The organization of clinical trials for oncology at IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale" Napoli and the impact of the OECI accreditation process.
The Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale Tumori "Fondazione G. Pascale" (INT-Pascale) is the largest Clinical Care and Research Cancer Center in Southern Italy. The mission is prevention, diagnosis, and care of cancer and innovative research in oncology. In 2013, INT-Pascale joined the Organisation of European Cancer Institutes (OECI) accreditation and classification project along with other Italian IRCCS cancer centers. One of the major OECI requirements that a cancer center must fulfill in order to achieve and maintain OECI certification is a strong emphasis in translational and clinical research: increasing the number of patients enrolled in clinical trials, establishing easily accessible databases for operators, and informing all possible stakeholders, including patients. A characterizing theme of INT-Pascale is a strong commitment to clinical experimental studies. In the 2007-2014 period, 440 clinical trials were activated at INT-Pascale; in this period, the number of clinical trials and observational studies has had an increment achieving in 2014, respectively, the share of 60 clinical trials and 35 observational studies activated. Optimization of clinical trials management and dissemination of the clinical research culture at INT-Pascale are main objectives to be achieved through several actions and procedures being implemented as a component of the OECI improvement plan. Participation in the OECI program has represented an important challenge to improve quality and processes related to promoting, prioritizing, and monitoring clinical trials at INT-Pascale.


Non-invasive and invasive imaging of vulnerable coronary plaque.
Vulnerable plaque is characterized by a large necrotic core and an overlying thin fibrous cap. Non-invasive imaging modalities such as computed tomography angiography (CTA) and magnetic resonance imaging (MRI) allow for the assessment of morphological plaque characteristics, while positron emission tomography (PET) enables the detection of metabolic activity within the atherosclerotic lesions. Invasive imaging modalities such as intravascular ultrasound (IVUS), optical-coherence tomography (OCT), and intravascular MRI (IV-MRI) display plaques at a high spatial resolution. Near-infrared spectroscopy (NIRS) allows for the detection of chemical components of atherosclerotic plaques. In this review, we describe state-of-the-art non-invasive and invasive imaging modalities and stress the combination of their advantages to identify vulnerable plaque features.


Prevalence of type II endoleak after elective endovascular aneurysm repair with polytetrafluoroethylene- or polyester-based endografts.
Type II endoleak is the most frequent complication after endovascular abdominal aneurysm repair. Polytetrafluoroethylene and polyester (PE) are the two most commonly used graft materials in endovascular aneurysm repair (EVAR) devices. Biological properties of the material might influence the appearance and persistence of type II endoleak (T2EL). Therefore, the aim of this study was to evaluate potential differences in the prevalence of T2EL after EVAR between polytetrafluoroethylene (PTFE) and PE endografts in patients electively treated for an infrarenal abdominal aortic aneurysm. A single-center, retrospective, observational study was conducted between January 2011 and January 2022. Preoperative, procedural, and follow-up data were derived from electronic health records. Imaging included computed tomography scans, and/or duplex ultrasound examination. The primary end point was the prevalence of T2EL diagnosed within 1 year after EVAR. Secondary end points included the prevalence of T2EL throughout follow-up, early (≤30 days) and late (>30 days) T2EL, the rate of T2EL disappearance during the follow-up period, the prevalence of type I and III endoleak, and T2EL-related reinterventions. Follow-up was available for 394 patients, 245 in the PE and 149 in the PTFE group. The prevalence of T2EL diagnosed within 1 year after endovascular repair was 11.8% in the PE group and 21.5% in the PTFE group (P = .010). There was no significant difference in early (≤30 days) and late (>30 days) T2EL between groups (P = .270 and P = .311). There was no difference in the freedom from endoleak type II reinterventions between groups (P = .877). The prevalence of T2EL after elective EVAR is significantly higher with the use of PTFE-based endografts compared with PE-based endografts. This difference is mostly based on T2EL diagnosed after 30 days of follow-up.


Chemical Cues from Entomopathogenic Nematodes Vary Across Three Species with Different Foraging Strategies, Triggering Different Behavioral Responses in Prey and Competitors.
Chemical cues play important roles in predator-prey interactions. Semiochemicals can aid predator foraging and alert prey organisms to the presence of predators. Previous work suggests that predator traits differentially influence prey behavior, however, empirical data on how prey organisms respond to chemical cues from predator species with different hunting strategies, and how foraging predators react to cues from potential competitors, is lacking. Furthermore, most research in this area has focused on aquatic and aboveground terrestrial systems, while interactions among belowground, soiling-dwelling organisms have received relatively little attention. Here, we assessed how chemical cues from three species of entomopathogenic nematodes (EPNs), each with a different foraging strategy, influenced herbivore (cucumber beetle) and natural enemy (EPN) foraging behavior. We predicted these cues could serve as chemical indicators of increased predation risk, prey availability, or competition. Our findings revealed that foraging cucumber beetle larvae avoided chemical cues from Heterorhabditis bacteriophora (active-foraging cruiser EPNs), but not Steinernema carpocapsae (ambusher EPNs) or Steinernema riobrave (intermediate-foraging EPNs). In contrast, foraging H. bacteriophora EPNs were attracted to cues produced by the two Steinernema species but not conspecific cues. Notably, the three EPN species produced distinct blends of olfactory cues, with only a few semi-conserved compounds across species. These results indicate that a belowground insect herbivore responds differently to chemical cues from different EPN species, with some EPN species avoiding prey detection. Moreover, the active-hunting EPNs were attracted to heterospecific cues, suggesting these cues indicate a greater probability of available prey, rather than strong interspecific competition.


The role of c-fos in cell death and regeneration of retinal ganglion cells.
To investigate the effect of c-fos on apoptotic cell death and regeneration of damaged retinal ganglion cells (RGCs) in tissue culture of retinal explants. Retinas from transgenic mice carrying the exogenous c-fos gene under the control of the interferon (IFN)-alpha/beta inducible Mx-promoter (Mx-c-fos), c-fos-deficient mice, and littermate control mice were dissected and cultured in a three-dimensional collagen gel culture system, followed by an analysis of TdT-dUTP terminal nick-end labeling (TUNEL) staining and measurement of neurites that emerged from explants. Compared with littermate control mice, Mx-c-fos transgenic animals showed a higher ratio of TUNEL positivity in the RGC layer from early in the culture period that correlated with the small number of regenerating neurites. In contrast, the c-fos-null mutated mice showed a still-lower ratio of TUNEL-positive cells. Nevertheless, the number of regenerating neurites was significantly lower in the initial phase, although the drastic increase in density of neurite regeneration was observed in the late period of culture. These findings suggest that c-fos is involved in both apoptotic cell death and regeneration of damaged RGCs. Elucidation of the precise c-fos-mediated cascade involved in RGC apoptosis and regeneration is significant in realizing neuronal survival and regeneration.


NFATc1 balances quiescence and proliferation of skin stem cells.
Quiescent adult stem cells reside in specialized niches where they become activated to proliferate and differentiate during tissue homeostasis and injury. How stem cell quiescence is governed is poorly understood. We report here that NFATc1 is preferentially expressed by hair follicle stem cells in their niche, where its expression is activated by BMP signaling upstream and it acts downstream to transcriptionally repress CDK4 and maintain stem cell quiescence. As stem cells become activated during hair growth, NFATc1 is downregulated, relieving CDK4 repression and activating proliferation. When calcineurin/NFATc1 signaling is suppressed, pharmacologically or via complete or conditional NFATc1 gene ablation, stem cells are activated prematurely, resulting in precocious follicular growth. Our findings may explain why patients receiving cyclosporine A for immunosuppressive therapy display excessive hair growth, and unveil a functional role for calcium-NFATc1-CDK4 circuitry in governing stem cell quiescence.


Reliability and responsiveness of a graduated tuning fork in immune mediated polyneuropathies. The Inflammatory Neuropathy Cause and Treatment (INCAT) Group.
The interobserver and intraobserver reliability of the Rydel-Seiffer (RS) graduated tuning fork was evaluated in 113 patients with a clinically stable immune mediated polyneuropathy (83 patients who had had Guillain-Barré syndrome (GBS) in the past, 22 with a chronic inflammatory demyelinating polyneuropathy (CIDP), and eight with a polyneuropathy associated with a gammopathy of undetermined significance). Additionally, the responsiveness of this instrument was serially investigated in 20 patients with recently diagnosed GBS or CIDP and changing clinical conditions. The measures were done in triplicate at eight different locations in the limbs and the values were compared with the recently published vibration threshold reference values. Good interobserver and intraobserver agreements (quadratic weighted kappa=0.67-0.98) and high responsiveness values (standardised response mean scores>0.8) were demonstrated for the RS tuning fork. These results provide, in addition to literature findings, further evidence for incorporation of this easily applicable instrument in routine neurological examination.


The modern integrated anaesthesia workstation.
Over the years, the conventional anaesthesia machine has evolved into an advanced carestation. The new machines use advanced electronics, software and technology to offer extensive capabilities for ventilation, monitoring, inhaled agent delivery, low-flow anaesthesia and closed-loop anaesthesia. They offer integrated monitoring and recording facilities and seamless integration with anaesthesia information systems. It is possible to deliver tidal volumes accurately and eliminate several hazards associated with the low pressure system and oxygen flush. Appropriate use can result in enhanced safety and ergonomy of anaesthetic delivery and monitoring. However, these workstations have brought in a new set of limitations and potential drawbacks. There are differences in technology and operational principles amongst the new workstations. Understand the principles of operation of these workstations and have a thorough knowledge of the operating manual of the individual machines.


