Treatment results of nondamaging retinal laser therapy in diabetic macular edema.
Subthreshold nondamaging retinal laser therapy (NRT) provides a greater safety profile than conventional laser methods, but more data is needed on the efficacy and safety of subthreshold NRT in diabetic macular edema. To evaluate the efficacy and safety of NRT for the treatment of clinically significant macular edema (CSME) that is partially responsive or resistant to intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment. This was a retrospective case series study. Fifty eyes of 38 diabetic patients with CSME previously treated with at least 6-monthly intravitreal bevacizumab injections with/without intravitreal Ozurdex therapy were evaluated. The patients received 577-nm yellow wavelength laser therapy with PASCAL laser system (Topcon Medical Laser Systems, Santa Clara, CA, USA). Best-corrected visual acuity (BCVA) and central subfield thickness (CST) were evaluated before and 1, 3, 6, 12 and 24 months after laser treatment. Baseline mean CST was 368.06 ± 86.9 µm. The mean CST values at the 1-, 3-, 6-, 12-, and 24-month visits were 336.93 ± 79.8, 352.40 ± 113.5, 336.36 ± 109.3, 325.10 ± 104 µm, and 310.08 ± 84.7 µm, respectively. The mean CST decreased significantly at the first (p = 0.002) and second year visits (p < 0.001) when compared with pretreatment values. Although visual acuity was improved at the first year compared with baseline, this difference was not statistically significant (p = 0.03). There was no significant difference in visual acuities between pretreatment and posttreatment visits. During 24-month follow-up, while 37 eyes were treated with [mean: 5.7 ± 3.4 (1-14)] intravitreal anti-VEGF injections, 3 eyes were administered single-dose intravitreal steroids. Additional intravitreal injections were not required in 10 (20%) eyes. NRT is effective by itself or in combination with anti-VEGF agents in diabetic macular edema that is partially responsive or resistant to previous intravitreal injections. T role in treating this disorder should be assessed in more detail with prospective controlled studies.


Basic physics and imaging characteristics of ultrasound.
The imaging characteristics of diagnostic ultrasound (US) are determined by the ultrasonic properties of tissue. The velocity of propagation of US and the attenuation are the 2 most important parameters. These determine the frequency with which the tissues may be imaged, which in turn sets a fundamental limit on the axial and the lateral resolution. Ultrasonic imaging equipment is designed on the premise that the ultrasonic energy propagates through tissue in a straight line and that the ultrasonic beam is very narrow. In fact, the ultrasonic energy propagates through tissue as a beam of finite dimensions set by the physical dimensions of the transducer, the way it is constructed, and the way it is energized. Also, the velocity of propagation in different tissues varies and this can lead to deviation of the ultrasonic beam from the assumed direction of propagation. This breakdown in assumptions leads to the creation of artifacts that must be appreciated in the interpretation of ultrasonic images. For this reason skilled interpreters of ultrasonic images follow 3 golden rules: never make an interpretation on a single image; just because a feature is displayed do not consider that it is necessarily real; and just because a feature is not displayed do not consider that it is necessarily not there.


Copper(II) and nickel(II) complexes of beta-aminoketoxime ligand: syntheses, crystal structures, magnetism, and nickel(II) templated coupling of oxime with nitrile.
The syntheses, molecular structures, and magnetic properties of a dicopper(II) complex, [Cu(2)(HL(1))(2)](ClO(4))(2) (1), and its nickel(II) analog, [Ni(2)(HL(1))(2)](ClO(4))(2) (2), of a beta-amino ketoxime ligand (H(2)L(1) = 4,4,9,9-tetramethyl-5,8-diazadodecane-2,11-dione dioxime) are discussed. The metal centers in out-of-plane oximate bridged dinuclear complexes (1 and 2) display distorted trigonal bipyramidal geometry and form a six-membered M(2)(NO)(2) ring oriented in a boat conformation. The two copper(II) centers in 1 interact ferromagnetically giving rise to a triplet-spin ground state whereas the two nickel(II) centers in 2 interact antiferromagnetically to stabilize a singlet-spin state. Variable temperature magnetic susceptibility measurements establish the presence of a weak ferromagnetic coupling (J = 13 cm(-1)) in 1 and a weak anitiferromagnetic coupling (J = -12 cm(-1)) in 2. The exchange coupling constant derived from B3LYP computations in conjunction with broken symmetry spin-projection techniques for the oximate bridged dinuclear copper(II) complex shows excellent agreement with the corresponding experimental value. A square-planar mononuclear nickel(II) complex of the dioxime ligand, [Ni(H(2)L(1))](ClO(4))(2) (3), is reported along with its crystal structure, which reacts with acetonitrile to produce a six-coordinate mononuclear complex, [Ni(L(2))](ClO(4))(2) (4). The ligand (L(2)) in complex 4 is the iminoacyl derivative of oxime, where the coupling of oxime and acetonitrile takes place via a proton-assisted pathway. The iminoacylation of H(2)L(1) works with other nitriles like butyronitrile and benzonitrile. Computational studies support a proton-assisted coupling of oxime with nitrile. The critical transition states have been located for the iminoacylation reaction. Complex 4 can be converted back to complex 3 by reacting with sodium acetate in methanol.


Sensitive Cu2+-Cu2+ distance measurements in a protein-DNA complex by double-quantum coherence ESR.
Double quantum coherence (DQC) ESR spectroscopy is applied to measure the Cu(2+)-Cu(2+) distance in the EcoRI-DNA complex. A simple method is proposed to reduce the contribution of nuclear hyperfine and quadrupole interactions to such data. The effects of such interactions between the electron spin of Cu(2+) and neighboring nuclei on the DQC data make it difficult to measure the nanometer range interspin distance. The DQC data is in good agreement with results obtained by double electron electron resonance (DEER) spectroscopy. At the same time, the signal-to-noise ratio per shot in DQC is high. Taken together, these results provide impetus for further development of paramagnetic metal ion-based DQC techniques.


Automated microaxial tomography of cell nuclei after specific labelling by fluorescence in situ hybridisation.
Microaxial tomography provides a good means for microscopic image acquisition of cells or sub-cellular components like cell nuclei with an improved resolution, because shortcomings of spatial resolution anisotropy in optical microscopy can be overcome. Thus, spatial information of the object can be obtained without the necessity of confocal imaging. Since the very early developments of microaxial tomography, a considerable drawback of this method was a complicated image acquisition and processing procedure that requires much operator time. In order to solve this problem the Heidelberg 2pi-tilting device has been mounted on the Brno high-resolution cytometer as an attempt to bring together advanced microscopy and fast automated computer image acquisition and analysis. A special software module that drives all hardware components required for automated microaxial tomography and performs image acquisition and processing has been developed. First, a general image acquisition strategy is presented. Then the procedure for automation of axial tomography and the developed software module are described. The rotation precision has been experimentally proved followed by experiments with a specific biological example. For this application, also a method for the preparation of cell nuclei attached to glass fibres has been developed that allows for the first time imaging of three-dimensionally conserved, fluorescence in situ hybridisation-stained cell nuclei fixed to a glass fibre.


Tuberculosis of the oral cavity.
Tuberculosis (TB) of the tongue is not a common finding diagnosis, even if consider endemic areas. Tuberculosis of the tongue sometimes can mimic lingual neoplasm. Oral tuberculosis is rarely primary as mechanism, and frequently secondary to pulmonary tuberculosis. There are many suspect lesions that can be classified as tuberculosis, such as tumor mass, ulcerative lesion or fissure. It is very important for diagnosis to perform histopathological examination of the biopsy. We present here the case of a 74-year-old man who developed lingual tuberculosis with a tumor aspect concomitant with pulmonary tuberculosis. Histopathological and immunohistochemical examinations established the diagnosis of lingual tuberculosis.


Outcomes from an interprofessional, dementia-focused, telementoring program: a brief report.
Despite a burgeoning older-adult population, the number of health-care professionals with geriatric expertise continues to lag behind. In 2014, the American Geriatrics Society's position statement encouraged interprofessional training for health-care professionals. Telementoring remotely connects clinicians with specialists for education and group mentoring. This dementia-focused, 11-month, 1-hour each, telementoring program was modeled on the Alzheimer's Association ECHO. Our interprofessional expert panel consisted of a geriatrician, a geriatric psychiatrist, an adult nurse practitioner (with geriatric expertise), two geriatric pharmacists, a licensed social worker (coordinating a dementia day program), and a project coordinator. Learners were residents in family medicine and general psychiatry, physician assistant residents in mental health and geriatric psychiatry fellows (total = 31). There was a significant improvement in learner intentions to change medication prescribing by midpoint assessment (p = 0.04). Learners reported few barriers to incorporating skills they learned. An interprofessional telementoring program can help nongeriatric practitioners improve skills in caring for older adults.


The hemorrhagic coli pilus (HCP) of Escherichia coli O157:H7 is an inducer of proinflammatory cytokine secretion in intestinal epithelial cells.
Enterohemorrhagic Escherichia coli (EHEC) O157:H7, the causative agent of hemorrhagic colitis and the hemolytic uremic syndrome (HUS), produces long bundles of type IV pili (TFP) called hemorrhagic coli pili (HCP). HCP are capable of mediating several phenomena associated with pathogenicity: i) adherence to human and bovine epithelial cells; ii) invasion of epithelial cells; iii) hemagglutination of rabbit erythrocytes; iv) biofilm formation; v) twitching motility; and vi) specific binding to laminin and fibronectin. HCP are composed of a 19 kDa pilin subunit (HcpA) encoded by the hcpA chromosomal gene (called prepilin peptidase-dependent gene [ppdD] in E. coli K-12). In this study we investigated the potential role of HCP of E. coli O157:H7 strain EDL933 in activating the release of pro- and anti-inflammatory cytokines from a variety of host epithelial cells. We found that purified HCP and a recombinant HcpA protein induced significant release of IL-8 and TNF-alpha, from cultured polarized intestinal cells (T84 and HT-29 cells) and non-intestinal HeLa cells. Levels of proinflammatory IL-8 and TNF-alpha, but not IL-2, IL6, or IL-10 cytokines, were increased in the presence of HCP and recombinant HcpA after 6 h of incubation with >or=50 ng/ml of protein, suggesting that stimulation of IL-8 and TNF-alpha are dose and time-dependent. In addition, we also demonstrated that flagella are potent inducers of cytokine production. Furthermore, MAPK activation kinetics studies showed that EHEC induces p38 phosphorylation under HCP-producing conditions, and ERK1/2 and JNK activation was detectable after 3 h of EHEC infection. HT-29 cells were stimulated with epidermal growth factor stimulation of HT-29 cells for 30 min leading to activation of three MAPKs. The HcpA pilin monomer of the HCP produced by EHEC O157:H7 is a potent inducer of IL-8 and TNF-alpha release, an event which could play a significant role in the pathogenesis of hemorrhagic colitis caused by this pathogen.


pH-Triggered Assembly of Natural Melanin Nanoparticles for Enhanced PET Imaging.
Natural melanin nanoplatforms have attracted attention in molecular imaging. Natural melanin can be made into small-sized nanoparticles, which penetrate tumor sites deeply, but unfortunately, the particles continue to backflow into the blood or are cleared into the surrounding tissues, leading to loss of retention within tumors. Here, we report a pH-triggered approach to aggregate natural melanin nanoparticles by introducing a hydrolysis-susceptible citraconic amide on the surface. Triggered by pH values lower than 7.0, such as the tumor acid environment, the citraconic amide moiety tended to hydrolyze abruptly, resulting in both positive and negative surface charges. The electrostatic attractions between nanoparticles drove nanoparticle aggregation, which increased accumulation in the tumor site because backflow was blocked by the increased size. Melanin nanoparticles have the natural ability to bind metal ions, which can be labeled with isotopes for nuclear medicine imaging. When the melanin nanoparticles were labeled by 68Ga, we observed that the pH-induced physical aggregation in tumor sites resulted in enhanced PET imaging. The pH-triggered assembly of natural melanin nanoparticles could be a practical strategy for efficient tumor targeted imaging.


