Comparison of eight prehospital stroke scales to detect intracranial large-vessel occlusion in suspected stroke (PRESTO): a prospective observational study.
Due to the time-sensitive effect of endovascular treatment, rapid prehospital identification of large-vessel occlusion in individuals with suspected stroke is essential to optimise outcome. Interhospital transfers are an important cause of delay of endovascular treatment. Prehospital stroke scales have been proposed to select patients with large-vessel occlusion for direct transport to an endovascular-capable intervention centre. We aimed to prospectively validate eight prehospital stroke scales in the field. We did a multicentre, prospective, observational cohort study of adults with suspected stroke (aged ≥18 years) who were transported by ambulance to one of eight hospitals in southwest Netherlands. Suspected stroke was defined by a positive Face-Arm-Speech-Time (FAST) test. We included individuals with blood glucose of at least 2·5 mmol/L. People who presented more than 6 h after symptom onset were excluded from the analysis. After structured training, paramedics used a mobile app to assess items from eight prehospital stroke scales: Rapid Arterial oCclusion Evaluation (RACE), Los Angeles Motor Scale (LAMS), Cincinnati Stroke Triage Assessment Tool (C-STAT), Gaze-Face-Arm-Speech-Time (G-FAST), Prehospital Acute Stroke Severity (PASS), Cincinnati Prehospital Stroke Scale (CPSS), Conveniently-Grasped Field Assessment Stroke Triage (CG-FAST), and the FAST-PLUS (Face-Arm-Speech-Time plus severe arm or leg motor deficit) test. The primary outcome was the clinical diagnosis of ischaemic stroke with a proximal intracranial large-vessel occlusion in the anterior circulation (aLVO) on CT angiography. Baseline neuroimaging was centrally assessed by neuroradiologists to validate the true occlusion status. Prehospital stroke scale performance was expressed as the area under the receiver operating characteristic curve (AUC) and was compared with National Institutes of Health Stroke Scale (NIHSS) scores assessed by clinicians at the emergency department. This study was registered at the Netherlands Trial Register, NL7387. Between Aug 13, 2018, and Sept 2, 2019, 1039 people (median age 72 years [IQR 61-81]) with suspected stroke were identified by paramedics, of whom 120 (12%) were diagnosed with aLVO. Of all prehospital stroke scales, the AUC for RACE was highest (0·83, 95% CI 0·79-0·86), followed by the AUC for G-FAST (0·80, 0·76-0·84), CG-FAST (0·80, 0·76-0·84), LAMS (0·79, 0·75-0·83), CPSS (0·79, 0·75-0·83), PASS (0·76, 0·72-0·80), C-STAT (0·75, 0·71-0·80), and FAST-PLUS (0·72, 0·67-0·76). The NIHSS as assessed by a clinician in the emergency department did somewhat better than the prehospital stroke scales with an AUC of 0·86 (95% CI 0·83-0·89). Prehospital stroke scales detect aLVO with acceptable-to-good accuracy. RACE, G-FAST, and CG-FAST are the best performing prehospital stroke scales out of the eight scales tested and approach the performance of the clinician-assessed NIHSS. Further studies are needed to investigate whether use of these scales in regional transportation strategies can optimise outcomes of patients with ischaemic stroke. BeterKeten Collaboration and Theia Foundation (Zilveren Kruis).


Infection dynamics of Marteilia refringens in flat oyster Ostrea edulis and copepod Paracartia grani in a claire pond of Marennes-Oléron Bay.
The protozoan parasite Marteilia refringens has been partly responsible for the severe decrease in the production of the European flat oyster Ostrea edulis Linnaeus in France since the 1970s. The calanoid copepod Paracartia grani Sars was recently found to be a host for M. refringens in French shallow-water oyster ponds ('claires'). This study reconsidered M. refringens transmission dynamics in the light of this finding, taking into account not only oyster infection dynamics and environmental factors but also data concerning the copepod host. P. grani population dynamics in the claire under study revealed that this species is the dominant planktonic copepod in this confined ecosystem. During winter, M. refringens overwintered in O. edulis, with P. grani existing only as resting eggs in the sediment. The increase in temperature in spring controlled and synchronized both the release of M. refringens sporangia in the oyster feces, and the hatching of the benthic resting eggs of the copepod. Infection of oysters by M. refringens was limited to June, July and August, coinciding with (1) the highest temperature recorded in the claire, and (2) the highest abundance of P. grani. PCR detection of M. refringens in P. grani during the summer period was linked to the release of parasite sporangia by the oyster. Our results are supported by previous results on the effective transmission of this parasite from the oyster to the copepod.


De Novo Transcriptome Assembly and Comparative Analysis Elucidate Complicated Mechanism Regulating Astragalus chrysochlorus Response to Selenium Stimuli.
Astragalus species are medicinal plants that are used in the world for years. Some Astragalus species are known for selenium accumulation and tolerance and one of them is Astragalus chrysochlorus, a secondary selenium accumulator. In this study, we employed Illumina deep sequencing technology for the first time to de novo assemble A. chrysochlorus transcriptome and identify the differentially expressed genes after selenate treatment. Totally, 59,656 unigenes were annotated with different databases and 53,960 unigenes were detected in NR database. Transcriptome in A. chrysochlorus is closer to Glycine max than other plant species with 43,1 percentage of similarity. Annotated unigenes were also used for gene ontology enrichment and pathway enrichment analysis. The most significant genes and pathways were ABC transporters, plant pathogen interaction, biosynthesis of secondary metabolites and carbohydrate metabolism. Our results will help to enlighten the selenium accumulation and tolerance mechanisms, respectively in plants.


Influence of Age on Efficacy and Safety of Spironolactone in Heart Failure.
The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics. TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45% who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories (<65, 65 to 74, and ≥75 years). The mean age was 72 ± 10 years (range 50 to 97 years) with 41% over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; p < 0.001), particularly in older age groups (p interaction = 0.02). Findings in the whole TOPCAT cohort were consistent with results from the Americas region. In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302).


Etiology of three recent diseases of citrus in São Paulo State: sudden death, variegated chlorosis and huanglongbing.
The state of São Paulo (SSP) is the first sweet orange growing region in the world. Yet, the SSP citrus industry has been, and still is, under constant attack from various diseases. In the 1940s, tristeza-quick decline (T-QD) was responsible for the death of 9 million trees in SSP. The causal agent was a new virus, citrus tristeza virus (CTV). The virus was efficiently spread by aphid vectors, and killed most of the trees grafted on sour orange rootstock. Control of the disease resided in replacing sour orange by alternative rootstocks giving tolerant combinations with scions such as sweet orange. Because of its drought resistance, Rangpur lime became the favourite alternative rootstock, and, by 1995, 85% of the SSP sweet orange trees were grafted on this rootstock. Therefore, when in 1999, many trees grafted on Rangpur lime started to decline and suddenly died, the spectre of T-QD seemed to hang over SSP again. By 2003, the total number of dead or affected trees was estimated to be over one million. The new disease, citrus sudden death (CSD), resembles T-QD in several aspects. The two diseases have almost the same symptoms, they spread in time and space in a manner strikingly similar, and the pathological anatomy of the bark at the bud union is alike. Transmission of the CSD agent by graft-inoculation has been obtained with budwood inoculum taken not only on CSD-affected trees (grafted on Rangpur lime), but also on symptomless trees (grafted on Cleopatra mandarin) from the same citrus block. This result shows that symptomless trees on Cleopatra mandarin are tolerant to the CSD agent. Trees on rootstocks such as Sunki mandarin or Swingle citrumelo are also tolerant. Thus, in the CSD-affected region, control consists in replacing Rangpur lime with compatible rootstocks, or in approach-grafting compatible rootstock seedlings to the scions of trees on Rangpur lime (inarching). More than 5 million trees have been inarched in this way. A new disease of sweet orange, citrus variegated chlorosis (CVC), was observed in 1987 in the Triangulo Mineiro of Minas Gerais State and the northern and north-eastern parts of SSP. By 2000, the disease affected already 34% of the 200 million sweet orange trees in SSP. By 2005, the percentage had increased to 43%, and CVC was present in all citrus growing regions of Brazil. Electron microscopy showed that xylem-limited bacteria were present in all symptomatic sweet orange leaves and fruit tissues tested, but not in similar materials from healthy, symptomless trees. Bacteria were consistently cultured from twigs of CVC-affected sweet orange trees but not from twigs of healthy trees. Serological analyses showed the CVC bacterium to be a strain of Xylella fastidiosa. The disease could be reproduced and Koch's postulates fulfilled, by mechanically inoculating a pure culture of X. fastidiosa isolate 8.1.b into sweet orange seedlings. The genome of a CVC strain of X. fastidiosa was sequenced in SSP in the frame of a project supported by FAPESP and Fundecitrus. X. fastidiosa is the first plant pathogenic bacterium, the genome of which has been sequenced. Until recently, America was free of huanglongbing (HLB), but in March 2004 and August 2005, symptoms of the disease were recognized, respectively in the State of São Paulo (SSP) and in Florida, USA. HLB was known in China since 1870 and in South Africa since 1928. Because of its destructiveness and its rapid spread by efficient psyllid insect-vectors, HLB is probably the most serious citrus disease. HLB is caused by a phloem sieve tube-restricted Gram negative bacterium, not yet available in culture. In the 1990s, the bacterium was characterized by molecular techniques as a member of the alpha proteobacteria designated Candidatus Liberibacter africanus for the disease in Africa, and Candidatus Liberibacter asiaticus for HLB in Asia. In SSP, Ca. L. asiaticus is also present, but most of the trees are infected with a new species, Candidatus Liberibacter americanus.


