FITNESS CONSEQUENCES OF OUTCROSSING IN IMPATIENS CAPENSIS: TESTS OF THE FREQUENCY-DEPENDENT AND SIB-COMPETITION MODELS.
Using field and greenhouse experiments, we tested two hypotheses that could account for the maintenance of outcrossing in Impatiens capensis. Seedlings derived from cleistogamous (CL) and chasmogamous (CH) flowers were grown under competitive conditions while flanked by neighbors that were either related or unrelated. In both experiments, CH progeny sometimes expressed more phenotypic variability than CL progeny. In the greenhouse experiment, CH progeny attained the same weight as CL progeny, and the relatedness of neighboring plants did not affect the growth of either type. In the field experiment, CL and CH progeny performed similarly when grown with related competitors. However, CH progeny were somewhat larger when planted with nonsibs, while CL progeny were somewhat smaller under those conditions. Thus, there is no evidence that either frequency-dependent selection or the avoidance of competition among siblings favors the maintenance of outcrossing in this species. We also modeled the relative variability of selfed and outcrossed progeny under several reproductive systems. When females mate with one male (progeny are full sibs), selfed progeny are often more variable than outcrossed progeny. When females engage in both selfing and outcrossing, variation among progeny is frequently maximized at an intermediate selfing rate. The sib-competition mechanism, under a range of genetic models, is not apt to promote outcrossing, since selfed progeny are commonly more variable than outcrossed progeny.


Hypoglycemia in mice injected with interferon inducers is not mediated by interferon.
Injection of mice with several viral and nonviral inducers of interferon resulted in a marked hypoglycemia. Interferon is not responsible for this effect since inoculation of a potent antiserum to interferon (which neutralized the endogenous interferon) did not prevent hypoglycemia and administration of potent interferon preparations did not lower blood sugar. Hypoglycemia induced by Newcastle disease virus and polyriboinosinic-polyribocytidylic acid was further exacerbated by injection of insulin.


Patterned poly(2-hydroxyethyl methacrylate) brushes on silicon surfaces behave as "tentacles" to capture ferritin from aqueous solution.
We have used a very large scale integration process to generate well-defined patterns of polymerized 2-hydroxyethyl methacrylate (HEMA) on patterned Si(100) surfaces. An atom transfer radical polymerization initiator covalently bonded to the patterned surface was employed for the graft polymerization of HEMA to prepare the poly(2-hydroxyethyl methacrylate) (PHEMA) brushes. After immersing wafers presenting lines of these polymers in water and cyclohexane, we observed brush- and mushroom-like regions, respectively, for the PHEMA brushes, with various pattern resolutions. The PHEMA brushes behaved as "tentacles" that captured ferritin complexes from aqueous solution through entanglement between the brushes and the ferritin proteins, whose ferritins were trapped due to the collapsing of the PHEMA. Using high-resolution scanning electron microscopy, we observed patterned ferritin iron cores on the Si surface after thermal removal of the patterned PHEMA brushes and ferritin protein sheaths.


Of two minds or one? A registered replication of Rydell et al. (2006).
Evaluative conditioning (EC) is proposed as a mechanism of automatic preference acquisition in dual-process theories of attitudes (Gawronski, B., & Bodenhausen, G. V. (2006). Associative and propositional processes in evaluation: An integrative review of implicit and explicit attitude change. Psychological Bulletin, 132(5), 692-731. doi: 10.1037/0033-2909.132.5.692 ). Evidence for the automaticity of EC comes from studies claiming EC effects for subliminally presented stimuli. An impression-formation study showed a selective influence of briefly presented primes on implicitly measured attitudes, whereas supraliminally presented behavioural information about the target person was reflected in explicit ratings (Rydell, R. J., McConnell, A. R., Mackie, D. M., & Strain, L. M. (2006). Of two minds forming and changing valence-inconsistent implicit and explicit attitudes. Psychological Science, 17(11), 954-958. doi:10.1111/j.1467-9280.2006.01811.x) This finding is considered one of the strongest pieces of evidence for dual process theories (Sweldens, S., Corneille, O., & Yzerbyt, V. (2014). The role of awareness in attitude formation through evaluative conditioning. Personality and Social Psychology Review, 18(2), 187-209. doi: 10.1177/1088868314527832 ), and it is therefore crucial to assess its reliability and robustness. The present study presents two registered replications of the Rydell et al. (2006) study. In contrast to the original findings, the implicit measures did not reflect the valence of the subliminal primes in both studies.


Laboratory indices of prognosis in HIV infection.
The progression of a HIV seropositive patient from an asymptomatic infection or persistent generalised lymphadenopathy to AIDS is dependent on many factors. The most useful prognostic indicators appear to be CD4 + lymphocyte count, beta 2-microglobulin level, anti-p24 antibody titre and p24 antigenaemia. The use of a combination of prognostic indices can enhance the accuracy of the prediction.


[Enhanced Removal of Pollutants in Constructed Wetlands with Manganese Sands].
Manganese (Mn) sands have been widely used in water purification due to their strong oxidation and adsorption abilities. However, there are few reports on the use of manganese sands as filler material in constructed wetlands. Based on previous studies, we speculated that the addition of manganese sands in constructed wetlands would enhance the removal of pollutants from the source water, and the resulting Mn(Ⅱ) could then be oxidized by the rhizosphere and soil microorganisms in the wetlands. To test this hypothesis, this study explored the enhanced removal of pollutants in wetlands constructed with manganese sands as substrates and Phragmites as plants, and also examined the role of Phragmites rhizosphere microorganisms in water purification. By comparing the treatment effects between the wetlands constructed with and without manganese sands (control), we found that the wetland containing manganese sands exhibited significantly improved removal of dissolved organic carbon and total nitrogen, as well as removal of ammonia nitrogen during periods of lower temperature. The 16S rRNA sequencing showed that the addition of manganese sands could increase the richness and diversity of Phragmites rhizosphere microorganisms, but had limited impacts on the microbial community structure, which might be an important factor for enhancing the water treatment performance of constructed wetlands. This study provides a new method for the technological optimization of constructed wetlands.


Superconducting Scanning Tunneling Microscope Tip to Reveal Sub-millielectronvolt Magnetic Energy Variations on Surfaces.
Combining the complex ordering ability of molecules with their local magnetic properties is a little-explored technique to tailor spin structures on surfaces. However, revealing the molecular geometry can be demanding. Nickelocene (Nc) molecules present a large spin-flip excitation leading to clear changes of conductance at the excitation-threshold bias. Using a superconducting tip, we have the energy resolution to detect small shifts of the Nc spin-flip excitation thresholds, permitting us to reveal the different individual environments of Nc molecules in an ordered layer. This knowledge allows us to reveal the adsorption configuration of a complex molecular structure formed by Nc molecules in different orientations and positions. As a consequence, we infer that Nc layers present a strong noncollinear magnetic-moment arrangement.


Bidirectional dopaminergic modulation of excitatory synaptic transmission in orexin neurons.
Orexin neurons in the lateral hypothalamus (LH)/perifornical area (PFA) are known to promote food intake as well as provide excitatory influence on the dopaminergic reward pathway. Dopamine (DA), in turn, inhibits the reward pathway and food intake through its action in the LH/PFA. However, the cellular mechanism by which DA modulates orexin neurons remains largely unknown. Therefore, we examined the effect of DA on the excitatory neurotransmission to orexin neurons. Whole-cell patch-clamp recordings were performed using acute rat hypothalamic slices, and orexin neurons were identified by their electrophysiological and immunohistochemical characteristics. Pharmacologically isolated action potential-independent miniature EPSCs (mEPSCs) were monitored. Bath application of DA induced a bidirectional effect on the excitatory synaptic transmission dose dependently. A low dose of DA (1 microM) increased mEPSC frequency, which was blocked by the D1-like receptor antagonist SCH 23390, and mimicked by the D1-like receptor agonist SKF 81297. In contrast, higher doses of DA (10-100 microM) decreased mEPSC frequency, which could be blocked with the D2-like receptor antagonist, sulpiride. Quinpirole, the D2-like receptor agonist, also reduced mEPSC frequency. None of these compounds affected the mEPSCs amplitude, suggesting the locus of action was presynaptic. Furthermore, DA (1 microM) induced an increase in the action potential firing, whereas DA (100 microM) hyperpolarized and ceased the firing of orexin neurons, indicating the effect of DA on excitatory synaptic transmission may influence the activity of the postsynaptic cell. In conclusion, our results suggest that D1- and D2-like receptors have opposing effects on the excitatory presynaptic terminals impinging onto orexin neurons.


[Involvement of opiate receptors in the mode of action of trimebutine].
Several studies in dogs, cats, rabbits and humans have suggested that the motility stimulating properties of trimebutine (TMB) are mediated by peripheral opiate receptors. The present work deals with the capacity of TMB and its N-desmethyl metabolite (NDTMB) to displace mu, delta and kappa specific ligands from their receptors using guinea-pig brain membranes and ileal myenteric plexus synaptosomal membrane preparations. The activity of both compounds on the twitch response induced by transmural stimulation on the guinea-pig ileum as well as the mouse and rabbit vas deferens was also investigated. These preparations have been proposed to be specific for the mu, delta and kappa receptor subtypes respectively. TMB (0.2 to 1.8 microM) and NDTMB (0.3 to 6 microM) displayed a good affinity for all receptor subtypes in brain and myenteric plexus preparations. Both compounds also inhibited the twitch response of all three isolated organ preparations. The decreasing order of IC50's of TMB ranged from 0.75 microM in the guinea-pig ileum to 7.1 and 39 microM in the vas deferens of the rabbit and the mouse respectively. These results indicate that TMB and NDTMB possess mu, delta as well as kappa agonist properties without true specificity for one or the other of these subtypes. They also confirm that activation of peripheral mu, delta and kappa opiate receptors mediate the gastrointestinal motility effect of TMB.


miR-29b and retinoic acid co-delivery: a promising tool to induce a synergistic antitumoral effect in non-small cell lung cancer cells.
The high incidence, late diagnosis, and aggressive profile of lung cancer limit the treatment options, causing a reduced survival rate. Consequently, RNAi-based therapy appears as a potential approach to treat non-small cell lung cancer (NSCLC). This approach is based on the delivery of small RNAs, involved in the regulation of key cell pathways, to treat complex diseases among others. Concerning that, the aim of this work was focused on the co-delivery of miR-29b and retinoic acid (RA) into NSCLC cells by multifunctional micellar nanosystems (Pluronic® P123 or Pluronic® P103 linked to polyethyleneimine (PEI)). The developed P103-PEI-RA/miR-29b (10/1) presented better results and most attractive properties, promoting efficient delivery of miR-29b, as well as revealing a significant antitumoral activity promoted by a synergistic effect between miR-29b expression and RA deliver. Furthermore, the developed therapeutic approach was able to significantly decrease cell viability and migration, as well as induce cell cycle arrest and epigenetic regulation in NSCLC cells. Thus, this work outcome enables to discover a hopeful system to deliver therapeutic miRNAs, crafting a novel RNAi-based therapy combined with RA to treat NSCLC. Graphical abstract.


