Multivariate control charts for monitoring a bivariate correlated count process with application to meningococcal disease.
In recent years, with the increasing number and complexity of infectious diseases, the idea of using control charts to monitor public health and disease has been proposed. In this paper, we study multivariate control charts for monitoring a bivariate integer-valued autocorrelation process with bivariate Poisson distribution and select the optimal control scheme by comparing the performance of control charts. Furthermore, the meningococcal patient event in two states in Australia serves as an example to illustrate the application of these methods. The results show that the D exponentially weighted moving average control scheme can detect the changes in the mean value faster, which is a significant advantage.


Negative feedback of T cell activation through inhibitory adapters and costimulatory receptors.
Antigen recognition by the T cell receptor (TCR) complex induces the formation of a TCR signalosome by recruiting various signaling molecules, generating the recognition signals for T cell activation. The activation status and functional outcome are positively and negatively regulated by dynamic organization of the signalosome and by costimulation signals. We have studied the negative regulation of T cell activation, particularly through inhibitory adapters and costimulation receptors that are little expressed in resting cells but are induced upon T cell activation. We described Grb-associated binder 2 (Gab2) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as a representative inhibitory adapter and a negative costimulation receptor, respectively, both of which exhibit negative feedback. Gab2 functions as a signal branch for activation vs. inhibition, as phosphorylation of either Src homology 2 (SH2) domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) or Gab2 by zeta-associated protein of 70 kDa (ZAP-70) determines the fate of the response. As a professional inhibitory receptor, CTLA-4 inhibits T cell response by competition of ligand binding with positive costimulator receptor CD28, and also induces inhibitory signaling. The trafficking and the cell surface expression of CTLA-4 are dynamically regulated and induced. CTLA-4 is accumulated in lysosomes and secreted to the T cell-APC contact site upon TCR stimulation. As T cell activation proceeds, these inhibitory adapters and costimulation receptors are induced and suppress/regulate the responses as negative feedback.


Structural Evolution of Pt, Au and Cu Anodes by Electrolysis up to Contact Glow Discharge Electrolysis in Alkaline Electrolytes*.
Applying a voltage to metal electrodes in contact with aqueous electrolytes results in the electrolysis of water at voltages above the decomposition voltage and plasma formation in the electrolyte at much higher voltages referred to as contact glow discharge electrolysis (CGDE). While several studies explore parameters that lead to changes in the I-U characteristics in this voltage range, little is known about the evolution of the structural properties of the electrodes. Here we study this aspect on materials essential to electrocatalysis, namely Pt, Au, and Cu. The stationary I-U characteristics are almost identical for all electrodes. Detailed structural characterization by optical microscopy, scanning electron microscopy, and electrochemical approaches reveal that Pt is stable during electrolysis and CGDE, while Au and Cu exhibit a voltage-dependent oxide formation. More importantly, oxides are reduced when the Au and Cu electrodes are kept in the electrolysis solution after electrolysis. We suspect that H2 O2 (formed during electrolysis) is responsible for the oxide reduction. The reduced oxides (which are also accessible via electrochemical reduction) form a porous film, representing a possible new class of materials in energy storage and conversion studies.


Lrg1 Regulates β (1,3)-Glucan Masking in Candida albicans through the Cek1 MAP Kinase Pathway.
Candida albicans is among the most prevalent opportunistic human fungal pathogens. The ability to mask the immunogenic polysaccharide β (1,3)-glucan from immune detection via a layer of mannosylated proteins is a key virulence factor of C. albicans We previously reported that hyperactivation of the Cek1 mitogen-activated protein (MAP) kinase pathway promotes β (1,3)-glucan exposure. In this communication, we report a novel upstream regulator of Cek1 activation and characterize the impact of Cek1 activity on fungal virulence. Lrg1 encodes a GTPase-activating protein (GAP) that has been suggested to inhibit the GTPase Rho1. We found that disruption of LRG1 causes Cek1 hyperactivation and β (1,3)-glucan unmasking. However, when GTPase activation was measured for a panel of GTPases, the lrg1ΔΔ mutant exhibited increased activation of Cdc42 and Ras1 but not Rho1 or Rac1. Unmasking and Cek1 activation in the lrg1ΔΔ mutant can be blocked by inhibition of the Ste11 MAP kinase kinase kinase (MAPKKK), indicating that the lrg1ΔΔ mutant acts through the canonical Cek1 MAP kinase cascade. In order to determine how Cek1 hyperactivation specifically impacts virulence, a doxycycline-repressible hyperactive STE11ΔN467 allele was expressed in C. albicans In the absence of doxycycline, this allele overexpressed STE11ΔN467 , which induced production of proinflammatory tumor necrosis factor alpha (TNF-α) from murine macrophages. This in vitro phenotype correlates with decreased colonization and virulence in a mouse model of systemic infection. The mechanism by which Ste11ΔN467 causes unmasking was explored with RNA sequencing (RNA-Seq) analysis. Overexpression of Ste11ΔN467 caused upregulation of the Cph1 transcription factor and of a group of cell wall-modifying proteins which are predicted to impact cell wall architecture.IMPORTANCECandida albicans is an important source of systemic infections in humans. The ability to mask the immunogenic cell wall polymer β (1,3)-glucan from host immune surveillance contributes to fungal virulence. We previously reported that the hyperactivation of the Cek1 MAP kinase cascade promotes cell wall unmasking, thus increasing strain immunogenicity. In this study, we identified a novel regulator of the Cek1 pathway called Lrg1. Lrg1 is a predicted GTPase-activating protein (GAP) that represses Cek1 activity by downregulating the GTPase Cdc42 and its downstream MAPKKK, Ste11. Upregulation of Cek1 activity diminished fungal virulence in the mouse model of infection, and this correlates with increased cytokine responses from macrophages. We also analyzed the transcriptional profile determined during β (1,3)-glucan exposure driven by Cek1 hyperactivation. Our report provides a model where Cek1 hyperactivation causes β (1,3)-glucan exposure by upregulation of cell wall proteins and leads to more robust immune detection in vivo, promoting more effective clearance.


Scope of practice issues in forensic nursing.
1. There is significant role variation, across the Western world, in relation to how forensic nurses practice. 2. The authors conducted a pilot survey of forensic nurses in Australia, New Zealand, the United States, and the United Kingdom to examine forensic nursing practice, role definition, and role boundaries. 3. Issues arising from the data include the visibility of forensic nurses, the client group, forensic-specific education, and role development.


How Antimalarials and Antineoplastic Drugs can Interact in Combination Therapies: A Perspective on the Role of PPT1 Enzyme.
Antimalarial drugs from different classes have demonstrated anticancer effects in different types of cancer cells, but their complete mode of action in cancer remains unknown. Recently, several studies reported the important role of palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme, as the molecular target of chloroquine and its derivates in cancer. It was also found that PPT1 is overexpressed in different types of cancer, such as breast, colon, etc. Our group has found a synergistic interaction between antimalarial drugs, such as mefloquine, artesunate and chloroquine and antineoplastic drugs in breast cancer cells, but the mechanism of action was not determined. Here, we describe the importance of autophagy and lysosomal inhibitors in tumorigenesis and hypothesize that other antimalarial agents besides chloroquine could also interact with PPT1 and inhibit the mechanistic target of rapamycin (mTOR) signalling, an important pathway in cancer progression. We believe that PPT1 inhibition results in changes in the lysosomal metabolism that result in less accumulation of antineoplastic drugs in lysosomes, which increases the bioavailability of the antineoplastic agents. Taken together, these mechanisms help to explain the synergism of antimalarial and antineoplastic agents in cancer cells.


Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals: a cross-sectional study.
Visceral adipose tissue (VAT) and truncal fat predict cardiometabolic disease. Intervention trials suggest that saturated fatty acids (SFA), e.g. palmitic acid, promote abdominal and liver fat storage whereas polyunsaturated fatty acids (PUFA), e.g. linoleic acid, prevent fat accumulation. Such findings require investigation in population-based studies of older individuals. We aimed to investigate the relationships of serum biomarkers of PUFA intake as well as serum levels of palmitic acid, with abdominal and total adipose tissue content. In a population-based sample of 287 elderly subjects in the PIVUS cohort, we assessed fatty acid composition in serum cholesterol esters (CE) and phospholipids (PL) by gas chromatography and the amount of VAT and abdominal subcutaneous (SAT) adipose tissue by magnetic resonance imaging (MRI), liver fat by MR spectroscopy (MRS), and total body fat, trunk fat and leg fat by dual-energy X-ray absorptiometry (DXA). Insulin resistance was estimated by HOMA-IR. VAT and trunk fat showed the strongest correlation with insulin resistance (r = 0.49, P < 0.001). Linoleic acid in both CE and PL was inversely related to all body fat depots (r = -0.24 to -0.33, P < 0.001) including liver fat measured in a sub-group (r = -0.26, P < 0.05, n = 73), whereas n-3 PUFA showed weak inverse (18:3n-3) or positive (20:5n-3) associations. Palmitic acid in CE, but not in PL, was directly correlated with VAT (r = 0.19, P < 0.001) and trunk fat (r = 0.18, P = 0.003). Overall, the significant associations remained after adjusting for energy intake, height, alcohol, sex, smoking, education and physical activity. The inverse correlation between linoleic acid and VAT remained significant after further adjustment for total body fat. Serum linoleic acid is inversely related to body fat storage including VAT and trunk fat whereas palmitic acid was less consistently but directly associated, in line with recent feeding studies. Considering the close link between VAT and insulin resistance, a potential preventive role of plant-based PUFA in VAT accumulation warrants further study.


