Stathmin1 expression is associated with aggressive phenotypes and cancer stem cell marker expression in breast cancer patients.
Stathmin1 (STMN1) regulates progression in various cancers. The present study aimed to determine the relationship between STMN1 expression and several cancer-related markers in breast cancer. Using immunohistochemistry, we evaluated STMN1, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, epidermal growth factor receptor (EGFR), CK5/6, CD44, CD24, aldehyde dehydrogenase 1, E-cadherin, epithelial cell adhesion molecule, and vimentin in 237 breast cancer patients and the clinical significance of STMN1. STMN1 expression was evaluated in 51 breast cancer cell lines, and the prognostic value of STMN1 was calculated. Higher STMN1 expression was detected in cancer tissues and was predominantly localized in the cytoplasm. High STMN1 expression was associated with the triple negative subtype, nuclear grade progression, high expression of Ki-67, EGFR, CK5/6, E-cadherin and high CD44/low CD24. According to gene expression-based outcome for breast cancer online and the Kaplan-Meier plotter, STMN1 expression was higher in basal-type cell lines than in luminal-type cell lines, and overall survival and post-progression survival in the high STMN1 expression breast cancer patients were shorter than in low STMN1 expression patients. High STMN1 expression is a possible marker of breast cancer aggressiveness in association with proliferation, phenotype and cancer stem cell type.


The ethics of physical restraints in critical care.
The use of restraints in the critical care setting represents an extreme end on the continuum of behavioral management. Restraints increase a person's vulnerability to neglect, harm, and exploitation and are associated with significant physical harm and devastating psychologic consequences. The central values of respect for persons, preventing harm, and promoting positive outcomes often conflict when physical restraints are used. This article explores the ethical issues confronting critical care nurses as they weigh the potential harms associated with restraints against the primary commitment to the patient's health and safety. The challenge for critical care nurses is to establish more humane and dignified forms of care for critically ill patients.


Reversal of deleterious effect of hypertension on the liver by inhibition of endoplasmic reticulum stress.
Hypertension is an important risk factor for cardiovascular diseases. Besides cardiovascular system, it could cause damage to liver. It has been shown that endoplasmic reticulum stress (ERS) plays a crucial role in the pathogenesis of hypertension. ERS inhibitor tauroursodeoxycholic-acid (TUDCA) has favorable effects on various pathologies including cardiovascular, metabolic and hepatic diseases. In this study, the hepatoprotective effect and mechanism of TUDCA were investigated in the deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Male Wistar rats were used and divided into four groups: Control, DOCA, TUDCA and DOCA + TUDCA. Hypertension was induced by DOCA-salt administration for twelve weeks after the unilateral nephrectomy. TUDCA was given for the last 4 weeks. Systolic blood pressure was measured by using tail-cuff method. At the end of the treatment, liver was isolated and weighed. The expressions of various proteins and histopathological evaluation were examined in the liver. TUDCA markedly decreased systolic blood pressure in the hypertensive animals. Hypertension caused increase in the expressions of glucose-regulated protein-78 (GRP78), matrix metalloproteinase-2 (MMP-2) and phospho-inhibitor κB-α (p-IκB-α) and the decrease in the expression of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase2 (SERCA2) and phospho-extracellular signal-regulated kinase (p-ERK) in the liver. Alterations in these protein expressions were not detected in the TUDCA-treated hypertensive group. Also, hepatic balloon degeneration, inflammation and fibrosis were observed in the hypertensive group. TUDCA improved inflammation and fibrosis in the hypertensive liver. Our findings indicate that the detrimental effect of DOCA-salt-induced hypertension on the liver was defended by the inhibition of ERS. Hepatic ERS and its treatment should be taken into consideration for therapeutic approaches to hypertension.


Active Induction of a Multiple Sclerosis-Like Disease in Common Laboratory Mouse Strains.
Experimental autoimmune encephalomyelitis (EAE) is a neuroinflammatory disease with facets in common with multiple sclerosis (MS). It is induced in susceptible mammalian species, with rodents as the preferred hosts, and has been used for decades as a model to investigate the immunopathogenesis of MS as well as for preclinical evaluation of candidate MS therapeutics. Most commonly, EAE is generated by active immunization with central nervous system (CNS) antigens, such as whole CNS homogenate, myelin proteins, or peptides derived from these proteins. However, EAE actually represents a spectrum of diseases in which specific combinations of host/CNS antigen exhibit defined clinical profiles, each associated with unique immunological and pathological features. Similar to MS, EAE is a complex disease where development and progression are also modulated by environmental factors; therefore, the establishment of any given EAE variant can be challenging and requires careful optimization. Here, we describe protocols for three EAE variants, successfully generated in our laboratory, and provide additional information as to how to maintain their unique features and reproducibility.


Formulation and evaluation of dextromethorphan hydrobromide sustained release tablets.
Sustained release (SR) matrix tablets of dextromethorphan hydrobromide were prepared by wet granulation using hydroxypropyl methyl cellulose (HPMC-K-100 CR) as the hydrophilic rate controlling polymer. The effect of the concentration of the polymer and different fillers on the in vitro drug release rate was studied. The studies indicated that the drug release can be modulated by varying the concentration of the polymer and the fillers. A complete cross-over bioavailability study of the optimized formulation of the developed sustained tablets and marketed immediate release tablets was performed on six healthy male volunteers. The extent of absorption of drug from the SR tablets was significantly higher than that for the marketed dextromethorphan hydrobromide tablet because of lower elimination rate and longer half-life.


Mechano-bactericidal actions of nanostructured surfaces.
Antibiotic resistance is a global human health threat, causing routine treatments of bacterial infections to become increasingly difficult. The problem is exacerbated by biofilm formation by bacterial pathogens on the surfaces of indwelling medical and dental devices that facilitate high levels of tolerance to antibiotics. The development of new antibacterial nanostructured surfaces shows excellent prospects for application in medicine as next-generation biomaterials. The physico-mechanical interactions between these nanostructured surfaces and bacteria lead to bacterial killing or prevention of bacterial attachment and subsequent biofilm formation, and thus are promising in circumventing bacterial infections. This Review explores the impact of surface roughness on the nanoscale in preventing bacterial colonization of synthetic materials and categorizes the different mechanisms by which various surface nanopatterns exert the necessary physico-mechanical forces on the bacterial cell membrane that will ultimately result in cell death.


Labor demand in the time of COVID-19: Evidence from vacancy postings and UI claims.
We use job vacancy data collected in real time by Burning Glass Technologies, as well as unemployment insurance (UI) initial claims and the more traditional Bureau of Labor Statistics (BLS) employment data to study the impact of COVID-19 on the labor market. Our job vacancy data allow us to track the economy at disaggregated geography and by detailed occupation and industry. We find that job vacancies collapsed in the second half of March. By late April, they had fallen by over 40%. To a first approximation, this collapse was broad based, hitting all U.S. states, regardless of the timing of stay-at-home policies. UI claims and BLS employment data also largely match these patterns. Nearly all industries and occupations saw contraction in postings and spikes in UI claims, with little difference depending on whether they are deemed essential and whether they have work-from-home capability. Essential retail, the "front line" job most in-demand during the current crisis, took a much smaller hit, while leisure and hospitality services and non-essential retail saw the biggest collapses. This set of facts suggests the economic collapse was not caused solely by the stay-at-home orders, and is therefore unlikely to be undone simply by lifting them.


Structural analysis of the mylohyoid muscle as a septum dividing the floor of the oral cavity for the purposes of dental implant surgery: variety of muscle attachment positions and ranges of distribution.
The objective was to investigate the details of the attachments of the mylohyoid muscle to the mandible anterior to the hyoid and mylohyoid lines to understand the positional relationship between the sublingual space and the mylohyoid, knowledge that is essential for dental implant surgery in the incisal region, as well as the routes of communication between the sublingual space and other spaces. While evaluating the presence or absence of an anterior mylohyoid muscle fiber attachment to the mandible, sublingual gland herniation, spaces between muscle fascicles were also recorded as sites of penetration. The mean muscle thickness in each of these areas was also calculated. In all specimens, the mylohyoid originated not only from the mylohyoid line but also from the lingual surface of the center of the mandibular body (the mandibular symphysis) below the mental spines. The mylohyoid muscle fascicles were thickest in the posterior region, and further anterior to this, they tended to become thinner. Sublingual gland herniations passing through the mylohyoid were noted in the anterior and central regions, but not in the posterior region. Penetration between the muscle fascicles was most common in the central region, and no such penetration was evident in the posterior region. These results suggest that the mylohyoid functions only incompletely as a septum, and that routes of communication from the sublingual space to the submandibular space may be present in both the anterior and central muscle fascicles of the mylohyoid. Therefore, bleeding complications during dental implant placement in the anterior mandible can be serious issues. There is a potential for sublingual hematoma that could compromise the airway by pressing the tongue against the soft palate into the pharynx.


Are gadolinium-based contrast media really safer than iodinated media for digital subtraction angiography in patients with azotemia?
Gadolinium chelates, intended as intravenous contrast media for magnetic resonance imaging, have been regarded as nonnephrotoxic and recommended to replace iodinated contrast media in patients with azotemia who are undergoing digital subtraction angiography (DSA). High intraarterial doses (up to 220 mmol of gadodiamide) have been used, with a 40% incidence of nephropathy. The authors discourage the use of gadolinium for DSA for several reasons. (a) There exist no randomized studies comparing the nephrotoxic effects of gadolinium-based and iodinated media at equal-attenuating concentrations and doses. (b) Gadolinium-based media are hypertonic, a pathogenetic factor in contrast medium-induced nephropathy after renal angiography, with an osmolality two to seven times that of plasma. Iodinated media in concentrations that are equally attenuating with gadolinium-based media can be made isotonic. (c) In vitro measurements indicate that 0.5 mol/L gadolinium chelates are equally attenuating with 60-80 mg iodine per milliliter at the commonly used 70-90-kV range used for DSA. Thus, 50 mL of 0.5 mol/L gadolinium chelate ( approximately 0.3 mmol/kg in an 80-kg person) would be equally attenuating with a dose of 3-4 g of iodine in an iodinated medium (eg, 50 mL iohexol at 60-80 mg I/mL or 10-13 mL at 300 mg I/mL). (d) By combining these data on attenuation and results of toxicity studies in mice, the general toxicity of gadolinium chelates may be six to 25 times higher than that of equal-attenuating doses of iodinated media at 70-kV DSA. Thus, the authors believe that at equal-attenuating doses for DSA, modern iodinated contrast media should result in a lower toxic load on the body than with presently available gadolinium chelates.