Mechanism for safe remote activation of networked surgical and PoC devices using dynamic assignable controls.
The number of devices within an operating room (OR) increases continuously as well as the complexity of the complete system. One key enabler to handle the complexity is an interoperable and vendor independent system of networked medical devices. To build up such an interoperable system we use the proposed IEEE 11073 SDC standards (IEEE P11073-10207, -20701, -20702) for networked point-of-care (PoC) and surgical devices. One of the major problems within the OR is that typically every device has its own control unit. This leads to unsatisfying situations like a high number of foot switches that causes operating errors or the problem that the physician cannot reach the control unit of the device where parameters have to be changed or an activation should be triggered. Dynamically assignable controls will solve these problems. This paper describes mechanisms that allow a safe remote activation of safety critical device functionalities based on a potentially unsafe off-the-shelf network with problems like connection loss and jitter. The proposed systems is based on a periodic reactivation of the device functionality and the additional use safety related information that is included into the activate operation command. The main advantage is that all described mechanisms make use of the self-description capability provided by the IEEE 11073 SDC. This enables a real interoperability and plug-and-play functionality because both the medical device and the control client do not need any a priori knowledge about each other.


Deformity Correction of the Midfoot/Hindfoot/Ankle.
The correction of the deformed arthritic foot and ankle is a complicated and somewhat controversial topic. After conservative methods fail, there is a wide range of possible bony procedures and arthrodesis that maybe performed. The appropriate work up and understanding of the pathomechanics is vital to the correct choice of procedures to correct these deformities. Once the work up and procedure selection is done, the operation must also be technically performed well and with efficiency, as most often the condition is corrected with a variety of procedures. This article discusses some of the most common procedures necessary to fully correct deformity of the midfoot, hindfoot, and ankle. This article will also discuss the authors' technique and pearls.


Efferent innervation of the cochlea.
The origin of the efferent innervation of the cochlea was investigated in the guinea pigs. Horseradish peroxidase (HRP) was injected into the cochlea and transported to the brainstem by retrograde axonal transport of the efferent fibers, showing the origin of the crossed an uncrossed olivocochlear bundles of Rasmussen. HRP-labeled neurons were found in various nuclei of the superior olivary complex bilaterally. Ipsilateral to the injected cochlea ther were three times more cells than on the contralateral side. About 40% of the total number of labeled neurons, a remarkable quantity, occurred in the ipsilateral lateral superior olivary nucleus. Moreover, extraolivary origin of the efferent innervation of the cochlea could be demonstrated bilaterally in the ventral nucleus of the lateral lemniscus.


The α2δ Subunit and Absence Epilepsy: Beyond Calcium Channels?
Spike-wave discharges, underlying absence seizures, are generated within a cortico-thalamo-cortical network that involves the somatosensory cortex, the reticular thalamic nucleus, and the ventrobasal thalamic nuclei. Activation of T-type voltage-sensitive calcium channels (VSCCs) contributes to the pathological oscillatory activity of this network, and some of the first-line drugs used in the treatment of absence epilepsy inhibit T-type calcium channels. The α2δ subunit is a component of high voltage-activated VSCCs (i.e., L-, N-, P/Q-, and R channels) and studies carried out in heterologous expression systems suggest that it may also associate with T channels. The α2δ subunit is also targeted by thrombospondins, which regulate synaptogenesis in the central nervous system. To discuss the potential role for the thrombospondin/α2δ axis in the pathophysiology of absence epilepsy. We searched PubMed articles for the terms "absence epilepsy", "T-type voltage-sensitive calcium channels", "α2δ subunit", "ducky mice", "pregabalin", "gabapentin", "thrombospondins", and included papers focusing this Review's scope. We moved from the evidence that mice lacking the α2δ-2 subunit show absence seizures and α 2δ ligands (gabapentin and pregabalin) are detrimental in the treatment of absence epilepsy. This suggests that α2δ may be protective against absence epilepsy via a mechanism that does not involve T channels. We discuss the interaction between thrombospondins and α2δ and its potential relevance in the regulation of excitatory synaptic formation in the cortico-thalamo-cortical network. We speculate on the possibility that the thrombospondin/α2 δ axis is critical for the correct functioning of the cortico-thalamo-cortical network, and that abnormalities in this axis may play a role in the pathophysiology of absence epilepsy.


The patient's view.
The medical practitioner has always had to juggle several roles. First and foremost, the doctor is a healer, a provider of curative services. Second, he is an examiner, an assessor of the patient's health status. Third, he is a researcher, always trying to push the boundaries of medical knowledge. Fourth, he is a rationer of services, he decides how best to apportion the limited resources at his disposal. Traditionally, the patient-doctor relationship has been largely exclusive in nature and the doctor would quite comfortably slip in and out of these roles, his focus centred on his patient's interests. In this era of large corporate health care providers, multi-billion-biotechnology industry, mammoth pharmaceutical companies, medical insurance schemes and international trade instruments, it has become increasingly difficult for the doctor to juggle these four roles. He is constantly subjected to conflicting demands. Patients' interests do not always come first anymore and patients are beginning to realise this. They no longer trust the medical profession unreservedly. There has been steady erosion of the patient-doctor relationship most clearly evidenced by the rising tide of litigation against doctors. There needs to be a reappraisal of these roles that the doctor plays. The conflicts must be recognised and addressed. Patients need to be informed and their interests must be protected if the doctor-patient relationship is to be restored. Medical malpractice suits are on the increase. The tort system as it exists is failing both doctors and patients. The question we must ask is what are patients looking for when they sue doctors? Most of the time they need compensation for the injuries suffered. Sometimes they are looking for accountability, they want the doctor to be punished in some way. Sometimes they merely want to air their grievances and know that they are heard. The current system more often than not takes too long to compensate, the process is a gamble and doctors who are clearly negligent quietly settle and are rarely censured. We need to revamp the existing system to allow for speedy and equitable compensation; true accountability; and articulation and auditing of standards of practice.


A pharmacological modulation of opiate withdrawal using an up-/down-regulation of the noradrenergic system in opiate-dependent rats.
Chronic opioid exposure induces neuroadaptative changes in several brain systems. Amongst others the alpha adrenergic system appears to be extremely sensitive to opioid exposure and has, therefore, been proposed to play a key role in opiate withdrawal symptoms. In order to better understand the influence of the noradrenergic system in opioid withdrawal and be able to develop new therapeutic strategies, we studied the effect of pre-treatment with the alpha2 agonist (clonidine) and alpha2 antagonist (yohimbine) on naloxone-precipitated withdrawal in opiate-dependent rats. As is already known clonidine pre-treatment significantly enhances autonomic and behavioural signs of opioid withdrawal whereas yohimbine significantly attenuates them with dose-related effect. We also tested the effect of clonidine (0.1 mg/kg) during naloxone-precipitated opiate withdrawal in rats pre-treated with yohimbine (5 mg/kg) and we observed that yohimbine pre-treatment potentiates clonidine efficiency in decreasing opiate withdrawal signs. This study supports the possibility of using a noradrenergic antagonist in order to regulate adrenoreceptors chronically exposed to opioids, therefore interfering with the intensity of naloxone-precipitated opiate withdrawal and potentiating later effectiveness of noradrenergic agonists like clonidine. These results may have various applications in clinical opiate detoxification protocols and are discussed through an up-/down- regulation of adrenoreceptors.


Event-Triggered Neural Control of Nonlinear Systems With Rate-Dependent Hysteresis Input Based on a New Filter.
In controlling nonlinear uncertain systems, compensating for rate-dependent hysteresis nonlinearity is an important, yet challenging problem in adaptive control. In fact, it can be illustrated through simulation examples that instability is observed when existing control methods in canceling hysteresis nonlinearities are applied to the networked control systems (NCSs). One control difficulty that obstructs these methods is the design conflict between the quantized networked control signal and the rate-dependent hysteresis characteristics. So far, there is still no solution to this problem. In this paper, we consider the event-triggered control for NCSs subject to actuator rate-dependent hysteresis and failures. A new second-order filter is proposed to overcome the design conflict and used for control design. With the incorporation of the filter, a novel adaptive control strategy is developed from a neural network technique and a modified backstepping recursive design. It is proved that all the control signals are semiglobally uniformly ultimately bounded and the tracking error will converge to a tunable residual around zero.


Identification of immune-related hub genes and analysis of infiltrated immune cells of idiopathic pulmonary artery hypertension.
Idiopathic pulmonary artery hypertension (IPAH) is a rare but life-threaten disease. However, the mechanism underlying IPAH is unclear. In this study, underlying mechanism, infiltration of immune cells, and immune-related hub genes of IPAH were analyzed via bioinformatics. GSE15197, GSE48149, GSE113439, and GSE117261 were merged as lung dataset. Weighted gene correlation network analysis (WGCNA) was used to construct the co-expression gene networks of IPAH. Gene Ontology and pathway enrichment analysis were performed using DAVID, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA). Infiltration of immune cells in lung samples was analyzed using CIBERSORT. GSE22356 and GSE33463 were merged as peripheral blood mononuclear cells (PBMCs) dataset. Immune-related differentially expressed genes (IRDEGs) of lung and PBMCs dataset were analyzed. Based on the intersection between two sets of IRDEGs, hub genes were screened using machine learning algorithms and validated by RT-qPCR. Finally, competing endogenous RNA (ceRNA) networks of hub genes were constructed. The gray module was the most relevant module and genes in the module enriched in terms like inflammatory and immune responses. The results of GSEA and GSVA indicated that increasement in cytosolic calcium ion, and metabolism dysregulation play important roles in IPAH. The proportions of T cells CD4 memory resting and macrophage M1 were significantly greater in IPAH group, while the proportions of monocytes and neutrophils were significantly lower in IPAH group. IRDEGs of two datasets were analyzed and the intersection between two set of IRDEGs were identified as candidate hub genes. Predictive models for IPAH were constructed using data from PBMCs dataset with candidate hub genes as potential features via LASSO regression and XGBoost algorithm, respectively. CXCL10 and VIPR1 were identified as hub genes and ceRNA networks of CXCL10 was constructed. Inflammatory response, increasement in cytosolic calcium ion, and metabolism dysregulation play important roles in IPAH. T cells CD4 memory resting and macrophage M1 were significantly infiltrated in lung samples from patients with IPAH. IRDEGs of lung dataset and PBMCs dataset were analyzed, and CXCL10 and VIPR1 were identified as hub genes.


