Preliminary results of the luna aneurysm embolization system in a rabbit model: a new intrasaccular aneurysm occlusion device.
Recent advances in endovascular devices have been aimed at providing high density, mesh-like metallic materials across the aneurysm neck, in place of coil technology. Therefore our aim was to report the in vivo preclinical performance of a self-expanding intrasaccular embolization device. Elastase-induced aneurysms were created in 12 rabbits. Each aneurysm was embolized with a Luna AES. DSA was performed preimplantation; 5, 10, and 30 minutes postimplantation; and at 1 month in 12 rabbits and at 3 months in 8 rabbits. Early postimplantation intra-aneurysmal flow was graded as unchanged, moderately diminished, or completely absent. One- and 3-month DSAs were graded by using a 3-point scale (complete, near-complete, or incomplete occlusion). Aneurysms were harvested for gross and microscopic histologic evaluation at 1 month (n = 4) and at 3 months (n = 8). Tissues within the aneurysm dome and across the aneurysm neck were assessed by using HE staining. Ten (83%) of 12 aneurysms demonstrated complete cessation of flow within 30 minutes of device implantation. At 1-month follow-up, 10 (83%) of 12 aneurysms were completely occluded. At 3 months, 7 of 8 (88%) aneurysms remained completely occluded. One-month gross examination in 4 rabbits demonstrated that membranous tissue completely covered the device in 3 subjects (75%). Microscopic examination showed that 3 aneurysms had loose connective tissue filling the aneurysm cavity. Three-month gross and microscopic examinations demonstrated membranous tissue completely covering the device, loose connective tissue filling the aneurysm cavity, and neointima formation crossing the aneurysm neck in 8 of 8 (100.0%) subjects. The Luna AES achieved high rates of complete angiographic occlusion and showed promising histologic findings in the rabbit aneurysm model.


Mechanobiology of dynamic enzyme systems.
This Perspective paper advances a hypothesis of mechanosensation by endothelial cells in which the cell is a dynamic crowded system, driven by continuous enzyme activity, that can be shifted from one non-equilibrium state to another by external force. The nature of the shift will depend on the direction, rate of change, and magnitude of the force. Whether force induces a pathophysiological or physiological change in cell biology will be determined by whether the dynamics of a cellular system can accommodate the dynamics and magnitude of the force application. The complex interplay of non-static cytoskeletal structures governs internal cellular rheology, dynamic spatial reorganization, and chemical kinetics of proteins such as integrins, and a flaccid membrane that is dynamically supported; each may constitute the necessary dynamic properties able to sense external fluid shear stress and reorganize in two and three dimensions. The resulting reorganization of enzyme systems in the cell membrane and cytoplasm may drive the cell to a new physiological state. This review focuses on endothelial cell mechanotransduction of shear stress, but may lead to new avenues of investigation of mechanobiology in general requiring new tools for interrogation of mechanobiological systems, tools that will enable the synthesis of large amounts of spatial and temporal data at the molecular, cellular, and system levels.


Non-alcoholic fatty liver disease: a practical approach to treatment.
Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population in many developed countries. Between 10% and 30% of patients with NAFLD have non-alcoholic steatohepatitis (NASH) that can progress to cirrhosis. There are metabolic risk factors common to both NAFLD and cardiovascular disease, so patients with NASH have an increased risk of liver-related and cardiovascular death. Management of patients with NAFLD depends largely on the stage of disease, emphasising the importance of careful risk stratification. There are four main areas to focus on when thinking about management strategies in NAFLD: lifestyle modification, targeting the components of the metabolic syndrome, liver-directed pharmacotherapy for high risk patients and managing the complications of cirrhosis.


Laminectomy for thoracic spinal canal stenosis.
Stenosis of the thoracic spinal canal is a relatively rare disorder with numerous causes. Clinical manifestations include signs and or symptoms consistent with focal thoracic radiculopathy and/or myelopathy. Several surgical approaches for the decompression of the stenotic thoracic canal have been described. Laminectomy is typically reserved for only those cases in which dorsal compression of the neural elements is demonstrated; it is contraindicated when the epidural compression is primarily ventral in location.


Behavioral consequences of marginal iron deficiency during development in a murine model.
Marginal iron deficiency is a common nutritional disorder in human populations world-wide; however, the neurobehavioral effects of chronic marginal iron (Fe) intakes during development are poorly characterized in animals. For this reason, we investigated whether mice reared on marginal Fe diets during pre- and postnatal development would experience neurobehavioral deficits. Swiss-Webster mice reared on either control (75 ppm Fe) or marginal iron (12.5 ppm) diets were assessed for changes in behavior on postnatal days 30, 40, and 50 using a neurobehavioral test battery. Because alterations in tissue mineral status can lead to an oxidative stress, markers of both protein (glutamine synthetase) and lipid oxidation (TBARS) were measured. Marginal iron animals exhibited a 20-55% reduction in grip strength. Although both marginal iron males and females demonstrated persistent lowering of body weights, statistical analysis using weight as the covariate demonstrated that the grip strength reductions were independent of body weight changes. This reduction in grip strength occurred in conjunction with a 25-45% lowering of brain iron in the marginal iron animals. Despite dramatic reductions in both brain and liver iron, hematocrits were unaffected by dietary iron reductions. Oxidative stress was indicated by an elevation in noniron-stimulated TBARS in the cerebellum of marginal iron animals. These data suggest that a chronic marginal Fe deficiency during critical periods of growth can result in functional changes in motor development even in the absence of iron deficiency anemia; furthermore, alterations in mineral status and oxidative stress may be mechanisms contributing to these observed changes.


Pheno-Deep Counter: a unified and versatile deep learning architecture for leaf counting.
Direct observation of morphological plant traits is tedious and a bottleneck for high-throughput phenotyping. Hence, interest in image-based analysis is increasing, with the requirement for software that can reliably extract plant traits, such as leaf count, preferably across a variety of species and growth conditions. However, current leaf counting methods do not work across species or conditions and therefore may lack broad utility. In this paper, we present Pheno-Deep Counter, a single deep network that can predict leaf count in two-dimensional (2D) plant images of different species with a rosette-shaped appearance. We demonstrate that our architecture can count leaves from multi-modal 2D images, such as visible light, fluorescence and near-infrared. Our network design is flexible, allowing for inputs to be added or removed to accommodate new modalities. Furthermore, our architecture can be used as is without requiring dataset-specific customization of the internal structure of the network, opening its use to new scenarios. Pheno-Deep Counter is able to produce accurate predictions in many plant species and, once trained, can count leaves in a few seconds. Through our universal and open source approach to deep counting we aim to broaden utilization of machine learning-based approaches to leaf counting. Our implementation can be downloaded at https://bitbucket.org/tuttoweb/pheno-deep-counter.


[Expression of 4F2-activation antigen in middle ear cholesteatoma].
Cholesteatoma consists of a keratinising squamous epithelium in the middle ear cavity. The human 4F2 antigen appears at the end of the phase G0 and at the beginning of the phase G1, remaining detectable throughout mitosis. This antigen is therefore considered to be an activation marker. In this study the presence and distribution of 4F2 in the cholesteatoma epithelium was investigated using monoclonal antibodies and the alkaline-phosphatase-anti-alkaline-phosphatase method. Normal skin showed positive immunostaining exclusively in the basal keratinocytes. In contrast, all cholesteatomas showed a suprabasal expression of the 4F2 antigen. The results confirm the hyperproliferative character of cholesteatoma epithelium.


Vascular permeability in a human tumour xenograft: molecular charge dependence.
Molecular charge is one of the main determinants of transvascular transport. There are, however, no data available on the effect of molecular charge on microvascular permeability of macromolecules in solid tumours. To this end, we measured tumour microvascular permeability to different proteins having similar size but different charge. Measurements were performed in the human colon adenocarcinoma LS174T transplanted in transparent dorsal skinfold chambers in severe combined immunodeficient (SCID) mice. Bovine serum albumin (BSA) and IgG were fluorescently labelled and were either cationized by conjugation with hexamethylenediamine or anionized by succinylation. The molecules were injected i.v. and the fluorescence in tumour tissue was quantified by intravital fluorescence microscopy. The fluorescence intensity and pharmacokinetic data were used to calculate the microvascular permeability. We found that tumour vascular permeability of cationized BSA (pI-range: 8.6-9.1) and IgG (pI: 8.6-9.3) was more than two-fold higher (4.25 and 4.65x10(-7) cm s(-1)) than that of the anionized BSA (pI approximately 2.0) and IgG (pI: 3.0-3.9; 1.11 and 1.93x10(-7) cm s(-1), respectively). Our results indicate that positively charged molecules extravasate faster in solid tumours compared to the similar-sized compounds with neutral or negative charges. However, the plasma clearance of cationic molecules was approximately 2x faster than that of anionic ones, indicating that the modification of proteins enhances drug delivery to normal organs as well. Therefore, caution should be exercised when such a strategy is used to improve drug and gene delivery to solid tumours.


Deadly stays: A 10-year autopsy study of deaths in hotels in Antalya, Turkey.
The hotel industry is essential for travelers, for both touristic and business purposes. Deaths in hotel rooms, which can occur in various manners from various causes, can result in serious problems for the industry. This study evaluated 8137 autopsies performed by the Antalya Group Administration of the Turkish Council of Forensic Medicine between January 1, 2010, and December 31, 2019. All deaths occurred during a hotel accommodation and within hotel borders, including their respective beach areas, and those who collapsed during their hotel stay and died shortly afterward in a hospital or on their way to a hospital were included. A total of 900 cases were identified and ultimately included in this study. According to the autopsy reports, the decedents who died during their stays were from 42 different countries and had a mean age of 54.3 ± 18.55 years. Most decedents were from Russia (n = 251, 27.9%). The most common manner of death was natural causes (n = 552, 61.3%) followed by accidents (n = 284, 31.6%), suicides (n = 40, 4.4%), and homicides (n = 7, 0.8%). Existing cardiovascular diseases (n = 379, 42.1%) were the leading cause of death, followed by drowning in the sea (n = 116, 12.9%) or a pool (n = 58, 6.4%). Most of the causes of deaths identified within this study are preventable with timely intervention or resuscitation. Providing medical personnel 24/7 with adequate equipment in accommodation options, and enabling hotels to take appropriate measures may decrease preventable deaths and improve international travel.


