Assessment of insecticide risk to human health in groundwater in Northern China by using the China-PEARL model.
Insecticides are extensively used in China and may leach to groundwater, which is used as a source of drinking water in Northern China. However, the risk of insecticide leaching to groundwater and the subsequent risk to human health caused by the consumption of insecticide-contaminated drinking water remain unclear. A total of 336 predicted environmental concentrations (PECs) were simulated for 32 commonly used insecticides, and 171 PECs were calculated for 20 metabolites in six agricultural dry-land scenario locations of Northern China with eight target crops. In 264 of the 336 cases, the PEC in groundwater is ≤0.1 µg L-1 . Carbofuran, imidacloprid, trichlorfon and oxidative metabolites of aldicarb are the most leached chemicals in groundwater. The most vulnerable crop is cotton, whereas soil treatment is the most vulnerable application type. Urumqi and Weifang are the most vulnerable among the six scenario locations. Less than 3% of 336 cases show unacceptable risk of insecticide-contaminated groundwater, thereby requiring higher risk assessment and risk mitigation. The unacceptable cases are the leaching of carbofuran for cotton growing in Urumqi and Weifang, and leaching of metabolites of aldicarb in cotton and tobacco scenarios. Popular insecticides used in Northern China are generally safe to groundwater. © 2017 Society of Chemical Industry.


'To be able to support her, I must feel calm and safe': pregnant women's partners perceptions of professional support during pregnancy.
Professional support does not always meet the needs of expectant fathers or co-mothers. The way in which professional support is offered during pregnancy varies internationally, depending on the country. In order to attain a greater understanding of partners' experiences of professional support, it is necessary to further illuminate their perceptions of it. The aim of this study was therefore to explore pregnant women's partners' perceptions of professional support during pregnancy. Qualitative research design. Partners of pregnant women were interviewed during gestational week 36-38. Individual semi-structured interviews were used to explore the partners' perceptions. The data was analysed using a phenomenographic approach. The study was performed in a county in south-western Sweden; the data collection was conducted from November 2014 to February 2015. Fourteen partners (expectant fathers and co-mothers) of women who were expectant first-time mothers with singleton pregnancies, were interviewed. The findings of the study are presented through four descriptive categories: Ability to absorb adequate information; Possibility to meet and share with other expectant parents; Confirmation of the partner's importance; and Influence on the couple relationship. Using a theoretical assumption of the relationship between the categories showed that the fourth category was influenced by the other three categories. The partners perceived that professional support during pregnancy could influence the couple relationship. The partners' ability to communicate and to experience togetherness with the women increased when the expectant couple received professional support together. The support created also possibilities to meet and share experiences with other expectant parents. In contrast, a lack of support was found to contribute to partners' feelings of unimportance. It was essential that the midwives included the partners by confirming that they were individuals who had different needs for various types of professional support. The partners perceived it easier to absorb information when it was adequate and given with a pedagogic that made the partners become interested and emotionally engaged.


X marks the spot in autoimmunity.
Autoimmune diseases mostly affect females. Besides hormones, several factors related to chromosome X have been called in action to explain this sex predominance. This paper provides an overview on the role of chromosome X (chrX) in explaining why females have higher susceptibility to autoimmunity. The work outlines some essential concepts regarding chrX inactivation, escape from chrX inactivation and the evolutionary history of chrX. In addition, we will discuss the concept of gene escape in immune cells, with examples related to specific X-linked genes and autoimmune diseases. There is growing evidence that many genes present on chrX escape inactivation, and some of them have significant immune-mediated functions. In immune cells of female individuals the escape of these genes is not constant, but the knowledge of the mechanisms controlling this plasticity are not completely understood. Future studies aimed at the characterization of these modifications at single-cell resolution, together with conformational 3D studies of the inactive X chromosome, will hopefully help to fill this gap of knowledge.


[Brain Metastasis of Triple Negative Breast Cancer after Pathological Complete Response to Neoadjuvant Chemotherapy - A Case Report].
We report the case of a patient with triple negative breast cancer(TNBC)who showed isolated brain metastasis relatively soon after pathological complete response(pCR)to neoadjuvant chemotherapy. A 45-year-old woman with a diagnosis of TNBC(T2N1M0, Stage II B)received neoadjuvant chemotherapy with 5-FU/epirubicin/cyclophosphamide(FEC), followed by docetaxel. After the neoadjuvant chemotherapy, she underwent mastectomy and axillary lymph node dissection. Histological examination of the resected specimens revealed pCR. Brain metastasis, however, developed 7 months after the resection. She underwent total removal of the brain tumor and 50 Gy irradiation to the right frontal lobe. Histological examination confirmed a diagnosis of metastasis from TNBC. She is doing well with no evidence of disease 81 months after resection of the brain metastasis. This case and a review of the literature suggest that the clinician should be aware that brain metastasis from breast cancer may develop even after achieving pCR to neoadjuvant chemotherapy. Surgical resection followed by radiotherapy may provide a survival benefit for selected patients with isolated brain metastasis from breast cancer.


[A case of small cell carcinoma of the esophagus].
A small cell carcinoma of the esophagus is a rare entity; only 101 cases have been reported in the world literature. In a 59-year-old man, complaining of dysphagia, a tumorous lesion was detected in the esophagus at the upper GI series. The histologic diagnosis of biopsy revealed an undifferentiated carcinoma or a malignant lymphoma. Preoperative radiotherapy was carried out, effectively decreasing the large tumorous lesion in size. Thereafter an esophagectomy and an esophagogastric anastomosis were done. The histologic diagnosis of the resected specimen revealed a small cell carcinoma of an intermediate cell type. The tumor cells failed to show cytoplasmic argyrophilia and an ultrastructural examination did not display any cells containing membrane-bound neurosecretory granules.


Formation of a complex between yeast proteinases A and B.
Sephadex G-100 gel filtration of a purified mixture of tryptophan-synthase-inactivating enzymes I and II from Saccharomyces cerevisiae, which had previously been identified as yeast proteinases A and B, yields two coincident peaks of tryptophan-synthase-inactivating activity and proteinase A and B activities. The peaks correspond to molecular weights of approximately 100 000 and 50 000. It could be demonstrated, with purified proteinases A and B, that the high molecular weight peaks is due to the formation of a stoichiometric complex between proteinases A and B. The AB complex can easily be separated into its constituent enzymes by DEAE-Sephadex chromatography. When in the AB complex, proteinase B molecules still bind the specific proteinase B inhibitor from yeast.


Characterization of E. coli cell disintegrates from a bead mill and high pressure homogenizers.
The protein releases, the particle size distribution and the viscosity of disrupted E. coli suspensions from Dyno Mill KDL, Manton Gaulin 15 M-8TA and Microfluidizer M-110 were determined. The effects of these parameters on separation of the cell debris from the protein solution by centrifugation and by filtration were also examined. All three disintegration methods investigated give approximately the same protein and enzyme releases but considerably different physical properties of the cell disintegrates which influences centrifugation and filtration. The separation degree of biomass during centrifugation is only slightly affected by increasing degree of disruption (increasing protein releases) in the bead mill, while an increase in the degree of disruption in the two high pressure homogenizers drastically reduces the centrifugal degree of separation. However, increasing degrees of disruption result in shorter filtration times during filtration for all three disintegration methods. The results show further that the cell concentration only has a minor influence on protein releases in the Microfluidizer high-pressure homogenizer, while an increase in the biomass content reduces the separability of the cell disintegrate both in filtration and in centrifugation.


Monitoring CO2 intrusion and associated geochemical transformations in a shallow groundwater system using complex electrical methods.
The risk of CO(2) leakage from a properly permitted deep geologic storage facility is expected to be very low. However, if leakage occurs it could potentially impact potable groundwater quality. Dissolved CO(2) in groundwater decreases pH, which can mobilize naturally occurring trace metals commonly contained in aquifer sediments. Observing such processes requires adequate monitoring strategies. Here, we use laboratory and field experiments to explore the sensitivity of time-lapse complex resistivity responses for remotely monitoring dissolved CO(2) distribution and geochemical transformations that may impact groundwater quality. Results show that electrical resistivity and phase responses correlate well with dissolved CO(2) injection processes. Specifically, resistivity initially decreases due to increase of bicarbonate and dissolved species. As pH continues to decrease, the resistivity rebounds toward initial conditions due to the transition of bicarbonate into nondissociated carbonic acid, which reduces the total concentration of dissociated species and thus the water conductivity. An electrical phase decrease is also observed, which is interpreted to be driven by the decrease of surface charge density as well as potential mineral dissolution and ion exchange. Both laboratory and field experiments demonstrate the potential of field complex resistivity method for remotely monitoring changes in groundwater quality due to CO(2) leakage.


Undocumented Immigration, Drug Problems, and Driving Under the Influence in the United States, 1990-2014.
To examine the influence of undocumented immigration in the United States on 4 different metrics of drug and alcohol problems: drug arrests, drug overdose fatalities, driving under the influence (DUI) arrests, and DUI deaths. We combined newly developed state-level estimates of the undocumented population between 1990 and 2014 from the Center for Migration Studies with arrest data from the Federal Bureau of Investigation Uniform Crime Reports and fatality information from the Fatality Analysis Reporting System and the Centers for Disease Control and Prevention Underlying Cause of Death database. We used fixed-effects regression models to examine the longitudinal association between increased undocumented immigration and drug problems and drunk driving. Increased undocumented immigration was significantly associated with reductions in drug arrests, drug overdose deaths, and DUI arrests, net of other factors. There was no significant relationship between increased undocumented immigration and DUI deaths. This study provides evidence that undocumented immigration has not increased the prevalence of drug or alcohol problems, but may be associated with reductions in these public health concerns.