Neural mechanisms of three-dimensional vision.
We can see things in three dimensions because the visual system re-constructs the three-dimensional (3D) configurations of objects from their two-dimensional (2D) images projected onto the retinas. The purpose of this paper is to give an overview of the psychological background and recent physiological findings concerning three-dimensional vision. Psychophysical and computational studies have suggested that in the visual system the 3D surface orientation is first estimated independently from individual depth cues--such as binocular disparity, as well as various monocular cues including texture gradients--and then the information from these different depth cues is integrated to construct a generalized representation of the 3D surface geometry. Neurons involved in low-level disparity processing, or the detection of local absolute disparity, were found mainly in the occipital cortex, whereas neurons involved in high-level disparity processing, or the reconstruction of 3D surface orientation through the computation of disparity gradients, were found mainly in the parietal area caudal intraparietal sulcus (CIP). Neurons sensitive to texture gradients, which is one of the major monocular cues, were also found in CIP. The majority of these neurons were sensitive to disparity gradients as well, suggesting their involvement in the computation of 3D surface orientation. In CIP, neurons sensitive to multiple depth cues were widely distributed together with those sensitive to a specific depth cue, suggesting CIP's involvement in the integration of depth information from different sources. In addition, human and monkey imaging studies have indicated convergence of multiple depth cues in CIP. These neurophysiological findings suggest that CIP plays a critical role in 3D vision by constructing a generalized representation of the 3D surface geometry of objects.


Voltage-controlled ferroelastic switching in Pb(Zr0.2Ti0.8)O3 thin films.
We report a voltage controlled reversible creation and annihilation of a-axis oriented ∼10 nm wide ferroelastic nanodomains without a concurrent ferroelectric 180° switching of the surrounding c-domain matrix in archetypal ferroelectric Pb(Zr0.2Ti0.8)O3 thin films by using the piezo-response force microscopy technique. In previous studies, the coupled nature of ferroelectric switching and ferroelastic rotation has made it difficult to differentiate the underlying physics of ferroelastic domain wall movement. Our observation of distinct thresholds for ferroelectric and ferroelastic switching allows us investigate the ferroelastic switching cleanly and demonstrate a new degree of nanoscale control over the ferroelastic domains.


Morphological development and cytochrome c oxidase activity in Streptomyces lividans are dependent on the action of a copper bound Sco protein.
Copper has an important role in the life cycle of many streptomycetes, stimulating the developmental switch between vegetative mycelium and aerial hyphae concomitant with the production of antibiotics. In streptomycetes, a gene encoding for a putative Sco-like protein has been identified and is part of an operon that contains two other genes predicted to handle cellular copper. We report on the Sco-like protein from Streptomyces lividans (Sco(Sl)) and present a series of experiments that firmly establish a role for Sco(Sl) as a copper metallochaperone as opposed to a role as a thiol-disulphide reductase that has been assigned to other bacterial Sco proteins. Under low copper concentrations, a Δsco mutant in S. lividans displays two phenotypes; the development switch between vegetative mycelium and aerial hyphae stalls and cytochrome c oxidase (CcO) activity is significantly decreased. At elevated copper levels, the development and CcO activity in the Δsco mutant are restored to wild-type levels and are thus independent of Sco(Sl). A CcO knockout reveals that morphological development is independent of CcO activity leading us to suggest that Sco(Sl) has at least two targets in S. lividans. We establish that one Sco(Sl) target is the dinuclear Cu(A) domain of CcO and it is the cupric form of Sco(Sl) that is functionally active. The mechanism of cupric ion capture by Sco(Sl) has been investigated, and an important role for a conserved His residue is identified.


Women's perceptions of everyday occupations: outcomes of the Redesigning Daily Occupations (ReDO) programme.
The aim was to (i) assess the outcomes of the 16-week Redesigning Daily Occupations (ReDO) programme for women on sick leave due to stress-related disorders, in terms of occupational value, satisfaction with everyday occupations, and participation level; (ii) investigate the relationships between those outcomes and return-to-work rate. A total of 42 women receiving ReDO and 42 receiving care as usual (CAU) were included in a matched-control study with measurements before and after the rehabilitation. Seventy-eight participated on both occasions. They completed self-report questionnaires regarding the aforementioned outcomes. Return-to-work data were obtained from the registers of the Social Insurance Offices. Increases in concrete, symbolic, and self-reward values were found in both groups, but no statistically significant difference between the groups was demonstrated. The ReDO group improved more than the CAU group, however, on satisfaction with everyday occupations and participation level. Occupational value, but not satisfaction with everyday occupations, was related to return to work. Everyday occupations were shown to be relevant outcomes after work rehabilitation. They could play an important role in future development of profession-specific evidence of occupational therapy. Further support was obtained for viewing occupational value and satisfaction with everyday occupations as theoretically distinct phenomena.


Rapid Spin Depolarization in the Layered 2D Ruddlesden-Popper Perovskite (BA)(MA)PbI.
We report temperature-dependent spectroscopy on the layered (n = 4) two-dimensional (2D) Ruddlesden-Popper perovskite (BA)(MA)PbI. Helicity-resolved steady-state photoluminescence (PL) reveals no optical degree of polarization. Time-resolved PL shows a photocarrier lifetime on the order of nanoseconds. From simultaneously recorded time-resolved differential reflectivity (TRΔR) and time-resolved Kerr ellipticity (TRKE), a photocarrier lifetime of a few nanoseconds and a spin relaxation time on the order of picoseconds was found. This stark contrast in lifetimes clearly explains the lack of spin polarization in steady-state PL. While we observe clear temperature-dependent effects on the PL dynamics that can be related to structural dynamics, spin relaxation is nearly T-independent. Our results highlight that spin relaxation in 2D (BA)(MA)PbI occurs at time scales faster than the exciton recombination time, which poses a bottleneck for applications aiming to utilize this degree of freedom.


Hybridization, introgression, and the nature of species boundaries.
Species can be defined as populations that are diagnosably distinct, reproductively isolated, cohesive, or exclusive groups of organisms. Boundaries between species in sympatry are maintained by intrinsic barriers to gene exchange; these boundaries may not be uniform in space, in time, or across the genome. Here, we explore the nature of the species boundary, defined as the phenotypes/genes/genome regions that remain differentiated in the face of potential hybridization and introgression. We emphasize that species boundaries are semipermeable, with permeability (gene exchange) being a function of genome region. The early evidence for semipermeable species boundaries came from data on differential introgression in hybrid zones. This "genic view" of species was common in the hybrid zone literature even when few molecular markers were available to characterize genome-wide patterns of variation. Now, molecular tools allow detailed characterization of differentiation between diverging lineages and patterns of variation across natural hybrid zones, but the questions being asked by evolutionary biologists have remained much the same. Recent data (from DNA sequences and genotypes) reinforce earlier conclusions about the semipermeable nature of most species boundaries. However, debate persists over the nature and extent of genome divergence that accompanies speciation.


Licit prescription drug use in a Swedish population according to age, gender and socioeconomic status after adjusting for level of multi-morbidity.
There is a great variability in licit prescription drug use in the population and among patients. Factors other than purely medical ones have proven to be of importance for the prescribing of licit drugs. For example, individuals with a high age, female gender and low socioeconomic status are more likely to use licit prescription drugs. However, these results have not been adjusted for multi-morbidity level. In this study we investigate the odds of using licit prescription drugs among individuals in the population and the rate of licit prescription drug use among patients depending on gender, age and socioeconomic status after adjustment for multi-morbidity level. The study was carried out on the total population aged 20 years or older in Östergötland county with about 400 000 inhabitants in year 2006. The Johns Hopkins ACG Case-mix was used as a proxy for the individual level of multi-morbidity in the population to which we have related the odds ratio for individuals and incidence rate ratio (IRR) for patients of using licit prescription drugs, defined daily doses (DDDs) and total costs of licit prescription drugs after adjusting for age, gender and socioeconomic factors (educational and income level). After adjustment for multi-morbidity level male individuals had less than half the odds of using licit prescription drugs (OR 0.41 (95% CI 0.40-0.42)) compared to female individuals. Among the patients, males had higher total costs (IRR 1.14 (95% CI 1.13-1.15)). Individuals above 80 years had nine times the odds of using licit prescription drugs (OR 9.09 (95% CI 8.33-10.00)) despite adjustment for multi-morbidity. Patients in the highest education and income level had the lowest DDDs (IRR 0.78 (95% CI 0.76-0.80), IRR 0.73 (95% CI 0.71-0.74)) after adjustment for multi-morbidity level. This paper shows that there is a great variability in licit prescription drug use associated with gender, age and socioeconomic status, which is not dependent on level of multi-morbidity.


E. coli Transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation.
Transcription and DNA repair are coupled in E. coli by the Mfd protein, which dissociates transcription elongation complexes blocked at nonpairing lesions and mediates recruitment of DNA repair proteins. We show that Mfd influences the elongation state of RNA polymerase (RNAP); transcription complexes that have reverse translocated into the backtracked position, a potentially important intermediate in RNA proofreading and repair, are restored to the forward position by the activity of Mfd, and arrested complexes are rescued into productive elongation. Mfd may act through a translocase activity that rewinds upstream DNA, leading either to translocation or to release of RNA polymerase when the enzyme active site cannot continue elongation.


