Nursing satisfaction and job enrichment in Turkey.
Survey research was conducted with the aim of better understanding nurses' perceptions of organizational factors which relate to their job satisfaction and motivation in Turkey. Nurses (N = 290) who were employed at a training and research hospital, part of the Turkish Republic Ministry of Health, were included. The questionnaire used was developed for this study based on Hackman and Oldman's job enrichment theory. The results showed that only one third of the nurse leaders and one in five of the staff nurses reported being satisfied with their job. The participants saw the five core job dimensions of Hackman and Oldman's work design model: skill variety, task identity, task significance, autonomy, and feedback as important for nurses. Nursing was described by the participants as hard and challenging, but they also found it meaningful and said that it gave them the opportunity to use their skills and abilities.


Malignant progression and blockade of angiogenesis in a murine transgenic model of neuroblastoma.
Targeted expression of MYCN to the neural crest [under control of the rat tyrosine hydroxylase (TH) promoter] causes neuroblastoma in transgenic mice (TH-MYCN) and is a well-established model for this disease. Because high levels of MYCN are associated with enhanced tumor angiogenesis and poor clinical outcome in neuroblastoma, we serially characterized malignant progression, angiogenesis, and sensitivity to angiogenic blockade in tumors from these animals. Tumor cells were proliferative, secreted high levels of the angiogenic ligand vascular endothelial growth factor (VEGF), and recruited a complex vasculature expressing the angiogenic markers VEGF-R2, alpha-SMA, and matrix metalloproteinases MMP-2 and MMP-9, all of which are also expressed in human disease. Treatment of established murine tumors with the angiogenesis inhibitor TNP-470 caused near-complete ablation, with reduced proliferation, enhanced apoptosis, and vasculature disruption. Because TNP-470 has been associated with neurotoxicity, we tested the recently described water-soluble HPMA copolymer-TNP-470 conjugate (caplostatin), which showed comparable efficacy and was well tolerated without weight loss or neurotoxicity as measured by rotarod testing. This study highlights the importance of angiogenesis inhibition in a spontaneous murine tumor with native tumor-microenvironment interactions, validates the use of mice transgenic for TH-MYCN as a model for therapy in this common pediatric tumor, and supports further clinical development of caplostatin as an antiangiogenic therapy in childhood neuroblastoma.


Hexose transporters GLUT1 and GLUT3 are colocalized with hexokinase I in caveolae microdomains of rat spermatogenic cells.
Postmeiotic spermatogenic cells, but not meiotic spermatogenic cells respond differentially with glucose-induced changes in [Ca2+]i indicating a differential transport of glucose via facilitative hexose transporters (GLUTs) specifically distributed in the plasma membrane. Several studies have indicated that plasma membrane in mammalian cells is not homogeneously organized, but contains specific microdomains known as detergent-resistant membrane domains (DRMDs), lipid rafts or caveolae. The association of these domains and GLUTs isoforms has not been characterized in spermatogenic cells. We analyzed the expression and function of GLUT1 and GLUT3 in isolated spermatocytes and spermatids. The results showed that spermatogenic cells express both glucose transporters, with spermatids exhibiting a higher affinity glucose transport system. In addition, spermatogenic cells express caveolin-1, and glucose transporters colocalize with caveolin-1 in caveolin-enriched membrane fractions. Experiments in which the integrity of caveolae was disrupted by pretreatment with methyl-beta-cyclodextrin, indicated that the involvement of cholesterol-enriched plasma membrane microdomains were involved in the localization of GLUTs and uptake of 2-deoxyglucose. We also observed cofractionation of GLUT3 and caveolin-1 in low-buoyant density membranes together with their shift to higher densities after methyl-beta-cyclodextrin treatment. GLUT1 was found in all fractions isolated. Immunofluorescent studies indicated that caveolin-1, GLUT1, and hexokinase I colocalize in spermatocytes while caveolin-1, GLUT3, and hexokinase I colocalize in spermatids. These findings suggest the presence of hexose transporters in DRMDs, and further support a role for intact caveolae or cholesterol-enriched membrane microdomains in relation to glucose uptake and glucose phosphorylation. The results would also explain the different glucose-induced changes in [Ca2+]i in both cells.


MADAP, a flexible clustering tool for the interpretation of one-dimensional genome annotation data.
A recurring task in the analysis of mass genome annotation data from high-throughput technologies is the identification of peaks or clusters in a noisy signal profile. Examples of such applications are the definition of promoters on the basis of transcription start site profiles, the mapping of transcription factor binding sites based on ChIP-chip data and the identification of quantitative trait loci (QTL) from whole genome SNP profiles. Input to such an analysis is a set of genome coordinates associated with counts or intensities. The output consists of a discrete number of peaks with respective volumes, extensions and center positions. We have developed for this purpose a flexible one-dimensional clustering tool, called MADAP, which we make available as a web server and as standalone program. A set of parameters enables the user to customize the procedure to a specific problem. The web server, which returns results in textual and graphical form, is useful for small to medium-scale applications, as well as for evaluation and parameter tuning in view of large-scale applications, requiring a local installation. The program written in C++ can be freely downloaded from ftp://ftp.epd.unil.ch/pub/software/unix/madap. The MADAP web server can be accessed at http://www.isrec.isb-sib.ch/madap/.


Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations.
Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis.


Evaluation of spermicidal activity of saponosides from Saponaria officinalis/Caryophyllaceae, Glycyrrhizia glabra/Fabaceae and Herniaria glabra/Caryophyllaceae.
Chemical spermicides currently marketed and widely used are known to have many side effects. Thereby, and in order to look for more tolerated natural spermicidal agents, the aim of this work was to evaluate the spermicidal potential of saponin extracts from the roots of Saponaria officinalis/Caryophyllaceae, Glycyrrhizia glabra/Fabaceae, and Herniaria glabra/Caryophyllaceae by studying their in vitro effects on sperm mobility and vitality. Methanolic saponin extracts from the plants roots were performed. Sperm suspensions were prepared by centrifugation on a PureSperm® density gradient (70 and 45%) and incubated with various concentrations of saponin extracts (50, 250, 500 and 750 μg/mL) at 37°C. The spermicidal activity was evaluated by studying the mobility and vitality of spermatozoa at different time intervals ranging from 10 to 240 minutes. A dose and time dependent effect on sperm mobility and vitality was observed for our extracts.Extracts from Saponaria officinalis roots induced an irreversible immobilization and a total non-viability of sperm within 10 minutes at a concentration of 750 μg/mL. A similar effect was observed within 30 minutes at 750 μg/mL for Herniaria glabra extract and within 90 minutes at 500 μg/ml for Glycyrrhizia glabra extract. The results of our study showed that the saponin extracts of our plants roots possess potent in vitro dose and time dependant spermicidal effect. These natural products could therefore represent a safer and better tolerated alternative to chemical spermicides.


Hyperbaric oxygen therapy and cancer--a review.
Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, and metastasis. Hyperbaric oxygen (HBO) treatment has for centuries been used to improve or cure disorders involving hypoxia and ischemia, by enhancing the amount of dissolved oxygen in the plasma and thereby increasing O(2) delivery to the tissue. Studies on HBO and cancer have up to recently focused on whether enhanced oxygen acts as a cancer promoter or not. As oxygen is believed to be required for all the major processes of wound healing, one feared that the effects of HBO would be applicable to cancer tissue as well and promote cancer growth. Furthermore, one also feared that exposing patients who had been treated for cancer, to HBO, would lead to recurrence. Nevertheless, two systematic reviews on HBO and cancer have concluded that the use of HBO in patients with malignancies is considered safe. To supplement the previous reviews, we have summarized the work performed on HBO and cancer in the period 2004-2012. Based on the present as well as previous reviews, there is no evidence indicating that HBO neither acts as a stimulator of tumor growth nor as an enhancer of recurrence. On the other hand, there is evidence that implies that HBO might have tumor-inhibitory effects in certain cancer subtypes, and we thus strongly believe that we need to expand our knowledge on the effect and the mechanisms behind tumor oxygenation.


Genetics-genomics competencies and nursing regulation.
The aim of this article is to explore the interaction between the integration of genetics-genomics competencies into nursing curricula and regulatory standards. By taking a global perspective of activity in this field, we aim to develop a framework that can inform strategic planning in relation to international genetics-genomics and nursing education. We focus our exploration around a small-scale international survey on the progress, achievements, and critical success factors of 10 countries in relation to the integration of genetics-genomics into nursing education, with exemplars from three of those countries. Analysis of the data generated 10 themes, each with several subthemes that play a critical role in the development of genetics-genomics in nursing education and practice. The themes were organized into three overarching themes: nursing in genetics, genetics in nursing, and recognition and support. Genetics-genomics competence is not fully integrated into nursing education at an appropriate level in any country, nor was it reflected robustly in current standards for registration and licensure. Strong leadership from the specialist genetics community plays a critical role in defining genetics-genomics competence but the engagement of nursing professionals at senior levels in both government and regulatory institutions is essential if nurses are to be active participants in the innovations offered by genomic healthcare. Safe and effective nursing practice must incorporate the needs of those with, at risk for, or susceptible to genetic-genomic conditions, as well as those who might benefit from the application of genomic technologies in the diagnosis and management of common conditions such as cancer and heart disease. The scope of such practice can be articulated though competence statements. Professional regulation defines the standard of competence that practicing nurses should demonstrate at initial registration and licensure.