Concentrations, sources and risks of polycyclic aromatic hydrocarbons in sediments from the Parnaiba Delta basin, Northeast Brazil.
The Parnaíba River is the main river in the Parnaíba Delta basin, the largest delta in the Americas. About 18 polycyclic aromatic hydrocarbons (PAHs) were identified and the environmental risk associated with the sediments was evaluated. The study found that PAHs levels ranged from 5.92 to 1521.17 ng g-1, which was classified as low to high pollution, and that there were multiple sources of pollution along the river, with pyrolytic sources predominating, mainly from urban activity such as trucking, although the influence of rural activity cannot be ruled out. PAHs correlated with black carbon and organic matter and showed high correlation with acenaphthylene, phenanthrene, pyrene, benzo(a)anthracene, chrysene, benzo(ghi)perylene, and ∑PAHs. The benzo(a)pyrene levels were classified as a risk to aquatic life because the threshold effect level and the probable effect level were exceeded. In addition, the sediments were classified as slightly contaminated with a benzo(a)pyrene toxicity equivalent value of 108.43 ng g-1. Thus, the priority level PAH exhibited carcinogenic and mutagenic activity that posed a potential risk to human health.


Preliminary findings of an adapted evidence-based woman-focused HIV intervention on condom use and negotiation among at-risk women in Pretoria, South Africa.
This article presents the results of a randomized trial in South Africa of an adapted evidence-based Woman-Focused intervention on condom use with primary sex partners. The preliminary findings show that regardless of HIV status, condom negotiation was significantly associated with condom use at the 3- and 6-month follow-ups. By intervention group, significant intervention effects were found at 6-month follow-up for HIV-positive and HIV-unknown status women in the Woman-Focused intervention who were more likely than women in the Standard intervention to report condom use with a primary male partner. Among HIV-positive women, those in the Woman-Focused group and those with greater sexual control were more likely to report condom use at the 6-month follow-up. The findings indicate that gender-based interventions for women may result in increased condom negotiation skills.


Video aided extinction measurement: A competitive method for dust density diagnostics.
Among the most popular methods to measure dust density in a laboratory setup are 1D extinction, Abel inversion for circularly symmetric geometries, and computer tomography (CT) for arbitrary geometries. We present a new method based on a 1D extinction measurement in correlation with a video taken at an acute angle. It works well with limited optical access and has a good time resolution (at least several hertz). It measures the dust density within a slice of a nanodust cloud with precision comparable to other methods. Depending on the setup, this video aided extinction measurement can replace CT.


Searching for the delta: 5-aminosalicylic Acid therapy for Crohn's disease.
Crohn's disease (CD) is a chronic inflammatory condition that often requires lifelong medical therapy for the induction and maintenance of remission. Oral mesalamine (5-aminosalicylic acid [5-ASA]) therapy has several forms, which can be categorized into oral formulations and prodrugs. The ability to demonstrate the efficacy of 5-ASA is limited in most clinical trials by the nonspecific endpoints of the Crohn's Disease Activity Index. Overall, clinical trials have not shown 5-ASA therapy to be superior to placebo for the induction of remission, with the exception of sulfasalazine in colonic CD. 5-ASA therapy has also not been shown to be superior to placebo for maintenance of medically induced remission; however, mesalamine may have a modest effect in surgically induced remission. Further research is needed regarding the optimal monitoring and therapy for patients with mild CD who often achieve remission with placebo in clinical trials.


The role of deliberative decision making, parenting, and friends in adolescent risk behaviors.
Adolescents may engage in risk behaviors that jeopardize their futures. Although adolescent risk-taking has long been attributed to faulty decision making, surprisingly little research has directly examined this link. This study examined the role of deliberative decision making (the tendency to consider options and consequences before making a decision) and social contextual variables (parenting and friend influences) in alcohol and drug use, risky sex, and delinquency. Participants were 7,748 adolescents (50% female) in grades 7-11 from the Add Health dataset (M age = 14.87, SD = 1.54). Hierarchical regression analyses revealed that deliberative decision making and contextual variables were associated with risk behavior concurrently and 1 year later. Furthermore, deliberative decision making interacted with social contextual variables in some models, indicating that deliberative decision making may be especially important in certain contexts. These findings suggest that both cognitive and social factors need to be considered to explain adolescents' decisions to engage in risk behavior.


Kitlow stem cells cause resistance to Kit/platelet-derived growth factor alpha inhibitors in murine gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GIST) are related to interstitial cells of Cajal (ICC) and often contain activating stem cell factor receptor (Kit) or platelet-derived growth factor receptor alpha (Pdgfra) mutations. Kit/Pdgfra inhibitors such as imatinib mesylate have increased progression-free survival in metastatic GIST but are not curative. In mouse models we investigated whether Kit(low) ICC progenitors could represent an inherently Kit/Pdgfra inhibitor-resistant reservoir for GIST. Isolated Kit(low)Cd44(+)Cd34(+) cells were characterized after serial cloning. The tumorigenic potential of spontaneously transformed cells was investigated in nude mice. The Kit(low)Cd44(+)Cd34(+) cells' responsiveness to Kit activation and blockade was studied by enumerating them in Kit(K641E) mice (a GIST model), in mice with defective Kit signaling, and pharmacologically. Single isolated Kit(low)Cd44(+)Cd34(+) cells were clonogenic and capable of self-renewal and differentiation into ICC. In nude mice, spontaneously transformed cells formed malignant tumors expressing GIST markers. The Kit(low)Cd44(+)Cd34(+) cells were resistant to in vitro Kit blockade, including by imatinib, and occurred in normal numbers in mice with reduced Kit signaling. In Kit(K641E) mice, the mutant ICC stem cells were grossly hyperplastic but remained imatinib-resistant. In contrast, the cancer stem, cell-targeting drug salinomycin blocked the proliferation of Kit(low)Cd44(+)Cd34(+) cells and increased their sensitivity to imatinib. Kit(low)Cd44(+)Cd34(+) progenitors are true stem cells for normal and hyperplastic ICC and give rise to GIST. Resistance to Kit/Pdgfra inhibitors is inherent in GIST and is caused by the native ICC stem cells' lack of dependence on Kit for survival, which is maintained after the acquisition of oncogenic Kit mutation. Cancer stem cell drugs may target these cells.


Smoking or alcohol dependence among Indigenous Australians: treatment may be needed, not just education.
In trying to help Aboriginal and Torres Strait Islander (Indigenous) individuals or communities to stop smoking or reduce the harms from alcohol, it is important to be aware of the strong biological basis of the drive to return to nicotine or alcohol. In this paper we briefly describe the social and neurobiological factors that drive a dependent smoker or drinker to keep using. We set out the current range of pharmacological treatments for dependence, their role in assisting a person to either stop using or avoid relapse, and we discuss issues relating to their use in Aboriginal Australians. There is a firm evidence base for the use of pharmacological treatments for nicotine or alcohol dependence, particularly in severe dependence or when counselling or non-pharmacological approaches have failed. Indigenous Australians should be able to access the full range of approaches to managing these conditions. Working in partnership with Indigenous health staff and agencies can help ensure that appropriate access to treatment and quality treatment delivery occurs.


Increased nicotianamine biosynthesis confers enhanced tolerance of high levels of metals, in particular nickel, to plants.
Nicotianamine, a plant-derived chelator of metals, is produced by the trimerization of S-adenosylmethionine catalyzed by nicotianamine synthase. We established transgenic Arabidopsis and tobacco plants that constitutively overexpress the barley nicotianamine synthase gene. Nicotianamine synthase overexpression resulted in increased biosynthesis of nicotianamine in transgenic plants, which conferred enhanced tolerance of high levels of metals, particularly nickel, to plants. Promoter activities of four nicotianamine synthase genes in Arabidopsis were all increased in response to excess nickel, suggesting that nicotianamine plays an important role in the detoxification of nickel in plants. Furthermore, transgenic tobacco plants with a high level of nicotianamine grew well in a nickel-enriched serpentine soil without developing any symptoms of nickel toxicity. Our results indicate that nicotianamine plays a critical role in metal detoxification, and this can be a powerful tool for use in phytoremediation.


Linking human tick bite risk with tick abundance in the environment: A novel approach to quantify tick bite risk using orienteers in Scotland.
The rate that people are bitten by ticks is critical in determining the risk of tick-borne infections but is rarely quantified accurately. Often tick abundance in the environment is used as a proxy for tick bite risk, but the relationship with risk is poorly understood. We used a novel citizen science approach to measure tick bite rate in orienteers, to assess the relationship between tick abundance and tick bite risk and to identify risk factors for tick bites. Eleven orienteering events were attended in Scotland between August 2018 and September 2019. The number of tick bites in orienteers, and the time and distance of activity were collected using an online questionnaire. Tick abundance in the same areas used for the orienteering events was estimated by surveying ticks on ground vegetation using blanket drags. Among orienteers, mean incidence was 409 tick bites per 1,000 person-hours. Tick abundance and tick bite rate were strongly correlated, indicating that data from questing tick surveys is a useful proxy for the risk of human tick bites. Tick bite rate was better explained by the activity duration than distance covered and was higher in orienteers that ran earlier in the day, exposed to higher temperatures and in woodland habitats. This study highlights the value of the citizen science approach used, which crucially included submission of activity reports both with and without ticks, to generate robust data on tick bite rate. Accurately measuring tick bite rate and understanding environmental factors that influence it are essential in mitigating the risk of tick-borne diseases.


Slowly progressive aphemia: a neuropsychological, conventional, and functional MRI study.
Slowly progressive aphemia (SPA) is a rare focal degenerative disorder characterized by severe dysarthria, frequent orofacial apraxia, dysprosody, phonetic and phonemic errors without global cognitive deterioration for many years. This condition is caused by a degeneration of anterior frontal lobe regions, mainly of the left frontal operculum. We report a case of SPA with a course of 8 years, evaluated by repeated neuropsychological, conventional, and functional MRI examinations. In our case, neuropsychological examinations showed a progressive impairment of speech articulation including dysprosody, phonetic and phonemic errors, and slight writing errors. No global cognitive deterioration was detected and the patient is still completely autonomous. Morphological and functional investigations showed, respectively, a progressive atrophy and progressive impairment of the left frontal region, confirming the role of the opercular region in determining this rare syndrome. During verbal task generation as the cortical activation of this region gradually decreased, the language articulation worsened.