The use of viscoelastic haemostatic assays in non-cardiac surgical settings: a systematic review and meta-analysis.
Thrombelastography (TEG) and rotational thromboelastometry (ROTEM) are viscoelastic haemostatic assays (VHA) which exploit the elastic properties of clotting blood. The aim of this systematic review and meta-analysis was to evaluate the usefulness of these tests in bleeding patients outside the cardiac surgical setting. We searched the Cochrane Library, MEDLINE, EMBASE and SCOPUS. We also searched clinical trial registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. We found 4 randomised controlled trials (RCTs) that met our inclusion criteria with a total of 229 participants. The sample size was small (from 28 to 111 patients) and the follow-up periods very heterogenous (from 4 weeks to 3 years). Pooled data from the 3 trials reporting on mortality (199 participants) do not show any effect of the use of TEG on mortality as compared to standard monitoring (based on the average treatment effect from a fixed-effects model): Risk Ratio (RR) 0.71; 95% Confidence Interval (CI): 0.43 to 1.16. Likewise, the use of VHA does not reduce the need for red blood cells (mean difference -0.64; 95% CI: -1.51 to 0.23), platelet concentrates (mean difference -1.12; 95% CI: -3.25 to 1.02), and fresh frozen plasma (mean difference -0.91; 95% CI: -2.02 to 0.19) transfusion. The evidence on mortality and other outcomes was uncertain (very low-certainty evidence, down-graded due to risk of biases, imprecision, and inconsistency). Overall, the certainty of the evidence provided by the trials was too low for us to be certain of the benefits and harms of viscoelastic haemostatic assay in non-cardiac surgical settings. More, larger, and better-designed RCTs should be carried out in this area.


Haptic Communication in Collaborative Virtual Environments.
To understand the interaction between haptic and verbal communication, we quantified the relative effect of verbal, haptic, and haptic-plus-verbal feedback in a collaborative virtual pointing task. Collaborative virtual environments (CVEs) provide a medium for interaction among remote participants. Better understanding of the role of haptic feedback as a supplement to verbalization can improve the design of CVEs. Thirty-six participants were randomly paired into 18 dyads to complete a 2-D pointing task in a CVE. In a mixed experimental design, participants completed the task in three communication conditions: haptic only (H), verbal only (V), and haptic plus verbal (HV). The order of the conditions presented to the participants was counterbalanced. The time to task completion, path length, overshoot, and root mean square error were analyzed. Overall, performance in the V and HV conditions was significantly better than in the H condition. H was the least efficient communication channel but elicited response with the shortest reaction time. When verbalization was not available, the use of the haptic device was more likely to be exaggerated to ensure information transmission. When verbalization was used, participants converged on the use of a Cartesian coordinate system for communicating spatial information. Haptic communication can be used to complete a collaborative virtual task but is less efficient than verbal communication. A training period may help to improve the efficiency of haptic communication. These results can be used to design remote collaboration tasks incorporating haptic components and for improving the design of CVEs that support haptic communication.


High paternal testosterone may protect against postpartum depressive symptoms in fathers, but confer risk to mothers and children.
Following the birth of an infant, decreases in testosterone and increases in depressive symptoms have been observed in fathers. Paternal testosterone may reflect fathers' investment in pair-bonding and paternal caregiving and, as such, may be associated with maternal and familial well-being. This study tests associations between paternal testosterone, paternal and maternal postpartum depressive symptoms, and subsequent family functioning. Within 149 couples, fathers provided testosterone samples when infants were approximately nine months old and both parents reported on postpartum depressive symptoms at two, nine, and 15months postpartum. Fathers with lower aggregate testosterone reported more depressive symptoms at two and nine months postpartum. Mothers whose partners had higher evening testosterone reported more depressive symptoms at nine and 15months postpartum. Maternal relationship satisfaction mediated this effect, such that mothers with higher testosterone partners reported more relationship dissatisfaction, which in turn predicted more maternal depressive symptoms. Higher paternal testosterone and paternal depressive symptoms at nine months postpartum each independently predicted greater fathering stress at 15months postpartum. Higher paternal testosterone also predicted more mother-reported intimate partner aggression at 15months postpartum. In addition to linear relationships between testosterone and depression, curvilinear relationships emerged such that fathers with both low and high testosterone at nine months postpartum reported more subsequent (15-month) depressive symptoms and fathering stress. In conclusion, whereas higher paternal testosterone may protect against paternal depression, it contributed to maternal distress and suboptimal family outcomes in our sample. Interventions that supplement or alter men's testosterone may have unintended consequences for family well-being.


Foray search: an effective systematic dispersal strategy in fragmented landscapes.
In the absence of evidence to the contrary, population models generally assume that the dispersal trajectories of animals are random, but systematic dispersal could be more efficient at detecting new habitat and may therefore constitute a more realistic assumption. Here, we investigate, by means of simulations, the properties of a potentially widespread systematic dispersal strategy termed "foray search." Foray search was more efficient in detecting suitable habitat than was random dispersal in most landscapes and was less subject to energetic constraints. However, it also resulted in considerably shorter net dispersed distances and higher mortality per net dispersed distance than did random dispersal, and it would therefore be likely to lead to lower dispersal rates toward the margins of population networks. Consequently, the use of foray search by dispersers could crucially affect the extinction-colonization balance of metapopulations and the evolution of dispersal rates. We conclude that population models need to take the dispersal trajectories of individuals into account in order to make reliable predictions.


Cost-Effectiveness of isoniazid preventive therapy among HIV-infected patients clinicaly screened for latent tuberculosis infection in Dar es Salaam, Tanzania: A prospective Cohort study.
One of the reasons why Isoniazid preventive therapy (IPT) for Tuberculosis (TB) is not widely used in low income countries is concerns on cost of excluding active TB. We analyzed the cost-effectiveness of IPT provision in Tanzania having ruled out active TB by a symptom-based screening tool. Data on IPT cost-effectiveness was prospectively collected from an observational cohort study of 1283 HIV-infected patients on IPT and 1281 controls; followed up for 24 months. The time horizon for the analysis was 2 years. Number of TB cases prevented and deaths averted were used for effectiveness. A micro costing approach was used from a provider perspective. Cost was estimated on the basis of clinical records, market price or interviews with medical staff. We annualized the cost at a discount of 3%. A univariate sensitivity analysis was done. Results are presented in US$ at an average annual exchange rate for the year 2012 which was Tanzania shillings 1562.4 for 1 US $. The number of TB cases prevented was 420/100,000 persons receiving IPT. The number of deaths averted was 979/100,000 persons receiving IPT. Incremental cost due to IPT provision was US$ 170,490. The incremental cost effective ratio was US $ 405.93 per TB case prevented and US $ 174.15 per death averted. These costs were less than 3 times the 768 US $ Gross Domestic Product (GDP) per capita for Tanzania in the year 2014, making IPT provision after ruling out active TB by the symptom-based screening tool cost-effective. The results were robust to changes in laboratory and radiological tests but not to changes in recurrent, personnel, medication and utility costs. IPT should be given to HIV-infected patients who screen negative to symptom-based TB screening questionnaire. Its cost-effectiveness supports government policy to integrate IPT to HIV/AIDS care and treatment in the country, given the availability of budget and the capacity of health facilities.


Registration of high-density cross sectional images to the fundus image in spectral-domain ophthalmic optical coherence tomography.
We previously developed a technique to acquire a SLO (scanning laser ophthalmoscope) like fundus intensity image from the raw spectra measured with spectral-domain optical coherence tomography (OCT), the same spectra used to generate a 3D OCT data set. This technique offers simultaneous fundus and OCT images and, therefore, solves the problem of registering a cross sectional OCT image to fundus features. However, the registration of high density OCT images is still an unsolved problem because no useful fundus image can be generated from the high density scans. High density OCT images can significantly improve the image quality and enhance the visualization of retinal structure, especially the structure of small lesions. We have developed a feature-based algorithm, which can register a high density OCT image on the fundus image generated from normal density scans. The algorithm was successfully tested for both normal and diseased eyes.


Massive parallel gene expression profiling of RINm5F pancreatic islet beta-cells stimulated with interleukin-1beta.
Interleukin 1 (IL-1) is a pleiotropic cytokine with the potential to kill pancreatic beta-cells, and this unique property is thought to be involved in the pathogenesis of type I diabetes mellitus. We therefore determined the quantitative expression of 24,000 mRNAs of RINm5F, an insulinoma cell line derived from rat pancreatic beta-cells, before and after challenge with 30 and 1,000 pg/ml of recombinant human IL-1beta. The highest concentration resulted in decreased insulin production and cell death over a period of 4 days. Using three different time points, 2, 4 and 24 hours after challenge, we found that 146 full-length genes and a large number of expressed sequence tags were differentially regulated 3-fold or more. Most of the differentially regulated transcripts have not previously been described to be regulated by IL-1beta in beta-cells. We have analysed the expression data and sorted the genes into groups according to functional relations on the basis of knowledge of the structure or function ascribed to the individual genes. Many of the differentially regulated genes are known to play a role in immune- and stress-related pathways as well as in insulin secretion and vesicle trafficking, e.g. alpha-endosulfine and K+ channel Kir6.2 are differentially regulated. A number of transcripts in the biosynthesis pathway for cholesterol are also differentially regulated.