A Review of the Health Implications of Heavy Metals in Food Chain in Nigeria.
Heavy metals such as Zn, Pb, Fe, and Cu are abundant in the environment and contribute largely to the sustainability and equilibrium of ecosystem processes. However, because of their bioaccumulation, nondegradability, and the excessive amounts in which they exist, these metals contaminate the food chain and subsequently become a source of toxicity to human beings and the entire ecological function. This is a major issue of concern within the study of environmental science and geochemistry. Although there is a global significance to the issue, it seems more immediate for the developing countries (DCs) such as Nigeria, where the pressure of the teeming population escalates the exigency for human sustainability, food security, and total eradication of hunger. Within the Nigerian context, many studies have examined this all-important issue, but most of these studies are fragmented and limited within the purview of mostly individual states and localities within the country. Taken on a wider geographical scale, the discussions and perspectives of these studies on heavy metal contamination of the food chain offer insufficient insight and expose merely a snapshot of the actual situation. As a result of this, a country-wide knowledge base of the implications of heavy metals on the food chain is lacking. Thus, the present study synthesises existing literature and their findings to create a knowledge base on the vulnerability of the food chain in Nigeria. Aquatic foods, fruits, vegetables, and major staple food such as tubers are the major host of carcinogenic and mutagenic components of heavy metals in Nigeria. This study motivates the Standard Organisation of Nigeria (SON), along with other food and agricultural agencies, to intensify their efforts in monitoring and analysing food components, and we advise consumers to eat with certain degrees of caveat.


A critical assessment for the value of markers to gate-out undesired events in HLA-peptide multimer staining protocols.
The introduction of antibody markers to identify undesired cell populations in flow-cytometry based assays, so called DUMP channel markers, has become a practice in an increasing number of labs performing HLA-peptide multimer assays. However, the impact of the introduction of a DUMP channel in multimer assays has so far not been systematically investigated across a broad variety of protocols. The Cancer Research Institute's Cancer Immunotherapy Consortium (CRI-CIC) conducted a multimer proficiency panel with a specific focus on the impact of DUMP channel use. The panel design allowed individual laboratories to use their own protocol for thawing, staining, gating, and data analysis. Each experiment was performed twice and in parallel, with and without the application of a dump channel strategy. The introduction of a DUMP channel is an effective measure to reduce the amount of non-specific MULTIMER binding to T cells. Beneficial effects for the use of a DUMP channel were observed across a wide range of individual laboratories and for all tested donor-antigen combinations. In 48% of experiments we observed a reduction of the background MULTIMER-binding. In this subgroup of experiments the median background reduction observed after introduction of a DUMP channel was 0.053%. We conclude that appropriate use of a DUMP channel can significantly reduce background staining across a large fraction of protocols and improve the ability to accurately detect and quantify the frequency of antigen-specific T cells by multimer reagents. Thus, use of a DUMP channel may become crucial for detecting low frequency antigen-specific immune responses. Further recommendations on assay performance and data presentation guidelines for publication of MULTIMER experimental data are provided.


Novel epitopes identified from efflux pumps of Mycobacterium tuberculosis could induce cytotoxic T lymphocyte response.
Overcoming drug-resistance is one of the major challenges to control tuberculosis (TB). The up-regulation of efflux pumps is one common mechanism that leads to drug-resistance. Therefore, immunotherapy targeting these efflux pump antigens could be promising strategy to be combined with current chemotherapy. Considering that CD8+ cytotoxic T lymphocytes (CTLs) induced by antigenic peptides (epitopes) could elicit HLA-restricted anti-TB immune response, efflux pumps from classical ABC family (Mycobacterium tuberculosis, Mtb) were chosen as target antigens to identify CTL epitopes. HLA-A2 restricted candidate peptides from Rv2937, Rv2686c and Rv2687c of Mycobacterium tuberculosis were predicted, synthesized and tested. Five peptides could induce IFN-γ release and cytotoxic activity in PBMCs from HLA-A2(+) PPD(+) donors. Results from HLA-A2/K(b) transgenic mice immunization assay suggested that four peptides Rv2937-p168, Rv2937-p266, Rv2686c-p151, and Rv2686c-p181 could induce significant CTL response in vivo. These results suggested that these novel epitopes could be used as immunotherapy candidates to TB drug-resistance.


Temporal data mining for the assessment of the costs related to diabetes mellitus pharmacological treatment.
Diabetes care and chronic disease management represent data-intensive contexts which allow Local Healthcare Agencies (ASL) to collect a huge amount of information. Time is often an essential component of such information, given the strong importance of the temporal evolution of the considered disease and of its treatment. In this paper we show the application of a temporal data mining technique to extract temporal association rules over an integrated repository including both administrative and clinical data related to a sample of diabetic patients. We will show how the method can be used to highlight cases and conditions which lead to the highest pharmaceutical costs. Considering the perspective of a Regional Healthcare Agency, this method could be properly exploited to assess the overall standards and quality of care, while lowering costs.


The relative importance of avoidance and restoration-oriented stressors for grief and depression in bereaved parents.
Previous research has identified a number of individual risk factors for parental bereavement including the sex of the parent, the sex of the child, avoidance-focussed coping style and time since death. These factors emerged from research where variables were tested univariately and their relative importance is currently unknown. The current research, therefore, aims to investigate which risk factors are important, multivariately, for the outcomes of grief and depression in parents following the death of their child. Psychosocial measures were completed by 106 bereaved parents four years post-loss, recruited from death records in Scotland. The cause of the child's death included long-term illness and stillbirths as well as sudden and violent deaths. In multivariate regression analyses, depression was predicted by higher avoidance-focussed coping and higher number of restoration-oriented stressors such as relationship difficulties, problems at work and financial issues. Grief was predicted by higher avoidance, restoration stressors and level of continuing bonds. The present study adds to the knowledge about the phenomenon of parental bereavement with participants recruited directly from death records rather than through support, clinical or obituary sources. Factors previously found to be associated with outcomes when tested univariately such as sudden, violent death or sex of the parent were not significant when tested multivariately. This study highlights that different vulnerability factors exist for grief and depression in bereaved parents.


[Lumbar Back Pain and Impaired Vision - an Alarming Differential Diagnosis].
Lumbar Back Pain and Impaired Vision - an Alarming Differential Diagnosis Abstract. Aortic dissection is much less common than other causes of back pain, yet associated with a high mortality. Despite major advances in noninvasive imaging, the correct diagnosis is made in less than half of the cases. End-organ malperfusion can lead to a broad spectrum of symptoms making diagnosis difficult. This clinical case illustrates the importance of a careful history and thorough clinical examination, as well as noninvasive imaging without delay in order to improve the prognosis and chances of survival.


Autonomous manoeuvring systems for collision avoidance on single carriageway roads.
The accurate perception of the surroundings of a vehicle has been the subject of study of numerous automotive researchers for many years. Although several projects in this area have been successfully completed, very few prototypes have actually been industrialized and installed in mass produced cars. This indicates that these research efforts must continue in order to improve the present systems. Moreover, the trend to include communication systems in vehicles extends the potential of these perception systems transmitting their information via wireless to other vehicles that may be affected by the surveyed environment. In this paper we present a forward collision warning system based on a laser scanner that is able to detect several potential danger situations. Decision algorithms try to determine the most convenient manoeuvre when evaluating the obstacles' positions and speeds, road geometry, etc. Once detected, the presented system can act on the actuators of the ego-vehicle as well as transmit this information to other vehicles circulating in the same area using vehicle-to-vehicle communications. The system has been tested for overtaking manoeuvres under different scenarios and the correct actions have been performed.


A Comparison of Base-calling Algorithms for Illumina Sequencing Technology.
Recent advances in next-generation sequencing technology have yielded increasing cost-effectiveness and higher throughput produced per run, in turn, greatly influencing the analysis of DNA sequences. Among the various sequencing technologies, Illumina is by far the most widely used platform. However, the Illumina sequencing platform suffers from several imperfections that can be attributed to the chemical processes inherent to the sequencing-by-synthesis technology. With the enormous amounts of reads produced, statistical methodologies and computationally efficient algorithms are required to improve the accuracy and speed of base-calling. Over the past few years, several papers have proposed methods to model the various imperfections, giving rise to accurate and/or efficient base-calling algorithms. In this article, we provide a comprehensive comparison of the performance of recently developed base-callers and we present a general statistical model that unifies a large majority of these base-callers.


[The impact of migratory processes on the epidemiology of tuberculosis in the Stavropol' territory].
Tuberculosis morbidity in the Stavropol territory has recently increased from 31.5 to 43.0 per 100,000. It is particularly high among migrants: 499.0 per 100,000 migrants in 1995. There are high incidence rates of tuberculosis and the migrants from Chechnya were shown to adversely affect the epidemiology of tuberculosis in the Stavropol territory, on the contamination processes in the native children in particular.


Density-dependent selection closes an eco-evolutionary feedback loop in the stick insect Timema cristinae.
Empirical demonstrations of feedbacks between ecology and evolution are rare. Here, we used a field experiment to test the hypothesis that avian predators impose density-dependent selection (DDS) on Timema cristinae stick insects. We transplanted wild-caught T. cristinae to wild bushes at 50 : 50 cryptic : conspicuous morph ratio and manipulated density by transplanting either 24 or 48 individuals. The frequency of the conspicuous morph was reduced by 73% in the low-density treatment, but only by 50% in the high-density treatment, supporting a hypothesis of negative DDS. Coupled with previous studies on T. cristinae, which demonstrate that maladaptive gene flow reduces population density, we support an eco-evolutionary feedback loop in this system. Furthermore, our results support the hypothesis that predator satiation is the mechanism driving DDS. We found no effects of T. cristinae density on the abundance or species richness of other arthropods. Eco-evolutionary feedbacks, driven by processes like DDS, can have implications for adaptive divergence and speciation.