Trauma-informed care in a patient-centered medical home for adolescent mothers and their children.
Adolescent mothers experience higher rates of trauma and abuse, as well as increased risks for mental health disorders, compared to adolescent girls who are not mothers, making them a particularly vulnerable population and contributing to them feeling less supported by or allied with their medical provider. Women with a history of childhood abuse face increased rates of obstetric complications; their infants are at increased risk for low birthweight, developmental and intellectual delays, and behavioral problems. Trauma-informed care has become widespread in mental health settings; however, this model has not been as commonly applied to other settings, such as patient-centered medical homes (PCMHs). The Colorado Adolescent Maternity Program (CAMP) is an obstetric and pediatric medical home for pregnant and parenting adolescent girls through age 22 and their children located within Children's Hospital Colorado. With the integration of behavioral health into CAMP, and given the prevalence of trauma histories among adolescent mothers reported in the literature, programmatic and operational changes to clinical care were made using the Substance Abuse and Mental Health Services Administration's six key principles of a trauma-informed approach. Data showed that nearly 30% of participants reported a history of trauma. Following the inclusion of trauma-informed principles, patients had significantly higher rates of attendance at prenatal appointments (p < .001) and significantly lower rates of low birthweight babies (p = .02). Future programmatic changes and long-term assessment outcomes of this trauma-informed approach in a PCMH are also discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


[Lymphocytic hormonal receptors (author's transl)].
The recent development of technics of specific fixation using radio isotope-labelled tracer elements permits the demonstration of various types of receptors at the level of the lymphocyte membrane. Thus a new route is open in the understanding of the biochemical mechanisms controlling the physiology of the lymphocyte and its role in the immune response. Furthermore these lymphocyte receptors may represent to some degree, the state of the rarely accessible tissue receptors in human pathology. However, at present, the practical interest is limited by the absence of standardisation of technics and the heterogeneity of athe lymphocyte population studied.


The natural food grade inhibitor, lacticin 3147, reduced the incidence of mastitis after experimental challenge with Streptococcus dysgalactiae in nonlactating dairy cows.
Lacticin 3147 is a broad-spectrum bacteriocin produced by the food-grade organism Lactococcus lactis. Lacticin 3147 is active at a neutral pH and has been shown to be bactericidal to streptococci and staphylococci in vitro. The effectiveness of an intramammary teat seal formulation, and a teat seal containing lacticin 3147 was evaluated at drying off in 68 uninfected quarters of 18 cows. Following infusion of either teat seal or lacticin 3147 combined with teat seal, a deliberate infection challenge of Streptococcus dysgalactiae (approximately equal to 1.5 x 10(4) cfu per teat) was administered by direct inoculation into the teat sinus. During an 8-d experimental period following inoculation, 61% of control quarters and 6% of the treatment quarters either developed clinical mastitis or were shedding the challenge organism. Randomly amplified polymorphic DNA polymerase chain reaction genetic typing was used to confirm that both the new infections and the bacteria surviving in the teats at the end of the experiment were the challenge strain. The combination of teat seal and lacticin 3147 was well tolerated within the udder and elicited only a temporary increase in somatic cell count to 5.7 x 10(5)/ml (88 h after infusion) in a previously uninfected lactating udder quarter. Therefore, we concluded that this nonantibiotic approach to mastitis prevention may contribute to a reduction in the routine application of antibiotics at drying off in the future.


A novel aspect of the inhibition by arsenicals of binding-protein-dependent galactose transport in gram-negative bacteria.
The inhibitory effects of arsenate and arsenite on binding-protein-dependent transport systems are reconsidered. It is shown that arsenate inhibits binding-protein-dependent galactose transport in proteoliposomes energized either by dihydrolipoamide and NAD+ or by a membrane potential (under conditions where ATP metabolism is not implicated); this result is in contradiction with the current interpretation of arsenate inhibition of binding-protein-dependent transport systems (which is based on ATP depletion) and can be explained by reference to the recently discovered ATP inhibition of the binding-protein-dependent galactose transport. In whole cells, the greater inhibition by arsenate of lipoamide-dependent transport than of protonmotive-force-dependent transport may be explained by a modification by arsenate of the pools of several compounds metabolized by 2-oxo-acid dehydrogenases (which have been implicated in binding-protein-dependent transport). The inhibition of binding-protein-dependent galactose transport by arsenite is probably linked to the inhibition by arsenite of the galactose-stimulated lipoamide dehydrogenase activity implicated in this transport and is reminiscent of the known arsenite inhibition of lipoamide dehydrogenases.


[The comparative characteristic of two methods of detection of mutations of beta-globin gene].
Nowadays, two methods of detection of mutations of beta-globin gene are applied: amplification of refractory mutation system and reverse dot-blot-hybridization. The study was implemented to comparatively analyze effectiveness of these methods of molecular diagnostic in detection of thalassemic mutations in Azerbaijan. The examined sample consisted of 82 patients with both homozygous and heterozygous thalassemia and drepanothalassemia as well. In examined patients 146 mutant alleles were detected; 132 were thalassemic ones (16 various mutations) and 14 ranked among hemoglobinosis S (cod6(A>T)). The comparison of effectiveness of mentioned methods made it possible to conclude that both compared methods fit the diagnostic of thalassemic mutations. However the method of inverse dot-blot-hybridization has a number of advantages and is the best choice for Azerbaijan.


Coherence resonance in influencer networks.
Complex networks are abundant in nature and many share an important structural property: they contain a few nodes that are abnormally highly connected (hubs). Some of these hubs are called influencers because they couple strongly to the network and play fundamental dynamical and structural roles. Strikingly, despite the abundance of networks with influencers, little is known about their response to stochastic forcing. Here, for oscillatory dynamics on influencer networks, we show that subjecting influencers to an optimal intensity of noise can result in enhanced network synchronization. This new network dynamical effect, which we call coherence resonance in influencer networks, emerges from a synergy between network structure and stochasticity and is highly nonlinear, vanishing when the noise is too weak or too strong. Our results reveal that the influencer backbone can sharply increase the dynamical response in complex systems of coupled oscillators.


Evaluation of rosette infrasonic noise-reducing spatial filters.
This paper presents results from recent tests of rosette infrasonic noise-reducing spatial filters at the Pinon Flat Observatory in southern California. Data from 18- and 70-m aperture rosette filters and a reference port are used to gauge the reduction in atmospheric wind-generated noise levels provided by the filters and to examine the effect of these spatial filters on spatially coherent acoustic signals in the 0.02- to 10-Hz band. At wind speeds up to 5.5 m/s, the 18-m rosette filter reduces wind noise levels above 0.2 Hz by 15 to 20 dB. Under the same conditions, the 70-m rosette filter provides noise reduction of up to 15 to 20 dB between 0.02 and 0.7 Hz. Standing wave resonance inside the 70-m filter degrades the reception of acoustic signals above 0.7 Hz. The fundamental mode of the resonance, 15 dB above background, is centered at 2.65-Hz and the first odd harmonic is observed at 7.95 Hz in data from the large filter. Analytical simulations accurately reproduce the noise reduction and resonance observed in the 70-m filter at all wind speeds above 1.25 m/s. Resonance theory indicates that internal reflections that give rise to the resonance observed in the passband are occurring at the summing manifolds, and not at the inlets. Rosette filters are designed for acoustic arrivals with infinite phase velocity. The plane-wave response of the 70-m rosette filter has a strong dependence on frequency above 3.5 Hz at grazing angles of less than 15 degrees from the horizontal. At grazing angles, complete cancellation of the signal occurs at 5 Hz. Theoretical predictions of the phase and amplitude response of 18- and 70-m rosette filters, that take into account internal resonance and time delays between the inlets, compare favorably with observations derived from a cross-spectral analysis of signals from the explosion of a large bolide.


Effectiveness of monovalent and pentavalent rotavirus vaccine.
Previous US evaluations have not assessed monovalent rotavirus vaccine (RV1, a G1P[8] human rotavirus strain) effectiveness, because of its later introduction (2008). Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose RV1 and 3-dose pentavalent vaccine (RV5) series against rotavirus disease resulting in hospital emergency department or inpatient care. Children were eligible for enrollment if they presented to 1 of 5 hospitals (3 in Georgia, 2 in Connecticut) with diarrhea of ≤10 days' duration during January through June 2010 or 2011, and were born after RV1 introduction. Stools were collected; immunization records were obtained from providers and state electronic immunization information system (IIS). Case-subjects (children testing rotavirus antigen-positive) were compared with 2 control groups: children testing rotavirus negative and children selected from IIS. Overall, 165 rotavirus-case subjects and 428 rotavirus-negative controls were enrolled. Using the rotavirus-negative controls, RV1 VE was 91% (95% confidence interval [CI] 80 to 95) and RV5 VE was 92% (CI 75 to 97) among children aged ≥8 months. The RV1 VE against G2P[4] disease was high (94%, CI 78 to 98), as was that against G1P[8] disease (89%, CI 70 to 96). RV1 effectiveness was sustained among children aged 12 through 23 months (VE 91%; CI 75 to 96). VE point estimates using IIS controls were similar to those using rotavirus-negative controls. RV1 and RV5 were both highly effective against severe rotavirus disease. RV1 conferred sustained protection during the first 2 years of life and demonstrated high effectiveness against G2P[4] (heterotypic) disease.


Occupational exposure to hepatitis B in paramedics.
To determine their occupational risk for hepatitis B infection, 59 Seattle paramedics were tested for hepatitis B serum markers. Evidence of antibody to hepatitis B surface antigen (anti-HBs) or antibody to hepatitis B core antigen (anti-HBc) was found in 25%, a rate five times that of a similar Seattle population. Seropositivity did not correlate with age, race, clinical history, or length of service. Of the 15 paramedics with seropositivity to hepatitis B virus six initially had low titers of either anti-HBs or anti-HBc. Four of the six demonstrated persistent low-grade seropositivity on retesting. Paramedics are at increased risk of hepatitis B infection. The high frequency of low-titer anti-HBs suggests that frequent low-level exposure to hepatitis B virus occurs in this population; hepatitis B vaccine should be strongly considered for paramedics.


Bacterial pathogens associated with diarrhoea on the island of Crete.
Stool specimens from 3,600 diarrhoeal patients from the island of Crete, Greece, were examined for bacterial pathogens, during a three-year period (1992-1994). One or more pathogens were identified in 826 patients (22.9%), more often from children. Salmonella spp. were the most frequently isolated organisms in 13.6% of the patients, followed by Campylobacter in 4.7%, and enteropathogenic Escherichia coli (EPEC) in 3.9%. Yersinia enterocolitica was found in 0.7%, Shigella spp. in 0.7% and Aeromonas hydrophila in 0.05%. Vibrio spp. and enterohaemorragic E. coli were not identified in the stools tested. Resistance to ampicillin was observed in 36% of the Salmonella, 62% of the Shigella, and 27% of the EPEC isolates. Cotrimoxazole resistance was observed in 42% of the Shigella and 12% of the EPEC isolates, while tetracycline and the quinolones were inactive against almost half and erythromycin against 20% of the Campylobacter isolates. This is the first study investigating bacterial pathogens associated with diarrhoea on the island of Crete.