The effect of vitamin C on the erythrocyte antioxidant enzymes in intoxicated-lead rat offsprings.
Lead exposure or lead poisoning is known to cause a large spectrum of physiological, biochemical, and behavioural disorders in animals. This study was aimed at assessing the effect of vitamin C on the erythrocyte superoxide dismutase, glutathione peroxidase and the glutathione reductase activities in intoxicated- lead rat offsprings. This study was performed on the pups from female Wistar albino rats. The rats were divided into 4 groups and the treatments were administered through drinking water. Group1 (control group) consumed distilled water. Group 2 (lead group) consumed a solution of lead acetate (300mg/L). Group3 (lead + vitamin C) consumed a solution of lead (300mg/L) which was supplemented with vitamin C (2g/L). Group4 (vitamin group) consumed a solution of vitamin C (2g/L). The enzyme activities were determined in all the 4 groups. The administration of lead showed a decrease in the enzyme activities. The superoxide dismutase activity was increased after the administration of lead in combination with vitamin C. The lead treated rats showed significantly lower body weights at birth and at weaning. The vitamin C treatment showed a significant increase in the body weight. The haemoglobin levels were significantly decreased in the lead-treated rats. The addition of vitamin C to the lead treatment and vitamin C alone could elevate the haemoglobin levels significantly. The results of this study showed that lead alterates the erythrocyte antioxidant enzyme activities. There was an increase in the superoxide dismutase activity following the treatment with vitamin C. This study suggests that the treatment with vitamin C during lactation has a therapeutic effect in the treatment of lead intoxication. The administration of vitamin C prevents haemoglobin reduction in the erythrocytes.


Beyond the 'back yard': Lay knowledge about Aedes aegypti in northern Australia and its implications for policy and practice.
Controlling dengue fever in Australia and internationally, relies heavily upon the actions of residents as well as community education and awareness of the risks. Although it has been well established in medical anthropology that the success of health interventions is highly dependent upon a clear grasp of lay knowledge of disease, limited attention has been given to lay understandings of dengue fever and its vectors in the extant literature. We begin addressing this hiatus through an examination of north Queensland residents' knowledge of the breeding habitats of Aedes aegypti mosquitoes. Building on the insights of earlier social research, we use factor analysis to examine the results of a series of randomly selected telephone surveys and compare responses over time and between cities. Our analysis confirms that many people assume that Ae. aegypti is ubiquitous in the landscape, that it lives and breeds not only around the home, but also in a variety of geographical spaces located beyond the suburban 'backyard', and beyond the control of local residents. Lay understandings appear to be placing people at risk from dengue, influencing the mosquito management practices of local residents and acting as a source of resistance to public health messages that focus on individual responsibility. A way forward through the provision of new information that challenges key assumptions is provided in the discussion. We argue that rather than dismissing lay understandings as ignorance, strategies, practices and policy based on a detailed understanding of this knowledge will mean that practitioners are better able to address these assumptions and will likely be more effective at educating the public of the risks posed by dengue.


Epileptic Seizure Detection Based on Bidirectional Gated Recurrent Unit Network.
Visual inspection of long-term electroencephalography (EEG) is a tedious task for physicians in neurology. Based on bidirectional gated recurrent unit (Bi-GRU) neural network, an automatic seizure detection method is proposed in this paper to facilitate the diagnosis and treatment of epilepsy. Firstly, wavelet transforms are applied to EEG recordings for filtering pre-processing. Then the relative energies of signals in several particular frequency bands are calculated and inputted into Bi-GRU network. Afterwards, the outputs of Bi-GRU network are further processed by moving average filtering, threshold comparison and seizure merging to generate the discriminant results that the tested EEG belong to seizure or not. Evaluated on CHB-MIT scalp EEG database, the proposed seizure detection method obtained an average sensitivity of 93.89% and an average specificity of 98.49%. 124 out of 128 seizures were correctly detected and the achieved average false detection rate was 0.31 per hour on 867.14 h testing data. The results show the superiority of Bi-GRU network in seizure detection and the proposed detection method has a promising potential in the monitoring of long-term EEG.


Age-dependent increase of IgE-binding and FcepsilonRI expression on circulating basophils in children.
Peripheral blood basophils are sparse in the circulation, but they express high-affinity receptors for IgE (FCepsilonRI) and bind IgE efficiently. The present study was performed to elucidate the role of IgE bound on the basophil surface in the development of allergic responses during infancy and early childhood. IgE-binding and FcepsilonRI expression on basophils were evaluated by two-color flow cytometry. Basophil-bound IgE increased rapidly and reached adult levels during infancy in atopic patients, while it gradually increased with advancing age in parallel with serum IgE in normal controls. IgE-binding and FcepsilonRI expression in atopic children were higher than in normal controls among various age groups. They correlated with serum IgE levels but reached a plateau when serum IgE exceeded 300 ng/mL. A low, but significant level of FcepsilonRI expression was observed on cord blood basophils, although IgE-binding was usually undetectable. Incubation of cord blood with IgE rapidly saturated the preexisting IgE receptors and basophil-bound IgE levels increased. When neonatal basophils were cultured for 48 h with IgE, FcepsilonRI expression was upregulated dose-dependently and IgE-binding increased further. The up-regulation of FcepsilonRI was completely inhibited by cycloheximide, indicating that it was dependent on de novo protein synthesis. These results suggest that IgE-binding on basophils serves as a sensitive indicator of allergic sensitization, and that IgE functions as a positive regulator of FcepsilonRI expression in vivo.


DeepEM3D: approaching human-level performance on 3D anisotropic EM image segmentation.
Progress in 3D electron microscopy (EM) imaging has greatly facilitated neuroscience research in high-throughput data acquisition. Correspondingly, high-throughput automated image analysis methods are necessary to work on par with the speed of data being produced. One such example is the need for automated EM image segmentation for neurite reconstruction. However, the efficiency and reliability of current methods are still lagging far behind human performance. Here, we propose DeepEM3D, a deep learning method for segmenting 3D anisotropic brain electron microscopy images. In this method, the deep learning model can efficiently build feature representation and incorporate sufficient multi-scale contextual information. We propose employing a combination of novel boundary map generation methods with optimized model ensembles to address the inherent challenges of segmenting anisotropic images. We evaluated our method by participating in the 3D segmentation of neurites in EM images (SNEMI3D) challenge. Our submission is ranked #1 on the current leaderboard as of Oct 15, 2016. More importantly, our result was very close to human-level performance in terms of the challenge evaluation metric: namely, a Rand error of 0.06015 versus the human value of 0.05998. The code is available at https://github.com/divelab/deepem3d/. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Iron supplementation during pregnancy - a cross-sectional study undertaken in four German states.
Iron deficiency but also iron overload during pregnancy has been associated with unwanted health effects. In Germany, iron supplements are only recommended for pregnant women with diagnosed iron deficiency/anaemia. Prevalence of anaemia among pregnant women was reported at 24.4% in 2011. However, limited data suggest that more than 60% of women in Germany use iron supplements during gestation. Against this background, we investigated the prevalence of iron supplement intake among pregnant women and explored determining factors in order to assess whether women are following the advice to only supplement iron in case of a diagnosed iron deficiency/anaemia. A cross-sectional study was carried out in four German states in 2015 where, with the help of midwives, women in childbed were asked to retrospectively answer a questionnaire about iron intake from various sources and reasons for supplementing iron during their recent pregnancy. We used Chi-square-tests and logistic regression analysis to evaluate associations between iron supplementation and other nutritional, sociodemographic and maternal variables and to assess attitudes of women meeting versus not meeting the official recommendation on iron supplement intake during pregnancy. Of 207 participants, 65.2% had supplemented iron. 84.4% reported to have done this because of a diagnosed iron deficiency/anaemia. Iron intake ranged from 5 to 200 mg/day, and duration of supplementation varied between two weeks and throughout gestation. Of women who reported to have been diagnosed with iron deficiency/anaemia, 47.5% had supplemented ≥80 mg/day iron, while 26.2% had taken iron in lower amounts ≤40 mg/day. Six percent of the participating women had not supplemented iron in spite of a diagnosed iron deficiency/anaemia, whereas 19.7% of women without iron deficiency/anaemia still had supplemented iron (range: 7 to 80 mg/day). The majority of pregnant women used iron supplements in case of a diagnosed iron deficiency/anaemia. However, not all women with iron deficiency/anaemia supplemented (sufficient amounts of) iron, while there was also indiscriminate use of iron supplements in women without iron deficiency/anaemia. Further research is warranted to confirm these findings in representative samples.


Prevalence and distribution of murine mammary tumor virus antigen detectable by immunocytochemistry in spontaneous breast tumors of wild mice.
Mouse mammary tumor virus (MuMTV) antigens were detected by immunoperoxidase cytochemistry in spontaneous breast tumors of wild mice from two widely separated areas of southern California. Eleven of 25 (44%) tumors from Lake Casitas (LC) mice and 4 of 5 tumors from Bouquet Canyon mice were positive. Included among the tumors lacking detectable MuMTV antigen were well-differentiated type A and type B carcinomas as well as tumors with an atypical pattern. In the antigen-positive tumors the distribution of staining was patchy and extremely variable in extent (less than 1-70% stained cells). The intensity and extent of staining were generally greater in breast tumors from hybrids of LC wild mice and C5LBL/10Sn or AKR inbred mice. A good correlation was found in the same tumors between immunoperoxidase staining, detection of MuMTV gp52 antigen by radioimmunoassay, and detection of type B particles by electron microscopy. All of the breast tumors in LC mice were positive for type C virus particles.