Different use of T cell receptor transducing modules in two populations of gut intraepithelial lymphocytes are related to distinct pathways of T cell differentiation.
Most gut intraepithelial cells (IEL) of the mouse are T cells that bear CD8 molecules, present either as alpha-beta chain heterodimers (CD8 beta+) or as alpha chain homodimers (CD8 beta-). All CD8 beta+ IEL bear alpha/beta T cell receptors (TCR); CD8 beta- IEL bear either alpha/beta or gamma/delta TCR and are considered to be a thymus-independent (TI) population, probably arising locally from a small fraction of CD3- IEL containing the recombinant activating gene RAG proteins. Here we report that TI CD8 beta- IEL, whether bearing alpha/beta or gamma/delta TCR, contain, in normal mice, mRNAs for both zeta and Fc epsilon RI gamma chains. These chains are present in their CD3-TCR complexes as homo- or heterodimers. In contrast, only zeta chain mRNA and homodimers are found in gut CD8 alpha/beta+ IEL and in peripheral T lymphocytes. Intestinal CD3- precursor cells contain only gamma chain, and CD3- IL-2R+ thymocyte precursors only zeta chain mRNAs. Only very primitive thymocyte precursors contain detectable gamma chain mRNA, and it thus appears that Fc epsilon RI gamma chain use is switched off at a very early stage during thymocyte differentiation. Thus, T cell differentiation in the gut epithelium differs from that occurring in the thymus, from which CD8 beta+ IEL appear to derive. Use of different TCR transducing modules and CD8 accessory molecules between the TI and the thymus-derived T cell populations provides an explanation for their difference in reactivity to antigenic stimulations and thus in selection of repertoires.


Costs of breast cancer care in Mexico: analysis of two insurance coverage scenarios.
Breast cancer (BC) is a major cause of disease and death worldwide. In addition to its contribution to mortality and disability, it is a major economic burden both public and private. To estimate the average direct medical cost/year of care for the diagnosis and treatment of BC in two coverage scenarios in Mexico: What is 'ideal' based on service usage patterns according to international guidelines and what is 'current' using the service usage patterns of suppliers in Mexico. The pattern and intensity of use of procedures for the care of BC in the Mexican Social Security Institute (IMSS) for 2009 were identified and prices were associated using the guidelines from the System of Social Protection in Health (SPSS) and the IMSS for the current scenario and the ideal scenario, international patterns (Breast Health Global Initiative BHGI after its acronym in English) were used and prices were associated from the SPSS guidelines. The annual average direct medical cost per patient in the 'current' scenario was 8557 US$, while the cost in the 'ideal' scenario was 4554 US$. There are differences in costs between 'what we do' and 'what should be done', due to differences in the implementation of the interventions for the treatment of the different stages of the disease. A proportional increase in the average cost was also identified as the diagnosis stage advanced (from I to III). Given that in Mexico there is universal insurance coverage for the treatment of BC, it is necessary to use economic resources more efficiently. It is necessary to continue to examine this topic in more depth and the next step will be to assess the effectiveness of both scenarios in order to provide enough evidence for the decision-making process.


Automated Assessment of Disease Progression in Acute Myeloid Leukemia by Probabilistic Analysis of Flow Cytometry Data.
Flow cytometry (FC) is a widely acknowledged technology in diagnosis of acute myeloid leukemia (AML) and has been indispensable in determining progression of the disease. Although FC plays a key role as a posttherapy prognosticator and evaluator of therapeutic efficacy, the manual analysis of cytometry data is a barrier to optimization of reproducibility and objectivity. This study investigates the utility of our recently introduced nonparametric Bayesian framework in accurately predicting the direction of change in disease progression in AML patients using FC data. The highly flexible nonparametric Bayesian model based on the infinite mixture of infinite Gaussian mixtures is used for jointly modeling data from multiple FC samples to automatically identify functionally distinct cell populations and their local realizations. Phenotype vectors are obtained by characterizing each sample by the proportions of recovered cell populations, which are, in turn, used to predict the direction of change in disease progression for each patient. We used 200 diseased and nondiseased immunophenotypic panels for training and tested the system with 36 additional AML cases collected at multiple time points. The proposed framework identified the change in direction of disease progression with accuracies of 90% (nine out of ten) for relapsing cases and 100% (26 out of 26) for the remaining cases. We believe that these promising results are an important first step toward the development of automated predictive systems for disease monitoring and continuous response evaluation. Automated measurement and monitoring of therapeutic response is critical not only for objective evaluation of disease status prognosis but also for timely assessment of treatment strategies.


Current evidence for the use of coffee and caffeine to prevent age-related cognitive decline and Alzheimer's disease.
Although nothing has been proven conclusively to protect against cognitive aging, Alzheimer's disease or related dementias, decades of research suggest that specific approaches including the consumption of coffee may be effective. While coffee and caffeine are known to enhance short-term memory and cognition, some limited research also suggests that long-term use may protect against cognitive decline or dementia. In vitro and pre-clinical animal models have identified plausible neuroprotective mechanisms of action of both caffeine and other bioactive components of coffee, though epidemiology has produced mixed results. Some studies suggest a protective association while others report no benefit. To our knowledge, no evidence has been gathered from randomized controlled trials. Although moderate consumption of caffeinated coffee is generally safe for healthy people, it may not be for everyone, since comorbidities and personal genetics influence potential benefits and risks. Future studies could include short-term clinical trials with biomarker outcomes to validate findings from pre-clinical models and improved epidemiological studies that incorporate more standardized methods of data collection and analysis. Given the enormous economic and emotional toll threatened by the current epidemic of Alzheimer's disease and other dementias, it is critically important to validate potential prevention strategies such as coffee and caffeine.


Bicyclist safety performance functions for a U.S. city.
Efforts have intensified to apply a more evidence-based approach to traffic safety. One such effort is the Highway Safety Manual, which provides typical safety performance functions (SPFs) for common road types. SPFs model the mathematical relationship between frequency of crashes and the most significant causal factors. Unfortunately, the manual provides no SPFs for bicyclists, despite disproportionately high fatalities among this group. In this paper, a method for creating city-specific, bicycle SPFs is presented and applied to Boulder, Colorado. This is the first time a bicycle SPF has been created for a U.S. city. Such functions provide a basis for both future investigations into safety treatment efficacy and for prioritizing intersections to better allocate scarce funds for bicycle safety improvements. As expected, the SPFs show that intersections with higher bicyclist traffic and higher motorist traffic have higher motorist-cyclist collisions. The SPFs also demonstrate that intersections with more cyclists have fewer collisions per cyclist, illustrating that cyclists are safer in numbers. Intersections with fewer than 200 entering cyclists have substantially more collisions per cyclist.


Pigment epithelium-derived factor supports normal Müller cell development and glutamine synthetase expression after removal of the retinal pigment epithelium.
In conditions in which the retinal pigment epithelium (RPE) is dystrophic, carries a genetic mutation, or is removed physically, Müller cells undergo degenerative changes that contribute to the retinal pathology. We previously demonstrated that pigment epithelium-derived factor (PEDF), a glycoprotein secreted by the RPE cells with neuroprotective and differentiation properties, protects against photoreceptor degeneration induced by RPE removal. The purpose of the present study was to analyze the putative gliosupportive activity of PEDF on Müller cells of RPE-deprived retinas and assess whether protection of Müller cells was correlated with improved photoreceptor outer segment assembly. Eyes were dissected from Xenopus laevis tadpoles, and the RPE was removed before culturing in medium containing purified PEDF, PEDF plus anti-PEDF, or medium alone. Control eyes matured with an adherent RPE or in medium containing PEDF plus nonimmune serum. Müller cell ultrastructure was examined. Glial fibrillary acidic protein (GFAP) and glutamine synthetase were localized immunocytochemically, and the corresponding protein levels were quantified. In control retinas, Müller cells were structurally intact and formed adherens junctions with neighboring photoreceptors. In addition, they did not express GFAP, whereas glutamine synthetase expression was high. RPE removal dramatically altered the ultrastructure and biosynthetic activity of Müller cells; Müller cells failed to form adherens junctions with photoreceptors and glutamine synthetase expression was suppressed. PEDF prevented the degenerative glial response; Müller cells were ultrastructurally normal and formed junctional complexes with photoreceptors. PEDF also preserved the expression of glutamine synthetase at near-normal levels. The morphogenetic effects of PEDF were blocked by the anti-PEDF antibody. Our study documents the glioprotective effects of PEDF and suggests that maintenance of the proper Müller cell ultrastructure and expression of glutamine synthetase may be necessary to support the proper assembly of photoreceptor outer segments.


Raman scattering and anomalous Stokes-anti-Stokes ratio in MoTe2 atomic layers.
Stokes and anti-Stokes Raman scattering are performed on atomic layers of hexagonal molybdenum ditelluride (MoTe2), a prototypical transition metal dichalcogenide (TMDC) semiconductor. The data reveal all six types of zone center optical phonons, along with their corresponding Davydov splittings, which have been challenging to see in other TMDCs. We discover that the anti-Stokes Raman intensity of the low energy layer-breathing mode becomes more intense than the Stokes peak under certain experimental conditions, and find the effect to be tunable by excitation frequency and number of atomic layers. These observations are interpreted as a result of resonance effects arising from the C excitons in the vicinity of the Brillouin zone center in the photon-electron-phonon interaction process.