[Female students and medical and dental student magazines].
Female students participation in the magazines edited by the Students Centers of Medicine and Odontology is analysed in this work. For the first one it's considered the period 1901-1909 and for the second one, the study includes the years 1914-1958. In both cases the different periods of the publication are explained, mentioning the female students actuation. The author encloses the corresponding bibliography.


Expression of multidrug resistance-associated protein 1 in hepatocellular carcinoma is associated with a more aggressive tumour phenotype and may reflect a progenitor cell origin.
Hepatocellular carcinoma (HCC) responds poorly to chemotherapy owing to multidrug resistance (MDR). Recent studies showed that part of HCC could be of progenitor cell origin. Because some MDR-conferring transporters [multidrug resistance-associated protein 1 (MRP1), MDR1, MRP3 and breast cancer resistance protein (BCRP)] are expressed in hepatic progenitor cells (HPCs), expression in HCC might reflect a progenitor cell origin and provide the tumour cells with a MDR phenotype. The transcriptional profile of transporter genes was assessed in 139 HCCs earlier subjected to global gene expression analysis. In addition, we performed real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry for MRP1, MRP3, MDR1, BCRP and biliary/HPC markers keratin 7 and/or keratin 19 (K7/K19) on an independent set of 23 HCCs and surrounding liver. Micro-array analysis showed that MRP1 was the only transporter with increased mRNA levels in HCC compared with the surrounding tissue. MRP1 mRNA levels were significantly higher in HCCs with poor survival and the 'hepatoblast subtype' of HCC, thought to be derived from HPCs. In 11 of 23 HCCs of the independent set, we found a diffuse protein expression of MRP1 compared with negative hepatocytic expression observed in normal (surrounding) hepatocytes. MRP1 was expressed in K19(+) non-neoplastic HPCs and K19(+) tumour cells. In addition, MRP3 and BCRP were expressed in K7/K19(+) tumour cells. MRP1 expression was high in poorly differentiated HCCs, large tumours (>7 cm) and microvascular invasive tumours. MRP1 correlated with K19 mRNA and protein expression in two independent series of HCC. In addition, MRP1 was, together with MRP3 and BCRP, colocalized with K7/K19 in the tumour. Therefore, MRP1 expression could be a reflection of the HPC origin of this subgroup of HCCs and may result in an aggressive tumour phenotype.


Near infrared bioluminescence resonance energy transfer from firefly luciferase--quantum dot bionanoconjugates.
The bioluminescence resonance energy transfer (BRET) between firefly luciferase enzymes and semiconductive quantum dots (QDs) with near infrared emission is described. The QD were phase transferred to aqueous buffers using a histidine mediated phase transfer route, and incubated with a hexahistidine tagged, green emitting variant of firefly luciferase from Photinus pyralis (PPyGRTS). The PPyGRTS were bound to the QD interface via the hexahistidine tag, which effectively displaces the histidine layer and binds directly to the QD interfaces, allowing for short donor-acceptor distances (∼5.5 nm). Due to this, high BRET efficiency ratios of ∼5 were obtained. These PPyGRTS-QD bio-nano conjugates were characterized by transmission electron microscopy, thermal gravimetric analysis, Fourier transform infrared spectroscopy and BRET emission studies. The final optimized conjugate was easily observable by night vision imaging, demonstrating the potential of these materials in imaging and signaling/sensing applications.


Max Weber's antinomies of the Fall: Paradisiacal ethics and the populist Zeitgeist.
This article points out that the way the biblical myth of the Fall has been interpreted in the Judeo-Christian tradition is a crucial heuristic in the works of Max Weber, an assessment that hitherto largely remained unnoticed. Nevertheless, Weber's understanding of everyday action is closely related to the various religious interpretations of what deprivations were suffered by humanity as a consequence of Adam's original sin and the paradisiacal yearning for salvation it engenders. Moreover, Weber's interpretation of the Fall is characteristic for his tragic sociology in the sense that it guarantees the freedom to subjectively create self-conscious meaning that is, however, no longer embedded in a context of common knowledge. His solution to this epistemological problem involves a Nietzschean heroic existentialism whereby individuals give personality to one's character by freely choosing their own values. Yet, he also realizes that many will not be able to choose by themselves and, therefore, will be attracted by charismatic leaders that can invoke a paradisiacal community of choice. Weber's modern antinomical interpretation of the Fall is still relevant today because it provides insight in the epistemological underpinnings of the contemporary populist Zeitgeist.


Starfish oocyte maturation: 1-methyladenine triggers a drop of cAMP concentration related to the hormone-dependent period.
Oocyte maturation (meiosis reinitiation) in starfish is induced by the natural hormone 1-methyladenine (1-MeAde). Oocytes of Evasterias troschelii contain 0.43 pmole cyclic AMP/mg protein and 0.47 pmole cyclic GMP/mg protein. Upon stimulation by 1-MeAde the oocytes undergo a moderate (10-30%) decrease in their cAMP concentration. The concentration of cGMP remains unaltered. Oocytes treated with forskolin, an activator of adenylate cyclase, increase their cAMP concentration over 35-fold, up to 16 pmole cAMP/mg protein. When stimulated by 1-MeAde these forskolin-pretreated oocytes undergo a major (50-70%) decrease in their cAMP concentration. A similar decrease is triggered by mimetics of 1-MeAde, such as dithiothreitol, arachidonic acid (AA), and 8-hydroxyeicosatetraenoic acid (8-HETE), but not by adenine which is inactive. 1-MeAde-stimulated oocytes of Pisaster ochraceus also undergo a decrease in cAMP content, the size of which is increased by forskolin. Although a decrease in cAMP begins at sub-threshold 1-MeAde concentrations, the maximal decrease occurs at the same concentration of 1-MeAde needed for maturation induction and a further 1000-fold increase of the 1-MeAde concentration has no further effect. Upon removal of 1-MeAde, the cAMP concentration immediately increases to its original level. Sequential addition and removal of 1-MeAde triggers a sequential decrease and increase of the cAMP concentration, illustrating the continuous requirement for 1-MeAde for eliciting the decrease. Successive additions of 1-MeAde, however, do not trigger further decreases of the cAMP concentration. The temperature dependences of the cAMP concentration decrease and of the hormone-dependent period (HDP; the time of contact with 1-MeAde required for induction of maturation) are closely related. Forskolin, which increases the cAMP concentration, also increases the duration of the HDP (2.5-fold), delays the time course of protein phosphorylation burst and germinal vesicle breakdown, and inhibits AA- and 8-HETE-induced maturation. We conclude that 1-MeAde triggers a drop in cAMP concentration, which is tightly associated with the hormone-dependent period of oocyte maturation.


Circadian variation of epidermal growth factor receptor in mouse liver.
The liver undergoes a biochemical and morphological circadian transformation. In this paper, we document circadian variation in the binding parameters of the hepatic epidermal growth factor receptor (EGFR). Liver membranes were prepared from ad libitum fed or fasted male CD2F1 mice killed at different circadian phases at 4 h intervals. Bmax (maximum binding) and Kd (dissociation constant) varied in a rhythmic fashion. The range of change for Bmax along the 24 h time scale was 423%. For Kd, it was 162%. Both peaked late in the dark span, and decreased late in the light span. Fasting and EGF treatment reduced Bmax and the amplitude of circadian variation.


Effect of regional fat loss assessed by DXA on insulin resistance and dyslipidaemia in obese women.
To investigate the impact of reduction in total fat mass (FM) and regional FMs on indices of insulin resistance and dyslipidaemia in obese women (BMI > 30 kg/m(2)) after a 1-year weight loss (WL) program; and, secondly, to investigate the potential predictive effect of baseline insulin resistance on reduction in total and regional FMs. In 35 women with > 4 kg weight loss, body composition by DXA (dual X-ray absorptiometry), fasting insulin, C-Peptide, insulin resistance (HOMA-IR), insulin sensitivity (QUICKI), metabolic clearance rate (MCRestOGTT) and serum lipids were assessed. Mean WL was 9.6%; trunk and leg FM were reduced proportionally (14.9-14.7%). Improvement in HOMA-IR was 34.7%, insulin 30.7%, QUICKI 8.6% and MCRest OGTT 74%. The reduction in total, trunk and leg FM were similarly correlated with improvement in indices of insulin resistance (p < 0.001-0.05) and also with initial HOMA-IR (p = 0.000-0.02). In linear regressions improvement in HOMA-IR was similarly related with these FMs (p = 0.008), and initial HOMA predicted loss of trunk FM (p = 0.01). In multivariate analysis improvement in HOMA-IR was explained by loss of total FM (R(2) = 0.20, p = 0.004); improvement of QUICKI by loss of leg FM (R(2) = 0.33, p < 0.001). Loss of leg FM and trunk FM had similar importance for the improvement in insulin resistance. Baseline HOMA-IR predicted the potential for reduction in trunk FM.


N-Methyl-D-aspartate Glutamate Receptor Modulates Cardiovascular and Neuroendocrine Responses Evoked by Hemorrhagic Shock in Rats.
Here, we report the participation of N-methyl-D-aspartate (NMDA) glutamate receptor in the mediation of cardiovascular and circulating vasopressin responses evoked by a hemorrhagic stimulus. In addition, once NMDA receptor activation is a prominent mechanism involved in nitric oxide (NO) synthesis in the brain, we investigated whether control of hemorrhagic shock by NMDA glutamate receptor was followed by changes in NO synthesis in brain supramedullary structures involved in cardiovascular and neuroendocrine control. Thus, we observed that intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK801, 0.3 mg/kg) delayed and reduced the magnitude of hemorrhage-induced hypotension. Besides, hemorrhage induced a tachycardia response in the posthemorrhage period (i.e., recovery period) in control animals, and systemic treatment with MK801 caused a bradycardia response during hemorrhagic shock. Hemorrhagic stimulus increased plasma vasopressin levels during the recovery period and NMDA receptor antagonism increased concentration of this hormone during both the hemorrhage and postbleeding periods in relation to control animals. Moreover, hemorrhagic shock caused a decrease in NOx levels in the paraventricular nucleus of the hypothalamus (PVN), amygdala, bed nucleus of the stria terminalis (BNST), and ventral periaqueductal gray matter (vPAG). Nevertheless, treatment with MK801 did not affect these effects. Taken together, these results indicate that the NMDA glutamate receptor is involved in the hemorrhagic shock by inhibiting circulating vasopressin release. Our data also suggest a role of the NMDA receptor in tachycardia, but not in the decreased NO synthesis in the brain evoked by hemorrhage.