Relationship of life-course drinking patterns to diabetes, heart problems, and hypertension among those 40 and older in the 2005 U.S. National Alcohol Survey.
The goal of this study was to estimate relationships between life-course drinking patterns and the risks of self-reported diabetes, heart problems, and hypertension. Respondents to the 2005 National Alcohol Survey, age 40 and older, reported ever having a doctor or health professional diagnose each of the health-problem outcomes. Retrospective earlier-life drinking patterns were characterized by lifetime abstention and the frequency of 5+ drinking days (i.e., days on which five or more drinks were consumed) in the respondent's teens, 20s, and 30s. Past-year drinking patterns were measured through intake volume and 5+ days. Potential confounders in the domains of demographics, socioeconomic resources, and other health-risk variables-that is, depression, distress, sense of coherence, body mass index, tobacco use, marijuana use, childhood abuse, and family history of alcohol problems--were controlled through propensity-score matching. After matching, lifetime abstainers were found to be at increased risk of diabetes compared with both lifetime and current moderate drinkers. Exdrinkers were found to be at increased risk of diabetes, heart problems, and hypertension. Higher volume drinkers without monthly 5+ days were found to be at reduced risk of diabetes relative to moderate-volume current drinkers. Heavy-occasion drinkers were found to be at increased risk of hypertension. Regular lower quantity alcohol intake may be protective against adult onset of diabetes, but no evidence of protection from heart problems or hypertension was found. Both life course-defined and past year-defined drinking groups exhibit substantial clustering of confounding risk variables, indicating the need for modeling strategies like propensity-score matching. Increased risks among exdrinkers suggest a substantial "sick-quitter" effect.


Geographical and environmental approaches to urban malaria in Antananarivo (Madagascar).
Previous studies, conducted in the urban of Antananarivo, showed low rate of confirmed malaria cases. We used a geographical and environmental approach to investigate the contribution of environmental factors to urban malaria in Antananarivo. Remote sensing data were used to locate rice fields, which were considered to be the principal mosquito breeding sites. We carried out supervised classification by the maximum likelihood method. Entomological study allowed vector species determination from collected larval and adult mosquitoes. Mosquito infectivity was studied, to assess the risk of transmission, and the type of mosquito breeding site was determined. Epidemiological data were collected from November 2006 to December 2007, from public health centres, to determine malaria incidence. Polymerase chain reaction was carried out on dried blood spots from patients, to detect cases of malaria. Rapid diagnostic tests were used to confirm malaria cases among febrile school children in a school survey.A geographical information system was constructed for data integration. Altitude, temperature, rainfall, population density and rice field surface area were analysed and the effects of these factors on the occurrence of confirmed malaria cases were studied. Polymerase chain reaction confirmed malaria in 5.1% of the presumed cases. Entomological studies showed An. arabiensis as potential vector. Rice fields remained to be the principal breeding sites. Travel report was considered as related to the occurrence of P. falciparum malaria cases. Geographical and environmental factors did not show direct relationship with malaria incidence but they seem ensuring suitability of vector development. Absence of relationship may be due to a lack of statistical power. Despite the presence of An. arabiensis, scarce parasitic reservoir and rapid access to health care do not constitute optimal conditions to a threatening malaria transmission. However, imported malaria case is suggestive to sustain the pocket transmission in Antananarivo.


[Ultrastructure of cells comprising an intact population of several strains of S. typhimurium and E. coli].
The authors describe the ultrastructure of cells composing the intact population of several S. typhimurium and E. coli strains. Four morphological cell variants were revealed in the population of three salmonella strains. Cells of the first variant had the structure characteristic of all the Gram negative bacteria, and smooth contour surface structures, among which the membrane of the cell wall, its rigid component and the cytoplasmic membrane were differentiated readily. The second variant differed from the first one by the presence of deep individual folds of the surface structures invaginating into the cell. In comparison with the former two types of cells, the two latter variants were characterized by a lesser size, dense cytoplasm and a marked tortuosity of the cell contours in which only the wall components could be revealed. It is supposed that the fourth variant had a structure characteristic of the R-form of cells, the first one--of the S-form, and the second and third variants could be referred to the transitional S leads to R-forms. Increased density of the cytoplasm and rugose character of the surface structures could be attributed to increased dehydration of the cytoplasm of the dissociating cells. No marked polymorphism was revealed in the E. coli cells.


Paradoxical impact of cholesterol on lipid packing and cell stiffness.
Cell stiffness or deformability is a fundamental property that is expected to play a major role in multiple cellular functions. It is well known that cell stiffness is dominated by the intracellular cytoskeleton that, together with the plasma membrane, forms a membrane-cytoskeleton envelope. However, our understanding of how lipid composition of plasma membrane regulates physical properties of the underlying cytoskeleton is only starting to emerge. In this review, we first briefly describe the impact of cholesterol on the physical properties of lipid bilayers in model membranes and in living cells, with the dominant effect of increasing the order of membrane lipids and decreasing membrane fluidity. Then, we discuss accumulating evidence that removal of cholesterol, paradoxically, decreases the mobility of membrane proteins and increases cellular stiffness, with both effects being dependent on the integrity of the cytoskeleton. Finally, we discuss emerging evidence that oxidized modifications of low-density lipoproteins (oxLDL) have the same effects on endothelial biomechanical properties as cholesterol depletion, an effect that is mediated by the incorporation of oxysterols into the membrane.


Chromodomain helicase DNA-binding 4 (CHD4) regulates early B cell identity and V(D)J recombination.
B lymphocytes develop from uncommitted precursors into immunoglobulin (antibody)-producing B cells, a major arm of adaptive immunity. Progression of early progenitors to antibody-expressing cells in the bone marrow is orchestrated by the temporal regulation of different gene programs at discrete developmental stages. A major question concerns how B cells control the accessibility of these genes to transcription factors. Research has implicated nucleosome remodeling ATPases as mediators of chromatin accessibility. Here, we describe studies of chromodomain helicase DNA-binding 4 (CHD4; also known as Mi-2β) in early B cell development. CHD4 comprises multiple domains that function in nucleosome mobilization and histone binding. CHD4 is a key component of Nucleosome Remodeling and Deacetylase, or NuRD (Mi-2) complexes, which assemble with other proteins that mediate transcriptional repression. We review data demonstrating that CHD4 is necessary for B lineage identity: early B lineage progression, proliferation in response to interleukin-7, responses to DNA damage, and cell survival in vivo. CHD4-NuRD is also required for the Ig heavy-chain repertoire by promoting utilization of distal variable (VH ) gene segments in V(D)J recombination. In conclusion, the regulation of chromatin accessibility by CHD4 is essential for production of antibodies by B cells, which in turn mediate humoral immune responses to pathogens and disease.


Core position alignment in polymer optical waveguides fabricated using the Mosquito method.
We fabricate multimode polymer optical waveguides with circular graded-index (GI) cores which are aligned in parallel at desired positions using the Mosquito method. In the Mosquito method, three-dimensional wiring patterns can be formed with a simple process. However, the core position is likely to deviate from the designed position because of multiple fabrication factors. Hence, in this paper, the dominant parameters to influence on the core height in the cladding are investigated both theoretically and experimentally. In particular, a linear relationship between the core height and the needle-tip height is confirmed with theoretical fluid analysis. Using this relationship, we succeeded in fabricating a waveguide in which the maximum variation of the core height from the designed value is controlled to be less than 10 µm.


Prognostic factors for small cell neuroendocrine carcinoma of the uterine cervix: an institutional experience.
This study aimed to determine the clinicopathologic characteristics that affected the survival in patients with small cell neuroendocrine carcinoma of the uterine cervix (SNEC). All patients with SNEC treated at Chiang Mai University Hospital between January 1995 and October 2011 were retrospectively reviewed with histologic confirmation of SNEC diagnosis. The prognostic predictors for survival were assessed using competing risk regression analysis concerning the probabilities of competing events. One hundred thirty histologically confirmed patients with SNEC met the study criteria. The median overall survival and median cancer-specific survival (CSS) for entire group were 47.8 and 58.1 months, respectively. Five-year CSS for patients with early-stage disease was 62.6% and for patients with advanced-stage disease was 18.1% (P < 0.001). Among the patients with surgically treated early-stage disease, those with adjuvant chemotherapy had a better 5-year survival rate than those with surgery alone, those with adjuvant radiotherapy, and those with adjuvant chemoradiation therapy (P = 0.041). In multivariable analyses, decreased survival in patients with early-stage disease was associated with age older than 60 years at diagnosis (hazards ratio [HR], 4.9; P = 0.007) and deep stromal invasion (HR, 2.9; P = 0.011). Among the patients with advanced-stage disease, decreased survival was associated with age at diagnosis (older than 60 years: HR, 9.9; P < 0.001 and younger than 45 years: HR, 3.4; P = 0.035) and International Federation of Gynecology and Obstetrics stage IV (HR, 7.4; P = 0.024). International Federation of Gynecology and Obstetrics stage, age at diagnosis, and deep stromal invasion were important prognostic factors for CSS in patients with SNEC. Adjuvant chemotherapy may provide survival benefits in surgically treated patients with early-stage SNEC.


Beyond the alpha angle: Alternative measurements for quantifying cam-type deformities in femoroacetabular impingement.
To assess alternative measurements to the alpha angle as a tool for distinguishing between symptomatic and asymptomatic cam-type deformities of the femoral head. Magnetic resonance imaging (MRI) examinations of 106 individuals (age 20-50 years) from a previous study on the alpha angle were analyzed, including 53 femoroacetabular impingement (FAI) patients with cam-type deformities and 53 age-/sex-matched asymptomatic volunteers. On radially reformatted MR images two independent radiologists assessed femoral offset and femoral distance (FD) around the femoral head circumference. Intraclass correlation coefficient (ICC) and receiver operating characteristic (ROC) were obtained. The mean offset was smallest in the anterosuperior position for both readers: reader 1 measured 6.2 ± 2.9 mm (standard deviation) in patients and 7.3 ± 1.8 mm in volunteers (P = 0.002, patients vs. volunteers); reader 2 measured 6.1 ± 3.3 mm in patients and 7.1 ± 2.9 mm in volunteers (P = 0.111). The mean FD was highest in the anterosuperior position for reader 1 (patients 3.3 ± 1.4 mm; volunteers 1.7 ± 2.2 mm; P < 0.001) and in the anterior position for reader 2 (patients 3.1 ± 1.7 mm; volunteers 2.0 ± 1.5 mm; P = 0.001). Overall interobserver agreement (ICC) was good (offset 0.657/FD 0.632). ROC analysis for offset measurements showed the largest area under the curve in anterosuperior position for reader 1 (0.666) and in posterosuperior position for reader 2 (0.612). For FD measurements, the area under the curve was largest in anterosuperior position for both readers (0.793/0.798). While FD measurements were superior to offset measurements and showed similar results to the alpha angle, neither FD nor offset measurements are a reliable tool for discrimination between FAI patients with cam-type deformities and asymptomatic volunteers.