Disparities in children's exposure to environmental tobacco smoke in the United States, 2007.
This study examined racial/ethnic, socioeconomic, and geographic disparities in children's exposure to environmental tobacco smoke (ETS) or secondhand smoke in the home. The 2007 National Survey of Children's Health (N = 90,853) was used to calculate the prevalence of children's exposure to ETS. State-level data on home smoking ban from the 2006-2007 Current Population Survey-Tobacco Use Supplement were used to supplement analyses. Logistic regression was used to estimate adjusted odds of exposure. In 2007, 7.6% of US children, or 5.5 million children, lived in households where someone smoked inside the home. The prevalence varied from a low of 1.1% for Utah and 1.9% for California to a high of 17.9% for West Virginia and 17.6% in Kentucky. After adjustment for sociodemographic factors, children in Ohio, West Virginia, Kentucky, and Pennsylvania had 12 times higher odds and those in Wisconsin, Missouri, Delaware, and the District of Columbia had 10 times higher odds of being exposed to ETS than children in Utah. Compared with children from higher socioeconomic backgrounds, Hispanic ethnicity, and non-English-speaking households, children from lower socioeconomic backgrounds had 7.3 to 10.6 times higher adjusted odds; non-Hispanic white, black, American Indian, and mixed-race children had 2.0 to 2.6 times higher odds; and children from English-speaking households had 4.1 times higher odds of ETS exposure. Considerable disparities exist in children's exposure to ETS, with geographic pattern strongly related to home smoking ban. Greater exposure to ETS among children in several states and disadvantaged socioeconomic groups is likely to exacerbate existing health disparities.


Relationship Between Cerebral Blood Oxygenation and Electrical Activity During Mental Stress Tasks: Simultaneous Measurements of NIRS and EEG.
The incidence of stress-induced psychological and somatic diseases has been increasing rapidly, and it is important to clarify the neurophysiological mechanisms of stress response in order to establish effective stress management methods. We previously reported that the prefrontal cortex (PFC) plays an important role in stress response. In the present study, we employed near-infrared spectroscopy (NIRS) and electroencephalography (EEG) to investigate the characteristics of PFC activity during mental arithmetic tasks. A two-channel NIRS device was used to measure hemoglobin (Hb) concentration changes in the bilateral PFC during a mental arithmetic task (2 min) in normal adults. Simultaneously, EEG was used to also measure bilateral PFC activity during the same task. We evaluated concentration changes of oxy-Hb induced by the task while analyzing α wave changes using power spectrum analysis. It was observed that oxy-Hb in the bilateral PFC increased significantly during the task (p < 0.05), while α wave power in the PFC decreased significantly (p < 0.01). The present results indicate that mental stress tasks caused the activation of the bilateral PFC. Simultaneous measurements of NIRS and EEG are useful for evaluating the neurophysiological mechanism of stress responses in the brain.


New trends in the immunopathogenesis of psoriasis.
Psoriasis is a chronic hypeproliferative inflammatory skin disease characterized by abnormal keratinocyte hyperproliferation and differentiation, intra-epidermal accumulation of neutrophil granulocytes, and dermal inflammatory infiltrate that mostly consists of T-cells. Today, psoriasis is definitely recognized as a T-cell-mediated inflammatory disease. Infiltration of T-cells seems to be the primary event that precedes the keratinocyte hyperproliferation. It is suggested that systemic lymphocyte activation is followed by the local accumulation of specific CD4+ T-cells and subsequently by the activation of intradermal CD8+ T-cells. So far, it seems that CD4+ T-cells create an appropriate type-1 cytokine environment for CD8+ T-cells activation that eventually trigger the psoriatic cascade. Thus, T-cells are responsible for initiation and maintenance of psoriasis. The precise mechanism how activated T-cells trigger psoriasis is yet unknown. However, it seems that the specific immune reaction to a putative antigen, mediated by T-cells leads to creation of psoriatic lesions. The immune reaction constantly driven by bacterial superantigens or epidermal self-antigens eventually leads to development of psoriatic lesions. The psoriatic process is a dynamic process that includes interaction between Th1- and Tc1-cells as well as between T-cells and keratinocytes. The better understanding of the immunopathogenesis of psoriasis would allow for development of specific T-cell-targeted and/or cytokine-targeted new therapies.


Reproducibility of histological assessments of disease activity in UC.
Histopathology is potentially an important outcome measure in UC. Multiple histological disease activity (HA) indices, including the Geboes score (GS) and modified Riley score (MRS), have been developed; however, the operating properties of these instruments are not clearly defined. We assessed the reproducibility of existing measures of HA. Five experienced pathologists with GI pathology fellowship training and expertise in IBD evaluated, on three separate occasions at least two weeks apart, 49 UC colon biopsies and scored the GS, MRS and a global rating of histological severity using a 100 mm visual analogue scale (VAS). The reproducibility of each grading system and for individual instrument items was quantified by estimates of intraclass correlation coefficients (ICCs) based on two-way random effects models. Uncertainty of estimates was quantified by 95% two-sided CIs obtained using the non-parametric cluster bootstrap method. Biopsies responsible for the greatest disagreement based on the ICC estimates were identified. A consensus process was used to determine the most common sources of measurement disagreement. Recommendations for minimising disagreement were subsequently generated. Intrarater ICCs (95% CIs) for the total GS, MRS and VAS scores were 0.82 (0.73 to 0.88), 0.71 (0.63 to 0.80) and 0.79 (0.72 to 0.85), respectively. Corresponding inter-rater ICCs were substantially lower: 0.56 (0.39 to 0.67), 0.48 (0.35 to 0.66) and 0.61 (0.47 to 0.72). Correlation between the GS and VAS was 0.62 and between the MRS and VAS was 0.61. Although 'substantial' to 'almost perfect' ICCs for intrarater agreement were found in the assessment of HA in UC, ICCs for inter-rater agreement were considerably lower. According to the consensus process results, standardisation of item definitions and modification of the existing indices is required to create an optimal UC histological instrument.


Primate population dynamics over 32.9 years at Ngogo, Kibale National Park, Uganda.
We present census data for eight primate species spanning 32.9 years along the same transect at Ngogo, Kibale National Park, Uganda, demonstrating major changes in the composition of the primate community. Correlated with an estimated decline of ∼89% in the red colobus population was an increase in encounter rates with chimpanzee parties. Our data, along with the unusually high rates of predation by chimpanzees on red colobus at Ngogo and the fact that the chimpanzee community at Ngogo is the largest ever recorded, support the conclusion that the red colobus decline was caused primarily by chimpanzee predation. This seems to be the first documented case of predation by one nonhuman primate causing the population decline in another. We evaluated disease and interspecific competition as other possible causes of the red colobus decline, but judged them to be relatively insignificant compared with predation by chimpanzees. Notable changes in encounter rates with other primate species may have resulted from forest expansion. Those for mangabeys, redtails, and black and white colobus increased significantly. Encounter rates increased for l'Hoest's monkeys too, but the increased sightings may have been an artifact of increased habituation. Sightings of blue monkey and baboon groups declined. There was no significant change in encounter rates for all species combined. The Ngogo primate community seemed to be in a nonequilibrium state, changing from one dominated by two species, a folivore (red colobus) and a frugivorous omnivore (redtails), to one dominated by three species of frugivorous omnivores (redtails, mangabeys, and chimpanzees). This study demonstrates the importance of long-term monitoring in understanding population dynamics and the role of intrinsic variables in shaping the species composition of a community.


Comparison of Agar Dilution to Broth Microdilution for Testing In Vitro Activity of Cefiderocol against Gram-Negative Bacilli.
Cefiderocol (CFDC) is a siderophore cephalosporin with activity against Gram-negative bacterial species that are resistant to carbapenems and other drugs. The MICs of CFDC were determined for 610 Gram-negative bacilli, including 302 multinational Enterobacterales isolates with characterized mechanisms of beta-lactam resistance, 180 clinical isolates from the Mayo Clinic and Mayo Clinic Laboratories not characterized for specific resistance mechanisms, and 128 isolates with CFDC MICs of ≥8 μg/ml obtained from International Health Management Associates, Inc. (IHMA, Schaumburg, IL). Broth microdilution using standard cation-adjusted Mueller-Hinton broth (BMD) and iron-depleted cation-adjusted Mueller-Hinton broth (ID-BMD), and agar dilution (AD) using standard Mueller-Hinton agar were performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. MICs were interpreted according to the investigational CLSI, FDA, and EUCAST breakpoints, and results were compared. MICs inhibiting 50 and 90% of organisms (MIC50 and MIC90, respectively), essential agreement (EA), categorical agreement (CA), and error of different types were determined. Results showed considerable discordance between AD and ID-BMD. CFDC showed low EA and CA rates and high error rates for AD in comparison to ID-BMD. Overall, this study does not support use of standard AD for determining CFDC MICs.


Resveratrol Inhibits Diabetic-Induced Müller Cells Apoptosis through MicroRNA-29b/Specificity Protein 1 Pathway.
The aim of this study was to evaluate the anti-apoptosis effects of resveratrol (RSV) on diabetic rats retinal Müller cells in vivo and in vitro and to further investigate the roles of microRNA-29b (miR-29b)/specificity protein 1 (SP1) in the anti-apoptosis mechanism of RSV. Retina was obtained from normal and diabetic rats with or without RSV (5 and 10 mg/kg/day) treatments at 1-7 months. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and Annexin V/PI staining were used to detect apoptosis. Immunofluorescence was used to assess distribution of SP1 in retina. MiR-29b and SP1 messenger RNA (mRNA) expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). SP1, Bax, and bcl-2 protein expression was evaluated by western blotting. Caspase-3 activity was detected by assay kit. Our study showed that the TUNEL-positive cells were mainly localized in the inner nuclear layer (INL) of retina and RSV administration effectively suppressed streptozotocin (STZ)-induced apoptosis of retinal cells in INL in vivo (P < 0.001). Our study also showed that RSV administration effectively suppressed high glucose (HG)-induced retinal Müller cells' apoptosis in vitro (P < 0.001). Furthermore, our study revealed that the diabetes-induced downregulated expression of miR-29b and upregulated expression of SP1 could be rescued by RSV in vivo and in vitro (P < 0.05). The anti-apoptosis effect and downregulated SP1 expression effect of RSV was prevented by miR-29b inhibitor (P < 0.05). MiR-29b mimic increased the above-mentioned effects of RSV (P < 0.001). These findings indicate that RSV is a potential therapeutic option for diabetic retinopathy (DR) and that miR-29b/SP1 pathway play roles in the anti-apoptosis mechanism of RSV.