[Effects of different fibrin glue combination modes on the proliferation and viability of dental follicle cells].
This study explores the effects of different fibrin glue combination modes on the survival, proliferation, and apoptosis of dental follicle cells (DFCs), as well as to evaluate the feasibility and effectiveness of fibrin glue as transplantation material. The membranes of surviving DFCs were marked using 3,3'-dioctadecyloxa carbocyanine perchlorate (DIO), and the cell number was counted by using ImageJ2x software. The apoptotic cells were marked with prodium iodide (PI). Compared with that of the 3D-2 and 2D-1 groups, the degradation speed of the 3D-1 group was the slowest. DFCs could survive and grow well in fibrinogen with a concentration of 15 mg · mL⁻¹ supplemented with thrombin with a concentration of 2 U · mL⁻¹. In particular, the 3D-1 combination mode was significantly conducive to cell proliferation and stretching. Fibrin glue can be used as an effective cell transplantation material. The different combination modes have certain effects on cell proliferation. The 3D-1 combination mode is more conducive to the survival and proliferation of DFCs than other modes.


In silico generation of alternative hypotheses using causal mapping (CMAP).
Previously, we introduced causal mapping (CMAP) as an easy to use systems biology tool for studying the behavior of biological processes that occur at the cellular and molecular level. CMAP is a coarse-grained graphical modeling approach in which the system of interest is modeled as an interaction map between functional elements of the system, in a manner similar to portrayals of signaling pathways commonly used by molecular cell biologists. CMAP describes details of the interactions while maintaining the simplicity of other qualitative methods (e.g., Boolean networks).In this paper, we use the CMAP methodology as a tool for generating hypotheses about the mechanisms that regulate molecular and cellular systems. Furthermore, our approach allows competing hypotheses to be ranked according to a fitness index and suggests experimental tests to distinguish competing high fitness hypotheses. To motivate the CMAP as a hypotheses generating tool and demonstrate the methodology, we first apply this protocol to a simple test-case of a three-element signaling module. Our methods are next applied to the more complex phenomenon of cortical oscillations observed in spreading cells. This analysis produces two high fitness hypotheses for the mechanism that underlies this dynamic behavior and suggests experiments to distinguish the hypotheses. The method can be widely applied to other cellular systems to generate and compare alternative hypotheses based on experimentally observed data and using computer simulations.


PlexProbes enhance qPCR multiplexing by discriminating multiple targets in each fluorescent channel.
The probe technology described in this paper facilitates detection and discrimination of multiple targets in a single fluorescent channel during PCR. This provides a strategy for doubling the number of targets that can be analysed simultaneously on existing PCR instruments. These probes are referred to as PlexProbes and produce fluorescence that can be switched 'on' or 'off' in the presence of target by manipulating the temperature. During PCR, fluorescence can be measured at multiple temperatures allowing discrimination of specific targets at defined temperatures. In a single fluorescent channel, a model duplex assay allowed either real-time or endpoint detection of Chlamydia trachomatis (CT) at 52°C and end-point detection of Neisseria gonorrhoeae (GC) at 74°C. Using this model system, as few as 40 copies of each specific target could be detected as single infection or co-infection, regardless of the presence or absence of the other target. A PlexProbe prototype assay for sexually transmitted infections (PP-STI) which simultaneously enables detection and differentiation of six targets using only three fluorescent channels was then constructed and evaluated. The PP-STI assay detects GC (2 gene targets), CT, Mycoplasma genitalium (MG), Trichomonas vaginalis (TV) and an internal control (IC). To evaluate assay performance, a panel of archived clinical samples (n = 337) were analysed using PP-STI and results compared to those obtained with a commercially available diagnostic assay. The overall agreement between results obtained with the PP-STI assay and the reference test was greater than 99.5%. PlexProbes offer a method of detecting more targets from a single diagnostic test, empowering physicians to make evidence-based treatment decisions while conserving time, labour, sample volume and reagent costs.


Risk factors analysis of COVID-19 patients with ARDS and prediction based on machine learning.
COVID-19 is a newly emerging infectious disease, which is generally susceptible to human beings and has caused huge losses to people's health. Acute respiratory distress syndrome (ARDS) is one of the common clinical manifestations of severe COVID-19 and it is also responsible for the current shortage of ventilators worldwide. This study aims to analyze the clinical characteristics of COVID-19 ARDS patients and establish a diagnostic system based on artificial intelligence (AI) method to predict the probability of ARDS in COVID-19 patients. We collected clinical data of 659 COVID-19 patients from 11 regions in China. The clinical characteristics of the ARDS group and no-ARDS group of COVID-19 patients were elaborately compared and both traditional machine learning algorithms and deep learning-based method were used to build the prediction models. Results indicated that the median age of ARDS patients was 56.5 years old, which was significantly older than those with non-ARDS by 7.5 years. Male and patients with BMI > 25 were more likely to develop ARDS. The clinical features of ARDS patients included cough (80.3%), polypnea (59.2%), lung consolidation (53.9%), secondary bacterial infection (30.3%), and comorbidities such as hypertension (48.7%). Abnormal biochemical indicators such as lymphocyte count, CK, NLR, AST, LDH, and CRP were all strongly related to the aggravation of ARDS. Furthermore, through various AI methods for modeling and prediction effect evaluation based on the above risk factors, decision tree achieved the best AUC, accuracy, sensitivity and specificity in identifying the mild patients who were easy to develop ARDS, which undoubtedly helped to deliver proper care and optimize use of limited resources.


Expanded pyridiniums: bis-cyclization of branched pyridiniums into their fused polycyclic and positively charged derivatives--assessing the impact of pericondensation on structural, electrochemical, electronic, and photophysical features.
This study evaluates the impact of the extension of the π-conjugated system of pyridiniums on their various properties. The molecular scaffold of aryl-substituted expanded pyridiniums (referred to as branched species) can be photochemically bis-cyclized into the corresponding fused polycyclic derivatives (referred to as pericondensed species). The representative 1,2,4,6-tetraphenylpyridinium (1(H)) and 1,2,3,5,6-pentaphenyl-4-(p-tolyl)pyridinium (2(Me)) tetra- and hexa-branched pyridiniums are herein compared with their corresponding pericondensed derivatives, the fully fused 9-phenylbenzo[1,2]quinolizino[3,4,5,6-def]phenanthridinium (1(H)f) and the hitherto unknown hemifused 9-methyl-1,2,3-triphenylbenzo[h]phenanthro[9,10,1-def]isoquinolinium (2(Me)f). Combined solid-state X-ray crystallography and solution NMR experiments showed that stacking interactions are barely efficient when the pericondensed pyridiniums are not appropriately substituted. The electrochemical study revealed that the first reduction process of all the expanded pyridiniums occurs at around -1 V vs. SCE, which indicates that the lowest unoccupied molecular orbital (LUMO) remains essentially localized on the pyridinium core regardless of pericondensation. In contrast, the electronic and photophysical properties are significantly affected on going from branched to pericondensed pyridiniums. Typically, the number of absorption bands increases with extended activity towards the visible region (down to ca. 450 nm in MeCN), whereas emission quantum yields are increased by three orders of magnitude (at ca. 0.25 on average). A relationship is established between the observed differential impact of the pericondensation and the importance of the localized LUMO on the properties considered: predominant for the first reduction process compared with secondary for the optical and photophysical properties.


Association Between Socio-Affective Symptoms and Glutathione and CD4 and CD8 Lymphocytes in College Students.
Background: The prevalence of anxiety and depression in young students is associated with biosocial factors and scholastic stress. However, few studies have evaluated emotional-affective symptoms that are related to the immune system and antioxidant parameters in young individuals without diagnoses of affective disorders. Aim: This study aims to assess the relationship between emotional-affective symptoms and glutathione concentrations and CD4 and CD8 lymphocyte counts in college students. Methods: College students (n = 177) completed standardized psychometric instruments, including the Perceived Stress Scale, Hamilton Anxiety Scale, Beck Depression Inventory, Familiar Social and Friends Support Scale, and Rosenberg Scale. Blood samples were biochemically analyzed. Analyses of variance were conducted between four groups according to symptom severity. Results: A considerable prevalence of stress, anxiety, and depression symptoms was observed and negatively correlated with self-esteem and socio-familiar support. Perceived stress was sexually dimorphic. Although biochemical parameters were within reference ranges, glutathione, CD4, and CD8 tended to be lower in participants with anxiety and depression symptoms, which may be of predictive value. Conclusion: The relationship between antioxidant/immune parameters and socio-affective scores is latent in undiagnosed college students who might develop affective disorders. The findings suggest that during the initial development of affective disorders, stress management strategies should be implemented to help college students cope with the academic load and monitor negative changes in their physiological state.


