for their efficacy in MLL-rearranged infant ALL in in vivo models. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum associated degradation (ERAD) is a conserved mechanism to remove misfolded proteins from the ER by targeting them to the proteasome for degradation. To assess the role of ERAD in filamentous fungi, we have examined the consequences of disrupting putative ERAD components in the filamentous fungus Aspergillus niger. Deletion of derA, doaA, hrdC, mifA, or mnsA in A. niger yields viable strains, and with the exception of doaA, no significant growth phenotype is observed when compared to the parental strain. The gene deletion mutants were also made in A. niger strains containing single- or multicopies of a glucoamylase-glucuronidase (GlaGus) gene fusion. The induction of the unfolded protein response (UPR) target genes ( bipA and pdiA) was dependent on the copy number of the heterologous gene and the ERAD gene deleted. The highest induction of UPR target genes was observed in ERAD mutants containing multiple copies of the GlaGus gene. Western blot analysis revealed that deletion of the derA gene in the multicopy GlaGus overexpressing strain resulted in a 6-fold increase in the intracellular amount of GlaGus protein detected. Our results suggest that impairing some components of the ERAD pathway in combination with high expression levels of the heterologous protein results in higher intracellular protein levels, indicating a delay in protein degradation. [ABSTRACT FROM AUTHOR]

Most cluster headache patients respond to oxygen therapy, but approximately 20% do not. The aim of the present study was to assess which factors differ between cluster headache patients who respond to oxygen therapy and those who do not. We included patients from the headache clinic of Atrium Medical Centre Heerlen ( n = 53) and patients who responded to a cluster headache web-site ( n = 62). Participants completed a questionnaire with questions on cluster headache and factors that might be of significance with respect to the response to oxygen. Non-responders had less often smoked in the past ( p = 0.014), had longer cluster headache attacks ( p = 0.049), and more often reported interictal headache ( p = 0.02) than responders. Logistic regression analysis showed these variables to be independent risk factors for not responding to oxygen and a clinical prediction model is provided. The area under the receiver operating characteristic curve was 0.75. We conclude that cluster headache patients who smoked in the past, had shorter attacks and were pain-free interictally respond best to oxygen inhalation. The results did not provide clues for the mechanism of action of oxygen therapy. [ABSTRACT FROM AUTHOR]

Mutants with a defective non-homologous-end-joining (NHEJ) pathway have boosted functional genomics in filamentous fungi as they are very efficient recipient strains for gene-targeting approaches, achieving homologous recombination frequencies up to 100%. For example, deletion of the ku70 homologous gene kusA in Aspergillus niger resulted in a recipient strain in which deletions of essential or non-essential genes can efficiently be obtained. To verify that the mutant phenotype observed is the result of a gene deletion, a complementation approach has to be performed. Here, an intact copy of the gene is transformed back to the mutant, where it should integrate ectopically into the genome. However, ectopic complementation is difficult in NHEJ-deficient strains, and the gene will preferably integrate via homologous recombination at its endogenous locus. To circumvent that problem, we have constructed autonomously replicating vectors useful for many filamentous fungi which contain either the pyrG allele or a hygromycin resistance gene as selectable markers. Under selective conditions, the plasmids are maintained, allowing complementation analyses; once the selective pressure is removed, the plasmid becomes lost and the mutant phenotype prevails. Another disadvantage of NHEJ-defective strains is their increased sensitivity towards DNA damaging conditions such as radiation. Thus, mutant analyses in these genetic backgrounds are limited and can even be obscured by pleiotropic effects. The use of sexual crossings for the restoration of the NHEJ pathway is, however, impossible in imperfect filamentous fungi such as A. niger. We have therefore established a transiently disrupted kusA strain as recipient strain for gene-targeting approaches. [ABSTRACT FROM AUTHOR]