Distribution patterns of Quercus ilex from the last interglacial period to the future by ecological niche modeling.
The plants' geographic distribution is affected by natural or human-induced climate change. Numerous studies at both the global and regional levels currently focus on the potential changes in plant distribution areas. Ecological niche modeling can help predict the likely distribution of species according to environmental variables under different climate scenarios. In this study, we predicted the potential geographic distributions of Quercus ilex L. (holm oak), a keystone species of the Mediterranean ecosystem, for the Last Interglacial period (LIG: ~130 Ka), the Last Glacial Maximum (LGM: ~22 Ka), mid-Holocene (MH: ~6 Ka), and future climate scenarios (Representative Concentration Pathway (RCP) 4.5 and 8.5 scenarios) for 2050-2070 obtained from CCSM4 and MIROC-ESM global climate scenarios respectively. The models were produced with algorithms from the R-package "biomod2" and assessed by AUC of the receiver operating characteristic plot and true skill statistics. Aside from BIOCLIM (SRE), all model algorithms performed similarly and produced projections that are supported by good evaluation scores, although random forest (RF) slightly outperformed all the others. Additionally, distribution maps generated for the past period were validated through a comparison with pollen data acquired from the Neotoma Pollen Database. The results revealed that southern areas of the Mediterranean Basin, particularly coastal regions, served as long-term refugia for Q. ilex, which was supported by fossil pollen data. Furthermore, the models suggest long-term refugia role for Anatolia and we argue that Anatolia may have served as a founding population for the species. Future climate scenarios indicated that Q. ilex distribution varied by region, with some areas experiencing range contractions and others range expands. This study provides significant insights into the vulnerability of the Q. ilex to future climate change in the Mediterranean ecosystem and highlights the crucial role of Anatolia in the species' historical distribution.


Effects of tumor necrosis factor on cell growth and expression of transferrin receptors in human fibroblasts.
Human recombinant tumor necrosis factor (TNF) stimulated the growth of confluent human fibroblasts (FS-4) in the presence of fetal calf serum. Epidermal growth factor (EGF) similarly stimulated cellular growth; however other mitogenic factors such as insulin, fibroblast growth factor, 12-O-tetradecanoyl-phorbol-12-acetate and Ca2+ ionophore A23187 did not. The growth-stimulating action of TNF was not synergistic with the activity of EGF in the presence of serum. TNF induced a rapid increase in the binding of transferrin to the cell surface, followed by a return to the basal level within 5 min. A similar increase in transferrin binding was observed in FS-4 cells exposed to EGF. In contrast, insulin caused a prolonged stimulation of transferrin binding. These results suggest that TNF and EGF generate similar or identical intracellular signals for cellular growth and the regulation of transferrin receptor expression.


Primary intracranial choriocarcinoma: a case report.
A 10-year-old girl had a primary choriocarcinoma of the posterior third ventricle. Craniotomy a few hours before death did not yield any tumor tissue. At autopsy, an extensively hemorrhagic tumor abutted the pineal gland. Immunostains were positive for beta-human chorionic gonadotropin (beta-HCG) but were negative for alpha-fetoprotein and carcinoembryonic antigen. The presence of beta-HCG in serum or cerebrospinal fluid may be used as a diagnostic marker and monitor of therapy. HCG is, however, not a unique marker for trophoblastic neoplasms, as a significant number of intracranial germinomas contain cells that are beta-HCG positive. Because of the rarity of primary extragenital choriocarcinomas and the much more common occurrence of metastases of genital choriocarcinomas, it is doubtful whether any investigation less than detailed autopsy can prove the extragenital origin of the tumor.


A model of unsteady-state transvascular fluid and protein transport in the lung.
Models of steady-state fluid and solute transport in the microcirculation are used primarily to characterize filtration and permeability properties of the transport barrier. Important transient relationships, such as the rate of fluid accumulation in the tissue, cannot be predicted with steady-state models. In this paper we present three simple models of unsteady-state fluid and protein exchange between blood plasma and interstitial fluid. The first treats the interstitium as a homogeneous well-mixed compliant compartment, the second includes an interstitial gel, and the third allows for both gel and free fluid in the interstitium. Because we are primarily interested in lung transvascular exchange we used the multiple-pore model and pore sizes described by Harris and Roselli (J. Appl. Physiol.: Respirat . Environ. Exercise Physiol. 50: 1-14, 1981) to characterize the microvascular barrier. However, the unsteady-state transport theory presented here should apply to other organ systems and can be used with different conceptual models of the blood-lymph barrier. For a step increase in microvascular pressure we found good agreement between theoretical and experimental lymph flow and lymph concentrations in the sheep lung when the following parameter ranges were used: base-line interstitial volume, 150-190 ml; interstitial compliance, 7-10 ml/Torr; initial interstitial fluid pressure, -1 Torr; pressure in initial lymphatics, -5 to -6 Torr; and conductivity of the interstitium and lymphatic barrier, 4.25 X 10(-4) ml X s-1 X Torr-1. Based on these values the model predicts 50% of the total change in interstitial water volume occurs in the first 45 min after a step change in microvascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)


Spherical harmonics analysis of surface density fluctuations of spherical ionic SDS and nonionic C12E8 micelles: A molecular dynamics study.
The surface structure and its fluctuation of spherical micelles were investigated using a series of density correlation functions newly defined by spherical harmonics and Legendre polynomials based on the molecular dynamics calculations. To investigate the influence of head-group charges on the micelle surface structure, ionic sodium dodecyl sulfate and nonionic octaethyleneglycol monododecylether (C12E8) micelles were investigated as model systems. Large-scale density fluctuations were observed for both micelles in the calculated surface static structure factor. The area compressibility of the micelle surface evaluated by the surface static structure factor was tens-of-times larger than a typical value of a lipid membrane surface. The structural relaxation time, which was evaluated from the surface intermediate scattering function, indicates that the relaxation mechanism of the long-range surface structure can be well described by the hydrostatic approximation. The density fluctuation on the two-dimensional micelle surface has similar characteristics to that of three-dimensional fluids near the critical point.


Sleep spindles predict neural and behavioral changes in motor sequence consolidation.
The purpose of this study was to investigate the predictive function of sleep spindles in motor sequence consolidation. BOLD responses were acquired in 10 young healthy subjects who were trained on an explicitly known 5-item sequence using their left nondominant hand, scanned at 9:00 pm while performing that same task and then were retested and scanned 12 h later after a night of sleep during which polysomnographic measures were recorded. An automatic algorithm was used to detect sleep spindles and to quantify their characteristics (i.e., density, amplitude, and duration). Analyses revealed significant positive correlations between gains in performance and the amplitude of spindles. Moreover, significant increases in BOLD signal were observed in several motor-related areas, most of which were localized in the right hemisphere, particularly in the right cortico-striatal system. Such increases in BOLD signal also correlated positively with the amplitude of spindles at several derivations. Taken together, our results show that sleep spindles predict neural and behavioral changes in overnight motor sequence consolidation.


Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease.
The glucocorticoid receptor (GR) plays a crucial role in inflammatory responses. GR has several isoforms, of which the most deeply studied are the GRα and GRß. Recently it has been suggested that in addition to its negative dominant effect on GRα, the GRß may have a GRα-independent transcriptional activity. The GRß isoform was found to be frequently overexpressed in various autoimmune diseases, including inflammatory bowel disease (IBD). In this study, we wished to test whether the gene expression profile found in a GRß overexpressing intestinal cell line (Caco-2GRß) might mimic the gene expression alterations found in patients with IBD. Whole genome microarray analysis was performed in both normal and GRß overexpressing Caco-2 cell lines with and without dexamethasone treatment. IBD-related genes were identified from a meta-analysis of 245 microarrays available in online microarray deposits performed on intestinal mucosa samples from patients with IBD and healthy individuals. The differentially expressed genes were further studied using in silico pathway analysis. Overexpression of GRß altered a large proportion of genes that were not regulated by dexamethasone suggesting that GRß may have a GRα-independent role in the regulation of gene expression. About 10% of genes differentially expressed in colonic mucosa samples from IBD patients compared to normal subjects were also detected in Caco-2 GRß intestinal cell line. Common genes are involved in cell adhesion and cell proliferation. Overexpression of GRß in intestinal cells may affect appropriate mucosal repair and intact barrier function. The proposed novel role of GRß in intestinal epithelium warrants further studies.


The place of public inquiries in shaping New Zealand's national mental health policy 1858-1996.
This paper discusses the role of public inquiries as an instrument of public policy-making in New Zealand, using mental health as a case study. The main part of the paper analyses the processes and outcomes of five general inquiries into the state of New Zealand's mental health services that were held between 1858 and 1996. The membership, form, style and processes used by public inquiries have all changed over time in line with constitutional and social trends. So has the extent of public participation. The records of five inquiries provide periodic snapshots of a system bedevilled by long-standing problems such as unacceptable standards, under-resourcing, and poor co-ordination. Demands for an investigation no less than the reports and recommendations of public inquiries have been the catalyst of some important policy changes, if not immediately, then by creating a climate of opinion that supported later change. Inquiries played a significant role in establishing lunatic asylums, in shaping the structure of mental health legislation, establishing and maintaining a national mental health bureaucracy within the machinery of government, and in paving the way for deinstitutionalisation. Ministers and their departmental advisers have mediated this contribution. Public inquiries have helped shape New Zealand's mental health policy, both directly and indirectly, at different stages of evolution. In both its advisory and investigative forms, the public inquiry remains an important tool of public administration. The inquiry/cause and policy/effect relationship is not necessarily immediate but may facilitate changes in public opinion with corresponding policy outcomes long after any direct causal link could be determined. When considered from that long-term perspective, the five inquiries can be linked to several significant and long-term contributions to mental health policy in New Zealand.