Genetic variation in the mitochondrial 16S rRNA gene of the American dog tick, Dermacentor variabilis (Acari: Ixodidae).
Genetic variation in the mitochondrial (mt) 16S ribosomal RNA (rRNA) gene was examined for the American dog tick, Dermacentor variabilis (Say, 1821). Nine different haplotypes were detected among 369 adult D. variabilis collected from four localities in Canada. There were eight variable nucleotide positions in the 404 bp sequence alignment. Individuals of haplotype 1 occurred at frequency of >75% at all localities. Five haplotypes were detected at only one of the four localities. High haplotype diversity and low nucleotide diversity, combined with significantly negative Fs values for ticks at three localities, suggest a recent population expansion. Genetic differences were found between populations at different localities, but a Mantel regression analysis revealed no association between genetic differences and geographical distances. There was also no association between tick haplotype and the prevalence of the bacterium, Rickettsia montanensis Weiss and Moulder, 1984, in D. variabilis among localities or on opposite sides of Blackstrap Lake (Saskatchewan). The 16S rDNA haplotypes from Canadian populations of D. variabilis formed a clade with those from the eastern and central U.S.A., to the exclusion of D. variabilis from geographically isolated populations in the western U.S.A. Although sample sizes for D. variabilis in the eastern U.S.A. are small, there may be genetic divergence between populations in Canada and those in the eastern U.S.A., which may have implications for studies on the pathogenic agents transmitted by D. variabilis to its hosts.


Interactive 3D Visual Analysis of Atmospheric Fronts.
Atmospheric fronts play a central role in meteorology, as the boundaries between different air masses and as fundamental features of extra-tropical cyclones. They appear in numerous conceptual model depictions of extra-tropical weather systems. Conceptually, fronts are three-dimensional surfaces in space possessing an innate structural complexity, yet in meteorology, both manual and objective identification and depiction have historically focused on the structure in two dimensions. In this work, we -a team of visualization scientists and meteorologists- propose a novel visualization approach to analyze the three-dimensional structure of atmospheric fronts and related physical and dynamical processes. We build upon existing approaches to objectively identify fronts as lines in two dimensions and extend these to obtain frontal surfaces in three dimensions, using the magnitude of temperature change along the gradient of a moist potential temperature field as the primary identifying factor. We introduce the use of normal curves in the temperature gradient field to visualize a frontal zone (i.e., the transitional zone between the air masses) and the distribution of atmospheric variables in such zones. To enable for the first time a statistical analysis of frontal zones, we present a new approach to obtain the volume enclosed by a zone, by classifying grid boxes that intersect with normal curves emanating from a selected front. We introduce our method by means of an idealized numerical simulation and demonstrate its use with two real-world cases using numerical weather prediction data.


Internal ribosome entry site structural motifs conserved among mammalian fibroblast growth factor 1 alternatively spliced mRNAs.
Fibroblast growth factor 1 (FGF-1) is a powerful angiogenic factor whose gene structure contains four promoters, giving rise to a process of alternative splicing resulting in four mRNAs with alternative 5' untranslated regions (5' UTRs). Here we have identified, by using double luciferase bicistronic vectors, the presence of internal ribosome entry sites (IRESs) in the human FGF-1 5' UTRs, particularly in leaders A and C, with distinct activities in mammalian cells. DNA electrotransfer in mouse muscle revealed that the IRES present in the FGF-1 leader A has a high activity in vivo. We have developed a new regulatable TET OFF bicistronic system, which allowed us to rule out the possibility of any cryptic promoter in the FGF-1 leaders. FGF-1 IRESs A and C, which were mapped in fragments of 118 and 103 nucleotides, respectively, are flexible in regard to the position of the initiation codon, making them interesting from a biotechnological point of view. Furthermore, we show that FGF-1 IRESs A of murine and human origins show similar IRES activity profiles. Enzymatic and chemical probing of the FGF-1 IRES A RNA revealed a structural domain conserved among mammals at both the nucleotide sequence and RNA structure levels. The functional role of this structural motif has been demonstrated by point mutagenesis, including compensatory mutations. These data favor an important role of IRESs in the control of FGF-1 expression and provide a new IRES structural motif that could help IRES prediction in 5' UTR databases.


Platelet-dependent modulation of polymorphonuclear leukocyte chemiluminescence.
Human blood platelets decreased luminol-enhanced chemiluminescence of human polymorphonuclear leukocytes (PMNL) stimulated with FMLP or Ca2+-ionophore A23187 by 56 or 47%, respectively. Horseradish peroxidase potentiated the decreasing effect of platelets on A23187-stimulated PMNL (92% inhibition) or reversed inhibition of FMLP-induced chemiluminescence to 94% potentiation, indicating dependence of platelet activity on availability of extracellular peroxidase. Moreover, platelet activity may depend also on the extent of platelet activation, as non-activated platelets (in the presence of FMLP) were found to potentiate PMNL-generated chemiluminescence, while platelets activated with A23187 displayed the opposite effect. Interference of platelets with formation and liberation of superoxide anion was indicated by platelet-modified isoluminol chemiluminescence. Superoxide dismutase with catalase and sodium azide were used, respectively, to differentiate the intracellular and the extracellular part of the chemiluminescence signal. Platelets were found to be capable of modifying both components of chemiluminescence, i.e., oxygen metabolites produced on the plasma membrane as well as on membranes of intracellular granules.


Lrig3 regulates neural crest formation in Xenopus by modulating Fgf and Wnt signaling pathways.
Leucine-rich repeats and immunoglobulin-like domains 3 (Lrig3) was identified by microarray analysis among genes that show differential expression during gastrulation in Xenopus laevis. Lrig3 was expressed in the neural plate and neural crest (NC) at neurula stages, and in NC derivatives and other dorsal structures during tailbud stages. A prominent consequence of the morpholino-induced inhibition of Lrig3 expression was impaired NC formation, as revealed by the suppression of marker genes, including Slug, Sox9 and Foxd3. In the NC induction assay involving Chordin plus Wnt3a-injected animal caps, Lrig3 morpholino inhibited expression of Slug, Sox9 and Foxd3, but not of Pax3 and Zic1. In line with this, Lrig3 knockdown prevented NC marker induction by Pax3 and Zic1, suggesting that Lrig3 acts downstream of these two genes in NC formation. Injection of Lrig3 and Wnt3a led to low-level induction of NC markers and enhanced induction of Fgf3, Fgf4 and Fgf8 in animal caps, suggesting a positive role for Lrig3 in Wnt signaling. Lrig3 could attenuate Fgf signaling in animal caps, did interact with Fgf receptor 1 in cultured cells and, according to context, decreased or increased the induction of NC markers by Fgf. We suggest that Lrig3 functions in NC formation in Xenopus by modulating the Wnt and Fgf signaling pathways.


[Method of treating chronic injuries of the knee joint extensor system].
A new less traumatic method of double alloplasty for longstanding injuries of the extensor system of the knee joint is described which gives a complete reestablishment of the extremity functioning.


A case-control study of pesticides and fetal death due to congenital anomalies.
We examined the association between late fetal death due to congenital anomalies (73 cases, 611 controls) and maternal residential proximity to pesticide applications in ten California counties. A statewide database of all applications of restricted pesticides was linked to maternal address to determine daily exposure status. We examined five pesticide chemical classes. The odds ratios from logistic regression models, adjusted for maternal age and county, showed a consistent pattern with respect to timing of exposure; the largest risks for fetal death due to congenital anomalies were from pesticide exposure during the 3rd-8th weeks of pregnancy. For exposure either in the square mile of the maternal residence or in one of the adjacent 8 square miles, odds ratios ranged from 1.4 (95% confidence interval = 0.8-2.4) for phosphates, carbamates, and endocrine disruptors to 2.2 (95% confidence interval = 1.3-3.9) for halogenated hydrocarbons. Similar odds ratios were observed when a more restrictive definition of nonexposure (not exposed to any of the five pesticide classes during the 3rd-8th weeks of pregnancy) was used. The odds ratios for all pesticide classes increased when exposure occurred within the same square mile of maternal residence.


miR-106b modulates cancer stem cell characteristics through TGF-β/Smad signaling in CD44-positive gastric cancer cells.
Cancer stem cells have the capacity to form new tumors and are thus considered to be a cause of metastasis and tumor recurrence. However, many of the mechanisms determining cancer stem cell characteristics are still unknown. MicroRNAs (miRNAs) are possible modulators of cancer stem cell generation and may be involved in the retention of cancer stem cell characteristics. The aim of this study was to examine the miRNA expression profiles regulating the cancer stem-like cell characteristics in gastric cancer. We sorted gastric cancer stem-like cells using the stem cell marker CD44 by fluorescence-activated cell sorting. CD44(+) cells formed more and larger spheres compared with CD44(-) cells. Cancer stem cell markers were overexpressed in CD44(+) cells. CD44(+) cells showed increased expression of mesenchymal cell markers, whereas epithelial markers were downregulated. In miRNA microarray, the miR-106b family comprising miR-106b, miR-93, and miR-25 was significantly upregulated in CD44(+) cells than in CD44(-) cells. Smad7, which inhibits transforming growth factor-β (TGF-β)/Smad signaling as a target of the miR-106b family, was downregulated in CD44(+) cells. Furthermore, expression of TGF-β/Smad signal molecules was activated in CD44(+) cells, in accordance with the action of the miR-106b family. Inhibition of miR-106b showed suppression of the TGF-β/Smad signaling pathway and decreased self-renewal capacity and cell invasiveness. Our study suggests that CD44(+) gastric cancer cells show cancer stem cell properties with epithelial-mesenchymal transition (EMT). Increased miR-106b family expression regulated cancer stem-like cell properties, particularly EMT characteristics, through the TGF-β/Smad signaling pathway in CD44(+) stem-like cells. Taken together, these results indicate that targeting miR-106b may be an effective form of cancer therapy in gastric cancer through the modulation of cancer stem cell characteristics.


Formation and function of sperm tail structures in association with sperm motility defects.
Male infertility is an increasing problem partly due to inherited genetic variations. Mutations in genes involved in formation of the sperm tail cause motility defects and thus male infertility. Therefore, it is crucial to understand the protein networks required for sperm differentiation. Sperm motility is produced through activation of the sperm flagellum, which core structure, the axoneme, resembles motile cilia. In addition to this, cytoskeletal axonemal structure sperm tail motility requires various accessory structures. These structures are important for the integrity of the long tail, sperm capacitation, and generation of energy during sperm passage to fertilize the oocyte. This review discusses the current knowledge of mechanisms required for formation of the sperm tail structures and their effect on fertility. The recent research based on animal models and genetic variants in relation to sperm tail formation and function provides insights into the events leading to fertile sperm production. Here we compile a view of proteins involved in sperm tail development and summarize the current knowledge of factors contributing to reduced sperm motility, asthenozoospermia, underline the mechanisms which require further research, and discuss related clinical aspects on human male infertility.