Listeria monocytogenes persistence in food-associated environments: epidemiology, strain characteristics, and implications for public health.
Over the last 10 to 15 years, increasing evidence suggests that persistence of Listeria monocytogenes in food processing plants for years or even decades is an important factor in the transmission of this foodborne pathogen and the root cause of a number of human listeriosis outbreaks. L. monocytogenes persistence in other food-associated environments (e.g., farms and retail establishments) may also contribute to food contamination and transmission of the pathogen to humans. Although L. monocytogenes persistence is typically identified through isolation of a specific molecular subtype from samples collected in a given environment over time, formal (statistical) criteria for identification of persistence are undefined. Environmental factors (e.g., facilities and equipment that are difficult to clean) have been identified as key contributors to persistence; however, the mechanisms are less well understood. Although some researchers have reported that persistent strains possess specific characteristics that may facilitate persistence (e.g., biofilm formation and better adaptation to stress conditions), other researchers have not found significant differences between persistent and nonpersistent strains in the phenotypic characteristics that might facilitate persistence. This review includes a discussion of our current knowledge concerning some key issues associated with the persistence of L. monocytogenes, with special focus on (i) persistence in food processing plants and other food-associated environments, (ii) persistence in the general environment, (iii) phenotypic and genetic characteristics of persistent strains, (iv) niches, and (v) public health and economic implications of persistence. Although the available data clearly indicate that L. monocytogenes persistence at various stages of the food chain contributes to contamination of finished products, continued efforts to quantitatively integrate data on L. monocytogenes persistence (e.g., meta-analysis or quantitative microbial risk assessment) will be needed to advance our understanding of persistence of this pathogen and its economic and public health impacts.


Variant Review with the Integrative Genomics Viewer.
Manual review of aligned reads for confirmation and interpretation of variant calls is an important step in many variant calling pipelines for next-generation sequencing (NGS) data. Visual inspection can greatly increase the confidence in calls, reduce the risk of false positives, and help characterize complex events. The Integrative Genomics Viewer (IGV) was one of the first tools to provide NGS data visualization, and it currently provides a rich set of tools for inspection, validation, and interpretation of NGS datasets, as well as other types of genomic data. Here, we present a short overview of IGV's variant review features for both single-nucleotide variants and structural variants, with examples from both cancer and germline datasets. IGV is freely available at https://www.igv.org Cancer Res; 77(21); e31-34. ©2017 AACR.


Motion segmentation and depth ordering using an occlusion detector.
We present a novel method for motion segmentation and depth ordering from a video sequence in general motion. We first compute motion segmentation based on differential properties of the spatio-temporal domain, and scale-space integration. Given a motion boundary, we describe two algorithms to determine depth ordering from two- and three- frame sequences. An remarkable characteristic of our method is its ability compute depth ordering from only two frames. The segmentation and depth ordering algorithms are shown to give good results on 6 real sequences taken in general motion. We use synthetic data to show robustness to high levels of noise and illumination changes; we also include cases where no intensity edge exists at the location of the motion boundary, or when no parametric motion model can describe the data. Finally, we describe human experiments showing that people, like our algorithm, can compute depth ordering from only two frames, even when the boundary between the layers is not visible in a single frame.


Causal Effect of Tooth Loss on Functional Capacity in Older Adults in England: A Natural Experiment.
Tooth loss is associated with reduced functional capacity, but so far, there is no relevant causal evidence reported. We investigated the causal effect of tooth loss on the instrumental activities of daily living (IADL) among older adults in England. Natural experiment study with instrumental variable analysis. The English Longitudinal Study of Aging (ELSA) combined with the participants' childhood exposure to water fluoride due to the community water fluoridation. Five thousand six hundred and thirty one adults in England born in 1945-1965 participated in the ELSA wave seven survey (conducted in 2014-2015; average age: 61.0 years, 44.6% men). The number of natural teeth predicted by the exogenous geographical and historical variation in exposure to water fluoride from age 5 to 20 years old (instrumental variable) was used as an exposure variable. The outcome, having any limitations in IADL (preparing a hot meal, shopping for groceries, making telephone calls, taking medications, doing work around the house or garden, or managing money), was assessed by self-reported questionnaires. Linear probability model with Two-Stage Least Squares estimation was fitted. Being exposed to fluoridated water was associated with having more natural teeth in later life (coefficient: 0.726; 95% confidence interval (CI) = 0.311, 1.142; F = 11.749). Retaining one more natural tooth reduced the probability of having a limitation in IADL by 3.1 percentage points (coefficient: -0.031; 95% CI = -0.060, -0.002). Preventing tooth loss maintains functional capacity among older adults in England. Given the high prevalence of tooth loss, this effect is considerable. Further research on the mechanism of the observed causal relationship is needed.


Perception and opinion of nursing faculties regarding advocacy role: A qualitative research.
The nursing literature emphasizes that there are still inadequacies, differences, and inconsistencies in the definition of nurses' advocacy role, and that nursing education plays an important role in educating nurses for patient advocacy. The aim of this descriptive qualitative study is to determine nurse academics' perception of and opinions about advocacy in nursing. The study group consisted of five academics working as nurse educators in a university. A questionnaire and focus group interview methods were used to collect the data. A framework that consisted of three categories, including the scope of advocacy in nursing; today's health system and advocacy; nurses' foundation/knowledge base for an advocacy role was set by considering the opinions of participants. It was emphasized that nurse academics regarded advocacy as an ethical obligation and saw it from a broad perspective including social justice, that changing health system has increased the importance of advocacy role in nursing, that the personality characteristics of prospective nurses are important, and that nursing education should be improved in terms of advocacy.


Hybrid Bionic Nerve Interface for Application in Bionic Limbs.
Intuitive and perceptual neuroprosthetic systems require a high degree of neural control and a variety of sensory feedback, but reliable neural interfaces for long-term use that maintain their functionality are limited. Here, a novel hybrid bionic interface is presented, fabricated by integrating a biological interface (regenerative peripheral nerve interface (RPNI)) and a peripheral neural interface to enhance the neural interface performance between a nerve and bionic limbs. This interface utilizes a shape memory polymer buckle that can be easily implanted on a severed nerve and make contact with both the nerve and the muscle graft after RPNI formation. It is demonstrated that this interface can simultaneously record different signal information via the RPNI and the nerve, as well as stimulate them separately, inducing different responses. Furthermore, it is shown that this interface can record naturally evoked signals from a walking rabbit and use them to control a robotic leg. The long-term functionality and biocompatibility of this interface in rabbits are evaluated for up to 29 weeks, confirming its promising potential for enhancing prosthetic control.


Conjugal transfer system of the IncN plasmid pKM101.
The conjugal transfer system of the broad-host range IncN plasmid pKM101 was analyzed genetically. Its organization differed significantly from that of the F plasmid. The tra genes are located in three regions, each between 3 and 4 kilobases in length. All of the genes in the first two regions are required for sensitivity to "donor-specific" phage which bind to the plasmid-mediated sex pilus, and these genes therefore are involved in the synthesis, and possibly retraction, of the sex pilus. The plasmid's origin of transfer was localized to a 1.2-kilobase region at an extreme end of the transfer region. Using two different methods, we have identified 11 complementation groups required for transfer. One of these, traC, is of special interest in that mutations at this locus can be partially suppressed if, prior to mating, cells carrying a traC mutant plasmid are incubated with cells which elaborate sex pili but are unable to transfer their plasmids. One possible explanation for this is that pilus-elaborating cells can donate traC gene product to a traC mutant in a form that can be reused.


Antioxidant/lipoxygenase inhibitory activities and chemical compositions of selected essential oils.
Twenty-five essential oils were tested for antioxidant activities using a conjugated diene assay, the aldehyde/carboxylic acid assay, the DPPH free radical scavenging assay, and the malonaldehyde/gas chromatography (MA/GC) assay. They were also tested for lipoxygenase inhibitory activities using the lipoxygenase inhibitor-screening assay. Thyme oil exhibited the greatest antioxidant effect in all assays (80-100%) except in the DPPH assay (60%). Clove leaf oil showed activities comparable to those of thyme oil (53-100%). Cinnamon leaf oil showed strong activities in the aldehyde/carboxylic acid assay (100%) and DPPH assay (84%), but only moderate activities in the conjugated diene assay (24%) and MA/GC assay (48%). Basil oil exhibited a strong effect in the DPPH assay (86%) and moderate activities in the MA/GC assay (35%). Bergamot oil exhibited 100% antioxidant activity in the aldehyde/carboxylic acid assay. Eucalyptus and chamomile oils showed appreciable activities only in the conjugated diene assay. Bitter orange oil exhibited moderate antioxidant activity (53%) only in the MA/GC assay. Aloe vera oil exhibited the greatest lipoxygenase inhibitory activity (96%), followed by thyme oil (86%) and bergamot oil (85%) at a concentration of 0.5 microg/mL. Chamomile oil showed slight lipoxygenase inhibitory activity at 0.5 microg/mL but strong lipoxygenase inducing activity at 5 microg/mL (-123%). Thyme and clove leaf oils contained high levels of thymol (23%) and eugenol (77%), respectively, as a principal of the antioxidant activity. The results obtained in the present study suggest that some essential oils possess strong medicinal activities, which can be utilized for treatment of certain diseases.


Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study.
This study was planned to investigate the efficacy of neuromuscular rehabilitation and Johnstone Pressure Splints in the patients who had ataxic multiple sclerosis. Twenty-six outpatients with multiple sclerosis were the subjects of the study. The control group (n = 13) was given neuromuscular rehabilitation, whereas the study group (n = 13) was treated with Johnstone Pressure Splints in addition. In pre- and posttreatment data, significant differences were found in sensation, anterior balance, gait parameters, and Expanded Disability Status Scale (p < 0.05). An important difference was observed in walking-on-two-lines data within the groups (p < 0.05). There also was a statistically significant difference in pendular movements and dysdiadakokinesia (p < 0.05). When the posttreatment values were compared, there was no significant difference between sensation, anterior balance, gait parameters, equilibrium and nonequilibrium coordination tests, Expanded Disability Status Scale, cortical onset latency, and central conduction time of somatosensory evoked potentials and motor evoked potentials (p > 0.05). Comparison of values revealed an important difference in cortical onset-P37 peak amplitude of somatosensory evoked potentials (right limbs) in favor of the study group (p < 0.05). According to our study, it was determined that physiotherapy approaches were effective to decrease the ataxia. We conclude that the combination of suitable physiotherapy techniques is effective multiple sclerosis rehabilitation.