PurposeTo report the surgical outcomes of 24 patients undergoing single-staged three horizontal muscles squint surgery for extra-large angle exotropia.Patients and methodsProspective case series of 24 consecutive patients with primary exotropia >60 prism diopters (PD) at distant and underwent single-staged three horizontal muscles squint surgery from 2003 to 2006. Surgery consisted of bilateral lateral rectus recession of 9.0 mm for 50 PD exotropic correction. For every 5 PD remaining angle exceeding 50 PD, we additionally performed 1.0 mm of unilateral medial rectus resection. The mean follow-up period was 15.8 months (range 6.0–38.0 months; SD 9.5 months).ResultsThe mean age at surgery was 31.2 years old (range 7–78 years old, SD 18.2 years old). The mean distant preoperative deviation was 71.3 PD (range 60–85 PD, SD 7.7 PD). No limitation of eye movement or diplopia was found. The success rate was higher in the intermittent group (88.2%) than the constant group (42.9%) (P=0.02) and in cases with preoperative deviation of <80 PD (84.2%) compared with those with deviation 80 PD (40.0%) (P=0.042).ConclusionMeasurement of preoperative deviation and the surgery for extra-large angle exotropia made management of this condition difficult. Single-staged three horizontal muscles squint surgery can be one of the options. Further researches on management of exotropia of >80 PD are warranted. [ABSTRACT FROM AUTHOR]

The tumor suppressor protein p53 has a critical role in safeguarding the integrity of the genome. Its functions are well understood but factors responsible for the transcriptional regulation of the p53 gene are almost entirely unknown. The DNA replication-related element (DRE)/DNA replication-related element-binding factor (DREF) transcriptional regulatory system is established as a master key to cell proliferation in Drosophila. DREF binds specifically to DRE sequences in the Drosophila p53 (dmp53) gene promoter as shown using anti-DREF antibodies in chromatin immunoprecipitation assays. Furthermore, a rough eye phenotype because of overexpression of DREF in Drosophila eye imaginal disks could be suppressed by half dose reduction of the dmp53 gene. In addition, the level of mRNA of dmp53 was decreased in DREF-knockdown cells and transient expression of the luciferase gene under control of the wild-type dmp53 gene promoter showed strong promoter activity in S2 cells, but this was almost completely abrogated with a DRE-mutated promoter. Requirement of DREs for dmp53 promoter activity was further confirmed by anti-β-galactosidase antibody-staining of various tissues from transgenic flies carrying dmp53 promoter-lacZ fusion genes. These results indicate that DREF is necessary for dmp53 gene promoter activity. [ABSTRACT FROM AUTHOR]

The serological pattern, “anti-HBc alone”, characterized by the presence of antibodies against the core antigen of hepatitis B virus (anti-HBc) as the only marker of hepatitis B, is not rare in a diagnostic setting. Depending on the prevalence of HBV infection and the patient group investigated, 1–31% of positive anti-HBc results are isolated positive findings. Anti-HBc alone is frequently observed in intravenous drug addicts, HIV-infected individuals, patients who are coinfected with HBV and hepatitis C virus, and pregnant women. However, it is not clear how this profile should be interpreted. Several studies have shown that anti-HBc alone is not only compatible with acute and resolved HBV infection but also with chronic infection. The reasons for the lack of HBsAg and anti-HBs in anti-HBc-alone individuals are not clear, but several mechanisms and possibilities have been suggested that could explain this phenomenon, some of which are delineated in this article. [ABSTRACT FROM AUTHOR]

PurposeTo assess surgical, visual, refractive, and aesthetic outcomes 13 years after mersilene mesh frontalis sling (MMFS) operation for severe unilateral congenital ptosis performed in 10 infants before 1 year of age.MethodsLongitudinal follow-up of an interventional case series by structured ocular examinations, external photographs, and questionnaire-based interviews.ResultsMean age at surgery was 6.9±2.7 months. After a mean follow-up of 13.0±0.6 years, one patient (10%) had recurrent ptosis with the upper lid 2 mm below the superior limbus at 3 months postoperatively. Best-corrected visual acuities were within two Snellen lines between the two eyes in all patients. Astigmatic errors were 1.20±1.00 D and 1.10±1.70 D between operated and unoperated eyes. Four patients had 2 mm lid lag on down-gaze and one of them had 2 mm lagophthalmos. Mean satisfaction scores (scale of 1 to 100) for lid position, cosmesis, function, and to the procedure were 83.3±11.8, 77.0±22.9, 89.4±5.5, and 86.8±6.3, respectively. No case of overcorrection, sling extrusion, stitch granuloma, or exposure keratopathy was noted.ConclusionsIn view of the low recurrence rate (10%) and absence of serious complication or need for revision after 13 years, the use of MMFS seems effective and feasible in infants less than 1 year old. Achieving compatible long-term stability, satisfactory aesthetic, and visual outcomes, MMFS may offer an alternative to delaying operations for autogenous fascia lata harvesting in infants requiring early ptosis correction. [ABSTRACT FROM AUTHOR]