Proton magnetic resonance spectroscopy imaging in the study of human brain cancer.
Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive imaging technique that provides metabolic information on brain tumor. This biochemical information can be processed and presented as density maps of several metabolites, among them N-acetylaspartate (marker of neuronal viability), choline (marker of membrane turnover), creatine (related to the energy state of the cells), myo-Inositol (exclusively found in astrocytes), lipids and lactate (observed in necrosis and other pathological processes) which mean relevant information in the context of brain tumors. Thus, this technique is a multiparametrical molecular imaging method that can complete the magnetic resonance imaging (MRI) study enabling the detection of biochemical patterns of different features and aspects of brain tumors. In this article, the role of MRSI as a molecular imaging technique to provide biochemical information on human brain tumors is reviewed. The most frequent questions and situations in the study of human brain tumors in clinical settings will be considered, as well as the distinction of neoplastic lesions from non neoplastic, the tumor type identification, the study of heterogeneity and infiltration of normal appearing white matter and the therapy following with detection of side effects. The great amount of data in MRSI acquisition compared to the single voxel techniques requires the use of automated methods of quantification, but the possibility to obtain self-reference in the non-affected areas allows different strategies for data handling and interpretation, as presented in the literature. The combination of MRSI with other physiological MRI techniques and positron emission tomography is also included in this review.


Detection of cytomegalovirus in urine from newborns by using polymerase chain reaction DNA amplification.
Polymerase chain reaction (PCR) amplification was used to detect cytomegalovirus (CMV) in tissue culture and in urine specimens from newborns. Synthetic oligonucleotide primer pairs were used to amplify DNA from the major immediate-early and the late antigen genes of CMV. Amplified products were detected by gel electrophoresis and by dot-blot hybridization with oligonucleotide probes. Using one or both of the primer pairs and associated probes, we found 46 different tissue culture isolates of CMV that were positive; no reaction products were detected when the same primers and probes were used to amplify other herpes family viruses or human genomic DNA. Urine samples from 44 congenitally infected infants were positive when tested with one or both primer pairs and probes. When compared with tissue culture, detection by gel electrophoresis provided a sensitivity of 93%, a specificity of 100%, and a predictive value of a positive result of 100%. Dot-blot analysis raised the sensitivity to 100%. We conclude that PCR amplification may be a valuable tool for diagnosing congenital CMV infection.


Suicide gene therapy for plasma cell tumors.
Suicide gene therapy for plasma cell tumors was attempted in severe combined immunodeficient (SCID) mice injected with human myeloma cell lines. Initially, a ganciclovir-induced bystander effect was observed in vitro using myeloma cells transduced with a herpes simplex thymidine kinase (HSVtk) gene. Transduced cells injected subcutaneously (SC) into SCID mice could be eradicated by the administration of ganciclovir (GCV). Furthermore, an in vivo bystander effect was noticed when mice received mixtures of HSVtk-positive and nontransduced cells. Unexpectedly, a "distant bystander" effect was observed as tumors in regions inoculated with only nontransduced cells were significantly smaller and had increased frequency of apoptotic figures and decreased mitotic frequency in GCV-treated mice transplanted with HSVtk-positive cells at a different region compared with control mice.


[The clinico-pathological aspects of acute exacerbation of arteriosclerosis obliterance].
Arteriosclerosis obliterance (ASO) is defined as the ischemic status of lower extremity produced by a stenotic and/or occlusive lesion of lumens of major arterial stress based on the pathology of atherosclerotic change. The sign and symptom of ASO are usually thought to be progressed slowly by natural progression process of atherosclerosis, however, in certain occasion, the progression of clinicopathological status of leg ischemia is acute as well as grave, so as to manifest rest pain or necrosis of the lower extremity. The basic mechanism of acute exacerbation of lower leg ischemia is attributed to the acute extended thrombus formation in arterial lumen. The factors influencing to the thrombus formation are represented as Virchow's Trias such as the changes in arterial wall, the stasis of blood flow and the coagulability of blood. One of the characteristic feature associated with massive and extended ischemia of lower leg is myonephropathic metabolic syndrome proposed by Haimovich in 1960. This syndrome is particularly seen immediately following the restoration of blood flow to the severely damaged leg and characterized by renal as well as systemic organs disorder. The relationship between the extent of muscle damage and the duration of ischemia is analysed through our data.


Radioisotope-guided surgery in patients with neuroendocrine tumours.
We evaluated a hand-held scintillation detector for intra-operative localisation of somatostatin-receptor-positive tumours in situ, and after excision, as an addition to preoperative scintigraphy with [111In-DTPA-Phe1]octreotide. Using the hand-held detector, the suspect tumour/normal tissue ratio R(in situ) between measurements was calculated for 23 patients with neuroendocrine tumours. The count rates of excised tumour and normal tissue were also measured ex vivo and their ratio R(ex vivo) was calculated. In midgut carcinoid (MC) patients (all scintigraphy positive), 4/29 macroscopically identified tumours gave false R(in situ). Tumour/blood 111In activity (T/B) ratios measured in a gamma counter were all high (27-650). In patients with medullary thyroid carcinoma (8/10 scintigraphy positive), misleading R(in situ) were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in MC patients. 2/4 patients with endocrine pancreatic tumours (EPTs) had positive scintigraphy, reliable intra-operative measurements, and very high T/B ratios (910-1,500). 1 patient with a gastric carcinoid had correct R(in situ) and R(ex vivo), with high T/B ratios (71-210). 1 patient with sporadic insulinoma had negative scintigraphy and 1 patient with neuroendocrine carcinoma of the uterus also had low T/B ratios. In most cases, in situ measurements added little information to preoperative scintigraphy and surgical findings. The very high T/B ratios seen in MC tumours and some EPTs seem promising for future radiotherapy via somatostatin receptors.


Distribution, structure and function of Nordic eelgrass (Zostera marina) ecosystems: implications for coastal management and conservation.
This paper focuses on the marine foundation eelgrass species, Zostera marina, along a gradient from the northern Baltic Sea to the north-east Atlantic. This vast region supports a minimum of 1480 km2 eelgrass (maximum >2100 km2), which corresponds to more than four times the previously quantified area of eelgrass in Western Europe.Eelgrass meadows in the low salinity Baltic Sea support the highest diversity (4-6 spp.) of angiosperms overall, but eelgrass productivity is low (<2 g dw m-2 d-1) and meadows are isolated and genetically impoverished. Higher salinity areas support monospecific meadows, with higher productivity (3-10 g dw m-2 d-1) and greater genetic connectivity. The salinity gradient further imposes functional differences in biodiversity and food webs, in particular a decline in number, but increase in biomass of mesograzers in the Baltic.Significant declines in eelgrass depth limits and areal cover are documented, particularly in regions experiencing high human pressure. The failure of eelgrass to re-establish itself in affected areas, despite nutrient reductions and improved water quality, signals complex recovery trajectories and calls for much greater conservation effort to protect existing meadows.The knowledge base for Nordic eelgrass meadows is broad and sufficient to establish monitoring objectives across nine national borders. Nevertheless, ensuring awareness of their vulnerability remains challenging. Given the areal extent of Nordic eelgrass systems and the ecosystem services they provide, it is crucial to further develop incentives for protecting them. © 2014 The Authors. Aquatic Conservation: Marine and Freshwater Ecosystems published by John Wiley & Sons, Ltd.


Controlled Interconversion of Superposed-Bistriangle, Octahedron, and Cuboctahedron Cages Constructed Using a Single, Terpyridinyl-Based Polyligand and Zn(2.).
Metallomacromolecular architectural conversion is expanded by the characterization of three different structures. A quantitative, single-step, self-assembly of a shape-persistent monomer, containing a flexible crown ether moiety, gives an initial Archimedean-based cuboctahedron that has been unequivocally characterized by 1D and 2D NMR spectroscopy, mass spectrometry, and collision cross section analysis. Both dilution and exchange of counterions, transforms this cuboctahedron into two identical octahedrons, which upon further dilution convert into four, superposed, bistrianglar complexes; increasing the concentration reverses the process. Ion binding studies using the cuboctahedral cage were undertaken.


HIV/AIDS Risk and Prevention Issues Among Inuit Living in Nunavut Territory of Canada.
HIV infections occur across the Arctic but their incidence among aboriginal populations varies vastly. At the time this research was initiated there were no data on their occurrence, risk of HIV/AIDS or preventive strategies among Inuit living in the Nunavut territory of Canada. This review is the first to assess the risk of HIV infection among Inuit and evaluate current prevention strategies among Canadian-Inuit populations. The contents of this article are based on the author's own research, undertaken during 3 visits to the Canadian Arctic and the published literature. Disproportionately high rates of Chlamydia and Gonorrhoea within Inuit communities confirm the potential threat of silent HIV transmission. Inuit awareness of HIV/AIDS issues remains inadequate. It is easy to blame distorted perceptions fuelled by the media, religious influence and socio-cultural factors. Aboriginal and Inuit groups, including youth, women and injection drug abusers are at increased risk of infection. The adaptability of proven prevention methods including condom use and male circumcision are discussed. Access to treatment, adherence and resistance issues in the North Canada, require attention. HIV/AIDS poses a considerable threat to Canadian Inuit public health. The most important problem to be addressed is Inuit lack of awareness and understanding of HIV. Education is the single most effective means of prevention. Inuit-specific and culture-sensitive interventions are recommended. Further research opportunities exist to investigate Inuit understanding over HIV/AIDS issues and to assess local prevention efforts.


Retrospective analyses of the reading development of grade 4 students with reading disabilities: risk status and profiles over 5 years.
This study presents a longitudinal examination of the development of reading and reading-related skills of 22 Grade 4 children identified as having reading disabilities (RD) who had been followed since kindergarten. The analyses were conducted to investigate the patterns of emergence of RD as well as reading ability and risk status across the 5 years. The findings of the study are presented with an examination of the trajectories of the children with RD as compared to Grade 4 typical readers (matched for grade, gender, language status, and school) with a similar profile on literacy skills in kindergarten. The results demonstrate the heterogeneous nature of the trajectory of RD in school-age children; although many of the children with RD were at risk in kindergarten, there was a subsample who did not demonstrate reading and phonological difficulties until the third and fourth grades.