Spondylitis in a humpback whale (Megaptera novaeangliae) from the southeast Pacific.
A 7.25 m long male humpback whale (Megaptera novaeangliae) with spondylitis was found beached on August 13, 1994 at Ancon, Ecuador (2 degrees 23' S, 80 degrees 47' W). The condition involved at least 11 vertebrae, 7 lumbar (L4 to L11) and 4 caudal (Ca1 to Ca4). Partial fusion of vertebrae was observed as a result of intervertebral bony proliferation, likely impeding full motion. The relatively young age of this specimen and the severity of the deformities suggest an infectious, rather than degenerative, process. The gross findings are most consistent with some type of spondyloarthritis. Although this condition has previously been identified in a number of cetacean species, the pathogenesis, population impact and ecologic implications have not been fully assessed. This is the third case described for humpback whales and the first for a humpback whale from the SE Pacific.


Topographic variations in biomechanical and biochemical properties in the ankle joint: an in vitro bovine study evaluating native and engineered cartilage.
The purposes of this study were to identify differences in the biomechanical and biochemical properties among the articulating surfaces of the ankle joint and to evaluate the functional and biological properties of engineered neocartilage generated using chondrocytes from different locations in the ankle joint. The properties of the different topographies within the ankle joint (tibial plafond, talar dome, and distal fibula) were evaluated in 28 specimens using 7 bovine ankles; the femoral condyle was used as a control. Chondrocytes from the same locations were used to form 28 neocartilage constructs by tissue engineering using an additional 7 bovine ankles. The functional properties of neocartilage were compared with native tissue values. Articular cartilage from the tibial plafond, distal fibula, talar dome, and femoral condyle exhibited Young modulus values of 4.8 ± 0.5 MPa, 3.9 ± 0.1 MPa, 1.7 ± 0.2 MPa, and 4.0 ± 0.5 MPa, respectively. The compressive properties of the corresponding tissues were 370 ± 22 kPa, 242 ± 18 kPa, 255 ± 26 kPa, and 274 ± 18 kPa, respectively. The tibial plafond exhibited 3-fold higher tensile properties and 2-fold higher compressive and shear moduli compared with its articulating talar dome; the same disparity was observed in neocartilage. Similar trends were detected in biochemical data for both native and engineered tissues. The cartilage properties of the various topographic locations within the ankle are significantly different. In particular, the opposing articulating surfaces of the ankle have significantly different biomechanical and biochemical properties. The disparity between tibial plafond and talar dome cartilage and chondrocytes warrants further evaluation in clinical studies to evaluate their exact role in the pathogenesis of ankle lesions. Therapeutic modalities for cartilage lesions need to consider the exact topographic source of the cells or cartilage grafts used. Furthermore, the capacity of generating neocartilage implants from location-specific chondrocytes of the ankle joint may be used in the future as a tool for the treatment of chondral lesions.


Endorsement of "European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea" by World Sleep Society.
Guidelines for management of sleep disorders from national or regional societies provide recommendations that may be regionally appropriate but may not always be practical or relevant in other parts of the world. A task force of experts from the World Sleep Society's (WSS) International Sleep Medicine Guidelines Committee and Sleep and Breathing Disorders Task Force reviewed the European Respiratory Society's guideline on non-CPAP therapies for obstructive sleep apnea (OSA) with respect to its relevance and applicability to the practice of sleep medicine by sleep specialists in various regions of the world. The task force and the WSS guidelines committee endorsed the European Respiratory Society's guideline with respect to the utilization of bariatric surgery, mandibular advancement devices, positioning devices, myofunctional therapy, hypoglossal neurostimulation, maxilo-mandibular surgery, and carbonic anhydrase inhibitors for the treatment of OSA. The task force and the WSS guidelines committee noted that there is substantial new evidence for the role of soft tissue, upper airway surgery, not included in the guidelines paper.


DL-propranolol and chlorpromazine following admission for schizophrenia. A controlled comparison.
Similar improvement followed when propranolol and chlorpromazine were randomly used as the first drug after admission. Forty-six patients with florid symptoms of schizophrenia were assigned at random to have either racemic propranolol (24) or chlorpromazine (22). Each individual's drug was adjusted to an optimal dose, and the progress of the groups was followed for 12 weeks. Thirty-five patients remained in the study for 6 weeks, and 27 for 12 weeks. By weeks 6 and 12 the total schizophrenia scores on a modified Brief Psychiatric Rating Scale had improved significantly when the results from both groups were combined. The numbers leaving the study, and the amount and rate of improvement, were similar for both groups, but with a possible advantage to chlorpromazine. Side-effects, which usually were mild, were commoner in the chlorpromazine group.


Missed lower extremity and spine fractures in athletes.
The majority of missed fractures in athletes are not overlooked because of difficulties recognizing them on radiographs; rather, these fractures occur less commonly and often exist without accompanying disabilities, which makes their diagnosis more of a challenge. To complicate matters, evaluation of an injured athlete is often completed in the setting of the playing field, where distractions can be abundant. The physician treating sports-related injuries must not only follow the general principles of fracture evaluation and management, but must also be aware of the commonly understated fractures associated with the athlete's lower extremities and spine.


[Fatigue and anemia].
We herein report on an 80-year old male patient with a history of muscle weakness, fatigue and weight loss since several months. Because of a pathologic synacthen test in combination with decreased levels of ACTH, we diagnosed a secondary chronic adrenal insufficiency. Because of a normochromic, normocytic, and hypo-proliferative anemia, bone marrow puncture was performed, showing an anemia of chronic disease. We initiated hydrocortisone and anemia and patients' symptoms were fully reconstituted.


Breast cancer diagnosis by analysis of serum N-glycans using MALDI-TOF mass spectroscopy.
Blood and serum N-glycans can be used as markers for cancer diagnosis, as alterations in protein glycosylation are associated with cancer pathogenesis and progression. We aimed to develop a platform for breast cancer (BrC) diagnosis based on serum N-glycan profiles using MALDI-TOF mass spectroscopy. Serum N-glycans from BrC patients and healthy volunteers were evaluated using NosQuest's software "NosIDsys." BrC-associated "NosID" N-glycan biomarkers were selected based on abundance and NosIDsys analysis, and their diagnostic potential was determined using NosIDsys and receiver operating characteristic curves. Results showed an efficient pattern recognition of invasive ductal carcinoma patients, with very high diagnostic performance [area under the curve (AUC): 0.93 and 95% confidence interval (CI): 0.917-0.947]. We achieved effective stage-specific differentiation of BrC patients from healthy controls with 82.3% specificity, 84.1% sensitivity, and 82.8% accuracy for stage 1 BrC and recognized hormone receptor-2 and lymph node invasion subtypes based on N-glycan profiles. Our novel technique supplements conventional diagnostic strategies for BrC detection and can be developed as an independent platform for BrC screening.


Does mental simulation of following a path improve navigation performance without vision?
We recorded the paths of subjects who walked along a memorized hexagonal route without vision, and studied the impact of previous mental simulation of this activity on how well the path could be reproduced from memory. We compared two kinds of mental simulation to actual physical practice, rest, or simple memorization of the path. The results indicated that mental simulation led to better reproduction of the global shape of a path than rest, and in fact mental simulation was as effective as actual physical practice. However, this result occurred only for 'simple shapes' when the lengths of the sides of the path were kept constant. Nevertheless, this level of performance was not reached when the complexity of the shape was increased by altering the lengths of sides, even when keeping constant the angles between consecutive sides. This finding indicates that the internal representation of space depends on geometric properties of the environment in which the subjects operate. Mental simulation appears to affect both a map-like and route-like representation of the environment.


Effect of reading on surface electromyogram recordings in patients with blepharospasm.
To compare the surface electromyogram recordings between patients with benign essential blepharospasm and controls while maintaining primary gaze and reading in downgaze. A university-based, prospective case series of 7 benign essential blepharospasm patients and 7 normal patients. Bilateral lower eyelid preseptal orbicularis oculi muscle potentials were recorded via surface electromyogram and video while performing a standardized 60-second task that was divided in 3 equal 20-second subtasks. Specifically, patients were asked to maintain primary gaze for the first 20-second interval, to read quietly for the second interval, and again maintain primary gaze for the third 20-second interval. Fourteen trials capturing bilateral recordings were performed in each group; qualitative and quantitative analysis of the surface electromyogram recordings was performed and compared both between patient groups and between subtasks. Blepharospasm patients were also asked to describe the effect of reading on their spasms. Specifically, they were asked before the study if reading lessened or worsened their spasms and then were asked poststudy if their symptoms lessened or worsened during the reading task. The mean surface electromyogram potential of the orbicularis muscle was significantly less in normal eyes when compared with blepharospasm eyes for each task. Furthermore, the mean surface electromyogram potential during the reading task was significantly reduced when compared with the primary gaze task in all eyes. Only blepharospasm patients noticed this reduction subjectively. Although conventional wisdom regarding blepharospasm suggests that reading is an exacerbating factor, short durations of reading seem to relieve spasms. This may be due to the effect of downgaze on the blink reflex and may offer possible areas of investigation for novel blepharospasm treatments.


[The antiphlogistic effect of the ginkgolide BN 52 021 in the chemically burned rabbit eye].
BN 52 021, a specific antagonist of PAF receptors, was tested in the early-phase treatment of chemically burned eyes in 30 rabbits. The local application of BN 52 021 eyedrops-1% (water-soluble preparation, 5 times daily, in comparison with the other eye as a control) led to a visible anti-inflammatory effect (microscopically and macroscopically) of the chemically burned anterior eye segment. There was only a moderate increase of the concentration of PGF2 alpha after the chemical burn. The use of specific PAF antagonists seems to have a real chance for treatment of inflammatory reactions of the anterior eye segment. A combination with other mediator antagonists should be tested in further experiments.