Research of the protection actions of derived 2-oxoindole in acute stress.
Correction of pathological anxiety and stress level of frustration leads to the development of new anxiolytics, notably including derivatives of 2-oksoyndolyn- 3-hlyoksylic acid. The aim of work - to study the effect of 2-oksyindolin-3-hlyoksylic acid on emotional and behavioral reactions of rats subjected to behavioral stress tests of different averiability. In experiments on 150 white mature male rats Wistar investigated the effects of 2-oksoindolin (2-hydroxy-N-naphthalene-1-yl-2-(2-hydroxy-1,2- dihydro-indole-3-ylidene)-acetamide) with laboratory codes 18 when intraperitoneally administered to acute immobilization stress on Sel'ye on emotional and behavioral responses of animals to test «open field», «a raised cross maze» and test «conflict behavior» (option Vogel). Established that the prophylactic use of the compound 18 in a test of "open field" warned the stress changes in the latent period of the first movement, likely increased the number of exits to the center installation, warned breach vertical and horizontal motor activity and significantly increased the number of acts of grooming and reduced the number of boluses compared with stress without correction. Revealed changes suggest that the substance 18 prevents anxiety disorders conduct stress genesis. In the test «a raised cross maze» of 2-oksoindolin significantly increased the number of outputs rats in open arms maze and reduced the number of fecal balls compared with those in the control disorders. In the study antyconflict action found that the compound increased the number of approaches to the drinkers, but the activity in this test yielded diazepam. Installed conservation action anksyolityc 2-hydroxy-N-naphthalene-1-yl-2-(2-hydroxy-1,2-dihydro-indole-3-ylidene)-atsetamidu acute stress may be associated with indirect stimulation of GABA - benzdiazepin receptor complex, by strengthening endogenous GABA affinity to the receptors and/or indirect stimulation of GABA receptors by other neurotransmitter systems, including serotonergic, which makes compounds for further study the possibility of post stress with anxiety disorders.


Preparation of antibody against horseradish peroxidase using hybridoma technology.
Monoclonal antibody against horseradish peroxidase (HRP) has many applications which peroxidase anti-peroxidase. Peroxidase-antiperoxidase (PAP) complex formation is its most known and important usage. This complex is used in many immunohistochemical and immunocytochemical staining techniques. The aim of this study was the preparation of anti-HRP monoclonal antibody through hybridoma technology. The BALB/c mice were immunized by repeated injections of HRP. After the confirmation of their immunization by ELISA test, the spleen lymphocytes and SP2/0 myeloma cells were hybridized using PEG as fusing agent. The hybridoma cells were then selected by culturing in HAT medium. Identification and selection of anti-HRP producing clones were done by ELISA test on culture supernatants of the obtained clones. To acquire the monoclones, limiting dilution was performed twice and the effect of finally obtained antibodies on enzyme activity was investigated by a specific ELISA test. In vivo tumor induction method was used for production of concentrated antibody. At last class and subclass of the obtained antibodies were determined by Isostrip Kit. After seven rounds of cell fusions, 224 clones were obtained, from which, six ones were anti-HRP producers. Two clones (P1F11 and P2F6) with higher antibody secretion were selected and subcloned. Both derived hybridoma monoclones (P1F11D2 and P2F6F3) were producing antibodies from IgG1 subclass with kappa (Kappa) light chains which didn't affect the enzyme activity. The electrophoresis of ascetic fluid of tumor induced mice showed an obvious band in gamma (gamma) position. The obtained monoclonal antibodies are from IgG class and don't affect the enzyme activity, therefore it seems that they are suitable for PAP complex production.


Simple assessment of cerebral hemodynamics using single-slab 3D time-of-flight MR angiography in patients with cervical internal carotid artery steno-occlusive diseases: comparison with quantitative perfusion single-photon emission CT.
Visualization of the peripheral arteries on single-slab 3D time-of-flight (TOF) MR angiography (MRA) can reflect blood flow velocity. The velocity in the middle cerebral artery (MCA) may correlate with cerebrovascular reactivity (CVR) to acetazolamide, which can be used to assess hemodynamic impairment. The goal of this study was to compare the signal intensity of the MCA on MRA versus CVR quantified by perfusion single-photon emission CT (SPECT). The signal intensity of the MCA on single-slab 3D time-of-flight MRA was graded according to the ability to visualize the MCA in 108 cerebral hemispheres of 87 patients with unilateral or bilateral cervical internal carotid artery (ICA) steno-occlusive diseases. SPECT-CVR was also calculated by measuring cerebral blood flow before and after acetazolamide challenge. Ten healthy subjects were studied to obtain control SPECT-CVR values. All subjects provided written informed consent before the study. CVR was significantly lower in cerebral hemispheres with reduced MCA signal intensity than in those with normal intensity (P < .05). When the reduced signal intensity of the MCA on MRA was defined as abnormal, and when a CVR less than the mean--2 SD of healthy subjects was defined as reduced, MRA grading resulted in a 86.2% sensitivity and 69.6% specificity, with 51.0% positive-predictive and 93.2% negative-predictive values to detect reduced CVR. This simple MRA method can assess hemodynamic impairment with a high negative-predictive value.


Cognitive outcome after epilepsy surgery in children.
The ultimate goal of epilepsy surgery in young children is to stop seizures, interrupt the downhill course of the epileptic encephalopathy, and improve developmental capacities. Postoperative outcome after childhood epilepsy surgery should therefore not only be expressed in terms of seizure freedom, cognitive outcome is an equally important outcome measure. Insight in the mutually dependent variables that can determine pre and postoperative cognitive developmental abilities will improve prediction of outcome and presurgical counseling of parents. The purpose of this review is to discuss the literature regarding cognitive outcome and the predictors of postoperative cognitive functioning after epilepsy surgery in children, particularly those with "catastrophic" epilepsy. There are only few studies in which the relation between possible determinants and cognitive outcome or change was statistically tested in a multivariable manner. Duration of epilepsy, presurgical Developmental Quotient (DQ) or Intelligence Quotient (IQ), and postoperative seizure freedom were the only factors reported in different studies to be independently related to eventual cognitive outcome after epilepsy surgery. Underlying etiology, gender, age at surgery, presurgical DQ/IQ, postoperative seizure freedom, cessation of antiepileptic medication, and follow-up interval have all been described in different surgical cohorts to be independently related to a postoperative change of IQ or DQ scores. To appreciate how each of the pre-epileptic, presurgical, and postoperative variables may independently influence eventual cognitive outcome and postoperative cognitive improvement, we need multicenter studies with large homogenous surgical populations, using standardized tests and multivariable analyses.


The Challenge of Additionality: The Impact of Central Grants for Primary Healthcare on State-Level Spending on Primary Healthcare in India.
In planning for universal health coverage, many countries have been examining their fiscal decentralization policies with the goal of increasing efficiency and equity via "additionalities." The concept of "additionality," when the government of a lower administrative level increases the funding allocated to a particular issue when extra funds are present, is often used in these contexts. Although the definition of "additionality" can be used more broadly, for the purposes of this paper we focus narrowly on the additional allocation of primary healthcare expenditures. This paper explores this idea by examining the impact of central level primary healthcare expenditure, on individual state level contributions to primary healthcare expenditure within 16 Indian states between 2005 and 2013. In examining 5 main variables, we compared differences between government expenditures, contributions, and revenues for Empowered Action Group (EAG) states, and non-EAG states. EAG states are normally larger states that have weaker public health infrastructure and hence qualify for additional funding. Finally, using a model that captured the quantity of central level primary healthcare expenditure distributions to these states, we measured its impact on each state's own contributions to primary healthcare spending. Our results show that, at the state level, growth in per capita central level primary healthcare expenditure has increased by 110% from 2005-2013, while state's own contributions to primary healthcare expenditure per capita increased by 32%. Further analyses show that a 1% change disbursement from the central level leads to a -0.132%, although not significant, change by states in their own expenditure. The effect for wealthier states is -0.151% and significant and for poorer states the effect is smaller at -0.096% and not significant. This analysis suggests that increases in central level primary healthcare expenditure to states have an inverse relationship with primary healthcare expenditures by the state level. Furthermore, this effect is more pronounced in wealthier Indian states. This finding has policy implications on India's decision to increase block grants to states in place of targeted program expenditures.


Polarization-controlled optimal scatter suppression in transient absorption spectroscopy.
Ultrafast transient absorption spectroscopy is a powerful technique to study fast photo-induced processes, such as electron, proton and energy transfer, isomerization and molecular dynamics, in a diverse range of samples, including solid state materials and proteins. Many such experiments suffer from signal distortion by scattered excitation light, in particular close to the excitation (pump) frequency. Scattered light can be effectively suppressed by a polarizer oriented perpendicular to the excitation polarization and positioned behind the sample in the optical path of the probe beam. However, this introduces anisotropic polarization contributions into the recorded signal. We present an approach based on setting specific polarizations of the pump and probe pulses, combined with a polarizer behind the sample. Together, this controls the signal-to-scatter ratio (SSR), while maintaining isotropic signal. We present SSR for the full range of polarizations and analytically derive the optimal configuration at angles of 40.5° between probe and pump and of 66.9° between polarizer and pump polarizations. This improves SSR by (or compared to polarizer parallel to probe). The calculations are validated by transient absorption experiments on the common fluorescent dye Rhodamine B. This approach provides a simple method to considerably improve the SSR in transient absorption spectroscopy.


Spliceosomal snRNAs in the unicellular eukaryote Trichomonas vaginalis are structurally conserved but lack a 5'-cap structure.
Few genes in the divergent eukaryote Trichomonas vaginalis have introns, despite the unusually large gene repertoire of this human-infective parasite. These introns are characterized by extended conserved regulatory motifs at the 5' and 3' boundaries, a feature shared with another divergent eukaryote, Giardia lamblia, but not with metazoan introns. This unusual characteristic of T. vaginalis introns led us to examine spliceosomal small nuclear RNAs (snRNAs) predicted to mediate splicing reactions via interaction with intron motifs. Here we identify T. vaginalis U1, U2, U4, U5, and U6 snRNAs, present predictions of their secondary structures, and provide evidence for interaction between the U2/U6 snRNA complex and a T. vaginalis intron. Structural models predict that T. vaginalis snRNAs contain conserved sequences and motifs similar to those found in other examined eukaryotes. These data indicate that mechanisms of intron recognition as well as coordination of the two catalytic steps of splicing have been conserved throughout eukaryotic evolution. Unexpectedly, we found that T. vaginalis spliceosomal snRNAs lack the 5' trimethylguanosine cap typical of snRNAs and appear to possess unmodified 5' ends. Despite the lack of a cap structure, U1, U2, U4, and U5 genes are transcribed by RNA polymerase II, whereas the U6 gene is transcribed by RNA polymerase III.