Transcatheter aortic valves inadequately relieve stenosis in small degenerated bioprostheses.
Transcatheter aortic valves (TAVs) are a promising treatment for high risk surgical patients suffering from degeneration of previously implanted bioprostheses (valve-in-valve therapy). However, unlike native stenosed aortic valves which have accommodated Edwards SAPIEN transcatheter valves after valvuloplasty, rigid bioprostheses may prevent full TAV stent expansion and disrupt leaflet function. We hypothesized that current 23 mm TAVs would not completely relieve severe stenosis in small bioprosthetic valves. The objective of this study was to study the hemodynamics of TAVs in degenerated bioprostheses. Twelve TAVs designed to mimic the 23 mm SAPIEN valve were created. Using a pulse duplicator, hemodynamics of valve-in-valve implantation were measured within 19, 21, and 23 mm Carpentier-Edwards PERIMOUNT degenerated bioprostheses (n=6 each). Bioprosthetic degeneration was simulated using BioGlue to achieve a mean pressure gradient of 50 mmHg. TAVs significantly reduced the mean pressure gradient (50.9+/-4.7-9.1+/-4.1 mmHg, P<0.001) and total energy loss (870.3+/-157.4-307.8+/-87.3 mJ, P<0.001) in 23 mm degenerated bioprostheses. In 21 mm bioprostheses, the pressure gradient (52.3+/-7.0-19.5+/-5.0 mmHg, P<0.001) and energy loss (785.5+/-128.1-477.8+/-123.2 mJ, P=0.007) were reduced significantly. However, no significant changes in the pressure gradient (57.1+/-4.3-46.5+/-9.3 mmHg, P=0.086) or energy loss (839.3+/-49.3-960.5+/-158.1 mJ, P=0.144) were obtained after TAVI implantation in 19 mm bioprostheses. Incomplete stent expansion resulted in leaflet distortion and central regurgitation when implanted in 19 and 21 mm bioprostheses. The bioprosthetic annulus and stent posts offered a suitable landing zone for TAVs. However, oversized transcatheter valves were constrained by the rigid bioprostheses resulting in inadequate resolution of bioprosthetic stenosis. Hemodynamics of valve-in-valve intervention was worse than comparable size surgical valve replacements, particularly in 19 and 21 mm valves. Small degenerated bioprostheses require modification of current TAV design to yield acceptable hemodynamics.


Unmet needs of breast cancer patients relative to survival duration.
The present study aims to evaluate the prevalence of unmet needs among breast cancer survivors, to assess the relationships between unmet needs and depression and quality of life, and to explore the extent to which unmet needs of breast cancer patients relate to the time elapsed since surgery. Among 1,250 eligible patients who participated in the study, 1,084 cases (86.7%) were used for analysis. Clinicopathological and social parameters were reviewed and the Supportive Care Needs Survey, Functional Assessment of Cancer Therapy- Breast cancer instrument, and Beck Depression Inventory were administered. The frequency of unmet needs, the association between unmet needs and depression and/or quality of life (QOL) and the impact of the time elapsed since surgery on the patients' unmet needs were analyzed. The highest levels of unmet needs were found to be in the health system and information domain. Patients with a survival duration of less than 1 year since surgery showed significantly higher unmet needs in all need domains except the sexuality domain (p<0.001) than participants in the other groups. Patients with a survival duration of 1-3 years also experienced significantly higher psychological and information needs than long-term survivors (>5 years). In addition, unmet needs were significantly associated with depression (p<0.001) and QOL (p<0.001). The present study demonstrated that long-term breast cancer survivors had a significantly lower level of unmet needs than patients with survival duration of less than 3 years after surgery and patients with survival duration of less than 1 year since surgery suffered the greatest unmet needs. QOL might be enhanced if interventions are made for specific unmet needs of each patient group.


Ontogenetic changes in root and shoot respiration, fresh mass and surface area of Fagus crenata.
To date, studies on terrestrial plant ecology and evolution have focused primarily on the trade-off patterns in the allocation of metabolic production to roots and shoots in individual plants and the scaling of whole-plant respiration. However, few empirical studies have investigated the root : shoot ratio by considering scaling whole-plant respiration at various sizes throughout ontogeny. Here, using a whole-plant chamber system, we measured the respiration rates, fresh mass and surface area of entire roots and shoots from 377 Fagus crenata individuals, from germinating seeds to mature trees, collected from five different Japanese provenances. Non-linear regression analysis was performed for scaling of root and shoot respiration, fresh mass and surface area with body size. Whole-plant respiration increased rapidly in germinating seeds. In the seedling to mature tree size range, the scaling of whole-plant respiration to whole-plant fresh mass was expressed as a linear trend on the log-log coordinates (exponent slightly greater than 0.75). In the same body size range, root and shoot respiration vs. whole-plant fresh mass were modelled by upward-convex (exponent decreased from 2.35 to 0.638) and downward-convex trends (exponent increased from -0.918 to 0.864), respectively. The root fraction in whole-plant respiration, fresh mass and surface area shifted continuously throughout ontogeny, increasing in smaller seedlings during early growth stages and decreasing in larger trees. Our results suggest a gradual shift in allocation priorities of metabolic energy from roots in seedlings to shoots in mature trees, providing insights into how roots contribute to shoot and whole-plant growth during ontogeny. The models of root : shoot ratio in relation to whole-plant physiology could be applied in tree growth modelling, and in linking the different levels of ecological phenomena, from individuals to ecosystems.


Effect of visible light on benzo(a)pyrene binding to DNA of cultured human skin epithelial cells.
The ubiquity of the photosensitive carcinogen benzo(a)pyrene (BP) and visible light in the environment suggests that their interaction might lead to photoproducts harmful to humans. To test the combined impact of these two agents on human epithelial cells, binding of BP to cellular DNA was assessed following treatment of cultures with BP and low-intensity (4.6 watts/sq m) intermittent (12 hr daily, 3 to 5 days) cool white fluorescent light. Light exposure reduced the formation of covalent BP adducts 20-fold (from 150 to 7 pmol BP per mg DNA) in cells treated with 1 microgram BP per ml and completely inhibited cytotoxicity; even with 10 microgram BP per ml, light exposure markedly inhibited cytotoxicity. However, at low BP dosage (0.1 microgram/ml), covalent adducts (2 pmol/mg DNA) to cellular DNA are produced and their formation is not influenced by light. These adducts persisted for at least 7 days following treatment; this observation suggests that chronic low-level exposure of human epithelium to BP may lead to an accumulation of DNA damage.


[Thyroid gland pathology in children population exposed to the combination of iodine deficiency and fluoride pollution of environment].
The article presents results of study of the impact of iodine deficiency and technogenic fluoride on the state of the thyroid gland in children. On the example of two districts of the city of Bratsk there were executed dynamic investigations (2002 and 2012), including the estimation of the pollution of ambient air and soil by fluorine compounds, levels of iodine intake by the body, the clinical examination of children aged from 5 to 7 years d and interviewing of their parents. In the course of the medical examination there were executed: physical examination by the pediatrician, endocrinologist, ultrasound examination of the thyroid gland, the determination both of serum hormone content by radioimmunoassay and urinary excretion offluorine and iodine. Concentrations of hydrogen fluoride and a solidfluorides in ambient air led to the accumulation offluoride ion in the soil. The iodine entering with drinking water and food, was established to provide only 37.5-50% of the daily requirement of iodine. Increased fluoride ion content in urine and milk teeth in children is associated with the concentrations of the fluorine-containing pollutants in the ambient air and soil. The fluoride pollution against the background of the natural iodine deficiency was established to increase the frequency of functional and morphological disorders of the thyroid gland in children.


Pharmacogenetic biomarkers for predicting drug response.
Drug response shows significant interpatient variability and evidence that genetics influences outcome of drug therapy has been known for more than five decades. However, the translation of this knowledge to clinical practice remains slow. Using examples from clinical practice six considerations about the implementation of pharmacogenetics (PGx) into routine care are discussed: the need for PGx biomarkers; the sources of genetic variability in drug response; the amount of variability explained by PGx; whether PGx test results are actionable; the level of evidence needed for implementation of PGx and the sources of information regarding interpretation of PGx data.


[Transmembrane ion currents in pulmonary artery smooth muscle].
Transmembrane ionic currents were investigated in the rabbit pulmonary artery smooth muscle under voltage clamp conditions with the use of the double sucrose gap method. With depolarizing pulses, there developed a fast inactivated outward current that was followed by a steady-state outward current. Tetraethylammonium (TEA) partly suppressed the outward current, and the fast inward current that preceded the fast outward one could be seen in these conditions. Appearance of the fast inward current in TEA-containing solution suggests the overlapping of the fast inward and outward currents. It appears that the resultant transmembrane current has an outward direction since in normal conditions the permeability of the fast potassium channels exceeds that of calcium channels. Conditioning hyperpolarization increased and depolarization decreased the fast outward current indicating that at the resting membrane potential a part of the potassium channels is inactivated and this inactivation is removed by hyperpolarization.