Thin films of Ge–As–Se chalcogenide glasses have been deposited by thermal evaporation from bulk material and submitted to thermal treatments. The linear refractive index and optical band-gap for as-deposited and annealed films have been analyzed as function of the deposition parameters, chemical composition and mean coordination number (MCN). The chemical composition of the films was found to be directly affected by deposition rate, with low rates producing films with elevated Ge and reduced As content, whilst at high rates the Ge content was generally reduced and As levels increased compared with the bulk starting material. As a result films with close to the same stoichiometry as the bulk glass could be obtained by choosing appropriate deposition conditions. As-deposited films with MCN in between 2.44 and 2.55 showed refractive indices and optical band-gaps very close to those of the bulk glass whereas outside this range the film indices were higher and the optical gaps lower than those of the bulk glass. Upon annealing at close to their glass transition temperature, high MCN films evolved such that their indices and band-gaps approached the bulk glass values whereas at low MCN films resulted in no changes to the film properties. [ABSTRACT FROM AUTHOR]

Increased activity of CYP2E1 has been associated with increased risk of chemically-mediated cancers, through enhanced activation of a variety of procarcinogens. In this context, inhibition of CYP2E1 is potentially of significance in xenobiotic toxicity. The aim of the present study was to test the hypothesis that quinacrine inhibits hepatic CYP2E1. For this purpose, disulfiram (75 mg/kg i.p) as an inhibitor and isoniazid (100 mg/kg i.p) as an inducer of CYP2E1, as well as quinacrine (50 mg/kg i.p) were administered to Wistar rats and the hepatic activity of CYP2E1 was measured. The expression of CYP2E1 was further assessed by Western blot analysis. As expected, disulfiram inhibited, while isoniazid induced the activity and expression of the enzyme. Interestingly, treatment with quinacrine resulted in a significant decrease of CYP2E1 activity and expression. To investigate any similarities in the inhibition of CYP2E1 by quinacrine and disulfiram, molecular modeling techniques were adopted and revealed that quinacrine molecule anchors inside the same binding pocket of the protein where disulfiram is also attached. Finally, as assessed by the sister chromatid exchanges (SCE) assay, quinacrine was demonstrated to reduce the mutagenic effects of the tobacco-specific N-nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is known to be converted to active mutagen in the liver principally through CYP2E1. We suggest that these antimutagenic effects of quinacrine could be possibly attributed, at least in part, to its ability to block the bioactivation of NNK, mainly by the inhibition of CYP2E1. Our results, even preliminary, indicate that quinacrine as an inhibitor of CYP2E1 might be protective against chemically-induced toxicities such as NNK-induced mutagenicity. [ABSTRACT FROM AUTHOR]