Dissociative recombination of water cluster ions with free electrons: cross sections and branching ratios.
Dissociative recombination (DR) of water cluster ions H(+)(H(2)O)(n) (n=4-6) with free electrons has been studied at the heavy-ion storage ring CRYRING (Manne Siegbahn Laboratory, Stockholm University). For the first time, branching ratios have been determined for the dominating product channels and absolute DR cross sections have been measured in the energy range from 0.001 to 0.7 eV. Dissociative recombination is concluded to result in extensive fragmentation for all three cluster ions, and a maximum number of heavy oxygen-containing fragments is produced with a probability close to unity. The branching ratio results agree with earlier DR studies of smaller water cluster ions where the channel nH(2)O+H has been observed to dominate and where energy transfer to internal degrees of freedom has been concluded to be highly efficient. The absolute DR cross sections for H(+)(H(2)O)(n) (n=4-6) decrease monotonically with increasing energy with an energy dependence close to E(-1) in the lower part of the energy range and a faster falloff at higher energies, in agreement with the behavior of other studied heavy ions. The cross section data have been used to calculate DR rate coefficients in the temperature range of 10-2000 K. The results from storage ring experiments with water cluster ions are concluded to partly confirm the earlier results from afterglow experiments. The DR rate coefficients for H(+)(H(2)O)(n) (n=1-6) are in general somewhat lower than reported from afterglow experiments. The rate coefficient tends to increase with increasing cluster size, but not in the monotonic way that has been reported from afterglow experiments. The needs for further experimental studies and for theoretical models that can be used to predict the DR rate of polyatomic ions are discussed.


Oral anticoagulant therapy in atrial fibrillation older patients with previous bleeding.
Oral anticoagulant therapy (OAT) with direct oral anticoagulant (DOACs) is the established treatment to reduce thromboembolic risk in patients with atrial fibrillation (AF). Bleeding risk scores are useful to identify and correct factors associated with bleeding risk in AF patients on OAT. However, the clinical scenario is more complex in patients with previous bleeding event, and the decision about whether and when starting or re-starting OAT in these patients remains a contentious issue. Major bleeding is associated with a subsequent increase in both short- and long-term mortality, and even minimal bleeding may have prognostic importance because it frequently leads to disruption of antithrombotic therapy. There is an unmet need for guidance on how to manage antithrombotic therapy after bleeding has occurred. While waiting for observational and randomized data to accrue, this paper offers a perspective on managing antithrombotic therapy after bleeding in older patients with AF.


Hybrid nanotrimers for dual T1 and T2-weighted magnetic resonance imaging.
Development of multifunctional nanoparticle-based probes for dual T1- and T2-weighted magnetic resonance imaging (MRI) could allow us to image and diagnose the tumors or other abnormalities in an exceptionally accurate and reliable manner. In this study, by fusing distinct nanocrystals via solid-state interfaces, we built hybrid heteronanostructures to combine both T1 and T2- weighted contrast agents together for MRI with high accuracy and reliability. The resultant hybrid heterotrimers showed high stability in physiological conditions and could induce both simultaneous positive and negative contrast enhancements in MR images. Small animal positron emission tomography imaging study revealed that the hybrid heterostructures displayed favorable biodistribution and were suitable for in vivo imaging. Their potential as dual contrast agents for T1 and T2-weighted MRI was further demonstrated by in vitro and in vivo imaging and relaxivity measurements.


Highly aligned hierarchical intrafibrillar mineralization of collagen induced by periodic fluid shear stress.
Periodic fluid shear stress (FSS) is one of the main mechanical microenvironments in mineralization of bone matrix. To elucidate the mechanism of periodic FSS in collagen mineralization, a mechanical loading induced mineralization system is developed and compared with traditional polyacrylic acid (PAA) induced mineralization. Fourier transform infrared (FTIR) spectroscopy, calcium-to-phosphorus molar ratio and transmission electron microscopy (TEM) demonstrate that both periodic FSS and PAA can control the size of amorphous calcium phosphate (ACP) to avoid aggregation and help the formation of intrafibrillar mineralization. Differently, periodic FSS under a proper cycle and range can accelerate the conversion of ACP to apatite crystals and alleviate the reduced transformation caused by PAA. Under the action of template analogues, periodic FSS can also promote the formation of highly oriented hierarchical intrafibrillar mineralized (HIM) collagen. These findings are helpful for understanding the mechanism of collagen mineralization in natural bone matrix and contribute to the design of novel bone substitute materials with hierarchical structures.


[Membrane proteins as regulators of the complement system].
The data on structure, biochemical properties and functions of membrane proteins, performing cell defence against complement lysis, are summarized. Proteins DAE (decay accelerating factor) and CR1 (complement receptor of type 1) reduce the stability of complement convertases and cause their dissociation. MCP (membrane cofactor protein) and CR1 act as cofactors. In factor I mediated proteolysis of the convertase fragments C3b and C4b. The proteins C8bp-(C8-binding protein) and protectin affect membrane attack complex assembly. In contrast to MCP and CR1, which are integrative proteins, DAF, C8bp and protectin are bound to membranes with their glycophospholypid anchors. Tissue distribution of the proteins and the ways of their solubilization into biological fluids are reviewed.


Geographic and facility variation in inpatient stroke rehabilitation: multilevel analysis of functional status.
To examine geographic and facility variation in cognitive and motor functional outcomes after postacute inpatient rehabilitation in patients with stroke. Retrospective cohort design using Centers for Medicare and Medicaid Services (CMS) claims files. Records from 1209 rehabilitation facilities in 298 hospital referral regions (HRRs) were examined. Patient records were analyzed using linear mixed models. Multilevel models were used to calculate the variation in outcomes attributable to facilities and geographic regions. Inpatient rehabilitation units and facilities. Patients (N=145,460) with stroke discharged from inpatient rehabilitation from 2006 through 2009. Not applicable. Cognitive and motor functional status at discharge measured by items in the CMS Inpatient Rehabilitation Facility-Patient Assessment Instrument. Variation profiles indicated that 19.1% of rehabilitation facilities were significantly below the mean functional status rating (mean ± SD, 81.58±22.30), with 221 facilities (18.3%) above the mean. Total discharge functional status ratings varied by 3.57 points across regions. Across facilities, functional status values varied by 29.2 points, with a 9.1-point difference between the top and bottom deciles. Variation in discharge motor function attributable to HRR was reduced by 82% after controlling for cluster effects at the facility level. Our findings suggest that variation in motor and cognitive function at discharge after postacute rehabilitation in patients with stroke is accounted for more by facility than geographic location.


[The multiplication dynamics of pathogenic bacteria in relation to the trophic and temperature cultivation conditions].
The comparative study of the dynamics of multiplication of Listeria monocytogenes and Yersinia pseudotuberculosis in organic and synthetic media and in distilled water at temperatures of 37 degrees C and 6 degrees C was carried out. This study revealed that in organic media the multiplication of bacteria was good at 37 degrees C and 6 degrees C. In mineral media and distilled water their multiplication was observed only at 6 degrees C. Moreover, conditions necessary for the multiplication of pathogenic bacteria in distilled water were shown; these conditions depended on the inoculated dose, the number of autolyzed microbial cells and the state of the culture. Proofs of the multiplication of the bacteria under the conditions of minimum nutrition and low temperature were obtained with the use of labeled 3H-thymidine.


Correction of a large periradicular lesion and mucosal defect using combined endodontic and periodontal therapy: a case report.
The successful treatment of a large endodontically induced periradicular defect and soft tissue fenestration by combined endodontic and periodontal therapy is described. Endodontics was performed on the mandibular left central incisor, the apex was resected, and a retrograde amalgam was placed. The defect was thoroughly debrided and the exposed root surface was planed with curettes. Demineralized freeze-dried bone allograft and a nonresorbable membrane were placed over the defect and the exposed root surface. The membrane was removed in 6 months and there appeared to be bone regeneration with complete closure of the soft tissue fenestration. Endodontic therapy in combination with guided tissue regeneration and bone grafting may provide another modality of treatment for endodontically related hard and soft tissue defects.


Bipolar Radiofrequency Neurotomy to Treat Neck and Back Pain in Patients with Automatic Implantable Cardioverter Defibrillator.
We report 2 cases of successful treatment of neck and back pain with bipolar radiofrequency ablation (RFA) of the cervical and lumbar facet joints in patients with an automatic implantable cardioverter defibrillator (AICD).Two patients with complex cardiac histories and AICD devices were treated with bipolar RFA of the facet joints. One presented with axial neck pain and the other with axial back pain. The histories and physical examinations were consistent with facetogenic pain. Diagnostic medial branch block resulted in more than 70% pain relief lasting for several days, allowing patients to perform routine daily activities without significant pain. However, we were concerned about the use of conventional RFA of the medial branches of nerves for the fear of interference with the function of AICD by the RF currents and energy. We took advantage of the localized and limited current of bipolar RFA to perform this procedure for the cervical or lumbar facet joints avoiding any interference with the function of AICD. The procedures provided long-term pain relief to the patients, and marked improvement in their functional status without any evident complications related to the function of their AICD.This case report describes the safe and successful completion of bipolar RFA of the medial branch nerves to treat cervical and lumbar facetogenic pain in patients with AICD. This modality of treatment may be considered in patients with AICD. We are finding it to be increasingly common that patients who present with chronic neck and back pain have AICDs in place.


Making the transition from acute care to school nursing.
School nursing is an interdisciplinary specialty demanding diverse nursing skills. Many of these skills might best be acquired through experience in other settings. The school population presents many nursing challenges, and there may be no supportive circle of specialists and peers readily available to the new school nurse. Further, in some states there is a shortage of educational opportunities and practicums specific to school nursing; therefore, most school nurses enter school nursing with education that is not specific to the school setting and with skills acquired in other settings, often in acute care. The main challenge for many new school nurses is effectively transferring those skills to an educational setting. This article shares observations and ideas on ways that the new school nurse can effectively make the transition.