[Correlations of 99 Tc m-HL91 SPECT hypoxia imaging with HIF-1alpha and VEGF expression in non-small cell lung cancer].
(99)Tc(m)-HL91 ((99)Tc(m) labeled 4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime) is a potential noninvasive marker of tumor hypoxia. It has been reported that (99)Tc(m)-HL91 has validity for hypoxia imaging in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the (99)Tc(m)-HL91 SPECT hypoxia imaging of NSCLC, the expression of inducible hypoxia factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF), and to analyze their correlations with clinicopathological characteristics. Twenty NSCLC patients who underwent radical resection were enrolled into this study prospectively. (99)Tc(m)-HL91 SPECT scanning was performed in all patients at one or two days before surgery. After intravenous injection of approximately 740 MBq (99)Tc(m)-HL91, anterior, posterior and lateral planar images were collected at 2, 4 and 6 hours, respectively. Regions of interest (ROIs) were drawn in the tumor and the contralateral normal lung tissue, and the radioactivity ratio of tumor to normal tissue (T/N) was calculated. Immunohistochemistry was used to detect the expression of HIF-1alpha and VEGF in sequential histological sections of specimens. Among the 20 NSCLC patients, 13 showed positive expression of HIF-1alpha and 15 had positive expression of VEGF, with a positive rate of 65.0% and 75.0%, respectively. The uptake of (99)Tc(m)-HL91 was strongly correlated with the expression status of HIF-1alpha. No correlation between HIF-1alpha and VEGF expression levels was observed. The HIF-1alpha expression level was not correlated with histological subtype, but with lymph node involvement. The expression levels of HIF-1alpha and VEGF were positively correlated with tumor stage. The result of (99)Tc(m)-HL91 SPECT hypoxia imaging is found to be positively correlated with expression of HIF-1alpha in the non-small cell lung cancer. HIF-1alpha expression is positively correlated with VEGF expression. Furthermore, both HIF-1alpha and VEGF expressions are increasing with the increase of tumor stage.


Is mastectomy overtreatment for Paget's disease of the nipple?
The standard local management for Paget's disease of the nipple is currently mastectomy although this may well represent overtreatment. The place of breast conserving surgery is somewhat uncertain. We have reviewed the casenotes of 146 patients with Paget's disease of the nipple, and compared the mortality and recurrence rates between 74 women who had undergone mastectomy and 31 women who had breast conserving surgery. There was no significant difference in either local or overall treatment failure rates between these two treatment groups. We conclude that breast conserving treatment maybe an appropriate alternative to mastectomy for the management of Paget's disease, where clear margins of excision can be achieved. However, a randomized prospective study is needed to confirm this.


Efficacy of hybrid therapy in the form of right atrial ablation and adjunctive therapy in refractory atrial fibrillation in symptomatic patients.
Symptomatic atrial fibrillation is often treated with antiarrhythmic drugs. Responsiveness is poor and adverse effects common. Nonpharmacologic treatments consisting of the Maze procedure and catheter-based pulmonary vein isolation are highly successful but invasive with complications. Right atrial ablation is relatively simple in comparison. Success ranges between 20% and 80%. Some studies have shown improved response when combined with antiarrhythmic drugs (AADs). We performed a review of available literature to determine the efficacy of hybrid therapy in the form of right atrial ablation, AAD with cardioversion, and pacing in reducing atrial fibrillation burden. All human studies studying efficacy of right atrial ablation and postablation AAD therapy in refractory atrial fibrillation were considered. The primary outcome was reduction of atrial fibrillation burden. The secondary outcome was significant adverse events. We searched Medline, EMBASE, CINAHL, and Cochrane databases. Data collection, analysis, and selection of studies were done independently by two review authors. We included six studies with variable numbers of participants and outcomes. We defined success of hybrid therapy as reduced burden of atrial fibrillation. Total subjects studied was 189, 26% female and 74% male. Average age was 58 years. Left atrial diameter was less than 5 cm and mean ejection fraction was 64%. Mean atrial fibrillation duration was 3.35 years. Most patients had failed at least two AADs. Hybrid therapy was successful in 82% patients. All forms of hybrid therapy consisting of right atrial ablation and AAD therapy seem to be reasonably effective in relief of symptoms from refractory atrial fibrillation with minimal side effects; however, much larger randomized trials need to be performed before a significant superiority of any one may be established.


Adhesion between elastic bodies with randomly rough surfaces.
I have developed a theory of adhesion between an elastic solid and a hard randomly rough substrate. The theory takes into account the fact that partial contact may occur between the solids on all length scales. I present numerical results for the case where the substrate surface is self-affine fractal. When the fractal dimension is close to 2, complete contact typically occurs in the macroasperity contact areas. For a fractal dimension larger than 2.5, the area of (apparent) contact decreases continuously when the magnification is increased.


Harmful and Beneficial Effects of Anticoagulants in Patients With Cirrhosis and Portal Vein Thrombosis.
Vitamin K antagonists (VKAs) promote recanalization of portal vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT recanalization might be offset by major and minor bleeding associated with use of anticoagulants. We evaluated harmful and beneficial effects of VKA in patients with PVT and cirrhosis. We performed a retrospective study of 63 consecutive patients with cirrhosis given anticoagulants for the first detection of non-neoplastic PVT from 2003 to 2015 in Italy. We collected data on bleeding events in these patients and compared them with those from patients without cirrhosis with venous thromboembolism (VTE) (n = 160) for up to 4 years. Time in the therapeutic range, based on the international normalized ratio, was used to determine the quality of anticoagulation. We also collected data from 139 patients with cirrhosis who did not receive VKAs (controls), to analyze portal hypertension-related events. We performed survival analyses to determine the effects of VKA in patients with PVT vs controls. The group with VTE and the group with PVT were comparable in age, sex, and time in the therapeutic range, but patients with VTE received VKAs for a longer time period (31.1 ± 16.9 mo vs 23.3 ± 16.2 mo; P = .002). The incidence of major or minor bleeding was higher in patients with PVT than patients with VTE (major, 24% vs 7%; P = .012; minor, 29% vs 19%; P = .024). Patients with PVT had a higher rate of major bleeding from the upper-gastrointestinal tract than patients with VTE (P = .019), but there were no significant differences in other types of major bleeding (P = .376). Patients with PVT and controls had the same rate of upper-gastrointestinal bleeding. Complete recanalization in patients with PVT receiving VKA (n = 31) was independently associated with increased portal hypertension-related event-free and transplantation-free survival times. In a retrospective analysis of 63 patients with cirrhosis given anticoagulants for PVT, we found VKA use to increase risk of minor bleeding, compared with patients without cirrhosis given VKA. However, this risk is offset by the ability of VKA to increase portal hypertension-related, event-free, and transplantation-free survival of patients with PVT recanalization. Portal hypertension, rather than anticoagulants, could account for the difference in risk of major bleeding between patients with PVT vs patients with VTE.


Frozen bone marrow trephine biopsy--a technical evaluation.
The routine study of bone marrow trephine biopsies involves fixation, decalcification, paraffin-embedment, sectioning and staining. However, this process creates artifacts, produces shrinkage of tissue, consumes time and can result in sections of unsatisfactory cytological quality. It also renders the tissue unsuitable for enzyme-histochemical and immunohistochemical analyses. Frozen section of bone marrow without decalcification was evaluated as an alternative method for the study of bone marrow. This method was found to give sections with comparable cytological quality to that of paraffin-embedment, yielded sections for interpretation within 24 hours, and allowed enzyme-histochemical and immunohistochemical analyses to be applied successfully.


The Impact of Gut Microbiome on Maternal Fructose Intake-Induced Developmental Programming of Adult Disease.
Excessive or insufficient maternal nutrition can influence fetal development and the susceptibility of offspring to adult disease. As eating a fructose-rich diet is becoming more common, the effects of maternal fructose intake on offspring health is of increasing relevance. The gut is required to process fructose, and a high-fructose diet can alter the gut microbiome, resulting in gut dysbiosis and metabolic disorders. Current evidence from animal models has revealed that maternal fructose consumption causes various components of metabolic syndrome in adult offspring, while little is known about how gut microbiome is implicated in fructose-induced developmental programming and the consequential risks for developing chronic disease in offspring. This review will first summarize the current evidence supporting the link between fructose and developmental programming of adult diseases. This will be followed by presenting how gut microbiota links to common mechanisms underlying fructose-induced developmental programming. We also provide an overview of the reprogramming effects of gut microbiota-targeted therapy on fructose-induced developmental programming and how this approach may prevent adult-onset disease. Using gut microbiota-targeted therapy to prevent maternal fructose diet-induced developmental programming, we have the potential to mitigate the global burden of fructose-related disorders.


Membrane-bound neuregulin1 type III actively promotes Schwann cell differentiation of multipotent Progenitor cells.
Many steps of peripheral glia development appear to be regulated by neuregulin1 (NRG1) signaling but the exact roles of the different NRG1 isoforms in these processes remain to be determined. While glial growth factor 2 (GGF2), a NRG1 type II isoform, is able to induce a satellite glial fate in neural crest stem cells, targeted mutations in mice have revealed a prominent role of NRG1 type III isoforms in supporting survival of Schwann cells at early developmental stages. Here, we investigated the role of NRG1 isoforms in the differentiation of Schwann cells from neural crest-derived progenitor cells. In multipotent cells isolated from dorsal root ganglia, soluble NRG1 isoforms do not promote Schwann cell features, whereas signaling by membrane-associated NRG1 type III induces the expression of the Schwann cell markers Oct-6/SCIP and S100 in neighboring cells, independent of survival. Thus, axon-bound NRG1 might actively promote both Schwann cell survival and differentiation.


[Distal pancreatectomy with spleen preservation in a pseudopapillary pancreatic tumor case].
Pseudopapillary pancreatic tumors represent about 1-2% of all exocrine pancreatic tumors, studies in the literature about this type of tumor is limited. We present a female patient of 18 years hospitalized for nonspecific abdominal symptoms, diagnosed with corporeal pancreatic tumor approximately 3-4 cm. It takes practice surgical distal pancreatectomy with spleen preservation, pathological examination revealing a pseudopapillary pancreatic tumor. Postoperative evolution was favorable. Distal pancreatectomy with spleen preservation was indicated due to patient age.


Hepatoprotection by freshwater clam extract against CCl4-induced hepatic damage in rats.
Freshwater clam is traditionally used as a food and has been mentioned in ancient books to have a hepatoprotective effect. The hepatoprotective effect of freshwater clam extract was evaluated in the model of chronic hepatic fibrosis induced by carbon tetrachloride (CCl4). Male Sprague-Dawley rats were orally treated with freshwater clam extract (0.3, 0.6 and 1.5 g/kg of bw) or silymarin (0.2 g/kg of bw) along with the administration of CCl4 (0.5 ml/rat, 20% CCl4 in olive oil) for eight consecutive weeks. Blood samples were collected for assaying serum biochemical parameters. The livers were excised for evaluating peroxidation products and antioxidant substances, as well as the activities of antioxidant enzymes. Pathological histology was also performed. The data showed that supplementation of freshwater clam extract (0.6 g/kg bw) significantly reduced the serum levels of alanine aminotransferase and aspartate aminotransferase in rats treated with CCl4, and also decreased the thiobarbituric acid reactive substances, hydroxyproline and excessive inflammation in the livers of CCl4-treated rats. Histopathological analysis of the liver showed that freshwater clam extract (0.6 g/kg bw) markedly reduced the injury score of the fibrosis induced by CCl4 in rats. The data suggest that oral administration with freshwater clam extract might provide a novel and alternative approach for treating chronic liver failure.