The Impact of a Theory-Based mHealth Intervention on Disease Knowledge, Self-efficacy, and Exercise Adherence Among Ankylosing Spondylitis Patients: Randomized Controlled Trial.
Patient education is recommended as an integral part of disease management in ankylosing spondylitis (AS), a chronic rheumatic disease that predominantly affects young males and requires long-term disease management. Convenient and cost-effective approaches to deliver patient education are required to these patients. This study aimed to examine the effects of a theory-based educational intervention delivered through a social networking app, WeChat, on disease knowledge, self-efficacy, exercise adherence, and health outcomes in Chinese AS patients. This study was a single-blind randomized controlled trial conducted in a tertiary hospital in Chengdu, China. Eligible participants were randomly allocated to the intervention or control group. Participants in the control group received standard care. The intervention group received the health belief model (HBM)-based educational intervention, consisting of 4 individual educational sessions and educational information sharing through WeChat, the predominant social networking app in China. The primary outcomes were disease knowledge, self-efficacy, and exercise adherence. The secondary outcomes were disease activity and physical function. Data were collected at baseline and at the end of the intervention (12th week). Chi-square test, t test, Mann-Whitney U tests were used to examine the effects of educational intervention. This study included 118 patients with AS. The majority of participants were male (93/118, 78.8%). Around half of them were married (56/118, 47.5%), never smoked (70/118, 59.3%), and had college educational level or above (62/118, 52.5%). At posttest, participants in the intervention group had higher disease knowledge (all P<.001) and self-efficacy (P<.001), and a larger proportion of participants in the intervention group adhered to regular exercise routines than those in the control group (P=.003). The within-group analyses for the intervention group showed increases in all scores of disease knowledge (all P<.001) and self-efficacy score (P<.001), but only correct answer score (P=.04) and general knowledge score (P=.002) of disease knowledge in the control group improved. The within-group analysis for the control group found a decline of physical function (P=.002) but no significant change in disease activity (P>.05). The within-group analysis for the intervention group showed no significant change in disease activity or physical function (P>.05). At posttest, no statistically significant difference was found on disease activity or physical function between the intervention and control groups (P>.05). The HBM-based educational intervention through WeChat can effectively improve patient disease knowledge, self-efficacy, and exercise adherence. WeChat is feasible and effective to deliver patient education for patients with chronic diseases such as AS. This mHealth intervention can be integrated into routine rheumatology care. Chinese Clinical Trial Registry ChiCTR-IPR-16009293; https://tinyurl.com/swxt8xk7.


Hepatitis B virus vaccination in HIV-infected people: A review.
HBV immunization is highly recommended in people infected with HIV. However, the classical schedule used in the general population has been shown to be insufficient in people living with HIV. This review summarizes the main studies dealing with HBV vaccination in people living with HIV, depending on their baseline status (in particular, never vaccinated, already vaccinated, or with an isolated anti-HBc serological profile). It shows that reinforced 40µg intramuscular HBV vaccination schedules are now frequently recommended, either initially in people never vaccinated, or in the lack of an anamnestic response in other situations. Adjuvants cannot be currently recommended. Anti-HBs titers have to be checked 1 to 2 months following the last vaccine dose, and annually thereafter a booster is necessary if antiHBs titers decrease below 10 mIU/mL. In patients with a CD4 cell count <200/µL, guidelines recommend starting the vaccination regimen as soon as possible after HAART has been started.


5-lipoxygenase-activating protein stimulates the utilization of arachidonic acid by 5-lipoxygenase.
5-Lipoxygenase (5-LO) and its activating protein (FLAP) are both required for cellular leukotriene (LT) synthesis, with 5-LO catalyzing both the synthesis of (5S)-5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE) from arachidonic acid and the subsequent synthesis of LTA4 from 5-HPETE. We have previously expressed both human 5-LO and human FLAP to high levels in Spodoptera frugiperda (Sf9) insect cells, using recombinant baculoviruses. To study the mechanism by which FLAP activates 5-LO, we compared cellular 5-LO activity in Sf9 cells expressing this enzyme to that in Sf9 cells coexpressing FLAP and 5-LO. In this system, FLAP stimulates the utilization of arachidonic acid by 5-LO as a substrate, and increases the efficiency with which 5-LO converts 5-HPETE to LTA4. LT synthesis in cells coexpressing FLAP and 5-LO is inhibited by 3-[1-(p-chlorophenyl)-5-isopropyl-3-tert-butylthio-1H-indol-2-yl]-2,2- dimethyl-propanoic acid (MK-886), an LT biosynthesis inhibitor which specifically binds to FLAP. These studies in Sf9 cells, together with our recent demonstration that FLAP specifically binds arachidonic acid, suggests that FLAP activates 5-LO by acting as an arachidonic acid transfer protein.


Intra-operative liver ultrasound--a contribution to colorectal carcinoma staging.
Laparoscopic resection of colorectal carcinoma is now a well-established surgical technique with oncology treatment outcome similar to open surgery, yet performing better in some short-term variables. The technique, however, does not allow palpation of intra-abdominal organs and the liver in particular. This prospective study aims to assess the performance of laparoscopic intra-operative ulrasonography of the liver (L-IOUS) and compare its findings with pre-operative staging data. In total 70 patients, 53 men and 17 women, who were recruited into the study, were indicated for primary laparoscopic resection for colorectal carcinoma, with laparoscopic intra-operative ulrasonographic examination of the liver (L-IOUS) being used during the initial part of the operation. Before surgery, all patients underwent abdominal and pelvic contrast CT examinations. Ultrasonographic examination of the liver was included. In 14 patients L-IOUS detected a synchronous metastatic lesion of the liver as opposed to only six patients with pre-operative CT-positive findings. Furthermore, CT-positive metastases in three patients were not confirmed by L-IOUS. Several patients were diagnosed with benign lesions not disclosed during pre-operative assessment, e.g. haemangioma in 5 vs 2 patients, focal nodular hyperplasia in 3 vs 1 patient and liver cysts in 7 vs 5 patients. Results of the presented prospective study substantiate the use of laparoscopic intra-operative ultrasound of the liver (L-IOUS) within the standard staging protocol, as this seems to appropriately supplement the results of the pre-operative staging. In cases of colorectal carcinoma the method allows highly sensitive detection of occult synchronous liver metastases that could finally alter a therapeutic strategy.


An audit of knee radiographs performed for general practitioners.
The Royal College of Radiologists (RCR) has published guidelines concerning indications for imaging investigations. These include plain radiography of the knee, the indications for which are locking or signs of restricted movement. This audit consisted of 1153 knee radiographs in a 9 month period, results of a questionnaire sent to general practitioners (GPs), analysis of radiological reports and returned questionnaires (55% of cases), and subsequent comments from the GPs on receiving these results. Only 50% of cases fall within RCR guidelines, 90% of radiographs were normal or showed degenerative change. In 42% of cases, knee radiographs were requested to confirm previously expected degenerative change, and in 30% patient pressure was a significant factor. Most knee radiographs (87%) result in no significant change in management apart from continuation of symptomatic measures. Application of current guidelines, however, would miss some important diagnoses manifest clinically by persistent pain or effusion, for example loose body or Brodie's abscess. In cases of locking, where a radiograph may miss significant soft tissue abnormality, there was concern that reassurance was often gained by a normal examination. This audit shows that many knee radiographs are unnecessary. The guidelines appear appropriate with the proviso that persistent pain and effusion should be included as indications for investigation. Many GPs report medico-legal considerations as important reasons for unnecessary referrals, although the application of guidelines should be protection against this. The referral rate for knee radiographs before and after the communication of these results has not altered.


Ultrastrong and Tough Supramolecular Hydrogels from Multiurea Linkage Segmented Copolymers with Tractable Processablity and Recyclability.
Strong and tough synthetic hydrogels have received ever-increasing interests due to their potential applications as load-bearing structural materials. However, strong, tough, and recyclable hydrogels in different forms that can be generated by different methods according to various practical applications still remain an intrinsic bottleneck. A simple one-pot synthesis of multiurea linkage segmented linear copolymers with easy recyclability, hybridization, and processability, including compression molding, solution casting, and spinning methods, to yield ultrastrong and tough hydrogel films or stretchable hydrogel fibers with diameters ranged from macro-, micro-, to nanoscale, is reported here.


Relationship satisfaction and conflict over minor and major issues in romantic relationships.
In this study the question of whether conflicts over minor issues and over major issues were equally strongly related to satisfaction in romantic relationships was examined. Sixty-four women and 29 men completed the Hendrick (1988) Relationship Assessment Scale for their current main romantic relationship and a 12-item conflict scale (Cramer, 2000b) for minor and major issues. All the relationships were heterosexual. Satisfaction was significantly and equally negatively correlated with conflict over minor and major issues, suggesting that whether an issue is of major or minor importance does not affect satisfaction or dissatisfaction in a romantic relationship. Thus, assessing conflict over major issues may be unnecessary in predicting relationship satisfaction. Conflict over minor and major issues was significantly and positively correlated even when satisfaction was controlled, indicating consistency in conflict resolution.


Evaluation of four methods for detection of Clostridium difficile or C. difficile toxin: cytotoxin assay, culture, latex agglutination, and a new rapid immunoassay (C. difficile toxin A test).
The performance of C. difficile toxin A test (Oxoid, Basingstoke, UK), an immunoassay for the detection of C. difficile toxin A in fecal samples, for the diagnosis of C. difficile-associated diarrhea was compared with those of cytotoxin assay, culture, and a latex agglutination assay (Culturette Brand CDT Rapid Clostridium difficile test; Becton Dickinson, Cockeysville, MD). A total of 105 stool specimens from 71 patients were tested. Of the 105 specimens analyzed, 6 (5.7%) samples were positive by all four methods, 66 samples (62.9%) were concordant negative. Two patients fulfilled all clinical criteria for C. difficile-associated diarrhea but had negative results in the cytotoxicity tests. The sensitivity and specificity, as determined against cytotoxin assay results, were, respectively 52.4% and 93.9% for latex agglutination, 68.2% and 84.3% for rapid immunoassay and 36.4% and 92.8% for culture. No single laboratory test yields a definitive diagnosis of C. difficile-associated diarrhea at present. Test results by any of these methods must be used in conjunction with patient history when making the diagnosis to avoid indiscriminate treatment of individuals without disease or the lack of treatment for individuals with a serious infection. We consider the rapid and easy-to-perform C. difficile toxin A test not to be an essential adjunct for the diagnosis of C. difficile-associated diarrhea.