Cell-type-specific responses of RT4 neural cell lines to dibutyryl-cAMP: branch determination versus maturation.
This report describes the induction of cell-type-specific maturation, by dibutyryl-cAMP and testololactone, of neuronal and glial properties in a family of cell lines derived from a rat peripheral neurotumor, RT4. This maturation allows further understanding of the process of determination because of the close lineage relationship between the cell types of the RT4 family. The RT4 family is characterized by the spontaneous conversion of one of the cell types, RT4-AC (stem-cell type), to any of three derivative cell types, RT4-B, RT4-D, or RT4-E, with a frequency of about 10(-5). The RT4-AC cells express some properties characteristic of both neuronal and glial cells. Of these neural properties expressed by RT4-AC cells, only the neuronal properties are expressed by the RT4-B and RT4-E cells, and only the glial properties are expressed by the RT4-D cells. This in vitro cell-type conversion of RT4-AC to three derivative cell types is a branch point for the coordinate regulation of several properties and seems to resemble determination in vivo. In our standard culture conditions, several other neuronal and glial properties are not expressed by these cell types. However, addition of dibutyryl-cAMP induces expression of additional properties, in a cell-type-specific manner: formation of long cellular processes in the RT4-B8 and RT4-E5 cell lines and expression of high-affinity uptake of gamma-aminobutyric acid, by a glial-cell-specific mechanism, in the RT4-D6-2 cell line. These new properties are maximally expressed 2-3 days after addition of dibutyryl-cAMP. This indicates that conversion of RT4-AC to the derivative cell types is also a branch point for the regulation of cell-type-specific properties whose expression is responsive to cAMP. Thus, the potential for maturation in response to increased cAMP is a property that segregates in a cell-type-specific manner and is activated at the determinational level in this system.


Hypothalamic-pituitary-gonadal function in men with cirrhosis of the liver.
Hypothalamic-pituitary-gonadal function was studied in 37 cirrhotic males, 25 of whom were alcoholic. Irrespective of aetiology, cirrhotic patients had significantly reduced free testosterone concentrations. Despite low free testosterone concentrations and reduced or absent spermatogenesis, basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were normal in nearly all patients, suggesting impaired function of the hypothalamic-pituitary-gonadal axis. In 14 cirrhotic men, seven of whom had gynaecomastia, the ability of the pituitary to secrete LH and FSH in response to exogenous gonadotrophin releasing-hormone (LH/FSH-RH) was asssessed. A normal LH response to LH/FSH-RH was obtained in patients without gynaecomastia. An exaggerated LH response was found in four of seven with gynaecomastia, suggesting Leydig cell failure. The Leydig cell response to exogenous gonadotrophin in eight consecutive cirrhotic patients was probably abnormal but difficult to interpret as all but one were within conventionally accepted limits of normality. The patients without gynaecomastia gave a normal or minimally exaggerated FSH response to LH/FSH-RH. Six of seven with gynaecomastia gave a markedly exaggerated response suggesting failure of spermatogenesis, and all tested were either azoospermic of oligospermic. The single patient with a normal FSH response had a normal sperm count. The pituitary cells can therefore respond to LH/RSH-RH and the Leydig cells of the testes show some response to exogenous gonadotrophin. Similar abnormalities in hypothalamic-pituitary-gonadal function have recently been described in patients with normal liver function on chronic oestrogen therapy.


[Brain tractography in type 1 and 2 diabetes and cognitive impairment].
To study conductive white matter pathways in patients with type 1 and type 2 diabetes with- and without cognitive impairment. The study included 85 patients with type 1 and 95 patients with type 2 diabetes who were divided into those who had normal cognitive functions and those with cognitive impairment. The groups were comparable in age and duration of the disease. Screening of cognitive functions was performed using the Montreal Scale for the Evaluation of Cognitive Function (MoCA-test). Brain MRI was performed on 1.5 Tesla system. All statistical analyses and data processing were performed using Statistica (Statsoft) software (version 10) on Windows 7/XP Pro operating systems. The study revealed the prevalence of mild and moderate cognitive impairment in type 1 diabetes, medium and severe in type 2 diabetes, which were mainly manifested by memory, attention and optical-spatial disorders. Intergroup analysis of the brain tractography did not show any difference in the integrity of tracts in type 1 and type 2 diabetes, but the most significant risk factors of pathway impairment were identified. They include arterial hypertension (H=6.602833, p=0.0368), degree of polyneuropathy (H=15.30420, p=0.0005), degree of nephropathy (H=9.993923, p=0.0068), degree of retinopathy (H=8.445891, p=0.0376) for type 1 diabetes and age (H=7.381742, p=0.0607), (H=8.359127, p=0.0391) for type 2 diabetes. Cholesterol level contributes to the risk in both types (H=4.009380, p=0.0452; H=4.057357, p=0.0440; H=6.454558, p=0.0111). The corticospinal and commissural tracts are most susceptible to damage. There are no significant differences in axial cerebral tract diffusion in patients with type 1 and type 2 diabetes with- and without cognitive impairment. However, the most important risk factors for white matter structure damage, namely, arterial hypertension, diabetic complications, cholesterol levels and age, are verified.


Photoprotective and antioxidative mechanisms against oxidative damage in Fargesia rufa subjected to drought and salinity.
Drought and salinity are the two most common and frequently co-occurring abiotic stresses limiting plant productivity worldwide, yet it remains unclear whether bamboo species possess effective mechanisms to protect against oxidative damage caused by drought and salinity, either alone or in combination. In this study, we utilised Fargesia rufa Yi, a species important to forest carbon sequestration and endangered giant pandas, to evaluate physiological, biochemical and ultrastructural responses to drought, salinity and their combination. Under drought alone, F. rufa exhibited reduced water loss from leaves, photochemistry inhibition, pigment degradation, reactive oxygen species accumulation, lipid peroxidation, and damage to organelles compared with salinity and combined stress treatments. The superior performance under drought alone was attributed to greater thermal dissipation and the water-water cycle capacities, increased SOD/AsA-GSH cycle enzymes activities, and a favourable redox balance of antioxidants. Therefore, relative to salinity alone and drought+salinity, F. rufa plants under drought exhibit highly efficient mechanisms to protect against oxidative damage, which most likely allow accelerated recovery of photosynthetic plasticity once the stress is removed.


Homotypic cell aggregation induced by anti-CD44(Pgp-1) monoclonal antibodies and related to CD44(Pgp-1) expression.
The present study shows that a mAb (H4C4) developed against human peripheral blood adherent cells has the unusual property of inducing in vitro homotypic aggregation of several types of hemopoietic cells and cell lines. The Ag recognized by mAb H4C4 is a 85-kDa glycoprotein that corresponds to the human Ag CD44 (equivalent to murine Pgp-1), as determined by protein purification, immunologic cross-reactivity studies, and tryptic fragment sequencing. In addition to H4C4, other mAb directed against some, but not all, epitopes of CD44(Pgp-1) were capable of inducing cell aggregation. This process was temperature sensitive and was almost totally abrogated by cytochalasin B but was unaffected by sodium azide, colchicine, EGTA, trifluoperazine, or staurosporin. A role for CD44 (Pgp-1) in cell-to-cell adhesion was further indicated by an inverse relationship observed between spontaneous aggregation of some hemopoietic cell lines and cell-surface expression of CD44(Pgp-1). These observations provide evidence for a fundamental role of CD44(Pgp-1) in cellular aggregation phenomena with an involvement of the cytoskeleton.


A conversation about practice development and knowledge translation as mechanisms to align the academic and clinical contexts for the advancement of nursing practice.
Practice development (PD) and knowledge translation (KT) have emerged recently as methodologies which assist advancement in gathering and using evidence in practice. For nursing to benefit from these methodologies there is a need to advance the dialogue between academia and the service sector concerning the use and further development of these methodologies as well as how we create the most effective partnerships between academia and practice. To advance this dialogue and to gain insights into the similarities and differences between KT and PD and between the academic and the service sectors, four conversations from different leaders in these sectors have been gathered and are presented here. These four discrete narratives are presented to showcase the diversity of sector contexts in relation to PD and KT methodologies. Narrative One focuses on some of the theoretical and policy issues related to creating partnerships between traditional "knowledge creation systems" (universities) and "knowledge utilization systems" Narrative Two discusses how a large school of nursing responded to the challenge of creating partnerships for practice development in an attempt to bridge the academic/service divide and produce benefits to both organisations. Narratives Three and Four describe the view of practice development from the service side. The final section of the paper presents an agenda for discussion and action based on the emerging set of principles.


Subepithelial infiltrates: a probable sign of corneal transplant rejection.
A previously undescribed slit-lamp manifestation of a probable corneal transplant rejection reaction was found in 22 patients among 145 who underwent penetrating keratoplasty during a two-year period. The reaction consisted of subepithelial infiltrates that were located only in the donor tissue; were without associated conjunctivitis; and that occurred six weeks to 21 months postoperatively, either alone or in association with epithelial and/or endothelial rejection; and that responded well to topical corticosteroid treatment. In one case, the subepithelial infiltrates preceded a severe endothelial rejection by only a few days. The lesions are a warning that all is not well and that corticosteroid therapy should be instituted or increased.


Vasopressin modulates social recognition-related activity in the left temporoparietal junction in humans.
The neuropeptide vasopressin is a key molecular mediator of social behavior in animals and humans, implicated in anxiety and autism. Social recognition, the ability to assess the familiarity of others, is essential for appropriate social interactions and enhanced by vasopressin; however, the neural mechanisms mediating this effect in humans are unknown. Using functional magnetic resonance imaging (fMRI) and an implicit social recognition matching task, we employed a double-blinded procedure in which 20 healthy male volunteers self-administered 40 UI of vasopressin or placebo intranasally, 45 min before performing the matching task in the scanner. In a random-effects fMRI analysis, we show that vasopressin induces a regionally specific alteration in a key node of the theory of mind network, the left temporoparietal junction, identifying a neurobiological mechanism for prosocial neuropeptide effects in humans that suggests novel treatment strategies.


