Band-structure modulation in carbon nanotube T junctions.
We show that the band structure of metallic carbon nanotubes can be dramatically altered by the local electrostatic field. This is realized by coupling chemically functionalized nanotubes to form T junctions. The bar of the T is the conducting channel and the leg of the T is used for local gating. Transport measurements reveal that an energy gap develops upon application of a local electric field in both devices with or without linker molecules at the junction. We propose that the mechanism of the band gap modulation in the T junctions without linker molecules is the field effect, with the linker molecules introducing additional electromechanical and chemical effects.


Designing Health Apps to Support Dietetic Professional Practice and Their Patients: Qualitative Results From an International Survey.
Dietitians are engaging with mobile health (mHealth) technologies, particularly with diet and nutrition apps in their patient care. Despite the plethora of apps available, the majority are not designed with a dietitian's input. The aim of this study was to identify the user preferences of dietitians in relation to tools, resources, and design features for smartphone health apps that would support their dietetic professional practice and their patients. As part of a larger international Web-based survey of health-app use among dietitians, three open-ended responses were included for specific exploration of app design features and additional resources or tools that could guide the development of apps for use in dietetic practice and patient care. Inductive thematic analysis of responses was conducted using the qualitative data analysis program, NVivo version 11 (QSR International Pty Ltd), to understand the design preferences and features valued by dietitians. The responses from 381 dietitian respondents were analyzed. Five key themes were identified. Dietitians wanted access to credible apps, suggesting that dietetic associations should have greater involvement in reviewing and endorsing evidence-based apps for use in dietary counseling. Improvements to the usability of apps, relating to their ease of use and design, were also raised, as self-monitoring of dietary behaviors using existing nutrition apps was deemed to be burdensome. Furthermore, apps providing dietitian-oriented support were favored, for example, those with the ability to streamline the dietary assessment process, so that dietitians could spend more time on dietary counseling and negotiating patient goals for dietary and lifestyle behavior change. Provision of patient-oriented support, such as functionality to tailor apps to patient-specific needs, was also considered important. Finally, respondents valued apps that could integrate into their work systems to enhance the quality of the dietitian-patient relationship. App developers should draw upon the features and characteristics valued by dietitians to guide their development of apps that support dietetic practice and enhance patient care. Moreover, to achieve better dietitian and patient-centered app design, it is imperative that app developers take a collaborative approach with dietitians, their professional associations, and their patients.


Improved biphasic calcium phosphate combined with periodontal ligament stem cells may serve as a promising method for periodontal regeneration.
The study aimed to investigate if a construct of porous improved biphasic calcium phosphate (BCP) combined with osteogenically induced periodontal ligament stem cells (PDLSCs) could repair periodontal defect. Human PDLSCs were cultured, identified, and osteogenically induced, and then seeded on the improved BCP, assessed by scanning electron microscopy and MTT method. Afterwards, PDLSC-seeded scaffolds were used in six Beagle dogs' alveolar bone dehiscence model, and new bone formation was assessed by three-dimensional micro-computed tomographic imaging, fluorescence, and light microscopy at 4th, 8th and 12th week postoperatively. Results showed that PDLSCs were positive for STRO-1 and vimention, while negative for cytokeratin. They had the capacity to undergo osteogenic differentiation in vitro. When seeded on the improved BCP, PDLSCs exhibited significantly great viability. The use of PDLSC-seeded improved BCP promoted effective periodontal regeneration. In conclusion, this study demonstrates the potential of improved BCP combined with PDLSCs as a promising method for periodontal regeneration.


Antifibrotic Effects of Human Amniotic Membrane Transplantation in Established Biliary Fibrosis Induced in Rats.
Liver fibrosis is characterized by excessive accumulation of extracellular matrix components in the liver parenchyma that distorts the normal architecture and hepatic function. Progressive fibrosis could end in the advanced stage known as cirrhosis, resulting in the need to resort to liver transplantation. Amniotic membrane (AM) has emerged as an innovative therapeutic approach for chronic liver diseases due to its anti-inflammatory, antiscarring, and wound-healing effects. We have recently shown that AM can be used as a patch on the liver surface at the same time of fibrosis induction, resulting in significantly reduced progression and severity of biliary fibrosis. Here we investigated the effects of human AM on the established rat model of liver fibrosis, induced by the bile duct ligation (BDL). We also explored the effect of AM on the expression of transforming growth factor-1 (TGF-1), the main profibrogenic factor in hepatic fibrosis, and the proinflammatory cytokines, tumor necrosis factor- (TNF-), interleukin-6 (IL-6), and anti-inflammatory cytokine IL-10. Two weeks after BDL, the liver was covered with a fragment of AM or left untreated. Six weeks later, the fibrosis was first assessed by the semiquantitative Knodell and the METAVIR scoring systems and, thereafter, by CellProfiler digital image analysis to quantify the area occupied by collagen deposition, ductular reactions (DRs), activated myofibroblasts, and TGF-1. The hepatic cytokines were determined by ELISA. AM-treated rats showed a significantly lower score compared to the control BDL rats (2.50.9 vs. 3.50.3, respectively; p0.05). The collagen deposition, DRs, number of activated myofibroblasts, and TGF-1 were all reduced to about 50% of levels observed in untreated BDL rats. These findings suggest that AM, when applied as a patch onto the liver surface, is useful for treating well-established cholestatic fibrosis, and the mechanism was partly by means of downregulating the profibrotic factor TGF-1 and IL-6.