Nearsightedness of electronic matter as seen by a physicist and a chemist.
The theorem of Hohenberg and Kohn, that the electron density is a unique functional of the external potential, applies to a closed system with a fixed number of electrons. Transferability of the electron density of an atom between two systems, necessary to account for the fundamental role of a functional group with characteristic properties in chemistry, however, is a problem in the physics of an open system. Transferability in chemistry requires a new theorem stated in terms of the density: that the electron density of an atom in a molecule or crystal determines its additive contribution to all properties of the total system, its transferability being determined by a paralleling degree of transferability in the atom's virial field, the virial of the Ehrenfest force exerted on its electron density. Transferability of the virial field is found in spite of unavoidable changes in the external potential that occur on transfer. The properties of an atom in a molecule are determined by the Heisenberg equation of motion for a "proper open system" derived from the principle of stationary action. The theorem is grounded in the common sense observation that two atoms that "look the same", i.e., have the same charge distribution, must possess identical properties. Transferability is discussed in terms of the properties of the electron density, the one-density and the two-density matrix, the latter demonstrating that both the Coulombic and exchange contributions to the energy of a group are separately transferable. It is demonstrated that the exchange indices determined by the two-density matrix provide a readily determinable measure of the effective range of the exchange energy.


Organization of the centromeric region of chromosome XIV in Saccharomyces cerevisiae.
A 15.1 kb fragment of the yeast genome was allocated to the centromeric region of chromosome XIV by genetic mapping. It contained six bona fide genes, RPC34, FUN34, CIT1 (Suissa et al., 1984), RLP7, PET8 and MRP7 (Fearon and Mason, 1988) and two large open reading frames, DOM34 and TOM34. RPC34 and RLP7 define strictly essential functions, whereas CIT1, PET8 and MRP7 encode mitochondrial proteins. The PET8 product belongs to a family of mitochondrial carrier proteins. FUN34 encodes a putative transmembraneous protein that is non-essential as judged from the normal growth of the fun34-::LUK18(URA3) allele even on respirable substrates. TOM34 codes for a putative RNA binding protein, and DOM34 defines a hypothetical polypeptide of 35 kDa, with no significant homology to known proteins. The region under study also contains two divergently transcribed tDNAs, separated only by a chimeric transposable element. This tight tDNA linkage pattern is commonly encountered in yeast, and a general hypothesis is proposed for its emergence on the Saccharomyces cerevisiae genome. RPC34, RLP7, PET8 and MRP7 are unique on the yeast genome, but the remaining genes belong to an extant centromeric duplication between chromosome III and XIV.


Aerosol enrichment of the surfactant PFO and mediation of the water--air transport of gaseous PFOA.
Aerosol-mediated transport of perfluorooctanoate (PFO) from a water body to the atmosphere and the subsequent emission of gas-phase perfluorooctanoic acid (PFOA) was investigated. The potential for this process to facilitate long-range transport of PFOA/PFO was assessed. In a laboratory experiment, aerosols were generated and collected from deionized, fresh, and ocean waters spiked with PFO and analyzed by LC-MS/MS. Gas-phase samples were also collected from the system and analyzed for PFOA. Aerosols were found to have significantly higher concentrations of PFO than the parent water body (< or = 80 times for ocean waters). The PFOA, at equilibrium with the PFO in the aqueous aerosol, partitioned rapidly (t 1/2 = 7.2 s) out of the aerosol droplet. This suggests that rainout rates are likely to be longer than previously hypothesized. These results imply that water bodies are not a permanent sink for atmospheric PFOA as previous studies have suggested. The occurrence of contamination in remote regions may not depend solely on the previously hypothesized indirect sources but also on the long-range transport, via the gas phase, of direct releases of PFOA to both the aquatic and atmospheric environments.


Hemispatial neglect: clinic, pathogenesis, and treatment.
Hemispatial neglect is characterized by a failure of awareness on the side of space and body opposite the site of injury, has been extensively studied for its theoretical interest in revealing brain mechanisms of awareness and attention. More recently, it has become apparent that hemispatial neglect reflects not only damage of specific anatomical regions, but also the large-scale dysfunction of networks of brain regions specialized in attention, motor, and multimodal sensory processing. Finally, although previous studies showed that the symptoms of hemispatial neglect could be effectively, albeit transiently, improved by a variety of behavioral, pharmacological, and physical interventions, only recently have treatment studies begun to show long-lasting therapeutic effects. Future advances will require the integration of advanced brain imaging methods to identify abnormal brain circuitries and-in combination with sensory, cognitive, and neural stimulation-methods to modulate activity in those circuitries.


Clinical use of polyvalent intravenous immunoglobulins during intensive polychemotherapy in children with acute lymphoblastic leukemia.
Acute lymphoblastic leukemia (ALL) is seen in almost 30% of cases of cancer among children. Drop in absolute neutrophil count (ANC) and immunosuppression during chemotherapy are causing the significant increase in the risk of other complications, which can lead to prolonged hospitalization, higher costs of therapy and increased mortality. The analysis concerned 78 patients treated for ALL at the Department of Pediatric Oncology, Hematology and Transplantology. The indications for the use of immunoglobulins, the regimen of administration, the dose and adverse reactions were analyzed. Intravenous immunoglobulins (IVIGs) were used in 66 (85%) of 78 patients. The standard risk group (SR) was represented by 10 (15%) patients, intermediate (IR) - 29 (44%), and high (HR) - 27 (41%). The most common were 1 and 2-day administrations - 60% and 28%, respectively, of transfusions. The spread of the IVIG doses used ranged from 43 mg to 882 mg/kg body weight. In the SR and IR groups, preparations were transfused at the reinduction stage, while in the HR-consolidation. Among the indications for IVIG, the most common was hypogammaglobulinemia-117 (42%), neutropenia-69 (25%) and infection-62 (22%). During the implementation of 279 patterns of immunoglobulin preparations, 8 (3%) post-transfusion reactions were registered. The vast majority of ALL patients required immunoglobulin substitution during polychemotherapy. The supply of preparations is safe, however, there are no unambiguous guidelines regarding their dosage.


A Universal Intensity Standardization Method Based on a Many-to-One Weak-Paired Cycle Generative Adversarial Network for Magnetic Resonance Images.
In magnetic resonance imaging (MRI), different imaging settings lead to various intensity distributions for a specific imaging object, which brings huge diversity to data-driven medical applications. To standardize the intensity distribution of magnetic resonance (MR) images from multiple centers and multiple machines using one model, a cycle generative adversarial network (CycleGAN)-based framework is proposed. It utilizes a unified forward generative adversarial network (GAN) path and multiple independent backward GAN paths to transform images in different groups into a single reference one. To preserve image details and prevent resolution loss, two jump connections are applied in the CycleGAN generators. A weak-pair strategy is designed to fully utilize the prior knowledge of the organ structure and promote the performance of the GANs. The experiments were conducted on a T2-FLAIR image database with 8192 slices from 489 patients. The database was obtained from four hospitals and five MRI scanners and was divided into nine groups with different imaging parameters. Compared with the representative algorithms, the peak signal-to-noise ratio, the histogram correlation, and the structural similarity were increased by 3.7%, 5.1%, and 0.1% on average, respectively; the gradient magnitude similarity deviation, the mean square error, and the average disparity were reduced by 19.0%, 15.7%, and 9.9% on average, respectively. Experiments also showed the robustness of the proposed model with a different training set configuration and effectiveness of the proposed framework over the original CycleGAN. Therefore, the MR images with different imaging settings could be efficiently standardized by the proposed method, which would benefit various data-driven applications.


A Novel Tension Machine Promotes Bone Marrow Mesenchymal Stem Cell Osteoblastic and Fibroblastic Differentiation by Applying Cyclic Tension.
Bone marrow mesenchymal stem cells (BMSCs) are intraosseous stem cells, and the effects of tensile strain on BMSC differentiation mediate several bone-related treatments. To study the response of BMSCs under tension, we designed and developed a small cellular tension instrument, iStrain. When iStrain applied tension on BMSCs, these cells exhibited convergence in the alignment direction and lengthening of the cell processes and cell body. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting demonstrated that iStrain-mediated cyclic tension promotes the differentiation of BMSCs toward osteogenesis and fibrogenesis. And the mRNA and protein expression of differentiation-related genes changes with the extension of tension time.


Autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway.
Autophagy plays important roles in self-renewal and differentiation of stem cells. Hepatic progenitor cells (HPCs) are thought to have the ability of self-renewal as well as possess a bipotential capacity, which allows them to differentiate into both hepatocytes and bile ductular cells. However, how autophagy contributes to self-renewal and differentiation of hepatic progenitor cells is not well understood. In this study, we use a well-established rat hepatic progenitor cell lines called WB-F344, which is treated with 3.75 mM sodium butyrate (SB) to promote the differentiation of WB-F344 along the biliary phenotype. We found that autophagy was decreased in the early stage of biliary differentiation, and maintained a low level at the late stage. Activation of autophagy by rapamycin or starvation suppressed the biliary differentiation of WB-F344. Further study reported that autophagy inhibited Notch1 signaling pathway, which contributed to biliary differentiation and morphogenesis. In conclusions, autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway.


[Endoscopic preoperative intralesional injection of OK-432 in early gastric cancer].
The study group consisted of 35 patients with early gastric cancer, 16 of whom were admitted for preoperative immunotherapy. Ten to 40 K.E. of OK-432 was injected intralesionally by endoscope, and then gastrectomy was performed. After the intralesional injection, fever, nausea, vomiting and epigastralgia occurred. In cancer lesion and regional lymph node, histological findings from OK-432 treated group were compared to those of the control group. Lymphoid cell infiltration at cancer lesion was marked in OK-432 treated group, and degenerated cancer cells were found in 3 cases. On the other hand, lymphoid follicles showed a marked statistical increase in OK-432 treated group. Also the cases with marked lymphoid follicle showed increased numbers of peripheral blood lymphocyte. From the results, intralesional injection of OK-432 may confirm the tumor-associated antigenicity and serves as a useful method to potentiate the specific and/or non-specific immunity in regional lymph nodes.