Omega-3 fatty acids in first-episode schizophrenia - a randomized controlled study of efficacy and relapse prevention (OFFER): rationale, design, and methods.
Polyunsaturated fatty acid (PUFA) metabolism abnormalities have been long implicated in the etiology of schizophrenia. Although several randomized clinical trials have been carried out to assess the efficacy of omega-3 PUFA as add-on therapy in reducing psychopathology in populations of chronic patients with schizophrenia, only a few concern first-episode schizophrenia. The majority of these studies used a 12-week intervention based on ethyl-eicosapentaenoic acid (ethyl-EPA), however, with conflicting results. An intervention based on docosahexaenoic acid plus EPA has not been used in first-episode schizophrenia studies so far. No add-on supplementation studies have been carried out in medicated first-episode schizophrenia patients to assess the efficacy of omega-3 PUFA in preventing relapses. A randomized placebo-controlled one-center trial will be used to compare the efficacy of 26-week intervention, composed of either 1320 mg/day of EPA and 880 mg/day of DHA, or olive oil placebo with regard to symptom severity and relapse rate in first-episode schizophrenia patients. Eighty-two patients (aged 16-35) will be recruited for the study. Eligible patients will be randomly allocated to one of two intervention arms: an active arm or a placebo arm (olive oil). The primary outcome measure of the clinical evaluation is schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale (PANSS). Other outcomes include depressive symptoms, patient functioning and the level of insight. Correlates of change measured during the study will include structural brain changes, oxidative stress and defense, as well as neuroplasticity indicators. Metabolic syndrome components will also be assessed throughout the study. By comparing 26-week administration of EPA + DHA or (placebo) olive oil as add-on therapy in reducing symptom severity and one-year relapse rate in patients with first episode schizophrenia, it is intended to provide new insights into the efficacy of omega-3 PUFA and correlates of change, and contribute to the improvement of mental health care for individuals suffering from schizophrenia. This study has been registered at Clinical Trials.gov with the following number: NCT02210962 .


Nicotine effects on rat seizures susceptibility and hippocampal neuronal degeneration.
Nicotine is a widely used drug of abuse exerting number of effects on the central nervous system. The study was aimed at the effects of nicotine in various doses on the excitability of cerebral cortex and - by using the methods of histochemistry - to identify possible signs of neuronal degeneration after nicotine administration. Cortical afterdischarges were elicited by repeated stimulation of the right sensorimotor cortex. The duration of evoked ADs was monitored in animals treated with nicotine (0.75 or 1.0mg/kg) and in animals treated with saline. Methods of histochemistry (Fluoro-Jade B and bis-benzimide) were used to detect possible neuronal degeneration in hippocampus or in cerebral cortex. No Fluoro-Jade B positive cells were found in hippocampi of control animals, or animals treated with nicotine. ADs length was significantly influenced by administration of nicotine. Nicotine in 0.75 or 1.0 mg/kg dose leads to the decrease in ADs duration, influences the seizure susceptibility, and doesn't cause any detectable neuronal damage.


Overlapping and distinct functions for cofilin, coronin and Aip1 in actin dynamics in vivo.
Actin-filament disassembly is crucial for actin-based motility, to control filament network architecture and to regenerate subunits for assembly. Here, we examined the roles of three actin cytoskeletal proteins, coronin, cofilin and Aip1, which have been suggested to combine in various ways to control actin dynamics by promoting or regulating disassembly. We studied their functions during the endocytosis process in budding yeast, where actin-filament dynamics at the cortical actin 'patch' contribute to the formation and movement of endocytic vesicles. We found that all three proteins were recruited during the late phase of the life of the actin patch. They all arrived at the same time, when actin and other actin-associated proteins were leaving the patch. Cofilin point mutations influenced the localization of coronin and Aip1, but the complete loss of coronin had no effect on localization of cofilin or Aip1. Using quantitative patch motion analysis and comparing mutant alleles, the phenotypes for mutations of the three genes showed some commonalities, but also some striking differences. Cofilin was clearly the most important; it displayed the most severe mutant phenotypes affecting actin-patch assembly and movement. Together, the results suggest that all three proteins work together to promote actin disassembly, but not in a simple way, and not with equal importance.


Expression of aberrant functional and nonfunctional transcripts of the FHIT gene in Burkitt's lymphomas.
The 3p14.2 chromosome region, which contains the FHIT gene and the FRA3B fragile site, is frequently altered in carcinomas. We analyzed the expression of the FHIT gene in 21 Burkitt's lymphoma cell lines and normal lymphoid populations. Seventeen (80%) of these cell lines had a common aberrant FHIT transcript as well as the normal transcript. Exon 2 was often aberrantly spliced to several coding exons, skipping exons 3 and 4, which overlap FRA3B. Other aberrant transcripts lacked exons 4-7 or exons 5-8. Exon 5, which has the initiation codon, was the most commonly affected. In two cell lines, Raji and KK124, there were aberrant transcripts retaining only the coding exons, which were able to make a normal protein, as demonstrated by in vitro transcription-translation analysis. In these aberrant messages, the additional deletion of 11 nucleotides at the beginning of exon 10 resulted in loss of translation. The cell line Ramos did not have a normal transcript. Some transcripts had common insertions of unknown origin that replaced coding exons, mainly exons 6 and 7. None of these aberrant messages coded for a protein, whether normal or aberrant. Within an individual cell line, aberrant messages appeared to result from sequential splicing reactions of a transcriptional unit derived from one allele. There was no correlation between aberrant FHIT transcription and the type of Burkitt's lymphoma regarding chromosomal translocation or presence of Epstein-Barr virus. In normal tonsils, spleen, and peripheral blood lymphocytes, aberrant transcripts were not detected and might represent a very minor subpopulation if detectable.


Annotated zoogeography of non-marine Tardigrada. Part III: North America and Greenland.
This paper is the third monograph of the series that describes the global records of limno-terrestrial water bears (Tardigrada). Here, we provide a comprehensive list of non-marine tardigrades recorded from the North America, providing an updated and revised taxonomy accompanied by geographic co-ordinates, habitat, and biogeographic comments. It is hoped this work will serve as a reference point and background for further zoogeographical and taxonomical studies.


Interventions for the treatment of Morton's neuroma.
Morton's neuroma is a common, paroxysmal neuralgia affecting the web spaces of the toes, typically the third. The pain is often so debilitating that patients become anxious about walking or even putting their foot to the ground. Insoles, corticosteroid injections, excision of the nerve, transposition of the nerve and neurolysis of the nerve are commonly used treatments. Their effectiveness is poorly understood. To examine the evidence from randomised controlled trials concerning the effectiveness of interventions in adults with Morton's neuroma. We searched the Cochrane Neuromuscular Disease Group trials register (searched January 2003), MEDLINE (January 1966 to January Week 2 2003), EMBASE (January 1980 to February Week 2 2003), and CINAHL (January 1982 to February Week 1 2003). Randomised or quasi-randomised (methods of allocating participants to an intervention which were not strictly random e.g. date of birth, hospital record, number alternation) controlled trials of interventions for Morton's neuroma were selected. Studies where participants were not randomised into intervention groups were excluded. Two reviewers selected trials for inclusion in the review, assessed their methodological quality and extracted data independently. Three trials involving 121 people were included. There is, at most, a very limited indication that transposition of the transected plantar digital nerve may yield better results than standard resection of the nerve in the long term. There is no evidence to support the use of supinatory insoles. There are, at best, very limited indications to suggest that dorsal incisions for resection of the plantar digital nerve may result in less symptomatic post-operative scars when compared to plantar excision of the nerve. There is insufficient evidence with which to assess the effectiveness of surgical and non-surgical interventions for Morton's neuroma. Well designed trials are needed to begin to establish an evidence base for the treatment of Morton's neuroma pain.


Helical nanoparticle-induced enantiospecific adsorption of N3 dyes.
It is of fundamental demand for heterogeneous asymmetric catalysis on generating intrinsically chiral metal catalysts without modification of chiral ligands on which molecular substrates can be enantiospecifically adsorbed, which is lack of investigation. Herein, we demonstrate that the anchoring of N3 dyes on plasmonic helical nanoparticles (PhNPs) made of silver through the formation of NCS-Ag contacts leads to enantiospecific adsorption of N3 dyes. The enantiospecific configuration of the immobilized N3 dyes is primarily determined by the helical handedness, and the maximization of the adsorption enantiospecificity occurs at a nominal helical pitch of ∼15 nm, probably ascribed to the formation of supramolecular chiral complexes and/or the helical handedness-induced break of mirror symmetry of adsorption configuration. This study may pave the way for developing of PhNPs to function as intrinsically chiral catalysts and devising an alternative method to operate heterogeneous asymmetric catalysis with high enantioselectivity, which is practically desired for the manufacture of prominent single-enantiomer chemicals.


Exact and approximate arithmetic in an Amazonian indigene group.
Is calculation possible without language? Or is the human ability for arithmetic dependent on the language faculty? To clarify the relation between language and arithmetic, we studied numerical cognition in speakers of Mundurukú, an Amazonian language with a very small lexicon of number words. Although the Mundurukú lack words for numbers beyond 5, they are able to compare and add large approximate numbers that are far beyond their naming range. However, they fail in exact arithmetic with numbers larger than 4 or 5. Our results imply a distinction between a nonverbal system of number approximation and a language-based counting system for exact number and arithmetic.