Dissociable effects of salience on attention and goal-directed action.
Everyday behavior frequently involves encounters with multiple objects that compete for selection. For example, driving a car requires constant shifts of attention between oncoming traffic, rearview mirrors, and traffic signs and signals, among other objects. Behavioral goals often drive this selection process [1, 2]; however, they are not the sole determinant of selection. Physically salient objects, such as flashing, brightly colored hazard signs, or objects that are salient by virtue of learned associations with reward, such as pictures of food on a billboard, often capture attention regardless of the individual's goals [3-6]. It is typically thought that strongly salient distractor objects capture more attention and are more disruptive than weakly salient distractors [7, 8]. Counterintuitively, though, we found that this is true for perception, but not for goal-directed action. In a visually guided reaching task [9-11], we required participants to reach to a shape-defined target while trying to ignore salient distractors. We observed that strongly salient distractors produced less disruption in goal-directed action than weakly salient distractors. Thus, a strongly salient distractor triggers suppression during goal-directed action, resulting in enhanced efficiency and accuracy of target selection relative to when weakly salient distractors are present. In contrast, in a task requiring no goal-directed action, we found greater attentional interference from strongly salient distractors. Thus, while highly salient stimuli interfere strongly with perceptual processing, increased physical salience or associated value attenuates action-related interference.


Hemin attenuates cisplatin-induced acute renal injury in male rats.
The aim of this study is to investigate the protective effects of hemin (the heme oxygenase-1 [OH-1] inducer) against nephrotoxic effects induced by cisplatin [cis-diamminedichloroplatinum II (CP)] in male rats. The evaluation was performed through monitoring renal redox parameters: lipid peroxidation (LPO), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GR), and reduced glutathione (GSH). The work also examined renal function tests (urea and creatinine), tissue proinflammatory mediator like nitric oxide (NO), and kidney cytopathology. A single intraperitoneal dose of CP (10 mg/kg b.w.) caused significant elevation of blood urea, serum creatinine, and renal LPO and NO, along with significant decline of the activities of GPx and GR, but renal SOD activity and GSH level were statistically insignificant as compared to control group. Subcutaneous injection of hemin (40 µmol/kg b.w.) partially ameliorated CP-induced renal damage, based on suppression of blood urea, serum creatinine, the renal MDA and NO levels, and increased antioxidant capacity in CP-treated rats. The results of histopathological and ultrastructural investigations supported the renoprotective effect of hemin against CP-induced acute toxicity. The induction of HO-1 by hemin is a promising approach in the treatment of CP-induced nephrotoxicity. However, further preclinical studies are warranted to test effectiveness of CP/hemin on the outcome of tumor chemotherapy.


Esophagogastrectomy for carcinoma in cirrhotic patients.
Esophagogastrectomy for carcinoma of the esophagus or cardia has been performed in 32 patients with histologically proven hepatic cirrhosis. Thirty-one esophagogastrectomies were performed through a separate abdominal and right thoracic approach in 25 patients, a left thoracoabdominal approach in five patients, and without thoracotomy in two patients. One patient had a colon interposition. Seven patients died after operation (21%) as a result of anastomotic leakage in two patients, hepatorenal in four patients and portal thrombosis in one patient. The type of procedure did not influence mortality. The most common postoperative complication was the development of ascites (68%), and when associated with hepatorenal syndrome (in four patients) there was significant mortality (p less than 0.05). Sepsis was present in the terminal stages of all nonsurvivors. A prothrombin time less than or equal to 60% of normal values was the only significant preoperative predictive factor of mortality, with none of the three patients surviving below this level (p less than 0.05). It is concluded that the presence of cirrhosis is not a contraindication to esophagogastrectomy for carcinoma when curative resection can be undertaken. Hepatic reserve is the determinant factor of operative prognosis. Operative risk is acceptable if patients are classified as Child's class A, and prothrombin time is over 60% of normal values. Operation should be delayed when acute alcoholic hepatitis is present. Intraoperative discovery of cirrhosis is not a contraindication to resection when the above criteria are met.


CO2 and Nd:YAG laser-induced pulmonary parenchymal lung injury in a rabbit model.
Laser exposure of the pulmonary parenchyma during treatment of emphysema and other clinical indications causes acute lung injury. Animal investigations are needed to understand and control laser-induced lung injury. We hypothesized that lung injury is deeper from Nd:YAG laser exposures than CO2 exposures because of deeper penetration of Nd:YAG wavelength light. We compared the temporal evolution of histologic injury in rabbits resulting from continuous mode shallow CO2 and Nd:YAG laser pulmonary parenchymal exposures applied in rabbits. Forty-six New Zealand white (NZW) rabbits underwent treatment with CO2 laser (n=18), Nd:YAG laser (n=18), or sham thoracotomy control (n=10) to the visceral pleural surface using 1 min of exposure (5 watts, defocused to 70 W/cm2 power density for both lasers). Animals were killed at 0, 4, 7, 21, and 49 d after exposure. Lung injury, similar to that seen clinically in humans, developed in all laser-treated animals. Injury progressed from ischemia and vascular congestion, to edema and necrosis, followed by pleural and parenchymal fibrosis. The acute injury was qualitatively distinct and slightly deeper in CO2 than Nd:YAG-treated animals (p<0.02) despite the shallower depth of penetration of the CO2 laser. These findings may imply that higher absorption coefficient for CO2 laser energy results in greater focal temperatures and injury in the areas of direct exposure, and suggest that Nd:YAG laser exposure at these settings may cause shallower injury than CO2 lasers in humans undergoing clinical treatment.


Constant i.v. infusions of nalbuphine or buprenorphine for pain after abdominal surgery.
A double-blind, sex-stratified, study compared the analgesic efficacy and side effects of nalbuphine 10 mg ml-1 (group N) and buprenorphine 0.15 mg ml-1 (group B) administered as a continuous infusion (0.2 ml kg-1/24 h), after abdominal surgery. Patients could request additional i.m. analgesic for pain. The study groups were well matched. The trial was stopped after 55 patients had been studied (nalbuphine 29, buprenorphine 26), because nine patients in the nalbuphine group had inadequate pain relief (P less than 0.01) shortly after surgery (mean 2.5 h). Analysis of the results on an "intention to treat" basis showed that the patients who received buprenorphine had significantly greater pain relief at 1, 3, 6 and 20 h after surgery. Patients who received buprenorphine were assessed by the physiotherapist to have less pain and better chest expansion. More additional analgesic was given to the patients receiving nalbuphine. In the patients receiving buprenorphine, the mean ventilatory rate was less (N = 19 b.p.m., B = 14 b.p.m.) (P less than 0.001) and the increase in PaCO2 was greater (N = 0.5 kPa, B = 1.1 kPa) (P less than 0.001), compared with the value before operation. Side effects were equal, and no serious adverse effects were observed in either group.


A comparison of the effect of frusemide and bumetanide on the diuretic response and fibrinolytic mechanism in man.
A double-blind, crossover trial has compared the diuretic response of ten normal male subjects to the oral administration of frusemide (40 mg) and bumetanide (1 mg). Both drugs gave a similar profile, with acute onset and cessation of response, and a marked peak effect. There was no significant difference between the times taken for each drug to produce its peak diuretic effect. The peak rate of diuretic response, and the total response for six hours after drug ingestion, were significantly greater after bumetanide, with respect to urinary volume and sodium excretion. The peak rate of magnesium excretion was greater after bumetanide. There was no difference between the drugs with respect to potassium, calcium or creatinine excretion or the urinary Na/K ratio. Following peak diuresis, potassium excretion did not show a linear return to its control value. At the time of peak diuresis, both drugs caused a significant reduction of euglobulin lysis time; levels of available plasmin were significantly lowered after frusemide, and levels of active plasmin were significantly raised after bumetanide. The significance of these findings in relation to the fibrinolytic mechanism is discussed. Estimations of plasma viscosity, serum total protein and magnesium concentrations showed that maximal haemoconcentration occurred several hours after diuresis.


Rare Causes of Gastrointestinal Bleeding: Focus on Pancreatic Pathology and Visceral Artery Aneurysms.
Beside the common situations of upper gastrointestinal bleeding (GIB) managed by endoscopy, there are clinical situations when the endoscopic approach is limited by the amount of blood, the hemodynamic instability, the intermittent nature of bleeding and a proper diagnosis and treatment requires radiological interventional methods and even surgery. The pancreatic pathology is rarely considered as a possible cause for patients that presents in emergencies with GIB. The rupture of visceral artery aneurysms (VAAs), without underlying pancreatic pathology, should also be regarded in the differential diagnosis of GIB. Even the natural history of VAAs is not well understood, there is a potential risk of bleeding in the gastrointestinal tract, peritoneal cavity and retroperitoneal space, that can result in death. In this paper, we aim to review the rare causes of GIB focusing on pancreatic pathology and VAAs, unrevealed by the underlying pathology and presenting in the emergency department with bleeding symptoms and signs.


[What's new about total knee arthroplasty].
Osteoarthritis of the knee is one of the most common problems in the orthopedic practice and its surgical technique is still challenging. This Mini-Review presents patient specific cutting blocks for the implantation of a total knee arthroplasty.


Cytochrome P450-catalyzed metabolism of ezlopitant alkene (CJ-12,458), a pharmacologically active metabolite of ezlopitant: enzyme kinetics and mechanism of an alkene hydration reaction.
Experiments were conducted to characterize the metabolism of ezlopitant alkene (CJ-12,458), an active metabolite of ezlopitant, in human liver microsomes. In incubations with human liver microsomes and cofactors required for cytochrome P450 (CYP) activity, CJ-12,458 was converted to two metabolites: a diol (CP-611,781) and a 1 degrees alcohol (CP-616,762). In human liver microsomes, apparent K(M) values of 5.4 and 8.5 microM were determined for the formation of diol and 1 degrees alcohol metabolites, respectively. High K(M) activities were also observed for formation of these metabolites; however, the aforementioned low K(M) activities accounted for greater than 90% of the total intrinsic clearance. In pooled human liver microsomes, formation of both metabolites was partially inhibited by both quinidine and ketoconazole, suggesting that CYP2D6 and CYP3A enzymes are involved in the metabolism of CJ-12,458. This evidence was corroborated through the use of heterologously expressed CYP enzymes and correlation analysis with a panel of human liver microsomes. The data suggest that CYP2D6 is quantitatively more important than CYP3A in the metabolism of CJ-12,458 by a factor of about 2 to 1. The conversion of an alkene to a 1 degrees alcohol represents a novel biotransformation reaction. Incubations using (18)O(2), (2)H(2)O, [(2)H(5)]CJ-12,458, and [(2)H]NADPH were conducted and the 1 degrees alcohol product was characterized by ion trap mass spectrometry. From these data, a mechanism for this reaction is proposed involving epoxidation, an exocyclic hydride shift, and reduction at the benzylic position.