EZH2-mediated Puma gene repression regulates non-small cell lung cancer cell proliferation and cisplatin-induced apoptosis.
Polycomb group (PcG) proteins are highly conserved epigenetic effectors that maintain the silenced state of genes. EZH2 is the catalytic core and one of the most important components of the polycomb repressive complex 2 (PRC2). In non-small cell lung cancer (NSCLC) cells and primary lung tumors, we found that PRC2 components, including EZH2, are overexpressed. High levels of EZH2 protein were associated with worse overall survival rate in NSCLC patients. RNA interference mediated attenuation of EZH2 expression blunted the malignant phenotype in this setting, exerting inhibitory effects on cell proliferation, anchorage-independent growth, and tumor development in a xenograft mouse model. Unexpectedly, we discovered that, in the suppression of EZH2, p53 upregulated modulator of apoptosis (PUMA) expression was concomitantly induced. This is achieved through EZH2 directly binds to the Puma promoter thus epigenetic repression of PUMA expression. Furthermore, cisplatin-induced apoptosis of EZH2-knocking down NSCLC cells was elevated as a consequence of increased PUMA expression. Our work reveals a novel epigenetic regulatory mechanism controlling PUMA expression and suggests that EZH2 offers a candidate molecular target for NSCLC therapy and EZH2-regulated PUMA induction would synergistically increase the sensitivity to platinum agents in non-small cell lung cancers.


Multiple viral plaques with sebaceous differentiation associated with an unclassified papillomavirus type in a cat.
CASE HISTORY AND CLINICAL FINDINGS A 15-year-old neutered male domestic short-haired cat was presented due to multiple 0.5-2 cm-diameter crusting plaques in the left preauricular region, over the bridge of nose, and in the right periocular region. The plaques did not appear to cause discomfort. HISTOPATHOLOGICAL FINDINGS Biopsy samples of four plaques were examined histologically. Three plaques consisted of well-demarcated foci of mild epidermal hyperplasia overlying markedly hyperplastic sebaceous glands. Approximately 60% of the hyperplastic cells contained a large cytoplasmic vacuole that ranged from being clear to containing prominent grey-blue fibrillar material. The fourth plaque was composed solely of epidermal hyperplasia, consistent with previous descriptions of feline viral plaques. MOLECULAR BIOLOGY Papillomavirus DNA was amplified from all four plaques using PCR. A single DNA sequence was amplified from the plaques with sebaceous differentiation. This sequence was identical to the FdPV-MY sequence previously suggested to be from a putative unclassified papillomavirus type. Felis catus papillomavirus type 2 sequences were amplified from the plaque typical of feline viral plaques. Immunohistochemistry to detect p16CDKN2A protein (p16) showed marked immunostaining throughout the hyperplastic epidermis and adnexal structures within the plaques with sebaceous differentiation. DIAGNOSIS Multiple feline viral plaques with variable sebaceous differentiation. CLINICAL RELEVANCE Feline viral plaques with sebaceous differentiation have not been previously reported in cats. The presence of unique cell changes within these lesions, the detection of an unclassified papillomavirus type, and the p16 immunostaining within these plaques suggest that they may have been caused by the papillomavirus that contains the FdPV-MY sequence.


An efficient thermostable organophosphate hydrolase and its application in pesticide decontamination.
In vitro evolution of enzymes represents a powerful device to evolve new or to improve weak enzymatic functions. In the present work a semi-rational engineering approach has been used to design an efficient and thermostable organophosphate hydrolase, starting from a lactonase scaffold (SsoPox from Sulfolobus solfataricus). In particular, by in vitro evolution of the SsoPox ancillary promiscuous activity, the triple mutant C258L/I261F/W263A has been obtained which, retaining its inherent stability, showed an enhancement of its hydrolytic activity on paraoxon up to 300-fold, achieving absolute values of catalytic efficiency up to 10(5) M(-1) s(-1). The kinetics and structural determinants of this enhanced activity were thoroughly investigated and, in order to evaluate its potential biotechnological applications, the mutant was tested in formulations of different solvents (methanol or ethanol) or detergents (SDS or a commercial soap) for the cleaning of pesticide-contaminated surfaces.


[Effect of a new antiulcer drug, leminoprazole, on the gastric mucosal H+,K(+)-ATPase activity in rats].
The inhibitory action of leminoprazole on the activity of rat gastric mucosal H+,K(+)-ATPase was investigated in vitro and ex vivo. Leminoprazole and omeprazole concentration-dependently inhibited the H+,K(+)-ATPase activity, and their IC50 values were 31 microM and 24 microM, respectively, at pH7.4. Leminoprazole dose-dependently inhibited the H+,K(+)-ATPase activity at 3 and 6 hr after the administration at 10-100 mg/kg, p.o. Leminoprazole (60 mg/kg, p.o.) inhibited the H+,K(+)-ATPase activity persistently, and the duration of its inhibitory action was much longer than that of omeprazole (30 mg/kg, p.o.). In pylorus-ligated rats, good correlations between the respective inhibitory rates against gastric acid output and H+,K(+)-ATPase activity was found after the administration of leminoprazole. These results suggest that leminoprazole inhibits the gastric acid secretion by its ability to inhibit the H+,K(+)-ATPase activity in rats; its inhibitory activity was comparable to that of omeprazole. In addition, leminoprazole (100 mg/kg) inhibited the H+,K(+)-ATPase activity even when administered intragastrically after pylorus-ligation, suggesting that this drug can inhibit H+,K(+)-ATPase activity directly from the gastric lumen. Moreover, leminoprazole (100 mg/kg, p.o.) when administered repeatedly for 2 or 4 weeks inhibited the H+,K(+)-ATPase activity to the same degree as the single administration.


Proteomic profiling of the hypothalamus in two mouse models of narcolepsy.
Narcolepsy is a disabling neurological disorder of sleepiness linked to the loss of neurons producing orexin neuropeptides in the hypothalamus. Two well-characterized phenotypic mouse models of narcolepsy, loss-of-function (orexin-knockout), and progressive loss of orexin (orexin/ataxin-3) exist. The open question is whether the proteomics signatures of the hypothalamus would be different between the two models. To address this gap, we utilized a label-free proteomics approach and conducted a hypothalamic proteome analysis by comparing each disease model to that of wild type. Following data processing and statistical analysis, 14 484 peptides mapping to 2282 nonredundant proteins were identified, of which 39 proteins showed significant differences in protein expression across groups. Altered proteins in both models showed commonalties in pathways for mitochondrial dysfunction and neuronal degeneration, as well as altered proteins related to inflammatory demyelination, insulin resistance, metabolic responses, and the dopaminergic and monoaminergic systems. Model-specific alterations in insulin degraded enzyme (IDE) and synaptosomal-associated protein-25 were unique to orexin-KO and orexin/ataxin-3, respectively. For both models, proteomics not only identified clinically suspected consequences of orexin loss on energy homeostasis and neurotransmitter systems, but also identified commonalities in inflammation and degeneration despite the entirely different genetic basis of the two mouse models.


Loss of KCC2 in GABAergic Neurons Causes Seizures and an Imbalance of Cortical Interneurons.
K-Cl transporter KCC2 is an important regulator of neuronal development and neuronal function at maturity. Through its canonical transporter role, KCC2 maintains inhibitory responses mediated by γ-aminobutyric acid (GABA) type A receptors. During development, late onset of KCC2 transporter activity defines the period when depolarizing GABAergic signals promote a wealth of developmental processes. In addition to its transporter function, KCC2 directly interacts with a number of proteins to regulate dendritic spine formation, cell survival, synaptic plasticity, neuronal excitability, and other processes. Either overexpression or loss of KCC2 can lead to abnormal circuit formation, seizures, or even perinatal death. GABA has been reported to be especially important for driving migration and development of cortical interneurons (IN), and we hypothesized that properly timed onset of KCC2 expression is vital to this process. To test this hypothesis, we created a mouse with conditional knockout of KCC2 in Dlx5-lineage neurons (Dlx5 KCC2 cKO), which targets INs and other post-mitotic GABAergic neurons in the forebrain starting during embryonic development. While KCC2 was first expressed in the INs of layer 5 cortex, perinatal IN migrations and laminar localization appeared to be unaffected by the loss of KCC2. Nonetheless, the mice had early seizures, failure to thrive, and premature death in the second and third weeks of life. At this age, we found an underlying change in IN distribution, including an excess number of somatostatin neurons in layer 5 and a decrease in parvalbumin-expressing neurons in layer 2/3 and layer 6. Our research suggests that while KCC2 expression may not be entirely necessary for early IN migration, loss of KCC2 causes an imbalance in cortical interneuron subtypes, seizures, and early death. More work will be needed to define the specific cellular basis for these findings, including whether they are due to abnormal circuit formation versus the sequela of defective IN inhibition.


Current good manufacturing practice for blood and blood components; notification of consignees and transfusion recipients receiving blood and blood components at increased risk of transmitting hepatitis C virus infection ("lookback"). Final rule.
The Food and Drug Administration (FDA) is requiring establishments collecting Whole Blood or blood components, including Source Plasma and Source Leukocytes, to establish, maintain, and follow an appropriate system for identifying blood and blood components previously donated by a donor who tests reactive for evidence of hepatitis C virus (HCV) infection on a subsequent donation identified either by current testing or after a review of historical testing records, or when the collecting establishment is made aware of other reliable test results or information indicating evidence of HCV infection. Such collections may be at increased risk of transmitting HCV infection. FDA is requiring collecting establishments to quarantine prior in-date blood and blood components from such a donor, to notify consignees of prior in-date blood and blood components from such a donor for quarantine purposes, and to perform further testing on the donor. FDA is also requiring consignees to notify transfusion recipients of blood and blood components from such a donor, as appropriate. In addition, FDA is revising the human immunodeficiency virus (HIV) "lookback" requirements for greater consistency with the HCV "lookback" requirements, and extending the record retention period to 10 years. FDA is taking this action to help ensure the continued safety of the blood supply and to help ensure that information is provided to recipients of blood and blood components that may have been at increased risk of transmitting HIV or HCV infection. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled "Guidance for Industry: 'Lookback' for Hepatitis C Virus (HCV): Product Quarantine, Consignee Notification, Further Testing, Product Disposition, and Notification of Transfusion Recipients Based on Donor Test Results Indicating Infection with HCV'' (the "lookback" guidance). We are also issuing this final rule in conjunction with a companion interim final rule published by the Centers for Medicare and Medicaid Services (CMS) elsewhere in this issue of the Federal Register.