[Epidemiology of extrapulmonary tuberculosis].
The review paper presents data on the epidemiological features of extrapulmonary tuberculosis in Russia and other countries and on diagnostic problems. It considers the papers of the authors who propose different measures to enhance the efficiency of diagnosis of extrapulmonary tuberculosis.


Colorimetric and ratiometric pH responses by the protonation of phenolate within hemicyanine.
Compared to the nitrogen-reaction based pH optical responsive compounds, oxygen-reaction related pH sensors have attracted less attention. In this paper, hemicyanine based pH probes are designed by establishing the equilibrium between phenolate and phenol, and their reversible absorption and emission responses towards pH are evaluated. The indolium-phenol based tetramethylene hemicyanine (1a) has colorimetric responses at 455 and 578 nm due to the protonating and deprotonating processes; its emission spectra shows ratiometric changes at 594 and 654 nm with large Stokes shifts under acidic (139 nm) and basic conditions (76 nm). The bromide substituent of the hemicyanine (1b) has a lower pKa value compared with unsubstituted hemicyanine (1a), which suggests that adjustable pKa can be achieved by the modification of electron withdrawing groups. The theoretical calculations based on the density functional theory (DFT) were also used to explain the optical properties. Moreover, the in cellulo fluorescence imaging shows that the hemicyanine (1a) can be used for the detection of intracellular pH levels.


SCARECROW-LIKE23 and SCARECROW jointly specify endodermal cell fate but distinctly control SHORT-ROOT movement.
Intercellular signaling through trafficking of regulatory proteins is a widespread phenomenon in plants and can deliver positional information for the determination of cell fate. In the Arabidopsis root meristem, the cell fate determinant SHORT-ROOT (SHR), a GRAS domain transcription factor, acts as a signaling molecule from the stele to the adjacent layer to specify endodermal cell fate. Upon exiting the stele, SHR activates another GRAS domain transcription factor, SCARCROW (SCR), which, together with several BIRD/INDETERMINATE DOMAIN proteins, restricts movement of SHR to define a single cell layer of endodermis. Here we report that endodermal cell fate also requires the joint activity of both SCR and its closest homologue SCARECROW-LIKE23 (SCL23). We show that SCL23 protein moves with zonation-dependent directionality. Within the meristem, SCL23 exhibits short-ranged movement from ground tissue to vasculature. Away from the meristem, SCL23 displays long-range rootward movement into meristematic vasculature and a bidirectional radial spread, respectively. As a known target of SHR and SCR, SCL23 also interacts with SCR and SHR and can restrict intercellular outspread of SHR without relying on nuclear retention as SCR does. Collectively, our data show that SCL23 is a mobile protein that controls movement of SHR and acts redundantly with SCR to specify endodermal fate in the root meristem.


Efficient Algorithms for Genomic Duplication Models.
An important issue in evolutionary molecular biology is to discover genomic duplication episodes and their correspondence to the species tree. Existing approaches vary in the two fundamental aspects: the choice of evolutionary scenarios that model allowed locations of duplications in the species tree, and the rules of clustering gene duplications from gene trees into a single multiple duplication event. Here we study the method of clustering called minimum episodes for several models of allowed evolutionary scenarios with a focus on interval models in which every gene duplication has an interval consisting of allowed locations in the species tree. We present mathematical foundations for general genomic duplication problems. Next, we propose the first linear time and space algorithm for minimum episodes clustering jointly for any interval model and the algorithm for the most general model in which every evolutionary scenario is allowed. We also present a comparative study of different models of genomic duplication based on simulated and empirical datasets. We provided algorithms and tools that could be applied to solve efficiently minimum episodes clustering problems. Our comparative study helps to identify which model is the most reasonable choice in inferring genomic duplication events.


Temperament and relationships.
Temperamental characteristics of preschool children were related to relationships, mothers' mood, and children's feelings towards family members. Active scores were correlated with some problem behaviour and with negative aspects of interactions with mother and father. Active children felt themselves to be independent, while Timid children did not. Timid children had relatively more acute illnesses and worries and fears. Difficult scores were correlated with problem behaviour and with negative aspects of all the types of interaction assessed: mother-child, mother-father, father-child, and sibling-child. Furthermore, the more Difficult the child, the more Anxious, Outwardly Irritable, and Inwardly irritable the mother. In turn, Difficult children expressed relatively few positive and dependency feelings towards their mothers, and more negative feelings towards themselves.


Spectrum on demand light source (SOLS) for advanced photovoltaic characterization.
We report a multi-purpose spectrum-on-demand light source (SOLS), conceived primarily but not exclusively for the multiple and advanced characterization of photovoltaic (PV) materials and devices. The apparatus is a spectral shaper illumination device, providing a tunable and spectrally shaped light beam produced by modulating the intensity and/or wavelength range of a primary light source. SOLS stands out from the state of the art because it produces almost any spectrum on demand and delivers two types of output: a spectrally shaped and spatially homogeneous beam over its cross section for areal illumination or a spatially and spectrally split beam into its wavelength components, a unique capability suited to characterize lateral-tandem (Rainbow) solar cells. The tuneability from broadband to narrowband illumination enables two characterization devices into one, namely, a solar simulator for the determination of the power conversion efficiency and an external quantum efficiency measuring system. We expect the SOLS setup to accelerate material screening, enabling the discovery and optimization of novel multi-component materials and devices, in particular for emergent PV technologies like organic, metal halide perovskites, or multi-junction geometries, as well as novel PV applications such as indoors, building integrated, or agrivoltaics, among others.