Infiltration of Prostate Cancer by CD204+ and CD3+ Cells Correlates with ERG Expression and TMPRSS2-ERG Gene Fusion.
The aim of the study was to detect CD204 + and CD3 + cells in the infiltrate of benign prostatic hyperplasia, prostatic intraepithelial neoplasia and prostatic cancer in prostate specimens after radical prostatectomy. Another goal was to determine correlation of the intensity of the infiltration with ERG oncoprotein expression as well as with the presence of activat-ing translocation TMPRSS2-ERG. To confirm the translocation, we used fluorescence in situ hybridization. Imunohistochemistry was used to detect the presence of ERG oncoprotein and for assesment of the number of CD204+ and CD3+ infiltrat-ing cells. We determined the capability to infiltrate malignant structures accord-ing to differences in infiltration of benign and malignant prostate structures. Biometric analysis confirmed that the number of CD204+ macrophages in the malignant structure was significantly higher than in the benign prostatic hyperplasia regardless of the fusion pattern. Increased infiltration by CD3+ cells was only detected in malignant structures of the prostate in a group with normal signal pattern and in a group with TMPRSS2-ERG fusion. Expression of ERG positively correlated with CD204+ and CD3+ cells infiltration of malignant structures only in cases where the TMPRSS2-ERG fusion was found. In the group with a break in the TMPRSS2 gene, a positive correlation was only found between ERG expression and CD204+ macrophages infiltration. In cases with a normal signal pattern, no correlation was found. In the group with TMPRSS2-ERG fusion we observed significantly more cases with a good capability of CD204+ cells to infiltrate malignant structures, unlike the group with a normal signal pattern, where there were more cases with the weak reactivity of CD204 + cells to infiltrate the malignant structures. The same was observed for CD3+ cells. CD204+ macrophages and CD3+ T-lymphocytes in the group with TMPRSS2-ERG gene fusion, infiltrated the malignant prostate structures more intensely, but their effect on malignant transformation may be different. The association between the presence of the TMPRSS2-ERG fusion and the different capability of inflammatory cells to infiltrate malignant structures has not been reported so far. The results confirm the important role of the activated ERG gene, due to TMPRSS2-ERG fusion, in the development of inflammation of the prostate as well as the effect of inflammatory cells on the course of neoplastic process. This leads to considerations about introduc-ing immunomodulatory modalities into prostate cancer therapeutic protocols. Key words: prostate cancer - TMPRSS2-ERG gene fusion - ERG - immune response - CD204+ macrophages - CD3+ T-lymphocytes.


In vitro secondary structure of the genomic RNA of satellite tobacco mosaic virus.
Satellite tobacco mosaic virus (STMV) is a T = 1 icosahedral virus with a single-stranded RNA genome. It is widely accepted that the RNA genome plays an important structural role during assembly of the STMV virion. While the encapsidated form of the RNA has been extensively studied, less is known about the structure of the free RNA, aside from a purported tRNA-like structure at the 3' end. Here we use selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) analysis to examine the secondary structure of in vitro transcribed STMV RNA. The predicted secondary structure is unusual in the sense that it is highly extended, which could be significant for protecting the RNA from degradation. The SHAPE data are also consistent with the previously predicted tRNA-like fold at the 3' end of the molecule, which is also known to hinder degradation. Our data are not consistent with the secondary structure proposed for the encapsidated RNA by Schroeder et al., suggesting that, if the Schroeder structure is correct, either the RNA is packaged as it emerges from the replication complex, or the RNA undergoes extensive refolding upon encapsidation. We also consider the alternative, i.e., that the structure of the encapsidated STMV RNA might be the same as the in vitro structure presented here, and we examine how this structure might be organized in the virus. This possibility is not rigorously ruled out by the available data, so it remains open to examination by experiment.


Seroprevalence of antibodies against measles, rubella, mumps, varicella-zoster, and B. Pertussis in young adults of Madrid, Spain.
In recent years, there has been an increase in the number of cases of certain immunopreventable diseases in our country. A high proportion of these have been recorded among the young adult population. The aim of this study was to determine the seroprevalence of antibodies against immunopreventable diseases with the greatest health impacts on the young adult population (19-39 y of age) in Madrid. We collected a total of 1,153 serum samples from healthy volunteers undergoing routine medical visits and used ELISA to determine the presence of IgG antibodies against measles, rubella, mumps, and varicella zoster, as well as Bordetella pertussis. The Pearson's χ(2) test was used to compare prevalences, the Mann-Whitney U test was used to compare means, and the Kruskal-Wallis test was applied for variables with more than 2 categories. Statistical significance was achieved with p values of<0.05. The global prevalence of antibodies was 92.1% for measles, 94.4% for rubella, 88.3% for mumps, 92.8% for varicella zoster, and 70.2% for B. pertussis. No statistically significant differences were found between genders. The prevalence of antibodies against measles was more than 95% in the group of individuals born after 1986, and the percentage of individuals susceptible to rubella was less than 5% in women born after 1986. In spite of adequate vaccination coverage, in our region, a population of young adults exists who have not achieved the objectives of the WHO for the elimination of measles and congenital rubella syndrome.


Induction and Maintenance Adjuvant Mitomycin C Topical Therapy for Upper Tract Urothelial Carcinoma: Tolerability and Intermediate Term Outcomes.
Endoscopic management of upper tract urothelial carcinoma (UTUC) is associated with higher recurrences, which could be reduced by application of topical therapy. Adjuvant induction Bacillus Calmette-Guerin has shown inferior outcomes for UTUC compared to bladder cancer, and maintenance regimens for UTUC are unexplored. We report on the efficacy, safety, and tolerability of Mitomycin C (MMC) induction and maintenance adjuvant topical therapy for UTUC. Patients with UTUC who received adjuvant topical therapy after complete endoscopic control of Ta/T1 tumors were retrospectively reviewed. Patients were treated using percutaneous nephrostomy tube (NT) or cystoscopically placed weekly ureteral catheters, per patient preference, and all patients were offered induction and maintenance. Standardized follow-up of every 3 months in the first year, then at a minimum every 6 months, with ureteroscopy and at least annual CT, was performed. Primary outcomes were recurrence-free, progression-free, nephroureterectomy-free rate and cancer-specific and overall survival. Secondary outcomes were safety and treatment tolerability. Twenty-seven patients with 28 renal units received adjuvant topical therapy from January 2008 to March 2015. Median follow-up was 19 months (range 7-92). Three year recurrence-free, progression-free, and nephroureterectomy-free survival rates were 60% [confidence interval (95% CI): 42, 86%], 80% [95% CI: 64, 100%], and 76% [95% CI: 60, 97%]. Cancer-specific mortality rate was 0%, and 3-year overall survival was 92.9%. Nine patients experienced adverse outcomes, all related to interventions and none related to systemic toxicity. Induction and maintenance adjuvant topical MMC for endoscopically resected UTUC is feasible, well tolerated and shows promising intermediate term data on recurrence, progression, and nephroureterectomy-free survival.


Comparison between self-reported hepatitis B, hepatitis C, and HIV antibody status and oral fluid assay results in Irish prisoners.
Self-reported hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infection status was compared with the results of oral fluid assays of antibodies to these viruses in prisoners from nine of the 15 prisons in the Republic of Ireland. A total of 1205 out of 1366 prisoners completed a confidential questionnaire and 1193 provided analysable oral fluid specimens for testing for antibodies to HBV core antigen (anti-HBc), HCV (anti-HCV), and HIV (anti-HIV). The self-reported prevalence of hepatitis infection (hepatitis B: 5%; hepatitis C: 19%) was lower than that derived from oral fluid assays (anti-HBc: 9%; anti-HCV: 37%). The self-reported prevalence of HIV infection was similar to that found by oral fluid assay (2%). Many discrepancies were found between self-reported results and the results of oral fluid assays. Of those who reported being positive for HBV, HCV, or HIV, 48%, 5%, and 58%, respectively, tested negative on the oral fluid assay. Of those who reported a previous negative test result for HBV, HCV, or HIV, 10%, 37%, and 2%, respectively, had positive oral fluid assays. Self-reports of hepatitis and HIV infection status are unreliable and should not be used as a basis for planning preventive and treatment services for prisoners. All prisoners should have the opportunity to be tested for HBV, HCV, and HIV infection.


The Effects of Low-Dose Irradiation on Human Saliva: A Surface-Enhanced Raman Spectroscopy Study.
Biological effects of low-dose ionizing radiation (IR) have been unclear until now. Saliva, because of the ease of collection, could be valuable in studying low-dose IR effects by means of surface-enhanced Raman spectroscopy (SERS). The objective of our study was to compare the salivary SER spectra recorded before and after low-dose IR exposure in the case of pediatric patients (PP). Unstimulated saliva was collected from ten PP before and after irradiation with a cone beam computed tomography (CBCT) machine used for diagnostic purposes. The SERS measurements have been recorded on dried saliva samples using a solid nanosilver plasmonic substrate synthesized using an original method developed in our laboratory. The experimental results showed that salivary SER spectra are dominated by three vibrational bands (441,735 and 2107 cm-1) that can be assigned to bending and stretching vibrations of salivary thiocyanate (SCN-). After exposure, an immediate increase of vibrational bands assigned to SCN- has been recorded in the case of all samples, probably as a result of IR interaction with oral cavity. This finding suggests that SCN- could be used as a valuable biomarker for the detection and identification of low-dose radiation effects.


Neurodevelopmental consequences of early traumatic brain injury in 3-year-old children.
The purpose of this work was to determine cognitive and adaptive behavioral outcomes of children with traumatic brain injury acquired before age 2 years and to compare outcomes between inflicted versus noninflicted brain injury. All North Carolina children hospitalized in an ICU for a traumatic brain injury before age 2 years between the years 2000 and 2001 were eligible for study entry. A total of 112 surviving children were prospectively identified, 52 (46%) of whom had complete follow-up. Thirty-one control children were recruited from preschool settings. Control subjects were chosen to be demographically similar to case subjects. Child measures of cognition and adaptive behavior at age 3 years were measured and compared between children with and without traumatic brain injury and children with inflicted and noninflicted traumatic brain injury. Sixty percent of injured children were > 1 SD below normal on cognitive testing. Forty percent of injured children scored > 1 SD below normal on adaptive behavior testing. Children with inflicted traumatic brain injury performed more poorly on tests of cognition and adaptive behavior. Glasgow Coma Scale > or = 13, absence of seizures, income above twice the poverty guidelines, and high social capital were associated with improved outcomes. Injured children had lower scores than uninjured control children after adjustment for socioeconomic status. Very young children with mild-to-severe traumatic brain injury as measured by the Glasgow Coma Scale are at risk for global cognitive deficits more than a year after the time of injury. Inflicted brain injury is associated with more severe injury and worse outcomes. This is less optimistic than findings in this same cohort 1 year after injury. Family characteristics seem to play a role in recovery after injury.