[Long-term Trends and Sources of Atmospheric Halocarbons at Mount Taishan, Northern China].
Halocarbons are hot topics in atmospheric environment and climate change research. Combining observational data from six field campaigns at the summit of Mount Taishan (36.25°N, 117.10°E, 1534 m above sea level) with backward trajectory and receptor source analyses, this study analyzed the long-term trends and major emission sources of halocarbons in the regional background atmosphere of the North China Plain (NCP) from 2003 to 2018. The results showed that the volume fraction of species eliminated by the Montreal Protocol (MP) showed a significant downward trend; however, the MP-controlled and unregulated species showed an overall upward trend. Meanwhile, the median volume fraction of the MP-controlled and unregulated species at Mount Taishan were significantly higher than the mid-latitude median background values in the northern hemisphere. Mount Taishan air was mainly affected by four types of air masses, of which the air mass originating from NCP accounted for the highest proportion (41%). The major sources of halocarbons were biomass/biofuel burning (38.1%), refrigeration (26.2%), industrial and domestic solvent use (21.7%), solvent use in the electronic industry (8.7%), and leakage of chlorofluorocarbon (CFCs) banks (5.3%). This study fully demonstrates that MP has been effectively implemented in China and provides evidence and recommendations to further reduce and control the volume fraction of halocarbons.


Relay activity of 17-beta oestradiol and diethylstilbestrol in a mouse-rat system.
The biological activities of diethylstibestrol (DES) of 17 beta-oestradiol (17 beta E) were initially tested, based on the uterus enlargement induced by different doses given with food to immature female mice. In a second series of experiments, the drugs were given in higher doses per os to rats (relay animals) and after 24 h, the livers of the relay rats were removed. Parts of the livers were freeze-dried and were added (10% w/w) to the food of immature female mice, while the remainder underwent chemical analysis to determine the DES and 17 beta E content. When given directly to mice with their food, DES showed about six times more biological activity than 17 beta E. When given through the livers of relay rats, the biological activity of the livers from DES-and 17 beta E-treated relay rats was of the same magnitude. The content of 17 beta E in the livers of relay rats was 10-20 times higher than the DES. Such concentrations corresponded directly to the biological activity of livers. These data show that the bioavailability and the relative potency of xenobiotic drugs and natural hormones may be profoundly altered after passing through metabolic pathways, and may give useful indications for the evaluation of biological activity of residues and contaminants and their metabolites in the food.


Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study.
There is a need to develop surrogates for treatment efficacy in the neoadjuvant setting to speed-up drug development and stratify patients according to outcome. Preclinical studies showed that chemotherapy induces an antitumor immune response. In order to develop new surrogates for drug efficacy, we assessed the prognostic value of tumor-infiltrating lymphocytes (TIL) on residual disease after neoadjuvant chemotherapy (NACT) in patients with triple-negative breast cancer (TNBC). Three hundred four TNBC patients with residual disease after NACT were retrospectively identified in three different hospitals. Hematoxylin and eosin-stained slides from surgical postchemotherapy specimens were evaluated for intratumoral (It-TIL) and stromal (Str-TIL) TIL. Cases were classified as High-TIL if It-TIL and/or Str-TIL >60%. TIL were assessable for 278 cases. Continuous It-TIL and Str-TIL variables were strong prognostic factors in the multivariate model, both for metastasis-free [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.77-0.96, P = 0.01 and HR 0.85, 95% CI 0.75-0.98, P = 0.02 for Str-TIL and It-TIL, respectively] and overall survival (HR 0.86, 95% CI 0.77-0.97, P = 0.01 and HR 0.86, 95% CI 0.75-0.99, P = 0.03 for Str-TIL and It-TIL, respectively). The 5-year overall survival rate was 91% (95% CI 68% to 97%) for High-TIL patients (n = 27) and 55% (95% CI 48% to 61%) for Low-TIL patients (HR 0.19, 95% CI 0.06-0.61, log-rank P = 0.0017). The major prognostic impact of TIL was seen for patients with large tumor burden following NACT (residual tumor >2 cm and/or node metastasis). In all but one High-TIL case, It-TIL and Str-TIL values were lower on the prechemotherapy sample. The presence of TIL in residual disease after NACT is associated with better prognosis in TNBC patients. This parameter may represent a new surrogate of drug efficacy to test investigational agents in the neoadjuvant setting and a new prognostic marker to select patients at high risk of relapse.


Capillary electrophoretic analysis of carbohydrates derivatized by in-capillary condensation with 1-phenyl-3-methyl-5-pyrazolone.
Our previous papers on capillary electrophoresis (CE) have shown that samples can be derivatized in a capillary and the derivatives can be analyzed immediately after derivatization, provided that the derivatization reaction is so rapid as to complete in seconds. The present paper presents extended application of in-capillary derivatization to a much slower reaction such as the condensation of reducing carbohydrates with 1-phenyl-3-methyl-5-pyrazolone (PMP) which requires 30 min at 70 degrees C in pre-column derivatization by manual operation. It was necessary to first drive the introduced plugs of sample and reagent solutions to put them together at the entrance of the heated portion of a capillary, then to allow the superimposed plugs to react for a relevant period. We showed how to determine the introduction times of the sample and the reagent solutions as well as intermediate running buffer, the voltages to be applied for plug driving and product analysis, and the duration of voltage application, all of which are important for effective in-capillary derivatization. An example of the analysis of maltooligosaccharides by this technique is presented. It was shown that maltooligosaccharides were quantitatively derivatized with PMP in 35 min at 57 degrees C, and the derivatives could be analyzed in ca. 15 min by CE immediately after derivatization. Separation was satisfactory in 200 mM borate buffer, pH 8.2 containing sodium dodecyl sulfate to a concentration of 200 mM. Although the theoretical plate number, and accordingly the resolution, were significantly lower than the corresponding values in pre-capillary derivatization, reasonable reproducibility was ensured for both migration time (RSD 3.5% on average) and peak area (RSD less than 3%) under the optimized conditions. It is notable that sample amount could be lowered to the 10 fmol level, in contrast to the 10 pmol level in pre-capillary derivatization. In addition, since the technique employed here (the modified at-inlet technique of in-capillary derivatization) is easily automated, the established system will be highly beneficial for routine analysis of carbohydrates. Analysis by this technique was also shown to be useful for kinetic study of the derivatization reaction.


Review. Genetics of addictions: strategies for addressing heterogeneity and polygenicity of substance use disorders.
Addictions are common psychiatric disorders that exert high cost to the individual and to society. Addictions are a result of the interplay of multiple genetic and environmental factors. They are characterized by phenotypic and genetic heterogeneity as well as polygenicity, implying a contribution of different neurobiological mechanisms to the clinical diagnosis. Therefore, treatments for most substance use disorders are often only partially effective, with a substantial proportion of patients failing to respond. To address heterogeneity and polygenicity, strategies have been developed to identify more homogeneous subgroups of patients and to characterize genes contributing to their phenotype. These include genetic linkage and association studies as well as functional genetic analysis using endophenotypes and animal behavioural experimentation. Applying these strategies in a translational context aims at improving therapeutic response by the identification of subgroups of addiction patients for individualized, targeted treatment strategies. This article aims to discuss strategies addressing heterogeneity and polygenicity of substance use disorders by presenting results of recent research on genetic and environmental components of addiction. It will also introduce the European IMAGEN study that aims to integrate methodical approaches discussed in order to identify the genetic and neurobiological basis of behavioural traits relevant to the development of addictions.


The effects of quinolones and NSAIDs upon GABA-evoked currents recorded from rat dorsal root ganglion neurones.
Recent animal studies have demonstrated a proconvulsant effect of certain quinolone and non-steroidal anti-inflammatory drug combinations. Radioligand binding experiments have indicated that these actions may be mediated by antagonism of the GABAA receptor. The present study has further investigated this hypothesis in a functional assay by examining the effects of the quinolones ciprofloxacin and ofloxacin alone and in combination with either fenbufen or biphenyl acetic acid (BPAA) upon GABA-evoked currents recorded from voltage-clamped rat dorsal root ganglion neurones (DRG) maintained in cell culture. GABA-evoked whole cell currents were weakly but dose-dependently (30 microM-1 mM) reduced in the presence of ciprofloxacin and ofloxacin. The IC50 for ciprofloxacin was 100 microM but greater than 1 mM for ofloxacin. Application of either fenbufen (100 microM) or BPAA (100 microM) alone produced little effect on the GABA-evoked currents. However, the inhibitory action of ciprofloxacin was enhanced in the presence of 100 microM fenbufen by approximately five-fold whereas the antagonism of GABA responses by ofloxacin was unaffected. In contrast, BPAA (100 microM) had a dramatic effect on the inhibitory actions of both antibiotics such that the IC50 for ciprofloxacin and ofloxacin was reduced to 0.03 and 0.3 microM respectively. The present results support earlier binding studies and extend them by demonstrating electrophysiologically a potent quinolone/NSAID drug interaction at the GABAA receptor. The mechanism(s) of this novel interaction remains to be determined. These results are commensurate with clinical observations of an increased risk of fits in patients prescribed certain quinolones together with certain NSAIDs.


The long-term effects of articular impaction.
Ultimately, the long-term effects of articular impact injury remain unknown. Impact injury has long been considered an explanation for posttraumatic arthritis. It is an attractive hypothesis because often it is the only explanation we can put forth for why arthritis develops in an injured joint. There has been recent interest in the role of chondrocyte apoptosis in the pathogenesis of osteoarthritis. Chondrocyte apoptosis has also been observed with cartilage impact injury and may provide an explanation for how impact injury leads to osteoarthrosis. This paper reviews impact injury and its association with apoptosis as a potential etiology for posttraumatic arthritis.


Effects of intermittent pneumatic calf compression on postoperative thrombin and plasmin activity.
A previous study of neurosurgical patients demonstrated an imbalance between thrombin and plasmin action following surgery. The present study was designed to determine the effect of intermittent pneumatic calf compression on postoperative enzyme activity. Fibrinopeptide A (FPA) and B beta 1-42 levels, reflecting thrombin and plasmin action respectively, were measured daily in patients undergoing elective craniotomy. Two of 9 patients not receiving calf compression developed positive fibrinogen leg scans, while none of 5 patients receiving prophylaxis had positive scans. Calf compression was associated with a markedly altered pattern of changes in the fibrinopeptide values following surgery. Without compression, there was perturbation of the balance between thrombin and plasmin action on the day after surgery as reflected by an increase in the FPA/B beta 1-42 ratio. In contrast, in those receiving prophylaxis there was no change in this ratio on the first postoperative day. Calf compression both blunted the mean postoperative increase in the FPA level (1.8 nM vs 4.7 nM; p less than .05) and augmented the mean B beta 1-42 value (3.0 nM vs 0.2 nM; p less than .05) so that the mean increase in the FPA/B beta 1-42 ratio was only 0.1 with calf compression as compared to 2.2 without it (p less than .05). Systemic modulation of both the coagulation and fibrinolytic pathways thus occurred in association with calf compression.