Motion analysis of articulated objects from monocular images.
This paper presents a new method of motion analysis of articulated objects from feature point correspondences over monocular perspective images without imposing any constraints on motion. An articulated object is modeled as a kinematic chain consisting of joints and links, and its 3D joint positions are estimated within a scale factor using the connection relationship of two links over two or three images. Then, twists and exponential maps are employed to represent the motion of each link, including the general motion of the base link and the rotation of other links around their joints. Finally, constraints from image point correspondences, which are similar to that of the essential matrix in rigid motion, are developed to estimate the motion. In the algorithm, the characteristic of articulated motion, i.e., motion correlation among links, is applied to decrease the complexity of the problem and improve the robustness. A point pattern matching algorithm for articulated objects is also discussed in this paper. Simulations and experiments on real images show the correctness and efficiency of the algorithms.


Low iPTH can predict vascular and coronary calcifications in patients undergoing peritoneal dialysis.
There is substantial evidence that low levels of serum intact parathyroid hormone (iPTH) are associated with vascular calcium deposition and subsequent increased cardiovascular risk in chronic kidney disease patients. The purpose of this study was to determine the relationship between the serum iPTH level, and vascular and coronary artery calcifications (VCs, CACs) and arterial stiffness in peritoneal dialysis (PD) patients. In this cross-sectional study, 93 PD patients were included. VCs, CACs and arterial stiffness were measured by simple X-rays of the hands and pelvis, multi-slice coronary CT and brachial-ankle pulse wave velocity (BaPWV). Patients were divided into 3 groups according to iPTH levels. The prevalence of severe VCs (VC score ≥ 3) was highest in the low iPTH group (<150 pg/ml). In multivariate analysis, the presence of diabetes mellitus and a low iPTH were shown to be significant risk factors for severe VCs. In addition, a simple VC score of ≥ 1 was a significant variable for predicting severe CACs (CAC score ≥ 400). Low iPTH and the presence of diabetes mellitus are thought to be independent risk factors for predicting VCs. VCs determined by simple X-ray can further predict the coexistence of CACs that ultimately might contribute to increased cardiovascular risk in PD patients.


Controlled oxygen release from pyridone endoperoxides promotes cell survival under anoxic conditions.
In tissue engineering, survival of larger constructs remains challenging due to limited supply of oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated pyridone-derived endoperoxides has led to the development of water-soluble molecules that undergo retro-Diels-Alder reactions in aqueous environment releasing oxygen in high yield and with half-lives of up to 13 h. These molecules in combination with vitamin C as singlet oxygen quencher significantly improved survival of 3T3 fibroblasts and rat smooth muscle cells challenged with oxygen-depleted conditions.


Clostridium difficile infection in the hospitalized pediatric population: increasing trend in disease incidence.
To determine whether the incidence of Clostridium difficile infection continues to increase in hospitalized pediatric patients, we evaluated data from a United States national inpatient database. For the period of 2003 to 2009, we found an increasing trend in the incidence of C. difficile infection. These data suggest greater effort be given to prevent and treat this infection in children.


The 2008 ACVP role delineation survey and initial data analysis: from the Role Delineation Task Force.
The American College of Veterinary Pathologists commissioned a role delineation survey to define the specialized tasks, knowledge, and tools that define the current practice of veterinary clinical pathology and veterinary anatomic pathology. The survey also identified when competence was acquired for each task (i.e., before certification or after certification). The response rate by diplomates was high, with approximately 50% of practicing pathologists within each specialty responding to each survey. Using the survey results, all tasks for each specialty were classified as either appropriate or unsuitable for testing in the certifying examinations. The role delineation survey data will facilitate the creation of test plans that objectively define the content in each certifying examination, the evaluation and enhancement of training curricula, and the optimization of continuing education opportunities for practicing veterinary pathologists.


Sleepiness induced by sleep-debt enhanced amygdala activity for subliminal signals of fear.
Emotional information is frequently processed below the level of consciousness, where subcortical regions of the brain are thought to play an important role. In the absence of conscious visual experience, patients with visual cortex damage discriminate the valence of emotional expression. Even in healthy individuals, a subliminal mechanism can be utilized to compensate for a functional decline in visual cognition of various causes such as strong sleepiness. In this study, sleep deprivation was simulated in healthy individuals to investigate functional alterations in the subliminal processing of emotional information caused by reduced conscious visual cognition and attention due to an increase in subjective sleepiness. Fourteen healthy adult men participated in a within-subject crossover study consisting of a 5-day session of sleep debt (SD, 4-h sleep) and a 5-day session of sleep control (SC, 8-h sleep). On the last day of each session, participants performed an emotional face-viewing task that included backward masking of nonconscious presentations during magnetic resonance scanning. Finally, data from eleven participants who were unaware of nonconscious face presentations were analyzed. In fear contrasts, subjective sleepiness was significantly positively correlated with activity in the amygdala, ventromedial prefrontal cortex, hippocampus, and insular cortex, and was significantly negatively correlated with the secondary and tertiary visual areas and the fusiform face area. In fear-neutral contrasts, subjective sleepiness was significantly positively correlated with activity of the bilateral amygdala. Further, changes in subjective sleepiness (the difference between the SC and SD sessions) were correlated with both changes in amygdala activity and functional connectivity between the amygdala and superior colliculus in response to subliminal fearful faces. Sleepiness induced functional decline in the brain areas involved in conscious visual cognition of facial expressions, but also enhanced subliminal emotional processing via superior colliculus as represented by activity in the amygdala. These findings suggest that an evolutionally old and auxiliary subliminal hazard perception system is activated as a compensatory mechanism when conscious visual cognition is impaired. In addition, enhancement of subliminal emotional processing might cause involuntary emotional instability during sleep debt through changes in emotional response to or emotional evaluation of external stimuli.


Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.


Safety evaluation of turmeric polysaccharide extract: assessment of mutagenicity and acute oral toxicity.
Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight.


Poor responders in IVF--is there any evidence-based treatment for them?
Despite the vast experience in controlled ovarian hyperstimulation, there are still women who respond poorly to gonadotropins, which results in few oocytes at retrieval, reduced number of embryos for transfer and consequently unsatisfactory pregnancy rates. Although such patients are quite common in IVF practice, the exact prevalence of so-called "poor responders" is difficult to estimate due to the variety of applied definitions. The urgent need for an internationally accepted definition of poor ovarian response (POR) was addressed by an ESHRE Workshop held in Bologna in 2010, where the consensus was reached and criteria were finally established. The application of this uniform definition may allow a correct estimate of POR prevalence and, what is more important, designing proper trials to assess and finally compare the interventions used in POR patients. The article describes the possible physiology of POR and patient characteristics, mentions risk factors and laboratory tests of decreased ovarian reserve. Finally it reviews the possible management of POR with different stimulation protocols in the light of EBM. Basing on published meta-analyses, various additional alternatives (such as estradiol priming, the addition of rLH, growth hormone, androgens and androgen-modulating agents, aspirin) are also summarized. Despite the two decades of trying, there is still no consensus on what is best for POR. No single treatment can be recommended over another, as the evidence for all of them is insufficient. It is obvious that interventions used in POR require properly designed large randomized studies, because until now there is no evidence-based treatment for that particular group of patients.


Sleep in Type 1 Diabetes: Implications for Glycemic Control and Diabetes Management.
To highlight recent findings from studies of sleep in type 1 diabetes (T1D), with a focus on the role of sleep in self-management, the cognitive and psychosocial outcomes related to sleep disturbances, and factors associated with sleep disturbances specific to T1D. People with T1D experience higher rates of sleep disturbances than people without diabetes, and these disturbances have negative implications for glycemic control and diabetes management, as well as psychosocial and cognitive outcomes. Inconsistent sleep timing (bedtime and wake time) has emerged as a potential target for interventions, as variability in sleep timing has been linked with poorer glycemic control and adherence to treatment. Sleep-promoting interventions and new diabetes technology have the potential to improve sleep in people with T1D. Sleep is increasingly considered a critical factor in diabetes management, but more multi-method and longitudinal research is needed. We emphasize the importance of sufficient and consistent sleep for people with T1D, and the need for providers to routinely assess sleep among patients with T1D.


Secular trends in the incidence, mortality, and survival rate of gastric cancer in a general Japanese population: the Hisayama study.
To examine secular trends in the incidence and mortality of gastric cancer in a Japanese community, Hisayama, we established three study-cohorts of Hisayama residents aged > or =40 years in 1961 (1637 subjects), 1974 (2054), and 1988 (2602). Each cohort was followed up for ten years. The age-standardized mortality from gastric cancer significantly decreased from 2.4 per 1000 person-years in the first cohort to 0.8 in the third cohort for men, and from 1.0 to 0.2, respectively, for women (p < 0.01 for trend in both sexes). The five-year survival rate after gastric cancer significantly improved from the first (32.6%) to the third cohort (73.0%, p < 0.01) for men and from 43.2% to 72.3% (p < 0.05), respectively, for women. The age-standardized incidence of cancer in men was not different among the cohorts (4.3 per 1000 person-years in the first, 5.0 in the second, and 4.9 in the third cohort), while it decreased significantly in women (2.0, 1.8, and 1.2, respectively, p < 0.01 for trend). In conclusion, our findings suggest that in a Japanese population, the mortality from gastric cancer declined during the past 40 years, due mainly to the improvement of survival in both sexes and a decrease in the incidence for women.