[Dental injury in anaesthesiology--risk group and liability].
Dental injury is one of the most anaesthesia-related complications. It can cause a patient's functional, esthetic, financial, and emotional annoyance. The incidence of dental injury is said to range from 1:6000 to 1:1000. The upper incisors are by far the most often injured teeth. Removable dentures should be taken out prior to anaesthesia. A tooth guard can be used as a prophylactic measure. However, with that tracheal intubation can be complicated because of the reduced view at the epiglottis and the vocal cords. If a dental injury occurred, the patient should be seen by a dentist as soon as possible to undergo appropriate treatment with no delay.


[Efficiency of complex therapy in the treatment of non-alcoholic steatohepatitis and prevention of liver fibrosis].
The article describes a positive effect of adjuvant therapy (diet therapy, tsitrarginin, trental) on regression of fatty liver disease, inflammation and prevention of liver fibrosis through influence on the system of L-arginine-NO, exchange of collagen proteins, anti-inflammatory cytokines in patients with steatohepatitis and second type diabetes mellitus.


Clinical Value of Multiparametric Whole-Body Magnetic Resonance Imaging over Whole-Spine Magnetic Resonance Imaging in Patients with Neurofibromatosis Type I.
To determine the clinical value of multiparametric whole-body (WBMRI) over whole-spine magnetic resonance imaging (WSMRI) in patients with neurofibromatosis type 1 (NF1). A consecutive series of 30 patients with known NF1 underwent WBMRI screening using anatomic, diffusion, and contrast imaging over a 30-month period. Thirteen of 30 patients also had WSMRI. Tumors were classified per location and morphology and were software segmented to determine numbers and volumes. Extra tumor burden detected by WBMRI was assessed. The comparison was made between WBMRI and WSMRI in 13 patients who had both types of scans. Enhancement characteristics were noted and 2 readers recorded apparent diffusion coefficient (ADC) in 30 patients with WBMRI scans. Interobserver performance was assessed using intraclass correlations. A 2-sample test was used for testing mean differences between tumors. The age of 30 patients with WBMRI and 13 patients with WSMRI were 39.4 ± 14.4 and 41.54 ± 10.79 years (mean ± standard deviation) and male/female ratio was 1:1.73 and 1:2.25, respectively. Only 1 patient was found to have a heterogeneously enhancing lumbar paraspinal malignant peripheral nerve sheath tumor, seen on both WBMRI and WSMRI. The additional total number of tumors on WBMRI was 2766 and 2602 tumors were missed on WSMRI. The volume of tumors was 16,053 cm3 and 15,614 cm3 of tumor burden was incrementally detected on WBMRI. Mean ADC of superficial tumors was significantly lower than that of deep tumors (1.93 ± 0.39 × 10-3 mm2/second and 2.26 ± 0.56 × 10-3 mm2/second, respectively; P = 0.009), whereas no ADC differences were seen in plexiform versus discrete tumors (P = 0.64). Interobserver performance for ADC was excellent (intraclass correlation, 0.84). Multiparametric WBMRI provides superior determination of tumor burden and should be considered as a preferred method for evaluation of patients with NF1.


Golgi ribbon disassembly during mitosis, differentiation and disease progression.
The Golgi apparatus is tightly integrated into the cellular system where it plays essential roles required for a variety of cellular processes. Its vital functions include not only processing and sorting of proteins and lipids, but also serving as a signaling hub and a microtubule-organizing center. Golgi stacks in mammalian cells are interconnected into a compact ribbon in the perinuclear region. However, the ribbon can undergo distinct disassembly processes that reflect the cellular state or environmental demands and stress. For instance, its most dramatic change takes place in mitosis when the ribbon is efficiently disassembled into vesicles through a combination of ribbon unlinking, cisternal unstacking and vesiculation. Furthermore, the ribbon can also be detached and positioned at specific cellular locations to gain additional functionalities during differentiation, or fragmented to different degrees along disease progression or upon cell death. Here, we describe the major morphological alterations of Golgi ribbon disassembly under physiological and pathological conditions and discuss the underlying mechanisms that drive these changes.


EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.
EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.


(An overview of) Synergistic reconstruction for multimodality/multichannel imaging methods.
Imaging is omnipresent in modern society with imaging devices based on a zoo of physical principles, probing a specimen across different wavelengths, energies and time. Recent years have seen a change in the imaging landscape with more and more imaging devices combining that which previously was used separately. Motivated by these hardware developments, an ever increasing set of mathematical ideas is appearing regarding how data from different imaging modalities or channels can be synergistically combined in the image reconstruction process, exploiting structural and/or functional correlations between the multiple images. Here we review these developments, give pointers to important challenges and provide an outlook as to how the field may develop in the forthcoming years. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 1'.


Multilevel Mapping of Sexual Dimorphism in Intrinsic Functional Brain Networks.
Differences in cognitive performance between males and females are well-described, most commonly in certain spatial and language tasks. Sex-related differences in cognition are relevant to the study of the neurotypical brain and to neuropsychiatric disorders, which exhibit prominent disparities in the incidence, prevalence and severity of symptoms between men and women. While structural dimorphism in the human brain is well-described, controversy exists regarding the existence and degree of sex-related differences in brain function. We analyzed resting-state functional MRI from 650 neurotypical young adults matched for age and sex to determine the degree of sexual dimorphism present in intrinsic functional networks. Multilevel modeling was pursued to create 8-, 24-, and 51-network models of whole-brain data to quantify sex-related effects in network activity with increasing resolution. We determined that sexual dimorphism is present in the majority of intrinsic brain networks and affects ∼0.5-2% of brain locations surveyed in the three whole-brain network models. It is particularly common in task-positive control networks and is pervasive among default mode networks. The size of sex-related effects varied by network but can be moderate or even large in size. Female > male effects were on average larger, but male > female effects spread across greater network territory. Using a novel methodology, we mapped dimorphic locations to meta-analytic association test maps derived from task fMRI, demonstrating that the neurocognitive footprint of intrinsic neural correlates is much larger in males. All results were replicated in a motion-matched sub-sample. Our findings argue that sex is an important biological variable in human brain function and suggest that observed differences in neurocognitive performance have identifiable intrinsic neural correlates.


Pneumonia in a heart-lung recipient after airway stent placement.
Recently, the self-expandable metallic stent (SEMS) has been added to our armamentarium. However, in the case presented here placement of the self-expandable metallic stent had catastrophic consequences 11 months later. We are of the opinion that airway stent placement may result in severe complications including clinical infection, and if it must be deployed, the proper size and positioning of the stent is always of the utmost importance.


Pediatric Central Nervous System Demyelinating Diseases.
This article provides an up-to-date summary of the categories, diagnosis, and management of pediatric demyelinating disorders. Understanding of the diverse spectrum of pediatric demyelinating disorders, including monophasic and multiphasic forms, has improved. Pediatric multiple sclerosis (MS) is the most common demyelinating disorder in children, and recent genetic and environmental risk research has clarified that pediatric MS is on the same continuum of disease as adult MS. Recent advances in the treatment of pediatric MS include clinical trials leading to regulatory agency-approved treatments. The identification of myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies in children has been a major advance, allowing for appropriate treatment and management of these syndromes. Antibody testing is now helping to define subtypes of pediatric demyelinating disorders, including myelin oligodendrocyte glycoprotein-seropositive and aquaporin-4-seropositive cases that are distinct from pediatric MS. Treatments for pediatric MS are being evaluated in clinical trials.


Sudden bilateral hearing loss after spinal anaesthesia.
Spinal anaesthesia is one of the most widely used regional anaesthesia techniques. Sudden bilateral hearing loss following spinal anaesthesia has only been reported in a few cases. This paper reports the case of a 50-year-old woman who developed sudden bilateral hearing loss following spinal anaesthesia for hallux valgus orthopaedic surgery. This is followed by a literature review. The patient's hearing improved almost completely on the morning of the 3rd day following surgery. No recurrence of hearing loss, tinnitus or vertigo was reported during the six-month follow-up period. Some complications regarding hearing may emerge after spinal anaesthesia. The possibility of hearing loss after spinal anaesthesia should be taken into consideration. Complaints such as hearing loss, tinnitus or vertigo should be taken seriously when reported, and the patient should be referred to an ENT clinic. This will ensure early diagnosis and treatment.


Performance of a Web-based Method for Generating Synoptic Reports.
The College of American Pathologists (CAP) requires synoptic reporting of all tumor excisions. To compare the performance of different methods of generating synoptic reports. Completeness, amendment rates, rate of timely ordering of ancillary studies (KRAS in T4/N1 colon carcinoma), and structured data file extraction were compared for four different synoptic report generating methods. Use of the printed tumor protocols directly from the CAP website had the lowest completeness (84%) and highest amendment (1.8%) rates. Reformatting these protocols was associated with higher completeness (94%, P < 0.001) and reduced amendment (1%, P = 0.20) rates. Extraction into a structured data file was successful 93% of the time. Word-based macros improved completeness (98% vs. 94%, P < 0.001) but not amendment rates (1.5%). KRAS was ordered before sign out 89% of the time. In contrast, a web-based product with a reminder flag when items were missing, an embedded flag for data extraction, and a reminder to order KRAS when appropriate resulted in improved completeness (100%, P = 0.005), amendment rates (0.3%, P = 0.03), KRAS ordering before sign out (100%, P = 0.23), and structured data extraction (100%, P < 0.001) without reducing the speed (P = 0.34) or accuracy (P = 1.00) of data extraction by the reader. Completeness, amendment rates, ancillary test ordering rates, and data extraction rates vary significantly with the method used to construct the synoptic report. A web-based method compares favorably with all other methods examined and does not reduce reader usability.


Pathogenicity evaluation of variants of uncertain significance at exon-intron junction by splicing assay in patients with Mowat-Wilson syndrome.
High-throughput sequencing has identified vast numbers of variants in genetic disorders. However, the significance of variants at the exon-intron junction remains controversial. Even though most cases of Mowat-Wilson syndrome (MOWS) are caused by heterozygous loss-of-function variants in ZEB2, the pathogenicity of variants at exon-intron junction is often indeterminable. We identified four intronic variants in 5/173 patients with clinical suspicion for MOWS, and evaluated their pathogenicity by in vitro analyses. The minigene analysis showed that c.73+2T>G caused most of the transcripts skipping exon 2, while c.916+6T>G led to partial skipping of exon 7. No splicing abnormalities were detected in both c.917-21T>C and c.3067+6A>T. The minigene analysis reproduced the splicing observed in the blood cells of the patient with c.73+2T>G. The degree of the exon skipping was concordant with the severity of MOWS; while the patient with c.73+2T>G was typical MOWS, the patient with c.916+6T>G showed milder phenotype which has been seldom reported. Our results demonstrate that mRNA splicing assays using the minigenes are valuable for determining the clinical significance of intronic variants in patients with not only MOWS but also other genetic diseases with splicing aberrations and may explain atypical or milder cases, such as the current patient.