The Impact of Web-Based Feedback on Physical Activity and Cardiovascular Health of Nurses Working in a Cardiovascular Setting: A Randomized Trial.
A disconcerting proportion of Canadian nurses are physically inactive and report poor cardiovascular health. Web-based interventions incorporating feedback and group features may represent opportune, convenient, and cost-effective methods for encouraging physical activity (PA) in order to improve the levels of PA and cardiovascular health of nurses. The purpose of this parallel-group randomized trial was to examine the impact of an intervention providing participants with feedback from an activity monitor coupled with a web-based individual, friend or team PA challenge, on the PA and cardiovascular health of nurses working in a cardiovascular setting. Methods: Nurses were randomly assigned in a 1:1:1 ratio to one of the following intervention "challenge" groups: (1) individual, (2) friend or (3) team. Nurses wore a Tractivity® activity monitor throughout a baseline week and 6-week intervention. Height, body mass, body fat percentage, waist circumference, resting blood pressure (BP) and heart rate were assessed, and body mass index (BMI) was calculated, during baseline and within 1 week post-intervention. Data were analyzed using descriptive statistics and general linear model procedures for repeated measures. Results: 76 nurses (97% female; age: 46 ± 11 years) participated. Weekly moderate-to-vigorous intensity PA (MVPA) changed over time (F = 4.022, df = 4.827, p = 0.002, η2 = 0.055), and was greater during intervention week 2 when compared to intervention week 6 (p = 0.011). Daily steps changed over time (F = 7.668, df = 3.910, p < 0.001, η2 = 0.100), and were greater during baseline and intervention weeks 1, 2, 3, and 5 when compared to intervention week 6 (p < 0.05). No differences in weekly MVPA or daily steps were observed between groups (p > 0.05). No changes in body mass, BMI or waist circumference were observed within or between groups (p > 0.05). Decreases in body fat percentage (-0.8 ± 4.8%, p = 0.015) and resting systolic BP (-2.6 ± 8.8 mmHg, p = 0.019) were observed within groups, but not between groups (p > 0.05). Conclusions: A web-based intervention providing feedback and a PA challenge initially impacted the PA, body fat percentage and resting systolic BP of nurses working in a cardiovascular setting, though increases in PA were short-lived. The nature of the PA challenge did not differentially impact outcomes. Alternative innovative strategies to improve and sustain nurses' PA should be developed and their effectiveness evaluated.


Molecular determinant for specific Ca/Ba selectivity profiles of low and high threshold Ca2+ channels.
Voltage-gated Ca(2+) channels (VGCC) play a key role in many physiological functions by their high selectivity for Ca(2+) over other divalent and monovalent cations in physiological situations. Divalent/monovalent selection is shared by all VGCC and is satisfactorily explained by the existence, within the pore, of a set of four conserved glutamate/aspartate residues (EEEE locus) coordinating Ca(2+) ions. This locus however does not explain either the choice of Ca(2+) among other divalent cations or the specific conductances encountered in the different VGCC. Our systematic analysis of high- and low-threshold VGCC currents in the presence of Ca(2+) and Ba(2+) reveals highly specific selectivity profiles. Sequence analysis, molecular modeling, and mutational studies identify a set of nonconserved charged residues responsible for these profiles. In HVA (high voltage activated) channels, mutations of this set modify divalent cation selectivity and channel conductance without change in divalent/monovalent selection, activation, inactivation, and kinetics properties. The Ca(V)2.1 selectivity profile is transferred to Ca(V)2.3 when exchanging their residues at this location. Numerical simulations suggest modification in an external Ca(2+) binding site in the channel pore directly involved in the choice of Ca(2+), among other divalent physiological cations, as the main permeant cation for VGCC. In LVA (low voltage activated) channels, this locus (called DCS for divalent cation selectivity) also influences divalent cation selection, but our results suggest the existence of additional determinants to fully recapitulate all the differences encountered among LVA channels. These data therefore attribute to the DCS a unique role in the specific shaping of the Ca(2+) influx between the different HVA channels.


Hip dysplasia in the African Bantu.
Dysplasia of the hip is almost unknown in the Bantu peoples of Africa, except in cases of arthrogryposis and in those with partly European ancestry. Evidence is produced to show that the importance of intrinsic genetic factors in hip dysplasia far outweighs that of the extrinsic factors. These are of great importance only if allowed to act on a hip in which genetic factors have already determined dysplasia. Evidence is also produced to contradict the theory that the "piggyback" carrying method used by Bantu mothers is the reason for the immunity from dysplasia of the hip. The absence of "primary" osteoarthritis of the hip is noted, and the range of hip disorders leading to "secondary" osteoarthritis in the adult African is compared with that in the adult European. Three patients are described, one in each of the groups mentioned above, the third having an isolated "typical" congenital dislocation of one hip. The methods of study used were enquiry into obstetric history and into carrying methods, and arthrography to confirm clinical findings. The experience of other surgeons working in Africa is recorded.