Epidermal growth factor receptor mRNA in peripheral blood of patients with pancreatic, lung, and colon carcinomas detected by RT-PCR.
The epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors. An RT-PCR assay was used to detect EGFR mRNA in the blood of 43 patients with pancreatic, lung (NSCLC), colon, and renal carcinomas. After an initial serum tube was drawn to clear the line of detached epithelial cells, a 3 ml sample of EDTA-anticoagulated blood was collected from each cancer patient and healthy control. Total RNA was isolated from each sample and from cancer cell lines. After reverse transcription using specific priming, outer and nested primers for EGFR were employed for cDNA amplification. RNA integrity was confirmed with RT-PCR amplification using beta2-microglobulin primers. PCR products were electrophoresed on agarose gels containing ethidium bromide and visualized. The assay was validated using Southern blotting and was capable of detecting a lower limit of 100 fg of total RNA from the A431 cell line. EGFR-positive cells were detected in 3/10 (30%) non-small cell lung cancer patients, 2/11 (18%) pancreatic cancer patients, and 2/16 (12.5%) colon cancer patients, but in 0/6 (0%) patients with renal carcinoma (16% of solid tumor patients overall). All 23 healthy controls were negative. This study is the first to apply RT-PCR for the detection of EGFR mRNA in the peripheral blood of patients with pancreatic and renal carcinomas, and it lends further support for the use of EGFR mRNA as a marker of CTCs in the blood of patients with certain types of solid tumors.


Molecular surveillance on Streptococcus pneumoniae carriage in non-elderly adults; little evidence for pneumococcal circulation independent from the reservoir in children.
Carriage of Streptococcus pneumoniae in adults is rarely detected by the gold standard culture method. With molecular tests of high sensitivity now available, we analysed upper respiratory tract samples collected during autumn/winter 2012/2013 from parents of PCV7-vaccinated infants and from childless adults, directly comparing culture and qPCR-based S. pneumoniae detection. As compared to the gold standard of testing nasopharyngeal swabs, qPCR-based analysis of oral samples significantly improved detection of pneumococcal carriage (5% versus 20%, p < 0.0001) with higher carriage rates in parents compared to childless adults (34% versus 7%; p < 0.001). Molecular methods also increased the number of serotype-carriage events detected with higher carriage frequencies of serotypes 3 and 7A/F and lower of serotypes 6C/D and 15A/B/C in parents compared to their infant children. We provide evidence that culture-based methods severely underestimate adult carriage rates and for the superiority of testing oral samples over nasopharyngeal swabs. The substantial circulation of pneumococci in parents is however, not representative for the entire adult population. While age-associated differences in serotype carriage suggests reservoirs outside infants as potential sources of vaccine-serotypes contributing to weakening of vaccine herd effects, we find no evidence for reservoirs in adults contributing to serotype replacement in carriage.


Comparison of 16 mm OSU-Nag and COMS eye plaques.
OSU-NAG eye plaques use fewer sources than COMS-plaques of comparable size, and do not employ a Silastic seed carrier insert. Monte Carlo modeling was used to calculate 3D dose distributions for a 16 mm OSU-NAG eye plaque and a 16 mm COMS eye plaque loaded with either Iodine-125 or Cesium-131 brachytherapy sources. The OSU-NAG eye plaque was loaded with eight sources forming two squares, whereas the COMS eye plaque was loaded with thirteen sources approximating three isocentric circles. A spherical eyeball 24.6 mm in diameter and an ellipsoid-like tumor 6 mm in height and 12 mm in the major and minor axes were used to evaluate the doses delivered. To establish a fair comparison, a water seed carrier was used instead of the Silastic seed carrier designed for the traditional COMS eye plaque. Calculations were performed on the dose distributions along the eye plaque axis and the DVHs of the tumor, as well as the 3D distribution. Our results indicated that, to achieve a prescription dose of 85 Gy at 6 mm from the inner sclera edge for a six-day treatment, the OSU-NAG eye plaque will need 6.16 U/source and 6.82U/source for 125I and 131Cs, respectively. The COMS eye plaque will require 4.02 U/source and 4.43 U/source for the same source types. The dose profiles of the two types of eye plaques on their central axes are within 9% difference for all applicable distances. The OSU-NAG plaque delivers about 10% and 12% more dose than the COMS for 125I and 131Cs sources, respectively, at the inner sclera edge, but 6% and 3% less dose at the opposite retina. The DVHs of the tumor for two types of plaques were within 6% difference. In conclusion, the dosimetric quality of the OSU-NAG eye plaque used in eye plaque brachytherapy is comparable to the COMS eye plaque.


Reconstructive management of contralateral breast cancer in patients who previously underwent unilateral breast reconstruction.
When a patient who has had unilateral breast reconstruction presents with a new cancer on the opposite side, the reconstructive management of the second breast can be unclear. This study was performed to determine whether reconstruction of the second breast is oncologically reasonable and to evaluate the reconstructive options available to these patients. Patients who had mastectomy with unilateral breast reconstruction between 1988 and 1994 and who had a minimal follow-up of 5 years from the initial breast cancer were reviewed. Of 469 patients reviewed, 18 patients (4 percent) were identified who developed contralateral breast cancer. Mean age at the initial breast cancer presentation was 43 years (range, 26 to 57 years), and mean age at presentation with contralateral breast cancer was 48 years (range, 36 to 67). The mean interval between the initial and contralateral breast cancer presentations was 5 years (range, 1 to 10 years). Mean follow-up from the time of contralateral breast cancer was 5 years (range, 1 to 9 years). In most cases, contralateral breast cancer presented at an early stage (13 of 18 patients; 72 percent), and a shift to an earlier stage at presentation of the contralateral cancer was evident compared with the initial breast cancer. Of the 18 patients who developed contralateral breast cancer, 16 (89 percent) had no evidence of disease, one was alive with disease, and one died. Reconstructive management after the initial mastectomy included 16 transverse rectus abdominis myocutaneous flaps (seven free and nine pedicled), one latissimus dorsi myocutaneous flap with implant, and one superior gluteal free flap. Surgical management of the second breast after contralateral breast cancer included breast conservation in two patients, mastectomy without reconstruction in four, and mastectomy with reconstruction in 12. Reconstruction of the second breast included one free transverse rectus abdominis myocutaneous flap, three extended latissimus dorsi flaps, two latissimus dorsi myocutaneous flaps with implants, three implants alone, two Rubens flaps, and one superior gluteal free flap. No major complications were noted after the reconstruction of the second breast. The best symmetry was obtained when similar methods and tissues were used on both sides. The incidence of contralateral breast cancer after mastectomy and unilateral breast reconstruction is low. In most cases, contralateral breast cancer presents at an earlier stage compared with the initial breast cancer, and the prognosis is good. In patients who develop a contralateral breast cancer after mastectomy and unilateral breast reconstruction, the reconstruction of the second breast after mastectomy is oncologically reasonable and should be offered to provide optimal breast symmetry and a better quality of life. The best result is obtained when similar methods and tissues are used on both sides.


Sex change in a coral-reef fish: dependence of stimulation and inhibition on relative size.
The removal of a single dominant individual has been shown to trigger a sex change in some coral-reeffish. In the saddleback wrasse (Thalassoma duperrey), however, female-to-male sex change requires visual stimulation from smaller conspecifics. This change is not dependent on the sex or color of the stimulus fish and can be inhibited by larger conspecifics. On the reef, a female probably changes sex when the relative numbers of larger and smaller conspecifics change within her home range.


Breast cancer education for Navajo women: a pilot study evaluating a culturally relevant video.
This pilot study evaluated a culturally specific video designed to teach Navajo women about breast cancer treatment options. Fourteen Navajo women diagnosed with breast cancer and 26 healthcare providers participated in a mixed-method evaluation that documented their perceptions immediately and 6 months after viewing the video. After initial viewing, women reported reduced anxiety about treatment and interest in support groups. Six months later, women said the video prompted them to seek more information from printed sources and their provider. Younger Navajo women who were 44 to 51 years old were more likely to attend support groups than women who were 55-67 years. Providers corroborated the positive effects of the video. The providers believed the video encouraged patients to seek information about breast cancer and to ask questions about treatment plans and side effects. A culturally relevant video for Navajo women can be an effective teaching tool and can enhance patient-provider communication.


Deformation and shape of flexible, microscale helices in viscous flow.
We examine experimentally the deformation of flexible, microscale helical ribbons with nanoscale thickness subject to viscous flow in a microfluidic channel. Two aspects of flexible microhelices are quantified: the overall shape of the helix and the viscous frictional properties. The frictional coefficients determined by our experiments are consistent with calculated values in the context of resistive-force theory. The deformation of helices by viscous flow is well described by nonlinear finite extensibility. Under distributed loading, the pitch distribution is nonuniform, and from this we identify both linear and nonlinear behavior along the contour length of a single helix. Moreover, flexible helices are found to display reversible global to local helical transitions at a high flow rate.


Obsessive-Compulsive Disorder in Adults with High-Functioning Autism Spectrum Disorder: What Does Self-Report with the OCI-R Tell Us?
Little is known about the symptom profile of obsessive-compulsive disorder (OCD) in individuals who have autism spectrum disorders (ASD). It is also unknown whether self-report questionnaires are useful in measuring OCD in ASD. We sought to describe the symptom profiles of adults with ASD, OCD, and ASD + OCD using the Obsessive Compulsive Inventory-Revised (OCI-R), and to assess the utility of the OCI-R as a screening measure in a high-functioning adult ASD sample. Individuals with ASD (n = 171), OCD (n = 108), ASD + OCD (n = 54) and control participants (n = 92) completed the OCI-R. Individuals with ASD + OCD reported significantly higher levels of obsessive-compulsive symptoms than those with ASD alone. OCD symptoms were not significantly correlated with core ASD repetitive behaviors as measured on the ADI-R or ADOS-G. The OCI-R showed good psychometric properties and corresponded well with clinician diagnosis of OCD. Receiver operating characteristic analysis suggested cut-offs for OCI-R Total and Checking scores that discriminated well between ASD + versus -OCD, and fairly well between ASD-alone and OCD-alone. OCD manifests separately from ASD and is characterized by a different profile of repetitive thoughts and behaviors. The OCI-R appears to be useful as a screening tool in the ASD adult population.


Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels.
The voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane mediates metabolic flow, Ca(2+), and cell death signaling between the endoplasmic reticulum (ER) and mitochondrial networks. We demonstrate that VDAC1 is physically linked to the endoplasmic reticulum Ca(2+)-release channel inositol 1,4,5-trisphosphate receptor (IP(3)R) through the molecular chaperone glucose-regulated protein 75 (grp75). Functional interaction between the channels was shown by the recombinant expression of the ligand-binding domain of the IP(3)R on the ER or mitochondrial surface, which directly enhanced Ca(2+) accumulation in mitochondria. Knockdown of grp75 abolished the stimulatory effect, highlighting chaperone-mediated conformational coupling between the IP(3)R and the mitochondrial Ca(2+) uptake machinery. Because organelle Ca(2+) homeostasis influences fundamentally cellular functions and death signaling, the central location of grp75 may represent an important control point of cell fate and pathogenesis.


The Relationship Between the Global Burden of Influenza From 2017 to 2019 and COVID-19: Descriptive Epidemiological Assessment.
SARS-CoV-2 and influenza are lipid-enveloped viruses with differential morbidity and mortality but shared modes of transmission. With a descriptive epidemiological framing, we assessed whether recent historical patterns of regional influenza burden are reflected in the observed heterogeneity in COVID-19 cases across regions of the world. Weekly surveillance data reported by the World Health Organization from January 2017 to December 2019 for influenza and from January 1, 2020 through October 31, 2020, for COVID-19 were used to assess seasonal and temporal trends for influenza and COVID-19 cases across the seven World Bank regions. In regions with more pronounced influenza seasonality, COVID-19 epidemics have largely followed trends similar to those seen for influenza from 2017 to 2019. COVID-19 epidemics in countries across Europe, Central Asia, and North America have been marked by a first peak during the spring, followed by significant reductions in COVID-19 cases in the summer months and a second wave in the fall. In Latin America and the Caribbean, COVID-19 epidemics in several countries peaked in the summer, corresponding to months with the highest influenza activity in the region. Countries from regions with less pronounced influenza activity, including South Asia and sub-Saharan Africa, showed more heterogeneity in COVID-19 epidemics seen to date. However, similarities in COVID-19 and influenza trends were evident within select countries irrespective of region. Ecological consistency in COVID-19 trends seen to date with influenza trends suggests the potential for shared individual, structural, and environmental determinants of transmission. Using a descriptive epidemiological framework to assess shared regional trends for rapidly emerging respiratory pathogens with better studied respiratory infections may provide further insights into the differential impacts of nonpharmacologic interventions and intersections with environmental conditions. Ultimately, forecasting trends and informing interventions for novel respiratory pathogens like COVID-19 should leverage epidemiologic patterns in the relative burden of past respiratory pathogens as prior information.


Bacillary angiomatosis with atypical clinical presentation in an immunocompetent patient.
Bacillary angiomatosis is a recently described infectious disease that usually affects immunosupressed hosts with a previous history of contact with cats. We report a rare case of bacillary angiomatosis in an immunocompetent 59-year-old woman with no history of previous exposure to cats, and atypical clinical features (fever and subcutaneous nodules with ulceration on the left ankle). Histopathology of the lesion showed extensive ulceration and reactive tumor-like vascular proliferation of the blood vessels with swollen endothelial cells and an inflammatory infiltrate including neutrophils and lymphocytes in the dermis and subcutis. Staining with the Warthin-Starry method demonstrated the presence of clustered bacilli located in the extracellular matrix adjacent to the proliferating endothelial cells. Diagnosis was confirmed with the detection of Bartonella spp. DNA in the affected skin and in bone marrow using polymerase chain reaction.


CDK targets Sae2 to control DNA-end resection and homologous recombination.
DNA double-strand breaks (DSBs) are repaired by two principal mechanisms: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR is the most accurate DSB repair mechanism but is generally restricted to the S and G2 phases of the cell cycle, when DNA has been replicated and a sister chromatid is available as a repair template. By contrast, NHEJ operates throughout the cell cycle but assumes most importance in G1 (refs 4, 6). The choice between repair pathways is governed by cyclin-dependent protein kinases (CDKs), with a major site of control being at the level of DSB resection, an event that is necessary for HR but not NHEJ, and which takes place most effectively in S and G2 (refs 2, 5). Here we establish that cell-cycle control of DSB resection in Saccharomyces cerevisiae results from the phosphorylation by CDK of an evolutionarily conserved motif in the Sae2 protein. We show that mutating Ser 267 of Sae2 to a non-phosphorylatable residue causes phenotypes comparable to those of a sae2Delta null mutant, including hypersensitivity to camptothecin, defective sporulation, reduced hairpin-induced recombination, severely impaired DNA-end processing and faulty assembly and disassembly of HR factors. Furthermore, a Sae2 mutation that mimics constitutive Ser 267 phosphorylation complements these phenotypes and overcomes the necessity of CDK activity for DSB resection. The Sae2 mutations also cause cell-cycle-stage specific hypersensitivity to DNA damage and affect the balance between HR and NHEJ. These findings therefore provide a mechanistic basis for cell-cycle control of DSB repair and highlight the importance of regulating DSB resection.


The Alpha and Omega of Galactosylceramides in T Cell Immune Function.
Glycosphingolipids are a subgroup of glycolipids that contain an amino alcohol sphingoid base linked to sugars. They are found in the membranes of cells ranging from bacteria to vertebrates. This group of lipids is known to stimulate the immune system through activation of a type of white blood cell known as natural killer T cell (NKT cell). Here we summarize the extensive research that has been done to identify the structures of natural glycolipids that stimulate NKT cells and to determine how these antigens are recognized. We also review studies designed to understand how glycolipid variants, both natural and synthetic, can alter the responses of NKT cells, leading to dramatic changes in the global immune response.


Effect of WIC Food Package Changes on Dietary Intake of Preschool Children in New Mexico.
This study examined WIC policy change effects on dietary intake of preschool children from WIC-participating households in rural New Mexico communities. Dietary intake of children enrolled in Head Start in 8 communities was compared before and after 2009 WIC food package changes. Following the policy change, participants reported significantly increased consumption of lower-fat milk, reduced consumption of saturated fat (grams), and decreased consumption of vegetables without potatoes. No significant differences in fruit, fruit juice, vegetables including potatoes, whole-grains and saturated fat (percent-energy) consumption were observed. WIC policy changes have the potential to improve children's saturated fat intake. More research with robust designs is necessary to examine long-term effects of WIC policy changes.


Perceived need and attitudes towards communication skill training in recently admitted undergraduate medical students.
The Medical Council of India intends to implement an attitude, ethics, and communication training module for medical students. This study investigates undergraduate students' attitudes towards communication skills training (CST). Forms were distributed to 81 recently admitted undergraduates, of whom 76 responded, in an anonymous cross-sectional survey. Single questions assessed knowledge of communication skills (CS), need for formal curriculum, and importance of CST. Attitudes toward CS were measured using a modified Communication Skills Attitude Scale. While 72% participants considered CST to be important and 68.4% reported a need for formal training, 43% felt CST would have a better image if it sounded more like a science subject. Forty percent of the students were ambiguous about willingness to trust information on communication skills given by non-clinical lecturers, whereas 15.8% were not receptive. Fifty-five percent felt nobody would fail because of poor communication skills, and 46% felt that the ability to pass exams would get them through medical school. We found a high prevalence of unfavourable attitudes about CS (as a subject). Course implementers should be mindful of and address attitudes towards CST while delivering the content of the course.


Comparative losses of quantitative and molecular genetic variation in finite populations of Drosophila melanogaster.
Quantitative genetic variation, the main determinant of the ability to evolve, is expected to be lost in small populations, but there are limited data on the effect, and controversy as to whether it is similar to that for near neutral molecular variation. Genetic variation for abdominal and sternopleural bristle numbers and allozyme heterozygosity were estimated in 23 populations of Drosophila melanogaster maintained at effective population sizes of 25, 50, 100, 250 or 500 for 50 generations, as well as in 19 highly inbred populations and the wild outbred base population. Highly significant negative regressions of proportion of initial genetic variation retained on inbreeding due to finite population size were observed for both quantitative characters (b = -0.67 +/- 0.14 and -0.58 +/- 0.11) and allozyme heterozygosity (b = -0.79 +/- 0.10), and the regression coefficients did not differ significantly. Thus, quantitative genetic variation is being lost at a similar rate to molecular genetic variation. However, genetic variation for all traits was lost at rates significantly slower than predicted by neutral theory, most likely due to associative overdominance. Positive, but relatively low correlations were found among the different measures of genetic variation, but their low magnitudes were attributed to large sampling errors, rather than differences in the underlying processes of loss.


Proposed evolutionary changes in the role of myelin.
Myelin is the multi-layered lipid sheet periodically wrapped around neuronal axons. It is most frequently found in vertebrates. Myelin allows for saltatory action potential (AP) conduction along axons. During this form of conduction, the AP travels passively along the myelin-covered part of the axon, and is recharged at the intermittent nodes of Ranvier. Thus, myelin can reduce the energy load needed and/or increase the speed of AP conduction. Myelin first evolved during the Ordovician period. We hypothesize that myelin's first role was mainly energy conservation. During the later "Mesozoic marine revolution," marine ecosystems changed toward an increase in marine predation pressure. We hypothesize that the main purpose of myelin changed from energy conservation to conduction speed increase during this Mesozoic marine revolution. To test this hypothesis, we optimized models of myelinated axons for a combination of AP conduction velocity and energy efficiency. We demonstrate that there is a trade-off between these objectives. We then compared the simulation results to empirical data and conclude that while the data are consistent with the theory, additional measurements are necessary for a complete evaluation of the proposed hypothesis.