Conducting Concurrent Electroencephalography and Functional Near-Infrared Spectroscopy Recordings with a Flanker Task.
Concurrent EEG and fNIRS recordings offer an excellent opportunity to gain a full understanding of the neural mechanism of cognitive processing by inspecting the relationship between the neural and hemodynamic signals. EEG is an electrophysiological technology that can measure the rapid neuronal activity of the cortex, whereas fNIRS relies on the hemodynamic responses to infer brain activation. The combination of EEG and fNIRS neuroimaging techniques can identify more features and reveal more information associated with the functioning of the brain. In this protocol, fused EEG-fNIRS measurements were performed for concurrent recordings of evoked-electrical potentials and hemodynamic responses during a Flanker task. In addition, the critical steps for setting up the hardware and software system as well as the procedures for data acquisition and analysis were provided and discussed in detail. It is expected that the present protocol can pave a new avenue for improving the understanding of the neural mechanisms underlying various cognitive processes by using the EEG and fNIRS signals.


Hybridization chain reaction performed on a metal surface as a means of signal amplification in SPR and electrochemical biosensors.
A more specific and intense signal is desirable for most kinds of biosensors for biomedical or environmental applications, and it is especially so for label-free biosensors. In this paper, we show that hybridization chain reaction (HCR) can be exploited for the easily detectable accumulation of nucleic acids on metal surfaces as an event triggered by specific recognition between a probe and a target nucleic acid. We show that this process could be exploited to increase the sensitivity in the detection of nucleic acids derived from a pathogenic microorganism. This strategy can be straightforwardly implemented on SPR biosensors (commercial or custom-built) or on label-free electrochemical biosensors. Together with signal amplification, HCR can serve as a confirmation of the specificity of target recognition, as it involves the specific matching with a separate base sequence in the target nucleic acid. Furthermore, the kinetics of the target binding and the HCR can be easily distinguished from each other, providing an additional means of confirmation of the specific recognition.


Kinesin-8 and Dis1/TOG collaborate to limit spindle elongation from prophase to anaphase A for proper chromosome segregation in fission yeast.
High-fidelity chromosome segregation relies on proper microtubule regulation. Kinesin-8 has been shown to destabilise microtubules to reduce metaphase spindle length and chromosome movements in multiple species. XMAP215/chTOG polymerases catalyse microtubule growth for spindle assembly, elongation and kinetochore-microtubule attachment. Understanding of their biochemical activity has advanced, but little work directly addresses the functionality and interplay of these conserved factors. We utilised the synthetic lethality of fission yeast kinesin-8 (Klp5-Klp6) and XMAP215/chTOG (Dis1) to study their individual and overlapping roles. We found that the non-motor kinesin-8 tailbox is essential for mitotic function; mutation compromises plus-end-directed processivity. Klp5-Klp6 induces catastrophes to control microtubule length and, surprisingly, Dis1 collaborates with kinesin-8 to slow spindle elongation. Together, they enforce a maximum spindle length for a viable metaphase-anaphase transition and limit elongation during anaphase A to prevent lagging chromatids. Our work provides mechanistic insight into how kinesin-8 negatively regulates microtubules and how this functionally overlaps with Dis1 and highlights the importance of spindle length control in mitosis.


Bayesian analyses of genetic parameters for growth traits in Nellore cattle raised on pasture.
This study was carried out to investigate (co)variance components and genetic parameters for growth traits in beef cattle using a multi-trait model by Bayesian methods. Genetic and residual (co)variances and parameters were estimated for weights at standard ages of 120 (W120), 210 (W210), 365 (W365), and 450 days (W450), and for pre- and post-weaning daily weight gain (preWWG and postWWG) in Nellore cattle. Data were collected over 16 years (1993-2009), and all animals were raised on pasture in eight farms in the North of Brazil that participate in the National Association of Breeders and Researchers. Analyses were run by the Bayesian approach using Gibbs sampler. Additive direct heritabilities for W120, W210, W365, and W450 and for preWWG and postWWG were 0.28 ± 0.013, 0.32 ± 0.002, 0.31 ± 0.002, 0.50 ± 0.026, 0.61 ± 0.047, and 0.79 ± 0.055, respectively. The estimates of maternal heritability were 0.32 ± 0.012, 0.29 ± 0.004, 0.30 ± 0.005, 0.25 ± 0.015, 0.23 ± 0.017, and 0.22 ± 0.016, respectively, for W120, W210, W365, and W450 and for preWWG and postWWG. The estimates of genetic direct additive correlation among all traits were positive and ranged from 0.25 ± 0.03 (preWWG and postWWG) to 0.99 ± 0.00 (W210 and preWWG). The moderate to high estimates of heritability and genetic correlation for weights and daily weight gains at different ages is suggestive of genetic improvement in these traits by selection at an appropriate age. Maternal genetic effects seemed to be significant across the traits. When the focus is on direct and maternal effects, W210 seems to be a good criterium for the selection of Nellore cattle considering the importance of this breed as a major breed of beef cattle not only in Northern Brazil but all regions covered by tropical pastures. As in this study the genetic correlations among all traits were high, the selection based on weaning weight might be a good choice because at this age there are two important effects (maternal and direct genetic effects). In contrast, W120 should be preferred when the objective is improving the maternal ability of the dams. Furthermore, selection for postWWG can be used if the animals show both heavier weaning weights and high growth rate after weaning because it is possible to shorten the time between weaning and slaughter based on weaning weight, postWWG, and desired weight at the time of slaughter.


Identification of atrial natriuretic factor within ventricular tissue in hamsters and humans with congestive heart failure.
In normal mammals, atrial natriuretic factor (ANF) is present within atrial myocardial cells but is absent from ventricular myocardium. In primitive organisms ANF is present within both atria and ventricle, suggesting that the ventricle may participate both in the synthesis and release of the hormone. The current study was designed to test the hypothesis that ventricular ANF develops as a homeostatic response to intravascular volume overload. Studies were performed on cardiac tissue obtained from (i) normal and cardiomyopathic hamsters, (ii) autopsied humans with and without cardiac disease, and (iii) living humans with congestive heart failure (CHF) undergoing diagnostic right ventricular endomyocardial biopsy. The myocardium was examined for the presence of immunoreactive ANF using a two-stage immunohistochemical technique, with nonimmune rabbit sera used as a negative control. There was unequivocal evidence of focal subendocardial deposits of immunoreactive ANF present in both of the ventricles of all six cardiomyopathic hamsters, four of five autopsied human subjects with CHF, and five of seven biopsied humans. No immunoreactive ANF was observed within the ventricular myocardium of control hamsters or normal humans. Utilizing crude tissue homogenates and radioimmunoassay techniques, the quantity of ANF was determined in cardiac atria, ventricles, and noncardiac skeletal muscle. Heart failure is characterized by a reduction in atrial ANF and an increase in ventricular ANF. This study demonstrates immunoreactive ANF is present within the ventricular myocardium in cardiomyopathic hamsters and humans with CHF, and suggests that the ventricle may be capable of responding to chronic volume overload by producing ANF.


Rapid parasite adaptation drives selection for high recombination rates.
The Red Queen hypothesis proposes that sex is maintained through selection pressure imposed by coevolving parasites: susceptible hosts are able to escape parasite pressure by recombining their genome to create resistant offspring. However, previous theoretical studies have shown that the Red Queen typically selects against sex unless selection is strong, arguing that high rates of recombination cannot evolve when parasites are of low virulence. Here we show that under the biologically plausible assumption of a severe fitness cost for parasites that fail to infect, the Red Queen can cause selection for high recombination rates, and that the strength of virulence is largely irrelevant to the direction of selection for increased recombination rates. Strong selection on parasites and short generation times make parasites usually better adapted to their hosts than vice versa and can thus favor higher recombination rates in hosts. By demonstrating the importance of host-imposed selection on parasites, our findings resolve previously reported conflicting results.


[3H]GBR-12935 binding to dopamine uptake sites in rat striatum.
The binding of the selective dopamine uptake inhibitor [3H]GBR-12935 to rat striatum was studied. Competition by mazindol and dopamine against [3H]GBR-12935 binding revealed monophasic binding curves. The addition of 100 microM dopamine to the mazindol competition inhibited only 80% of the binding, indicating more than one [3H]GBR-12935 binding site in rat striatum. When a binding fraction that could be discriminated by 1 microM mazindol or 1 mM dopamine was defined as specific binding, a single site binding model was obtained. The [3H]GBR-12935 binding was of protein nature, since it was abolished after protease treatment. Drug inhibition studies with the addition of low concentrations of mazindol and dopamine resulted in alterations in apparent Kd values only, suggesting competitive inhibition by these compounds against [3H]GBR-12935 binding. It is concluded that the [3H]GBR-12935 binding to rat striatum discriminated by 1 microM mazindol reflects binding to the substrate recognition site for the dopamine uptake.