Diurnal variations in the content of preprocorticotropin-releasing hormone messenger ribonucleic acids in the hypothalamic paraventricular nucleus of rats of both sexes as measured by in situ hybridization.
The content of mRNA coding for the precursor of CRH in the hypothalamic paraventricular nucleus (PVH) was measured in intact male and estrogen-treated ovariectomized female rats at different times of the day using in situ hybridization histochemistry. Plasma corticosterone concentrations were measured in separate groups of animals at the same time points, with females showing higher levels than males at all times, and both sexes exhibiting the well characterized diurnal rhythm. There was a significant decrease (greater in females) in the content of prepro-CRH (ppCRH) mRNA between midday and midnight in rats of both sexes. Previous studies have demonstrated that the content of ppCRH mRNA in the PVH responds inversely to changes in the concentration of plasma corticosteroid in a concentration-dependent manner. The present study suggests that ppCRH mRNA in the PVH may respond in a similar way to fluctuating concentrations of plasma corticosterone throughout the day, and that although the exact mechanism remains to be elucidated, diurnal changes in the rate of CRH synthesis may be involved in the expression of diurnal rhythms within the hypothalamo-hypophysial-adrenal axis.


Blue and near-UV phosphorescence from iridium complexes with cyclometalated pyrazolyl or N-heterocyclic carbene ligands.
Two approaches are reported to achieve efficient blue to near-UV emission from triscyclometalated iridium(III) materials related to the previously reported complex, fac-Ir(ppz)(3) (ppz = 1-phenylpyrazolyl-N,C(2)'). The first involves replacement of the phenyl group of the ppz ligand with a 9,9-dimethyl-2-fluorenyl group, i.e., fac-tris(1-[(9,9-dimethyl-2-fluorenyl)]pyrazolyl-N,C(2)')iridium(III), abbreviated as fac-Ir(flz)(3). Crystallographic analysis reveals that both fac-Ir(flz)(3) and fac-Ir(ppz)(3) have a similar coordination environment around the Ir center. The absorption and emission spectra of fac-Ir(flz)(3) are red shifted from those of fac-Ir(ppz)(3). The fac-Ir(flz)(3) complex gives blue photoluminescence (PL) with a high efficiency (lambda(max) = 480 nm, phi(PL) = 0.38) at room temperature. The lifetime and quantum efficiency were used to determine the radiative and nonradiative rates (1.0 x 10(4) and 2.0 x 10(4) s(-1), respectively). The second approach utilizes N-heterocyclic carbene (NHC) ligands to form triscyclometalated Ir complexes. Complexes with two different NHC ligands, i.e., iridium tris(1-phenyl-3-methylimidazolin-2-ylidene-C,C(2)'), abbreviated as Ir(pmi)(3), and iridium tris(1-phenyl-3-methylbenzimidazolin-2-ylidene-C,C(2)'), abbreviated as Ir(pmb)(3), were both isolated as facial and meridianal isomers. Comparison of the crystallographic structures of the fac- and mer-isomers of Ir(pmb)(3) with the corresponding Ir(ppz)(3) isomers indicates that the imidazolyl-carbene ligand has a stronger trans influence than pyrazolyl and, thus, imparts a greater ligand field strength. Both fac-Ir(pmi)(3) and fac-Ir(pmb)(3) complexes display strong metal-to-ligand-charge-transfer absorption transitions in the UV (lambda = 270-350 nm) and phosphoresce in the near-UV region (E(0)(-)(0) = 380 nm) at room temperature with phi(PL) values of 0.02 and 0.04, respectively. The radiative decay rates for fac-Ir(pmi)(3) and fac-Ir(pmb)(3) (5 x 10(4) s(-1) and 18 x 10(4) s(-1), respectively) are somewhat higher than that of fac-Ir(flz)(3), but the nonradiative rates are two orders of magnitude faster (i.e., (2-4) x 10(6) s(-1)).


Recent advances in the immunology of chronic rejection.
Chronic allograft rejection is a slowly progressive, insidious process in which the host immune system continues to mount an immunological attack on a transplanted organ, ultimately resulting in the failure of the graft. To varying degrees, all solid organ grafts are at risk for chronic rejection and undergo a stereotypic process of injury and inflammation, eventually leading to parenchymal fibrosis. The clinical consequences of chronic rejection are particularly apparent in thoracic transplantation, where both patient and graft survival decline steadily over time and the opportunities for re-transplantation or long-term extracorporeal support are limited. A variety of antigen-dependent and antigen-independent factors are known to modulate the propensity for an organ to undergo chronic rejection. Recent clinical and laboratory research has suggested that distinct immunologic mechanisms may underlie the process of chronic rejection. Ultimately, strategies to induce long-term tolerance to alloantigens will be necessary to prevent chronic rejection and to abrogate the deleterious sequelae of chronic immunosuppression.


Aurora kinase B expression in breast carcinoma: cell kinetic and genetic aspects.
Mitotic deregulations may contribute significantly to cell division errors and the development of aggressive tumor cells. The mitotic kinase Aurora B is essential for chromosome segregation. Its gene is located at 17p13 in close proximity to the TP53 gene. Although the frequent alteration of this locus is well known, the information about the AURKB status and protein expression is limited. 50 breast carcinoma cases were evaluated for 17p13 status and chromosome 17 ploidy by FISH and for Aurora B protein by immunohistochemistry. Aurora B protein expression showed a strong correlation with cell proliferation (regression coefficient = 0.77). Therefore, the Aurora B/MIB-1 index was used as a measure of expression, which showed a wide range (1-35%, mean 0.32, SD ± 0.28). A gain in the 17p13 chromosome locus could not be shown while a deletion was stated in 10/50 cases including a subset with TP53 and AURKB codeletion in 6/10 cases. The loss of TP53/AURKB loci strongly correlated with aneusomy (p < 0.0001). Elevated Aurora B expression frequently occurs due to an increased cell proliferation rate in breast carcinoma. Codeletion of TP53 and AURKB at 17p13 indicates a concerted mechanism leading to the survival of cell clones with deficient mitotic kinase function which could contribute to the formation of aneuploid cells and an aggressive tumor phenotype.