Electro-optic properties of switchable gratings made of polymer and nematic liquid-crystal slices.
We report the diffraction properties at wavelengths of 632.8 and 1550 nm for volume transmission gratings made of a sequence of continuously aligned nematic liquid-crystal layers separated by isotropic polymer slices. The gratings are generated by holographically curing a solution of liquid crystal diluted in an isotropic prepolymer by means of a laser beam at a wavelength of 352 nm with a total intensity of approximately 10 mW/cm2. A diffraction efficiency of 98% was measured, and an electric field as low as 5 V/microm switches off the phase grating. Measured angular spectra are fitted by use of the modified coupled-mode theory including the effects of grating birefringence.


Protein kinase B (c-akt) regulates hematopoietic lineage choice decisions during myelopoiesis.
Hematopoiesis is a highly regulated process resulting in the formation of all blood lineages. Aberrant regulation of phosphatidylinositol-3-kinase (PI3K) signaling has been observed in hematopoietic malignancies, suggesting that regulated PI3K signaling is critical for regulation of blood cell production. An ex vivo differentiation system was used to investigate the role of PI3K and its downstream effector, protein kinase B (PKB/c-akt) in myelopoiesis. PI3K activity was essential for hematopoietic progenitor survival. High PKB activity was found to promote neutrophil and monocyte development, while, conversely, reduction of PKB activity was required to induce optimal eosinophil differentiation. In addition, transplantation of beta2-microglobulin (-/-) NOD/SCID mice with CD34(+) cells ectopically expressing constitutively active PKB resulted in enhanced neutrophil and monocyte development, whereas ectopic expression of dominant-negative PKB induced eosinophil development in vivo. Inhibitory phosphorylation of C/EBPalpha on Thr222/226 was abrogated upon PKB activation in hematopoietic progenitors. Ectopic expression of a nonphosphorylatable C/EBPalpha mutant inhibited eosinophil differentiation ex vivo, whereas neutrophil development was induced, demonstrating the importance of PKB-mediated C/EBPalpha phosphorylation in regulation of granulopoiesis. These results identify an important novel role for PKB in regulation of cell fate choices during hematopoietic lineage commitment.


Factors associated with depression among individuals with chronic fatigue syndrome: findings from a nationally representative survey.
Most previous research regarding chronic fatigue syndrome (CFS) and depression has relied on clinical samples. The current research determined the prevalence and correlates of depression among individuals with CFS in a community sample. The nationally representative Canadian Community Health Survey, conducted in 2000/2001, included an unweighted sample size of 1045 individuals who reported a diagnosis of CFS and had complete data on depression. Respondents with CFS who were depressed (n = 369) were compared to those who were not depressed (n = 676). Chi-square analyses, t-tests and a logistic regression were conducted. Thirty-six per cent of individuals with CFS were depressed. Among individuals with CFS, depression was associated with lower levels of mastery and self-esteem. In the logistic regression analyses, the odds of depression among individuals with CFS were higher for females, younger respondents, those with lower incomes and food insecurity and those whose activities were limited by pain. Two in five depressed individuals had not consulted with any mental health professional in the preceding year. Twenty-two per cent of depressed respondents had seriously considered suicide in the past year. Individuals with CFS who were depressed were particularly heavy users of family physicians, with an average of 11.1 visits annually (95% confidence interval = 10.7, 11.6). It is important for clinicians to assess depression and suicidal ideation among their patients with CFS, particularly among females, those reporting moderate to severe pain, low incomes and inadequate social support.


The impact of interventions to improve attendance in female cancer screening among lower socioeconomic groups: a review.
To review the scientific evidence on the effectiveness of interventions to promote attendance to breast and cervical cancer screening among lower socioeconomic groups. We performed a computerized literature search looking for relevant papers published between 1997 and 2006. Papers were classified into three groups based on the type of intervention evaluated: (1) implementation of organized population screening programs; (2) different strategies of enhancing attendance within an organized program; (3) local interventions in disadvantaged populations. The available evidence supports the hypothesis that while organized population screening programs are successful in increasing overall participation rates, they may not per se substantially reduce social inequalities. Some strategies were consistently found to enhance access to screening among lower socioeconomic groups, including cost-reducing interventions (e.g. offering free tests and eliminating geographical barriers), a greater involvement of primary-care physicians and individually tailored pro-active communication that addresses barriers to screening. Evidence from studies suggests that the attendance of deprived women to cancer screening can be improved with organized screening programs tailored to their needs. The same may apply to the prevention of adverse outcomes of other health conditions, such as hypertension, hypercholesterolemia, and diabetes.


Anti-galectin compounds as potential anti-cancer drugs.
Galectins form a family of carbohydrate-binding proteins defined by their affinity for beta-galactosides containing glycoconjugates. The carbohydrate recognition domain (CRD) is responsible for the specificity of galectins for saccharides. This binding may result in modulated cell proliferation, cell death and cell migration, three processes that are intimately involved in cancer initiation and progression. Galectins can also display protein-protein types of interactions with their binding partners. Certain galectins directly involved in cancer progression seem to be promising targets for the development of novel therapeutic strategies to combat cancer. Indeed, migrating cancer cells resistant to apoptosis still constitute the principal target for the cytotoxic drugs used to treat cancer patients. Reducing the levels of migration in apoptosis-resistant cancer cells can restore certain levels of sensitivity to apoptosis (and so to pro-apoptotic drugs) in restricted-migration cancer cells. Anti-galectin agents can restrict the levels of migration of several types of cancer cell and should therefore be used in association with cytotoxic drugs to combat metastatic cancer. We provide experimental proof in support of this concept. While the present review focuses on various experimental strategies to impair cancer progression by targeting certain types of galectins, it pays particular attention to glioblastomas, which constitute the ultimate level of malignancy in primary brain tumors. Glioblastomas form the most common type of malignant brain tumor in children and adults, and no glioblastoma patient has been cured to date.


The end of the era of generosity? Global health amid economic crisis.
In the past decade donor commitments to health have increased by 200 percent. Correspondingly, there has been a swell of new players in the global health landscape. The unprecedented, global response to a single disease, HIV/AIDS, has been responsible for a substantial portion of this boon. Numerous health success have followed this windfall of funding and attention, yet the food, fuel, and economic crises of 2008 have shown the vulnerabilities of health and development initiatives focused on short term wins and reliant on a constant flow of foreign funding. For too long, the international community has responded to global health and development challenges with emergency solutions that often reflect the donor's priorities, values, and political leanings, rather than funding durable health systems that can withstand crises. Progress towards achieving the Millennium Development Goals has stalled in many countries. Disease specific initiatives have weakened health systems and limited efforts to improve maternal and child health. As we enter this era of scarce resources, there is a need to return to the foundations of the Alma Ata Declaration signed thirty years ago with the goal of providing universal access to primary healthcare. The global health community must now objectively evaluate how we can most effectively respond to the crises of 2008 and take advantage of this moment of extraordinary attention for global health and translate it into long term, sustainable health improvements for all.


Placebo Surgery Controlled Trials: Do They Achieve What They Set Out To Do? A Systematic Review.
To explore whether placebo surgery controlled trials achieve what they set out to do by investigating discrepancy between projected and actual design aspects of trials identified through systematic review methods. Interest in placebo surgery controlled trials is growing in response to concerns regarding unnecessary surgery and the societal cost of low-value healthcare. As questions about the justifiability of using placebo controls in surgery have been addressed, attention is now being paid to more practical concerns. Six databases were searched from inception - May 2020 (MEDLINE, Embase, Emcare, APA PsycInfo, CINAHL, Cochrane Library). Placebo surgery controlled trials with a published protocol were included. Three authors extracted "projected" design aspects from protocols and "actual" design aspects from main findings papers. Absolute and relative difference between projected and actual design aspects were presented for each trial. Trials were grouped according to whether they met their target sample size ("completed") and were concluded in a timely fashion. Pairs of authors assessed risk of bias. Of 24 trials with data available to analyse; 3 were completed and concluded within target timeframe; 10 were completed and concluded outside the target timeline; 4 were completed without clear target timeframes; 2 were incomplete and concluded within the target framework; 5 were incomplete and concluded outside the target timeline. Trials which reached the recruitment target underestimated trial duration by 88% and number of recruitment sites by 87%. Trialists need to factor additional time and sites into future placebo surgery controlled trials. A robust reporting framework of projected and actual trial design is imperative for trialists to learn from their predecessors. PROSPERO (CRD42019133296).


Autoimmunity in wiskott-Aldrich syndrome: an unsolved enigma.
Wiskott-Aldrich Syndrome (WAS) is a severe X-linked Primary Immunodeficiency that affects 1-10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP) expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was(-/-) mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections, and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22 to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease, and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients.


[Presenting a battery for assessing spatial neglect. Norms and effects of age, educational level, sex, hand and laterality].
The aim of this study was to build up a battery for assessing spatial neglect, then to analyse the norms and potential effects of age, education level, sex, hand used, and laterality. It was also to contribute evaluating the pseudoneglect phenomenon described by Heilman, which consists in a tendency of normal subjects to neglect the right peripersonal space. Tasks selected were presented to important groups of normal subjects, most often larger than 450. The battery comprised of a bell cancellation test, scene copy, clock drawing, two line bisection tasks, identification of overlapping figures, text reading, writing task, and the representational task of the France map. For each of them, different variables were selected, especially investigating the difference between performance in the right and the left hemispaces. This study allowed defining the threshold values (percentiles 5 and 95) for deciding of the pathological character of a patient performance. It also showed that the pseudoneglect phenomenon is more obvious in some tasks such as line bisection, and probably also in the representational task of the France map and writing. His importance and at times his side were influenced by the factors we studied, with between tasks differences, but also by the nature of the task to be performed, and especially his verbal component.