How Perceived Pain Influence Sleep and Mood More Than The Reverse: A Novel, Exploratory Study with Patients Awaiting Total Hip Arthroplasty.
Objectives: Attributions about how comorbid symptoms worsen or improve each other are central cognitive components of chronic pain that are shown to facilitate or impede the recovery process. Still, these attributions have been poorly illuminated in chronic pain patients. The present study explored perceptions of how sleep, pain, and mood influence each other in patients awaiting total hip arthroplasty (THA). Design and Methods: In this cross-sectional study, 291 patients (mean age 67.8, 65.3% female) rated 12 statements about how much a given symptom (pain, sleep, mood) changed when another symptom (pain, sleep, mood) worsened or improved on a response scale ranging from much worse (-2) via no change (0) to much better (2). Sleep (Bergen Insomnia Scale), pain (McGill Pain Questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale) were assessed as background variables. Results: Of the patients in the study, 56% reported symptoms indicating insomnia. Anxiety and depression were indicated in 16 and 10%, respectively. Over 80% rated their pain as horrible/unbearable and reported that pain occurred always/daily. When experiencing increased pain, a majority perceived that sleep (90%) and mood (70%) worsened, whilst experiencing reduced pain improved sleep and mood in 50%. Poor sleep increased pain and worsened mood in 45 and 60% of the patients, respectively. Better sleep was perceived to reduce pain and improve mood in 50%. Worsened mood increased pain (46%) and worsened sleep (52%). Improved mood decreased pain and improved sleep in 25 and 35%, respectively. Discussion: In this study, a novel approach was used to investigate perceptions of reciprocal relationships between symptoms. We found that THA patients perceived interrelationships between pain, sleep and mood. These perceived interrelations were stronger when symptoms worsened than when symptoms improved. They also held stronger beliefs about the effect of pain on sleep and mood, than the effect of sleep and mood on pain. Attributions are central in illness perception and ultimately affect illness behavior. For patients who perceive symptoms to interrelate, the door has already been opened to utilize these attributions in treatments aiming to disrupt vicious cycles, hence supporting the use of multimodal treatments.


Dispersal of thermophilic Desulfotomaculum endospores into Baltic Sea sediments over thousands of years.
Patterns of microbial biogeography result from a combination of dispersal, speciation and extinction, yet individual contributions exerted by each of these mechanisms are difficult to isolate and distinguish. The influx of endospores of thermophilic microorganisms to cold marine sediments offers a natural model for investigating passive dispersal in the ocean. We investigated the activity, diversity and abundance of thermophilic endospore-forming sulfate-reducing bacteria (SRB) in Aarhus Bay by incubating pasteurized sediment between 28 and 85 °C, and by subsequent molecular diversity analyses of 16S rRNA and of the dissimilatory (bi)sulfite reductase (dsrAB) genes within the endospore-forming SRB genus Desulfotomaculum. The thermophilic Desulfotomaculum community in Aarhus Bay sediments consisted of at least 23 species-level 16S rRNA sequence phylotypes. In two cases, pairs of identical 16S rRNA and dsrAB sequences in Arctic surface sediment 3000 km away showed that the same phylotypes are present in both locations. Radiotracer-enhanced most probable number analysis revealed that the abundance of endospores of thermophilic SRB in Aarhus Bay sediment was ca. 10(4) per cm(3) at the surface and decreased exponentially to 10(0) per cm(3) at 6.5 m depth, corresponding to 4500 years of sediment age. Thus, a half-life of ca. 300 years was estimated for the thermophilic SRB endospores deposited in Aarhus Bay sediments. These endospores were similarly detected in the overlying water column, indicative of passive dispersal in water masses preceding sedimentation. The sources of these thermophiles remain enigmatic, but at least one source may be common to both Aarhus Bay and Arctic sediments.


In vitro estrogenic activity of binary and multicomponent mixtures with bisphenol A.
Bisphenol A and its analogs are environmental contaminants with well known estrogenic and anti-androgenic activities. In studies of human biomonitoring, simultaneous exposure to multiple bisphenols was shown in different biological samples, at picomolar to low nanomolar concentrations. Evaluation of their combined toxicities will therefore be a more realistic and reliable predictor for estimation of health risks than evaluation of only the single chemicals. In the present study, estrogenic activities of individual bisphenols were evaluated, along with their binary and multicomponent mixtures including three- and four-component mixtures, using the Organisation for Economic Co-operation and Development validated transactivation assay with the hERα-Hela9903 cell line. Concentration-dependent estrogenic activity was confirmed for all of the tested bisphenols, in the nanomolar to micromolar range. Estrogenic activities of binary and multicomponent mixtures followed a concentration addition model. Although exposure to individual bisphenols remains below their effective doses, we demonstrate that as a mixture, they can contribute additively to toxicity. This study thus emphasizes the importance of mixture toxicity evaluation for risk assessment of compounds that act like the bisphenols.


Cortical ablation and drug-induced changes in striatal ascorbic acid oxidation and behavior in the rat.
Rats whose frontoparietal cortex had been bilaterally ablated were allowed 21 days for recovery and then treated with apomorphine (APO), 1 mg/kg SC or scopolamine (SCOP), 0.6 mg/kg SC. Soon after a behavioral test, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), and dehydroascorbic acid (DHAA) levels were determined by HPLC/EC in striatal synaptosomes (left side) and whole striatum (right side). SCOP behavioural effects were attenuated by cortical ablation, while those of APO were affected to a lesser extent. In the striatum of unoperated and sham-operated rats DHAA contents and DHAA/AA ratio resulted increased after drugs administration. No change in AA oxidation was observed in the striatum of ablated rats. In the synaptosomes of unoperated and sham-operated rats both drugs led to a decrease in DHAA contents and DHAA/AA ratio. In unoperated and sham-operated rats APO and SCOP caused a decrease of the DOPAC/DA ratio in the whole striatum and striatal synaptosomes. In ablated rats APO caused a decrease of DOPAC/DA ratio in the whole striatum and synaptosomes, while SCOP effects on DA turnover resulted attenuated in the whole striatum and abolished in synaptosomes. We conclude that drug-induced AA oxidation is likely to occur in the extracellular space and requires intact corticostriatal glutamatergic pathways. The latter may play an enabling role in SCOP behavioral effects.


Cell transformation by kFGF requires secretion but not glycosylation.
The Kfgf gene, which encodes a member of the fibroblast growth factor family, was originally discovered by assaying human tumor DNA for dominantly transforming oncogenes. The 22-kD kFGF product contains a single site for asparagine-linked glycosylation and an amino-terminal signal peptide for vectorial synthesis into the endoplasmic reticulum and eventual secretion. To determine whether these features are necessary for transformation, we have constructed mutants of kFGF that are impaired for glycosylation or secretion. All mutants retained the ability to induce DNA synthesis when added to quiescent cells, and the absence of glycosylation had no appreciable effect on the transformation efficiency on NIH3T3 cells. In contrast, mutants of kFGF that remain in the cytoplasm or are retained in the secretory pathway, through addition of a KDEL motif, score negative in standard transformation assays. Since transformation by either the glycosylated or unglycosylated form of kFGF can be reversed by addition of suramin, the data imply that secretion of kFGF, or surface localization of the ligand/receptor complex, is a prerequisite for transformation.


Dihydrosphingosine-induced programmed cell death in tobacco BY-2 cells is independent of H₂O₂ production.
Sphinganine or dihydrosphingosine (d18:0, DHS), one of the most abundant free sphingoid Long Chain Base (LCB) in plants, has been recently shown to induce both cytosolic and nuclear calcium transient increases and a correlated Programmed Cell Death (PCD) in tobacco BY-2 cells. In this study, in order to get deeper insight into the LCB signaling pathway leading to cell death, the putative role of Reactive Oxygen Species (ROS) has been investigated. We show that DHS triggers a rapid dose-dependent production of H₂O₂ that is blocked by diphenyleniodonium (DPI), indicating the involvement of NADPH oxidase(s) in the process. In addition, while DPI does not block DHS-induced calcium increases, the ROS production is inhibited by the broad spectrum calcium channel blocker lanthanum (La³+). Therefore, ROS production occurs downstream of DHS-induced Ca²+ transients. Interestingly, DHS activates expression of defense-related genes that is inhibited by both La³+ and DPI. Since DPI does not prevent DHS-induced cell death, these results strongly indicate that DHS-induced H₂O₂ production is not implicated in PCD mechanisms but rather would be associated to basal cell defense mechanisms.


Assessment of mental workload and its association with work ability in control room operators.
Modern technology has reduced physical workload and imposed high mental workload on the control room operators in industrial settings. The present study was conducted among control room operators to assess their mental workload, investigate their workability, examine the relationship between mental workload and workability, and determine the factors associated with workability. This cross-sectional study was carried out among 213 control room operators in six Iranian process industries. Task Load Index (NASA-TLX) was used to assess the mental workload, and Work Ability Index (WAI) was used to determine workability. The relationships between demographic characteristics and dimensions of mental workload and workability were examined by univariate tests. Logistic regression analysis was also used to determine the factors associated with the operators' workability. The results showed a high mental workload in the study population (82.38±8.8). Yet, the operators showed a good and excellent level of workability (56.4%). Pearson's correlation coefficient revealed a significant inverse linear relationship between the mean score of mental workload and workability (r=-0.581). Besides, regression modeling demonstrated that mental demand (OR=0.90), temporal demand (OR=0.90), effort (OR=0.91), frustration (OR=0.92), from NASA-TLX subscales were significantly associated with workability. Moreover, mental and temporal demands were important factors associated with reduced workability. Monitoring tasks imposes high mental workload on the control room operators, which may result in adverse effects on their workability as well as on the safety of the system.