Seatbelts contribute to location of lesion in moderate to severe closed head trauma.
The relationship between seatbelt use and injury severity, brain lesion location, and functional outcome was investigated in 163 individuals who sustained traumatic brain injuries in motor vehicle collisions. Of this group, 31 were using a seatbelt at the time of the accident and 132 were not. Restrained motor vehicle occupants were significantly more likely to sustain damage to subcortical brain structures than unrestrained occupants. Conversely, unrestrained occupants sustained a greater frequency of posterior brain lesions. In addition, demographic and behavioral variables were significantly related to increased likelihood of seatbelt use. Analyses revealed no significant differences between groups for injury severity variables and functional outcome measures. Seatbelts alter the body's response to forces applied in motor vehicle collisions, creating disparities in lesion sites between restrained and unrestrained motor vehicle occupants. The relationship between seatbelt use and injury severity and functional outcome is discussed.


Coagulation factors in nephrotic syndrome.
Nephrotic syndrome (NS) is associated with several disorders of hemostasis: thrombocytosis and platelet hyperaggregability; increased plasma levels of factors V and VIII, and of fibrinogen with blood hyperviscosity; decreased plasma levels of natural anticoagulants: free protein S, and antithrombin III compensated by increased levels of alpha 2-macroglobulin; lowered fibrinolytic activity. Intensity of hypercoagulability is related to the degree of hypoalbuminemia; however, the role of hypercoagulability in the increased incidence of thromboembolic events, including renal vein thrombosis, is not proved. Clotting disorders are due to urinary losses of anticoagulants or to increased liver synthesis of procoagulants stimulated by hypoalbuminemia. Moreover, changes in clotting factors levels may be due to intravascular thrombin formation (marked by increased plasma levels of fibrinopeptide A). During active phases of glomerulonephritides (GN) with NS, thrombin formation might in fact arise in glomeruli, following activation of the glomerular hemostasis system. Isolated glomeruli from human crescentic GN, rabbit nephrotoxic GN and rat HgCl2 autoimmune GN produce excessive amounts of procoagulant (tissue factor) activity (PCA). Sequential studies of the self-limited HgCl2 GN showed that glomerular PCA, proteinuria and glomerular fibrin deposits peaked concomitantly at the acme of the disease, suggesting that immunologically mediated glomerular damage had triggered the extrinsic coagulation pathway.


Evidence of oxidative stress in familial amyloidotic polyneuropathy type 1.
To evaluate the oxidative state in patients with familial amyloidotic polyneuropathy type 1 (FAP1). From 3 unrelated families, patients with FAP1 carrying a transthyretin Met-30 mutation were studied. The diagnosis was confirmed by genetic analysis. Eleven of 21 patients carried the mutation; all were symptomatic and were clinically assessed using a clinical score. All of the patients were evaluated for copper-zinc superoxide dismutase type 1 activity in red blood cells using spectrophotometry. Plasma total reactive antioxidant potential was studied using a chemiluminescent method. The results were compared with those obtained from an age-matched control group. A public and academic multidisciplinary research clinic. Six of the 11 FAP1-positive patients disclosed superoxide dismutase type 1 activity values greater than 55 U/mg of protein (upper control limit), whereas 9 of 10 patients in whom total reactive antioxidant potential was measured had values below the lower limit of the control group. No relationship was found between the levels of superoxide dismutase type 1 activity and the severity of the clinical involvement. Oxidative stress may be part of the mechanisms leading to tissue damage in patients with FAP1. The lack of correlation between the laboratory findings and the severity of clinical involvement may signal that oxidative processes are at work throughout the natural history of the disease.


Metabolic Evaluation of Epilepsy: A Diagnostic Algorithm With Focus on Treatable Conditions.
Although inborn errors of metabolism do not represent the most common cause of seizures, their early identification is of utmost importance, since many will require therapeutic measures beyond that of common anti-epileptic drugs, either in order to control seizures, or to decrease the risk of neurodegeneration. We translate the currently-known literature on metabolic etiologies of epilepsy (268 inborn errors of metabolism belonging to 21 categories, with 74 treatable errors), into a 2-tiered diagnostic algorithm, with the first-tier comprising accessible, affordable, and less invasive screening tests in urine and blood, with the potential to identify the majority of treatable conditions, while the second-tier tests are ordered based on individual clinical signs and symptoms. This resource aims to support the pediatrician, neurologist, biochemical, and clinical geneticists in early identification of treatable inborn errors of metabolism in a child with seizures, allowing for timely initiation of targeted therapy with the potential to improve outcomes.


Population genomics and climate adaptation of a C4 perennial grass, Panicum hallii (Poaceae).
Understanding how and why genetic variation is partitioned across geographic space is of fundamental importance to understanding the nature of biological species. How geographical isolation and local adaptation contribute to the formation of ecotypically differentiated groups of plants is just beginning to be understood through population genomic studies. We used whole genome sequencing combined with association study of climate to discover the drivers of differentiation in the perennial C4 grass Panicum hallii. Sequencing of 89 natural accessions of P.hallii revealed complex population structure across the species range. Major population genomic separation was found between subspecies P.hallii var. hallii and var. filipes as well as between at least four major unrecognized subgroups within var. hallii. At least 139 genomic SNPs were significantly associated with temperature or precipitation across the range and these SNPs were enriched for non-synonymous substitutions. SNPs associated with temperature and aridity were more often found in or near genes than expected by chance and enriched for putative involvement in dormancy processes, seed maturation, response to hyperosmosis and salinity, abscisic acid metabolism, hormone metabolism, and drought recovery. Both geography and climate adaptation contribute significantly to patterns of genome-wide variation in P.hallii. Population subgroups within P.hallii may represent early stages in the formation of ecotypes. Climate associated loci identified here represent promising targets for future research in this and other perennial grasses.


Resilience to aging is a heterogeneous characteristic defined by physical stressors.
Physical resilience, the capacity to respond to and recover from a stressful event, declines with advancing age. Individuals respond differently to physical stressors across their lifespans. While the biological underpinnings of resilience remain unclear, a plausible determinant is the capacity of an individual's cellular and molecular levels to return to homeostasis after a physical challenge. Impaired resilience may not only be a consequence of aging but could also be a contributing factor to the aging process. Therefore, resilience at relatively younger ages could be predictive of future health and lifespan. By utilizing standardized physical challenges and measuring stress response patterns, the relative resilience of individuals can be quantified and classified. Current preclinical research suggests that several physical stressors could be used to measure resilience in clinical aging studies. A mechanistic understanding of why some individuals are more resilient to physical stressors than others could help identify protective factors and therapeutic ways to promote healthy aging.


Branchio-oculo-facial syndrome in a newborn caused by a novel TFAP2A mutation.
We present an 18-day old boy with bilateral cervical cutaneous defect in the retroauricular region, low-set and posteriorly rotated ears, bilateral microphtalmia and bilateral pseudocleft of the upper lip. Histopathological evaluation of cervical cutaneous defect showed ulceration on the surface and ectopic thymus tissue in the deep dermis with cortex, medulla and Hassal's corpuscles. Clinical findings led to the diagnosis of Branchio-oculo-facial syndrome, characterized by branchial defects (erythematous cutaneous defects in cervical region), ocular anomalies (microphthalmia, anophthalmia, lacrimal duct obstruction, coloboma, cataract, ptosis) and facial defects (cleft lip and/or palate, pseudocleft or abnormal philtrum). DNA sequencing showed a novel heterozygous mutation, c.731T>C (p.L244P), in TFAP2A gene confirming the diagnosis of this rare autosomal dominant developmental disorder with variable clinical findings.


[Plastic closure of anterior fossa with simultaneous reconstruction of superior and middle facial zones].
The article describes surgical treatment of a patient with traumatic brain injury combined with anterior fossa defect, CSF leak, bony fractures of superior and middle facial zones. Multidisciplinary surgical team including neurosurgeon, maxillofacial surgeon and ophthalmologist performed single-step operation which consisted of skull base defect closure, cranialization of frontal sinus and reconstruction of its anterior wall by titanium mesh, reposition and fixation of bony fragments of nasoorbital complex, maxilla, surgical fixation of occlusion by cortical screws. The surgery resulted in cessation of CSF leak, restoration of orbital geometry which lead to regression of diplopia and oculomotor disorders. Cosmetic defect was eliminated. This case report demonstrates high effectiveness of multidisciplinary approach in surgical treatment of complex craniofacial injuries.


A map of photolytic and tryptic cleavage sites on the beta heavy chain of dynein ATPase from sea urchin sperm flagella.
NH2-terminal analysis of the alpha and beta heavy chain polypeptides (Mr greater than 400,000) from the outer arm dynein of sea urchin sperm flagella, compared with that of the 230,000- and 200,000-Mr peptides formed upon photocleavage of dynein by irradiation at 365 nm in the presence of vanadate and ATP, shows that the NH2 termini of the intact chains are acetylated and that the 230,000- and 200,000 Mr peptides constitute the amino- and carboxy-terminal portions of the heavy chains, respectively. Tryptic digestion of the beta heavy chain is known to separate it into two particles, termed fragments A and B, that sediment at 12S and 6S (Ow, R. A., W.-J. Y. Tang, G. Mocz, and I. R. Gibbons, 1987. J. Biol. Chem. 262:3409-3414). Immunoblots against monoclonal antibodies specific for epitopes on the beta heavy chain, used in conjunction with photoaffinity labeling, show that the ATPase-containing fragment A is derived from the amino-terminal region of the beta chain, with the two photolytic sites thought to be associated with the purine-binding and the gamma-phosphate-binding areas of the ATP-binding site spanning an approximately 100,000 Mr region near the middle of the intact beta chain. Fragment B is derived from the complementary carboxy-terminal region of the beta chain.


[Effect of imizin and transamine on the bioelectrical activity of the ventrolateral columns of the spinal cord].
It was established in experiments on spinal rats that imizine (2.5-10 mg/kg) decreased spontaneous activity and that evoked by stimulation of the sciatic nerve and intraarterial injection of bradykinin in the dorsal horns and ventrolateral columns of the spinal cord. Transamine (1-5 mg/kg) reduced the evoked activity in the dorsal horns and ventrolateral columns but potentiated spontaneous activity in these structures. Naloxone (1 mg/kg) reduced the effect of imizine (5 mg/kg) on the bradykinin-induced nociceptive activity in the ventrolateral columns of the spinal cord.