Minimally invasive orbital decompression for Graves' ophthalmopathy.
We reviewed a 7-year experience at a tertiary-care, academic medical center with balanced, minimally invasive decompression for Graves' ophthalmopathy, in an effort to define the goals, risks, and outcomes of surgical intervention. Endoscopic medial decompression was performed in 26 patients; 23 underwent lateral decompression as well, and 13 also had inferior decompression. Septoplasty, turbinate reduction, and orbital rim augmentation were performed as needed. The indications for surgery were threat to vision (n = 10) and proptosis with a desire to return to the predisease state (rehabilitative, n = 16). The exophthalmos improved by a mean of 4.4 mm (p < .001). All patients who had surgery for threatened vision had improved vision after the operation. There were 3 patients with new-onset postoperative diplopia, 2 of whom underwent strabismus surgery. There was 1 case of postoperative sinusitis, which resolved with oral antibiotics and nasal decongestion, and 1 case of transient ulnar neuropathy. There were no other intraoperative or postoperative complications. Modern methods of orbital decompression provide a minimally invasive, effective, and relatively safe approach to the treatment of Graves' ophthalmopathy.


On-the-Fly Integration of Data from a Spin-Diffusion-Based NMR Experiment into Protein-Ligand Docking.
INPHARMA (interligand nuclear Overhauser enhancement for pharmacophore mapping) determines the relative orientation of two competitive ligands in the protein binding pocket. It is based on the observation of interligand transferred NOEs mediated by spin diffusion through protons of the protein and is, therefore, sensitive to the specific interactions of each of the two ligands with the protein. We show how this information can be directly included into a protein-ligand docking program to guide the prediction of the complex structures. Agreement between the experimental and back-calculated spectra based on the full relaxation matrix approach is translated into a score contribution that is combined with the scoring function ChemPLP of our docking tool PLANTS. This combined score is then used to predict the poses of five weakly bound cAMP-dependent protein kinase (PKA) ligands. After optimizing the setup, which finally also included trNOE data and optimized protonation states, very good success rates were obtained for all combinations of three ligands. For one additional ligand, no conclusive results could be obtained due to the ambiguous electron density of the ligand in the X-ray structure, which does not disprove alternative ligand poses. The failures of the remaining ligand are caused by suboptimal locations of specific protein side chains. Therefore, side-chain flexibility should be included in an improved INPHARMA-PLANTS version. This will reduce the strong dependence on the used protein input structure leading to improved scores overall, not only for this last ligand.


In vitro anti-Helicobacter pylori effects of medicinal mushroom extracts, with special emphasis on the Lion's Mane mushroom, Hericium erinaceus (higher Basidiomycetes).
Although the medicinal mushroom Hericium erinaceus is used extensively in traditional Chinese medicine to treat chronic superficial gastritis, the underlining pharmaceutical mechanism is yet to be fully understood. In this study, minimum inhibitory concentration (MIC) values of extracts prepared from the fruiting bodies of 14 mushroom species (H. erinaceus, Ganoderma lucidum, Cordyceps militaris, Pleurotus eryngii, P. ostreatus, Agrocybe aegerita, Lentinus edodes, Agaricus brasiliensis, A. bisporus, Coprinus comatus, Grifola frondosa, Phellinus igniarius, Flammulina velutipes, and Hypsizygus marmoreus) were determined against Helicobacter pylori using laboratory strains of ATCC 43504 and SS1 as well as 9 clinical isolates via an in vitro microplate agar diffusion assay. Ethanol extracts (EEs) of 12 mushrooms inhibited the growth of H. pylori in vitro, with MIC values <3 mg/mL. EEs of H. erinaceus and G. lucidum also inhibited Staphylococcus aureus (MIC 7360;10 mg/mL) but had no effect on the growth of two Escherichia coli test strains (MIC >10 mg/mL). MIC values of ethyl acetate fractions (EAFs) of H. erinaceus against 9 clinical isolates of H. pylori ranged between 62.5 and 250 µg/mL. The bacteriostatic activity of EAFs was found to be concentration-dependant, and the half maximal inhibitory concentration and minimum bactericidal concentration values for H. pylori ATCC 43504 were 73.0 and 200 µg/mL, respectively. The direct inhibitory effect of EEs and EAFs of H. erinaceus against H. pylori could be another pharmaceutical mechanism of medicinal mushrooms-besides the immunomodulating effect of polysaccharides, suggested previously-in the treatment of H. pylori-associated gastrointestinal disorders. Further research to identify the active component(s) is currently undertaking in our laboratory.


Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury.
Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells. We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls. Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally. Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66). Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques.


Review of current guidelines related to the diagnosis and treatment of rhinosinusitis.
Rhinosinusitis is one of the most common medical complaints, affecting nearly 31 million US citizens annually. Multiple medical professionals including emergency medicine, internal medicine, allergy, and otolaryngology treat rhinosinusitis, resulting in high-practice variability. This review will discuss recommendations of the 2007 American Academy of Otolaryngology - Head and Neck Surgery's multispecialty panel on evidence based clinical practice guidelines for diagnosis and treatment of rhinosinusitis. The task force for recommendations defines rhinosinusitis as follows: acute bacterial, viral, chronic, or recurrent acute rhinosinusitis. For acute rhinosinusitis three symptoms are required: purulent nasal discharge with nasal obstruction and/or facial pain-pressure-fullness lasting between 10 days and 4 weeks. For viral rhinosinusitis, imaging is not recommended and treatment is symptomatic. For acute bacterial rhinosinusitis in an otherwise healthy patient, symptomatic relief is recommended including pain control. Amoxicillin is the first-line antibiotic of choice if needed. Radiographic imaging should be considered if an infectious complication is suspected. Chronic rhinosinusitis is likely when symptoms persist for greater than 12 weeks, with computed tomography being the gold standard for diagnostic testing. Nasal endoscopy and allergy/immune testing are also considered. Accurate diagnosis of rhinosinusitis with recommended treatments should standardize management. However, these recommendations are guidelines and the clinician's judgment is highly important.


5-Aminoimidazole-4-carboxamide ribonucleotide-transformylase and inosine-triphosphate-pyrophosphatase genes variants predict remission rate during methotrexate therapy in patients with juvenile idiopathic arthritis.
For children with juvenile idiopathic arthritis (JIA) who fail to respond to methotrexate, the delay in identifying the optimal treatment at an early stage of disease can lead to long-term joint damage. Recent studies indicate that relevant variants to predict methotrexate response in JIA are those in 5-aminoimidazole-4-carboxamide ribonucleotide-transformylase (ATIC), inosine-triphosphate-pyrophosphatase (ITPA) and solute-liquid-carrier-19A1 genes. The purpose of the study was, therefore, to explore the role of these candidate genetic factors on methotrexate response in an Italian cohort of children with JIA. Clinical response to methotrexate was evaluated as clinical remission stable for a 6-month period, as ACRPed score and as change in Juvenile Arthritis Disease score. The most relevant SNPs for each gene considered were assayed on patients' DNA. ITPA activity was measured in patients' erythrocytes. Sixty-nine patients with JIA were analyzed: 52.2 % responded to therapy (ACRPed70 score), while 37.7 % reached clinical remission stable for 6 months. ATIC rs2372536 GG genotype was associated with improved clinical remission (adjusted p value = 0.0090). For ITPA, rs1127354 A variant was associated with reduced clinical remission: (adjusted p value = 0.028); this association was present even for patients with wild-type ITPA and low ITPA activity. These preliminary results indicate that genotyping of ATIC rs2372536 and ITPA rs1127354 variants or measuring ITPA activity could be useful to predict methotrexate response in children with JIA after validation by further prospective studies on a larger patient cohort.


Environmental perceptions and objective walking trail audits inform a community-based participatory research walking intervention.
Given the documented physical activity disparities that exist among low-income minority communities and the increased focused on socio-ecological approaches to address physical inactivity, efforts aimed at understanding the built environment to support physical activity are needed. This community-based participatory research (CBPR) project investigates walking trails perceptions in a high minority southern community and objectively examines walking trails. The primary aim is to explore if perceived and objective audit variables predict meeting recommendations for walking and physical activity, MET/minutes/week of physical activity, and frequency of trail use. A proportional sampling plan was used to survey community residents in this cross-sectional study. Previously validated instruments were pilot tested and appropriately adapted and included the short version of the validated International Physical Activity Questionnaire, trail use, and perceptions of walking trails. Walking trails were assessed using the valid and reliable Path Environmental Audit Tool which assesses four content areas including: design features, amenities, maintenance, and pedestrian safety from traffic. Analyses included Chi-square, one-way ANOVA's, multiple linear regression, and multiple logistic models. Numerous (n = 21) high quality walking trails were available. Across trails, there were very few indicators of incivilities and safety features rated relatively high. Among the 372 respondents, trail use significantly predicted meeting recommendations for walking and physical activity, and MET/minutes/week. While controlling for other variables, significant predictors of trail use included proximity to trails, as well as perceptions of walking trail safety, trail amenities, and neighborhood pedestrian safety. Furthermore, while controlling for education, gender, and income; for every one time per week increase in using walking trails, the odds for meeting walking recommendations increased 1.27 times, and the odds for meeting PA recommendation increased 3.54 times. Perceived and objective audit variables did not predict meeting physical activity recommendations. To improve physical activity levels, intervention efforts are needed to maximize the use of existing trails, as well as improve residents' perceptions related to incivilities, safety, conditions of trail, and amenities of the walking trails. This study provides important insights for informing development of the CBPR walking intervention and informing local recreational and environmental policies in this southern community.