Longitudinal selenium status in healthy British adults: assessment using biochemical and molecular biomarkers.
Human selenium (Se) requirements are currently based on biochemical markers of Se status. In rats, tissue glutathione peroxidase-1 (Gpx1) mRNA levels can be used effectively to determine Se requirements; blood Gpx1 mRNA levels decrease in Se-deficient rats, so molecular biology-based markers have potential for human nutrition assessment. To study the efficacy of molecular biology markers for assessing Se status in humans, we conducted a longitudinal study on 39 subjects (age 45 +/- 11) in Reading, UK. Diet diaries (5 day) and blood were obtained from each subject at 2, 8, 17 and 23 weeks, and plasma Se, glutathione peroxidase (Gpx3) enzyme activity, and selenoprotein mRNA levels were determined. There were no significant longitudinal effects on Se biomarkers. Se intake averaged 48 +/- 14 microg/d. Plasma Se concentrations averaged 1.13 +/- 0.16 micromol/l. Plasma Se v. energy-corrected Se intake (ng Se/kJ/d) was significantly correlated, but neither Gpx3 activity v. Se intake (ng Se/kJ/d) nor Gpx3 activity v. plasma Se was significantly correlated. Collectively, this indicates that subjects were on the plateaus of the response curves. Selenoprotein mRNAs were quantitated in total RNA isolated from whole blood, but mRNA levels for Gpx1, selenoprotein H, and selenoprotein W (all highly regulated by Se in rodents), as well selenoprotein P, Gpx3, and phospholipid hydroperoxide glutathione peroxidase were also not significantly correlated with plasma Se. Thus selenoprotein molecular biomarkers, as well as traditional biochemical markers, are unable to further distinguish differences in Se status in these Se replete subjects. The efficacy of molecular biomarkers to detect Se deficiency needs to be tested in Se-deficient populations.


Imprecision of adaptation in Escherichia coli chemotaxis.
Adaptability is an essential property of many sensory systems, enabling maintenance of a sensitive response over a range of background stimulus levels. In bacterial chemotaxis, adaptation to the preset level of pathway activity is achieved through an integral feedback mechanism based on activity-dependent methylation of chemoreceptors. It has been argued that this architecture ensures precise and robust adaptation regardless of the ambient ligand concentration, making perfect adaptation a celebrated property of the chemotaxis system. However, possible deviations from such ideal adaptive behavior and its consequences for chemotaxis have not been explored in detail. Here we show that the chemotaxis pathway in Escherichia coli shows increasingly imprecise adaptation to higher concentrations of attractants, with a clear correlation between the time of adaptation to a step-like stimulus and the extent of imprecision. Our analysis suggests that this imprecision results from a gradual saturation of receptor methylation sites at high levels of stimulation, which prevents full recovery of the pathway activity by violating the conditions required for precise adaptation. We further use computer simulations to show that limited imprecision of adaptation has little effect on the rate of chemotactic drift of a bacterial population in gradients, but hinders precise accumulation at the peak of the gradient. Finally, we show that for two major chemoeffectors, serine and cysteine, failure of adaptation at concentrations above 1 mM might prevent bacteria from accumulating at toxic concentrations of these amino acids.


Incidence of HIV infection and associated factors among female sex workers in Côte d'Ivoire, results of the ANRS 12361 PrEP-CI study using recent infection assays.
This study aimed to estimate, using an HIV Recent Infection Testing Algorithm (RITA), the HIV incidence and its associated factors among female sex workers (FSW) in Côte d'Ivoire. A cross-sectional study was conducted in 2016-2017 in Abidjan and San Pedro's region among FSW aged ≥ 18 years. In addition, a sociodemographic questionnaire, HIV screening was carried out by two rapid tests. In the event of a positive result, a dried blood spot sample was taken to determine, using a RITA adapted to the Ivorian context, if it was a recent HIV infection. A total of 1000 FSW were surveyed with a median age of 25 years (interquartile range: 21-29 years). 39 (3.9%) tested positive for HIV. The incidence of HIV was estimated to be 2.3 per 100 person-years, with higher incidence rates among those 24 years old or less (3.0% vs. 1.9%), non-Ivorian FSW (3.2% vs. 1.9%) and those with the lowest education level (4.6% in FSW who never went to school vs. 2.6%). The incidence seemed to be associated with the sex work practice conditions: higher incidence among FSW whose usual price was less than 3.50$ (4.3% vs.1.0%), FSW who had a larger number of clients on the last day of work (6.1% in those with 7 clients or more vs. 1.8%), FSW who reported not always using condoms with their clients (8.5% vs. 1.5%) and FSW who reported agreeing to sex without a condom in exchange for a large sum of money (10.1% vs. 1.2%). This study confirms that FSW remain highly exposed to HIV infection. Exposure to HIV is also clearly associated with certain sex-work factors and the material conditions of sex work. Efforts in the fight against HIV infection must be intensified to reduce new infections among FSW.


Ultralight fractal structures from hollow tubes.
A fractal design is shown to be highly efficient both as a load bearing structure and as a general metamaterial. Through changing the hierarchical order of the structure, the scaling of material required for stability against loading can be manipulated. We show that the transition from solid to hollow beams changes the scaling in a manner analogous to increasing the hierarchical order by one. An example second order solid beam frame is constructed using rapid prototyping techniques. The optimal hierarchical order of the structure is found for different values of loading. Possible fabrication methods and applications are then discussed.


Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial.
Lonely older adults have increased expression of pro-inflammatory genes as well as increased risk for morbidity and mortality. Previous behavioral treatments have attempted to reduce loneliness and its concomitant health risks, but have had limited success. The present study tested whether the 8-week Mindfulness-Based Stress Reduction (MBSR) program (compared to a Wait-List control group) reduces loneliness and downregulates loneliness-related pro-inflammatory gene expression in older adults (N = 40). Consistent with study predictions, mixed effect linear models indicated that the MBSR program reduced loneliness, compared to small increases in loneliness in the control group (treatment condition × time interaction: F(1,35) = 7.86, p = .008). Moreover, at baseline, there was an association between reported loneliness and upregulated pro-inflammatory NF-κB-related gene expression in circulating leukocytes, and MBSR downregulated this NF-κB-associated gene expression profile at post-treatment. Finally, there was a trend for MBSR to reduce C Reactive Protein (treatment condition × time interaction: (F(1,33) = 3.39, p = .075). This work provides an initial indication that MBSR may be a novel treatment approach for reducing loneliness and related pro-inflammatory gene expression in older adults.


Gibson's theory of affordances and situational awareness occurring in urban departments of pediatrics, medicine, and emergency medicine.
The Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS®) program provides a situation-monitoring tool that allows health-care professionals to perform an environmental scan. This process includes scanning the status of the patient, team members, and the environment, to ensure that patient care is progressing toward the goal. It is assumed that health-care professionals will act in a certain way by providing feedback and support based on the scan. However, there is limited research supporting the impact of the clinical environment on behavior among health-care professionals. This qualitative research used in situ simulation and a theoretical sampling of six day and overnight shift clinical teams (n = 34) from three departments in an urban hospital in New York City: pediatric medicine, emergency medicine, and internal medicine. Notebook entries by the participants at three intervals during the case and a debriefing following the cases captured participant views, observations, and concerns about the immediate clinical environment. In all six cases, and with every shift, there were documented examples of someone in the environment who saw something but did not speak up, possibly making a difference in regard to patient safety and the outcomes in the case. Some of the noted reasons include not wanting to be wrong, not wanting to hurt someone's feelings, or not being sure. Our research explored the environmental scan that health-care team members conducted in three unique department settings, including how they perceived affordances, and the reasons why individuals may not speak up when another team member is not performing properly. Each person possesses a unique awareness and deficit of available affordances because of his/her position in the environment. Patient safety is somewhat reliant on the views and observations of each team member. Educators should use these outcomes to justify teamwork and communication training that includes targeted emphasis on providing candid feedback, situation monitoring, and mutual support.


Acteoside inhibits PMA-induced matrix metalloproteinase-9 expression via CaMK/ERK- and JNK/NF-κB-dependent signaling.
Acteoside, an active phenylethanoid glycoside found in bitter tea and many medicinal plants, displays chemopreventive properties. The aim of our study was to determine the effect of acteoside on tumor invasion and migration; the possible mechanisms involved in this inhibition were investigated in human fibrosarcoma HT-1080 cells. We employed invasion, migration and gelatin zymography assays to characterize the effect of acteoside on HT-1080 cells. Transient transfection assays were performed to investigate gene promoter activities, and immunoblot analysis to study its molecular mechanisms of action. We found that acteoside suppresses phorbol-12-myristate-13-acetate (PMA)-enhanced matrix metalloproteinase-9 (MMP-9) expression at the protein, mRNA, and transcriptional levels through the suppression of NF-κB activation. In addition, acteoside repressed the PMA-induced phosphorylation of ERK1/2 (ERK, extracellular regulated kinase) and JNK1/2. Further, we found that acteoside decreased the PMA-induced influx of Ca(2+) and repressed PMA-induced calmodulin-dependent protein kinase (CaMK) phosphorylation. Furthermore, treatment with BAPTA/AM, W7, or capsazepine markedly decreased PMA-induced MMP-9 secretion and cell migration, as well as ERK and JNK/NF-κB activation. Acteoside inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+) -dependent CaMK/ERK and JNK/NF-κB-signaling pathways. Acteoside therefore has the potential to be a potent anticancer agent in therapeutic strategies for fibrosarcoma metastasis.


