Dosimetric impact of image artifact from a wide-bore CT scanner in radiotherapy treatment planning.
Traditional computed tomography (CT) units provide a maximum scan field-of-view (sFOV) diameter of 50 cm and a limited bore size, which cannot accommodate a large patient habitus or an extended simulation setup in radiation therapy (RT). Wide-bore CT scanners with increased bore size were developed to address these needs. Some scanners have the capacity to reconstruct the CT images at an extended FOV (eFOV), through data interpolation or extrapolation, using projection data acquired with a conventional sFOV. Objects that extend past the sFOV for eFOV reconstruction may generate image artifacts resulting from truncated projection data; this may distort CT numbers and structure contours in the region beyond the sFOV. The purpose of this study was to evaluate the dosimetric impact of image artifacts from eFOV reconstruction with a wide-bore CT scanner in radiotherapy (RT) treatment planning. Testing phantoms (i.e., a mini CT phantom with equivalent tissue inserts, a set of CT normal phantoms and anthropomorphic phantoms of the thorax and the pelvis) were used to evaluate eFOV artifacts. Reference baseline images of these phantoms were acquired with the phantom centrally positioned within the sFOV. For comparison, the phantoms were then shifted laterally and scanned partially outside the sFOV, but still within the eFOV. Treatment plans were generated for the thoracic and pelvic anthropomorphic phantoms utilizing the Eclipse treatment planning system (TPS) to study the potential effects of eFOV artifacts on dose calculations. All dose calculations of baseline and test treatment plans were carried out using the same MU. Results show that both body contour and CT numbers are altered by image artifacts in eFOV reconstruction. CT number distortions of up to -356 HU for bone tissue and up to 323 HU for lung tissue were observed in the mini CT phantom. Results from the large body normal phantom, which is close to a clinical patient size, show average CT number changes of up to -49 HU. Wider distribution (i.e., standard deviation) of the HU values was seen when the phantom was placed at more than 2.8 cm beyond the 50 cm sFOV. Anthropomorphic phantom studies with several standard beam configurations show that body contour distortion causes tumor dose calculation reduction of 3.0 and 1.9% for 6 and 23 MV x-rays, respectively, when not accounting for tissue heterogeneities during dose computation. When heterogeneity correction is used in planning, the competing effects of the body contour distortion and the CT number distortion cause a smaller error in tumor dose calculation. Less than 0.9% error in calculated dose was observed in volumetric modulated are therapy (VMAT) treatment plans. The image artifacts from eFOV reconstruction alter the CT numbers and body contours of the imaged objects, which has the potential to produce inaccuracies in dose calculations during radiotherapy treatment planning. The radiation therapy team should be aware of these image artifacts and their effects on target dose calculations during CT simulation as well as treatment planning.


Spin labelling for integrative structure modelling: a case study of the polypyrimidine-tract binding protein 1 domains in complexes with short RNAs.
A combined method, employing NMR and EPR spectroscopies, has demonstrated its strength in solving structures of protein/RNA and other types of biomolecular complexes. This method works particularly well when the large biomolecular complex consists of a limited number of rigid building blocks, such as RNA-binding protein domains (RBDs). A variety of spin labels is available for such studies, allowing for conventional as well as spectroscopically orthogonal double electron-electron resonance (DEER) measurements in EPR. In this work, we compare different types of nitroxide-based and Gd(iii)-based spin labels attached to isolated RBDs of the polypyrimidine-tract binding protein 1 (PTBP1) and to short RNA fragments. In particular, we demonstrate experiments on spectroscopically orthogonal labelled RBD/RNA complexes. For all experiments we analyse spin labelling, DEER method performance, resulting distance distributions, and their consistency with the predictions from the spin label rotamers analysis. This work provides a set of intra-domain calibration DEER data, which can serve as a basis to start structure determination of the full length PTBP1 complex with an RNA derived from encephalomycarditis virus (EMCV) internal ribosomal entry site (IRES). For a series of tested labelling sites, we discuss their particular advantages and drawbacks in such a structure determination approach.


Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia.
To find out whether botulinum toxin alters the excitability of cortical motor areas, we studied intracortical inhibition with transcranial magnetic stimulation in patients with upper limb dystonia before, 1 month after, and 3 months after the injection of botulinum toxin type A in the affected muscles. Eleven normal subjects and 12 patients with dystonia involving the upper limbs (7 with generalized dystonia, 2 with segmental dystonia, and 3 with focal dystonia) were studied. Patients were assessed clinically with the Dystonia Movement Scale. Paired magnetic stimuli were delivered by two Magstim 200 magnetic stimulators connected through a Bistim module to a figure-of-eight coil placed over the motor area of the forearm muscles. Paired stimulation was given at rest. A subthreshold (80% of motor threshold) conditioning stimulus was delivered 3 and 5 msec before the suprathreshold (120% of motor threshold) test stimulus. Electromyographic signals were recorded over the flexor or extensor muscles of the forearm on the affected side. We measured the amplitude of the test motor evoked potential (expressed as a percentage of the unconditioned motor evoked potential). All results were compared using ANOVA. In all patients, a botulinum toxin type A injection (50-100 mouse units) reduced dystonic movements in the arm. In normal subjects, electromyographic recordings showed significant inhibition of the test response. Before botulinum toxin injection, patients had less test response inhibition than normal subjects. One month after injection, patients had test response inhibition similar to that of normal subjects. At 3 months after injection, they again had less inhibition than normal subjects or patients at 1 month after injection. In conclusion, our data suggest that botulinum toxin can transiently alter the excitability of the cortical motor areas by reorganizing the inhibitory and excitatory intracortical circuits. The cortical changes probably originate through peripheral mechanisms.


Crystal Packing Reveals a Potential Autoinhibited KRAS Dimer Interface and a Strategy for Small-Molecule Inhibition of RAS Signaling.
KRAS GTPases harbor oncogenic mutations in more than 25% of human tumors. KRAS is considered to be largely undruggable due to the lack of a suitable small-molecule binding site. Here, we report a unique crystal structure of His-tagged KRASG12D that reveals a remarkable conformational change. The Switch I loop of one His-KRASG12D structure extends into the Switch I/II pocket of another His-KRASG12D in an adjacent unit cell to create an elaborate interface that is reminiscent of high-affinity protein-protein complexes. We explore the contributions of amino acids at this interface using alanine-scanning studies with alchemical free energy perturbation calculations based on explicit-solvent molecular dynamics simulations. Several interface amino acids were found to be hot spots as they contributed more than 1.5 kcal/mol to the protein-protein interaction. Computational analysis of the complex revealed the presence of two large binding pockets that possess physicochemical features typically found in pockets considered druggable. Small-molecule binding to these pockets may stabilize this autoinhibited structure of KRAS if it exists in cells to provide a new strategy to inhibit RAS signaling.


Transduction efficiency of MLV but not of HIV-1 vectors is pseudotype dependent on human primary T lymphocytes.
The success of several gene therapeutic approaches requires efficient transduction of human primary T lymphocytes. For this it is important to enhance the transduction efficiency, and this can be achieved by various means, mainly technical development of transduction procedures and use of different vectors and vector pseudotypes. We analyzed the transduction efficiency of an HIV-1 vector encoding enhanced green fluorescent protein (GFP) as a marker gene and pseudotyped with the envelopes of MLV-A, MLV-10A1, GaLV, RD114, and VSV for human primary T lymphocytes in comparison to an MLV vector pseudotyped with the same envelopes. Pseudotyping of the MLV vector with the envelopes of 10A1 and GaLV resulted in efficient transduction of preactivated human primary T lymphocytes (32.4% and 32.7% CD3+/GFP+ cells, respectively) while MLV-A (14.0%), RD114 (8.8%), and VSV (1.5%) envelopes were less efficient when using titrated vector stocks equilibrated to a multiplicity of infection of 1. In contrast, the HIV-1 vectors pseudotyped with these envelope proteins transduced preactivated T lymphocytes with similar efficiency (approx. 20% CD3+/GFP+ cells). Thereby, CD4+ and CD8+ T lymphocyte subpopulations were transduced at equivalent levels. The similar performance of the different HIV-1 vector pseudotypes may be due in part to the similar half-lives of the vector particles. Independently of the envelope used for pseudotyping neither the MLV nor the HIV-1 vectors yielded any significant transduction in nonactivated T lymphocytes (below 0.55% of GFP+ cells)


Arteriovenous malformation embocure score: AVMES.
Cerebral arteriovenous malformations (CAVMs) may be treated with microsurgery, radiosurgery, endovascular surgery, or a combination of these modalities. Grading scales are available to aid the assessment of curative risk for microsurgery and radiosurgery. No grading system has been developed to assess the curative risk of endovascular surgery. To report our retrospective application of the AVM embocure score to patients treated at our institution between 2005 and 2011 METHODS: We performed a retrospective review of 39 patients with CAVM treated at our institution between 2005 and 2011 with the primary aim of achieving a curative embolization. After reviewing all the different variables associated with the conventional Onyx embolization technique for CAVMs, we identified the following as the most relevant characteristics influencing the chances for complete angiographic embolization and complication risk: the number of arterial pedicles and draining veins, size of AVM nidus, and vascular eloquence. We sought to develop a scoring system to assess the complication risk for a curative embolization of CAVM with liquid embolic Onyx (Covidien, Irvine, California, USA). We developed the AVM embocure score (AVMES). This scoring system ranges from 3 to 10 and is the arithmetic sum of the number of arterial pedicles feeding the AVM (≤3, 4-6, >6), the number of draining veins (≤3, 4-6, >6), the size of the AVM nidus in centimeters (≤3, 4-6, >6), and the vascular eloquence (0-1). We applied AVMES to the same cohort of patients and validated the predictability of complete angiographic embolization and expected clinical risk of complication. In lesions with an AVMES of 3 (n=8), there was a 100% rate of complete AVM obliteration and 0% rate of major complications. In AVMES 4 (n=12) lesions, there was 75% complete obliteration rate, with 8% major morbidity. In AVMES 5 (n=9) lesions, there was 78% complete obliteration and 11% major morbidity. In AVMES >5 (n=10) there was 20% complete obliteration and 30% major morbidity. Receiver-operator curve analysis showed that this scoring system was robust in its discriminative ability, with an area under the curve (AUC) of 0.8356 for complete obliteration without complication, AUC=0.8240 for complete obliteration regardless of the presence of major morbidity, and AUC=0.7529 for major morbidity. The AVMES complements existing scoring systems for microsurgery and radiosurgery. It provides a valuable tool for risk assessment during the complex decision-making process in treating AVMs that accounts for angioarchitectural features of particular relevance to endovascular surgeons.