We integrated soil models with an established ecosystem process model (SIPNET, simplified photosynthesis and evapotranspiration model) to investigate the influence of soil processes on modelled values of soil CO2 fluxes ( R Soil). Model parameters were determined from literature values and a data assimilation routine that used a 7-year record of the net ecosystem exchange of CO2 and environmental variables collected at a high-elevation subalpine forest (the Niwot Ridge AmeriFlux site). These soil models were subsequently evaluated in how they estimated the seasonal contribution of R Soil to total ecosystem respiration (TER) and the seasonal contribution of root respiration ( R Root) to R Soil. Additionally, these soil models were compared to data assimilation output of linear models of soil heterotrophic respiration. Explicit modelling of root dynamics led to better agreement with literature values of the contribution of R Soil to TER. Estimates of R Soil/TER when root dynamics were considered ranged from 0.3 to 0.6; without modelling root biomass dynamics these values were 0.1–0.3. Hence, we conclude that modelling of root biomass dynamics is critically important to model the R Soil/TER ratio correctly. When soil heterotrophic respiration was dependent on linear functions of temperature and moisture independent of soil carbon pool size, worse model-data fits were produced. Adding additional complexity to the soil pool marginally improved the model-data fit from the base model, but issues remained. The soil models were not successful in modelling R Root/ R Soil. This is partially attributable to estimated turnover parameters of soil carbon pools not agreeing with expected values from literature and being poorly constrained by the parameter estimation routine. We conclude that net ecosystem exchange of CO2 alone cannot constrain specific rhizospheric and microbial components of soil respiration. Reasons for this include inability of the data assimilation routine to constrain soil parameters using ecosystem CO2 flux measurements and not considering the effect of other resource limitations (for example, nitrogen) on the microbe biomass. Future data assimilation studies with these models should include ecosystem-scale measurements of R Soil in the parameter estimation routine and experimentally determine soil model parameters not constrained by the parameter estimation routine. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the prevalence and factors associated with posterior pole and peripheral retinal lesions in Chinese subjects with high myopia.MethodsThree hundred and thirty-seven asymptomatic adults with high myopia of refractive error −6 D were examined in a cross-sectional community-based study. All subjects underwent cycloplegic refraction, ultrasound biometry and dilated fundal examination. Statistical analysis was performed to assess factors associated with the presence of posterior pole and peripheral retinal lesions.ResultsThe mean age of the 337 subjects was 36.0 years and the mean spherical equivalent refractive error was −10.2 D. Thirty-eight eyes (11.3%, 95% CI=8.1–15.2%) were found to have one or more posterior pole lesions and subjects with posterior pole lesion had significantly older age, longer axial length and higher degree of myopia (all P<0.001) compared with subjects without posterior pole lesion. After controlling for axial length, both the severity of refractive error and older age were significantly associated with the presence of posterior pole lesion (both P<0.001). For peripheral retinal lesions, 189 eyes (56.1%, 95% CI=50.6–61.5%) were found to have one or more peripheral retinal lesions. The presence of peripheral retinal lesion was associated with younger age and higher degree of refractive error (P=0.046 and 0.002, respectively).ConclusionPosterior pole and peripheral retinal degenerative lesions were found in a considerable proportion of subjects with high myopia. As some of these retinal lesions might predispose to visual impairment, highly myopic individuals should be educated on the symptoms of various eye conditions and seek care immediately if symptoms arise.Eye (2008) 22, 209–213; doi:10.1038/sj.eye.6702573; published online 1 September 2006 [ABSTRACT FROM AUTHOR]

Sodium cobaltate (NaxCoO2) has emerged as a material of exceptional scientific interest due to the potential for thermoelectric applications, and because the strong interplay between the magnetic and superconducting properties has led to close comparisons with the physics of the superconducting copper oxides. The density x of the sodium in the intercalation layers can be altered electrochemically, directly changing the number of conduction electrons on the triangular Co layers. Recent electron diffraction measurements reveal a kaleidoscope of Na+ ion patterns as a function of concentration. Here we use single-crystal neutron diffraction supported by numerical simulations to determine the long-range three-dimensional superstructures of these ions. We show that the sodium ordering and its associated distortion field are governed by pure electrostatics, and that the organizational principle is the stabilization of charge droplets that order long range at some simple fractional fillings. Our results provide a good starting point to understand the electronic properties in terms of a Hubbard hamiltonian that takes into account the electrostatic potential from the Na superstructures. The resulting depth of potential wells in the Co layer is greater than the single-particle hopping kinetic energy and as a consequence, holes preferentially occupy the lowest potential regions. Thus we conclude that the Na+ ion patterning has a decisive role in the transport and magnetic properties. [ABSTRACT FROM AUTHOR]

Human astroviruses (HAstV) are recognized as an important cause of gastroenteritis in young children worldwide. This study describes the molecular characteristics of astroviruses isolated in Brazil, using RT-PCR and molecular sequencing of segments of all three viral ORFs. Genetic analysis of a 348-nucleotide segment from ORF 2 demonstrated that the Brazilian isolates belong to HAstV genotypes 1 to 5 and 8. ORF 1b sequences displayed a high degree of nucleotide identity even between different genotypes, which disfavours HAstV genotyping in this region. ORF 1a sequence analysis classified all Brazilian samples as genogroup A. The complete sequences of HAstV genotype 4 (putative serotype 4) and genotype 5 (putative serotype 5) were determined for the first time. [ABSTRACT FROM AUTHOR]