Is the Whipple procedure harmful for long-term outcome in treatment of chronic pancreatitis? 15-years follow-up comparing the outcome after pylorus-preserving pancreatoduodenectomy and Frey procedure in chronic pancreatitis.
The aim of this study was to report on 15-year long-term results of a randomized controlled trial comparing extended drainage procedure (Frey) and classical resectional procedure [pylorus-preserving pancreatoduodenectomy (PD)] in patients with chronic pancreatitis. Chronic pancreatitis is a common inflammatory disease with a prevalence of 10 to 30 cases per 100,000 inhabitants. It is characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. Different surgical procedures are used in treatment of persistent pain. Sixty-four patients suffering from chronic pancreatitis with inflammatory mass in the pancreatic head were randomly assigned in 2 treatment groups (PD, n = 32) and (Frey, n = 32). The perioperative course of the randomized controlled trial and the 7 years follow-up have been previously published. All participating patients were contacted with a standardized, validated questionnaire (EORTC QLQ C30) to evaluate the long-term survival, quality-of-life pain, and exocrine and endocrine function. In the 15-year long-term follow-up, the pain control was good and comparable between both groups, but the quality of life was better after Frey procedure in regard of the physical status [PD: 100 (0-100) vs PD: 60 (0-100) (P = 0.011)]. No significant differences in terms of the Pain Score were detected between both groups [PD: 7 (0-100) vs Frey 4 (0-100) P = 0.258]. Seven patients after Frey OP and 6 patients after PD were free of pain. Analyzing the postoperative overall survival, a higher long-term mortality was found after PD (53%) than that found after Frey procedure (30%) resulting in a longer mean survival (14.5 ± 0.8 vs 11.3 ± 0.8 years; P = 0.037). No correlation between endocrine or exocrine pancreatic function and pain was found, whereas continuous alcohol consumption was associated with poorer outcome regarding quality of life (P < 0.001) and pain score (P < 0.001). PD and Frey procedure provide good and permanent pain relief and improvement of the quality of life in long-term follow-up. In addition, a longer survival was found after the organ sparing resection. Together with better short-term results, the organ-sparing procedure seems to be favorable in treatment of chronic pancreatitis.


Implementation of WHO multimodal strategy for improvement of hand hygiene: a quasi-experimental study in a Traditional Chinese Medicine hospital in Xi'an, China.
Hand hygiene (HH) is an essential component for preventing and controlling of healthcare-associated infection (HAI), whereas compliance with HH among health care workers (HCWs) is frequently poor. This study aimed to assess compliance and correctness with HH before and after the implementation of a multimodal HH improvement strategy launched by the World Health Organization (WHO). A quasi-experimental study design including questionnaire survey generalizing possible factors affecting HH behaviors of HCWs and direct observation method was used to evaluate the effectiveness of WHO multimodal HH strategy in a hospital of Traditional Chinese Medicine. Multimodal HH improvement strategy was drawn up according to the results of questionnaire survey. Compliance and correctness with HH among HCWs were compared before and after intervention. Also HH practices for different indications based on WHO "My Five Moments for Hand Hygiene" were recorded. In total, 553 HCWs participated in the questionnaire survey and multimodal HH improvement strategy was developed based on individual, environment and management levels. A total of 5044 observations in 23 wards were recorded in this investigation. The rate of compliance and correctness with HH improved from 66.27% and 47.75% at baseline to 80.53% and 88.35% after intervention. Doctors seemed to have better compliance with HH after intervention (84.04%) than nurses and other HCWs (81.07% and 69.42%, respectively). When stratified by indication, compliance with HH improved for all indications after intervention (P < 0.05) except for "after body fluid exposure risk" and "after touching patient surroundings". Implementing the WHO multimodal HH strategy can significantly improve HH compliance and correctness among HCWs.


Biodegradable PEI modified complex micelles as gene carriers with tunable gene transfection efficiency for ECs.
In recent years, gene therapy has evoked an increasing interest in clinical treatments of coronary diseases because it is a potential strategy to realize rapid endothelialization of artificial vascular grafts. The balance of high transfection efficiency and low cytotoxicity of nonviral gene carriers is an important issue to be solved. In this study, we aim to establish a gene delivery system offering an elegant way to tune the transfection activity and cytotoxicity. Biodegradable complex micelles were prepared from polyethylenimine-b-poly(lactide-co-3(S)-methyl-morpholine-2,5-dione)-b-polyethylenimine (PEI-b-PLMD-b-PEI) and methoxy-poly(ethylene glycol)-b-poly(lactide-co-3(S)-methyl-morpholine-2,5-dione) (mPEG-b-PLMD) copolymers by a co-assembly method. Then the ZNF580 gene plasmid (pDNA) was encapsulated into the complex micelles. The hydrodynamic size and zeta potential of these complex micelles and micelles/pDNA complexes indicated that they were feasible for use in cellular uptake and gene transfection. As expected, the transfection efficiency and cytotoxicity of these micelles/pDNA complexes could be conveniently tuned by changing the mass ratio of mPEG-b-PLMD to PEI-b-PLMD-b-PEI (3/1, 2/2, 1/3 and 0/4) in the mixed mPEG/PEI shell. The transfection efficiency increased as the mass ratio of mPEG-b-PLMD/PEI-b-PLMD-b-PEI decreased from 3/1 to 0/4, while the cytotoxicity showed an opposite tendency. Moreover, ZNF580 protein expression determined by Western blot analysis and the migration of transfected endothelial cells (ECs) by wound healing assay were consistent with the result of transfection efficiency. All these results indicated that the co-assembled complex micelles could act as suitable gene carriers with tunable gene transfection efficiency and cytotoxicity, which should have great potential for the transfection of vascular ECs.


Effects of electroacupuncture on stress-induced gastric dysrhythmia and mechanisms involving autonomic and central nervous systems in functional dyspepsia.
Electroacupuncture (EA) is widely used as an effective method to treat stress-related disorders. However, its mechanisms remain largely unknown. The aim of this study was to investigate the effects and mechanisms of EA on gastric slow wave (GSW) dysrhythmia and c-Fos expression in the nucleus of the solitary tract (NTS) induced by stress in a rodent model of functional dyspepsia (FD). Rats in the neonatal stage were treated using intragastric iodoacetamide. Eight weeks later, the rats were implanted with electrodes in the stomach for the measurement of GSW and electrodes into accupoints ST36 for EA. Autonomic functions were assessed by spectral analysis of heart rate variability. Rats were placed for 30 min in a cylindrical plastic tube for acute restraint stress. The involvement of a central afferent pathway was assessed by measuring c-Fos-immunoreactive cells in the NTS. 1) EA normalized restraint stress-induced impairment of GSW in FD rats. 2) EA significantly increased vagal activity (P = 0.002) and improved sympathovagal balance (P = 0.004) under stress in FD rats. 3) In FD rats under restraint stress, plasma norepinephrine concentration was increased substantially (P < 0.01), which was suppressed with EA. 4) The EA group showed increased c-Fos-positive cell counts in the NTS compared with the sham EA group (P < 0.05) in FD rats. Acute restraint stress induces gastric dysrhythmia in a rodent model of FD. EA at ST36 improves GSW under stress in FD rats mediated via the central and autonomic pathways, involving the NTS and vagal efferent pathway.


Detection of dual-gene expression in arteries using an optical imaging method.
We evaluate the in vivo use of an optical imaging method to detect the vascular expression of green fluorescent protein (GFP) or red fluorescent protein (RFP), and to detect the simultaneous expression of GFP and RFP after transduction into arteries by a dual-promoter lentiviral vector driving their concurrent expression. This method involves using a charge-coupled device camera to detect fluorescence, a fiber optic probe to transmit light, and optical filters to distinguish each marker. In animal models, these vectors are locally delivered to target arteries, whereas the gene for a nonfluorescent cell-surface protein is transduced into contralateral arteries as the sham control. The images show distinct areas of bright fluorescence from GFP and RFP along the target arteries on excitation; no exogenous fluorescence is observed in the controls. Measured signal intensities from arteries transduced with the single- and dual-promoter vectors exceed the autofluorescence signal from the controls. Transgene expression of GFP and RFP in vivo is confirmed with confocal microscopy. We demonstrate the use of an optical imaging method to concurrently detect two distinct fluorescent proteins, potentially permitting the expression of multiple transgenes and their localization in the vasculature to be monitored.


Oblique-incidence sputtering of Ru intermediate layer for decoupling of intergranular exchange in perpendicular recording media.
During the Ru deposition process for granular type perpendicular magnetic recording media, both a reduction in the Ru intermediate layer thickness and lowering of sputtering gas pressure were successfully achieved by focusing on a self-shadowing effect. Oblique-incidence sputtering with a 60° incident angle under an Ar gas pressure of 0.6 Pa yielded (1) columnar Ru grains with a growth direction of 30° from the film normal, (2) c-plane sheet texture by epitaxial growth on the Pt underlayer, and (3) a flat envelope of the surface and a deep gap at grain boundaries. This change in the Ru structure significantly contributes to reducing exchange coupling among magnetic grains, especially in the initial growth region in an overlying granular medium.


Pancreatic cancer after remote peptic ulcer surgery.
Peptic ulcer surgery may carry an increased risk for pancreatic cancer development. Molecular analysis of K-ras codon 12, frequently mutated in conventional pancreatic cancers, might provide insight into the aetiological mechanisms. The relative risk of pancreatic cancer was computed by multivariate and person-year analysis in a cohort of 2633 patients who had undergone gastrectomy. Lung cancer risk was analysed as an indirect means of assessing smoking behaviour. K-ras codon 12 mutational analysis was performed on 15 postgastrectomy pancreatic cancers. There was an overall increased risk of pancreatic carcinoma of 1.8 (95% confidence interval, 1.3 to 2.6) five to 59 years postoperatively, which gradually increased to 3.6 at 35 years or more after surgery (chi(2) test for trend, p < 0.05). Multivariate analysis indicated that parameters other than postoperative interval did not influence the risk. Lung cancer risk was significantly increased after surgery, but no time trend was observed. The spectrum and prevalence of K-ras codon 12 mutations were comparable to conventional pancreatic cancer. Remote partial gastrectomy is associated with an increased risk of pancreatic cancer. Postgastrectomy and non-postgastrectomy pancreatic cancers may share similar aetiological factors, such as smoking. However, the neoplastic process in patients who have undergone gastrectomy appears to be accelerated by factors related to the surgery itself.