A family with a high incidence of cancer.
Five generations of a family have been studied. A high number have been found to have had cancer. Although the cancers have been mainly colon and rectum they have not been confined to the large bowel. Nineteen members of the family are under the age of 20. The management of these members is discussed.


Delayed solidification of soft glasses: new experiments, and a theoretical challenge.
When subjected to large amplitude oscillatory shear stress, aqueous Laponite suspensions show an abrupt solidification transition after a long delay time t(c). We measure the dependence of t(c) on stress amplitude, frequency, and on the age-dependent initial loss modulus. At first sight our observations appear quantitatively consistent with a simple soft-glassy rheology (SGR)-type model, in which barrier crossings by mesoscopic elements are purely strain-induced. For a given strain amplitude gamma0 each element can be classified as fluid or solid according to whether its local yield strain exceeds gamma0. Each cycle, the barrier heights E of yielded elements are reassigned according to a fixed prior distribution rho(E): this fixes the per-cycle probability R(gamma0) of a fluid elements becoming solid. As the fraction of solid elements builds up, gamma0 falls (at constant stress amplitude), so R(gamma0) increases. This positive feedback accounts for the sudden solidification after a long delay. The model thus appears to directly link macroscopic rheology with mesoscopic barrier height statistics: within its precepts, our data point towards a power law for rho(E) rather than the exponential form usually assumed in SGR. However, despite this apparent success, closer investigation shows that the assumptions of the model cannot be reconciled with the extremely large strain amplitudes arising in our experiments. The quantitative explanation of delayed solidification in Laponite therefore remains an open theoretical challenge.


Economic implications of evidence-based caries prevention in pediatric dental practice: a model-based approach.
This paper presents an economic model which can be used to assess the potential implications of evidence-based caries prevention in pediatric dental practice. Assessment of the evidence indicated that most children in the United States were likely to experience dental caries, though the severity of the disease would be minimal in most of them. Based on the evidence, it was concluded that annual recall examination and topical fluoride application would suffice as the norm for caries prevention. A model was developed to estimate the extent and cost of caries prevention in a traditional and an evidence-based pediatric dental practice. The model showed that evidence-based caries prevention resulted in a one-third decline in the number of recall examination visits provided, while the ensuing patient revenues from recall appointments declined by two-thirds in a calendar year. Evidence-based caries prevention will likely result in a significant decline in preventive services revenues and create additional capacity in pediatric dental practices. This economic impact will likely be absorbed by the current undersupply of pediatric dentists and by the reformulation of practice revenue streams.


Long-term durability of immune responses after hepatitis A vaccination among HIV-infected adults.
Vaccination provides long-term immunity to hepatitis A virus (HAV) among the general population, but there are no such data regarding vaccine durability among human immunodeficiency virus (HIV)-infected adults. We retrospectively studied HIV-infected adults who had received 2 doses of HAV vaccine. We analyzed blood specimens taken at 1 year, 3 years, and, when available, 6-10 years postvaccination. HAV immunoglobulin G (IgG) values of ≥10 mIU/mL were considered seropositive. We evaluated specimens from 130 HIV-infected adults with a median age of 35 years and a median CD4 cell count of 461 cells/mm(3) at or before time of vaccination. Of these, 49% had an HIV RNA load <1000 copies/mL. Initial vaccine responses were achieved in 89% of HIV-infected adults (95% confidence interval [CI], 83%-94%), compared with 100% (95% CI, 99%-100%) of historical HIV-uninfected adults. Among initial HIV-infected responders with available specimens, 90% (104 of 116; 95% CI, 83%-95%) remained seropositive at 3 years and 85% (63 of 74; 95% CI, 75%-92%) at 6-10 years. Geometric mean concentrations (GMCs) among HIV-infected adults were 154, 111, and 64 mIU/mL at 1, 3, and 6-10 years, respectively, compared with 1734, 687, and 684 mIU/mL among HIV-uninfected persons. Higher GMCs over time among HIV-infected adults were associated with lower log(10) HIV RNA levels (β = -.12, P = .04). Most adults with well-controlled HIV infections had durable seropositive responses up to 6-10 years after HAV vaccination. Suppressed HIV RNA levels are associated with durable HAV responses.


Benchmarking pKa prediction methods for Lys115 in acetoacetate decarboxylase.
Three different pKa prediction methods were used to calculate the pKa of Lys115 in acetoacetate decarboxylase (AADase): the empirical method PROPKA, the multiconformation continuum electrostatics (MCCE) method, and the molecular dynamics/thermodynamic integration (MD/TI) method with implicit solvent. As expected, accurate pKa prediction of Lys115 depends on the protonation patterns of other ionizable groups, especially the nearby Glu76. However, since the prediction methods do not explicitly sample the protonation patterns of nearby residues, this must be done manually. When Glu76 is deprotonated, all three methods give an incorrect pKa value for Lys115. If protonated, Glu76 is used in an MD/TI calculation, the pKa of Lys115 is predicted to be 5.3, which agrees well with the experimental value of 5.9. This result agrees with previous site-directed mutagenesis studies, where the mutation of Glu76 (negative charge when deprotonated) to Gln (neutral) causes no change in Km, suggesting that Glu76 has no effect on the pKa shift of Lys115. Thus, we postulate that the pKa of Glu76 is also shifted so that Glu76 is protonated (neutral) in AADase. Graphical abstract Simulated abundances of protonated species as pH is varied.


The Cretaceous Neornithine record and new Vegaviidae specimens from the López de Bertodano Formation (Upper Maastrichthian) of Vega Island, Antarctic Peninsula.
A worldwide revision of the Cretaceous record of Neornithes (crown birds) revealed that unambiguous neornithine taxa are extremely scarce, with only a few showing diagnostic features to be confidently assigned to that group. Here we report two new neornithine specimens from Vega Island (López de Bertodano Formation). The first is a synsacrum (MN 7832-V) that shows a complex pattern of transversal diverticula intercepting the canalis synsacri, as in extant neornithines. Micro-CT scanning revealed a camerate pattern of trabeculae typical of neornithines. It further shows the oldest occurrence of lumbosacral canals in Neornithes, which are related to a balance sensing system acting in the control of walking and perching. The second specimen (MN 7833-V) is a distal portion of a tarsometatarsus sharing with Vegavis iaai a straight apical border of the crista plantaris lateralis. Osteohistologically the tarsometatarsus shows a thick and highly vascularized cortex that lacks any growth marks, resembling Polarornis gregorii. The cortex is osteosclerotic as in other extinct and extant diving neornithines. These new specimens increase the occurrences of the Cretaceous avian material recovered from the Upper Cretaceous strata of the James Ross Sub-Basin, suggesting that a Vegaviidae-dominated avian assemblage was present in the Antarctic Peninsula during the upper Maastrichtian.


Parallel mapping of genotypes to phenotypes contributing to overall biological fitness.
Laboratory selection is a powerful approach for engineering new traits in metabolic engineering applications. This approach is limited because determining the genetic basis of improved strains can be difficult using conventional methods. We have recently reported a new method that enables the measurement of fitness for all clones contained within comprehensive genomic libraries, thus enabling the genome-scale mapping of fitness altering genes. Here, we demonstrate a strategy for relating these measurements to the individual phenotypes selected for in a particular environment. We first provide a mathematical framework for decomposing fitness into selectable phenotypes. We then employed this framework to predict that single-batch selections would enrich primarily for library clones with increased growth rate, serial-batch would enrich for a broad collection of clones enhanced via a combination of increased growth rate and/or reduced lag times, and that overlap among selected clones would be minimal. We used the SCalar Analysis of Library Enrichments (SCALEs) method to test these predictions. We mapped all genomic regions for which increased copy number conferred a selective advantage to Escherichia coli when cultured via single- or serial-batch in the presence of 1-naphthol. We identified a surprisingly large collection (163 total) of tolerance regions, including all previously identified solvent tolerance genes in E. coli. We show that the majority of the identified regions were unique to the different selection strategies examined and that such differences were indeed due to differences among enriched clones in growth rate and lag times over the solvent concentrations examined. The combination of a framework for decomposing overall fitness into selectable phenotypes along with a genome-scale method for mapping genes to such phenotypes lays the groundwork for improving the rational design of laboratory selections.


Virus-induced cell motility.
Many viruses induce profound changes in cell metabolism and function. Here we show that vaccinia virus induces two distinct forms of cell movement. Virus-induced cell migration was demonstrated by an in vitro wound healing assay in which infected cells migrated independently into the wound area while uninfected cells remained relatively static. Time-lapse microscopy showed that the maximal rate of migration occurred between 9 and 12 h postinfection. Virus-induced cell migration was inhibited by preinactivation of viral particles with trioxsalen and UV light or by the addition of cycloheximide but not by addition of cytosine arabinoside or rifampin. The expression of early viral genes is therefore necessary and sufficient to induce cell migration. Following migration, infected cells developed projections up to 160 microm in length which had growth-cone-like structures and were frequently branched. Time-lapse video microscopy showed that these projections were formed by extension and condensation of lamellipodia from the cell body. Formation of extensions was dependent on late gene expression but not the production of intracellular enveloped (IEV) particles. The requirements for virus-induced cell migration and for the formation of extensions therefore differ from each other and are distinct from the polymerization of actin tails on IEV particles. These data show that poxviruses encode genes which control different aspects of cell motility and thus represent a useful model system to study and dissect cell movement.