[Communicating the diagnosis to the patient with neurological diseases].
Communicating the diagnosis of a neurodegenerative disease entails a significant emotional burden for the patient, their family and/or caregivers Adequate information on the disease and symptoms that they are going to have to face can greatly help to improve their perception of the seriousness of the condition. Communicating bad news to the patients and their families is a very common practice in the medical activity but also a very difficult task. Most of the doctors have only received limited or non-regulated training on this subject. The studies published regarding methodology to be used when communicating the diagnosis have been analyzed beginning with the publication of Grau et al. on the satisfaction of patients suffering multiple sclerosis with the information received. Training programs for medical specialists or other health care professionals who act as case managers and the elaboration of protocols for the communicating of the diagnosis, such as those that are used in the clinical pathways, are necessary to improve scientific and human quality of the information given to the patient.


Investigation of the Anticancer Activity of Coordination-Driven Self-AssembledTwo-Dimensional Ruthenium Metalla-Rectangle.
Coordination-driven self-assembly is an effective synthetic tool for the construction of spatially and electronically tunable supramolecular coordination complexes (SCCs), which are useful in various applications. Herein, we report the synthesis of a two-dimensional discrete metalla-rectangle [(η6-p-cymene)4Ru4(C6H2O4)2(2)2](CF3SO3)4 (3) by the reaction of a dinuclear half-sandwich ruthenium (II) complex [Ru2(η6-p-cymene)2(C6H2O4)Cl2] (1) and bis-pyridyl amide linker (2) in the presence of AgO3SCF3. This cationic ruthenium metalla-rectangle (3) has been isolated as its triflate salt and characterized by analytical techniques including elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), 1H-1H correlation spectroscopy (COSY), 1H-1H nuclear Overhauser effect spectroscopy (NOESY), diffusion ordered spectroscopy (DOSY), and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). Significantly, the 2D cationic ruthenium metalla-rectangle showed better anticancer activity towards three different cell lines (A549, Caki-1 and Lovo) as compared with the parent ruthenium complex (1) and the commercially used drug, cisplatin.


Antibiotic-induced lipopolysaccharide (LPS) release from Salmonella typhi: delay between killing by ceftazidime and imipenem and release of LPS.
It has been suggested that the antibiotic-induced release of lipopolysaccharide (LPS) is an important cause of the development of septic shock in patients treated for severe infections caused by gram-negative bacteria. Beta-lactam antibiotics change the integrity of the bacterial cell envelope by binding to penicillin-binding proteins (PBP) in the membrane and thus may affect the amount of LPS that is released and the kinetics of that release. In this respect, ceftazidime at intermediate concentrations binds with a high affinity to PBP 3 and PBP 1a and thus can induce filament formation in addition to killing, whereas imipenem preferentially binds to PBP 2 and PBP 1b, leading to spheroplast formation and rapid cell lysis. We investigated the effects of these antibiotics on the killing and the release of the radioactively labelled LPS of Salmonella typhi Ty 21A. A mathematical model was developed to calculate the delay between bacterial killing and LPS release, designated the lag time. At antibiotic concentrations inducing equal killing, the amount of LPS released was the same for both antibiotics. Only after 6 h of incubation at antibiotic concentrations above 0.5 microg/ml, the amount of 3H-LPS released was slightly higher (approximately 1.2-fold) in incubations with ceftazidime than in those with imipenem, and the maximum releases of the total label were 33.2% +/- 0.89% and 27.1% +/- 0.45%, respectively. Despite the clear concentration-dependent effect on the bacterial killing and subsequent LPS release, the lag time was independent of the antibiotic concentration. For ceftazidime as well as imipenem the lag time amounted to approximately 60 min. In conclusion, our findings imply that the mechanism of antibiotic-induced LPS release is independent of the PBP affinities for these beta-lactam antibiotics. Furthermore, once the organism is killed by either imipenem or ceftazidime, the rate of LPS release from S. typhi does not differ according to the antibiotic with which the organism is killed, and there is little difference in the relative amount of LPS released.


Synthetic Studies on Heteropolycyclic Natural Products: Development of Divergent Strategy.
The divergent total syntheses of three types of heteropolycyclic natural products, namely gelsedine-type alkaloids, amathaspiramide alkaloids, and erythrina alkaloids, are outlined. A strategy involving a late-stage pluripotent common synthetic intermediate prepared via original and innovative transformations was employed. A brief description of the philosophy and criteria for choosing the synthetic targets and common synthetic precursors, as well as details regarding the development of the overall synthetic schemes from a common intermediate are discussed.


CALCIUM: UNUSUAL SOURCES IN THE HIGHLAND PERUVIAN DIET.
A dietary survey conducted in the southern highlands of Peru revealed two important sources of dietary calcium not previously reported. Mineral and ash calcium ingested as a food spice, and along with coca, raises the calcium intake from the low figures recorded by standard nutritional surveys to a more substantial level.


Insect pests of sweetpotato in Uganda: farmers' perceptions of their importance and control practices.
Insect pests are among the most important constraints limiting sweetpotato (Ipomoea batatas) production in Africa. However, there is inadequate information about farmers' knowledge, perceptions and practices in the management of key insect pests. This has hindered development of effective pest management approaches for smallholder farmers. A standard questionnaire was used to interview individual sweetpotato farmers (n = 192) about their perception and management practices regarding insect pests in six major sweetpotato producing districts of Uganda. The majority (93%) of farmers perceived insect pests to be a very serious problem. With the exception of Masindi and Wakiso districts where the sweetpotato butterfly (Acraea acerata) was the number one constraint, sweetpotato weevils (Cylas puncticollis and C. brunneus) were ranked as the most important insect pests. Insecticide use in sweetpotato fields was very low being highest (28-38% of households) in districts where A. acerata infestation is the biggest problem. On average, 65% and 87% of the farmers took no action to control A. acerata and Cylas spp., respectively. Farmers were more conversant with the presence of and damage by A. acerata than of Cylas spp. as they thought that Cylas spp. root damage was brought about by a prolonged dry season. Different levels of field resistance (ability of a variety to tolerate damage) of sweetpotato landraces to A. acerata (eight landraces) and Cylas spp. (six landraces) were reported by farmers in all the six districts. This perceived level of resistance to insect damage by landraces needs to be investigated. To improve farmers' capabilities for sweetpotato insect pest management, it is crucial to train them in the basic knowledge of insect pest biology and control.


Open Ephys electroencephalography (Open Ephys + EEG): a modular, low-cost, open-source solution to human neural recording.
Electroencephalography (EEG) offers a unique opportunity to study human neural activity non-invasively with millisecond resolution using minimal equipment in or outside of a lab setting. EEG can be combined with a number of techniques for closed-loop experiments, where external devices are driven by specific neural signals. However, reliable, commercially available EEG systems are expensive, often making them impractical for individual use and research development. Moreover, by design, a majority of these systems cannot be easily altered to the specification needed by the end user. We focused on mitigating these issues by implementing open-source tools to develop a new EEG platform to drive down research costs and promote collaboration and innovation. Here, we present methods to expand the open-source electrophysiology system, Open Ephys (www.openephys.org), to include human EEG recordings. We describe the equipment and protocol necessary to interface various EEG caps with the Open Ephys acquisition board, and detail methods for processing data. We present applications of Open Ephys + EEG as a research tool and discuss how this innovative EEG technology lays a framework for improved closed-loop paradigms and novel brain-computer interface experiments. The Open Ephys + EEG system can record reliable human EEG data, as well as human EMG data. A side-by-side comparison of eyes closed 8-14 Hz activity between the Open Ephys + EEG system and the Brainvision ActiCHamp EEG system showed similar average power and signal to noise. Open Ephys + EEG enables users to acquire high-quality human EEG data comparable to that of commercially available systems, while maintaining the price point and extensibility inherent to open-source systems.


Simple hand-held metal detectors are an effective means of detecting cardiac pacemakers in the deceased prior to cremation.
The hazard of undetected cardiac pacemakers exploding in crematoria is well described. This short report describes the use of an affordable hand-held metal detector to detect cardiac pacemakers. Over the course of a year, the metal detector located 100% of cardiac pacemakers in a district general hospital mortuary. A simple model using pigskin and fat is also used to demonstrate the effectiveness in vitro. Commercially purchased hand-held metal detectors should be used in all mortuaries responsible for detection and removal of cardiac pacemakers prior to cremation.


Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice.
Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs.


Repair of the quadriceps apparatus following patellectomy in recent fractures of the patella: a new technique, with results.
The importance of "double tourniquet" technique in repair of the quadriceps mechanism after total patellectomy in recent fractures of the patella is described and its advantages are discussed. The results following this method of repair in 17 total patellectomies have been studied and discussed.


Arthroscopic and open approaches for autologous matrix-induced chondrogenesis repair of the knee have similar results: a meta-analysis.
Cartilage defects are debilitating injuries that can reduce quality of life in patients. However, the poor regenerative properties of cartilage mean that cartilage repair remains challenging, and many methods have arisen to address that. Autologous matrix-induced chondrogenesis (AMIC®) is a popular technique to manage cartilage defects. Recent advances have allowed AMIC® to be done arthroscopically, instead of a mini-open arthrotomy approach. This systematic review and meta-analysis aims to investigate whether the arthroscopic approach to AMIC® provides better clinical outcomes than does the mini-open approach, in hopes of delineating a gold standard in cartilage repair. With reference to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search of the following databases (PubMed, Embase, Scopus, and Cochrane Library) was performed on 26th October 2022 using a combination of the following search terms: "autologous matrix induced", "chondrogenesis", and "knee". A total of 390 studies were identified, of which, 24 studies were included in our final analysis. The arthroscopic approach achieves lower Visual Analogue Scale for pain scores. The International Knee documentation Committee) score and Knee Injury and Osteoarthritis Outcome Score were comparable between arthroscopic and open approaches. The open approach achieves a higher Magnetic Resonance Observation of Cartilage Repair Tissue score. Incidence of reported postoperative complications of revision surgery and knee stiffness was higher for the open approach than for the arthroscopic approach, whereas deep vein thrombosis was higher in the arthroscopic approach. The AMIC® repair outcomes indicate that the arthroscopic approach does not hold a distinct advantage over the open approach. The choice of approach should consider surgeon expertise, location of lesion, and patient-specific factors. Systematic review and meta-analysis; Level III.