Australia's leading public health body delays action on the revision of the public health goal for blood lead exposures.
Globally, childhood blood lead levels have fallen precipitously in developed countries since the 1970s following action by international bodies such as the WHO and Food and Agricultural Organization (FAO) of the United Nations. These reductions have been affected by the activities of national agencies such as the US EPA and US Centers for Disease Control and Prevention in the establishment of air lead and blood lead standards, the introduction of legislation to remove lead from petrol, paint and consumer products and tighter restrictions on lead emissions. The outcome of recent major international reviews of research into the effects of low-level lead exposures (e.g. by WHO, USA health and environmental agencies, German and Canadian health bodies) has resulted in recommendations to reduce and eliminate lead exposures. By contrast, Australian policy responses to the incontrovertible evidence that adverse neurocognitive and behavioural effects that occur at levels well below the current national goal of 10μg/dL have stalled. The delayed response by Australia occurs at a time when blood lead levels in two of Australia's three primary lead mining and smelting cities: Port Pirie, South Australia and Broken Hill, New South Wales, are rising. In the third city, Mount Isa, Queensland, there is still no systematic, annual testing of childhood blood lead values. This is despite the fact that Mount Isa has the highest lead (and other toxic metals such as cadmium and arsenic) emissions to the environment (120tonnes of lead in 2011/12) from any single point source in Australia. It is clear that both state and national policy approaches to the ongoing risks of lead exposure need to be revised urgently and in line with contemporary international standards. Recommended changes should include a new lower blood lead intervention level of no more than 5μg/dL, with a national goal for all children under 5years of age to have a blood lead level of below 1μg/dL by 2020. In order to achieve any new lower exposure goals other relevant lead standards including air, dust, soil and water must also be revised downwards.


Development and Analysis of a Stable, Reduced Complexity Model Soil Microbiome.
The soil microbiome is central to the cycling of carbon and other nutrients and to the promotion of plant growth. Despite its importance, analysis of the soil microbiome is difficult due to its sheer complexity, with thousands of interacting species. Here, we reduced this complexity by developing model soil microbial consortia that are simpler and more amenable to experimental analysis but still represent important microbial functions of the native soil ecosystem. Samples were collected from an arid grassland soil and microbial communities (consisting mainly of bacterial species) were enriched on agar plates containing chitin as the main carbon source. Chitin was chosen because it is an abundant carbon and nitrogen polymer in soil that often requires the coordinated action of several microorganisms for complete metabolic degradation. Several soil consortia were derived that had tractable richness (30-50 OTUs) with diverse phyla representative of the native soil, including Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Verrucomicrobia. The resulting consortia could be stored as glycerol or lyophilized stocks at -80°C and revived while retaining community composition, greatly increasing their use as tools for the research community at large. One of the consortia that was particularly stable was chosen as a model soil consortium (MSC-1) for further analysis. MSC-1 species interactions were studied using both pairwise co-cultivation in liquid media and during growth in soil under several perturbations. Co-abundance analyses highlighted interspecies interactions and helped to define keystone species, including Mycobacterium, Rhodococcus, and Rhizobiales taxa. These experiments demonstrate the success of an approach based on naturally enriching a community of interacting species that can be stored, revived, and shared. The knowledge gained from querying these communities and their interactions will enable better understanding of the soil microbiome and the roles these interactions play in this environment.


Guideline-concordant management of opioid therapy among human immunodeficiency virus (HIV)-infected and uninfected veterans.
Whether patients receive guideline-concordant opioid therapy (OT) is largely unknown and may vary based on provider and patient characteristics. We assessed the extent to which human immunodeficiency virus (HIV)-infected and uninfected patients initiating long-term (≥ 90 days) OT received care concordant with American Pain Society/American Academy of Pain Medicine and Department of Veterans Affairs/Department of Defense guidelines by measuring receipt of 17 indicators during the first 6 months of OT. Of 20,753 patients, HIV-infected patients (n = 6,604) were more likely than uninfected patients to receive a primary care provider visit within 1 month (52.0% vs 30.9%) and 6 months (90.7% vs 73.7%) and urine drug tests within 1 month (14.8% vs 11.5%) and 6 months (19.5% vs 15.4%; all P < .001). HIV-infected patients were also more likely to receive OT concurrent with sedatives (24.6% vs 19.6%) and a current substance use disorder (21.6% vs 17.2%). Among both patient groups, only modest changes in guideline concordance were observed over time: urine drug tests and OT concurrent with current substance use disorders increased, whereas sedative coprescriptions decreased (all Ps for trend < .001). Over a 10-year period, on average, patients received no more than 40% of recommended care. OT guideline-concordant care is rare in primary care, varies by patient/provider characteristics, and has undergone few changes over time. The promulgation of OT clinical guidelines has not resulted in substantive changes over time in OT management, which falls well short of the standard recommended by leading medical societies. Strategies are needed to increase the provision of OT guideline-concordant care for all patients.


Development of a screening method for genetically modified soybean by plasmid-based quantitative competitive polymerase chain reaction.
A novel type of quantitative competitive polymerase chain reaction (QC-PCR) system for the detection and quantification of the Roundup Ready soybean (RRS) was developed. This system was designed based on the advantage of a fully validated real-time PCR method used for the quantification of RRS in Japan. A plasmid was constructed as a competitor plasmid for the detection and quantification of genetically modified soy, RRS. The plasmid contained the construct-specific sequence of RRS and the taxon-specific sequence of lectin1 (Le1), and both had 21 bp oligonucleotide insertion in the sequences. The plasmid DNA was used as a reference molecule instead of ground seeds, which enabled us to precisely and stably adjust the copy number of targets. The present study demonstrated that the novel plasmid-based QC-PCR method could be a simple and feasible alternative to the real-time PCR method used for the quantification of genetically modified organism contents.


Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review.
Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice. To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults. A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12 February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines. We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151 735 participants), resulting in 15 more per 1 000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09 - 6.80; low certainty of evidence; four observational studies, n=167 847 participants), resulting in 45 more per 1 000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews or trials. Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects.


Histopathological classification of hepatocellular carcinoma.
Recent advances in the understanding of HCC heterogeneity have shown not only distinct molecular classes with potential therapeutical implications but also have suggested that subclasses might be mirrored by tumour morphology and phenotype. The classification of HCC is therefore shifting from a more traditional, morphology-based approach to a more functional approach with clinical implications. The classical histological patterns (trabecular, pseudoglandular, solid, etc.) are still taken into account but in combination with other parameters such as cell grading, clonal changes, type and extent of vascularisation, tumour immunophenotype etc. This array of morpho-phenotypical features is expected to ultimately provide information about cell of origin, tumour behaviour and, hopefully, treatment sensitivity. In this chapter we will give a brief overview on modern principles of hepatic carcinogenesis by outlining the events/lesions bridging the microscopic dysplasia to advanced HCC. In this context special emphasis will be given to novel concepts and diagnostics and differential diagnosis of small HCC (of early and progressed type), which is the main target of the surveillance in the cirrhotic population. Novel and emerging subpopulations of HCC will also be considered, for example HCC with stem/progenitor cell phenotype and mixed hepatobiliary forms which are filling the traditional separation between two entities (HCC and cholangiocarcinoma), likely more inter-related than previously thought.


Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus.
A growing body of evidence has pointed to the β-carboline harmine as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with harmine and imipramine in rats. To this aim, rats were treated for 14 days once a day with harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open-field tests. Harmine and imipramine, at all doses tested, reduced immobility time of rats compared with the saline group. Imipramine increased the swimming time at 20 and 30 mg/kg and harmine increased swimming time at all doses. The climbing time increased in rats treated with imipramine (10 and 30 mg/kg) and harmine (5 and 10 mg/kg), without affecting spontaneous locomotor activity. Brain-derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine and harmine-treated rats by ELISA sandwich assay. Interestingly, chronic administration of harmine at the higher doses (10 and 15 mg/kg), but not imipramine, increased BDNF protein levels in rat hippocampus. Finally, these findings further support the hypothesis that harmine could bring about behavior and molecular effects, similar to antidepressants drugs.


Artificial insemination outcomes in beef females using bovine sperm with a detectable fertility-associated antigen.
In this study, semen samples from 25 bulls that had passed a breeding soundness evaluation were analyzed for the presence or absence of a 31-kDa protein, known as fertility-associated antigen (FAA), on spermatozoal membranes. Eighteen bulls had FAA on sperm (FAA-positive) and seven were devoid of FAA on sperm (FAA-negative). A single ejaculate from each bull was extended and frozen with 25 to 30 x 10(6) sperm in .5-mL straws. Crossbred replacement heifers (n = 865) were estrus-synchronized and artificially inseminated either at timed AI or 12 h after they were detected in estrus. Mature cows (n = 285) were inseminated 12 h after they were detected in estrus during a 45-d AI period. Pregnancy rates (pooled) to first AI service for females (n = 764) inseminated with FAA-positive sperm were 65.6% and were 49.7% for females (n = 386) inseminated with FAA-negative sperm (P < .005). Among the estrus-synchronized replacement heifers, pregnancy rates to synchronized AI service for heifers (n = 550) inseminated with FAA-positive sperm were 62% and were 45.7% for heifers (n = 315) inseminated with FAA-negative sperm (P < .005). These data indicate that pregnancy rates to first AI service at spontaneous and synchronized estrus are higher when using semen from bulls with detectable FAA on spermatozoal membranes compared to semen from bulls devoid of FAA on membranes. Fertility-associated antigen is an important determinant for fertility potential of sperm from bulls to be used in AI breeding programs.