Critical role for MyD88-mediated neutrophil recruitment during Clostridium difficile colitis.
Clostridium difficile can infect the large intestine and cause colitis when the normal intestinal microbiota is altered by antibiotic administration. Little is known about the innate immune signaling pathways that marshal inflammatory responses to C. difficile infection and whether protective and pathogenic inflammatory responses can be dissociated. Toll-like receptors predominantly signal via the MyD88 adaptor protein and are important mediators of innate immune signaling in the intestinal mucosa. Here, we demonstrate that MyD88-mediated signals trigger neutrophil and CCR2-dependent Ly6C(hi) monocyte recruitment to the colonic lamina propria (cLP) during infection, which prevent dissemination of bystander bacteria to deeper tissues. Mortality is markedly increased in MyD88-deficient mice following C. difficile infection, as are parameters of mucosal tissue damage and inflammation. Antibody-mediated depletion of neutrophils markedly increases mortality, while attenuated recruitment of Ly6C(hi) monocytes in CCR2-deficient mice does not alter the course of C. difficile infection. Expression of CXCL1, a neutrophil-recruiting chemokine, is impaired in the cLP of MyD88(-/-) mice. Our studies suggest that MyD88-mediated signals promote neutrophil recruitment by inducing expression of CXCL1, thereby providing critical early defense against C. difficile-mediated colitis.


Combination of Different Fecal Immunochemical Tests in Colorectal Cancer Screening: Any Gain in Diagnostic Performance?
A variety of fecal immunochemical tests (FITs) are used for colorectal cancer screening. FIT performance could be improved further. It is unclear, whether the combination of different FITs with different analytical characteristics (such as, different antibodies for the detection of fecal hemoglobin) can yield a better diagnostic performance. Fecal samples were obtained from 2042 participants of screening colonoscopy. All participants with advanced neoplasm (AN, colorectal cancer (n = 16) or advanced adenoma (n = 200)) and 300 randomly selected participants without AN were included. Nine quantitative FITs were evaluated simultaneously. Sensitivity and specificity was calculated for single tests (n = 9) and for their pairwise test combinations (n = 36) (requiring either both FITs (P++) or at least one FIT (P+) to be positive for defining a positive test result). Mean age of the participants (n = 516) was 63 (range: 50⁻79) years and 56% were men. At cutoffs yielding a specificity of 96.7% for single FITs, the median gain in specificity by P++ combination was +1.0%, whereas the median loss in sensitivity for AN was -4.2%. For P+ combination the median gain in sensitivity for AN was +2.8%, at a prize of median loss of -1.0% of specificity. Combinations of different FITs do not yield any relevant gain in diagnostic performance.


Multistage Anticoagulant Surfaces: A Synergistic Combination of Protein Resistance, Fibrinolysis, and Endothelialization.
Anticoagulant surface modification of blood-contacting materials has been shown to be effective in preventing thrombosis and reducing the dose of anticoagulant drugs that patients take. However, commercially available anticoagulant coatings, that is, both bioinert and bioactive coatings, are typically based on a single anticoagulation strategy. This puts the anticoagulation function of the coating at risk of failure during long-term use. Considering the several pathways of the human coagulation system, the synergy of multiple anticoagulation theories may provide separate, targeted effects at different stages of thrombosis. Based on this presumption, in this work, negatively charged poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol) methyl ether methacrylate) and positively charged poly(lysine-co-1-adamantan-1-ylmethyl methacrylate) were synthesized to construct matrix layers on the substrate by electrostatic layer-by-layer self-assembly (LBL). Amino-functionalized β-cyclodextrin (β-CD-PEI) was subsequently immobilized on the surface by host-guest interactions, and heparin was grafted. By adjusting the content of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), the interactions between modified surfaces and plasma proteins/cells were regulated. This multistage anticoagulant surface exhibits inertness at the initial stage of implantation, resisting nonspecific protein adsorption (POEGMA). When coagulation reactions occur, heparin exerts its active anticoagulant function in a timely manner, blocking the pathway of thrombosis. If thrombus formation is inevitable, lysine can play a fibrinolytic role in dissolving fibrin clots. Finally, during implantation, endothelial cells continue to adhere and proliferate on the surface, forming an endothelial layer, which meets the blood compatibility requirements. This method provides a new approach to construct a multistage anticoagulant surface for blood-contacting materials.


A video-game-based method to induce states of high and low flow.
Flow has been defined as a state of full immersion that may emerge when the skills of a person match the challenge of an activity. It is a special case of being on task, as during flow, keeping focused on the task feels effortless. Most experimental investigations of the neural or physiological correlates of flow contrast conditions with different levels of challenge. Yet comparing different levels of challenge that are too distant may trigger states where the participant is off task, such as boredom or frustration. Thus, it remains unclear whether previously observed differences ascribed to flow may rather reflect differences in how much participants were on task-trying their best-across the contrasted conditions. To remedy this, we introduce a method to manipulate flow by contrasting two video game play conditions at personalized levels of difficulty calibrated such that participants similarly tried their best in both conditions. Across three experiments (> 90 participants), higher flow was robustly reported in our high-flow than in our low-flow condition (mean effect size d = 1.31). Cardiac, respiratory, and skin conductance measures confirmed the known difference between a period of rest and the two on-task conditions of high and low flow, but failed to distinguish between these latter two. In light of the conflicting findings regarding the physiological correlates of flow, we discuss the importance of ensuring a low-flow baseline condition that maintains participants on task, and propose that the present method provides a methodological advance toward that goal.