Lack of K1b9 light chains in Basilea rabbits is probably due to a mutation in an acceptor site for mRNA splicing.
Rabbits of the Basilea strain do not produce normal K1b9 light chains but continue to produce immunoglobulins with light chains of the rare K2 isotype and of lambda type. To understand the molecular basis for this unusual expression of kappa light chains in Basilea rabbits, we undertook an analysis of their kappa genes. We isolated and sequenced the mutant kappa 1b9 gene and found a substitution of A for G in the highly conserved AG dinucleotide of the 3' acceptor splice site. Although we cannot rule out additional alterations of portions of the gene we did not sequence, this spontaneous change of the G found in the normal gene provides a likely molecular explanation for the loss of K1 light chain expression in Basilea rabbits.


Acute bilirubin encephalopathy and its associated risk factors in a tertiary care hospital, Pakistan.
To determine the incidence of acute bilirubin encephalopathy (ABE) and its risk factors in neonates presenting with hyperbilirubinemia in a tertiary care children hospital. This descriptive observational study was conducted from June 2018 to June 2019. A total of 300 infants who were admitted in neonatal ICU with diagnosis of hyperbilirubinemia in The Children's Hospital & The Institute of Child Health, Multan, Pakistan were included in this period. Incidence of ABE was noted. ABE was divided into two categories on the basis of severity of symptoms; mild ABE and moderate to severe ABE. Total serum bilirubin (TSB) in all neonates was measured in all patients in hospital laboratory using colorimetric method. ABO incompatibility and Rh factor incompatibility was also noted for each neonate. Out of 300 neonates who presented with hyperbilirubinemia, ABE was diagnosed in only 42 (14.0%) neonates (mild ABE in 17 (5.7%) and moderate in 25 (8.3%). Out of 42 neonates of ABE, total serum bilirubin levels were 20-29.9 mg/dL in 24 (40.5%) neonates, and >30 mg/dL in 18 (42.8%) neonates. Pre-term birth was a significant risk factor of ABE; 23.8% in ABE and 10.70% in non-ABE (p-value 0.01). During treatment, 02 (4.76%) neonates expired due to ABE. In present study, ABE was diagnosed in 14.0% neonates who presented with hyperbilirubinemia. We found pre-term delivery as a significant risk factor of ABE.


Ficolin-2 binds to serotype 35B pneumococcus as it does to serotypes 11A and 31, and these serotypes cause more infections in older adults than in children.
Among 98 serotypes of Streptococcus pneumoniae, only a small subset regularly causes invasive pneumococcal diseases (IPD). We previously demonstrated that serotype 11A binds to ficolin-2 and has low invasiveness in children. Epidemiologic data suggested, however, that serotype 11A IPD afflicts older adults, possibly indicating reduced ficolin-2-mediated immune protection. Therefore, we studied the epidemiology of ficolin-2-bound serotypes. We obtained IPD case data from the United States Centers for Disease Control and Prevention. We studied three prominent ficolin-2-bound serotypes and their acetyltransferase-deficient variants for ficolin-2 binding and ficolin-2-mediated complement deposition with flow-cytometry. We determined the age distributions of these serotypes from the obtained epidemiologic data. We discovered that the serotype 35B capsule is a novel ficolin-2 ligand due to O-acetylation via WciG. Ficolin-2-mediated complement deposition was observed on serotypes 11A and 35B but not serotype 31 or any O-acetyl transferase deficient derivatives of these serotypes. Serotypes 11A, 35B, and 31 cause more IPD among older adults than children. Studies of the three serotypes provide additional evidence for ficolin-2 providing innate immunity against IPD. The skewed age distribution of the three serotypes suggests that older adults have reduced ficolin-2-mediated immunity and are more susceptible to these serotypes.


Inhibiting the TGF-beta signalling pathway as a means of cancer immunotherapy.
Cancers have developed numerous mechanisms for escaping the immune response, either by successfully evading a fully functional immune system or by actively suppressing the immune system so that they are no longer recognised or effectively eliminated. Current evidence supports active cancer cell-mediated immunosuppression via the secretion of the potent immunosuppressive cytokine, transforming growth factor-beta (TGF-beta), as the most general and potent mechanism for human cancer cells to escape the immune system. Efforts to bypass TGF-beta-mediated immunosuppression thereby represent an attractive therapeutic strategy for the chemoprevention and treatment of human cancers, both by directly increasing the efficacy of immunosurveillance and by increasing the efficacy of current immunotherapy strategies. Current approaches are limited by their nonspecific effects on the TGF-beta signalling pathway, as TGF-beta pathways which specifically mediate immunosuppression have not yet been defined. Future efforts should be directed towards elucidating specific TGF-beta pathways so that these can be targeted for the chemoprevention and treatment of human cancers.


Managing wildfire events: risk-based decision making among a group of federal fire managers.
Managing wildfire events to achieve multiple management objectives involves a high degree of decision complexity and uncertainty, increasing the likelihood that decisions will be informed by experience-based heuristics triggered by available cues at the time of the decision. The research reported here tests the prevalence of three risk-based biases among 206 individuals in the USDA Forest Service with authority to choose how to manage a wildfire event (i.e., line officers and incident command personnel). The results indicate that the subjects exhibited loss aversion, choosing the safe option more often when the consequences of the choice were framed as potential gains, but this tendency was less pronounced among those with risk seeking attitudes. The subjects also exhibited discounting, choosing to minimize short-term over long-term risk due to a belief that future risk could be controlled, but this tendency was less pronounced among those with more experience. Finally, the subjects, in particular those with more experience, demonstrated a status quo bias, choosing suppression more often when their reported status quo was suppression. The results of this study point to a need to carefully construct the decision process to ensure that the uncertainty and conflicting objectives inherent in wildfire management do not result in the overuse of common heuristics. Individual attitudes toward risk or an agency culture of risk aversion may counterbalance such heuristics, whereas increased experience may lead to overconfident intuitive judgments and a failure to incorporate new and relevant information into the decision.


Spin torque-generated magnetic droplet solitons.
Dissipative solitons have been reported in a wide range of nonlinear systems, but the observation of their magnetic analog has been experimentally challenging. Using spin transfer torque underneath a nanocontact on a magnetic thin film with perpendicular magnetic anisotropy (PMA), we have observed the generation of dissipative magnetic droplet solitons and report on their rich dynamical properties. Micromagnetic simulations identify a wide range of automodulation frequencies, including droplet oscillatory motion, droplet "spinning," and droplet "breather" states. The droplet can be controlled by using both current and magnetic fields and is expected to have applications in spintronics, magnonics, and PMA-based domain-wall devices.


Purification and properties of LIQ 4, an antibacterial substance produced by Streptococcus faecalis var. liquefaciens K4.
An antibacterial substance (LIQ 4) produced by Streptococcus faecalis var. liquefaciens K 4 was isolated in extracellular and cell associated form. It markedly inhibited the growth of Gram-positive bacteria, whereas only a few Gram-negative bacteria were susceptible. LIQ 4 was purified by hydrophobic chromatography (Servachrome XAD-2; octyl-Sepharose CL-4B; Sephadex LH 60) and Sephacryl S-200. TLC yielded a fluorescent spot as the active component and several inactive ninhydrin-positive substances. These contaminating peptides strongly adsorbed to LIQ 4 and could only be removed by repeated reversed phase HPLC. Furthermore, HPLC separated LIQ 4 into seven closely related substances. All showed strong fluorescence under UV light, stained yellow with ninhydrin, and contained aspartate and lysine after acid hydrolysis. The molecular weight was estimated by Amicon ultrafiltration to be less than 2000. LIQ 4 was stable at 80 degrees C (30 min) and pH 2, but considerably inactivated above pH 8. It was apparently affected by proteolytic enzymes, but the activity could be fully restored upon heating.


Translocation of a Bak C-terminus mutant from cytosol to mitochondria to mediate cytochrome C release: implications for Bak and Bax apoptotic function.
One of two proapoptotic Bcl-2 proteins, Bak or Bax, is required to permeabilize the mitochondrial outer membrane during apoptosis. While Bax is mostly cytosolic and translocates to mitochondria following an apoptotic stimulus, Bak is constitutively integrated within the outer membrane. Membrane anchorage occurs via a C-terminal transmembrane domain that has been studied in Bax but not in Bak, therefore what governs their distinct subcellular distribution is uncertain. In addition, whether the distinct subcellular distributions of Bak and Bax contributes to their differential regulation during apoptosis remains unclear. To gain insight into Bak and Bax targeting to mitochondria, elements of the Bak C-terminus were mutated, or swapped with those of Bax. Truncation of the C-terminal six residues (C-segment) or substitution of three basic residues within the C-segment destabilized Bak. Replacing the Bak C-segment with that from Bax rescued stability and function, but unexpectedly resulted in a semi-cytosolic protein, termed Bak/BaxCS. When in the cytosol, both Bax and Bak/BaxCS sequestered their hydrophobic transmembrane domains in their hydrophobic surface groove. Upon apoptotic signalling, Bak/BaxCS translocated to the mitochondrial outer membrane, inserted its transmembrane domain, oligomerized, and released cytochrome c. Despite this Bax-like subcellular distribution, Bak/BaxCS retained Bak-like regulation following targeting of Mcl-1. Residues in the C-segment of Bak and of Bax contribute to their distinct subcellular localizations. That a semi-cytosolic form of Bak, Bak/BaxCS, could translocate to mitochondria and release cytochrome c indicates that Bak and Bax share a conserved mode of activation. In addition, the differential regulation of Bak and Bax by Mcl-1 is predominantly independent of the initial subcellular localizations of Bak and Bax.


Sentinel node biopsy for melanoma: a study of 241 patients.
The aim of this study was to evaluate the sentinel node biopsy (SNB) technique for melanoma using both radiocolloid and blue dye in 241 clinically N0 patients with melanomas >1.0 mm, or thinner lesions exhibiting regression/ulceration. We showed that an increase in injected radioactivity increased both the number of visualized nodes at lymphoscintigraphy and the number of SNs removed surgically. At least one SN was removed in 98% (236) of patients, and all nodes were identified with the probe. Seventy-four per cent of the 194 patients injected with blue dye had stained SNs. In 46% (144) of the lymph node basins, there was a discrepancy between the nodes visualized at lymphoscintigraphy and the nodes removed at surgery. There were 38 unusually located nodes. Only eight of these were removed surgically; none contained metastases. SN metastases were detected in 22% (53) of patients. There were nine haematoxylin and eosin (HE)-negatives, all of which were found by immunohistochemistry. The false negative rate for the SNB procedure was 4% (2/55). The complication rate was 6% after SNB and 29% after complete node dissection. In conclusion, SN status is a strong prognostic factor in melanoma patients, and SNB has made the approach to radical lymphadenectomy more rational.