Numerical study of a centrifugal blood pump with different impeller profiles.
Computational fluid dynamic simulations of the Kyoto-NTN magnetically suspended centrifugal blood pump with 16 forward-bending blades (16FB), 16 straight blades (16SB), and eight backward-bending blades (8BB) impellers were performed in this study. Commercial CFD software package FLUENT were used as the solver. The purpose of this study is to find out how the impeller blade profiles affect the inner flow and the performance of the centrifugal blood pump. The simulations were carried out with the same impeller rotating speed of 2,000 rpm and pump flow rate of 5 L/min to compare the three pump models. It was found that the 16SB impeller can produce higher pressure head than the 16FB and 8BB impellers under the same impeller rotating speed and pump flow rate. The flow particle tracing was carried out to estimate the blood damage level caused by the three different impeller profiles. It was found that the 16FB and 8BB models have caused the highest and lowest blood damage, respectively. The 16SB is recommended among the three pumps because it can generate the highest pressure head and induce mild blood damage index, although it was higher than that of the 8BB model.


Interannual and spatial variation in the parasite communities of Pacific sierra Scomberomorus sierra (Jordan et Starks) on Mexico's Pacific coast.
The parasite communities of predatory fish can be species rich and diverse, making them effective models for studying the factors influencing temporal and spatial variation in these communities. Over a ten-year period an initial study was done on the metazoan parasite communities of Scomberomorus sierra (Jordan et Starks) from four locations on the south-central Pacific coast of Mexico. Twenty-four metazoan parasite taxa were identified from 674 S. sierra specimens: three species of Monogenea, eight Digenea, one Cestoda, one Acanthocephala, four Nematoda, five Copepoda, and two Isopoda. The parasite communities were characterised by high ectoparasite species richness, with monogeneans and some didymozoid species being numerically dominant. Community structure and species composition varied between locations, seasons and sampling years. Similarity between the component parasite communities was generally low, despite the occurrence of a distinctive set of host-specialist parasites. Interannual or local variations in some biotic and abiotic environmental factors are possible causes of the observed variations in the structure and species composition of the parasite community of S. sierra. Ecological factors were therefore considered to have more influence than phylogenetic aspects (host phylogeny) on parasite community structure.


Instructional practices in mainstreamed secondary classrooms.
This study examined the skills of secondary students that teachers considered necessary for success in mainstreamed regular education classrooms and intervention strategies teachers would be willing to use. Teachers (N = 89) from three high schools rated the importance of 14 student skills and the reasonability of 35 intervention strategies. Student skills deemed important included following directions, coming to class prepared with materials, using class time wisely, and making up assignments and tests. Factor analysis of intervention strategy results revealed seven factors: using supplemental resources; simplifying instruction; providing support and extra instructional cues; enhancing classroom behavior management; facilitating grade improvement; modifying learning environment; and teaching study skills and providing a positive, cooperative learning environment. Secondary teachers appear to prefer intervention strategies that they can implement in their own classroom, that can apply to all students, and that require little extra time.


Liquid biopsy: Novel perspectives on the importance and spectrum of PIK3CA, PTEN and RET mutations in solid tumors.
Many people die from lung and breast cancer. Consequently, both physicians and researchers strive to provide reliable monitoring for disease, diagnosis and prognosis as well as resistance prediction. In the present study, a comprehensive liquid biopsy panel was performed on 474 patients to examine the importance and spectrum of recurrent somatic cancer mutations. Most patients visited the clinic with a diagnosis of advanced resistant cancer. The patients underwent a comprehensive liquid biopsy panel. Patients were divided into four groups based on cancer type as follows: Lung (n=379, 79.9%), breast (n=72, 15.2%), gastrointestinal (n=11, 2.3%) and other (n=12, 2.5%). Tier I-II-III classified variants were included in the study. The mean age was 60 years, with a range of 20-86 years. There were notably more male (n=272, 57.4%) than female patients (n=202, 42.6%). The most commonly mutated genes were TP53, EGFR, PIK3CA, RET, PTEN, MET, ATM and KRAS. The most common mutations were 'PIK3CA, c.3140A>G, p.His1047Arg', 'RET, c.2324delinsGAC, p.Glu775Glyfs*6', 'TP53, c.217G>C, p.Val73Leu', 'EGFR, c.2155G>A, p.Gly719Ser', 'PIK3CA, c.1624G>A, p.Glu542Lys', 'PTEN, c.397G>A, p.Val133Ile' and 'EGFR, c.2235_2249del, p.Glu746_Ala750del'. The PIK3CA, PTEN and RET variants showed a higher incidence in the breast and lung groups compared with other groups. To the best of our knowledge, the present study is the first to concentrate on PIK3CA, PTEN and RET mutations in the context of breast and lung adenocarcinoma and to evaluate both genetic variability and the effect of treatment. The present results showed that patients with solid tumors, particularly lung and breast cancer, may benefit from PIK3CA, PTEN and RET sequencing to assess clinical characteristics and prognosis. Discoveries regarding the gene structure and mechanisms of PIK3CA, PTEN and RET may inform more clinically meaningful therapeutic approaches for patients with cancer and serve an essential role in improving individual risk prediction, therapy and prognosis.


A population-based study of mortality due to muscular dystrophies across a 36-year period in Spain.
Muscular dystrophies (MD) are a group of rare hereditary degenerative diseases. Our aim was to analyze the mortality pattern in Spain from 1981 to 2016 to assess the temporal trend and discern possible geographic differences using population-based data. Annual deaths related to MD were obtained from the National Statistics Institute with codes 359.1 of the ICD-9 (1981-1998) and G71.0 of the ICD-10 (1999-2016). Age-adjusted mortality rates were calculated and changes in mortality trends were identified. The standardized mortality ratios (SMR) and their respective 95% confidence intervals were calculated by district for 1999-2016. Smoothed SMRs and posterior probability were also assessed and then mapped to look for patterns or geographic distribution. All rates were expressed per 1,000,000 inhabitants. A total of 2,512 deaths (73.8% men) were identified. The age-adjusted mortality rates varied from 0.63 (95% CI 0.40-0.95) in 1981 to 1.51 (95% CI 1.17-1.93) in 2016. MD mortality showed a significant increase of 8.81% per year (95% CI 5.0-12.7) from 1981 to 1990, remaining stable afterwards. Areas with risk of death higher than expected for Spain as a whole were identified, not showing a specific regional pattern. In conclusion, the rising trend in MD mortality might be attributable to advanced improvements in diagnostic techniques leading to a rise in prevalence. Further research on the districts with the highest mortality would be necessary.


Concordance of studies for nodal staging is prognostic for worse survival in esophageal cancer.
Pretreatment clinical staging in esophageal cancer influences prognosis and treatment strategy. Current staging strategies utilize multiple imaging modalities, and often the results are contradictory. No studies have examined the implications of concordance of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) when used for the evaluation of nodal disease. The objective of this study was to determine if concordance of CT, PET, or EUS for nodal disease predicts worse overall survival. We reviewed 615 esophageal cancer patients with pretreatment CT, PET, and EUS that underwent esophagectomy for survival outcomes based on concordance of studies for nodal disease. Concordant N+ is defined as two or three studies positive for nodal disease; non-concordant N+ is defined as only one positive study. Node-positive disease by any study predicted shorter survival than node-negative disease (42% vs. 73% 5-year survival; P<0.001). Additionally, non-concordant N+ patients had shorter survival than N- patients (52% vs. 73% 5-year survival; P<0.001). Concordant N+ patients had shorter survival than non-concordant N+ patients (38- vs. 61-month median survival; P=0.017). There were no statistically significant differences in survival based on specific combinations of studies. When PET was disregarded, patients with both CT+ and EUS+ had shorter survival than patients with either CT+ or EUS+ (39- vs. 58-month median survival; P=0.029). Pretreatment CT, PET, or EUS concordance for node-positive disease predicts shorter overall survival in patients that undergo esophagectomy for esophageal cancer. Predicting survival in esophageal cancer should consider the synergistic capabilities of CT, PET, and EUS in evaluating nodal status.


The Effect of Artemisinin-Based Drugs vs Non-artemisinin-based Drugs on Gametophyte Carrying in the Body After the Treatment of Uncomplicated Falciparum Malaria: A Systematic Review and Meta-analysis.
The WHO recommends Artemisinin-based combination therapy (ACTs) as the first-line treatment for malaria. This meta-analysis aims to analyze the effects of artemisinin and its derivatives as well as non-artemisinin drugs on the gametophytes in the host during the treatment of falciparum malaria. Fourteen studies were included in this analysis, and the artemisinin combination drugs involved were: artemether-lumefantrine (AL), artemisinin (AST), artemether-benflumetol (AB), dihydroartemisinin-piperaquine + trimethoprim + primaquine (CV8), amodiaquine + sulfadoxine-pyrimethamine (ASP), pyronaridine-phosphate + dihydroartemisinin (PP-DHA), dihydroartemisinin (DHA), and mefloquine + artesunate (MA), with 1702 patients. The control intervention measures involved the following: sulfadoxine-pyrimethamine (SP), mefloquine (MQ), atovaquone-proguanil (AT-PG), chloroquine + sulfadoxine-pyrimethamine (C-SP), quinine (Q), pyronaridine-phosphate (PP), pyronaridine (PN), and mefloquine + primaquine (MP), with 833 patients. The effect of ACTs was more obvious (OR = 0.37, 95%CI: 0.22-0.62, p < 0.05). In the control group of second malaria attacks, the difference between the two groups was not statistically significant (RD = 1.16, 95%CI: 0.81-1.66, p < 0.05); there was no significant difference in treatment failure during follow-up (RD = -0.01, 95%CI: 0.04-0.03, p < 0.05). There were also very few serious adverse events in both groups. ACTs showed good therapeutic effects in preventing gametocythemia but did not control the recrudescence rate and overall cure, which indicated the effectiveness of the combination of antimalarial drugs. Further research is required to explore which compatibility method is most conducive to the development of clinical malaria control.