Comparison of exertional indices following moderate training in collegiate athletes.
To better understand the inflammatory response to two divergent training modalities: running and weight training. prospective, repeat measures, observational study of subjects over the course of 8-10 weeks of training. Data analysis was consonant with this design and included a repeat measures ANOVA with multiple posthoc comparisons. The level of significance was set at 0.05. collegiate athletic training facilities. twenty-two subjects comprised the study group. These included both male and female collegiate athletes, ages 17-22 years of age with a mean height of 178.6 cm, a mean weight of 77.5 kg and a mean lean body mass of 67.2 kg. Exclusion criteria consisted of hemophilia or chronic conditions requiring anti-inflammatory medication. training for runners (n=11) consisted of multiple 5-km runs throughout the course of a 60-75 minute workout. For a comparable time period, weight trainers participated in multiple joint, total body strengthening workouts. four exertional indices were examined. These included serum levels of creatine kinase, lactate, Interleukin-6, and C-reactive protein. Assessments of these markers were made immediately before and after each training session. Three sessions were monitored over an 8-10 week period. The data show that moderate exertion is accompanied by modest increases in these markers. Mean serum values did not exceed 125 U/L for serum creatine kinase, 5 mM/I for lactates, and 2.6 pg/ml for IL-6. C-reactive protein was sporadically detectable in weight lifters only. These increases were detected immediately postexercise. Each training modality produced a unique profile for creatine kinase and IL-6, suggestive of a training effect. Overall, the levels for all exertional markers reported herein are well below those reported for exhaustive exercise. As consistent exhaustive efforts can catalyze overtraining syndromes, periodic assessments of these exertional indices could help to document the appropriateness of the training stimulus.


Reestablishment of transzonal projections and growth of bovine oocytes in vitro.
Transzonal projections (TZPs) that maintain bidirectional communication between oocytes and granulosa cells or cumulus cells are important structures for oocyte growth. However, whether TZPs develop between TZP-free oocytes and granulosa cells, and whether reestablished TZPs support oocyte growth, is unknown. We first examined changes in TZPs after denudation of bovine oocytes collected from early antral follicles (0.5-0.7 mm). Twenty-four hours after denudation, almost all the TZPs disappeared. We also examined the reestablishment of TZPs by coculturing TZP-free denuded oocytes (DOs) with mural granulosa cells (MGCs) collected from early antral follicles. In addition, to confirm if the reestablished TZPs were functional, the reconstructed complexes (DO+MGCs) were subjected to in vitro growth culture and found that the MGCs adhered to TZP-free DOs and TZPs were reestablished. During in vitro growth culture, DO+MGCs developed and formed antrum-like structures. After culture, the number of TZPs in DO+MGCs increased, and the oocytes grew fully and acquired meiotic competence. These results suggest that reestablished TZPs are able to support oocyte growth.


Adding sildenafil vaginal gel to clomiphene citrate in infertile women with prior clomiphene citrate failure due to thin endometrium: a prospective self-controlled clinical trial.
We aimed to investigate the effect of adding sildenafil vaginal gel to clomiphene citrate (CC) in infertile women with prior CC failure. This is a self- controlled clinical trial. Women with CC failure (in prior 5 cycles) and thin endometrium were recruited (N = 42). In their 6th (CC only) cycle, women continued on CC 100 mg/ day for 5 days, and had measurement of endometrial thickness and Doppler assessment of uterine arteries on day of HCG administration. In the 7th cycle, women (N = 36) were given usual dose of CC supplemented with sildenafil vaginal gel (5 gm, containing 50 mg sildenafil) twice daily from cycle day 8 to day of HCG administration. Endometrial thickness and uterine artery Doppler were measured on the day of HCG injection. In the 7th (CC + sildenafil vaginal gel) cycle, endometrial thickness was significantly higher than in the 6th (CC only) cycle (9.3 mm +/- 3.1mm versus 6.6 mm +/- 1.4 mm, respectively, P = < 0.001). Uterine artery pulsatility index dropped from 2.4 +/- 0.8 in 6th cycle to 1.6 +/- 1.3 in 7th cycle (P = 0.002). Clinical pregnancy rate increased but numbers were too small (only 3 pregnancies). Sildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow, and may improve pregnancy rate in patients with CC failure due to thin endometrium. Mucoadhesive vaginal gel formulation allowed shorter duration of sildenafil application, and less frequent daily dosing.


Real-time viscosity and mass density sensors requiring microliter sample volume based on nanomechanical resonators.
A microcantilever based method for fluid viscosity and mass density measurements with high temporal resolution and microliter sample consumption is presented. Nanomechanical cantilever vibration is driven by photothermal excitation and detected by an optical beam deflection system using two laser beams of different wavelengths. The theoretical framework relating cantilever response to the viscosity and mass density of the surrounding fluid was extended to consider higher flexural modes vibrating at high Reynolds numbers. The performance of the developed sensor and extended theory was validated over a viscosity range of 1-20 mPa·s and a corresponding mass density range of 998-1176 kg/m(3) using reference fluids. Separating sample plugs from the carrier fluid by a two-phase configuration in combination with a microfluidic flow cell, allowed samples of 5 μL to be sequentially measured under continuous flow, opening the method to fast and reliable screening applications. To demonstrate the study of dynamic processes, the viscosity and mass density changes occurring during the free radical polymerization of acrylamide were monitored and compared to published data. Shear-thinning was observed in the viscosity data at higher flexural modes, which vibrate at elevated frequencies. Rheokinetic models allowed the monomer-to-polymer conversion to be tracked in spite of the shear-thinning behavior, and could be applied to study the kinetics of unknown processes.


Strain-Inhibited Electromigration of Oxygen Vacancies in LaCoO3.
The oxygen vacancy profile in LaCoO3 exhibits rich phases with distinct structures, symmetries, and magnetic properties. Exploration of the lattice degree of freedom of LaCoO3 in the transition between these different structural phases may provide a route to enable new functionality in oxide materials with potential applications. To date, the oxygen vacancy profile transition in LaCoO3 has mainly been induced by transition-metal doping or thermal treatment. Epitaxial strain was proposed to compete with the lattice degree of freedom but has not yet been rationalized. Here, the experimental findings of strain-inhibited structural transition from perovskite to brownmillerite during the electromigration of oxygen vacancies in epitaxial LaCoO3 thin films are demonstrated. The results indicate that the oxygen vacancy ordering phase induced by the electric field is suppressed locally by both epitaxial strain field and external loads shown by in situ aberration-corrected (scanning)/ transmission electron microscopy. The demonstrated complex interplay between the electric and strain fields in the structural transitions of LaCoO3 opens up prospects for manipulating new physical properties by external excitations and/or strain engineering of a substrate.


Recent advances in microcontact printing.
Microcontact printing is a remarkable surface patterning technique. Developed about 10 years ago, it has triggered enormous interest from the surface science community, as well as from engineers and biologists. The last five years have been rich in improvements to the microcontact printing process itself, as well as in new technical innovations, many designed to suit new applications. In this review, we describe the evolution of microcontact printing over the past five years. The review is categorized into three main sections: the improvements made to the technique, new variations, and new applications.


Sleeping Sickness in the 'Omics Era.
Sleeping sickness is a neglected tropical disease caused by Trypanosoma brucei parasites, affecting the poorest communities in sub-Saharan Africa. The great efforts done by the scientific community, local governments, and non-governmental organizations (NGOs) via active patients' screening, vector control, and introduction of improved treatment regimens have significantly contributed to the reduction of human African trypanosomiasis (HAT) incidence during the last 15 years. Consequently, the WHO has announced the objective of HAT elimination as a public health problem by 2020. Studies at both parasite and host levels have improved our understanding of the parasite biology and the mechanisms of parasite interaction with its mammalian host. In this review, the impact that 'omics studies have had on sleeping sickness by revealing novel properties of parasite's subcellular organelles are summarized, by highlighting changes induced in the host during the infection and by proposing potential disease markers and therapeutic targets.


A three year follow-up of posterior doxadent restorations.
A new direct restorative material, a calcium aluminate cement, was introduced in the year 2000 and sold under the name Doxadent (Doxa AB, Uppsala, Sweden). The aim of this study was to evaluate Doxadent used in class I and II cavities. A total of 63 restorations were evaluated clinically, according to sligthly modified USPHS criteria, at baseline, after 6 mths, 1, 2 and 3 yrs. Four of the patients reported post-operative sensitivity. At 3 yrs, 62 restorations were evaluated. At 6 mths 9.5% non-acceptable Doxadent restorations were observed, 17.5% at 12 mths, 24.2% at 2 yrs and 21% at 3 yrs, which resulted in a cumulative failure frequency of 72.6% at the end of the 3-years for the new restorative material. Main reasons for failure were material or tooth fracture. It can be concluded that Doxadent showed a non-acceptable clinical failure rate as a posterior restorative, especially in class II cavities.


Plants' Natural Products as Alternative Promising Anti-Candida Drugs.
Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system.


Soluble Conformers of Aβ and Tau Alter Selective Proteins Governing Axonal Transport.
Despite the demonstration that amyloid-β (Aβ) can trigger increased tau phosphorylation and neurofibrillary tangle (NFT) formation in vivo, the molecular link associating Aβ and tau pathologies remains ill defined. Here, we observed that exposure of cultured primary neurons to Aβ trimers isolated from brain tissue of subjects with Alzheimer's disease led to a specific conformational change of tau detected by the antibody Alz50. A similar association was supported by postmortem human brain analyses. To study the role of Aβ trimers in vivo, we created a novel bigenic Tg-Aβ+Tau mouse line by crossing Tg2576 (Tg-Aβ) and rTg4510 (Tg-Tau) mice. Before neurodegeneration and amyloidosis, apparent Aβ trimers were increased by ∼2-fold in 3-month-old Tg-Aβ and Tg-Aβ+Tau mice compared with younger mice, whereas soluble monomeric Aβ levels were unchanged. Under these conditions, the expression of soluble Alz50-tau conformers rose by ∼2.2-fold in the forebrains of Tg-Aβ+Tau mice compared with nontransgenic littermates. In parallel, APP accumulated intracellularly, suggestive of a putative dysfunction of anterograde axonal transport. We found that the protein abundance of the kinesin-1 light chain (KLC1) was reduced selectively in vivo and in vitro when soluble Aβ trimers/Alz50-tau were present. Importantly, the reduction in KLC1 was prevented by the intraneuronal delivery of Alz50 antibodies. Collectively, our findings reveal that specific soluble conformers of Aβ and tau cooperatively disrupt axonal transport independently from plaques and tangles. Finally, these results suggest that not all endogenous Aβ oligomers trigger the same deleterious changes and that the role of each assembly should be considered separately. The mechanistic link between amyloid-β (Aβ) and tau, the two major proteins composing the neuropathological lesions detected in brain tissue of Alzheimer's disease subjects, remains unclear. Here, we report that the trimeric Aβ species induce a pathological modification of tau in cultured neurons and in bigenic mice expressing Aβ and human tau. This linkage was also observed in postmortem brain tissue from subjects with mild cognitive impairment, when Aβ trimers are abundant. Further, this modification of tau was associated with the intracellular accumulation of the precursor protein of Aβ, APP, as a result of the selective decrease in kinesin light chain 1 expression. Our findings suggest that Aβ trimers might cause axonal transport deficits in AD.