DMSO-induced denaturation of hen egg white lysozyme.
We report on the size, shape, structure, and interactions of lysozyme in the ternary system lysozyme/DMSO/water at low protein concentrations. Three structural regimes have been identified, which we term the "folded" (0 < φ(DMSO) < 0.7), "unfolded" (0.7 ≤ φ(DMSO) < 0.9), and "partially collapsed" (0.9 ≤ φ(DMSO) < 1.0) regime. Lysozyme resides in a folded conformation with an average radius of gyration of 1.3 ± 0.1 nm for φ(DMSO) < 0.7 and unfolds (average R(g) of 2.4 ± 0.1 nm) above φ(DMSO) > 0.7. This drastic change in the protein's size coincides with a loss of the characteristic tertiary structure. It is preceded by a compaction of the local environment of the tryptophan residues and accompanied by a large increase in the protein's overall flexibility. In terms of secondary structure, there is a gradual loss of α-helix and concomitant increase of β-sheet structural elements toward φ(DMSO) = 0.7, while an increase in φ(DMSO) at even higher DMSO volume fractions reduces the presence of both α-helix and β-sheet secondary structural elements. Protein-protein interactions remain overall repulsive for all values of φ(DMSO). An attempt is made to relate these structural changes to the three most important physical mechanisms that underlie them: the DMSO/water microstructure is strongly dependent on the DMSO volume fraction, DMSO acts as a strong H-bond acceptor, and DMSO is a bad solvent for the protein backbone and a number of relatively polar side groups, but a good solvent for relatively apolar side groups, such as tryptophan.


Comparative study of age estimation using dentinal translucency by digital and conventional methods.
Estimating age using the dentition plays a significant role in identification of the individual in forensic cases. Teeth are one of the most durable and strongest structures in the human body. The morphology and arrangement of teeth vary from person-to-person and is unique to an individual as are the fingerprints. Therefore, the use of dentition is the method of choice in the identification of the unknown. Root dentin translucency is considered to be one of the best parameters for dental age estimation. Traditionally, root dentin translucency was measured using calipers. Recently, the use of custom built software programs have been proposed for the same. The present study describes a method to measure root dentin translucency on sectioned teeth using a custom built software program Adobe Photoshop 7.0 version (Adobe system Inc, Mountain View California). A total of 50 single rooted teeth were sectioned longitudinally to derive a 0.25 mm uniform thickness and the root dentin translucency was measured using digital and caliper methods and compared. The Gustafson's morphohistologic approach is used in this study. Correlation coefficients of translucency measurements to age were statistically significant for both the methods (P < 0.125) and linear regression equations derived from both methods revealed better ability of the digital method to assess age. The custom built software program used in the present study is commercially available and widely used image editing software. Furthermore, this method is easy to use and less time consuming. The measurements obtained using this method are more precise and thus help in more accurate age estimation. Considering these benefits, the present study recommends the use of digital method to assess translucency for age estimation.


Large scale organisational intervention to improve patient safety in four UK hospitals: mixed method evaluation.
To conduct an independent evaluation of the first phase of the Health Foundation's Safer Patients Initiative (SPI), and to identify the net additional effect of SPI and any differences in changes in participating and non-participating NHS hospitals. Mixed method evaluation involving five substudies, before and after design. NHS hospitals in the United Kingdom. Four hospitals (one in each country in the UK) participating in the first phase of the SPI (SPI1); 18 control hospitals. The SPI1 was a compound (multi-component) organisational intervention delivered over 18 months that focused on improving the reliability of specific frontline care processes in designated clinical specialties and promoting organisational and cultural change. Senior staff members were knowledgeable and enthusiastic about SPI1. There was a small (0.08 points on a 5 point scale) but significant (P < 0.01) effect in favour of the SPI1 hospitals in one of 11 dimensions of the staff questionnaire (organisational climate). Qualitative evidence showed only modest penetration of SPI1 at medical ward level. Although SPI1 was designed to engage staff from the bottom up, it did not usually feel like this to those working on the wards, and questions about legitimacy of some aspects of SPI1 were raised. Of the five components to identify patients at risk of deterioration--monitoring of vital signs (14 items); routine tests (three items); evidence based standards specific to certain diseases (three items); prescribing errors (multiple items from the British National Formulary); and medical history taking (11 items)--there was little net difference between control and SPI1 hospitals, except in relation to quality of monitoring of acute medical patients, which improved on average over time across all hospitals. Recording of respiratory rate increased to a greater degree in SPI1 than in control hospitals; in the second six hours after admission recording increased from 40% (93) to 69% (165) in control hospitals and from 37% (141) to 78% (296) in SPI1 hospitals (odds ratio for "difference in difference" 2.1, 99% confidence interval 1.0 to 4.3; P = 0.008). Use of a formal scoring system for patients with pneumonia also increased over time (from 2% (102) to 23% (111) in control hospitals and from 2% (170) to 9% (189) in SPI1 hospitals), which favoured controls and was not significant (0.3, 0.02 to 3.4; P = 0.173). There were no improvements in the proportion of prescription errors and no effects that could be attributed to SPI1 in non-targeted generic areas (such as enhanced safety culture). On some measures, the lack of effect could be because compliance was already high at baseline (such as use of steroids in over 85% of cases where indicated), but even when there was more room for improvement (such as in quality of medical history taking), there was no significant additional net effect of SPI1. There were no changes over time or between control and SPI1 hospitals in errors or rates of adverse events in patients in medical wards. Mortality increased from 11% (27) to 16% (39) among controls and decreased from 17% (63) to 13% (49) among SPI1 hospitals, but the risk adjusted difference was not significant (0.5, 0.2 to 1.4; P = 0.085). Poor care was a contributing factor in four of the 178 deaths identified by review of case notes. The survey of patients showed no significant differences apart from an increase in perception of cleanliness in favour of SPI1 hospitals. The introduction of SPI1 was associated with improvements in one of the types of clinical process studied (monitoring of vital signs) and one measure of staff perceptions of organisational climate. There was no additional effect of SPI1 on other targeted issues nor on other measures of generic organisational strengthening.


Enhanced planar perovskite solar cells with efficiency exceeding 16% via reducing the oxygen vacancy defect state in titanium oxide electrode.
In this work, the influence of oxygen vacancy defect (OVD) in compact titanium oxide (c-TiO2) on the performance of planar perovskite solar cells (p-PSCs) is investigated, and the possible mechanisms are also proposed. To meet our objective, anatase c-TiO2 thin films with various OVD concentrations are prepared by changing the oxygen flux during the DC magnetron sputtering process and are characterized by the intensity of defect signals in the X-ray photoelectron spectra. We conclude that abundant OVDs can trigger an obviously increased majority carrier accumulation zone at the metal oxide/perovskite interface and enhanced capacitance, thereby greatly deteriorating photogenerated carrier collection efficiency. A detailed analysis of the study results also reveals that the presence of OVD in the bulk and surface of c-TiO2 can slow down electronic carrier transport and lower its electron quasi-Fermi level under illumination, leading to the detrimental charge recombination in p-PSCs. Furthermore, we report a remarkably enhanced p-PSC efficiency via preparing c-TiO2 using high oxygen flux and subsequent ultraviolet ozone treatment. As a consequence, repeatable power conversion efficiency (PCE) is propelled to as high as 16.62%, coupled with negligible hysteresis and increased stability. These results provide a significant implication for further perfecting efficient and stable p-PSCs for their record efficiency.


The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model.
Treatment of diabetes complications remains a substantial challenge. The aim of this study was to explore the ability of the soy isoflavone genistein in attenuating the signs that follow diabetes onset: nociceptive hypersensitivity, oxidative and inflammatory state, nerve growth factor (NGF) decrease and vascular dysfunctions. Genistein (3 and 6 mg/kg) was administered to C57BL/6J streptozotocin diabetic mice from the 2nd till the 5th week after disease induction. The hind paw withdrawal threshold to mechanical stimulation (tactile allodynia) was evaluated by a von Frey filament. The oxidative stress was assessed measuring: reactive oxygen species by fluorimetric analysis, both the lipoperoxide content, as malondialdehyde, the antioxidant enzymatic activities spectrophotometrically and the glutathione content spectrofluorimetrically. Proinflammatory cytokines and NGF were measured in the sciatic nerve by enzyme-linked immunosorbent assay. Aortic inducible (iNOS) and endothelial nitric oxide synthase (eNOS) protein content was measured by western immunoblotting. Genistein relieved diabetic peripheral painful neuropathy, reverted the proinflammatory cytokine and reactive oxygen species overproduction, and restored the NGF content in diabetic sciatic nerve. Furthermore it restored the GSH content and the GSH and GSSG ratio, improved the antioxidant enzymes activities, decreased reactive oxygen species and lipoperoxide level in the brain and liver. Finally it restored the iNOS and eNOS content and the superoxide dismutase activity in thoracic aorta. Hyperglycaemia and weight decrease were not affected. Genistein is able to reverse a diabetes established condition of allodynia, oxidative stress and inflammation, ameliorates NGF content and the vascular dysfunction, thus suggesting its possible therapeutic use for diabetes complications.


Fate of two strains of extended-spectrum beta-lactamase producing Escherichia coli in constructed wetland microcosm sediments: survival and change in antibiotic resistance profiles.
Free water surface constructed wetlands (FWS CW) are efficient technologies to limit the transfer of antibiotic resistant bacteria (ARB) originating from urban effluents into the aquatic environment. However, the decrease in ARB from inflow to outflow through the FWS CW may be explained by their transfer from the water body to the sediment. To investigate the behavior of ARB in the sediment of a FWS CW, we inoculated three microcosms with two strains of extended-spectrum beta-lactamase producing Escherichia coli (ESBL E. coli) belonging to two genotypes. Microcosms were composed of two sediments collected at two locations of an FWS CW from which the strains were isolated. Phragmites were planted in one of the microcosms. The survival curves of the two strains were close regardless of the genotype and the type of sediment. After a rapid decline, both strains were able to survive at low level in the sediments for 50 days. Their fate was not affected by the presence of phragmites. Changes in the bla content and antibiotic resistance of the inoculated strains were observed after three weeks of incubation, indicating that FWS CW sediments are favorable environments for spread of antibiotic resistance genes and for the acquisition of new antibiotic resistance.