Improving Outcomes in Patients Receiving Dialysis: The Peer Kidney Care Initiative.
The past decade has witnessed a marked reduction in mortality rates among patients receiving maintenance dialysis. However, the reasons for this welcome development are uncertain, and greater understanding is needed to translate advances in care into additional survival gains. To fill important knowledge gaps and to enable dialysis provider organizations to learn from one another, with the aim of advancing patient care, the Peer Kidney Care Initiative (Peer) was created in 2014 by the chief medical officers of 14 United States dialysis provider organizations and the Chronic Disease Research Group. Areas of particular clinical importance were targeted to help shape the public health agenda in CKD and ESRD. Peer focuses on the effect of geographic variation on outcomes, the implications of seasonality for morbidity and mortality, the clinical significance of understudied disorders affecting dialysis patients, and the debate about how best to monitor and evaluate progress in care. In the realm of geovariation, Peer has provided key observations on regional variation in the rates of ESRD incidence, hospitalization, and pre-ESRD care. Regarding seasonality, Peer has reported on variation in both infection-related and non-infection-related hospitalizations, suggesting that ambient environmental conditions may affect a range of health outcomes in dialysis patients. Specific medical conditions that Peer highlights include Clostridium difficile infection, which has become strikingly more common in patients in the year after dialysis initiation, and chronic obstructive pulmonary disease, the treatments for which have the potential to contribute to sudden cardiac death. Finally, Peer challenges the nephrology community to consider alternatives to standardized mortality ratios in assessing progress in care, positing that close scrutiny of trends over time may be the most effective way to drive improvements in patient care.


A prognostic DNA methylation signature for stage I non-small-cell lung cancer.
Non-small-cell lung cancer (NSCLC) is a tumor in which only small improvements in clinical outcome have been achieved. The issue is critical for stage I patients for whom there are no available biomarkers that indicate which high-risk patients should receive adjuvant chemotherapy. We aimed to find DNA methylation markers that could be helpful in this regard. A DNA methylation microarray that analyzes 450,000 CpG sites was used to study tumoral DNA obtained from 444 patients with NSCLC that included 237 stage I tumors. The prognostic DNA methylation markers were validated by a single-methylation pyrosequencing assay in an independent cohort of 143 patients with stage I NSCLC. Unsupervised clustering of the 10,000 most variable DNA methylation sites in the discovery cohort identified patients with high-risk stage I NSCLC who had shorter relapse-free survival (RFS; hazard ratio [HR], 2.35; 95% CI, 1.29 to 4.28; P = .004). The study in the validation cohort of the significant methylated sites from the discovery cohort found that hypermethylation of five genes was significantly associated with shorter RFS in stage I NSCLC: HIST1H4F, PCDHGB6, NPBWR1, ALX1, and HOXA9. A signature based on the number of hypermethylated events distinguished patients with high- and low-risk stage I NSCLC (HR, 3.24; 95% CI, 1.61 to 6.54; P = .001). The DNA methylation signature of NSCLC affects the outcome of stage I patients, and it can be practically determined by user-friendly polymerase chain reaction assays. The analysis of the best DNA methylation biomarkers improved prognostic accuracy beyond standard staging.


Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients.
A large number of cancer-associated gene products evoke immune recognition, but host reactions rarely impede disease progression. The weak immunogenicity of nascent tumors contributes to this failure in host defense. Therapeutic vaccines that enhance dendritic cell presentation of cancer antigens increase specific cellular and humoral responses, thereby effectuating tumor destruction in some cases. The attenuation of T cell activation by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) further limits the potency of tumor immunity. In murine systems, the administration of antibodies that block CTLA-4 function inhibits the growth of moderately immunogenic tumors and, in combination with cancer vaccines, increases the rejection of poorly immunogenic tumors, albeit with a loss of tolerance to normal differentiation antigens. To gain a preliminary assessment of the biologic activity of antagonizing CTLA-4 function in humans, we infused a CTLA-4 blocking antibody (MDX-CTLA4) into nine previously immunized advanced cancer patients. MDX-CTLA4 stimulated extensive tumor necrosis with lymphocyte and granulocyte infiltrates in three of three metastatic melanoma patients and the reduction or stabilization of CA-125 levels in two of two metastatic ovarian carcinoma patients previously vaccinated with irradiated, autologous granulocyte-macrophage colony-stimulating factor-secreting tumor cells. MDX-CTLA4 did not elicit tumor necrosis in four of four metastatic melanoma patients previously immunized with defined melanosomal antigens. No serious toxicities directly attributable to the antibody were observed, although five of seven melanoma patients developed T cell reactivity to normal melanocytes. These findings suggest that CTLA-4 antibody blockade increases tumor immunity in some previously vaccinated cancer patients.


Comparing the ocular surface temperature and dry eye condition of keratoconus with normal eyes using infrared thermal imaging.
This study was conducted to compare the ocular surface temperature in keratoconus eyes with that in normal eyes. A total of 27 participants were enrolled, with 10 and 17 participants in the keratoconus and control groups, respectively. Participants in the control group underwent an ophthalmic slit lamp examination and ocular thermography, while an additional corneal tomography was performed for those in the keratoconus group. For patients with keratoconus, the mean upper eyelid temperature (UET) was 32.36 ± 1.02 °C, inner canthus temperature (ICT) was 34.25 ± 0.83 °C, outer canthus temperature (OCT) was 33.62 ± 0.96 °C, initial central corneal temperature (initial CCT) was 33.04 ± 1.03 °C, sixth-second CCT (6 s-CCT) was 32.67 ± 1.19 °C, and the mean change in CCT measured within 6 s (change in CCT within 6 s) was 0.36 ± 0.26 °C. For controls, the values for UET, ICT, OCT, initial CCT, 6 s-CCT, and change in CCT within 6 s were 32.35 ± 1.13 °C, 34.14 ± 0.91 °C, 33.51 ± 1.02 °C, 33.22 ± 1.01 °C, 32.99 ± 1.01 °C, and 0.22 ± 0.17 °C, respectively. Except for the change in CCT within 6 s (p = 0.022), no significant differences were observed in UET (p = 0.973), ICT (p = 0.659), OCT (p = 0.697), initial CCT (p = 0.556) or 6 s-CCT (p = 0.310) between the two groups. The keratoconus eyes showed faster changes in CCT and evaporation of tear film after opening the eyes. Therefore, the keratoconus eyes had a higher incidence of dry eye conditions.


Consistent high-dimensional Bayesian variable selection via penalized credible regions.
For high-dimensional data, particularly when the number of predictors greatly exceeds the sample size, selection of relevant predictors for regression is a challenging problem. Methods such as sure screening, forward selection, or penalized regressions are commonly used. Bayesian variable selection methods place prior distributions on the parameters along with a prior over model space, or equivalently, a mixture prior on the parameters having mass at zero. Since exhaustive enumeration is not feasible, posterior model probabilities are often obtained via long MCMC runs. The chosen model can depend heavily on various choices for priors and also posterior thresholds. Alternatively, we propose a conjugate prior only on the full model parameters and use sparse solutions within posterior credible regions to perform selection. These posterior credible regions often have closed-form representations, and it is shown that these sparse solutions can be computed via existing algorithms. The approach is shown to outperform common methods in the high-dimensional setting, particularly under correlation. By searching for a sparse solution within a joint credible region, consistent model selection is established. Furthermore, it is shown that, under certain conditions, the use of marginal credible intervals can give consistent selection up to the case where the dimension grows exponentially in the sample size. The proposed approach successfully accomplishes variable selection in the high-dimensional setting, while avoiding pitfalls that plague typical Bayesian variable selection methods.


Ceftobiprole activity against over 60,000 clinical bacterial pathogens isolated in Europe, Turkey, and Israel from 2005 to 2010.
Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired pneumonia (HAP) (excluding patients with ventilator-associated pneumonia but including ventilated HAP patients) and community-acquired pneumonia in adults. The aim of this study was to evaluate the in vitro antimicrobial activity of ceftobiprole against prevalent Gram-positive and -negative pathogens isolated in Europe, Turkey, and Israel during 2005 through 2010. A total of 60,084 consecutive, nonduplicate isolates from a wide variety of infections were collected from 33 medical centers. Species identification was confirmed, and all isolates were susceptibility tested using reference broth microdilution methods. Ceftobiprole had high activity against methicillin-susceptible Staphylococcus aureus (MSSA) (100.0% susceptible), methicillin-susceptible coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci, and Streptococcus pneumoniae (99.3% susceptible), with MIC90 values of 0.25, 0.12, ≤ 0.06, and 0.5 μg/ml, respectively. Ceftobiprole was active against methicillin-resistant S. aureus (MRSA) (98.3% susceptible) and methicillin-resistant CoNS, having a MIC90 of 2 μg/ml. Ceftobiprole was active against Enterococcus faecalis (MIC50/90, 0.5/4 μg/ml) but not against most Enterococcus faecium isolates. Ceftobiprole was very potent against the majority of Enterobacteriaceae (87.3% susceptible), with >80% inhibited at ≤ 0.12 μg/ml. The potency of ceftobiprole against Pseudomonas aeruginosa (MIC50/90, 2/>8 μg/ml; 64.6% at MIC values of ≤ 4 μg/ml) was similar to that of ceftazidime (MIC50/90, 2/>16 μg/ml; 75.4% susceptible), but limited activity was observed against Acinetobacter spp. and Stenotrophomonas maltophilia. High activity was also observed against all Haemophilus influenzae (MIC90, ≤ 0.06 μg/ml) and Moraxella catarrhalis (MIC50/90, ≤ 0.06/0.25 μg/ml) isolates. Ceftobiprole demonstrated a wide spectrum of antimicrobial activity against this very large longitudinal sample of contemporary pathogens.


A simple means for accurate breast volume determination.
The authors have developed a simple, accurate, and inexpensive device for measuring the volume of the female breast. The concept is based on an adjustable geometrical conical form into which the breast is placed. The breast volume is then easily read from a graduated scale on the device. The device is available in sterile prepackaged form for intraoperative use. The various applications and advantages are described.