Intermittent PTH administration improves alveolar bone formation in type 1 diabetic rats with periodontitis.
Periodontitis is an infectious disease that manifests as alveolar bone loss surrounding the roots of teeth. Diabetes aggravates periodontitis-induced alveolar bone loss via suppression of bone formation. Intermittent parathyroid hormone (PTH) administration displays an anabolic effect on bone. In this study, we investigated the effect of intermittent PTH administration on alveolar bone loss in type 1 diabetic rats with periodontitis. Rats were divided into control (C), periodontitis (P), periodontitis treated with PTH (P + PTH), diabetes with periodontitis (DP), and diabetes with periodontitis treated with PTH (DP + PTH) groups. To induce type 1 diabetes, rats were injected with streptozotocin and periodontitis was induced bilaterally by applying ligatures to the mandibular first molars for 30 days. During the experimental period, the P + PTH and DP + PTH groups were subcutaneously injected with PTH (40 μg/kg) three times per week, whereas the C, P, and DP groups were injected with citrate buffer. To observe the mineralization of the alveolar bone, the DP and DP + PTH groups were injected with calcein on days 10 and 27, and with alizarin red on day 20. Thirty days after ligation, histological findings and fluorescence labeling were analyzed in the furcations of the mandibular first molars. Sclerostin-positive osteocytes were assessed by immunohistochemical analyses. The DP groups had smaller areas of alveolar bone than the other groups, and the DP + PTH group had a larger alveolar bone area than the DP group. The DP group had less osteoid formation than the C group, whereas the DP + PTH had greater osteoid formation than the DP group. Fluorescence labeling results revealed that the DP + PTH group had more mineral deposition on the alveolar bone than the DP group. The DP + PTH group exhibited lower percentage of sclerostin-positive osteocytes in alveolar bone than the DP group. Intermittent PTH administration diminishes alveolar bone loss and sclerostin expression in osteocytes, but increases osteoid formation and mineralization, suggesting that intermittent PTH administration attenuates diabetes-aggravated alveolar bone loss by the induction of bone formation. PTH-induced bone formation may be related to the regulation of osteocytic sclerostin expression in type 1 diabetic rats with periodontitis.


Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia.
Decreased plasma high-density-lipoprotein (HDL) cholesterol and apolipoprotein A-I levels have been associated with premature coronary artery disease. We identified a PstI restriction-endonuclease site flanking the human apolipoprotein A-I gene at its 3' end that is polymorphic. The absence and presence of this site, as determined by genomic blotting analysis of PstI-digested chromosomal DNA with the use of an apolipoprotein A-I gene probe, were associated with 3.3-kb and 2.2-kb hybridization bands, respectively. The 3.3-kb band appeared in 4.1 percent of 123 randomly selected control subjects and in 3.3 percent of 30 subjects with no angiographic evidence of coronary artery disease. In contrast, among 88 patients who had severe coronary disease before the age of 60, as documented by angiography, the 3.3-kb band occurred in 32 percent (P less than 0.0001). It was also found in 8 of 12 index cases (P less than 0.0001) of kindreds with familial hypoalphalipoproteinemia. In the two patient groups, the allele frequencies of the site that produced the 3.3-kb band were 17 and 42 percent, respectively, as compared with an allele frequency of only 2 percent in the control populations. Within kindreds with familial hypoalphalipoproteinemia and among first-degree relatives of patients with coronary artery disease, the 3.3-kb band was associated with decreased HDL cholesterol levels. Among all patients with coronary artery disease, 58 percent had HDL cholesterol levels below the 10th percentile of normal values; however, this frequency increased to 73 percent when patients with the 3.3-kb band were considered. These findings indicate that the polymorphism in the region between the apolipoprotein A-I and apolipoprotein C-III genes may be a useful marker for the risk of premature coronary artery disease and familial hypoalphalipoproteinemia.


Solid-state NMR and short-range order in crystalline oxides and silicates: a new tool in paramagnetic resonances.
Most applications of high-resolution NMR to questions of short-range order/disorder in inorganic materials have been made in systems where ions with unpaired electron spins are of negligible concentration, with structural information extracted primarily from chemical shifts, quadrupolar coupling parameters, and nuclear dipolar couplings. In some cases, however, the often-large additional resonance shifts caused by interactions between unpaired electron and nuclear spins can provide unique new structural information in materials with contents of paramagnetic cations ranging from hundreds of ppm to several per cent and even higher. In this brief review we focus on recent work on silicate, phosphate, and oxide materials with relatively low concentrations of paramagnetic ions, where spectral resolution can remain high enough to distinguish interactions between NMR-observed nuclides and one or more magnetic neighbors in different bonding configurations in the first, second, and even farther cation shells. We illustrate the types of information available, some of the limitations of this approach, and the great prospects for future experimental and theoretical work in this field. We give examples for the effects of paramagnetic transition metal, lanthanide, and actinide cation substitutions in simple oxides, pyrochlore, zircon, monazite, olivine, garnet, pyrochlores, and olivine structures.