An efficient compact-2D finite-difference time-domain method is presented for the numerical analysis of guided modes in waveguides that may include negative dielectric permittivity, negative magnetic permeability and negative refractive index materials. Both complex variable and real variable methods are given. The method is demonstrated for the analysis of channel-plasmon-polariton guided modes in triangular groves on a metal surface. The presented method can be used for a range of waveguide problems that were previously unsolvable analytically, due to complex geometries, or numerically, due to computational requirements of conventional three-dimensional finite-difference time-domain methods. A three-dimensional finite-difference time-domain algorithm that also allows analysis in the presence of bound or free electric and equivalent magnetic charges is presented and an example negative refraction demonstrates the method. [ABSTRACT FROM AUTHOR]

The quiescent cell population of tumours poses a barrier to the success of many cancer therapies. Most chemotherapeutic drugs target proliferating cells, but the growth fraction of many tumours is low. Based on the multicellular tumour spheroid model, a system was developed using human colon adenocarcinoma (DLD-1) cells to mimic the microenvironment of quiescent microregions of solid tumours. The quiescent tumour spheroids (TS(Q)) showed decreased expression of the proliferation marker Ki-67 and increased expression of the quiescence marker p27(kip1) compared to proliferating spheroids (TS(P)). The quiescent status of the TS(Q) was confirmed by long-term growth assessment. The quiescence was completely reversible demonstrating that the TS(Q) retained the ability to proliferate and morphological assessment by light microscopy confirmed the absence of significant apoptosis. When the efficacy of widely used chemotherapeutic drugs was determined, vinblastine, doxorubicin, cisplatin and 5-fluorouracil (5-FU) all produced significant cell death in the TS(P). However, while still effective, the potencies of doxorubicin and cisplatin were significantly reduced in TS(Q). In contrast, 5-FU and vinblastine did not produce cell death in the TS(Q). In summary, TS(Q) show considerable resistance to a panel of established chemotherapeutic agents and represent a useful model for evaluating the efficacy of drugs and other cancer therapies in quiescent tumours. [ABSTRACT FROM AUTHOR]

PURPOSE: To assess the intraocular pressure (IOP) and corneal endothelial changes, over a 6-month period, after a single injection of intravitreal triamcinolone (ivTA) in Chinese patients. METHODS: A total of 43 eyes of 43 consecutive Chinese patients with various macular diseases received a single bolus injection of 4 mg ivTA, of which, 14 eyes with significant cataracts underwent simultaneous phacoemulsification and primary intraocular lens implantation. IOP was measured preoperatively and weekly in the first month, and then monthly until 6 months postinjection. Specular microscopy was performed on 24 of the 29 eyes without simultaneous cataract surgery, preoperatively and at months 1, 3, and 6. RESULTS: All patients completed 6 months of follow-up. Nine out of 43 (20.9%) eyes had IOP>21 mmHg. Their mean maximum IOP was 29.2 mmHg (range 23.0–37.0), necessitating the use of 2.0 types of topical antiglaucomatous medications on average. The IOP elevation occurred at a mean of 5.2 weeks (range 1–17) postinjection. All IOPs returned to normal, without additional antiglaucomatous medications, by 6 months. There was no statistically significant difference (paired t-test, P<0.05) in the corneal endothelial cell count and other specular microscopy parameters up to 6 months after the injections. CONCLUSION: A single 4 mg bolus injection of ivTA appeared to have no harmful effects on the corneal endothelium. IvTA caused transient IOP elevations in 20.9% of Chinese patients, similar to that observed in Caucasians. As the IOP rise can occur as early as 1 week after the injection, early monitoring will help its early detection and prevent optic nerve damage.Eye (2005) 19, 625–630. doi:10.1038/sj.eye.6701585 Published online 28 May 2004 [ABSTRACT FROM AUTHOR]

Eye–hand coordination is geometrically complex. To compute the location of a visual target relative to the hand, the brain must consider every anatomical link in the chain from retinas to fingertips. Here we focus on the first three links, studying how the brain handles information about the angles of the two eyes and the head. It is known that people, even in darkness, reach more accurately when the eye looks toward the target, rather than right or left of it. We show that reaching is also impaired when the binocular fixation point is displaced from the target in depth: reaching becomes not just sloppy, but systematically inaccurate. Surprisingly, though, in normal Gaze-On-Target reaching we found no strong correlations between errors in aiming the eyes and hand onto the target site. We also asked people to reach when the head was not facing the target. When the eyes were on-target, people reached accurately, but when gaze was off-target, performance degraded. Taking all these findings together, we suggest that the brain's computational networks have learned the complex geometry of reaching for well-practiced tasks, but that the networks are poorly calibrated for less common tasks such as Gaze-Off-Target reaching. [ABSTRACT FROM AUTHOR]