Correlates of change in walking for exercise: an exploratory analysis.
This study was designed to identify correlates of change in walking for exercise. Respondents to a random sample mailed exercise survey were asked to complete a follow-up questionnaire 24 months after the first. Responses were obtained from 1,739 adults, reflecting an 86.6% return rate. Nonrespondents did not differ from respondents for baseline level of walking for exercise. Respondents overrepresented Caucasian and middle to high education (or income) adults. Residualized measures of change in walking for exercise served as the dependent variable, adjusted for baseline walking. Similarly, key independent variables, subject to change over time, were included after residualization. At both baseline and 24 months follow-up, adults walked for exercise an average of just under 1 hour per week, and 23.5% of the initially active adults ceased walking for exercise at 2 years. Multiple regression analyses explained more variance in walking for exercise among women than men. Change in dynamic variables such as friend's support and vigorous physical activity accounted for most of the explained variance. Results suggest that dynamic variables may need to be sustained to maintain walking for exercise. The limited explained variance suggests that more precise measures and additional determinants of walking for exercise need to be identified.


IL-34 is a Treg-specific cytokine and mediates transplant tolerance.
Cytokines and metabolic pathway-controlling enzymes regulate immune responses and have potential as powerful tools to mediate immune tolerance. Blockade of the interaction between CD40 and CD40L induces long-term cardiac allograft survival in rats through a CD8+CD45RClo Treg potentiation. Here, we have shown that the cytokine IL-34, the immunoregulatory properties of which have not been previously studied in transplantation or T cell biology, is expressed by rodent CD8+CD45RClo Tregs and human FOXP3+CD45RCloCD8+ and CD4+ Tregs. IL-34 was involved in the suppressive function of both CD8+ and CD4+ Tregs and markedly inhibited alloreactive immune responses. Additionally, in a rat cardiac allograft model, IL-34 potently induced transplant tolerance that was associated with a total inhibition of alloantibody production. Treatment of rats with IL-34 promoted allograft tolerance that was mediated by induction of CD8+ and CD4+ Tregs. Moreover, these Tregs were capable of serial tolerance induction through modulation of macrophages that migrate early to the graft. Finally, we demonstrated that human macrophages cultured in the presence of IL-34 greatly expanded CD8+ and CD4+ FOXP3+ Tregs, with a superior suppressive potential of antidonor immune responses compared with non-IL-34-expanded Tregs. In conclusion, we reveal that IL-34 serves as a suppressive Treg-specific cytokine and as a tolerogenic cytokine that efficiently inhibits alloreactive immune responses and mediates transplant tolerance.


Increased risk of chronic fatigue syndrome in patients with migraine: A retrospective cohort study.
The common concurrence of migraine and chronic fatigue syndrome (CFS) has been reported but whether migraine poses a higher risk of CFS remains unknown. In this retrospective case-control study, we examined the association between the 2 disorders by using a nationwide, population-based database in Taiwan. The data were retrieved and analyzed from the National Health Insurance Research Database (NHIRD) of Taiwan; 6902 newly diagnosed migraine cases from 2006-2010 were identified in a subset of the NHIRD, and 27,608 migraine-free individuals were randomly selected as the comparison cohort. The multivariate Cox proportional hazards regression model was used to investigate the risk of CFS in migraineurs after adjustment for demographic characteristics and comorbidities. After adjustment for the covariates, the risk of CFS was 1.5-fold higher in the migraine cohort than in the comparison cohort (52.72 vs. 28.85 per 10,000 person-years). Intriguingly, the risk was most prominent in the oldest group (≥ 65 years), with a 2.11-fold increased risk (95% confidence interval 1.31-3.41) of CFS. In addition, the adjusted cumulative incidence of CFS in the follow-up years was higher in the migraine group (log-rank test, P < .0001), and CFS incidence appeared to increase with the frequency of migraine diagnoses. The current study demonstrated an increased risk of CFS in migraineurs. Proposed mechanisms in previous studies such as mitochondrial dysfunction and central sensitization may underlie the shared pathophysiology of these seemingly distinct but potentially overlapping disorders.


Comparing Caenorhabditis elegans gentle and harsh touch response behavior using a multiplexed hydraulic microfluidic device.
The roundworm Caenorhabditis elegans is an important model system for understanding the genetics and physiology of touch. Classical assays for C. elegans touch, which involve manually touching the animal with a probe and observing its response, are limited by their low throughput and qualitative nature. We developed a microfluidic device in which several dozen animals are subject to spatially localized mechanical stimuli with variable amplitude. The device contains 64 sinusoidal channels through which worms crawl, and hydraulic valves that deliver touch stimuli to the worms. We used this assay to characterize the behavioral responses to gentle touch stimuli and the less well studied harsh (nociceptive) touch stimuli. First, we measured the relative response thresholds of gentle and harsh touch. Next, we quantified differences in the receptive fields between wild type worms and a mutant with non-functioning posterior touch receptor neurons. We showed that under gentle touch the receptive field of the anterior touch receptor neurons extends into the posterior half of the body. Finally, we found that the behavioral response to gentle touch does not depend on the locomotion of the animal immediately prior to the stimulus, but does depend on the location of the previous touch. Responses to harsh touch, on the other hand, did not depend on either previous velocity or stimulus location. Differences in gentle and harsh touch response characteristics may reflect the different innervation of the respective mechanosensory cells. Our assay will facilitate studies of mechanosensation, sensory adaptation, and nociception.


Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported.
Clinically diagnosed Alzheimer's disease and other dementing illnesses were assessed in a geographically defined US community. Of 3623 persons (80.8% of all community residents over 65 years of age) who had brief memory testing in their homes, a stratified sample of 467 persons underwent neurological, neuropsychological, and laboratory examination. Prevalence rates of Alzheimer's disease were calculated for the community population from the sample undergoing clinical evaluation. Of those over the age of 65 years, an estimated 10.3% (95% confidence limits, 8.1% and 12.5%) had probable Alzheimer's disease. This prevalence rate was strongly associated with age. Of those 65 to 74 years old, 3.0% (95% confidence limits, 0.8 and 5.2) had probable Alzheimer's disease, compared with 18.7% (95% confidence limits, 13.2 and 24.2) of those 75 to 84 years old and 47.2% (95% confidence limits, 37.0 and 63.2) of those over 85 years. Other dementing conditions were uncommon. Of community residents with moderate or severe cognitive impairment, 84.1% had clinically diagnosed Alzheimer's disease as the only probable diagnosis. These data suggest that clinically diagnosed Alzheimer's disease is a common condition and that its public health impact will continue to increase with increasing longevity of the population.


EST resources and establishment and validation of a 16k cDNA microarray from Atlantic cod (Gadus morhua).
The Atlantic cod, Gadus morhua, is an important species both for traditional fishery and increasingly also in fish farming. The Atlantic cod is also under potential threat from various environmental changes such as pollution and climate change, but the biological impact of such changes are not well known, in particular when it comes to sublethal effects that can be difficult to assert. Modern molecular and genomic approaches have revolutionized biological research during the last decade, and offer new avenues to study biological functions and e.g. the impact of anthropogenic activities at different life-stages for a given organism. In order to develop genomic data and genomic tools for Atlantic cod we conducted a program were we constructed 20 cDNA libraries, and produced and analyzed 44006 expressed sequence tags (ESTs) from these. Several tissues are represented in the multiple cDNA libraries, that differ in either sexual maturation or immulogical stimulation. This approach allowed us to identify genes that are expressed in particular tissues, life-stages or in response to specific stimuli, and also gives us information about potential functions of the transcripts. The ESTs were used to construct a 16k cDNA microarray to further investigate the cod transcriptome. Microarray analyses were preformed on pylorus, pituitary gland, spleen and testis of sexually maturing male cod. The four different tissues displayed tissue specific transcriptomes demonstrating that the cDNA array is working as expected and will prove to be a powerful tool in further experiments.


Indirect imaging of cardiac-specific transgene expression using a bidirectional two-step transcriptional amplification strategy.
Transcriptional targeting for cardiac gene therapy is limited by the relatively weak activity of most cardiac-specific promoters. We have developed a bidirectional plasmid vector, which uses a two-step transcriptional amplification (TSTA) strategy to enhance the expression of two optical reporter genes, firefly luciferase (fluc) and Renilla luciferase (hrluc), driven by the cardiac troponin T (cTnT) promoter. The vector was characterized in vitro and in living mice using luminometry and bioluminescence imaging to assess its ability to mediate strong, correlated reporter gene expression in a cardiac cell line and the myocardium, while minimizing expression in non-cardiac cell lines and the liver. In vitro, the TSTA system significantly enhanced cTnT-mediated reporter gene expression with moderate preservation of cardiac specificity. After intramyocardial and hydrodynamic tail vein delivery of an hrluc-enhanced variant of the vector, long-term fluc expression was observed in the heart, but not in the liver. In both the cardiac cell line and the myocardium, fluc expression correlated well with hrluc expression. These results show the vector's ability to effectively amplify and couple transgene expression in a cardiac-specific manner. Further replacement of either reporter gene with a therapeutic gene should allow non-invasive imaging of targeted gene therapy in living subjects.