Epidermoid cyst of the testis. Case report with a review of the literature.
Epidermoid cysts of the testis are rare, benign testicular tumors. Only 188 cases have been reported in the world literature until July 1986. There is controversy in the literature regarding whether local excision or enucleation of the cyst and sparing the testicle or orchiectomy is the preferred treatment approach of these lesions. A case with epidermoid cyst of testis, diagnosed correctly by ultrasound and frozen section and treated successfully by an excisional operation, is presented.


Multiple roles of the tuberous sclerosis complex genes.
Soon after proposing the "two-hit" hypothesis for tumorigenesis, Knudson pursued further experimental validation of the concept by using a rat model of dominantly inherited renal tumor. Today, the Eker rat is one of the best characterized models of tuberous sclerosis complex (TSC) and has been used extensively for study of the function of the TSC2 tumor suppressor gene. Along with TSC1, these two genes behave as expected for tumor suppressor genes with evidence for loss of heterozygosity in tumors and suppression of growth when expressed in proliferating cells. Despite much experimental work, the mechanisms of these genes have remained elusive until recently. This review summarizes some of the current concepts in our understanding of the biological and biochemical function of the TSC genes.


To RNA-binding and beyond: Emerging facets of the role of Rbfox proteins in development and disease.
The RNA-binding Fox-1 homologue (Rbfox) proteins represent an ancient family of splicing factors, conserved through evolution. All members share an RNA recognition motif (RRM), and a particular affinity for the GCAUG signature in target RNA molecules. The role of Rbfox, as a splice factor, deciding the tissue-specific inclusion/exclusion of an exon, depending on its binding position on the flanking introns, is well known. Rbfox often acts in concert with other splicing factors, and forms splicing regulatory networks. Apart from this canonical role, recent studies show that Rbfox can also function as a transcription co-factor, and affects mRNA stability and translation. The repertoire of Rbfox targets is vast, including genes involved in the development of tissue lineages, such as neurogenesis, myogenesis, and erythropoeiesis, and molecular processes, including cytoskeletal dynamics, and calcium handling. A second layer of complexity is added by the fact that Rbfox expression itself is regulated by multiple mechanisms, and, in vertebrates, exhibits tissue-specific expression. The optimum dosage of Rbfox is critical, and its misexpression is etiological to various disease conditions. In this review, we discuss the contextual roles played by Rbfox as a tissue-specific regulator for the expression of many important genes with diverse functions, through the lens of the emerging data which highlights its involvement in many human diseases. Furthermore, we explore the mechanistic details provided by studies in model organisms, with emphasis on the work with Drosophila. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Turnover and Surveillance > Regulation of RNA Stability RNA Processing > Splicing Regulation/Alternative Splicing.


Relation between smoking status of physicians and their enthusiasm to offer smoking cessation advice.
Are nonsmoking physicians more likely to give smoking cessation advice to their patients? To determine this, we sent a questionnaire individually to physicians in Tokyo. The average age of the 323 respondents was 59.8 +/- 12.9 (mean +/- SD); 84.8% of them were male and 21.1% were smokers. Among the respondents, 88.8% asked their patients about their smoking status, 79.9% advised smoking patients to stop, and 93.5% believed smoking cessation interventions to be necessary. Nonsmoking physicians were more likely to advise patients to stop smoking (85.6%) than smoking physicians (70.1%); the smoking physicians who themselves wished to reduce cigarette consumption or stop smoking were more likely to do so (85.0%) than those who did not wish to reduce or stop (43.5%). Moreover, more nonsmoking physicians seriously felt that smoking cessation interventions are necessary (31.2%) than did smoking physicians (6.5%). In conclusion, the smoking status and attitude towards smoking of physicians influences their enthusiasm to give advice to their patients against smoking.


Endolymphatic duct blockage: a randomized controlled trial of a novel surgical technique for Ménière's disease treatment.
To compare the effectiveness of the endolymphatic duct blockage (EDB) and the endolymphatic sac decompression (ESD) to control Ménière's disease symptoms and to evaluate their effect on hearing level. Prospective nonblinded randomized study. Tertiary medical center. Fifty-seven patients affected by a refractory Ménière's disease were included out of which 22 underwent an ESD and 35 underwent an EDB. Five periods of follow-up were considered: 0 to 1 week, 1 week to 6 months, 6 to 12 months, 12 to 18 months, and 18 to 24 months. Mean outcome measurements consisted of vertigo control, tinnitus, aural fullness, instability, and hearing level. Hearing level was evaluated using pure-tone average (PTA) and speech discrimination score (SDS). There was no significant difference between the 2 groups in the number of vertigo spells per months preoperatively (P = .153). Twenty-four months postoperatively, 96.5% of the EDB group had achieved a complete control of vertigo spells against 37.5% of the ESD group with a statistically significant difference (P = .002). There was a better control of tinnitus and aural fullness with EDB (P = .021 and P = .014, respectively). There was no statistically significant difference in hearing level preoperatively (P = .976) and 24 months postoperatively (P = .287) between the 2 groups. Hearing level was preserved in each group with no significant difference between the preoperative and the postoperative levels (P > .05). EDB is more effective than the traditional ESD in controlling the symptoms of Ménière's disease. It is a novel surgical technique with promising results for a complete treatment of Ménière's disease. There are no significant complications or adverse effect.


Preclinical studies using the intratumoral aromatase model for postmenopausal breast cancer.
To determine the most effective strategies for the treatment of postmenopausal hormone dependent breast cancer, we recently developed a model system in nude mice. In this model, estrogen receptor-positive human breast cancer cells (MCF-7) stably transfected with the aromatase gene are inoculated into ovariectomized, immunosuppressed (nude) mice. These cells synthesize sufficient estrogen from androgen substrate to stimulate their proliferation and the development of tumors. Moreover, estrogen secreted by the tumor cells maintains uterine weight comparable to that of the intact mouse. In the present study, we employed this model to investigate the effects of the aromatase inhibitor, letrozole (CGS 20267 [Femara]) on mammary tumor growth and on the uterus. We also used this model to predict the effects of combining two aromatase inhibitors, letrozole and anastrozole (Arimidex), with the antiestrogen tamoxifen (Nolvadex). Letrozole was found to be a highly potent inhibitor of tumor proliferation and more effective than tamoxifen. No stimulation of uterine growth was observed with the aromatase inhibitors. However, the combination of letrozole or anastrozole and tamoxifen was no more effective than either aromatase inhibitor alone. The agonistic effect of tamoxifen on the uterus was observed when it was given alone and when combined with the aromatase inhibitors. Furthermore, letrozole had the most potent antitumor activity when compared to other aromatase inhibitors and antiestrogens. No additional benefit was observed by combining these agents with tamoxifen over treatment with aromatase inhibitors alone.


Organizational and community resilience for COVID-19 and beyond: Leveraging a system for health and social services integration.
To examine how a preexisting initiative to align health care, public health, and social services influenced COVID-19 pandemic response. In-depth interviews with administrators and frontline staff in health care, public health, and social services in Contra Costa County, California from October, 2020, to May, 2021. Qualitative, semi-structured interviews examined how COVID-19 response used resources developed for system alignment prior to the pandemic. We interviewed 31 informants including 14 managers in public health, health care, or social services and 17 social needs case managers who coordinated services across these sectors on behalf of patients. An inductive-deductive qualitative coding approach was used to systematically identify recurrent themes. We identified four distinct components of the county's system alignment capabilities that supported COVID-19 response, including (1) an organizational culture of adaptability fostered through earlier system alignment efforts, which included the ability and willingness to rapidly implement new organizational processes, (2) trusting relationships among organizations based on prior, positive experiences of cross-sector collaboration, (3) capacity to monitor population health of historically marginalized community members, including information infrastructures, data analytics, and population monitoring and outreach, and (4) frontline staff with flexible skills to support health and social care who had built relationships with the highest risk community members. Prior investments in aligning systems provided unanticipated benefits for organizational and community resilience during the COVID-19 pandemic. Our results illustrate a pathway for investment in system alignment efforts that build capacity within organizations and relationships between organizations to enhance resilience to crisis. Our findings suggest the usefulness of an integrated concept of organizational and community resilience that understands the resilience of systems of care as a vital resource for community resilience during crisis.


Knockdown of Collagen Triple Helix Repeat Containing-1 Inhibits the Proliferation and Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma Cells.
Collagen triple helix repeat containing-1 (CTHRC1), a secreted glycoprotein, is frequently upregulated in human cancers. However, the functional role of CTHRC1 in renal cell carcinoma (RCC) remains unclear. Thus, the aim of this study was to explore the role of CTHRC1 in RCC. Our results demonstrated that CTHRC1 was upregulated in RCC tissues and cell lines. Knockdown of CTHRC1 significantly inhibits the proliferation in RCCs. Furthermore, knockdown of CTHRC1 significantly inhibited the epithelial-to-mesenchymal transition (EMT) process in RCCs, as well as suppressed RCC cell migration and invasion. Mechanistically, knockdown of CTHRC1 inhibited the expression of β-catenin, c-Myc, and cyclin D1 in RCC cells. In conclusion, the results of the present study indicated that CTHRC1 downregulation inhibited proliferation, migration, EMT, and β-catenin expression in RCC cells. Therefore, CTHRC1 may be a potential therapeutic target for the treatment of RCC.