Abstract. Previous studies in isolated, ventilated lungs have demonstrated by indirect measurements that oxidant generation occurs during pulmonary ischemia before reperfusion. To identify and quantify the types of free radical species generated during ischemia, we used electron paramagnetic resonance (EPR) spectroscopy in the presence and absence of the spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). EPR spectra obtained from the vascular effluent of isolated ferret lungs, contained a doublet signal (g = 2.005) indicative of ascorbyl radical. This signal doubled in magnitude after 180 min of ischemia, providing evidence of oxidant formation during ischemia. When DMPO, which reacts with radicals including superoxide anions and hydroxyl radicals, was added to the perfusate, the spectra contained ascorbyl radical signals but no DMPO-adducts. To clarify the relationship between ascorbyl radical and DMPO-adduct formation, additional studies were conducted in the presence and absence of ascorbate with isolated lung mitochondria as the source of free radicals. The results showed that in the presence of ascorbate, oxygen free radicals were not detected by EPR spin trapping with DMPO because of the formation of prominent ascorbyl radical signals. These data suggest that DMPO may be useful for the detection of reactive oxygen species in isolated lungs, provided the ascorbate can be sufficiently depleted. Alternatively, as shown by our results, EPR studies that... [ABSTRACT FROM AUTHOR]

Discusses how, as part of a "European Sardine/Anchovy Recruitment Program" (SARP), sardine larvae (Sardina pilchardus) were sampled off the Atlantic coast of Spain through the spawning season from March to June.

One attractive strategy to prevent or control allograft rejection is to genetically modify the donor tissue before transplantation. In this study, we have examined the feasibility of gene transfer to human corneal endothelium, using a number of recombinant adenovirus constructs. Ex vivo infection of human corneas with adenoviral vectors containing lacZ, under transcriptional control of either cytomegalovirus (CMV) or Rous sarcoma virus (RSV) promoters, provided high-level gene expression, which was largely restricted to endothelium. Expression of the reporter gene persisted at relatively high levels for up to 7 days, followed by a decline to indetectable levels by 28 days. RT-PCR analysis of lacZ transcription showed a similar picture with a short period (3–7 days) of RNA transcription after infection. In contrast, adenoviral DNA persisted for at least 56 days. Subsequently, we examined the expression of a potential therapeutic gene, CTLA-4 Ig fusion protein. Following infection of human corneas with adenoviral vectors encoding CTLA-4 Ig protein, high levels of the fusion protein were detected in corneal culture supernatants for up to 28 days. This protein was functionally active, as determined by binding to B7.1 (CD80)-expressing transfectants. This study suggests that genetic alteration of donor cornea before transplantation is a feasible approach for preventing or controlling allograft rejection. Similar gene-based strategies might also be feasible to prevent rejection of other transplanted tissues or organs. [ABSTRACT FROM AUTHOR]

The article discusses a study that examines whether gossypol, through the induction of protein NOXA, would sensitize chronic lymphocytic leukemia (CLL) cells to B-cell lymphoma 2 (BCL2) inhibitor ABT-737. It found that gossypol resensitized the CCL cells to ABT-737 in a concentration-dependent manner. It suggests that normal lymphocytes and platelets are resistant to the combination of ABT-737 and gossypol, which offers a therapeutic window to selectively kill CLL cells.