Genomic inference of a severe human bottleneck during the Early to Middle Pleistocene transition.
Population size history is essential for studying human evolution. However, ancient population size history during the Pleistocene is notoriously difficult to unravel. In this study, we developed a fast infinitesimal time coalescent process (FitCoal) to circumvent this difficulty and calculated the composite likelihood for present-day human genomic sequences of 3154 individuals. Results showed that human ancestors went through a severe population bottleneck with about 1280 breeding individuals between around 930,000 and 813,000 years ago. The bottleneck lasted for about 117,000 years and brought human ancestors close to extinction. This bottleneck is congruent with a substantial chronological gap in the available African and Eurasian fossil record. Our results provide new insights into our ancestry and suggest a coincident speciation event.


Robotic gaming prototype for upper limb exercise: Effects of age and embodiment on user preferences and movement.
Effective human-robot interactions in rehabilitation necessitates an understanding of how these should be tailored to the needs of the human. We report on a robotic system developed as a partner on a 3-D everyday task, using a gamified approach. To: (1) design and test a prototype system, to be ultimately used for upper-limb rehabilitation; (2) evaluate how age affects the response to such a robotic system; and (3) identify whether the robot's physical embodiment is an important aspect in motivating users to complete a set of repetitive tasks. 62 healthy participants, young (<30 yo) and old (>60 yo), played a 3D tic-tac-toe game against an embodied (a robotic arm) and a non-embodied (a computer-controlled lighting system) partner. To win, participants had to place three cups in sequence on a physical 3D grid. Cup picking-and-placing was chosen as a functional task that is often practiced in post-stroke rehabilitation. Movement of the participants was recorded using a Kinect camera. The timing of the participants' movement was primed by the response time of the system: participants moved slower when playing with the slower embodied system (p = 0.006). The majority of participants preferred the robot over the computer-controlled system. Slower response time of the robot compared to the computer-controlled one only affected the young group's motivation to continue playing. We demonstrated the feasibility of the system to encourage the performance of repetitive 3D functional movements, and track these movements. Young and old participants preferred to interact with the robot, compared with the non-embodied system. We contribute to the growing knowledge concerning personalized human-robot interactions by (1) demonstrating the priming of the human movement by the robotic movement - an important design feature, and (2) identifying response-speed as a design variable, the importance of which depends on the age of the user.


The impact of functional exercise on the reversal of acromegaly induced frailty: a case report.
Background: Acromegaly is an endocrine disease caused by the excess secretion of growth hormone and is responsible for the development of multiple comorbidities that can reduce physiologic reserve. The hypersecretion of growth hormone (GH) affects virtually every organ in the body and can predispose an individual to frailty; a state of vulnerability resulting from cumulative decline across multiple systems. Frailty results in a loss of physiologic reserve and vulnerability to adverse outcomes such as morbidity and mortality. Case Description: The patient was a 73-year-old male with acromegaly who declined into a cycle of frailty following coronary artery bypass graft (CABG) and aortic valve replacement surgery. Prolonged hospitalization and lack of adequate physical stress led to the depletion of reserve in the cardiopulmonary, cognitive, musculoskeletal, and neuromuscular systems, leaving a previously independent adult fully dependent for mobility. Outcomes: The patient participated in a twelve-week multicomponent physical therapy program in a skilled nursing facility. The exercise program was designed and administered to impact multiple systems and provide the necessary overload for adaptation. The patient demonstrated significant improvement in the Berg Balance Scale (BBS), Tinetti (POMA), Functional Outcome Scale (FOS), and returned to independent community ambulation.. Discussion: The case illustrates the effectiveness of a multicomponent functional-based exercise program to improve markers of frailty and reverse functional decline in a frail older adult with acromegaly.


Candidate Gene Networks for Acylsugar Metabolism and Plant Defense in Wild Tomato Solanum pennellii.
Many solanaceous plants secrete acylsugars, which are branched-chain and straight-chain fatty acids esterified to Glu or Suc. These compounds have important roles in plant defense and potential commercial applications. However, several acylsugar metabolic genes remain unidentified, and little is known about regulation of this pathway. Comparative transcriptomics between low- and high-acylsugar-producing accessions of Solanum pennellii revealed that expression levels of known and novel candidate genes (putatively encoding beta-ketoacyl-(acyl-carrier-protein) synthases, peroxisomal acyl-activating enzymes, ATP binding cassette (ABC) transporters, and central carbon metabolic proteins) were positively correlated with acylsugar accumulation, except two genes previously reported to be involved in acylglucose biosynthesis. Genes putatively encoding oxylipin metabolic proteins, subtilisin-like proteases, and other antimicrobial defense proteins were upregulated in low-acylsugar-producing accessions. Transcriptome analysis after biochemical inhibition of biosynthesis of branched-chain amino acids (precursors to branched-chain fatty acids) by imazapyr showed concentration-dependent downregulation of known and most acylsugar candidate genes, but not defense genes. Weighted gene correlation network analysis identified separate coexpressed gene networks for acylsugar metabolism (including six transcription factor genes and flavonoid metabolic genes) and plant defense (including genes putatively encoding NB-ARC and leucine-rich repeat sequences, protein kinases and defense signaling proteins, and previously mentioned defense proteins). Additionally, virus-induced gene silencing of two trichomes preferentially expressed candidate genes for straight-chain fatty acid biosynthesis confirmed their role in acylsugar metabolism.


ValLigURL: a server for ligand-structure comparison and validation.
A new web-based tool called ValLigURL is described. It can be used by practising crystallographers to validate the geometry of a ligand and to compare the conformation of a ligand with all instances of that ligand in the structural database (wwPDB). In addition, it can be used by structural bioinformaticians to survey the quality or conformational diversity of any ligand across the entire structural database. The server is freely accessible at the URL http://eds.bmc.uu.se/eds/valligurl.php.


You can't always get what you want: size assortative mating by mutual mate choice as a resolution of sexual conflict.
Assortative mating patterns for mate quality traits like body size are often observed in nature. However, the underlying mechanisms that cause assortative mating patterns are less well known. Sexual selection is one important explanation for assortment, suggesting that i) one (usually the female) or both sexes could show preferences for mates of similar size or ii) mutual mate choice could resolve sexual conflict over quality traits into assortment. We tested these hypotheses experimentally in the socially monogamous cichlid fish Pelvicachromis taeniatus, in which mate choice is mutual. In mate choice experiments, both sexes preferred large mates irrespective of own body size suggesting mating preferences are not size-assortative. Especially males were highly selective for large females, probably because female body size signals direct fitness benefits. However, when potential mates were able to interact and assess each other mutually they showed size-assortative mating patterns, i.e. the likelihood to mate was higher in pairs with low size differences between mates. Due to variation in body size, general preferences for large mating partners result in a sexual conflict: small, lower quality individuals who prefer themselves large partners are unacceptable for larger individuals. Relative size mismatches between mates translate into a lower likelihood to mate, suggesting that the threshold to accept mates depends on own body size. These results suggest that the underlying mechanism of assortment in P. taeniatus is mutual mate choice resolving the sexual conflict over mates, rather than preference for mates of similar size.


Quantitative imaging of mouse L-6 monoclonal antibody in breast cancer patients to develop a therapeutic strategy.
L-6, a mouse IgG2a anti-adenocarcinoma monoclonal antibody (MoAb) with favorable immunopathology and mouse biokinetics, was evaluated for cancer radioimmunotherapy by pharmacokinetic studies in 10 patients with breast cancer. The effect of escalating the preinfused protein dose was studied in two patients at each level, using 50, 100, 150, 200 and 400 mg of unlabeled L-6 prior to a 10 mCi imaging dose of 131I L-6. Quantitative imaging, and blood and urine clearances were obtained. After the 50 mg preinfusion, rapid blood clearance and lung extraction of the radiopharmaceutical occurred immediately post injection. Greater preload amounts of L-6 were associated with an increase in the intercept of the slow phase of the blood clearance from 17 to 22% injected dose (ID) with 50 mg to 70 to 80% ID with 400 mg (P less than 0.01). Lung uptake of the radiopharmaceutical immediately post injection decreased from 15 to 19% ID (50 mg) to 6 to 8% ID (400 mg). Tumors were visualized only after larger L-6 preloads, but in these patients small chest tumors contained 0.6-1.2% ID (0.1% ID/g maximum). This study suggests that L-6 reactive sites that are readily available in the lung can be saturated, so that a subsequent dose of I-131 L-6 is delivered to the tumor. This approach provides a new strategy for developing an effective method for radioimmunotherapy using a MoAb that has some cross-reactivity. Quantitative imaging contributed to detection of the cross-reactivity and the strategy for overcoming it.


[Situational awareness: you won't see it unless you understand it].
In dynamic, high-risk environments such as the modern operating theatre, healthcare providers are required to identify a multitude of signals correctly and in time. Errors resulting from failure to identify or interpret signals correctly lead to calamities. Medical training curricula focus largely on teaching technical skills and knowledge, not on the cognitive skills needed to interact appropriately with fast-changing, complex environments in practice. The term 'situational awareness' describes the dynamic process of receiving, interpreting and processing information in such dynamic environments. Improving situational awareness in high-risk environments should be part of medical curricula. In addition, the flood of information in high-risk environments should be presented more clearly and effectively. It is important that physicians become more involved in this regard.


[Mechanisms of the hypotensive action of captopril in essential hypertension].
Captopril effects were studied in 27 patients with second-stage essential hypertension following administration of a single 25 mg oral dose of the drug. Blood pressure (BP), blood angiotensin-1-converting enzyme (ACE) activity, active (APR) and inactive (IPR) plasma renin levels were measured every 30 minutes for 3 hours. Before and near the end of the acute test, urinary kallikrein and catecholamine excretions were measured, and systemic and regional hemodynamic changes assessed. BP decreased in 21 patients: 11 of those had low basal APR (group 1), and 10 had normal or moderately elevated APR (group 2). The greatest hypotensive effect was observed within 1.5 hours after the administration, coinciding with the most marked ACE inhibition. There was no significant intergroup difference with respect to the extent of the hypotensive effect. No correlation was found between the hypotensive effect and the degree of ACE inhibition. All patients showed significantly decreased arteriolar tone, increased venous distensibility, decreased total peripheral resistance, and expanded end diastolic volume, while their cardiac output and heart rate remained unaffected. Hypertensive patients with low APR gave no evidence of renin-angiotensin inhibition or kallikrein-kinin activation that might have accounted for the hemodynamic effect of captopril.