Pregnancies and their obstetric outcome in two selected age groups of teenage women in Greece.
The aim of this study was to evaluate the outcome of pregnancies in adolescents in the Department of Obstetrics and Gynaecology of Democritus University of Thrace, North-Eastern Greece. We retrospectively reviewed 194 cases of adolescent pregnancies, with an average maternal age of 16.5 years, from 1st January 2006 to December 30th 2008. Socioeconomic characteristics, type of delivery and complications, such as preterm labor, preeclampsia, intra- and post-partum complications, were evaluated. The median age at first intercourse was 14.2 years and the average period between first intercourse and pregnancy was 1.2 years. Most teen mothers (86.6%) did not use any contraceptive method. Among the teen mothers recruited for the study, 89.7% were married. Adolescent pregnancies accounted for 9.02% of all deliveries (2150) in our Department. In 49 (25.3%) of the pregnant adolescents, no previous pregnancy was reported. The rates of preterm birth of teen mothers were 11.3%, 41.3% and 47.4% in correlation to <32 weeks, 32-34 weeks and >34 weeks, respectively. In 95.4% of the cases, deliveries were not complicated. According to our results, the main complications, especially in very young girls, are preterm labor, anaemia, hypertensive disease, obstructed labor after premature rupture of the membranes and increased neonatal mortality and morbidity. Antenatal care is often inadequate. Early teenage pregnancies have always been considered of increased risk for obstetric complications. Prevention of adolescent pregnancy, by wide use of effective contraception programs, would decrease its frequency and intensive care of pregnant adolescents may reduce the pregnancy complications.


Assessment of reported uterine lesions diagnosed histologically after ovariohysterectomy in 1,928 pet rabbits (Oryctolagus cuniculus).
To assess variations in age, breed, and clinical signs in rabbits with neoplastic or nonneoplastic uterine lesions and to investigate potential relationships between endometrial adenocarcinoma and age at ovariohysterectomy or breed in rabbits. 1,928 rabbits that underwent ovariohysterectomy for treatment or prevention of possible uterine disease. With an online questionnaire distributed to 441 veterinary hospital members of the Japanese Society of Exotic Pet Medicine, data were retrospectively collected regarding age, breed, and findings on physical and histologic examinations for pet rabbits that underwent ovariohysterectomy between January 1, 2009, and April 30, 2018. Rabbits were grouped by reported age, breed, clinical signs, and uterine lesions, and results were assessed across groups. Logistic regression analysis was used to identify potential relationships between endometrial adenocarcinoma and breed or age at ovariohysterectomy in rabbits. The questionnaire response rate was 9.8% (43/441), with data reported for 1,928 rabbits (mixed breed, 600 [31.1%]; Netherland Dwarf, 520 [27.0%]; Holland Lop, 286 [14.8%]; or various other breeds, 522 [27.1%]). The most commonly reported neoplastic and nonneoplastic lesions were endometrial adenocarcinoma (1,035/1,928 [53.7%]) and endometrial hyperplasia (842 [43.7%]), respectively, and the most commonly reported clinical sign was hematuria or serosanguineous vaginal discharge (1,020/1,928 [52.9%]). As age at ovariohysterectomy increased, so did the odds (OR, 1.826; 95% CI, 1.640 to 2.033) of uterine adenocarcinoma. Results supported ovariohysterectomy in rabbits before 2 years of age as a key preventative measure to mitigate uterine disease, particularly endometrial adenocarcinoma.


Hemicellulosic polymers of cell walls of zea coleoptiles.
Hemicellulosic polymers comprised about 43% of the primary walls of Zea mays L. cv WF9 x Bear 38 coleoptiles; these polymers were separated by an alkali-gradient into three major fractions. Fraction 1 (GAX I) was solubilized from walls with 0.01 to 0.045 n KOH and consisted of novel glucuronoarabino(galacto)xylans. Nearly six of every seven residues of these xylans were substituted predominantly with single arabinosyl sidegroups. Fraction 2 (GAX II), material released by 0.45 to 0.8 n KOH, was also enriched with glucuronoarabinoxylan, but only two of every three xylose residues was substituted. This xylan was similar to those found in Zea and other Graminaceous species. Both of these xylan fractions contained uronic acid, terminal- and 4-linked galactosyl, and small amounts of 2-, 3-, 5-, and 3,5-linked arabinosyl units. Fraction 3 (MG-GAX) was released by 2.0 to 3.0 n KOH and consisted of about 60% mixed-linked glucan and about 40% glucuronoarabinoxylan. This fraction represented about half of the total hemicellulosic material of the primary walls of these coleoptiles.The molecular weight of the highly substituted GAX I was approximately 21 kilodaltons as determined by the ratio of reducing sugar to total sugar, but ultracentrifugation studies and gel chromatography on Sepharose 4B-200 indicated that GAX I formed larger aggregates of primarily 50 to 90 kilodaltons, whereas most of the GAX II and virtually all of the MG-GAX materials were excluded by Sepharose 4B; exclusion from the Sepharose was correlated with the presence of mixed-linked glucan. Only GAX II and MG-GAX material demonstrated any appreciable binding to cellulose in vitro.


In Vivo Modulation of T-DNA Encoded Amidohydrolase Activity in Transformed Tobacco Cells.
Auxin autonomous growth of most crown gall tumor cells requires the expression of two auxin biosynthesizing genes (tms 1 and tms 2) from the T-DNA of Agrobacterium tumefaciens. The potential role of the tms 2 locus to affect auxin accumulation was studied by measuring the activity of its gene product, indoleacetamide hydrolase (AH), in cloned cells of tobacco (Nicotiana tabacum) transformed by the A6 strain of Agrobacterium tumefaciens. AH activity followed a consistent pattern over a 30 day culture cycle with a peak at 10 to 14 days. This same pattern was observed in a number of independently isolated clones as well as in uncioned tumor tissue, suggesting that AH activation is a regular process in wounded, transformed cells. Transfer of unwounded tissue to fresh media resulted in a similar pattern of AH activation, but with the peak activity only about 50 percent of the cut tissues. These results show that the tms 2 encoded AH activity is modulated over the culture cycle, and that the modulation is affected by wounding and supplying fresh nutrients in the medium. AH activity correlated closely with free indoleacetic acid levels which suggests that it can be an important determinant in controlling free IAA levels in transformed cells.


Diapause and maintenance of facultative sexual reproductive strategies.
Facultative sex combines sexual and asexual reproduction in the same individual (or clone) and allows for a large diversity of life-history patterns regarding the timing, frequency and intensity of sexual episodes. In addition, other life-history traits such as a diapause stage may become linked to sex. Here, we develop a matrix modelling framework for addressing the cost of sex in facultative sexuals, in constant, periodic and stochastically fluctuating environments. The model is parametrized using life-history data from Brachionus calyciflorus, a facultative sexual rotifer in which sex and diapause are linked. Sexual propensity was an important driver of costs in constant environments, in which high costs (always > onefold, and sometimes > twofold) indicated that asexuals should outcompete facultative sexuals. By contrast, stochastic environments with high temporal autocorrelation favoured facultative sex over obligate asex, in particular, if the penalty to fecundity in 'bad' environments was large. In such environments, obligate asexuals were constrained by their life cycle length (i.e. time from birth to last reproductive adult age class), which determined an upper limit to the number of consecutive bad periods they could tolerate. Nevertheless, when facultative asexuals with different sexual propensities competed simultaneously against each other and asex, the lowest sex propensity was the most successful in stochastic environments with positive autocorrelation. Our results suggest that a highly specific mechanism (i.e. diapause linked to sex) can alone stabilize facultative sex in these animals, and protect it from invasion of both asexual and pure sexual strategies.This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'.


Cloning, expression and in vitro evaluation of recombinant canine Tum5, an angiostatic domain of mammalian type IV collagen.
The process of new blood vessel formation within and around neoplastic tissue, termed angiogenesis, is a significant factor in the development, progression and metastasis of malignant tumours in all species. A major cause of death in cancer patients is the development of treatment-resistant metastatic disease, which may be avoided by therapies that target the genetically stable population of vascular endothelial cells within tumours. Tumstatin is a small protein formed by the cleavage of the alpha-3 subunit of the non-collagenous domain of mammalian type IV collagen. Recombinant human Tumstatin has been shown to have potent angiostatic properties in vitro and in vivo. Tumstatin is a potent initiator of apoptosis and inhibits the proliferation and migration of vascular endothelial cells in cell culture. Recently, a fragment of Tumstatin, termed Tum5, has been shown to have biologic activity similar to the parent compound. The systemic administration of angiostatic proteins like Tum5 may result in the remission of established tumours, while preventing or delaying the onset of clinically detectable metastasis. Recombinant canine Tum5 (cTum5) was cloned and its protein expression induced in a prokaryotic vector. The resulting cTum5 protein caused dose-dependent inhibition of vascular endothelial cells in vitro, which appears to be mediated through apoptosis.


Plasma advanced glycation end-products and skin autofluorescence are increased in COPD.
Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. These conditions may lead to the formation of advanced glycation end-products (AGEs). In this study we investigated in 88 COPD patients and 55 control subjects (80% ex-smokers) the association of the plasma protein-bound AGEs N(ε)-(carboxymethyl)lysine (CML), pentosidine, N(ε)-(carboxyethyl)lysine (CEL), and AGE accumulation in skin by skin autofluorescence (AFR), with lung function. Mean ± sd plasma CML was decreased (COPD 61.6 ± 15.6 nmol · mmol(-1) lysine, never-smokers 80.7 ± 19.8 nmol · mmol(-1) lysine and ex-smokers 82.9 ± 19.3 nmol · mmol(-1) lysine) and CEL (COPD 39.1 ± 10.9 nmol · mmol(-1) lysine, never-smokers 30.4 ± 5.0 nmol · mmol(-1) lysine and ex-smokers 27.7 ± 6.4 nmol · mmol(-1) lysine) and AFR (COPD 3.33 ± 0.67 arbitrary units (AU), never-smokers 2.24 ± 0.45 AU and ex-smokers 2.31 ± 0.47 AU) were increased in COPD patients compared to controls. Disease state was inversely associated with CML, and linearly associated with CEL and AFR. Performing regression analyses in the total group, CEL and AFR showed a negative association and CML a positive association with lung function, even after correction for potential confounders. In conclusion, CEL and AFR were negatively and CML was positively associated with disease state. In the total group only the AGEs showed an association with forced expiratory volume in 1 s. Our data suggest that AGEs are involved in the pathophysiology of COPD, although their exact role remains to be determined.