Physical activity and diabetes: an application of the theory of planned behaviour to explain physical activity for Type 1 and Type 2 diabetes in an adult population sample.
Physical activity (PA) plays a key role in the management of Type 1 (T1D) and Type 2 diabetes (T2D) but there are few theory-based, effective programs to promote PA for individuals with diabetes. The purpose of this study was to investigate the utility of the Theory of Planned Behaviour (TPB) in understanding PA in an adult population with T1D or T2D. A total of 2311 individuals (691 T1D; 1614 T2D) completed self-report TPB constructs of attitude, subjective norms, perceived behavioural control (PBC), intention and PA at baseline and 1717 (524 T1D; 1123 T2D) completed the PA measure again at 6-month follow-up. Multi-group Structural Equation Modelling was conducted to: (1) test the fit of the TPB structure (2) determine the TPB structural invariance between the two types of diabetes and (3) to examine the explained variances in PA and compare the strength of associations of the TPB constructs in the two types of diabetes. The TPB constructs explained > or =40% of the variance in intentions for both diabetes groups. In cross-sectional models, the TPB accounted for 23 and 19% of the variance in PA for T1D and T2D, respectively. In prospective models, the TPB explained 13 and 8% of the variance in PA for T1D and T2D, respectively. When adjusting for past PA behaviour, the impact of PBC and intention on behaviour was reduced in both groups. The findings provide evidence for the utility of the TPB for the design of PA promotion interventions for adults with either T1D or T2D.


Good advice for endothelial cells: Get in line, relax tension, and go with the flow.
Endothelial cells (ECs) are continuously subjected to fluid wall shear stress (WSS) and cyclic strain caused by pulsatile blood flow and pressure. It is well established that these hemodynamic forces each play important roles in vascular disease, but their combined effects are not well understood. ECs remodel in response to both WSS and cyclic strain to align along the vessel axis, but in areas prone to atherogenesis, such an alignment is absent. In this perspective, experimental and clinical findings will be reviewed, which have revealed the characteristics of WSS and cyclic strain, which are associated with atherosclerosis, spanning studies on whole blood vessels to individual cells to mechanosensing molecules. Examples are described regarding the use of computational modeling to elucidate the mechanisms by which EC alignment contributes to mechanical homeostasis. Finally, the need to move toward an integrated understanding of how hemodynamic forces influence EC mechanotransduction is presented, which holds the potential to move our currently fragmented understanding to a true appreciation of the role of mechanical stimuli in atherosclerosis.


Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5.
The neuronal ceroid lipofuscinoses (NCLs), also referred to as Batten disease, are a group of neurodegenerative disorders characterised by the accumulation of an autofluorescent lipopigment in many cell types. Different NCL types are distinguished according to age of onset, clinical phenotype, ultrastructural characterisation of the storage material, and chromosomal location of the disease gene. At least eight genes underlie the NCLs, of which four have been isolated and mutations characterised: CLN1, CLN2, CLN3, CLN5. Two of these genes encode lysosomal enzymes, and two encode transmembrane proteins, at least one of which is likely to be in the lysosomal membrane. The basic defect in the NCLs appears to be associated with lysosomal function.


Three-dimensional (3D) ultrasound--a useful imaging technique in the assessment of neonatal brain.
Clinical application of ultrasound began about fifty years ago. From one-dimensional A-mode, through two-dimensional real time and Doppler examinations, a new era in clinical ultrasonography then began in the late eighties. Development of computer technology enabled introduction of 3D ultrasonography into clinical practice. In obstetrics ultrasound revolutionized fetal follow-up, but it was as important for the detection of intracranial pathology during the neonatal period and infancy. Two-dimensional real time ultrasonography was [table: see text] an exciting method that changed our understanding of the prevalence and pathophysiology of brain pathology in premature and term infants. Will application of 3D ultrasonography bring any substantial improvement to neuroimaging diagnostics in the newborn period? This article attempts to find the answer to this question, despite the limitations set by the short period of application of 3D neurosonography in neonates. The advantages of 3D brain ultrasonography application in neonates are: quicker and observer independent data acquisition, the possibility of off-line data analysis, projection of 3D data on a 2D plane with volumetric, color and power Doppler studies. Unavailability of equipment is the main reason why 3D ultrasonography was performed in only half of the newborns in whom it was indicated. Cost of equipment prevents introduction of 3D as a standard diagnostic procedure in neonates, although its diagnostic value is indisputable.


Improving recognition of psoriatic arthritis.
Psoriatic arthritis (PsA) is a common form of inflammatory arthritis but is underdiagnosed. Psoriasis affects over 1.5% of the UK population. Around 15% of these patients will be diagnosed with PsA, but up to 40% may have evidence of arthritis if reviewed thoroughly. PsA can be difficult to diagnose as patients present with a variety of different patterns of arthritis. Most patients with PsA have relatively mild skin psoriasis, but some have more significant disease. Only 10-20% develop arthritis before their skin disease. Many patients have mild skin psoriasis that they are unaware of, or have not had diagnosed. Joint involvement is far more variable in PsA, compared with rheumatoid arthritis, and patients may present with: monoarthritis; oligoarthritis; involvement of the distal interphalangeal joints; a rheumatoid arthritis-like picture with multiple joints involved including the small joints in the hand or axial disease producing symptoms similar to ankylosing spondylitis. Features such as dactylitis (uniform sausage-like swelling of the whole digit either finger or toe) and enthesitis (inflammation at the sites of muscle or tendon attachment to bone) may also help diagnose PsA. Skin disease is present in the majority of patients although not all. Hidden areas for psoriasis include: behind the ears; at the top of the natal cleft and around the umbilicus. Larger joints, particularly the knees, can develop very big effusions causing obvious swelling. Areas to test for enthesitis should include the Achilles tendon, plantar fascia, costochondral joints and the elbow. Patients with suspected PsA should be referred promptly to a rheumatologist for further assessment and treatment. Diagnosis of PsA can be made on clinical grounds but blood tests and radiographs are performed routinely to aid diagnosis. Initial therapy for PsA should include NSAIDs to ease pain and stiffness. Local injections of corticosteroids are recommended for peripheral arthritis (given IA) and dactylitis (usually by injection into the flexor tendon or adjacent joints). DMARDs are routinely used to treat all aspects of psoriatic disease, except spinal disease, and prescribing should be initiated by a specialist.


Decoupled genomic elements and the evolution of partner quality in nitrogen-fixing rhizobia.
Understanding how mutualisms evolve in response to a changing environment will be critical for predicting the long-term impacts of global changes, such as increased N (nitrogen) deposition. Bacterial mutualists in particular might evolve quickly, thanks to short generation times and the potential for independent evolution of plasmids through recombination and/or HGT (horizontal gene transfer). In a previous work using the legume/rhizobia mutualism, we demonstrated that long-term nitrogen fertilization caused the evolution of less-mutualistic rhizobia. Here, we use our 63 previously isolated rhizobium strains in comparative phylogenetic and quantitative genetic analyses to determine the degree to which variation in partner quality is attributable to phylogenetic relationships among strains versus recent genetic changes in response to N fertilization. We find evidence of distinct evolutionary relationships between chromosomal and pSym genes, and broad similarity between pSym genes. We also find that nifD has a unique evolutionary history that explains much of the variation in partner quality, and suggest MoFe subunit interaction sites in the evolution of less-mutualistic rhizobia. These results provide insight into the mechanisms behind the evolutionary response of rhizobia to long-term N fertilization, and we discuss the implications of our results for the evolution of the mutualism.


[Radiological examination of cerebral circulation in cerebrovascular disorders].
The authors provide the results of radiological examinations of cerebral circulation in 215 patients aged 16 to 67 years with different periods of cervical osteochondrosis. The intensity of hemispheric hemocirculation derangement depends on the stage of osteochondrosis. At the same time cerebral circulation disorders running their course by the type of transitory disturbances are not specific for the given group of patients and can also be seen in patients suffering from other diseases of the brain.


Issues in nursing care of pregnant patients with cancer.
The co-occurrence of pregnancy and cancer raises numerous psychological issues for the pregnant woman and her family. It also poses a variety of therapeutic dilemmas for the health care professionals involved in her care. Issues such as abortion versus continuing the pregnancy must be resolved quickly, and the selection and timing of chemotherapy, radiation, or surgery are affected by the pregnancy. Despite these problems, there is hope for a good outcome in many pregnancies. The role of nursing and how nurses can enhance the experience is discussed.


The efficacy of fermented foods in the treatment and management of diarrhoeal diseases: A systematic review and meta-analysis.
Background: Diarrhoeal disease is a major cause of global infant mortality, and compromises the ability of many countries with respect to achieving sustainable development goals. The WHO's recommendation of Oral Rehydration Solution (ORS) and zinc in the management of this disease, may not be readily available. Consideration and assessment of cultural practices in its management has been an area of increased interest over the last decade. Aim: This study aims to systematically evaluate efficacy of the consumption of traditional fermented foods as functional products for the treatment and management of diarrhoea. Methods: Following PRISMA guidelines, a systematic review was conducted of electronic databases (Cochrane Library, Ovid Medline and Pubmed) databases with no restrictions on language and publication date for RCTs that investigated the effect of consumption of fermented foods on the treatment of diarrhoea in children under five years of age. Results: Seven RCTs were included. Meta-analysis showed that compared to control, consumption of fermented foods significantly reduced mean duration of diarrhoea, -0.61 days; (95% CI, -1.04, -0.18); length of hospitalization, -0.35 days (95% CI, -0.69, -0.02); but not mean daily frequency of stool -2.00 (95% CI,-7.03, 3.04). Conclusion: Limited available evidence suggests that consumption of fermented foods may help reduce duration and severity of symptoms as a treatment of diarrhoea. More high quality research needs to be undertaken to investigate the efficacy of fermented food as an effective alternative to ORS as a potential WHO recommendation for management of diarrhoeal disease.


Quality of life terminology included in package inserts for US approved medications.
To identify and review prescription drugs approved in the US containing quality of life (QoL) terminology within the package inserts (PIs). The electronic Physician Desk Reference (PDR) was searched for the terminology 'Quality of Life' or 'QoL' as of December 2000. Summary basis of approvals (SBAs) served as the primary data sources were retrieved. The two categories evaluated within the SBAs were QoL components (year submitted, trials, efficacy, statistics, type of submission) and QoL instruments utilized within clinical studies. Eighteen medications comprising 20 indications with QoL claims were documented in the PIs. The first approved QoL claim was submitted in 1989 and the most recent was in 1998. Eight (40%) of the drug indications had QoL measures included in two trials. One quarter of the PI listings used QoL measures as primary efficacy endpoints. Many sponsors provided detailed information on the types or categories of QoL data collected. Many drug development programs incorporate QoL measures into clinical studies however only a few are accepted into the PI. Despite this study finding, the increased interest in assessing the value and full impact of new therapies has led to greater inclusion of all types of patient assessments in clinical trials.