Downstream fining by selective deposition in a laboratory flume.
There has long been debate about the relative importance of abrasion versus selective deposition of the coarsest clasts in causing downstream fining of sediment in river systems. Although high fining rates observed in many natural rivers seem to require strong selective deposition, the ability of selective deposition to produce downstream size sorting has never been measured under controlled conditions. In an experiment using a long flume and a poorly sorted, bimodal gravel feed, downstream fining was produced by a factor of 1.3 in median size and 1.8 in 90th percentile size, over a distance of 21 meters. The experimental conditions rule out abrasion effects. Selective deposition appears to be a natural consequence of the transport and deposition of sufficiently poorly sorted or bimodal gravels and appears to be capable of accounting for fining rates observed in natural gravel rivers.


Dietary sodium in chronic kidney disease: a comprehensive approach.
Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake.


An outbreak of respiratory tularemia caused by diverse clones of Francisella tularensis.
The bacterium Francisella tularensis is recognized for its virulence, infectivity, genetic homogeneity, and potential as a bioterrorism agent. Outbreaks of respiratory tularemia, caused by inhalation of this bacterium, are poorly understood. Such outbreaks are exceedingly rare, and F. tularensis is seldom recovered from clinical specimens. A localized outbreak of tularemia in Sweden was investigated. Sixty-seven humans contracted laboratory-verified respiratory tularemia. F. tularensis subspecies holarctica was isolated from the blood or pleural fluid of 10 individuals from July to September 2010. Using whole-genome sequencing and analysis of single-nucleotide polymorphisms (SNPs), outbreak isolates were compared with 110 archived global isolates. There were 757 SNPs among the genomes of the 10 outbreak isolates and the 25 most closely related archival isolates (all from Sweden/Finland). Whole genomes of outbreak isolates were >99.9% similar at the nucleotide level and clustered into 3 distinct genetic clades. Unexpectedly, high-sequence similarity grouped some outbreak and archival isolates that originated from patients from different geographic regions and up to 10 years apart. Outbreak and archival genomes frequently differed by only 1-3 of 1 585 229 examined nucleotides. The outbreak was caused by diverse clones of F. tularensis that occurred concomitantly, were widespread, and apparently persisted in the environment. Multiple independent acquisitions of F. tularensis from the environment over a short time period suggest that natural outbreaks of respiratory tularemia are triggered by environmental cues. The findings additionally caution against interpreting genome sequence identity for this pathogen as proof of a direct epidemiological link.


[Culturally constructed meanings for consumption of sweetened beverages among schoolchildren in Mexico City].
Demonstrate the importance of the cultural factors that currently motivate Mexican children to consume sweetened beverages and examine their implications for the design of programs for the promotion of healthy lifestyles. A qualitative phenomenological study involving nine peer interviews and four discussion groups was conducted among children aged 9 and 10 years in four public schools in southern Mexico City. The interviews employed nine photographs of beverages that are available in schools and homes. The aim was to identify the culinary rules associated with the consumption of sweetened beverages and the different views held by the children about the beverages. The complete interviews and group discussions were recorded and transcribed. Matrixes were developed for analysis of the subject categories identified during the study. The analysis was based on "continuous comparison" of the statements made by boys and girls, and among students from the four schools. Two main sociocultural elements, constructed in a given cultural framework, partly explain the children's current consumption patterns. The first, the nearly nonexistent concept that water is for drinking, with water consumption being limited to engagement in physical activity, in contrast to the wide range of circumstances and occasions found for the consumption of a sweetened beverage. Secondly, the identification of three principles that appear to underlie beverage consumption: the combination of salty food with sweet drinks, the important role of sweetened beverages at social events, and the close association between water consumption and the thirst induced by physical effort. The results show the importance of considering the role of socially significant elements in dietary practices and the need to also consider these elements when designing interventions for schoolchildren. It is also important to change the children's current views about what they drink, guiding and encouraging them to think of water as a drink to be consumed throughout the day and not only after physical activity. Finally, it is imperative in Mexico to guarantee free access to drinking water in schools and regulate food advertising that targets children.


The porous polyethylene/bioglass spherical orbital implant: a retrospective study of 170 cases.
To report patient outcomes after placement of porous polyethylene (PPE)/bioglass (BG) orbital implants for primary enucleation or secondary implantation. Retrospective chart review in one surgeon's practice (J.D.N.). A chart review of all patients who underwent placement of PPE/BG orbital implants was performed. Data included patient's age, gender, surgical indication, prior ocular surgery, medical history, procedure performed, implant size, and postoperative complications. PPE/BG implants were placed in 170 sockets. Seventy-seven patients were women, and 85 were men. One hundred forty patients underwent primary enucleation and placement of an implant, and 22 patients underwent secondary implantation. One hundred sixty-one patients did well after orbital implantation with a comfortable socket, quiet conjunctiva, and motility. Complications occurred in 9 patients (5.3%). Excessive discharge alone occurred in 2 patients (1.2%). Seven sockets undergoing primary enucleation and implant placement had implant exposure. One patient had an early exposure, and 6 had late exposures. All exposures were successfully treated with antibiotics or additional surgery. Secondary surgeries were required by some patients, but not due to implant complications, included ectropion repair in 5 patients (2.9%) and volume augmentation in 3 patients (1.7%). The PPE/BG orbital implant may be a useful implant for orbital reconstruction after primary enucleation or as a secondary implant.


Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update.
Purpose To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. Methods An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. Results Nine new observational studies, two systematic reviews, and an updated randomized controlled trial of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. Recommendations Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (nonulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or < 0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of > 1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher-risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors and details of the reference patient populations are included within the guideline. Additional information is available at www.asco.org/melanoma-guidelines and www.asco.org/guidelineswiki .


AKI in Hospitalized Patients with COVID-19.
Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associated with worse outcomes. However, AKI among hospitalized patients with COVID-19 in the United States is not well described. This retrospective, observational study involved a review of data from electronic health records of patients aged ≥18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality. Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patients with AKI required dialysis. The proportions with stages 1, 2, or 3 AKI were 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up. AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.


Immunochemical analysis of the gp120 surface glycoprotein of human immunodeficiency virus type 1: probing the structure of the C4 and V4 domains and the interaction of the C4 domain with the V3 loop.
We have probed the structure of the C4 and V3 domains of human immunodeficiency virus type 1 gp120 by immunochemical techniques. Monoclonal antibodies (MAbs) recognizing an exposed gp120 sequence, (E/K)VGKAMYAPP, in C4 were differentially sensitive to denaturation of gp120, implying a conformational component to some of the epitopes. The MAbs recognizing conformation-sensitive C4 structures failed to bind to a gp120 mutant with an alteration in the sequence of the V3 loop, and their binding to gp120 was inhibited by both V3 and C4 MAbs. This implies an interaction between the V3 and C4 regions of gp120, which is supported by the observation that the binding of some MAbs to the V3 loop was often enhanced by amino acid changes in an around the C4 region.


Vaccination willingness for COVID-19 among healthcare workers: a cross-sectional survey in a Swiss canton.
Vaccination is regarded as the most promising response to the COVID-19 pandemic. We assessed opinions about COVID-19 vaccination, willingness to be vaccinated, and reasons for vaccination hesitancy among healthcare workers. We conducted a cross-sectional, web-based survey among 3,793 healthcare workers in December 2020 in the Canton of Solothurn, Switzerland, before the start of the national COVID-19 vaccination campaign. Median age was 43 years (interquartile range [IQR] 31-53), 2,841 were female (74.9%). A total of 1,511 healthcare workers (39.8%) reported willingness to accept vaccination, whereas 1,114 (29.4%) were unsure and 1,168 (30.8%) would decline vaccination. Among medical doctors, 76.1% were willing, whereas only 27.8% of nurses expressed willingness. Among the 1,168 healthcare workers who would decline vaccination, 1,073 (91.9%) expressed concerns about vaccine safety and side effects. The willingness of healthcare workers to be vaccinated was associated with older age (adjusted odds ratio [aOR] 1.97, 95% confidence interval [Cl] 1.71-2.27) and having been vaccinated for influenza this year (aOR 2.70, 95% Cl 2.20-3.31). Healthcare workers who reported a lack of confidence in government were less likely to be willing to be vaccinated (aOR 0.58, 95% Cl 0.40-0.84), and women were less willing to be vaccinated than men (OR 0.33, 95% CI 0.28-0.38). Less than half of healthcare workers reported willingness to be vaccinated before the campaign start, but proportions varied greatly depending on profession and workplace. Strategies with clear and objective messages that particularly address the concerns of healthcare workers are needed if their willingness to be vaccinated against COVID-19 is to be further increased.