A study of the correlation between morphological findings and biological activities in clinically nonfunctioning pituitary adenomas.
The aims of this study are to review the histology of the clinically nonfunctioning pituitary adenomas (CNFPAs) we have observed and to determine whether or not the frequency of cavernous sinus invasion is different among each type of morphology. In addition, several proliferative markers, including Ki67, p53, E-cadherin, matrix metallo-proteinase 9 and pituitary tumor derived fibroblast growth factor receptor 4 (ptd-FGFR4), were also investigated in invasive and non-invasive tumors. Our consequent 213 CNFPAs were diagnosed as follows: 64% were silent gonadotroph adenomas, 18% were null cell adenomas, 12% were silent corticotroph adenomas, 4% were silent Subtype 3 adenomas, and 1% were other types of adenomas. Female patients or younger patients showed a significant preponderance in silent corticotroph adenomas and in silent Subtype 3 adenomas, respectively. Cavernous sinus invasion occurs most frequently in silent corticotroph adenomas (85%) followed by Subtype 3 adenomas (67%), null cell adenomas (38%), and silent gonadotroph adenomas (11%). There were no significant differences in the Ki67, p53, E-cadherin, matrix metallo-proteinase 9, and ptd-FGFR4 expression between tumors with and without cavernous sinus invasion. From a clinical standpoint, it is quite important to differentiate morphological type in CNFPAs to aid the clinician in assessing the clinical behavior and prognosis of the tumor. Therefore, we suggest that all CNFPAs be examined not only by conventional light microscopy but also by immunohistochemistry, preferably by electron microscopy, to achieve a correct morphological diagnosis.


Insights into the expression of ABH and Lewis antigens through human bone marrow transplantation.
Twelve information bone marrow transplants, with at least one difference in ABO and/or Lewis types between donor and recipient, were retrospectively studied. ABH and Lewis antigens were determined in plasma, erythrocytes, and lymphocytes. Donor lymphocytes acquired the ABH and Lewis antigens from the recipient's plasma in the same way that donor erythrocytes acquired the Lewis antigens from it. Lymphocytotoxicity detected type 1 ABH and Lewis antigens only, providing evidence for the existence of combined ABH and Lewis antigens on lymphocytes. This was in contrast with the ABH antigens on type 2 chains of red cells, which are devoid of Lewis specificities. The differences in genetic control, probable chemical structure, and cellular origin of these two types of ABH antigens are presented in a theoretical model that accounts for most of the known data.


Quantifying the complexity of the delayed logistic map.
Statistical complexity measures are used to quantify the degree of complexity of the delayed logistic map, with linear and nonlinear feedback. We employ two methods for calculating the complexity measures, one with the 'histogram-based' probability distribution function and the other one with ordinal patterns. We show that these methods provide complementary information about the complexity of the delay-induced dynamics: there are parameter regions where the histogram-based complexity is zero while the ordinal pattern complexity is not, and vice versa. We also show that the time series generated from the nonlinear delayed logistic map can present zero missing or forbidden patterns, i.e. all possible ordinal patterns are realized into orbits.


Cation sensors containing a (bpy)Re(CO)3 group linked to an azacrown ether via an alkenyl or alkynyl spacer: synthesis, characterisation, and complexation with metal cations in solution.
Two [(bpy)Re(CO)3L]+ complexes (bpy = 2,2'-bipyridine), where L contains an aza-15-crown-5 ether which is linked to Re via an alkenyl- or alkynyl-pyridine spacer, have been synthesised along with model complexes. Solutions of the complexes in acetonitrile have been studied by UV-Vis absorption spectroscopy, and by 1D and 2D 1H NMR spectroscopy. Strong UV-Vis bands, assigned to intraligand charge-transfer transitions localised at the L ligands, blue shift on protonation of the azacrown nitrogen atom or on complexation of alkali-metal (Li+, Na+ and K+) or alkaline-earth metal (Mg2+, Ca2+ and Ba2+) cations to the azacrown; the magnitude of the blue shift is dependent on the cation, with protonation giving the largest shift of ca. 100 nm. Cation binding constants in the range of log K= 1-4 depend strongly on the identity of the metal cation. Protonation or cation complexation causes downfield shifts in the 1H NMR resonances from most of the azacrown and L ligand protons, and their magnitudes correlate with those of the blue shifts in the UV-Vis bands; shifts in the azacrown 1H NMR resonances report on how the different metal cations interact with the macrocycle. UV-Vis and 1H NMR spectra of the free L ligands enable the effect of the Re centre to be assessed. Together, the data indicate that the alkene spacer gives a more responsive sensor than the alkyne spacer by providing stronger electronic communication across the L ligand.


Sleep quality and mood symptoms in conscripted frontline nurse in Wuhan, China during COVID-19 outbreak: A cross-sectional study.
The aim of this study was to investigate the prevalence of sleep problems, depression and anxiety symptoms among conscripted frontline nurses fighting coronavirus disease 2019 (COVID-19) in Wuhan.This study was a cross-sectional study conducted with 100 frontline nurses. Sleep quality, depression, and anxiety symptoms were measured using the Pittsburgh sleep quality index (PSQI), the Generalized Anxiety Disorder 7-Item Scale (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9), respectively.Mean sleep duration was 5.71 hours (SD = 1.09) and mean sleep latency was 33.49 minutes (SD = 28.87). A total of 76%, 81%, 45%, and 19% reported difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS) or early morning awakening (EMA), nightmares and using hypnotics respectively. Among 100 participants in this study, 60 (60%) had poor sleep quality, 46 (46%) suffered depression symptoms and 40 (40%) reported anxiety symptoms. Sleep quality (OR = 3.16, 95% CI: 1.17-8.52) and anxiety symptoms (OR = 8.07, 95% CI: 2.92-22.33) were significantly associated with depression symptoms. Depression symptoms (OR = 7.92, 95% CI: 2.89-21.73) were related to anxiety symptoms. Similarly, depression symptoms (OR = 3.24, 95% CI: 1.19-8.79) were associated with poor sleep quality.Sleep disturbance, depression, and anxiety symptoms are very common among frontline nurses who treating patients with COVID-19 in Wuhan, China. Comprehensive measures that involve psychosocial and personal behaviors should be implemented to improve sleep quality and prevent depression and anxiety symptoms.


Tetramethylcyclopentadienylselenium derivatives.
Bis(1,2,3,4-tetramethylcyclopentadienyl)selane (1) has been prepared by the reaction of tetramethylcyclopentadienyllithium (Cp(t)Li) with selenium bis(diethyldithiocarbamate). Treatment of Cp(t)Li with elemental selenium, followed by air oxidation, led to loss of the allylic hydrogen atom, and formation of the novel tricyclic compound 1,4,5,6,7,10,11,12-octamethyltricyclo[188.8.131.52]-2,8-diselenadodeca-3,5,9,11-tetraene (2). The sulfur analogue of 2 has been obtained by a similar procedure. The X-ray crystal structures of compounds 1 and 2 have been determined, and the molecular geometry observed for has been probed using DFT calculations.


Morphine antinociception on thermal sensitivity and place conditioning in male and female rats treated with intraplantar complete freund's adjuvant.
The experience of pain is characterized by the presence of a noxious sensory stimulus combined with negative affect, which is often treated clinically through administration of drugs such as morphine or other opioids. This study investigated the effects of morphine one and seven days after intraplantar administration of complete freund's adjuvant (CFA) in male and female rats. Hargreaves test for thermal nociception and conditioned place preference (CPP) were performed following subcutaneous administration of saline or morphine (1.0, 4.0, 8.0, 12.0 mg/kg). Hargreaves test results revealed that male rats were more sensitive to morphine antinociceptive actions as compared to female rats one day after CFA treatment; however, this sex difference was not detected seven days after CFA treatment. One day after CFA treatment, morphine doses of 8.0 and 12.0 mg/kg produced a CPP in male rats, while female rats exhibited CPP with only the 12.0 mg/kg dose. Seven days after CFA treatment, both male and female rats exhibited a CPP with morphine doses of 4.0 mg/kg and higher. These results reveal sexually dimorphic properties of morphine in the paw withdrawal latencies and conditioned place preference models, representing reflexive and non-reflexive behavioral assays employed to examine inflammatory nociception. Our findings also suggest that antinociceptive effects of morphine are dynamic across early and later periods of CFA-induced inflammatory pain.


Characteristics of ciprofloxacin-resistant Enterobacteriaceae isolates recovered from wastewater of an Algerian hospital.
Hospital effluents are a source of environmental pollution by drugs, antibiotic-resistant bacteria, and resistance genes. Quinolones, particularly ciprofloxacin, are commonly detected in these effluents, contributing to the emergence of antimicrobial resistance. The objective of this study was to characterize ciprofloxacin-resistant Enterobacteriaceae in hospital effluents. Isolates were selected on Tergitol-7 agar supplemented with ciprofloxacin and genotyped by ERIC-PCR. Antibiotic susceptibility testing was done using the disk diffusion method, and minimum inhibitory concentrations were determined using the agar dilution method. Resistance genes, integrons, phylogenetic groups, and sequence types were identified by PCR and sequencing. A total of 17 ciprofloxacin-resistant isolates were characterized: Escherichia coli, Escherichia vulneris, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter freundii, and Citrobacter koseri/farmeri. Isolates presented concomitant resistance to nalidixic acid, ciprofloxacin, ofloxacin, and pefloxacin. A diversity in mutation patterns in gyrA and parC genes and new amino-acid substitutions in GyrA subunit were observed. Quinolone plasmidic resistance genes qnrB1, qnrB2, qnrB5/19, qnrS1, and aac(6')-Ib-cr were detected. Resistance to other antibiotic classes was observed. Class 1 integrons and resistance genes blaCTX-M-15, blaOXA-1, sul1, sul2, sul3, tetA, tetB, aadA1/2, aadA5, aph(3')-Ia, aac(3)II, dfrA1, dfrA5, dfrA7, and dfrA12 were detected. Bacterial tolerance to cadmium, zinc, and mercury was observed with the presence of the merA gene. E. coli isolates belonged to phylogenetic groups A, B1, and D and to sequence types ST405, ST443, ST101, ST10, and ST347. This study highlighted bacterial multidrug resistance linked to ciprofloxacin and, consequently, the risk of bacterial exposure to this antibiotic.