Political Ideology and Stigmatizing Attitudes Toward Depression: The Swedish Case.
Stigmatizing attitudes toward persons with mental disorders is a well-established and global phenomenon often leading to discrimination and social exclusion. Although previous research in the United States showed that conservative ideology has been related to stigmatizing attitudes toward mental disorders, there is reason to believe that this mechanism plays a different role in the context of a universal welfare state with a multi-party system such as Sweden. Furthermore, "mental disorders" may signify severe psychotic disorders, which may evoke more negative attitudes. This suggests the importance of specific studies focusing on the more common phenomenon of depression. This paper investigates the relationship between political ideology and stigmatizing attitudes toward depression in Sweden. This study is part of the New Ways research program. Data were collected by the Laboratory of Opinion Research (LORE) at the University of Gothenburg in 2014 (N = 3246). Independent variables were political ideology and party affiliation. The dependent variable was the Depression Stigma Scale (DSS). Data were analyzed with linear regression analyses and analyses of variance. More conservative ideology (B = 0.68, standard error [SE] = 0.04, P<.001) and more conservative party affiliation (F(8 2920) = 38.45, P<.001) showed more stigmatizing attitudes toward depression. Item-level analyses revealed a difference where the supporters of the conservative party differed (P<.05) from supporters of the liberal party, with a higher proportion agreeing that "people could snap out of " depression if they wanted to; the populist right-wing party differed from the conservative party with a higher proportion agreeing on items displaying people with depression as "dangerous" and "unpredictable." Even self-stigma was highest among the populist right-wing party with 22.3% agreeing that "if I had depression I wouldn't tell…." Political ideology was associated with stigmatizing attitudes toward depression in Sweden. The results also confirm the need to distinguish between different forms of conservatism by observing social distance as being a more important driver among voters for the populist right-wing party compared with personal agency and responsibility among voters for the more traditional conservative party.


Immunohistochemical and histoplanimetrical study on the endothelial receptor involved in transportation of minute chylomicrons into subepithelial portal blood in intestinal villi of the rat jejunum.
A portion of the minute chylomicrons less than 75 nm in diameter are transcytosed from the extravascular tissue into the subepithelial blood capillaries (sBC) in the villous apices of the rat jejunum. However, the details of the transportation mechanism have not been clarified. In this study, the endothelial receptor involved in the transportation of minute chylomicrons into the sBC's lumina was immunohistochemically and histoplanimetrically examined in intestinal villi of the rat jejunum. Immunopositivity for very low density lipoprotein (VLDL) receptor was detected on the luminal and basal surfaces of the endothelial cells of sBC in approximately 68% of those apices of jejunal villi that possessed numerous chylomicrons in the lamina propria, while VLDL receptor was detected on the endothelial cells of sBC in only approximately 8% of intestinal villi that possessed few or no chylomicrons in the lamina propria. No immunopositivity for LDL receptor was detected in the sBC of all intestinal villi. These findings suggest that VLDL receptor is expressed by the endothelial cells of the sBC in conjunction with the filling of the lamina propria of jejunal villi with many chylomicrons produced by the villous columnar epithelial cells and that the VLDL receptor mediates the transportation of minute chylomicrons, maybe VLDL, into the subepithelial portal blood from the extravascular tissue of the rat jejunal villi.


Hungarian paediatricians' attitudes regarding the treatment and non-treatment of defective newborns: a comparative study.
The four compared surveys clearly show that paediatricians from different backgrounds encounter these moral dilemmas in their everyday practice. Hungarian paediatricians facing morally significant decisions of discontinuation of treatment in defective newborns were permissive toward passive euthanasia like their Australian and Canadian colleagues, but were almost unanimously against active euthanasia like their Polish colleagues. The results of our study revealed a strong paternalistic attitude among Hungarian doctors, unwillingness to include other professionals in a discussion of moral problems and neglect of the nurses' views in these matters. Many physicians in the Hungarian study group were not aware of the legal ramifications in such cases. These findings were similar to the results of the Polish study. It is plausible that the paternalistic attitude and ignorance of the relevant law is common in all 'former' socialist countries. The Australian, Canadian and Hungarian doctors displayed more understanding and tolerance towards passive euthanasia. Many physicians in all study groups seemed to be not familiar with the legal regulations of their own country. The paediatricians of the four studies showed the greatest difference in their attitudes towards active euthanasia, with the Australian community being more permissive, the Canadian, Polish and Hungarian community rejecting it.


Clinical outcome of laminoplasty for cervical ossification of the posterior longitudinal ligament with K-line (-) in the neck neutral position but K-line (+) in the neck extension position: A retrospective observational study.
Patients with cervical ossification of the posterior longitudinal ligament (OPLL) who are K-line (-) are thought to have poor clinical outcomes after laminoplasty. The aim of this study is to compare the clinical results of patients with OPLL who were K-line (-) in the neck neutral position but K-line (+) in the neck extension position (NEP group) with patients with OPLL who were K-line (+) in the neck neutral position (NNP group).Retrospectively, 42 patients who underwent cervical laminoplasty for OPLL by our surgical group during 2012 and 2013 were reviewed and were followed for at least 2 years. The patients were divided into 2 groups according to K-line status. Standing plain radiographs of the cervical spine were obtained pre- and postoperatively. Cervical spine alignment parameters included the C2-7 Cobb angle and range of motion (ROM) measured on lateral radiographs. Clinical evaluation included pre- and postoperative JOA, NDI, and VAS scores.Ten patients were classified in the NEP group, and 32 patients were classified in the NNP group. Preoperatively, the OPLL involved segments were 4.10 ± 1.66 in the NEP group and 2.53 ± 1.16 in the NNP group (P = .005). The canal-occupying ratios were 58.40 ± 11.11% in the NEP group and 29.08 ± 11.38% in the NNP group (P < .001). The mean Cobb angle of both the groups had not changed significantly at the last follow-up. The mean cervical ROM of both the groups had decreased at the last follow-up. The mean JOA score of the NEP group improved significantly from 9.70 ± 2.16 to 12.50 ± 2.27 (P = .014). The mean JOA score of the NNP group improved significantly from 11.91 ± 1.69 to 14.93 ± 1.58 (P < .001). The mean JOA recovery rate was 32.71 ± 40.45% in the NEP group and 59.00 ± 33.80% in the NNP group (P = .036). The NDI scores of both groups were significantly decreased, and the VAS scores of both groups had not changed significantly at the last follow-up.Laminoplasty is a relatively effective and safe procedure for patients with K-line (-) in the neck neutral position but K-line (+) in the neck extension position. Instead of anterior surgery, we recommend laminoplasty for those patients with OPLL extending to 3 or more segments.


Quality of fresh-cut baby spinach grown under a floating trays system as affected by nitrogen fertilisation and innovative packaging treatments.
Alternative techniques for cultivation of leafy vegetables such as a floating tray system and unconventional gas mixtures for post-harvest active modified atmosphere packaging (MAP) could be of interest in the minimally processed vegetable industry. The combined effect of three pre-harvest fertilisation doses (8, 12 or 16 mmol N L(-1)) and three post-harvest MAP conditions (passive, super-atmospheric or N2O-enriched) on the main quality attributes of fresh-cut baby spinach leaves throughout 10 days at 5 degrees C was studied. After 8 days of shelf life, spinach leaves fertilised with 8 and 16 mmol N L(-1) and stored under N2O-enriched MAP showed the lowest microbial growth, with good sensory quality. Such combined treatments also preserved the total antioxidant capacity sampled at harvest (8 g ascorbic acid equivalent antioxidant capacity kg(-1) f.w.). A decrease of 10-20% in total vitamin C content regardless of N fertilisation and packaging treatment was found during shelf life. Total phenolics content at harvest was 2 g gallic acid equivalents kg(-1) f.w., which was slightly decreased or preserved during shelf life while total chlorophylls were preserved for all treatments assayed around 550 mg kg(-1) f.w. No clear effect of fertilisation doses was observed during post-harvest storage on overall quality of fresh-cut baby spinach leaves, while N2O-enriched atmospheres seems to be a promising alternative to passive MAP for extending shelf life.


Invasive Ductal Carcinoma within a Benign Phyllodes Tumor.
BACKGROUND Phyllodes tumor (PT) is a rare neoplasm of the breast. Concomitant PT with invasive ductal carcinoma (IDC) is an even rarer occurrence. When ductal carcinoma in situ (DCIS) or IDC are detected within the specimen, the management changes from wide local excision to further staging work-up, including sentinel node biopsy and radiation. CASE REPORT We report the case of a 70-year-old presented with right breast mass whose pathology showed benign PT with concomitant IDC and DCIS. The patient elected for a wide excision of the mass with sentinel lymph node biopsy, which did not show any involvement. The patient was started on appropriate therapy. She is currently doing well. CONCLUSIONS This case highlights the importance of wide local excision for PT as well as prudent histologic examination to rule out other malignant components, as the presence of IDC distinctly changes management.


Comparison of suxamethonium and priming with atracurium for rapid sequence orotracheal intubation in a Nigerian adult population.
To compare suxamethonium with atracurium using the priming principle, for rapid sequence orotracheal intubation assessing onset time, time to successful laryngoscopy and intubation and quality of intubating conditions. A prospective double-blind, randomised study was performed in 90 ASA physical status I and II patients aged between 18 and 64 years undergoing elective surgery requiring endotracheal intubation between October 2002 and June 2003 in a university teaching hospital . All patients were premedicated with 5-10mg oral diazepam and randomly assigned to one of two groups to receive either suxamethonium as a bolus dose (group A) or atracurium (priming with 0.05 mg/kg followed by 0.55 mg/kg after induction of anaesthesia) (group B). In both groups, the trachea was intubated when there was maximal muscle relaxation, determined clinically by jaw muscle relaxation. Muscle paralysis using a PNS, quality of intubating conditions, and occurrence of muscle weakness due to the priming dose of atracurium, time to laryngoscopy and onset time were all noted. Onset time was 87.1 +/- 25.60s and 135.8 +/- 46.23s in groups A and B respectively (P < 0.05). Group A had a laryngoscopy time of 73.6 +/- 25.22s compared to 107.7 +/- 41.32s in group B (P < 0.05). Intubating conditions were significantly better in group A compared to group B (P < 0.05). The frequency of muscle weakness from the priming dose of atracurium was 6.6%. Atracurium, using the priming principle, is an option in our environment for modified rapid sequence induction when suxamethonium is contraindicated.


Low-frequency normal mode in DNA HhaI methyltransferase and motions of residues involved in the base flipping.
The results of normal-mode analyses are in accord with the proposal that a low-frequency motion of the HhaI methyltransferase enzyme is responsible for base flipping in bound DNA. The vectors of the low-frequency normal mode of residues Ser-85 and Ile-86 point directly to the phosphate and ribose moieties of the DNA backbone near the target base in position to rotate the dihedral angles and flip the base out of the DNA duplex. The vector of residue Gln-237 on the major groove is in the proper orientation to assist base separation. Our results favor the major groove pathway and the protein active process in base flipping.