Purpose: Marker-by-treatment analyses are promising new methods in internal medicine, but have not yet been implemented in orthopaedics. With this analysis, specific cut-off points may be obtained, that can potentially identify whether meniscal surgery or physical therapy is the superior intervention for an individual patient. This study aimed to introduce a novel approach in orthopaedic research to identify relevant treatment selection markers that affect treatment outcome following meniscal surgery or physical therapy in patients with degenerative meniscal tears.Methods: Data were analysed from the ESCAPE trial, which assessed the treatment of patients over 45 years old with a degenerative meniscal tear. The treatment outcome of interest was a clinically relevant improvement on the International Knee Documentation Committee Subjective Knee Form at 3, 12, and 24 months follow-up. Logistic regression models were developed to predict the outcome using baseline characteristics (markers), the treatment (meniscal surgery or physical therapy), and a marker-by-treatment interaction term. Interactions with p < 0.10 were considered as potential treatment selection markers and used these to develop predictiveness curves which provide thresholds to identify marker-based differences in clinical outcomes between the two treatments.Results: Potential treatment selection markers included general physical health, pain during activities, knee function, BMI, and age. While some marker-based thresholds could be identified at 3, 12, and 24 months follow-up, none of the baseline characteristics were consistent markers at all three follow-up times.Conclusion: This novel in-depth analysis did not result in clear clinical subgroups of patients who are substantially more likely to benefit from either surgery or physical therapy. However, this study may serve as an exemplar for other orthopaedic trials to investigate the heterogeneity in treatment effect. It will help clinicians to quantify the additional benefit of one treatment over another at an individual level, based on the patient's baseline characteristics.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

CONCLUSION:Long-term lid position is remarkably stable after surgical correction using PLT. PLT sling appears to be a safe and effective treatment for children with congenital ptosis requiring frontalis sling operation. It could be a good alternative to autogenous fascia lata, and further studies, to compare these two sling materials seem warranted.Eye (2005) 19, 546-548. doi:10.1038/sj.eye.6701539 Published online 20 August 2004 [ABSTRACT FROM AUTHOR]

Purpose: Although physical therapy is the recommended treatment in patients over 45 years old with a degenerative meniscal tear, 24% still opt for meniscal surgery. The aim was to identify those patients with a degenerative meniscal tear who will undergo surgery following physical therapy. Methods: The data for this study were generated in the physical therapy arm of the ESCAPE trial, a randomized clinical trial investigating the effectiveness of surgery versus physical therapy in patients of 45–70 years old, with a degenerative meniscal tear. At 6 and 24 months patients were divided into two groups: those who did not undergo surgery, and those who did undergo surgery. Two multivariable prognostic models were developed using candidate predictors that were selected from the list of the patients' baseline variables. A multivariable logistic regression analysis was performed with backward Wald selection and a cut-off of p < 0.157. For both models the performance was assessed and corrected for the models' optimism through an internal validation using bootstrapping technique with 500 repetitions. Results: At 6 months, 32/153 patients (20.9%) underwent meniscal surgery following physical therapy. Based on the multivariable regression analysis, patients were more likely to opt for meniscal surgery within 6 months when they had worse knee function, lower education level and a better general physical health status at baseline. At 24 months, 43/153 patients (28.1%) underwent meniscal surgery following physical therapy. Patients were more likely to opt for meniscal surgery within 24 months when they had worse knee function and a lower level of education at baseline at baseline. Both models had a low explained variance (16 and 11%, respectively) and an insufficient predictive accuracy. Conclusion: Not all patients with degenerative meniscal tears experience beneficial results following physical therapy. The non-responders to physical therapy could not accurately be predicted by our prognostic models. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Leishmaniasis is considered a neglected disease, which makes it an unattractive market for the pharmaceutical industry; hence, efforts in the search for biologically active substances are hampered by this lack of financial motivation. Thus, in the present study, we report the leishmanicidal activity and the possible mechanisms of action of compounds with promising activity against the species Leishmania (V.) braziliensis, the causative agent of the skin disease leishmaniasis. The natural compound 1a (piplartine) and the analog 2a were the most potent against promastigote forms with growth inhibition values for 50% of the parasite population (IC50) = 8.58 and 11.25 μM, respectively. For amastigote forms, the ICa50 values were 1.46 and 16.7 μM, respectively. In the molecular docking study, piplartine showed favorable binding energy (−7.13 kcal/mol) and with 50% inhibition of trypanothione reductase (IC50) = 91.1 μM. Preliminary investigations of the mechanism of action indicate that piplartine increased ROS levels, induced loss of cell membrane integrity, and caused accumulation of lipid bodies after 24 h of incubation at its lowest effective concentration (IC50), which was not observed for the synthetic analog 2a. The mode of action for the leishmanicidal activity of piplartine (1a) was assigned to involve affinity for the trypanothione reductase of Leishmania (V.) braziliensis TR. [ABSTRACT FROM AUTHOR]