Narcolepsy and adjuvanted pandemic influenza A (H1N1) 2009 vaccines - Multi-country assessment.
In 2010, a safety signal was detected for narcolepsy following vaccination with Pandemrix, an AS03-adjuvanted monovalent pandemic H1N1 influenza (pH1N1) vaccine. To further assess a possible association and inform policy on future use of adjuvants, we conducted a multi-country study of narcolepsy and adjuvanted pH1N1 vaccines. We used electronic health databases to conduct a dynamic retrospective cohort study to assess narcolepsy incidence rates (IR) before and during pH1N1 virus circulation, and after pH1N1 vaccination campaigns in Canada, Denmark, Spain, Sweden, Taiwan, the Netherlands, and the United Kingdom. Using a case-control study design, we evaluated the risk of narcolepsy following AS03- and MF59-adjuvanted pH1N1 vaccines in Argentina, Canada, Spain, Switzerland, Taiwan, and the Netherlands. In the Netherlands, we also conducted a case-coverage study in children born between 2004 and 2009. No changes in narcolepsy IRs were observed in any periods in single study sites except Sweden and Taiwan; in Taiwan incidence increased after wild-type pH1N1 virus circulation and in Sweden (a previously identified signaling country), incidence increased after the start of pH1N1 vaccination. No association was observed for Arepanrix-AS03 or Focetria-MF59 adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the case-control study nor for children born between 2004 and 2009 in the Netherlands case-coverage study for Pandemrix-AS03. Other than elevated narcolepsy IRs in the period after vaccination campaigns in Sweden, we did not find an association between AS03- or MF59-adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the sites studied, although power to evaluate the AS03-adjuvanted Pandemrix brand vaccine was limited in our study.


A novel screening method for cell wall mutants in Aspergillus niger identifies UDP-galactopyranose mutase as an important protein in fungal cell wall biosynthesis.
To identify cell wall biosynthetic genes in filamentous fungi and thus potential targets for the discovery of new antifungals, we developed a novel screening method for cell wall mutants. It is based on our earlier observation that the Aspergillus niger agsA gene, which encodes a putative alpha-glucan synthase, is strongly induced in response to cell wall stress. By placing the agsA promoter region in front of a selectable marker, the acetamidase (amdS) gene of A. nidulans, we reasoned that cell wall mutants with a constitutively active cell wall stress response pathway could be identified by selecting mutants for growth on acetamide as the sole nitrogen source. For the genetic screen, a strain was constructed that contained two reporter genes controlled by the same promoter: the metabolic reporter gene PagsA-amdS and PagsA-H2B-GFP, which encodes a GFP-tagged nuclear protein. The primary screen yielded 161 mutants that were subjected to various cell wall-related secondary screens. Four calcofluor white-hypersensitive, osmotic-remediable thermosensitive mutants were selected for complementation analysis. Three mutants were complemented by the same gene, which encoded a protein with high sequence identity with eukaryotic UDP-galactopyranose mutases (UgmA). Our results indicate that galactofuranose formation is important for fungal cell wall biosynthesis and represents an attractive target for the development of antifungals.


[Perinatal mortality 1 in Colima, Col. Case-control study].
Perinatal mortality 1 (PM1) includes deads occurred from 28th week of gestation to 1st week of extrauterine life. The aim of this study was to describe, from medical records, clinical-epidemiological characteristics of 19 perinatal mortality 19 cases and 36 controls occurred in 1998 at a General Hospital. Interruption of the fetal-placental circulation, cardiopathy and ventricular hemorrhages were the main causes of PM1. There were no differences in cases and controls about maternal age 27.6 +/- 7 vs 28.8 +/- 5 years (p = 0.52), gestational age by amenorrhea: 39.2 +/- 1.4 vs 39.0 +/- 1.4 weeks (p = 0.82) and weight: 2892 +/- 769 vs 3352 +/- 549 g (p 0.03) respectively. In our study, the risk of PM1 was increased when history of one to four parity was present (OR = 4.67, p = 0.03) and was decreased when history of nulliparity was present (OR = 0.21, p = 0.03). Ten cases of 19 were mortinates, nine were hebdomadal deads. There was no difference in their characteristics: maternal age 26.1 +/- 5 vs 29.6 +/- 8 years (p = 0.34), gestational age 37.7 +/- 3 vs 34.1 +/- 3 weeks (p = 0.05) and weight 3025 +/- 699 vs 2780 +/- 853 g (p = 0.53) respectively. Hebdomadal death occurred 44 +/- 5 hours after their born. Results demonstrate the importance of improving prenatal attention particularly on last weeks of gestation, even in normal pregnancies.


Multistep hopping and extracellular charge transfer in microbial redox chains.
Dissimilatory metal-reducing bacteria are microorganisms that gain energy by transferring respiratory electrons to extracellular solid-phase electron acceptors. In addition to its importance for physiology and natural environmental processes, this form of metabolism is being investigated for energy conversion and fuel production in bioelectrochemical systems, where microbes are used as biocatalysts at electrodes. One proposed strategy to accomplish this extracellular charge transfer involves forming a conductive pathway to electrodes by incorporating redox components on outer cell membranes and along extracellular appendages known as microbial nanowires within biofilms. To describe extracellular charge transfer in microbial redox chains, we employed a model based on incoherent hopping between sites in the chain and an interfacial treatment of electrochemical interactions with the surrounding electrodes. Based on this model, we calculated the current-voltage (I-V) characteristics and found the results to be in good agreement with I-V measurements across and along individual microbial nanowires produced by the bacterium Shewanella oneidensis MR-1. Based on our analysis, we propose that multistep hopping in redox chains constitutes a viable strategy for extracellular charge transfer in microbial biofilms.


Hedge Fund Managers With Psychopathic Tendencies Make for Worse Investors.
It is widely assumed that psychopathic personality traits promote success in high-powered, competitive contexts such as financial investment. By contrast, empirical studies find that psychopathic leaders can be charming and persuasive, but poor performers who mismanage, bully, and engage in unethical behavior. By coding nonverbal behaviors displayed in semistructured interviews, we identified the psychopathic, Machiavellian, and narcissistic tendencies in 101 hedge fund managers, and examined whether these traits were associated with financial performance over the course of 10 diverse years of economic volatility (2005-2015). Managers with greater psychopathic tendencies produced lower absolute returns than their less psychopathic peers, and managers with greater narcissistic traits produced decreased risk-adjusted returns. The discussion focuses on the costs of Dark Triad traits in financial investment, and organizational leadership more generally.


Exploring the transcriptional landscape of plant circadian rhythms using genome tiling arrays.
Organisms are able to anticipate changes in the daily environment with an internal oscillator know as the circadian clock. Transcription is an important mechanism in maintaining these oscillations. Here we explore, using whole genome tiling arrays, the extent of rhythmic expression patterns genome-wide, with an unbiased analysis of coding and noncoding regions of the Arabidopsis genome. As in previous studies, we detected a circadian rhythm for approximately 25% of the protein coding genes in the genome. With an unbiased interrogation of the genome, extensive rhythmic introns were detected predominantly in phase with adjacent rhythmic exons, creating a transcript that, if translated, would be expected to produce a truncated protein. In some cases, such as the MYB transcription factor AT2G20400, an intron was found to exhibit a circadian rhythm while the remainder of the transcript was otherwise arrhythmic. In addition to several known noncoding transcripts, including microRNA, trans-acting short interfering RNA, and small nucleolar RNA, greater than one thousand intergenic regions were detected as circadian clock regulated, many of which have no predicted function, either coding or noncoding. Nearly 7% of the protein coding genes produced rhythmic antisense transcripts, often for genes whose sense strand was not similarly rhythmic. This study revealed widespread circadian clock regulation of the Arabidopsis genome extending well beyond the protein coding transcripts measured to date. This suggests a greater level of structural and temporal dynamics than previously known.


Higher education and psychological distress: a 27-year prospective cohort study in Sweden.
Research identifies a positive link between education and a reduction of psychological distress, but few studies have analysed the long-term impact of education on psychological distress. This study followed the same cohort for 27 years, investigating the association between education and adult psychological distress. Further, it discuss whether the link can be understood through the mediating mechanisms of social and labour-market resources, furthermore, if the mechanisms operate differently for men and women. A 27-year prospective cohort study was performed at ages 16, 18, 21, 30 and 43. The cohort consisted of all students (n = 1083, of which 1001 are included in this study) in their final year of compulsory school in Sweden. Data were collected through comprehensive questionnaires (response rate 96.4%), and analysed with OLS regression, with psychological distress at age 21, 30 and 43 as dependent variable. Baseline psychological distress, measures of social and labour-market resources, and possible educational selection factors were used as independent variables. To compare the overall magnitude of educational differences, a kappa index was calculated. A positive relation between higher education and less psychological distress was found. When becoming older this relation weakens and a link between social and labour-market resources and psychological distress is observed, indicating that education in a long-term perspective operates through the suggested mechanisms. Additionally, the mechanisms work somewhat differently for men than for women: labour-market resources were significant for men and social resources were important for women. higher education is positively linked to less psychological distress, and the link can somewhat be understood through the mechanisms of social and labour-market resources.