Home fortification during the first 1000 d improves child development in Bangladesh: a cluster-randomized effectiveness trial.
Background: Nutrition during the first 1000 d is critical for brain development.Objective: We evaluated the effects on child development of home fortification with lipid-based nutrient supplements (LNSs) for mothers and/or children or micronutrient powder (MNP) for children.Design: We conducted a cluster-randomized effectiveness trial with 4 arms: 1) LNSs during pregnancy and the first 6 mo postpartum and LNSs for the offspring from 6 to 24 mo (LNS-LNS), 2) iron and folic acid (IFA) during pregnancy and the first 3 mo postpartum and LNSs for the children from 6 to 24 mo (IFA-LNS), 3) IFA (as above) and MNP for the offspring from 6 to 24 mo (IFA-MNP), and 4) IFA (as above) and no child supplement (IFA-Control). Women were enrolled at ≤20 wk of gestation; children were assessed at 12 (n = 3331), 18 (n = 3364), and 24 (n = 3379) mo.Results: Compared with the IFA-Control group, motor development scores were higher in the LNS-LNS (P = 0.016) and IFA-LNS groups (P = 0.006) at 18 mo and in the IFA-MNP group (P = 0.048) at 24 mo. Receptive language scores were higher for the LNS-LNS group (P = 0.028) at 18 mo and for all 3 groups at 24 mo (P = 0.008 for LNS-LNS, P = 0.022 for IFA-LNS, and P = 0.009 for IFA-MNP compared with IFA-Control). Expressive language scores did not differ at 18 mo (P = 0.236) but were higher in the LNS-LNS (P = 0.035) and IFA-MNP (P = 0.002) groups than in the IFA-Control group at 24 mo. Groups did not differ in personal-social scores at 18 (P = 0.233) or 24 (P = 0.146) mo or in executive function score at 24 mo (P = 0.467).Conclusion: Prenatal LNSs, postnatal LNSs, or both, or postnatal MNP had a positive effect on motor and language development in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT01715038.


Vibrio cholerae ensures function of host proteins required for virulence through consumption of luminal methionine sulfoxide.
Vibrio cholerae is a diarrheal pathogen that induces accumulation of lipid droplets in enterocytes, leading to lethal infection of the model host Drosophila melanogaster. Through untargeted lipidomics, we provide evidence that this process is the product of a host phospholipid degradation cascade that induces lipid droplet coalescence in enterocytes. This infection-induced cascade is inhibited by mutation of the V. cholerae glycine cleavage system due to intestinal accumulation of methionine sulfoxide (MetO), and both dietary supplementation with MetO and enterocyte knock-down of host methionine sulfoxide reductase A (MsrA) yield increased resistance to infection. MsrA converts both free and protein-associated MetO to methionine. These findings support a model in which dietary MetO competitively inhibits repair of host proteins by MsrA. Bacterial virulence strategies depend on functional host proteins. We propose a novel virulence paradigm in which an intestinal pathogen ensures the repair of host proteins essential for pathogenesis through consumption of dietary MetO.


Ectocommensal and ectoparasites in goldfish Carassius auratus (Linnaeus, 1758) in farmed in the State of São Paulo.
Concomitant infections by several parasitic genera are rare, very debilitating and often lethal to fish reared under commercial breeding conditions. Were describe a multiple and concurrent parasite infestation in cultured goldfish Carassius auratus with skin damage (nodules and/or ulceration). Fish with skin lesions underwent necropsy, and the skin and gills were scraped and examined. Histopathological examination with Hematoxylin-Eosin and Giemsa stain, and an ultrastructure study using transmission and scanning electron microscopy were conducted. In the skin, we identified multiple-parasite infestations by Gyrodactylidae, Epistylis sp., Trichodina sp., Ichthyophthirius multifiliis, Tetrahymena sp. and Ichthyobodo necator,associated with epithelial cell hyperplasia and epidermal sloughing. Although no gross lesions were observed, were identified a large number of parasites in the gills (Epistylis sp., Piscinoodinium sp., Ichthyophthirius multifiliis, Trichodina sp., Apiosoma sp., Hexamitasp. and cysts of a trematode digenean). The observed trematodes were not identified. The associated microscopic lesions were epithelial hypertrophic and hyperplasic and exhibited fusion of secondary lamellae and epithelial cell detachment. This is the first description of a protozoan Vorticella sp. parasitizing goldfish in Brazil. Multiple ectoparasitism by protozoa and Platyhelminthes, with or without apparent tissue damage, can be fatal for goldfish raised on farms with poor management.


Seasonal Variation of 'Candidatus Liberibacter asiaticus' Titers in New Shoots of Citrus in Distinct Environments.
The major citrus area of Brazil occupies near 450,000 ha between the Triângulo Mineiro (TM) region of Minas Gerais State and the south of São Paulo State (SPS). Significant climatic variation occurs between regions which could affect huanglongbing (HLB) progress, which is lower in TM. To investigate this possibility, young sweet orange shoots were sampled periodically over 2 years to determine 'Candidatus Liberibacter asiaticus' titers in naturally infected trees in orchards in Analândia, central SPS, and Frutal and Comendador Gomes, within TM. Data-loggers recorded local temperature and relative humidity hourly. In the laboratory, five 'Ca. L. asiaticus'-free Diaphorina citri adults were placed on each sampled shoot for 48 h to feed and acquire the pathogen. Shoots and insects were individually analyzed by quantitative polymerase chain reaction to determine 'Ca. L. asiaticus' titers. The incidence of 'Ca. L. asiaticus'-positive shoots, 'Ca. L. asiaticus' titers, and acquisition rates were lower for shoots from Comendador Gomes than those from Frutal or Analândia. Stronger association was observed between 'Ca. L. asiaticus' titers and the number of hours below 15°C (h < 15°C) or above 30°C (h > 30°C), and cumulative rainfall registered during the 15 days prior to sampling of shoots on each occasion. 'Ca. L. asiaticus' titers associated positively with h < 15°C and rainfall and negatively with h > 30°C. The slower spread and lower incidence of HLB in TM may be related to lower incidences of 'Ca. L. asiaticus'-positive young shoots and lower titers of 'Ca. L. asiaticus' in the same shoots as a consequence of the warmer and drier conditions.


[Morpho-functional changes of hippocampal CA1 area in Mongolian gerbils after ischemic postconditioning].
The aim of this study was to determine the effect of ischemic postconditioning on hippocampal CA1 neuronal survival and cytoplasmic activity of lactate dehydrogenase (LDH) in the gerbil model of cerebral ischemia-reperfusion injury. Ischemia was induced by bilateral common carotid artery occlusion (for 7 min) in male Mongolian gerbils (Meriones unguiculatus). Ischemic postconditioning protocol comprised 3 cycles of 15 s reperfusion/15 s ischemia. After 48 h of reperfusion, CA1 neuronal death was detected by Nissl staining and the cytoplasmic LDH was demonstrated histochemically in CA1 area of the hippocampus with a quantitative cytophotometric assessment of the enzyme activity. The results have shown that 7 min ischemia resulted in a significant decrease in the number of viable neurons (up to 24%) in the CA1 area of hippocampus; in addition, it reduced the activity of LDH in these neurons (from 0.260 +/- 0.009 to 0.190 +/- 0.006 relative units). The application of ischemic postconditioning significantly increased the number of viable neurons (up to 52.9%, P < 0.01) in the CA1 area of hippocampus, and it was accompanied by an increase in the activity of LDH (0.240 +/- 0.008 relative units, P < 0.001).


MRBLE-pep Measurements Reveal Accurate Binding Affinities for B56, a PP2A Regulatory Subunit.
Signal transduction pathways rely on dynamic interactions between protein globular domains and short linear motifs (SLiMs). The weak affinities of these interactions are essential to allow fast rewiring of signaling pathways and downstream responses but also pose technical challenges for interaction detection and measurement. We recently developed a technique (MRBLE-pep) that leverages spectrally encoded hydrogel beads to measure binding affinities between a single protein of interest and 48 different peptide sequences in a single small volume. In prior work, we applied it to map the binding specificity landscape between calcineurin and the PxIxIT SLiM (Nguyen, H. Q. et al. Elife 2019, 8). Here, using peptide sequences known to bind the PP2A regulatory subunit B56α, we systematically compare affinities measured by MRBLE-pep or isothermal calorimetry (ITC) and confirm that MRBLE-pep accurately quantifies relative affinity over a wide dynamic range while using a fraction of the material required for traditional methods such as ITC.


Insight into sulfur reactions in Li-S batteries.
Understanding and controlling the sulfur reduction species (Li2Sx, 1 ≤ x ≤ 8) under realistic battery conditions are essential for the development of advanced practical Li-S cells that can reach their full theoretical capacity. However, it has been a great challenge to probe the sulfur reduction intermediates and products because of the lack of methods. This work employed various ex situ and in situ methods to study the mechanism of the Li-S redox reactions and the properties of Li2Sx and Li2S. Synchrotron high-energy X-ray diffraction analysis used to characterize dry powder deposits from lithium polysulfide solution suggests that the new crystallite phase may be lithium polysulfides. The formation of Li2S crystallites with a polyhedral structure was observed in cells with both the conventional (LiTFSI) electrolyte and polysulfide-based electrolyte. In addition, an in situ transmission electron microscopy experiment observed that the lithium diffusion to sulfur during discharge preferentially occurred at the sulfur surface and formed a solid Li2S crust. This may be the reason for the capacity fade in Li-S cells (as also suggested by EIS experiment in Supporting Information ). The results can be a guide for future studies and control of the sulfur species and meanwhile a baseline for approaching the theoretical capacity of the Li-S battery.