Transgenic myocardial overexpression of prokineticin receptor-2 (GPR73b) induces hypertrophy and capillary vessel leakage.
Prokineticins are small secreted bioactive molecules. They exert their biological activity by binding to two G protein-coupled receptors. Previously, we have shown that the overexpression of prokineticin receptor-1 (PKR1) in transgenic (TG) mouse hearts induced neovascularization. Since PKR1 and PKR2 are 85% identical and expressed in cardiovascular tissues, we hypothesized that PKR2 may also contribute to cardiomyocyte growth and vascularization. We have generated TG mice overexpressing PKR2 in cardiomyocytes. TG mice exhibit increased hypertrophic gene expression and heart-to-body weight ratio accompanied by an increased length of cardiomyocytes at the age of 12 weeks. Increased left ventricular end-systolic and diastolic diameters without cardiac dysfunction at the age of 24 weeks indicate that TG mice have an eccentric hypertrophy with compensated cardiac function. Quantitative morphological analysis showed that TG hearts have a normal microvessel density and number of branch points. However, they exhibit increased abnormal endothelial cell shape and ultrastructure, changed cellular distribution of a tight junction protein zona occludens-1 (ZO-1), and vascular leakage in heart without a rise of angiogenic factor levels at early and late age. The application of media conditioned by H9c2 cardioblast cells overexpressing PKR2 significantly induced impaired ZO-1 localization in H5V endothelial cells, mimicking the TG model. These findings provide the first genetic evidence that cardiomyocyte PKR2 signalling leads to eccentric hypertrophy in an autocrine regulation and impaired endothelial integrity in a paracrine regulation without inducing angiogenesis. These TG mice may provide a new genetic model for heart diseases.


Phylogeny and historical biogeography of leafhopper subfamily Evacanthinae (Hemiptera: Cicadellidae) based on morphological and molecular data.
Phylogenetic relationships among major lineages of the Evacanthinae, a highly diverse leafhopper subfamily distributed worldwide, were explored by analysing a dataset of 100 discrete morphological characters and DNA sequence data from five gene regions. Sixty-seven taxa representing all evacanthine tribes and all regional faunas, and fourteen putative outgroup taxa were included. Maximum-likelihood and Bayesian analyses yielded similar tree topologies that were well resolved with strong support for the monophyly of Evacanthinae and its four previously included tribes, but indicated that Draconirvana Dietrich, was incorrectly placed to tribe and that Sophonia Walker, Evacanthus Le Peletier &Serville, Bundera Distant, Paraonukia Ishihara and Onukia Matsumura are not monophyletic. Divergence time analysis suggests that the deepest divergences coincided with breakup of Gondwana but that more recent divergences occurred largely within a single biogeographic realm during the Paleogene, with a few long-distance dispersal events. Biogeographical analyses suggest that Evacanthinae originated in Neotropical region. A new tribe, Pentoffiini trib.n., is established to include Pentoffia Kramer and Evanirvana Hill, the genus Draconirvana Dietrich, placement n. is transferred to Evacanthini from Nirvanini, a key to tribes is also given and illustrations of representative genera are provided.


Inter- and intra-observer variability of the Crowe and Hartofilakidis classification systems for congenital hip disease in adults.
Our study evaluated the reliability of the Crowe and Hartofilakidis classification systems for developmental dysplasia of the hip in adults. The anteroposterior radiographs of the pelvis of 145 patients with 209 osteoarthritic hips were examined twice by three experienced hip surgeons from three European countries and the abnormal hips were rated using both classifications. The inter- and intra-observer agreement was calculated. Interobserver reliability was evaluated using weighted and unweighted kappa coefficients and for the Crowe classification, among the three pairs there was a minimum kappa coefficient with linear weighting of 0.90 for observers A and C and a maximum kappa coefficient of 0.92 for observers B and C. For the Hartofilakidis classification, the minimum kappa value was 0.85 for observers A and B, and the maximum value was 0.93 for observers B and C. With regard to intra-observer reliability, the kappa coefficients with linear weighting between the two evaluations of the same observer ranged between 0.86 and 0.95 for the Crowe classification and between 0.80 and 0.93 for the Hartofilakidis classification. The reliability of both systems was substantial to almost perfect both for serial measurements by individual readers and between different readers, although the information offered was dissimilar.


Maintaining patient accounts performance during downsizing.
Patient accounts managers and chief financial officers (CFOs) are facing difficult issues during this current period of change in health care. The realities of today's lower rates of reimbursement and the uncertainties of healthcare reform have forced hospital management teams to reduce costs strategically to maintain adequate financial performance. One method often employed is "downsizing"--reducing staffing levels. Even those facilities that have not found it necessary to reduce staff through a formal layoff plan must seriously evaluate whether or not to replace employees who retire or terminate voluntarily. Patient accounts departments that have not yet been forced to downsize should be prepared for such an event; those that are currently struggling to maintain performance as a result of downsizing can improve their operations by addressing certain key areas.


Cumulative Index to Nursing and Allied Health Literature search strategies for identifying methodologically sound causation and prognosis studies.
We developed search strategies for detecting sound articles on causation and prognosis in Cumulative Index to Nursing and Allied Health Literature (CINAHL) in the year 2000. An analytic survey was conducted, comparing hand searches of 75 journals with retrievals from CINAHL for 5,020 search terms and 11,784 combinations for causation and 9,946 combinations for prognosis. For detecting sound causation studies, a three-term strategy maximized sensitivity at 97.0% with a specificity of 52.3%. For detecting sound prognosis studies, a three-term strategy maximized sensitivity at 92.2% with a specificity of 50.0%. These search filters will enhance the searching efforts of clinicians and researchers.


Intracarotid chemotherapy of glioblastoma after induced blood-brain barrier disruption.
Intracarotid chemotherapy has been suggested as an additional mode of therapy in patients with brain tumors. Seven comatose patients received intracarotid 5-fluorouracil and adriamycin after intracarotid infusion of 25% mannitol to open the blood-brain barrier at the tumor site. Five of seven patients became fully functional for 3-12 months. Another 11 patients entered the study, of which nine are currently receiving therapy and are functional, and two have died, one from brain herniation. The results are encouraging and support the need for further research of this therapeutic method.


Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides.
A synthetic peptide (SP-10-IIIB) with an amino acid sequence [Cys-Thr-Arg-Pro-Asn-Asn-Asn-Thr-Arg-Lys-Ser-Ile-Arg-Ile-Gln-Arg-Gly-Pro -Pro-Gly-(Tyr); amino acids 303-321] from the human immunodeficiency virus (HIV) isolate human T-cell lymphotropic virus type III (HTLV-III) HTLV-IIIB envelope glycoprotein gp120 was coupled to tetanus toxoid and used to raise goat antibodies to HIV gp120. Goat anti-SP-10-IIIB serum bound to the surface of HTLV-IIIB-infected CEM T cells but not to the surface of HTLV-IIIRF-infected or uninfected CEM T cells. Anti-SP-10-IIIB antibodies also selectively bound to gp120 from lysates of HTLV-IIIB cells in immunoblot assays. Twenty-one percent of sera (28 of 175) from patients seropositive for HIV contained antibodies that reacted with SP-10-IIIB in RIA. Human anti-SP-10-IIIB antibodies affinity purified from acquired immunodeficiency syndrome (AIDS) patient serum bound to HTLV-IIIB-infected cells and immunoprecipitated gp120. Goat antibodies to SP-10-IIIB neutralized HTLV-IIIB (80% neutralization titer of 1/600), inhibited HTLV-IIIB-induced syncytium formation, but did not neutralize HIV isolates HTLV-IIIRF or HTLV-IIIMN or inhibit syncytium formation with these isolates. Also, goat antiserum to an homologous synthetic peptide [SP-10-IIIRF(A), (Cys)-Arg-Lys-Ser-Ile-Thr-Lys-Gly-Pro-Gly-Arg-Val-Ile-Tyr] from gp120 of HIV isolate HTLV-IIIRF inhibited syncytium formation by HTLV-IIIRF, but did not inhibit syncytium formation by HTLV-IIIB or by HTLV-IIIMN. Thus, the amino acid sequences of SP-10-IIIB and SP-10-IIIRF(A) define homologous regions of gp120 that are important in type-specific virus neutralization. The identification of these type-specific neutralizing epitopes should facilitate the design of a polyvalent, synthetic vaccine for AIDS.


Small-vessel vasculitis leading to severe acute kidney injury after ipilimumab: a case report.
Immune checkpoint inhibitors are effective monoclonal antibodies used in cancer treatment, particularly in metastatic melanoma. They target proteins responsible for cancer cells evading the immune system. However, their use can lead to immune-related adverse events, with the skin and gastrointestinal tract being commonly affected. Kidney involvement is rarer, with interstitial nephritis being the most common manifestation. In a unique case, kidney biopsy-proven small-vessel vasculitis with arteriolar immune deposition was observed following ipilimumab administration.


EFFECTS OF COMPRESSION ON LYMPHEDEMA DURING RESISTANCE EXERCISE IN WOMEN WITH BREAST CANCER-RELATED LYMPHEDEMA: A RANDOMIZED, CROSS-OVER TRIAL.
The use of compression garments during exercise is recommended for women with breast cancer-related lymphedema, but the evidence behind this clinical recommendation is unclear. The aim of this randomized, cross-over trial was to compare the acute effects of wearing versus not wearing compression during a single bout of moderate-load resistance exercise on lymphedema status and its associated symptoms in women with breast cancer-related lymphedema (BCRL). Twenty-five women with clinically diagnosed, stable unilateral breast cancer-related lymphedema completed two resistance exercise sessions, one with compression and one without, in a randomized order separated by a minimum 6 day wash-out period. The resistance exercise session consisted of six upper-body exercises, with each exercise performed for three sets at a moderate-load (10-12 repetition maximum). Primary outcome was lymphedema, assessed using bioimpedance spectroscopy (L-Dex score). Secondary outcomes were lymphedema as assessed by arm circumferences (percent inter-limb difference and sum-of-circumferences), and symptom severity for pain, heaviness and tightness, measured using visual analogue scales. Measurements were taken pre-, immediately post- and 24 hours post-exercise. There was no difference in lymphedema status (i.e., L-Dex scores) pre- and post-exercise sessions or between the compression and non-compression condition [Mean (SD) for compression pre-, immediately post- and 24 hours post-exercise: 17.7 (21.5), 12.7 (16.2) and 14.1 (16.7), respectively; no compression: 15.3 (18.3), 15.3 (17.8), and 13.4 (16.1), respectively]. Circumference values and symptom severity were stable across time and treatment condition. An acute bout of moderate-load, upper-body resistance exercise performed in the absence of compression does not exacerbate lymphedema in women with BCRL.