A qualitative study on a novel peer collaboration care programme during the first COVID-19 outbreak: A SWOT analysis.
The pandemic has forced nursing teams to incorporate new programmes that modify the organization of care and the use of material resources. The purpose of this study was to describe the perspectives of the nursing team about the strengths/opportunities and weaknesses/threats of a novel peer collaboration care programme during the first outbreak of the pandemic. A qualitative case study with focus groups was conducted in June 2020. We included 23 participants (seven nurses, seven assistant nursing care technicians and nine charge nurses). Thematic and strengths/opportunities and weaknesses/threats analysis were performed. The strengths of the peer collaboration care programme are the optimization of care and protective equipment. Its weaknesses are that veteran nurses carry the entire burden, and the lack of personal protective equipment makes it difficult to implement the peer collaboration care programme. Finally, misinformation, lack of facilities and time to teach the peer collaboration care programme are considered threats. This strengths/opportunities and weaknesses/threats analysis has led to a comprehensive new project to improve the nursing care. The incorporation of the peer collaboration care programme contributed to the development of new organizational and management programmes for the COVID-19 pandemic. This study has gave empirical evidence to nurses and care managers to optimize and organize care, work, human and material resources during the pandemic.


Genetic parameters for tissue and fatty acid composition of backfat, perirenal fat and longissimus muscle in Large White and Landrace pigs.
Genetic parameters pertaining to the same chemical characteristics of three porcine tissues, that is backfat (BF), perirenal fat (PF) and longissimus muscle (LM), were estimated in centrally tested Large White and Landrace pigs. Animals were fed ad libitum. They were slaughtered at an average BW of 99.6 kg, and samples of BF (both inner and outer layers) and LM were removed at the 13th to 14th rib level of the carcass on the day after slaughter. The data set included 2483 animals recorded for average daily gain (ADG; 35 to 100 kg), estimated carcass lean percentage (LEAN) and lean tissue growth rate (LTGR). Among these animals, around 950 pigs were recorded for lipid content (L%) and water content (W%) of BF and LM and for fatty acid composition (FAC) of BF, whereas FAC of LM was measured on 297 pigs and L%, W%, and FAC of PF on around 210 pigs. Heritabilities (h2) and genetic correlations (ra) were estimated using REML-animal model methodology. Estimates of h2 for L%, W% and FAC of BF, PF and LM were of moderate-to-high magnitude: for example 0.47 ± 0.09 for L% of LM, 0.59 ± 0.11 for W% of BF, 0.45 ± 0.08 for the ratio of polyunsaturated to saturated fatty acids (P/S) of BF, 0.61 ± 0.15 and 0.29 ± 0.10 for the coefficient of unsaturation of lipids (UNSAT, average number of double bonds of unsaturated fatty acids) of PF and LM, respectively. Genetic correlations of L% with P/S or UNSAT were strongly negative (from -0.4 to -0.9) in BF and LM, but not in PF. The 'between-tissue' genetic correlations for homologous compositional traits were far from being unity (e.g. ra = 0.57 ± 0.05 'between' BF and PF for UNSAT). Genetic relationships between ADG and tissue compositional traits were globally weak. By contrast, genetic correlations were moderate-to-high between carcass leanness and tissue compositional traits, especially those of fat depots: for example -0.66 ± 0.14 between LEAN and L% of BF, 0.50 ± 0.07 between LEAN and UNSAT of PF, -0.44 ± 0.08 between LEAN and L% of LM, and 0.27 ± 0.03 between LEAN and UNSAT of LM. On the basis of the parameter estimates found here, breeding for higher LTGR is expected to increase the ratio of water to lipids and the unsaturation degree of lipids in subcutaneous BF and, to a lesser extent, in PF. Tissue composition and FAC of LM would be less affected.


A novel method for sampling the microbiota from the oral mucosa.
The purpose of this study was to develop a site-specific sampling method that could give representative and quantitative results for defined areas of the oral mucosa and would be easy to use. Two site-specific sampling methods (swab and filter paper imprint) were compared. The filter paper sampling method was developed for this study. Samples were collected from 14 volunteers. All samples were cultured under aerobic and anaerobic conditions. The number of viable bacteria and yeasts was determined and expressed per unit area. The filter paper recovered a significantly higher number of colony types of bacteria compared to the swab sample. Both collected a large number and variety of different oral microbes. The filter paper sampling method could be the optimal technique for quantitative site-specific oral mucosal samples and is highly suitable for both culture-based and non-culture-based identification of oral microbes.


BELMiner: adapting a rule-based relation extraction system to extract biological expression language statements from bio-medical literature evidence sentences.
Extracting meaningful relationships with semantic significance from biomedical literature is often a challenging task. BioCreative V track4 challenge for the first time has organized a comprehensive shared task to test the robustness of the text-mining algorithms in extracting semantically meaningful assertions from the evidence statement in biomedical text. In this work, we tested the ability of a rule-based semantic parser to extract Biological Expression Language (BEL) statements from evidence sentences culled out of biomedical literature as part of BioCreative V Track4 challenge. The system achieved an overall best F-measure of 21.29% in extracting the complete BEL statement. For relation extraction, the system achieved an F-measure of 65.13% on test data set. Our system achieved the best performance in five of the six criteria that was adopted for evaluation by the task organizers. Lack of ability to derive semantic inferences, limitation in the rule sets to map the textual extractions to BEL function were some of the reasons for low performance in extracting the complete BEL statement. Post shared task we also evaluated the impact of differential NER components on the ability to extract BEL statements on the test data sets besides making a single change in the rule sets that translate relation extractions into a BEL statement. There is a marked improvement by over 20% in the overall performance of the BELMiner's capability to extract BEL statement on the test set. The system is available as a REST-API at http://188.8.131.52:8484/BELXtractor/finder/. http://188.8.131.52:8484/BELXtractor/finder/.


Generativity in later life: Perceived respect from younger generations as a determinant of goal disengagement and psychological well-being.
It was hypothesized that actions to benefit the next generation would not lead to well-being unless they are perceived to be valued and respected and that the lack of perceived respect would further lead to disengagement from generative goals. Older persons responded to measures of generative concern, action, perceived respect, and psychological well-being at 2 time points 12 months apart. Structural equation modeling showed that at both time points, the effect of action on well-being was completely mediated by perceived respect. Moreover, a lack of perceived respect at baseline predicted a decrease in generative concern 12 months later, suggesting that, in later life, continuing concern is partly dependent on the attitudes of younger generations. When their attitudes are unfavorable, a downward spiral in generativity development and well-being is possible.


Tivozanib, a pan-VEGFR tyrosine kinase inhibitor for the potential treatment of solid tumors.
Tivozanib (AV-951; KRN-951), being developed by AVEO Pharmaceuticals Inc and Kyowa Hakko Kirin Co Ltd, is an orally active, ATP-competitive, small-molecule, quinoline-urea derivative that inhibits VEGFR tyrosine kinase for the potential treatment of cancer. In particular, tivozanib is able to markedly inhibit the ligand-induced phosphorylation of VEGFR-1, VEGFR-2 and VEGFR-3 at picomolar concentrations. In preclinical studies, tivozanib produced a significant inhibition of tumor growth and angiogenesis in several different xenograft tumor models in athymic rats. In a phase I clinical trial, tivozanib was safe and tolerable when administered at oral doses up to 1.5 mg on a schedule of 4 weeks on, 2 weeks off treatment. Results from a phase II clinical trial in patients with advanced renal cell carcinoma reported an overall response rate of 25.4% and a median progression-free survival of 11.8 months in patients treated with tivozanib as a single agent. Hypertension and dysphonia were the most frequent adverse events. At the time of publication, a phase III clinical trial was recruiting patients with advanced renal cancer to assess tivozanib in comparison with sorafenib. Clinical trials are currently ongoing to evaluate the safety and antitumor activity of tivozanib in breast, lung and colorectal cancer. Tivozanib might represent a promising anticancer agent in several different tumor types.


Effect of vitamin E supplementation on orthodontic tooth movement in Wistar rats: a prelimary study.
Background: Tooth movement induced by the application of orthodontic force was initiated by inflammatory process. Studies have shown that vitamin E has an anti-inflammatory and antioxidant properties which perhaps could inhibit the tooth to move. This study aimed to evaluate the effect of vitamin E supplementation on orthodontic tooth movement in Wistar rats. Methods: Wistar rats (n=56) were divided into two groups. Group 1 served as the control groups, while group 2 was given vitamin E for 14 days before application of orthodontic force. Each group was divided into four subgroups (n=7), corresponding to the number of days orthodontic force lasted, i.e. 0, 1, 3, 7 days. At each of these four time points, distance measurements and quantity of osteoblasts-osteoclasts were measured in each rat. Results: Tooth movement distance was increased for group 2 than group 1 for all time intervals, but this difference was only statistically different on day 3 ( p=0.001). For both groups, tooth movement was significantly different between each time interval in each group ( p=0.041). The mean number of osteoblast cells was increased for group 2 compared to group 1 for all time intervals (p<0.05), but was not significant different between time intervals ( p=0.897). The number of osteoclasts was not significantly different between groups, but it was statistically different between time intervals (p=0.004). Conclusion: The outcome of this study demonstrated that group 2 resulted a better tooth movement compared to group 1 on day 3, based on the distance measurement. The osteoclast cell numbers were the same within control groups, whilst the number of osteoblast cells in group 2 was significantly higher than those in group 1.


[Realization of Fast track surgery principles during cesarean section].
The aim of the study was to evaluate the efficiency of Fast Track Surgery (FTS) program application and determine the role of the anesthesiologist in its realization during planned Cesarean section. There were 2 randomized groups formed (basic and control), which contained 22 patients each. The groups were identical by all anthropometrical indicators. The FTS was applied in the basic group while the control group was led in traditional postoperative mode. The level of postoperative pain was estimated by Visual Analogue Scale (VAS) in rest and during cough 6, 12 and 24 hours after surgery, cortisol and glucose level dynamics, Baevskiy index, nausea and vomiting frequency, defecation and urination delay, presence of anxiety and weakness were assessed. The VAS and Baevskiy index were lower in the basic group during 12th and 24th hour of investigation, p < 0.05. There was no difference in dynamic cortisol levels in both groups. The values of cortisol levels didn't exceed those of presurgical levels. The tendency of hypoglycemia in control group that testified the prevalence of ketabolic proccesses was accompanied by weakness and orthostatic reactions. In both groups urination delay, nausea and vomiting were present. The obtained data proved the efficacy and safety of FTS during Cesarean section. The study shows that the decision of FTS has to be made by the anesthesiologist. It can improve perioperative conduction of patients and result in the promt stabilization of mother's condition after surgical intervention and result to the optimized contact with the child as well as reduce the period of hospital stay and decrease the expenses.