Effects of ovariectomy and oestradiol replacement on hypothalamic serotonergic and monoamine oxidase activity in the catfish, Heteropneustes fossilis: a study correlating plasma oestradiol and gonadotrophin levels.
Hypothalamic serotonin (5-HT; content and turnover) and monoamine oxidase (MAO) activity were measured in female catfish, Heteropneustes fossilis, after ovariectomy and supplementation with oestradiol-17 beta (OE2) in the recrudescent and quiescent phases. These factors were correlated with changes in plasma levels of OE2 and gonadotrophin. In the quiescent phase (December), neither ovariectomy nor OE2 supplementation had any significant effect on 5-HT content and MAO activity. Plasma levels of OE2 and gonadotrophin were undetectable in both control and treated fish, indicating that there was no feedback effect. In the recrudescent phase (prespawning, May), ovariectomy caused biphasic responses of MAO activity and 5-HT content. The enzyme activity decreased significantly after 2, 3, 4 and 5 weeks but increased significantly 6 weeks after ovariectomy. The 5-HT content varied in a biphasic manner with a significant increase at 2, 3 or 4 weeks and a significant decrease in week 6; there being no effect in week 5. 5-HT turnover was inhibited significantly only in week 4 after ovariectomy and did not show a biphasic pattern. In the ovariectomized groups, the OE2 level decreased significantly in a progressive manner with a maximum reduction in week 6. The plasma level of gonadotrophin showed a significant bimodal pattern of increase with the peak in week 4 after ovariectomy, indicating a strong negative feedback effect of OE2. The bimodal pattern of pituitary gonadotrophin release could be correlated with a similar pattern of increase in 5-HT content. OE2 treatment of fish which had been ovariectomized 3 weeks previously had dose-dependent effects on the enzyme; the low dose (0.1 microgram/g body weight) was stimulatory and the higher doses (0.5, 1.0 and 5.0 micrograms/g body weight) were inhibitory. The reverse was true for 5-HT content. Serotonergic turnover increased significantly only in the groups given high doses (1.0 and 5.0 micrograms/g body weight). The low dose of OE2 (0.1 micrograms/g body weight) restored the gonadotrophin and OE2 levels to those of the sham-ovariectomized vehicle-treated control group, whereas the high doses (0.5, 1.0 and 5.0 micrograms/g body weight) decreased the release of gonadotrophin in a dose-dependent manner. Our results suggest that OE2 modulates MAO activity to alter hypothalamic 5-HT in a seasonally dependent manner. The ovariectomy-induced changes in plasma levels of gonadotrophin appear to be mediated, at least partly, by the feedback action of OE2 on 5-HT metabolism.


A system for modelling cell-cell interactions during plant morphogenesis.
During the development of multicellular organisms, cells are capable of interacting with each other through a range of biological and physical mechanisms. A description of these networks of cell-cell interactions is essential for an understanding of how cellular activity is co-ordinated in regionalized functional entities such as tissues or organs. The difficulty of experimenting on living tissues has been a major limitation to describing such systems, and computer modelling appears particularly helpful to characterize the behaviour of multicellular systems. The experimental difficulties inherent to the multitude of parallel interactions that underlie cellular morphogenesis have led to the need for computer models. A new generic model of plant cellular morphogenesis is described that expresses interactions amongst cellular entities explicitly: the plant is described as a multi-scale structure, and interactions between distinct entities is established through a topological neighbourhood. Tissues are represented as 2D biphasic systems where the cell wall responds to turgor pressure through a viscous yielding of the cell wall. This principle was used in the development of the CellModeller software, a generic tool dedicated to the analysis and modelling of plant morphogenesis. The system was applied to three contrasting study cases illustrating genetic, hormonal and mechanical factors involved in plant morphogenesis. Plant morphogenesis is fundamentally a cellular process and the CellModeller software, through its underlying generic model, provides an advanced research tool to analyse coupled physical and biological morphogenetic mechanisms.


Delivering multiprofessional web-based psychosocial education: the lessons learnt.
Psychosocial care is one component of high-quality cancer/palliative care. The development of the internet has revolutionized the way we conduct business, shop, communicate with each other, and seek information. This article reports on the delivery of a web-based 16-week module: 'The management of cancer: psychosocial perspectives'. Twenty-nine students represented by a wide range of members of the multidisciplinary team registered for this module. Electronic-learning programmes are noted for high attrition rates, but, in this delivery, attrition rates and assessment performance were compatible with face-to-face programmes of learning. The delivery of this module indicates that there is scope for helping multiprofessional staff develop their knowledge and skills in psychosocial care.


Observation of topologically protected bound states in photonic quantum walks.
Topological phases exhibit some of the most striking phenomena in modern physics. Much of the rich behaviour of quantum Hall systems, topological insulators, and topological superconductors can be traced to the existence of robust bound states at interfaces between different topological phases. This robustness has applications in metrology and holds promise for future uses in quantum computing. Engineered quantum systems--notably in photonics, where wavefunctions can be observed directly--provide versatile platforms for creating and probing a variety of topological phases. Here we use photonic quantum walks to observe bound states between systems with different bulk topological properties and demonstrate their robustness to perturbations--a signature of topological protection. Although such bound states are usually discussed for static (time-independent) systems, here we demonstrate their existence in an explicitly time-dependent situation. Moreover, we discover a new phenomenon: a topologically protected pair of bound states unique to periodically driven systems.


[Assessment of sensitivity of commercial test-systems for HBsAg immunodetection according to their ability to detect HBsAg-mutants of hepatitis B virus].
Comparative study of widely distributed on Russian market commercial test-systems for HBsAg detection by enzyme immunoassay was performed. Panel of serum samples containing mutant forms of HBsAg was developed for the study. It showed that only 2 out of 7 studied test-systems are able to detect mutant forms of HBsAg with the same sensitivity as "wild-type" forms of HBsAg. Test-systems based only on monoclonal antibodies did not detect HBsAg with G145R substitution in concentration 5 ng/ml. The study confirms the relevance of problem of HBsAg-mutants detection for hepatitis B immunodiagnostics.


Growth, Yield and Biochemical Impact of Anti-transpirants on Sunflower Plant Grown under Water Deficit.
Climate change affecting on weather in many different ways especially drought and temperature rise. This will drastically down plant production, if not start looking for another source to increase water productivity to cope up with water stress conditions. In this study efforts were conducted to interpret the use of anti-transpirants to conserving irrigation water, aiding plant survival under dry conditions and protecting plant against drought stress. Two field experiments were carried out during 2017 and 2018 successive growing summer seasons at the experimental farm of National Research Centre, Nubaria, El-Beheira Governorate, Egypt. Anti-transparent ,i.e., chitosan (100 and 150 mg L-1), calcium carbonate (5 and 10 g L-1), salicylic acid (200 and 300 mg L-1) were foliar sprayed on sunflower plants grown under two water levels (normal 100% and deficit 50%). The results showed that water stress decreased growth criteria, photosynthetic pigments, osmoprotectants, yield components, oil and carbohydrate (%) as compared to 100% of irrigation requirements. Meanwhile, water deficit induced significant increases in (proline). Foliar treatments of sunflower plant with chitosan, calcium carbonate, salicylic acid increased growth criteria, yield components, photosynthetic pigments, total soluble sugars, proline and free amino acid as compared to control plant. Data also illustrated that, all used treatment improved seed yield, oil and carbohydrate% of sunflower plants. Generally, it could be concluded that 10 g L-1 CaCO3 and 300 mg L-1 SA at 50% level of water irrigation could be recommended for sunflower plant grown under similar field conditions in order to get optimum yield and to save irrigation water.


British Society for Rheumatology Biologics Register.
The British Society for Rheumatology (BSR) established a register of patients newly treated with biological agents, the BSR Biologics Register (BSRBR), which became active in January 2002. The goal is to register all patients in the United Kingdom with rheumatic diseases, newly starting treatment with these agents and to follow them up to determine the incidence of any short and long term hazards to health. The Register is also recruiting a comparison cohort of patients with rheumatoid arthritis treated with standard disease modifying antirheumatic drugs to determine the relative contributions of disease factors and other treatments apart from biological agents on any risks observed.


[Role of O-GlcNAc modification of cellular proteins in signal transduction].
Glycosylation, consisting in incorporation of single beta-N-acetyl-D-glucosamine residues attached by O-linkage to serine or threonine residues, is a common modification of cytoplasmic and nuclear proteins. Up to now about 200 proteins modified by O-GlcNAc have been identified including transcription factors, signaling components and metabolic enzymes. O-GlcNAc modified proteins can be also phosphorylated. In some cases O-GlcNAc and O-phosphate alternatively occupy the same sites. It has been suggested, that in signal transduction, instead of simple regulation by phosphorylation, more complex mechanism including glycosylation, is involved. Presented work focus on the structure and function of enzymes involved in O-GlcNAc modification and the role of this modification in regulating signal transduction and transcription.


Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia.
Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in the clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRSs) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project. Pseudocontrols generated from the nontransmitted parental alleles of the parents in these trios were compared with alleles in schizophrenia patients in assessing the replicability of PGC-derived susceptibility variants. Schizophrenia PRS at the P-value threshold (PT) of 0.1 explained 0.2% in the variance of disease status in this Han-Taiwanese samples, and the score itself had a P-value 0.05 for the association test with the disorder. Each patient underwent neurocognitive evaluation on sustained attention using the continuous performance test and executive function using the Wisconsin Card Sorting Test. We applied a structural equation model to construct the neurocognitive latent variable estimated from multiple measured indices in these 2 tests, and then tested the association between the PRS and the neurocognitive latent variable. Higher schizophrenia PRS generated at the PT of 0.1 was significantly associated with poorer neurocognitive performance with explained variance 0.5%. Our findings indicated that schizophrenia susceptibility variants modify the neurocognitive performance in schizophrenia patients.