Frequency analysis in different types of paroxysmal atrial fibrillation.
This study sought to investigate the regional frequency distribution from multiple bi-atrial sites in different types of paroxysmal atrial fibrillation (AF). A previous study showed a left atrium (LA) to right atrium (RA) frequency gradient in patients with paroxysmal AF. Forty-four patients (age = 60 +/- 16, male patients = 27) with paroxysmal AF originating from the pulmonary veins (PVs) (n = 31) or superior vena cava (SVC) (n = 13) were included. Frequency analysis was performed on the intracardiac electrograms (7 s, 1 kHz/channel) recorded from PV, posterior LA, coronary sinus (CS), posterolateral RA, and SVC. The largest peak frequency was identified as the dominant frequency (DF). In the PV-AF patients, there was a frequency gradient from the PV ostium to the LA, RA, and SVC (8.5 +/- 3.3 Hz vs. 5.9 +/- 1.1 Hz vs. 5.2 +/- 0.85 Hz vs. 5.5 +/- 0.48 Hz, respectively, p < 0.001). The highest DFs were mostly located at the arrhythmogenic PV ostium (58%). The DFs of the arrhythmogenic PV and PV ostium were significantly higher than those of the non-arrhythmogenic PVs and PV ostia (p < 0.05). In the SVC-AF patients, there was a frequency gradient from the SVC to the RA, LA, and PV (8.0 +/- 2.4 Hz vs. 5.9 +/- 1.1 Hz vs. 5.9 +/- 0.7 Hz vs. 5.8 +/- 0.7 Hz, respectively, p = 0.001). The highest DFs were mostly located inside the SVC (77%) instead of the SVC ostium (as compared with PV-AF patients, p = 0.035). The location of the highest DF depended on the arrhythmogenic PV or SVC. A frequency gradient was present between the arrhythmogenic thoracic vein and atrium in all patients.


Type X Toxoplasma gondii in a wild mussel and terrestrial carnivores from coastal California: new linkages between terrestrial mammals, runoff and toxoplasmosis of sea otters.
Sea otters in California are commonly infected with Toxoplasma gondii. A unique Type X strain is responsible for 72% of otter infections, but its prevalence in terrestrial animals and marine invertebrates inhabiting the same area was unknown. Between 2000 and 2005, 45 terrestrial carnivores (lions, bobcats, domestic cats and foxes) and 1396 invertebrates (mussels, clams and worms) were screened for T. gondii using PCR and DNA sequencing to determine the phylogeographic distribution of T. gondii archetypal I, II, III and Type X genotypes. Marine bivalves have been shown to concentrate T. gondii oocysts in the laboratory, but a comprehensive survey of wild invertebrates has not been reported. A California mussel from an estuary draining into Monterey Bay was confirmed positive for Type X T. gondii by multilocus PCR and DNA sequencing at the B1 and SAG1 loci. This mussel was collected from nearshore marine waters just after the first significant rainfall event in the fall of 2002. Of 45 carnivores tested at the B1, SAG1, and GRA6 typing loci, 15 had PCR-confirmed T. gondii infection; 11 possessed alleles consistent with infection by archetypal Type I, II or III strains and 4 possessed alleles consistent with Type X T. gondii infection. No non-canonical alleles were identified. The four T. gondii strains with Type X alleles were identified from two mountain lions, a bobcat and a fox residing in coastal watersheds adjacent to sea otter habitat near Monterey Bay and Estero Bay. Confirmation of Type X T. gondii in coastal-dwelling felids, canids, a marine bivalve and nearshore-dwelling sea otters supports the hypotheses that feline faecal contamination is flowing from land to sea through surface runoff, and that otters can be infected with T. gondii via consumption of filter-feeding marine invertebrates.


Surgical Excision Versus Ablation for Superficial Endometriosis-Associated Pain: A Randomized Controlled Trial.
To compare surgical excision and ablation of endometriosis for treatment of chronic pelvic pain. Randomized clinical trial with 12-month follow-up (Canadian Task Force classification I). Single academic tertiary care hospital. Women with minimal to mild endometriosis undergoing laparoscopy. Excision or ablation of superficial endometriosis at the time of robot-assisted laparoscopy. Primary outcome was visual analog scale (VAS) scoring at baseline and 6 and 12 months for menstrual pain, nonmenstrual pain, dyspareunia, and dyschezia. Secondary outcomes included survey results at baseline and 6 and 12 months from the Short Form Health Survey, Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, and the International Pelvic Pain Assessment. From December 2013 to October 2014, 73 patients were randomized intraoperatively to excision (n = 37) or ablation (n = 36) of endometriosis. Patients were followed at 6 and 12 months to evaluate the above outcomes. After ablation of endometriosis, dyspareunia (VAS scores) improved at 6 months (mean change [MC], -14.07; 95% confidence interval [CI], -25.93 to -2.21; p = .02), but improvement was not maintained at 12 months. Dysmenorrhea improved at 6 months (MC, -26.99; 95% CI, -41.48 to -12.50; p < .001) and 12 months (MC, -24.15; 95% CI, 39.62 to -8.68; p = .003) with ablation. No significant changes were seen in VAS scores after excision at 6 or 12 months. When comparing ablation and excision, the only significant difference was a change in dyspareunia at 6 months (MC, -22.96; 95% CI, -39.06 to -6.86; p = .01). Treatment with ablation improved dysmenorrhea at 6 and 12 months and improved dyspareunia at 6 months as compared with preoperative data. However, only dyspareunia demonstrated a significant difference between ablation and excision. Excision and ablation showed similar effectiveness for the treatment of pain associated with superficial endometriosis, with ablation showing more significant individual changes. Careful patient counseling regarding expectations of surgical intervention is vital in the management of endometriosis.


Analysis of percent free prostate-specific antigen (PSA) for prostate cancer detection: influence of total PSA, prostate volume, and age.
To determine whether the use of the free-to-total PSA ratio (percent free PSA) could increase the specificity of PSA testing for prostate cancer detection in men with serum PSA concentrations between 4.0 and 10.0 ng/mL, and to assess the influence of total PSA, prostate volume, and age on percent free PSA. Sera were obtained from 217 men with histologically confirmed diagnoses (139 prostate cancer, 78 benign). Free and total PSA concentrations were determined using Hybritech Tandem assays. Use of percent free PSA increased PSA specificity: 29% of negative biopsies would be spared while retaining 95% sensitivity. Percent free PSA increased with increasing age and prostate volume. Percent free PSA decreased as total PSA increased. A significant relation exists between percent free PSA and the probability of a positive biopsy; in this cohort, a patient with a low percent free PSA (< or = 10%) had a higher probability of cancer (63 +/- 9%) than a patient with a high percent free PSA (> or = 26%) (probability 2 +/- 3%). Percent free PSA may be used as an aid in distinguishing prostate cancer from benign disease in men with a total PSA between 4.0 and 10.0 ng/mL. Large prospective multicenter trials are required to develop consistent recommendations and determine the appropriate cutpoints and risk probabilities, controlling for total PSA, prostate volume, age, and biopsy history.


p-Coumaric acid mediated protection of H9c2 cells from Doxorubicin-induced cardiotoxicity: Involvement of augmented Nrf2 and autophagy.
Doxorubicin (Dox) is a widely administered chemotherapeutic drug and incidences of cardiotoxicity associated with its administration have been of general concern. Extensive research proposes several mechanisms as a cause of Dox induced cardiotoxicity. However, none of these studies have been able to suggest a find one, cure all antidote for the same. To this end, several studies involving plant based compounds or natural products have gained acclaim for their ability to address at least one factor contributing to drug induced pathogenesis. We had previously reported that p-coumaric (pCA) has a protective effect on Dox induced oxidative stress in rat-derived cardiomyoblasts. In this study we investigated the effects of pCA on the regulation of Nrf-2, mitochondrial viability, autophagy and apoptosis in Doxorubicin treated H9c2 cardiomyocytes. ROS induced mitochondrial stress, changes in mitochondrial membrane potential, loss of membrane integrity; nuclear damage as single/double stranded breaks, autophagy and the effects of pre and co-treatment of pCA on Nrf-2 mediated signaling was evaluated by various approaches. The effect of pCA on drug uptake was evaluated through confocal Raman Spectroscopy. We find that nuclear translocation of Nrf-2 is prominently marked by protein-specific antibody conjugated fluorophore in Dox treated cells especially. Cell survival is mediated to a certain extent by the expression of the anti-apoptotic BCl2 in pCA treated cells. However, mRNA levels of autophagy related (Atg) genes suggest that autophagy plays a decisive role in deciding cellular fate. Caspase-3 activation is also observed in pCA treated cells which suggest an alternative function of caspase-3 in pCA mediated cell survival. Expression of antioxidant enzymes confirm the oxidative stress induced by Dox treatment in cells and the modulation of cell redox homeostasis through treatment with pCA.


Structure Modulates Similarity-Based Interference in Sluicing: An Eye Tracking study.
In cue-based content-addressable approaches to memory, a target and its competitors are retrieved in parallel from memory via a fast, associative cue-matching procedure under a severely limited focus of attention. Such a parallel matching procedure could in principle ignore the serial order or hierarchical structure characteristic of linguistic relations. I present an eye tracking while reading experiment that investigates whether the sentential position of a potential antecedent modulates the strength of similarity-based interference, a well-studied effect in which increased similarity in features between a target and its competitors results in slower and less accurate retrieval overall. The manipulation trades on an independently established Locality bias in sluiced structures to associate a wh-remnant (which ones) in clausal ellipsis with the most local correlate (some wines), as in The tourists enjoyed some wines, but I don't know which ones. The findings generally support cue-based parsing models of sentence processing that are subject to similarity-based interference in retrieval, and provide additional support to the growing body of evidence that retrieval is sensitive to both the structural position of a target antecedent and its competitors, and the specificity or diagnosticity of retrieval cues.