[Renal artery stenosis: screening, diagnostic and therapeutic options].
Hypertension is a frequent disease and renal artery stenosis, as a potential cause of hypertension, can be cured. Therefore, we frequently need to exclude a renal artery stenosis in patients with hypertension in our daily routine. This calls for a screening procedure which is non-invasive, highly effective and not too expensive. This paper describes the advantages and limitations of colour Doppler ultrasound in diagnosing renal artery stenosis. Colour Doppler ultrasound with intrarenal Doppler analysis is an ideal tool in the screening for relevant renal artery stenosis in patients with hypertension. This technique, however, requires a careful approach and extrarenal abnormalities need to be considered.


A paralytic disease in nude mice associated with polyoma virus infection.
Nude mice (nu/nu), heterotransplanted with human tumours and kept in isolators, were found to suffer from wasting and posterior paralysis. Electron microscopy of spinal cord tissue revealed virus particles in the oligodendrocytes consistent in size (35 to 40 nm), morphology and distribution with those of the polyoma--SV40 sub-group of papovaviruses. Serology and restriction enzyme analysis of the virus genome showed that the virus was the murine polyoma A2 strain. Inoculation of uninfected nude mice with 10(7) TCID50 of polyoma A2 strain virus produced a similar disease in these mice with wasting and, after 10 to 23 weeks, paralysis of the hind legs of all surviving mice. Extensive myelin disruption was seen throughout the brain stem and sacral region of the spinal cord and high titres of polyoma virus were found in the whole brain (10(8.8) TCID50/brain) and in the spinal cord (10(6.8) TCID50/spinal cord).


Postoperative radiation therapy after vaginal surgery for endometrial cancer.
From 1958 to 1978, 88 consecutive patients affected by endometrial cancer were referred to the Radiology Institute of the University of Florence, for radiation therapy after vaginal hysterectomy and bilateral salpingo-oophorectomy. Five and ten-year actuarial survival rates are 71% and 62%. In the evaluable patients, results are analysed according to: extension of the tumor, as assessed by pathological evaluation (60 pats.), histologic grade of differentiation (44 pats.), and neoplastic infiltration of myometrium (32 pats.). When the tumor is limited to the uterine body, a 5-year actuarial survival is achieved in 89% of the cases; when the cervix or the adnexa and other pelvic structures are involved, this percentage decreases to 62.5% and 37.5%. The prognosis is also affected by the histological grade of differentiation and the depth of myometrial infiltration.


Duration and clearance of anal human papillomavirus (HPV) infection among women: the Hawaii HPV cohort study.
The association of anal cancer with human papillomavirus (HPV) infection is well established; however, little is known about the epidemiology of anal HPV in healthy women. We investigated patterns of duration and clearance of anal HPV infection in a cohort of healthy women in Hawaii. Viral and nonviral determinants of anal HPV clearance were examined in a longitudinal cohort study of 431 sexually active women. At baseline and at 4-month intervals, interviews were conducted and cervical and anal cell specimens were obtained for detection of HPV DNA. Of the 431 women, 50% experienced a total of 414 incident anal HPV infections, reported at 1 clinic visits from baseline through a follow-up period of average duration of 1.2 years. Of these infections, 58% cleared during follow-up. The clearance rate for a high-risk anal infection was 9.2 per 100 woman-months (95% confidence interval [CI], 6.9-11.9 per 100 woman-months), with a median duration of 150 days (95% CI, 132-243 days). The slowest clearing high-risk HPV types were HPV-59 (median clearance time, 350 days) and HPV-58 (median clearance time, 252 days). The median clearance times for HPV-16 and HPV-18, the predominant types associated with anal cancer, were 132 days and 212 days, respectively. Nonviral factors that delayed clearance of anal HPV included douching, long-term tobacco smoking, and anal sex. The majority of anal HPV infections resolve in a relatively short time. Although anal HPV is commonly acquired in healthy women, its rapid clearance suggests limited efficacy of HPV testing as an anal cancer screening tool.


Population-level interventions in government jurisdictions for dietary sodium reduction.
Excess dietary sodium consumption is a risk factor for high blood pressure, stroke and cardiovascular disease. Currently, dietary sodium consumption in almost every country is too high. Excess sodium intake is associated with high blood pressure, which is common and costly and accounts for significant burden of disease. A large number of jurisdictions worldwide have implemented population-level dietary sodium reduction initiatives. No systematic review has examined the impact of these initiatives. • To assess the impact of population-level interventions for dietary sodium reduction in government jurisdictions worldwide.• To assess the differential impact of those initiatives by social and economic indicators. We searched the following electronic databases from their start date to 5 January 2015: the Cochrane Central Register of Controlled Trials (CENTRAL); Cochrane Public Health Group Specialised Register; MEDLINE; MEDLINE In Process & Other Non-Indexed Citations; EMBASE; Effective Public Health Practice Project Database; Web of Science; Trials Register of Promoting Health Interventions (TRoPHI) databases; and Latin American Caribbean Health Sciences Literature (LILACS). We also searched grey literature, other national sources and references of included studies.This review was conducted in parallel with a comprehensive review of national sodium reduction efforts under way worldwide (Trieu 2015), through which we gained additional information directly from country contacts.We imposed no restrictions on language or publication status. We included population-level initiatives (i.e. interventions that target whole populations, in this case, government jurisdictions, worldwide) for dietary sodium reduction, with at least one pre-intervention data point and at least one post-intervention data point of comparable jurisdiction. We included populations of all ages and the following types of study designs: cluster-randomised, controlled pre-post, interrupted time series and uncontrolled pre-post. We contacted study authors at different points in the review to ask for missing information. Two review authors extracted data, and two review authors assessed risk of bias for each included initiative.We analysed the impact of initiatives by using estimates of sodium consumption from dietary surveys or urine samples. All estimates were converted to a common metric: salt intake in grams per day. We analysed impact by computing the mean change in salt intake (grams per day) from pre-intervention to post-intervention. We reviewed a total of 881 full-text documents. From these, we identified 15 national initiatives, including more than 260,000 people, that met the inclusion criteria. None of the initiatives were provided in lower-middle-income or low-income countries. All initiatives except one used an uncontrolled pre-post study design.Because of high levels of study heterogeneity (I2 > 90%), we focused on individual initiatives rather than on pooled results.Ten initiatives provided sufficient data for quantitative analysis of impact (64,798 participants). As required by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) method, we graded the evidence as very low due to the risk of bias of the included studies, as well as variation in the direction and size of effect across the studies. Five of these showed mean decreases in average daily salt intake per person from pre-intervention to post-intervention, ranging from 1.15 grams/day less (Finland) to 0.35 grams/day less (Ireland). Two initiatives showed mean increase in salt intake from pre-intervention to post-intervention: Canada (1.66) and Switzerland (0.80 grams/day more per person. The remaining initiatives did not show a statistically significant mean change.Seven of the 10 initiatives were multi-component and incorporated intervention activities of a structural nature (e.g. food product reformulation, food procurement policy in specific settings). Of those seven initiatives, four showed a statistically significant mean decrease in salt intake from pre-intervention to post-intervention, ranging from Finland to Ireland (see above), and one showed a statistically significant mean increase in salt intake from pre-intervention to post-intervention (Switzerland; see above).Nine initiatives permitted quantitative analysis of differential impact by sex (men and women separately). For women, three initiatives (China, Finland, France) showed a statistically significant mean decrease, four (Austria, Netherlands, Switzerland, United Kingdom) showed no significant change and two (Canada, United States) showed a statistically significant mean increase in salt intake from pre-intervention to post-intervention. For men, five initiatives (Austria, China, Finland, France, United Kingdom) showed a statistically significant mean decrease, three (Netherlands, Switzerland, United States) showed no significant change and one (Canada) showed a statistically significant mean increase in salt intake from pre-intervention to post-intervention.Information was insufficient to indicate whether a differential change in mean salt intake occurred from pre-intervention to post-intervention by other axes of equity included in the PROGRESS framework (e.g. education, place of residence).We identified no adverse effects of these initiatives.The number of initiatives was insufficient to permit other subgroup analyses, including stratification by intervention type, economic status of country and duration (or start year) of the initiative.Many studies had methodological strengths, including large, nationally representative samples of the population and rigorous measurement of dietary sodium intake. However, all studies were scored as having high risk of bias, reflecting the observational nature of the research and the use of an uncontrolled study design. The quality of evidence for the main outcome was low. We could perform a sensitivity analysis only for impact. Population-level interventions in government jurisdictions for dietary sodium reduction have the potential to result in population-wide reductions in salt intake from pre-intervention to post-intervention, particularly if they are multi-component (more than one intervention activity) and incorporate intervention activities of a structural nature (e.g. food product reformulation), and particularly amongst men. Heterogeneity across studies was significant, reflecting different contexts (population and setting) and initiative characteristics. Implementation of future initiatives should embed more effective means of evaluation to help us better understand the variation in the effects.