Effect of puboprostatic ligament preservation during robotic-assisted laparoscopic radical prostatectomy on early continence: Randomized controlled trial.
To prove the effectiveness of puboprostatic ligament-preserving robotic-assisted laparoscopic radical (RARP) on enhancing early continence. Ninety-two patients with localized adenocarcinoma of the prostate scheduled for RARP from April 2018 to January 2019 were prospectively single-blinded and randomized into two groups, standard RARP (Group A) and puboprostatic ligament-sparing RARP (Group B). The outcomes were continent status at Foley catheter removal and 3 months after surgery using the score from the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF), pad usage, pathological margin status, blood loss, operative time, and complications. Ninety-six patients were randomized (46 patients in each group), with a mean±SD age of 67.30±6.07 years. There were no differences in baseline characteristics. At 3 months after surgery, ICIQ-UI SF score (mean±SD) in Group A was significantly higher than Group B (8.74±4.28 vs. 6.93±3.96, p=0.038) but no difference at Foley catheter removal. Group A also had a significant higher score for interference with daily life (median [interquartile range, IQR]: 4 [1, 5] vs. 2 [0, 4]; p=0.041) and higher pad use (median [IQR]: 2 [0, 3] vs. 1 [1, 2]; p=0.041) at 3 months. One case in Group A had complete or severe incontinence (>5 pads/day) at 3 months. Groups A and B did not exhibit significant difference in margin status (p=0.828). There were no differences in operative time, blood loss, drain output or complications. Use of puboprostatic ligament-sparing RARP could be a method to accelerate early continence without affecting the final oncological outcome.


Microinjected profilin affects cytoplasmic streaming in plant cells by rapidly depolymerizing actin microfilaments.
Cytoplasmic streaming is a conspicuous feature of plant cell behaviour, in which organelles and vesicles shuttle along cytoplasmic strands that contain actin filaments. The mechanisms that regulate streaming and the formation of actin filament networks are largely unknown, but in all likelihood involve actin-binding proteins. The monomeric actin-binding protein, profilin, is a key regulator of actin-filament dynamics in animal cells and it has recently been identified in plants as a pollen allergen. We set out to determine whether plant profilin can act as a monomeric actin-binding protein and influence actin dynamics in plant cells in vivo. Recombinant birch-pollen profilin was purified by polyproline affinity chromatography and microinjected into Tradescantia blossfeldiana stamen hair cells. After profilin injection, a rapid and irreversible change in cellular organization and streaming was observed: within 1-3 minutes the transvacuolar cytoplasmic strands became thinner and snapped, and cytoplasmic streaming ceased. Fluorescein-labelled-phalloidin staining confirmed that this was due to depolymerization of actin filaments. To confirm that the effects observed were due to sequestration of monomeric actin, another monomeric actin-binding protein, DNase I, was injected and found to produce comparable results. Profilin can act as a potent regulator of actin organization in living plant cells. Its rapid effect on the integrity of cytoplasmic strands and cytoplasmic streaming supports a model in which organelle movements depend upon microfilaments that exist in dynamic equilibrium with the pool of monomeric actin.


Super-Stable, High-Quality Fe3 O4 Dendron-Nanocrystals Dispersible in Both Organic and Aqueous Solutions.
High-quality Fe3 O4 nanocrystals coated with stearate groups are successfully converted to dendron-coated nanocrystals (dendron-nanocrystals). Poly(ethylene glycol) oligomers are used as major terminal groups for the dendron ligands, which afford excellent dispersibility of the dendron-nanocrystals in a broad spectrum of solvents, ranging from dichloromethane to water.


A new experimental model for gallstone pancreatitis: short-termed pancreatico-biliary duct obstruction and exocrine stimulation with systemic hypotension in rats.
The effects of short-termed (2 hours) obstruction of pancreatico-biliary duct (PBDO) and exocrine stimulation (IDH) by caerulein infusion (0.2 microgram/kg.hr) with systemic hypotension (SH) (30% reduction of mean arterial pressure for 30 min) on the exocrine pancreas were evaluated in the rat. PBDO and IDH with SH caused more significant rises in portal serum amylase, cathepsin B and malate dehydrogenase levels, and pancreatic water content as well as more significant redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction in the subcellular fractionations than only PBDO, or PBDO with IDH, or PBDO with SH group. In addition, more accelerated lysosomal and mitochondrial fragility were observed in the PBDO and IDH with SH group. Moreover, PBDO and IDH with SH caused an activation of larger amount of trypsinogen in the pancreas compared with other groups (PBDO with IDH and PBDO with SH group). These results indicate that present model of short-termed PBDO and exocrine stimulation with systemic hypotension seems to be pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries by PBDO, particularly with exocrine stimulation and pancreatic ischaemia, probably via activation of trypsinogen to trypsin by lysosomal enzyme such as cathepsin B.


Clinical effects of diflunisal and paracetamol in impacted mandibular third molar surgery.
A double-blind, randomized, cross-over study to compare diflunisal and paracetamol for postoperative pain, swelling and trismus relief following impacted mandibular third molar surgery was designed. 25 patients received one of the drugs at one visit and the alternative at the other visit. First doses were given two hours preoperatively and continued twice daily for five days. The study was carried out to determine the effect of preoperatively used diflunisal on postoperative pain after surgical removal of the third molars as compared to paracetamol used in a similar manner. The degree of impaction, pain, swelling and mouth opening were assessed by standardized methods and possible adverse effects were also recorded separately. Statistical analysis was carried out by "Student's t test". (p < 0.01 statistically significant).