The ecology of COVID-19 and related environmental and sustainability issues.
Around the globe, human behavior and ecosystem health have been extensively and sometimes severely affected by the unprecedented COVID-19 pandemic. Most efforts to study these complex and heterogenous effects to date have focused on public health and economics. Some studies have evaluated the pandemic's influences on the environment, but often on a single aspect such as air or water pollution. The related research opportunities are relatively rare, and the approaches are unique in multiple aspects and mostly retrospective. Here, we focus on the diverse research opportunities in disease ecology and ecosystem sustainability related to the (intermittent) lockdowns that drastically reduced human activities. We discuss several key knowledge gaps and questions to address amid the ongoing pandemic. In principle, the common knowledge accumulated from invasion biology could also be effectively applied to COVID-19, and the findings could offer much-needed information for future pandemic prevention and management.


Phenotyping of apolipoprotein E using immobilized pH gradient gels for one-dimensional and two-dimensional separations.
Apolipoprotein E (apo E) is a normal component of several classes of plasma lipoproteins. Apo E phenotypes are closely related to total cholesterol, low density lipoprotein (LDL)-cholesterol and apo B concentration. The apo E 2/2 phenotype is related to the type III hyperlipoproteinemia due to the defective binding of apo E-2 to the hepatic receptors. The apo E 4/4 phenotype has been reported to be present in most elderly people suffering from the Alzheimer disease, and is associated with increased risk of coronary heart disease and Creutzfeld-Jakob disease. Therefore, apo E phenotyping is essential. The method described here uses a precast immobilized pH gradient, avoids time-consuming separation of lipoproteins from plasma, needs no pretreatment with neuraminidase and involves highly sensitive enhanced chemiluminescence for visualization. Therefore it has many advantages over previously published methods.


Impairment of plasma nitric oxide availability in senescent healthy individuals: apparent involvement of extracellular superoxide dismutase activity.
To verify the potential involvement of the age-dependent modifications of EC-SOD activity in the impairment of plasma NO availability with advancing age, 40 healthy men divided into 4 age groups for the purpose of comparison (young: 27.4 +/- 1.5 years; middle: 50.8 +/- 2.2, years; old: 70.0 +/- 1.8 years; very old: 86.1 +/- 1.1 years) were enrolled in this study. Plasma samples were used for measurements of the stable end-product nitrite/nitrate (NOx), as an expression of NO availability, EC-SOD activity, thiobarbituric acid reactive substances (TBARS) as a marker of lipid peroxidation, low density lipoprotein (LDL) copper-mediated oxidation in vitro and total antioxidant capacity (TEAC). Our results indicated a significant age-related progressive decrease of plasma NOx content and EC-SOD activity and their values were positively correlated (r = 0.713, p < 0.001). Increased TBARS amount together with reduced lag time for in vitro oxidation of LDL and decreased content of TEAC were observed with advancing age. Finally, EC-SOD values were negatively correlated with plasma TBARS values (r = -0.855, p < 0.001). Findings of the present study suggest that the decrease of antioxidant defence strategies play a primary role by compromising NO availability in normally aged individuals, particularly through a progressive decrease of EC-SOD activity.


A comparison of the induction of immortalized endothelial cell impermeability by astrocytes.
The suitability of various commercially available endothelial cell lines in studies of astrocytic/endothelial cell interactions was assessed. The endothelial-like cell line ECV304 was compared with T24/83, Eahy929, and b.End5 and rat cerebral endothelial cells in their ability, when co-cultured with rat (C6) glioma cells, to form a transendothelial electrical resistance (TEER), an indicator of tight junction formation which is an important property of the blood-brain barrier. As reported previously, the basal TEER of ECV304 cell monolayers was significantly enhanced upon co-culture, an effect reproduced by human 1321N1 astrocytes and primary rat astrocytes. T24/83 cells formed a patchy, gapped monolayer, which produced a poor basal TEER with little in the way of an increase upon co-culture. Similarly, all the other cell monolayers analysed demonstrated poor TEERs that were only moderately increased upon co-culture. These data confirm that while no endothelial cell line with ideal features is available, ECV304 cells remain an appropriate choice especially for studies of astrocyte/endothelial cell interactions.


Evaluation of wheelchair tire rolling resistance using dynamometer-based coast-down tests.
The objective of this study was to compare the rolling resistance of four common manual wheelchair tires (two pneumatic and two airless solid) and the solid tires used on a commercially available force- and moment-sensing wheel. Coast-down tests were performed with a wheelchair positioned on a two-drum dynamometer. Within each of three load conditions, tire type had a significant effect on rolling resistance (p < 0.001). The pneumatic tires had smaller rolling resistances and were less affected by load increases than the solid tires. Within the two tire types, higher air pressure or firmness and lower profile tread corresponded to less rolling resistance. Wheelchair users, clinicians, and researchers must consider the effect of tire type on wheelchair rolling resistance when selecting a manual wheelchair tire.


Mechanical Feedback Control for Multicellular Tissue Size Maintenance: A Minireview.
All living tissues and organs have their respective sizes, critical to various biological functions, such as development, growth, and homeostasis. As tissues and organs generally converge to a certain size, intrinsic regulatory mechanisms may be involved in the maintenance of size regulation. In recent years, important findings regarding size regulation have been obtained from diverse disciplines at the molecular and cellular levels. Here, I briefly review the size regulation of biological tissues from the perspective of control systems. This minireview focuses on how feedback systems engage in tissue size maintenance through the mechanical interactions of constituent cell collectives through intracellular signaling. I introduce a general framework of a feedback control system for tissue size regulation, followed by two examples: maintenance of epithelial tissue volume and epithelial tube diameter. The examples deliver the idea of how cellular mechano-response works for maintaining tissue size.


Systemic effects of deep brain stimulation on synergic control in Parkinson's disease.
We explored effects of deep brain stimulation (DBS) in patients with Parkinson's disease (PD) on the synergic control of fingers in a multi-finger force production task and of muscles in a task involving vertical posture. The finger task involved the four fingers of a hand producing accurate total force followed by a targeted quick force pulse. The postural task involved releasing a load from extended arms. The analysis of synergies was performed within the framework of the uncontrolled manifold hypothesis. DBS led to no significant changes in indices of stability during steady-state phases. In contrast, DBS improved indices of agility, quantified as anticipatory synergy adjustments that reduced stability of salient performance variables in preparation to their quick change. There were moderate-to-strong correlations between indices of both stability and agility measured in the multi-finger force production and multi-muscle whole-body action. Our results point at systemic changes in synergic control in PD. They show that DBS is effective in improving only one components of synergic control related to agility in performance being relatively ineffective for the stability component. The results show systemic brain mechanisms of synergies and suggest differential effects of DBS on indices of stability and agility.


Predictors of Treatment Outcomes for Substance-Abusing Women: A Retrospective Study.
This study examined whether client characteristics at admission predict Retention, Abstinence, and utilization of Required Services and Specialized Services for pregnant women in outpatient and residential substance abuse treatment. Retrospective data were collected with the Psychosocial History (PSH), a structured clinical interview that is an expansion of the Addiction Severity Index, designed specifically to assess substance abusing women. The PSH was administered at intake for 183 pregnant women admitted to outpatient (n = 133) or residential (n = 50) treatment. Factor analysis reduced predictors to five factors with composite scores, and multiple regression procedures determined client characteristics that predict treatment outcomes. The findings suggest the complexity of predicting treatment outcomes for pregnant women. Significant predictors were composites of variables that encompassed all aspects of women's personal and family lives including medical and psychiatric needs, family and parenting issues, housing, victimization, and clients' perceived needs for treatment and assistance in all of these areas. The results suggest the need for a holistic approach to substance abuse treatment and continued exploration of a broad range of psychosocial assessments at intake in order to develop substance abuse treatment programs that effectively address multiple aspects of women's lives.


Transcallosal Removal of a Choroid Plexus Tumor From the Lateral Ventricle in a Dog. Case Report.
A 6-years-old female Staffordshire terrier was referred for periodic generalized seizures and asymmetric visual deficits. Magnetic resonance imaging revealed a 23.2 × 19.3 × 23.0 mm soft tissue mass within the right lateral ventricle and consequential dilatation of the lateral ventricles. Surgically, an interhemispheric approach was performed next to the marginal gyrus after a right parieto-parasagittal craniotomy, and a large choroid plexus tumor was transcallosally removed. After 3 days, the dog was discharged to home, and supportive treatment was continued. Histology revealed a choroid plexus papilloma, which was also confirmed by immunohistochemistry. One month after surgery, a control MRI showed that the ventricles were still dilated, but there was no sign of recurrent tumor. The dog had two additional seizures at home during the month following the intervention and one more grand mal episode was observed 4 months after the surgery. Nine months after the surgery, the dog showed no seizure activity, but her vision had not yet returned.


Introduction of xylem differentiation in lactuca by ethylene.
Evidence was obtained to support the hypothesis that ethylene is involved in xylem differentiation in primary pith explants of Lactuca sativa L. cv Romaine cultured in vitro. Xylem elements differentiated when explants were supplied indole-3-acetic acid (IAA) in combination with either the ethylene biosynthetic precursor 1-aminocyclopropane-1-carboxylic acid (ACC), the ethylene-releasing agent 2-chloroethylphosphonic acid (CEPA), or kinetin. In contrast, no xylem elements differentiated in the presence of IAA, kinetin, ACC, or CEPA alone, or when kinetin was supplied together with ACC or CEPA. These results show that ethylene will substitute qualitatively for cytokinin during auxin-induced xylogenesis, and suggest that both ethylene and auxin are required for xylem differentiation in Lactuca.


Ridge alterations post-extraction in the esthetic zone: a 3D analysis with CBCT.
Dimensional alterations of the facial bone wall following tooth extractions in the esthetic zone have a profound effect on treatment outcomes. This prospective study in 39 patients is the first to investigate three-dimensional (3D) alterations of facial bone in the esthetic zone during the initial 8 wks following flapless tooth extraction. A novel 3D analysis was carried out, based on 2 consecutive cone beam computed tomographies (CBCTs). A risk zone for significant bone resorption was identified in central areas, whereas proximal areas yielded only minor changes. Correlation analysis identified a facial bone wall thickness of ≤ 1 mm as a critical factor associated with the extent of bone resorption. Thin-wall phenotypes displayed pronounced vertical bone resorption, with a median bone loss of 7.5 mm, as compared with thick-wall phenotypes, which decreased by only 1.1 mm. For the first time, 3D analysis has allowed for documentation of dimensional alterations of the facial bone wall in the esthetic zone of humans following extraction. It also characterized a risk zone prone to pronounced bone resorption in thin-wall phenotypes. Vertical bone loss was 3.5 times more severe than findings reported in the existing literature.