The movement and distribution of Helicoverpa armigera (Hübner) larvae on pea plants is affected by egg placement and flowering.
The distribution and movement of 1st instar Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) larvae on whole garden pea (Pisum sativum L.) plants were determined in glasshouse trials. This economically-important herbivore attacks a wide variety of agricultural, horticultural and indigenous plants. To investigate the mechanisms underlying larval intra-plant movement, we used early-flowering and wild-type plant genotypes and placed eggs at different vertical heights within the plants, one egg per plant. Leaf water and nitrogen content and cuticle hardness were measured at the different plant heights. Of 92 individual larvae, 41% did not move from the node of eclosion, 49% moved upwards and 10% moved downwards with the distance moved being between zero and ten plant nodes. Larvae from eggs placed on the lower third of the plant left the natal leaf more often and moved further than larvae from eggs placed in the middle or upper thirds. The low nutritive value of leaves was the most likely explanation for more movement away from lower plant regions. Although larvae on flowering plants did not move further up or down than larvae on non-flowering plants, they more often departed the leaflet (within a leaf) where they eclosed. The final distribution of larvae was affected by plant genotype, with larvae on flowering plants found less often on leaflets and more often on stipules, tendrils and reproductive structures. Understanding intra-plant movement by herbivorous insects under natural conditions is important because such movement determines the value of economic loss to host crops. Knowing the behaviour underlying the spatial distribution of herbivores on plants will assist us to interpret field data and should lead to better informed pest management decisions.


A collagen-like immunodeterminant on the surface of Streptococcus sanguis induces platelet aggregation.
The basis of similarities in the mechanism of human platelet aggregation induced by soluble collagen and the dental plaque bacterium Streptococcus sanguis was analyzed. Structural and functional comparisons were made by using molecular probes, including rabbit antibody fractions reactive with components on S. sanguis and a synthetic, collagen-like octapeptide mimicking segments from cyanogen bromide fragments 6 and 4 of types I and III collagen, respectively. When platelets were pretreated with tryptic peptides or class II antigen of S. sanguis or with the synthetic, collagen-like octapeptide, the onset of aggregation in response to S. sanguis and collagen was prolonged. When compared to other peptides of similar size and charge, the collagen-like peptide's action towards platelets was shown to be selective. Indeed, absorption of antiserum to S. sanguis cells with particulate type I collagen removed specificities directed at a single S. sanguis antigen. These observations suggested that a common platelet-interactive immunodeterminant on soluble types I and III collagens, particulate type I collagen, and S. sanguis cells was present. Selective inhibition by antibody was used to show structural similarities between the S. sanguis surface proteins and collagen. When either agonist was pretreated with anti-S. sanguis IgG or Fab fragments, the lag time to onset of platelet aggregation was increased. Greater increases in the lag time to aggregation was seen when S. sanguis cells or collagen were pretreated with anti-S. sanguis IgG or Fab fragments made relatively specific for the class II antigen. Neutralization of the platelet-interactive action of the octapeptide by anti-S. sanguis antibody fractions showed that the immunodeterminant common to S. sanguis and collagen triggered platelets in plasma to aggregate. Although the anti-S. sanguis antibodies could inhibit fibrillogenesis, this action was apparently independent of interactions with platelets. In contrast, S. sanguis could bind or adhere to platelets by different determinants. Our data suggest that platelets have at least two distinct sites that bind collagen or S. sanguis. One of these may be a common site for collagen and S. sanguis agonists.


Vertical Approach Ñ A Modified Method in Balloon Crossing of Mitral Valve in Inoue Balloon Mitral Valvuloplasty.
Recently, the shape of the J-tipped stylet used in Inoue balloon mitral valvuloplasty has been altered to form a tighter loop. Consequently, the distal balloon catheter tends to take a more vertical orientation when the stylet is inserted into the catheter during manipulation of the balloon catheter across the mitral valve. We describe a modified method Ñ a vertical approach Ñ to facilitate and expedite crossing of the mitral valve during Inoue balloon mitral valvuloplasty.


A multiplicity of constraints: How children learn word meaning.
This book is an excellent and accessible overview of the position that children learn the meanings of words by applying a variety of nonlinguistic cognitive tools to the problem. We take issue with Bloom's emphasis on Theory of Mind as an explanatory mechanism for language learning; and with his claim that only unitary objects are nameable.


Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system.
The rat zitter (zi) mutation induces hypomyelination and vacuolation in the central nervous system (CNS), which result in early-onset tremor and progressive flaccid paresis. By positional cloning, we found a marked decrease in Attractin (Atrn) mRNA in the brain of the zi/zi rat and identified zi as an 8-bp deletion at a splice donor site of Atrn. Atrn has been known to play multiple roles in regulating physiological processes that are involved in monocyte-T cell interaction, agouti-related hair pigmentation, and control of energy homeostasis. Rat Atrn gene encoded two isoforms, a secreted and a membrane form, as a result of alternative splicing. The zi mutation at the Atrn locus darkened coat color when introduced into agouti rats, as also described in mahogany (mg) mice, carrying the homozygous mutation at the Atrn locus. Transgenic rescue experiments showed that the membrane-type Atrn complemented both neurological alteration and abnormal pigmentation in zi/zi rats, but that the secreted-type Atrn complemented neither mutant phenotype. Furthermore, we discovered that mg mice exhibited hypomyelination and vacuolation in the CNS associated with body tremor. We conclude from these results that the membrane Atrn has a critical role in normal myelination in the CNS and would provide insights into the physiology of myelination as well as the etiology of myelin diseases.


DTI for assessing axonal integrity after contusive spinal cord injury and transplantation of oligodendrocyte progenitor cells.
We describe the feasibility of using diffusion tensor magnetic resonance imaging (DT-MRI) to study a contusive model of rat spinal cord injury following human stem cell transplantation at and around the site of injury. Rats receiving either a laminectomy or contusion injury were transplanted with oligodendrocyte precursor cells (OPCs). During the course of the study, bioluminescence imaging (BLI; up to 100 days) and somatosensory evoked potentials (SSEPs; up to 42 days) were used to evaluate cell survival and functional outcomes. Spinal cords were then analyzed ex vivo upon termination using diffusion tensor imaging (DTI). Improvements in fractional anisotropy (FA) at day 100 post-transplantation corresponded with cell survival and functional SSEP improvements. Thus, we illustrate the feasibility of DTI for evaluating axonal integrity in SCI after cell replacement therapies, and we provide examples utilizing OPC transplantations in a contusion rat model.


Regional program for the study of glomerulonephritis. Central Committee of the Toronto Glomerulonephritis Registry.
The Toronto Glomerulonephritis Registry, a regional program for studying the natural history of the different types of glomerulonephritis and the effects of drug therapy on them, was established 6 years ago in Toronto. Data for all patients with histologic evidence of glomerulonephritis seen at the 16 participating hospitals are collected on standard forms and stored in a computer. Randomized controlled trials of different types of therapy for five types of glomerulonephritis have been started under the coordination of the central registry. In view of the registry's low cost and high potential benefit, greater support for such projects is needed. Other centres should consider establishing similar registries to promote more rapid collection of cases and thus allow better evaluation of the development and treatment of this major cause of renal failure.


Higher baseline expression of the PTGS2 gene and greater decreases in total colonic fatty acid content predict greater decreases in colonic prostaglandin-E2 concentrations after dietary supplementation with ω-3 fatty acids.
This study evaluated whether mRNA expression of major genes regulating formation of prostaglandin (PG)E2 in the colon and colonic fatty acid concentrations are associated with the reduction in colonic mucosal PGE2 after dietary supplementation with omega-3 (ω-3) fatty acids. Supplementation with ω-3 fatty acids was done for 12 weeks using personalized dosing that was expected to reduce colonic PGE2 by 50%. In stepwise linear regression models, the ω-3 fatty acid dose and baseline BMI explained 16.1% of the inter-individual variability in the fold change of colonic PGE2 post-supplementation. Increases in mRNA gene expression after supplementation were, however, modest and were not associated with changes in PGE2. When baseline expression of PTGS1, PTGS2 and HPGD genes was included in the linear regression model containing dose and BMI, only PTGS2, the gene coding for the inducible form cyclooxygenase, was a significant predictor. Higher relative expression of PTGS2 predicted greater decreases in colonic PGE2, accounting for an additional 13.6% of the inter-individual variance. In the final step of the regression model, greater decreases in total colonic fatty acid concentrations predicted greater decreases in colonic PGE2, contributing to an additional 18.7% of the variance. Overall, baseline BMI, baseline expression of PTGS2 and changes in colonic total fatty acids together accounted for 48% of the inter-individual variability in the change in colonic PGE2. This is consistent with biochemical data showing that fatty acids which are not substrates for cyclooxygenases can activate cyclooxygenase-2 allosterically. Further clinical trials are needed to elucidate the factors that regulate the fatty acid milieu of the human colon and how this interacts with key lipid metabolizing enzymes. Given the central role of PGE2 in colon carcinogenesis, these pathways may also impact on colon cancer prevention by other dietary and pharmacological approaches.


Immunohistochemical localization of a ubiquitin ligase HRD1 in murine brain.
HRD1 is an E3 ubiquitin ligase and plays an important role in endoplasmic reticulum-associated degradation (ERAD). Parkin-associated endothelin receptor-like receptor (Pael-R) is a substrate of the E3 ubiquitin ligase parkin, which has been implicated in ER stress-induced cell death in dopamine neurons in autosomal recessive juvenile parkinsonism (AR-JP). Recently, we demonstrated that endogenous HRD1 interacts with Pael-R, and that HRD1 promotes the degradation of Pael-R and protects cell death caused by the accumulation of Pael-R. Another group recently reported that HRD1 suppresses the toxicity of polyglutamine-expanded huntingtin. However, the topographical localization of HRD1 protein in the brain, especially related to neurodegenerative disease, is unclear. In this study, we used immunohistochemistry to investigate the topographical localization of HRD1 in the brain and demonstrated that HRD1 immunoreactivity was expressed widely in the substantia nigra pars compacta (SNC) containing dopaminergic neurons and was expressed in the cerebral cortex, hippocampus, dentate gyrus, striatum, globus pallidus, and Purkinje cells of the cerebellar cortex. Furthermore, HRD1 immunoreactivity was detected in the neuronal cells but not in the glial cells. These results suggest that HRD1 may play an important role in maintaining higher brain function, including motor function or learning and memory. In addition, HRD1 may have substrates other than Pael-R that are implicated in neurodegenerative disorders.