The mechanism of action of colchicine. Colchicine binding to sea urchin eggs and the mitotic apparatus.
Colchicine forms a complex in vivo with a protein present in fertilized or unfertilized sea urchin eggs; similar binding was obtained in vitro with the soluble fraction from egg homogenates. Kinetic parameters and binding equilibrium constant were essentially the same in vivo and in vitro. The binding site protein was shown to have a sedimentation constant of 6S by zone centrifugation. The protein was present in extracts of the isolated mitotic apparatus at a concentration which was several times higher than in whole-egg homogenates. It was extracted from the mitotic apparatus at low ionic strength under conditions which lead to the disappearance of microtubules. No binding could be detected to the 27S protein, previously described by Kane, which is a major protein component of the isolated mitotic apparatus. The properties of the colchicine-bindinG protein, (binding constant, sedimentation constant, Sephadex elution volume) are similar to those obtained with the protein from mammalian cells, sea-urchin sperm tails, and brain tissue, and thus support the conclusion that the protein is a subunit of microtubules.


Intergenerational risk decision making: a practical example.
There is no such thing as intergenerational decision making, at least not yet. In fact, there is no such thing as intragenerational decision making in the context of maximizing overall social good given resource limitations, there are just decisions being made in an ad hoc fashion. Even if one assumes that there is such a thing as intragenerational decision making, no uniform standard or guidance exists to make societal decisions for the common good. Risks to society are judged unevenly within the same agency and across agencies. Decisions are made in isolation and not weighed in the societal context of what is intra or intergenerationally important. The National Academy of Public Administration (NAPA) has set forth a framework for intergenerational decision making that provides a consistent and fair basis for making tough decisions in order to address difficult issues such as the long-term disposal of nuclear wastes. NAPA recognizes that there is an intergenerational obligation that must encompass broader questions than the narrow issue of waste disposal since resources are finite and needs are great. The fundamental principles are based on sustainability with the overarching objective that "no generation should needlessly, now or in the future, deprive its successors of the opportunity to enjoy a quality of life equivalent to its own." Coupled with this objective are four supporting principles of trusteeship, sustainability, chain of obligation, and precaution. The NAPA process also recognizes that no decision can be final and that a "rolling future" view is better than making decisions for "all time." It attempts to balance the needs of the present with those of the future in an open and transparent process that is aimed at producing a decision, not just endless analysis. The U.S. Congress and president should develop a rational standard by which to judge laws that involve intra and intergenerational issues relative to the overall societal good. Present regulations need to be evaluated relative to a uniform level of risk and benefit to assess where the limited money available can do the most good for both the present and future generations in the context of NAPA sustainability principles. It is hoped that decision makers will take a serious look at this process since it can work to resolve stakeholder stalemate.


Induction of Broad Immunity against Invasive Salmonella Disease by a Quadrivalent Combination Salmonella MAPS Vaccine Targeting Salmonella Enterica Serovars Typhimurium, Enteritidis, Typhi, and Paratyphi A.
Bloodstream infections in low- and middle-income countries (LMICs) are most frequently attributed to invasive Salmonella disease caused by four primary serovars of Salmonella enterica: Typhi, Paratyphi A, Typhimurium, and Enteritidis. We showed previously that a bivalent vaccine targeting S. Typhi and S. Paratyphi A using a Multiple Antigen-Presenting System (MAPS) induced functional antibodies against S. Typhi and S. Paratyphi. In the current study, we describe the preclinical development of a first candidate quadrivalent combination Salmonella vaccine with the potential to cover all four leading invasive Salmonella serotypes. We showed that the quadrivalent Salmonella MAPS vaccine, containing Vi from S. Typhi, O-specific Polysaccharide (OSP) from S. Paratyphi A, S. Enteritidis and S. Typhimurium, combined with the Salmonella-specific protein SseB, elicits robust and functional antibody responses to each of the components of the vaccine. Our data indicates that the application of MAPS technology to the development of vaccines targeting invasive forms of Salmonella is practical and merits additional consideration.


Methods for treating soils contaminated with polychlorinated dibenzo-p-dioxins, dibenzofurans, and other polychlorinated aromatic compounds.
This review provides a summary of methods for treating soils contaminated with polychlorinated aromatic compounds, especially polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Unlike many other soil pollutants, PCDD/Fs bind tightly to the soil, which severely reduces the efficiency of most aqueous treatment procedures and leaves few realistic alternatives besides the traditional containment techniques (landfill, solidification/stabilization, and in situ vitrification). Incineration has long been, and still is, the most efficient destruction technique, with a removal efficiency of >99.9999%. However, supercritical water oxidation, base-catalyzed decomposition, steam distillation, and various extraction techniques, such as solvent and liquefied gas and subcritical water extraction, may provide removal efficiencies of >95%. Many of the alternative techniques are expected to be cheaper than incineration and may therefore be attractive for moderately polluted soils. However, some of them are at an early stage of development and need to be further tested before their true potential can be assessed.


Lobar vs thalamic and basal ganglion hemorrhage: clinical and radiographic features.
One hundred and twelve patients with spontaneous supratentorial intracerebral hemorrhages were reviewed to identify features which distinguish lobar intracerebral hemorrhage (LH; n = 42) from thalamic or basal ganglionic hemorrhage (TGH; n = 70). Chronic hypertension occurred more commonly in TGH (TGH 67%; LH 48%) while bleeding diathesis was more common in LH (LH 19%; TGH 6%). Clinical presentations were extremely variable and not associated with the type of hemorrhage. Bleeding into the ventricles and hydrocephalus occurred more often with TGH. At last follow-up, there were minimal differences between LH and TGH in overall mortality and functional outcome of the survivors. Alertness on admission was associated with a good outcome regardless of the type of hemorrhage, while a low Glasgow Coma Scale score, coma, ataxic respiration, abnormal pupil reactions, acute hypertension, large hemorrhage size and intraventricular blood were associated with a poor outcome. These data confirm etiological distinctions between LH and TGH, but fail to confirm previously reported differences in clinical presentation and outcome.


[Decubital ulcer--causes, surgical therapy and prognosis].
7.6 % (n = 134/1 769) of all inpatients in Leuven, but 30.1 % of risk patients suffer of pressure sores (Norton Scale 10.4 points). Predisposed are geriatric patients or those of intensive care units. While fasciocutaneous flap likewise the superior gluteal artery perforator flap are more resistant to mechanical forces, myocutaneous flaps are the working horse for pressure sores with deep-tissue pockets or osteitis (Campbell stage > IV). Partial resection of the median sacral crest or ischiectomy are obligatory. In analyzing a 16 years period only 33 percent of myocutaneous flaps healed uneventful, while due to multiple enumerations more than 50 percent presented complications. Partial flap and complete necrosis happened in 6 respectively in 2 percent. Rectus abdominis myocutaneous flap reconstruction as well as the free tissue transfer are useful alternatives to hip disarticulation with total thigh flap coverage or a complete fillet flap of the lower extremity. Independently of the selected closure 50 percent of all decubitus patients will develop recurrences in longterm follow up. Thus prevention is of utmost importance. In Europe the costs for the hospitalisation of a patient with concomitant decubital ulcers are 2.5-times higher than for an average, non-afflicted patient.


Decreased CD161 activating and increased CD158a inhibitory receptor expression on NK cells underlies impaired NK cell cytotoxicity in patients with multiple myeloma.
As innate immune cells natural killer (NK), NK-like T and CTLγδ are important in antitumour response in multiple myeloma (MM), the aim of this study was to investigate some functional and phenotypical characteristics of these cells in MM. 29 patients with MM prior to therapy, in clinical stage I-III and 15 healthy controls (HCs) were investigated. Percent of immune cells in peripheral blood, NK cell activity, expression of activating (CD161) and inhibitory (CD158a, CD158b) NK cell receptors on CD3-CD16+ NK cells were evaluated using 51-chromium-release assay and by flow cytometry. Production of interleukin (IL) 2 and tumour necrosis factor (TNF)α was analysed in supernatants from in vitro activated peripheral blood mononuclear cells. In patients with MM the percent of NK cells and their two subsets did not differ from controls, while NK-like T and CTLγδ cells were significantly decreased. Significant impairment of NK cell cytotoxicity, CD107a expression and interferon γ intracellular level was also shown. There was a significant decrease in CD161 and an increase in CD158a receptor expression on NK cells in these patients. Also IL-2 production was lowest in clinical stage III. However, TNF-α production did not differ between patients and HCs. Altered expression of CD161 activating and CD158a KIR inhibitory receptor is responsible for impaired antitumour activity of NK cells in MM patients. These new biomarkers may be helpful for patient selection for immunotherapy with cytokines, and novel KIR blocking monoclonal antibodies that enhance NK cell antimyeloma activity and provide clinical benefit.


Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy.
Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.