Improving resident handoffs for children transitioning from the intensive care unit.
Handoffs ensure patient safety during patient care transitions in the hospital setting. At our institution, verbal handoffs communicated by resident physicians are suggested practice for patients transferring from the PICU to the hospital medicine (HM) service. Despite their importance, these verbal handoffs occurred only 76% of the time before patient arrival on HM units. Our goal was to increase the completion rate of verbal handoffs to 100% within 5 months. Baseline data were collected in a daily survey of HM residents. Interventions were developed and tested on small, incremental change cycles. Key interventions included education about the importance of handoffs, standardization of the handoff process, standardization of handoff documentation, and identification and mitigation of handoff documentation failures. We tracked handoff completion rates by using statistical control charts. After success with improving the completion rate of patient handoffs to the HM service, we applied our process to handoffs from the PICU to all inpatient services. Median completion of verbal patient handoff increased from 76% to 100% within 6 weeks, with improvement sustained for 15 months. Physician compliance with electronic medical record documentation increased from 58% to 94% within 8 months. After spreading to all patients transferring out of the PICU, documentation of patient handoffs increased from 76% to 94% in 5 months. A system using improvement science methods was successful in increasing the reliability of resident verbal patient handoffs. Consistent documentation and internal redundancy with checklists were associated with sustained improvement.


The measurement of serum TNF-α levels in patients with lichen planus.
Lichen planus is a common mucocutaneous inflammatory skin disease with a multifactorial etiology. Cytokines play a key role in lichen planus pathogenesis. This study investigates the relationship between disease severity and levels of tumor necrosis factor-α (TNF-α), which is considered a primary cytokine that initiates cytotoxicity. Serum TNF-α levels were compared between a patient group (n = 34) and a control group (n = 20). TNF-α serum levels were measured using human TNF-α Enzyme-Linked Immunosorbent Assay (ELISA) test kits, and the two groups were statistically compared to each other. Mean serum TNF-α levels were found to be significantly higher in the patient group than in the control group (p < 0.005). However, no significant association was observed between TNF-α levels and oral mucosal involvement (p > 0.005). No relationship was detected between TNF-α levels and patients' sex. It is thought that TNF-α, a proinflammatory cytokine, may play an important role in the pathogenesis of lichen planus. TNF-α may be a simple and effective predictor to illustrate the inflammatory status in patients with lichen planus.


Chromosome condensation in mitosis and meiosis of rye (Secale cereale L.).
Structural investigation and morphometry of meiotic chromosomes by scanning electron microscopy (in comparison to light microscopy) of all stages of condensation of meiosis I + II show remarkable differences during chromosome condensation in mitosis and meiosis I of rye (Secale cereale) with respect to initiation, mode and degree of condensation. Mitotic chromosomes condense in a linear fashion, shorten in length and increase moderately in diameter. In contrast, in meiosis I, condensation of chromosomes in length and diameter is a sigmoidal process with a retardation in zygotene and pachytene and an acceleration from diplotene to diakinesis. The basic structural components of mitotic chromosomes of rye are "parallel fibers" and "chromomeres" which become highly compacted in metaphase. Although chromosome architecture in early prophase of meiosis seems similar to mitosis in principle, there is no equivalent stage during transition to metaphase I when chromosomes condense to a much higher degree and show a characteristic "smooth" surface. No indication was found for helical winding of chromosomes either in mitosis or in meiosis. Based on measurements, we propose a mechanism for chromosome dynamics in mitosis and meiosis, which involves three individual processes: (i) aggregation of chromatin subdomains into a chromosome filament, (ii) condensation in length, which involves a progressive increase in diameter and (iii) separation of chromatids.


Viability and sporulating capability of Coelomycetes preserved under a range of different storage regimes.
The viability and sporulating capability of 45 Coelomycetes strains were evaluated. Strain subcultures were maintained under mineral oil, in soil and on agar slant for different periods of time lasting as long as 50 years, 39 years and 2 years, respectively. Of the 34 strains preserved under mineral oil, 20 maintained their viability but lost the sporulating capability with exception of one strain of Pestalotiopsis guepinii. Of the 16 strains also preserved in soil only one was viable and it was not able to sporulate. All 12 endophytic strains, 11 preserved on agar slant and one under mineral oil remained viable; however, the strain preserved under mineral oil lost its sporulating capability, while the strains on agar slant were only able to sporulate after culturing on sterilized alfalfa twigs. The results demonstrate that routine monitoring, and the use of different preservation methods, specially with the addition of sterilized plant tissue on the culture media for promoting conidiomata formation, is necessary for the success of the Coelomycetes long-term preservation.


Combined surgery and irradiation for treatment of hypertrophic scars and keloids.
This is a study of 11 patients who received combined surgery and irradiation for intractable hypertrophic scars and keloids. All of the patients received early post-operative (within 24 hours) irradiation with a 6-MeV electron beam and a total dose ranging from 1500-2100 rads in five to nine fractions after surgical excision of the lesions. The subjects were followed-up for over six months and the results are as follows: seven had a good response; three had a partial response; and one experienced a recurrence. The overall response rate was 90%, and no radiation injuries to the skin or delayed healing of the wound were noted. These preliminary outcomes are encouraging, especially for those patients who can not tolerate or have not responded well to other treatment programs.


Identification of Novel IGF1R Kinase Inhibitors by Molecular Modeling and High-Throughput Screening.
The aim of this study was to identify small molecule compounds that inhibit the kinase activity of the IGF1 receptor and represent novel chemical scaffolds, which can be potentially exploited to develop drug candidates that are superior to the existing experimental anti-IGF1R therapeuticals. To this end, targeted compound libraries were produced by virtual screening using molecular modeling and docking strategies, as well as the ligand-based pharmacophore model. High-throughput screening of the resulting compound sets in a biochemical kinase inhibition assay allowed us to identify several novel chemotypes that represent attractive starting points for the development of advanced IGF1R inhibitory compounds.


Bilateral massive adrenal hemorrhage. Assessment of putative risk factors by the case-control method.
Case reports and case series have identified putative risk factors for the development of bilateral massive adrenal hemorrhage (BMAH) in humans. The anatomy and physiology of the adrenal gland allow development of a model to fit the pathophysiology behind these risk factors. Until now, these risk factors were not systematically tested using analytical epidemiologic studies. A case-control study was undertaken using sources of cases and controls from multiple teaching hospitals in Ontario, Canada. The results of multivariate logistic regression indicated that thrombocytopenia (odds ratio [OR] = 14.6, 95% confidence intervals [CI] = 3.0-70.1, p < 0.001), heparin exposure of any route or type beyond 3 days (4-6 days: OR = 17.0, CI = 1.9-154.6; > 6 days: OR = 33.5, CI = 4.3-262.6; p < 0.001), and sepsis (OR = 6.3, CI = 1.2-32.2, p = 0.019) were most strongly and independently associated with development of BMAH. Another weaker positive association included invasive radiologic procedure (OR = 4.4, CI = 0.9-22.1, p = 0.055). Neither major surgery or duration of hospitalization were independent risk factors. Although coronary artery disease and possibly diabetes and hypertension appeared to be markers for lower risk of BMAH, this may be a result of bias introduced by using hospital controls ("Berkson bias"), as the effect was not explained by a protective effect of vasoactive medications. Thus, a picture of the high-risk patient should include a patient who has been treated with heparin (any route or type) beyond 3 days and has had thrombocytopenia (not necessarily induced by heparin) during the course of an illness. If the setting includes unexplained abdominal, chest, or back pain; fever; confusion; hypotension or shock; abrupt anemia; or electrolyte disorders, clinicians should not hesitate to cover empirically with lifesaving glucocorticoids while awaiting results of confirmatory tests.


Venous haemodynamics after total knee arthroplasty: evaluation of active dorsal to plantar flexion and several mechanical compression devices.
We performed a crossover study to evaluate the haemodynamic effect of active dorsal to plantar flexion and seven pneumatic compression devices in ten patients who had a total knee arthroplasty. Using the Acuson 128XP/10 duplex ultrasound unit with a 5MHz linear array probe, we assessed the augmentation of peak venous velocity and venous volume above and below the junction of the greater saphenous and common femoral veins in order to study both the deep and superficial venous systems. The pneumatic compression devices evaluated included two foot pumps (A-V Impulse System and PlexiPulse Foot), a foot-calf pump (PlexiPulse Foot-Calf), a calf pump (VenaFlow System) and three calf-thigh pumps (SCD System, Flowtron DVT and Jobst Athrombic Pump). The devices differed in a number of ways, including the length and location of the sleeve and bladder, the frequency and duration of activation, the rate of pressure rise, and the maximum pressure achieved. A randomisation table was used to determine the order of the test conditions for each patient. The enhancement of peak venous velocity occurred primarily in the deep venous system below the level of the saphenofemoral junction. The increases in peak venous velocity were as follows: active dorsal to plantar flexion 175%; foot pumps, A-V Impulse System 29% and PlexiPulse 65%; foot-calf pump, PlexiPulse, 221%; calf pump, VenaFlow, 302% and calf-thigh pumps, Flowtron DVT 87%, SCD System 116% and Jobst Athrombic Pump 263%. All the devices augmented venous volume, the greatest effect being seen with those incorporating calf compression. The increases in ml/min were found in the deep venous system as follows: foot pumps, A-V Impulse System 9.6 and PlexiPulse Foot 16.7; foot-calf pump, PlexiPulse, 38.1; calf pump, VenaFlow, 26.2; calf-thigh pumps, Flowtron DVT 61.5, SCD System 34.7 and Jobst Athrombic Pump 82.3. Active dorsal to plantar flexion generated 8.5 ml for a single calf contraction.


Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency.
Engineered T cell therapies have revolutionized modern oncology, however processes for manufacturing T cell therapies vary and the impact of manufacturing processes On the cell product is poorly understood. Herein, we have used a commercially available hollow fiber membrane bioreactor (HFMBR) operated in a novel mode to demonstrate that T cells can be engineered with lentiviruses, grown to very high densities, and washed and harvested in a single, small volume bioreactor that is readily amenable to automation. Manufacturing within the HFMBR dramatically changed the programming of the T cells and yielded a product with greater therapeutic potency than T cells produced using the standard manual method. This change in programming was associated with increased resistance to cryopreservation, which is beneficial as T cell products are typically cryopreserved prior to administration to the patient. Transcriptional profiling of the T cells revealed a shift toward a glycolytic metabolism, which may protect cells from oxidative stress offering an explanation for the improved resistance to cryopreservation. This study reveals that the choice of bioreactor fundamentally impacts the engineered T cell product and must be carefully considered. Furthermore, these data challenge the premise that glycolytic metabolism is detrimental to T cell therapies.


The "heterogeneous" effect of government grants on bank lending.
This study aims to test whether banks can recognize different signals from different types of government grants received by their clients and respond differently. Using a novel panel data set from China, we construct a three-way fixed-effect regression model and empirically explore the effect of government grants received by banks' clients on banks' lending decisions. We find that banks have heterogeneous attitudes towards their clients when the clients receive different types of government grants. In particular, we discover that banks behave positively toward clients who receive "development supportive" grants but negatively toward clients who receive "helping hand" grants. The main results hold after a series of robustness tests. Our study offers fresh perceptions on how banks see government grants of their clients while making lending choices. Our finds will offer certain inspirations for government grant policies and bank lending decisions.


Subtle cues of predation risk: starlings respond to a predator's direction of eye-gaze.
For prey animals to negotiate successfully the fundamental trade-off between predation and starvation, a realistic assessment of predation risk is vital. Prey responses to conspicuous indicators of risk (such as looming predators or fleeing conspecifics) are well documented, but there should also be strong selection for the detection of more subtle cues. A predator's head orientation and eye-gaze direction are good candidates for subtle but useful indicators of risk, since many predators orient their head and eyes towards their prey as they attack. We describe the first explicit demonstration of a bird responding to a live predator's eye-gaze direction. We present wild-caught European starlings (Sturnus vulgaris) with human 'predators' whose frontal appearance and gaze direction are manipulated independently, and show that starlings are sensitive to the predator's orientation, the presence of eyes and the direction of eye-gaze. Starlings respond in a functionally significant manner: when the predator's gaze was averted, starlings resumed feeding earlier, at a higher rate and consumed more food overall. By correctly assessing lower risk and returning to feeding activity earlier (as in this study), the animal gains a competitive advantage over conspecifics that do not respond to the subtle predator cue in this way.


Propagation of light fields with radial or azimuthal polarization distribution at a transverse plane.
In terms of the angular spectrum representation, general expressions are given to describe the free-space propagation of electromagnetic fields with radial or azimuthal polarization structure at a transverse plane. The transverse distributions of the radial, azimuthal and longitudinal components of these fields are also analysed. In particular, the on-axis behavior upon free propagation is studied. Furthermore, the special but important case of those fields that retain their polarization character (radial or azimuthal) under propagation is also considered. The analytical results are illustrated by application to some examples.


Robust iron coordination complexes with N-based neutral ligands as efficient Fenton-like catalysts at neutral pH.
The homogeneous Fenton-like oxidation of organic substrates in water with hydrogen peroxide, catalyzed by six different metal coordination complexes with N-based neutral ligands, was studied at ambient conditions and initial pH 7, employing hydrogen peroxide as the terminal oxidant. At low catalyst concentration, the catalytic oxidative depletion of toluene achieved by selected catalysts was much more efficient than that obtained by the Fenton reagent at pH 3. The influence of pH, the water matrix and the catalyst/hydrogen peroxide concentration were investigated for the oxidation of toluene employing [FeCl2(bpmcn)] (1, bpmcn = N,N'-bis(2-pyridylmethyl)-N,N'-dimethyl-trans-1,2-diaminocyclohexane), the most efficient catalyst of the series. Moreover, the evolution of catalysts [FeCl2(bpmcn)] (1) and [Fe(OTf)2(Pytacn)] (3, Pytacn = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane, OTf = trifluoromethanesulfonate anion) during the course of the reaction was also studied by electrospray ionization mass spectrometry (ESI-MS). The oxidation products derived from toluene oxidation were also analyzed. A plausible mechanism of toluene degradation using [FeCl2(bpmcn)] (1) and [Fe(OTf)2(Pytacn)] (3) as catalysts was proposed, which involves the coexistence of a metal-based path, analogous to that operating in organic media where substrate oxidation is executed by an iron(V)-oxo-hydroxo species, in parallel to a Fenton-type process where hydroxyl radicals are formed.


Distribution of lutein and zeaxanthin stereoisomers in the human retina.
The distribution of macular pigment stereoisomers in the human retina has been mapped and a pathway to account for the presence of the non-dietary carotenoid, meso-zeaxanthin, is proposed. Adult neural retinas were cut into three concentric areas centered on the fovea, and the extracted carotenoids were analysed and purified by high-performance liquid chromatography. The dicarbamate or dibenzoate derivatives of the collected zeaxanthin fractions for each tissue sample were further analysed by HPLC to determine their stereoisomer composition. Whole retinas from infant eyes were similarly analysed. The results show that, relative to zeaxanthin, the concentration of lutein in the adult neural retina increases with radial distance from the fovea while that of meso-zeaxanthin decreases. Infant retinas were found to have more lutein and less meso-zeaxanthin, relative to zeaxanthin, than adult retinas. Small quantities of (3S, 3'S)-zeaxanthin were also found in the adult retina, particularly in the macula. It is proposed that lutein and zeaxanthin are transported into an individual's retina in the same proportions found in his or her blood serum. Some of the lutein is then converted into meso-zeaxanthin, primarily in the macula, by a mechanism which is less developed in infants than adults.


Reliability of assessing dye penetration along root canal fillings using methylene blue.
Methylene blue (MB) remains the most frequently used tracer for dye penetration tests of endodontic fillings, despite its chemical reactions with different materials. This study checked whether dye penetration displayed by MB is comparable to Rhodamine B (RB). One hundred and seventy-two root canals were filled with gutta-percha and six sealers. Samples were covered with nail varnish except for the apical area, and immersed in MB or RB solutions under negative pressure. After 24 h, roots were bisected, photographed and the maximal dye penetration recorded. Dye penetrations displayed by MB and RB were compared (Newman-Keuls test). MB and RB displayed comparable results for groups filled with AH Plus, EndoREZ and Polifil (P > 0.05). For Endofill, Sealer 26 and Sealapex, a significant lower dye penetration was observed when MB was used (P < 0.05). Laboratory tests using MB for measuring dye penetration through filled root canals can result in misleading conclusions.


Relationship of choroidal thickness with pulsatile hemodynamics in essential hypertensive patients.
Controversy exists about the association of choroidal thickness (CTh) with blood pressure (BP) values. There is some evidence suggesting that central hemodynamics changes are associated with microvascular disease. Our study was aimed to assess the relationships between CTh and clinic and 24-h BP and between CTh and estimated 24-h aortic pulse pressure (aPP), 24-h aortic systolic BP (aSBP), and 24-h aortic augmentation index (aAIx) in a group of hypertensive patients. We enrolled 158 hypertensive subjects (mean age 48 ± 13 years) all of which underwent evaluation of the choroidal district by Swept-Source optical coherence tomography (SS-OCT) and 24-h BP monitoring, in order to measure peripheral BP and to estimate central hemodynamic parameters. Inverse significant correlations of clinic PP, 24-h aPP, 24-h aSBP, and 24-h aAIx with thicknesses of central ring, inner ring, and outer ring of the choroid and its overall average were found. The strongest of these correlations was that relating 24-h aPP with overall average choroidal thickness (r = -.531; P < .001). When we divided the study population in subjects with 24-h aPP above and below the median value (35 mm Hg), CTh were thinner in subjects with higher values of 24-aPP as compared to those with lower ones, even after adjustment for age, and other potential confounders. The relationships of CTh with 24-h aPP remained significant also taking into account the effects of various covariates in linear multiple regression analyses. Our findings support the concept of a cross-talk between macro- and microcirculation.


Development of acute lymphoblastic leukemia and myeloproliferative disorder in transgenic mice expressing p210bcr/abl: a novel transgenic model for human Ph1-positive leukemias.
The Philadelphia (Ph) chromosome can be detected in chronic myelogenous leukemia (CML) and a significant number of acute lymphoblastic leukemia (ALL) cases. Generation of p210bcr/abl, a chimeric protein with enhanced kinase activity, is thought to be involved in the pathogenesis of these diseases. To elucidate the biological properties of p210bcr/abl and to create an animal model for human Ph1-positive leukemias, we generated transgenic mice expressing p210bcr/abl driven by the promoter of the tec gene, a cytoplasmic tyrosine-kinase preferentially expressed in the hematopoietic lineage. The founder mice showed excessive proliferation of lymphoblasts shortly after birth and were diagnosed as suffering from ALL based on surface marker and Southern blot analyses. Expression and enhanced kinase activity of the p210bcr/abl transgene product were detected in the leukemic tissues. In contrast, transgenic progeny exhibited marked granulocyte hyperplasia with thrombocytosis after a long latent period and developed myeloproliferative disorders (MPDs) closely resembling human CML. Expression of p210(bcr/abl) mRNA in the proliferating granulocytes was detected by RT-PCR. In particular, one MPD mouse showed remarkable proliferation of blast cells in the lung, which might represent an extramedullar blast crisis. The results demonstrate that the expression of p210bcr/abl in hematopoietic progenitor cells in transgenic mice can contribute to two clinically distinct hematopoietic malignancies, CML and ALL, indicating that this transgenic system provides a novel transgenic model for human Ph1-positive leukemias.