McMurray's Test and Joint Line Tenderness for Medial Meniscus Tear: Are They Accurate?
Meniscus tears are the most common injury of the knee. The McMurray's test and Joint line tenderness for diagnosing meniscus tear have been widely tested, but results reported by different authors vary. The wide variations reported have an impact on clinical decision concerning whether to go for other diagnostic tests before going for diagnostic arthroscopy, which is considered as the gold standard.The purpose of this study was to determine the diagnostic value of Joint line tenderness and McMurray's test, as clinical signs, to diagnose underlying medial meniscus tears. This was a prospective observational study done in Tribhuwan University Teaching Hospital. Patients undergoing knee arthroscopy were included in the study period of one year (from February 2011 to January 2012). Each patient was clinically examined with McMurray's test and joint line tenderness. The findings were then matched by the arthroscopic findings. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were then calculated. The sensitivity, specificity, positive predictive value , negative predictive value and accuracy for medial joint line tenderness in diagnosing medial meniscus tear were 50%, 61.7%, 51.8%, 60% and 56.45% respectively. The result was insignificant (p value=0.352). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for McMurray's test for diagnosing medial meniscus tear were 54%, 79%, 68% , 67.50% and 67.74% respectively. The result was significant (p value=0.007). Clinical tests like McMurray and joint line tenderness have low diagnostic value when applied individually. They may be useful when combined together with the background of clinical history. The decision to scope the knee should not be solely taken on the results of clinical tests.


Mechanisms of genioglossus responses to inspiratory resistive load in rabbits.
The purpose of the present study has been to determine whether pharyngeal dilator muscles participate in inspiratory load compensatory responses and if so, to elucidate role of upper airway mechanoreceptors in these responses. The experiments were performed on anaesthetized rabbits. Each animal was tested in three ways by the imposition of inspiratory resistive load: (1) at upper airways via face mask, (2) at the tracheostomic cannula placed below larynx (all upper airway receptors were 'bypassed') and (3) at the mouth after the section of the hypoglossus nerves (motor denervation of genioglossus muscle). The inspiratory load applied to the upper airways evoked significant increases in integrated genioglossus activity (to 129 +/- 14.7% of control) and its inspiratory duration (to 113 +/- 5% of control) already within the first loaded breath (P < 0.05). The increases in the inspiratory activity of musculius genioglossus were relatively greater than the simultaneous increases in the activity of the diaphragm. Motor denervation of the pharynx dilator muscles (including m. genioglossus) increased airway resistance to 184 +/- 19% of control (P < 0.05) and induced obstructive alterations in the breathing pattern during unloaded breathing: decrease in maximal inspiratory flow (-13%) and increase in the level of negative oesophageal pressure (+14%) and the peak diaphragm activity (+6%). After nervi hypoglossus sections additional increases in motor and pressure outputs were required in order to maintain unaltered ventilation at the same degree of loading as before denervation. The results indicate that the pharyngeal dilator muscles have a role in compensation of added inspiratory load. Activation of these muscles facilitate the load compensating function of 'pump' muscles by decreasing airway resistance. Tracheostomy did not reduce the genioglossus response to inspiratory loading, ruling out any role for upper airways receptors in the genioglossus response to inspiratory load compensations.


Effect of salbutamol on oxygen saturation in bronchiolitis.
Inhaled sympathomimetic agents are often used in bronchiolitis with little objective evidence of benefit. The arterial oxygen saturation (SaO2) reflects the adequacy of ventilation-perfusion balance. The aim of the current study was to determine the effect of inhaled salbutamol on SaO2. In a randomised, double blind study, 21 infants, admitted with bronchiolitis positive for respiratory syncytial virus, had continuous SaO2 measurements made before and after nebulised salbutamol or placebo. SaO2 was recorded over 30 minutes for a baseline, then during the 10 minutes of first nebulisation with either salbutamol or saline, then over 30 minutes after nebulisation, the 10 minutes of second nebulisation with the alternate regime, and another 30 minutes after this second nebulisation. Desaturation occurred after salbutamol and saline nebulisation. The fall in SaO2 with salbutamol was seen whether infants received it as the first or second nebulisation. The fall in SaO2 after saline was seen when given first, but not when given after salbutamol. The decrease in SaO2 was greater and more prolonged with salbutamol than with saline. Routine nebulised aerosol sympathomimetic treatment during acute bronchiolitis cannot be recommended.


Evaluation of the location of intervertebral cages during oblique lateral interbody fusion surgery to achieve sagittal correction.
Oblique lateral interbody fusion (OLIF) can achieve recovery of lumbar lordosis (LL) in minimally invasive manner. The current study aimed to evaluate the location of lateral intervertebral cages during OLIF in terms of LL correction. The subjects were patients who underwent OLIF for lumbar degenerative diseases, including lumbar spinal stenosis, spondylolisthesis, and discogenic low back pain. Their clinical outcome was evaluated using visual analogue scale on lower back pain (LBP), leg pain and numbness. The following parameters were retrospectively evaluated on plain radiographic images and computed tomography scans before and at 1 year after OLIF: the intervertebral height, vertebral translation, and sagittal angle. The cage position was defined by equally dividing the caudal endplate into five zones (I to V), and its association with segmental lordosis restoration was analyzed. Subjects were also evaluated for a postoperative endplate injury. Eighty patients (121 fused levels) with lumbar degeneration who underwent OLIF were included. There were no significant specific distribution in preoperative disc pathology such as disc angle, height, and translation. After OLIF, sagittal alignment was improved with an average correction angle of 3.8º at the instrumented segments in a level-independent fashion. All cases showed significant improvement in clinical outcomes, and had improvement in the radiological parameters (P<0.05). A detailed analysis of the cage position showed that the most significant sagittal correction and the most postoperative endplate injuries occurred in the farthest anterior zone (I). Cages with a 12-mm height were associated with more endplate injuries compared with shorter cages (8 or 10 mm). OLIF improves sagittal alignment with an average correction angle of 3.8º at the instrumented segments. We suggest that the optimal cage position for better lordosis correction and the fewest endplate injuries is zone II with a cage height of up to 10 mm.


Methylated Thioarsenates and Monothioarsenate Differ in Uptake, Transformation, and Contribution to Total Arsenic Translocation in Rice Plants.
Methylated and inorganic thioarsenates have recently been reported from paddy fields besides the better-known oxyarsenates. Methylated thioarsenates are highly toxic for humans, yet their uptake, transformation, and translocation in rice plants is unknown. Here, hydroponic experiments with 20 day old rice plants showed that monomethylmonothioarsenate (MMMTA), dimethylmonothioarsenate (DMMTA), and monothioarsenate (MTA) were taken up by rice roots and could be detected in the xylem. Total arsenic (As) translocation from roots to shoots was higher for plants exposed to DMMTA, MTA, and dimethylarsenate (DMAV) compared to MMMTA and monomethylarsenate (MMAV). All thioarsenates were partially transformed in the presence of rice roots, but processes and extents differed. MMMTA was subject to abiotic oxidation and largely dethiolated to MMAV already outside the plant, probably due to root oxygen loss. DMMTA and MTA were not oxidized abiotically. Crude protein extracts showed rapid enzymatic reduction for MTA but not for DMMTA. Our study implies that DMMTA has the highest potential to contribute to total As accumulation in grains either as DMAV or partially as DMMTA. DMMTA has once been detected in rice grains using enzymatic extraction. By routine acid extraction, DMMTA is determined as DMAV and thus escapes regulation despite its toxicity.


Prevalence of hip fracture risk factors in women aged 70 years and over.
We estimated the prevalence of common risk factors for hip fracture and the numbers needed to treat (NNT) to prevent a hip fracture in various high-risk population groups, using a postal risk factor survey of women aged 70 years and above from General Practices in Grampian and Yorkshire. Recorded risk factors included prior fracture of any type; low body weight; smoking; and family history of fracture. The prevalence rates of hip fracture risk factors were 34%, 7% and 11% for previous fracture, maternal hip fracture and smoking, respectively for the Grampian practices (low body weight being defined as falling in the lowest quartile) and 34%, 7% and 7% for a single practice in the York area. Applying previously published estimates of risk, NNT analysis produced a value of about 300 for women with no risk factors, whilst for women with three risk factors it was between 32 and 71, depending on which risk factors were present and assuming intervention reduced fracture rates by 30% or 50%. Groups of women at high risk of hip fracture can easily be identified in primary care and offered treatment, with realistic prospects of hip fracture prevention.


Integrative CRISPR Activation and Small Molecule Inhibitor Screening for lncRNA Mediating BRAF Inhibitor Resistance in Melanoma.
The incidence of melanoma, being one of the most commonly occurring cancers, has been rising since the past decade. Patients at advanced stages of the disease have very poor prognoses, as opposed to at the earlier stages. The conventional targeted therapy is well defined and effective for advanced-stage melanomas for patients not responding to the standard-of-care immunotherapy. However, targeted therapies do not prove to be as effective as patients inevitably develop V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF)-inhibitor resistance to the respective drugs. Factors which are driving melanoma drug resistance mainly involve mutations in the mitogen-activated protein kinase (MAPK) pathway, e.g., BRAF splice variants, neuroblastoma RAS viral oncogene homolog (NRAS) amplification or parallel survival pathways. However, those mechanisms do not explain all cases of occurring resistances. Therefore, other factors accounting for BRAFi resistance must be better understood. Among them there are long non-coding RNAs (lncRNAs), but these remain functionally poorly understood. Here, we conduct a comprehensive, unbiased, and integrative study of lncRNA expression, coupled with a Clustered Regularly Interspaced Short Palindromic Repeats/Cas9-mediated activation (CRISPRa) and small molecule inhibitor screening for BRAF inhibitor resistance to expand the knowledge of potentially druggable lncRNAs, their function, and pave the way for eventual combinatorial treatment approaches targeting diverse pathways in melanoma.


Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients.
Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term safety studies and visual assessment have not been thoroughly tested in retinitis pigmentosa patients. In our pre-clinical study, purified human fetal-derived retinal progenitor cells (RPCs) were transplanted into the diseased retina of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. Based on these results, we conducted a phase I clinical trial to establish the safety and tolerability of transplantation of RPCs in eight patients with advanced retinitis pigmentosa. Patients were studied for 24 months. After RPC transplantation in RCS rats, we observed moderate recovery of vision and maintenance of the outer nuclear layer thickness. Most importantly, we did not find tumor formation or immune rejection. In the retinis pigmentosa patients given RPC injections, we also did not observe immunological rejection or tumorigenesis when immunosuppressive agents were not administered. We observed a significant improvement in visual acuity (P < 0.05) in five patients and an increase in retinal sensitivity of pupillary responses in three of the eight patients between 2 and 6 months after the transplant, but this improvement did not appear by 12 months. Our study for the first time confirmed the long-term safety and feasibility of vision repair by stem cell therapy in patients blinded by retinitis pigmentosa. WHO Trial Registration, ChiCTR-TNRC-08000193 . Retrospectively registered on 5 December 2008.


Immunochemical studies of Staphylococcus aureus Oeding-Haukenes antigen a5: a phosphorus-containing polysaccharide.
Antigen a5 was isolated from strain 830 of Staphylococcus aureus by autolysis in phosphate buffer followed by alcohol precipitation. Purification was principally achieved by affinity chromatography on wheat germ agglutinin ultrogel and on anti-S. aureus teichoic acid immunosorbent. The a5 antigen was weakly immunogenic in rabbits. Chemical analysis showed that a5 is a teichoic acid composed of ribitol phosphate, N-acetylglucosamine and alanine. It has similar physico-chemical properties to the wall beta-N-acetylglucosamine ribitol teichoic acid of S. aureus but is serologically distinct.


Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies.
Plasmodium falciparum and P. vivax sporozoites were observed to invade cultured human hepatoma cells in vitro. Monoclonal antibodies to the circumsporozoite (CS) protein of each of these malarial species blocked invasion. Inhibition was species-specific, but was independent of the geographic origin of each strain. Because these monoclonal antibodies have been shown to diminish or abolish sporozoite infectivity to susceptible primate hosts, it is suggested that inhibition of invasion of sporozoites (ISI) into cultured cells may represent in in vitro assay for protective antibodies. This was confirmed by the finding that serum taken from volunteers immune to sporozoite challenge also totally blocked sporozoite invasion. The ISI assay also detected naturally acquired invasive-neutralizing antibodies in areas endemic for malaria. This ISI assay may therefore be useful in determining the incidence of inhibitory anti-sporozoite antibodies in general populations, and allow the monitoring of the effect of an anti-malarial vaccine using sporozoite-derived antigens.


Release of dissolved phosphorus from riparian wetlands: Evidence for complex interactions among hydroclimate variability, topography and soil properties.
In agricultural landscapes, establishment of vegetated buffer zones in riparian wetlands (RWs) is promoted to decrease phosphorus (P) emissions because RWs can trap particulate P from upslope fields. However, long-term accumulation of P risks the release of dissolved P, since the unstable hydrological conditions in these zones may mobilize accumulated particulate P by transforming it into a mobile dissolved P species. This study evaluates how hydroclimate variability, topography and soil properties interact and influence this mobilization, using a three-year dataset of molybdate-reactive dissolved P (MRDP) and total dissolved P (TDP) concentrations in soil water from two RWs located in an agricultural catchment in western France (Kervidy-Naizin), along with stream P concentrations. Two main drivers of seasonal dissolved P release were identified: i) soil rewetting during water-table rise after dry periods and ii) reductive dissolution of soil Fe (hydr)oxides during prolonged water saturation periods. These mechanisms were shown to vary greatly in space (according to topography) and time (according to intra- and interannual hydroclimate variability). The concentration and speciation of the released dissolved P also varied spatially depending on soil chemistry and local topography. Comparison of sites revealed a similar correlation between soil P speciation (percentage of organic P ranging from 35-70%) and the concentration and speciation of the released P (MRDP from <0.10 to 0.40mgl-1; percentage of MRDP in TDP from 25-70%). These differences propagated to stream water, suggesting that the two RWs investigated were the main sources of dissolved P to streams. RWs can be critical areas due to their ability to biogeochemically transform the accumulated P in these zones into highly mobile and highly bioavailable dissolved P forms. Hydroclimate variability, local topography and soil chemistry must be considered to decrease the risk of remobilizing legacy soil P when establishing riparian buffer zones in agricultural landscapes.


Fragment-to-Lead Medicinal Chemistry Publications in 2020.
Fragment-based drug discovery (FBDD) continues to evolve and make an impact in the pharmaceutical sciences. We summarize successful fragment-to-lead studies that were published in 2020. Having systematically analyzed annual scientific outputs since 2015, we discuss trends and best practices in terms of fragment libraries, target proteins, screening technologies, hit-optimization strategies, and the properties of hit fragments and the leads resulting from them. As well as the tabulated Fragment-to-Lead (F2L) programs, our 2020 literature review identifies several trends and innovations that promise to further increase the success of FBDD. These include developing structurally novel screening fragments, improving fragment-screening technologies, using new computer-aided design and virtual screening approaches, and combining FBDD with other innovative drug-discovery technologies.


Plasmon Waveguiding in Nanowires.
Nanowires supporting propagating surface plasmons can function as nanowaveguides to realize the light guiding with field confinement beyond the diffraction limit, providing fundamental building blocks for nanophotonic integrated circuits. This review covers the recent developments of plasmon waveguiding in nanowires, mainly including plasmon waveguiding in metal nanowires, coupling of nanowire plasmons and emitters, hybrid nanowire waveguides and plasmonic gain, and nanowire photonic devices. We first introduce the main techniques for fabricating metal nanowires, the plasmon modes in metal nanowires and the excitation/detection methods. We then discuss the fundamental properties of plasmon propagation and emission, including zigzag, chiral and spin-dependent propagation, mode conversion, loss and propagation length, group velocity, terminal emission, and leaky radiation. Then the interactions between nanowires and emitters are reviewed, especially the coupling of single nanowires and single quantum emitters. Finally, we briefly introduce the hybrid nanowire waveguide composed of a semiconductor nanowire and a metal film with an intervening thin insulator and highlight a few nanophotonic devices based on plasmonic nanowire networks or plasmonic-photonic hybrid nanowire structures.


[The basic causes of relapses in respiratory organ tuberculosis].
The authors analyze 1080 cases of recurrence of tuberculosis of the respiratory organs with emphasis of their causes. It was found that recurrences were observed in subjects over 40 years of age that were dismissed from dispensary prophylactic examination or observed in subgroup VII-A and more frequently than freshly diagnosed tuberculosis showing bacteria discharge and pulmonary destruction. It was found that the leading cause of recurrence is an inadequate course of chemotherapy.


[Multiple sclerosis and depression].
Depression has frequently been reported in multiple sclerosis. However, prevalence rates must be interpreted in the light of the conceptual and methodological limitations of these studies. Depression has traditionally been associated with response to the diagnosis of this disease, the presence of physical and cognitive limitations, the damage of specific neural systems and inmunomodulatory therapy. To assess the evolution of emotional state and its relationship with motor and cognitive slowness, in relapsing remitting patients with minimal levels of neurological disability. Data are reported for 35 patients with relapsing remitting multiple sclerosis, 27 treated with interferons and 8 without interferon treatment. Mood disturbance (Beck Depression Inventory, BDI), physical disability (Kurtzke Expanded Disability Status Scale, EDSS) and speed of information processing (reaction times) were assessed. The first testing was carried out before the start of treatment and the second testing one year later. The group of patients showed a total BDI score indicative of minimal depression associated with items expressing performance difficulties and somatic complaints. Emotional state was not related to physical disability but was related to processing speed measures. A significant improvement of depression was observed after one year of treatment with inmunomodulatory therapy.


Babesiosis as a cause of acute respiratory distress syndrome: a series of eight cases.
The characteristics of patients with Acute Respiratory Distress Syndrome (ARDS) as a complication of Babesia microti infection have not been systematically described. Adult patients admitted to the medical intensive care unit (MICU) of a tertiary care hospital in the Lower Hudson Valley of New York from 1/1/2008 to 8/1/2016 were evaluated for ARDS complicating babesiosis. Of 22 patients with babesiosis in the MICU, eight (36.4%; 95% CI: 19.7-57.0%) had ARDS. Six patients (75%) developed ARDS following initiation of anti-babesia drug therapy; however, the mean duration of symptoms in these patients exceeded that of patients who developed ARDS prior to initiation of treatment (7.50 ± 3.83d vs. 4.50 ± 0.71d, p = 0.34). Three patients (37.5%; 95% CI: 13.7-69.4%) expired without recovery from ARDS. In comparison, the mortality rate for the 14 MICU babesiosis patients without ARDS was 14.3% (p = 0.31). There was a trend toward younger age in survivors relative to non-survivors (mean age 54.6 ± 13.8y vs. 74.0 ± 6.24y, p = 0.07). Three of the five survivors did not require mechanical ventilation. The mean sequential organ failure assessment score of non-survivors was significantly higher than that of survivors (12.3 ± 1.15 vs. 6.0 ± 1.4, p = 0.0006). Among 22 critically ill adult patients with B. microti infection, ARDS developed in eight (35.4%), and three (37.5%) expired without resolution of the ARDS. ARDS often followed the initiation of anti-babesia drug therapy, raising the question of whether the death of the parasite per se contributed to its development. However, this observation was confounded by the longer duration of symptoms preceding initiation of drug therapy.