Use of captopril to reduce serum lipids in hypertensive patients with hyperlipidemia.
The effects on serum lipids of substituting captopril for other antihypertensive drugs were evaluated in 24 essential hypertensives with stable hypercholesterolemia (total cholesterol 250 to 350 mg/dL). Captopril, 50 mg bid, was substituted for one of the nondiuretic drugs the patients were already taking. Patients on a diuretic continued the same diuretic at the same dosage. After 6 months of treatment including captopril, patients returned for 3 months to their previous therapeutic scheme (rechallenge). Treatment with captopril caused a reduction in total cholesterol (-18%) and triglycerides (-26%) and an increase in high-density lipoprotein (HDL) cholesterol (+27%). When patients returned to their precaptopril therapy, total and HDL cholesterol returned to precaptopril values. These effects of captopril on lipid profile of hypertensive patients with hypercholesterolemia could be important for the reduction of cardiovascular complications in treated hypertensives.


HiPub: translating PubMed and PMC texts to networks for knowledge discovery.
We introduce HiPub, a seamless Chrome browser plug-in that automatically recognizes, annotates and translates biomedical entities from texts into networks for knowledge discovery. Using a combination of two different named-entity recognition resources, HiPub can recognize genes, proteins, diseases, drugs, mutations and cell lines in texts, and achieve high precision and recall. HiPub extracts biomedical entity-relationships from texts to construct context-specific networks, and integrates existing network data from external databases for knowledge discovery. It allows users to add additional entities from related articles, as well as user-defined entities for discovering new and unexpected entity-relationships. HiPub provides functional enrichment analysis on the biomedical entity network, and link-outs to external resources to assist users in learning new entities and relations. HiPub and detailed user guide are available at http://hipub.korea.ac.kr firstname.lastname@example.com, email@example.com Supplementary data are available at Bioinformatics online.


How Ready are Pediatricians and Family Physicians in Saudi Arabia to Perform Clinical Screening of Developmental Dysplasia of the Hip?
Developmental dysplasia of the hip (DDH) is one of the most common hip pathologies in pediatric age group and late diagnosis remains a major concern in Saudi Arabia. The aim of this study is to examine the ability of Saudi Arabian pediatricians and family physicians to conduct clinical screening for (DDH) by estimating their clinical knowledge and skills and analyzing the gaps therein to determine whether there is potential to launch a national screening protocol for DDH in Saudi Arabia. This is a multicenter cross-sectional study from three major regions in Saudi Arabia (Central, Eastern and Western provinces). The assessed aspects are risk factors, age of screening, incidence in Saudi Arabia, physical signs and diagnostic markers, and treatment, along with their 'clinical knowledge and skills' score. Half of the participants were pediatricians, while the rest were family physicians. More than a third of the participants were considered to have adequate knowledge, ie, above the mean score. Dimensions with the most significant knowledge gaps included the incidence of DDH in Saudi Arabia, adverse effects of swaddling, and the management of a high-risk infants presenting with a negative physical examination. Additionally, there were relatively low rates of awareness regarding positive risk factors as well as a generally poor ability to identify physical signs. Clinical knowledge and skill levels were significantly lower among family physicians. Pediatricians and family physicians in Saudi Arabia still need further training to improve their clinical skills for DDH screening. The proper administration of training programs could eventually enable the gradual implementation of a national systematic screening program.


Paenarthrobacter sp. GOM3 Is a Novel Marine Species With Monoaromatic Degradation Relevance.
Paenarthrobacter sp. GOM3, which is a strain that represents a new species-specific context within the genus Paenarthrobacter, is clearly a branched member independent of any group described thus far. This strain was recovered from marine sediments in the Gulf of Mexico, and despite being isolated from a consortium capable of growing with phenanthrene as a sole carbon source, this strain could not grow successfully in the presence of this substrate alone. We hypothesized that the GOM3 strain could participate in the assimilation of intermediate metabolites for the degradation of aromatic compounds. To date, there are no experimental reports of Paenarthrobacter species that degrade polycyclic aromatic hydrocarbons (PAHs) or their intermediate metabolites. In this work, we report genomic and experimental evidence of metabolic benzoate, gentisate, and protocatechuate degradation by Paenarthrobacter sp. GOM3. Gentisate was the preferred substrate with the highest volumetric consumption rate, and genomic analysis revealed that this strain possesses multiple gene copies for the specific transport of gentisate. Furthermore, upon analyzing the GOM3 genome, we found five different dioxygenases involved in the activation of aromatic compounds, suggesting its potential for complete remediation of PAH-contaminated sites in combination with strains capable of assimilating the upper PAH degradation pathway. Additionally, this strain was characterized experimentally for its pathogenic potential and in silico for its antimicrobial resistance. An overview of the potential ecological role of this strain in the context of other members of this taxonomic clade is also reported.


[The CRF test in psychiatry. Preliminary studies].
The HPA axis exploration in the endogenous depressions indicates an hyperactivity of this system. But the reason of this perturbation is not definite. The corticotropin-releasing factor (CRF) test has been described from research work carried out by Vale et al. In the endogenous depressions, this test enables us to specify physiopathological factors of the HPA axis dysfunction. Some research suggest an hypothalamic and limbic CRF hypersecretion in the endogenous depressions. But the results are not consistent principally because of the diversity of technical protocols. So the authors try to take stock of the CRF test specificity. They report the results obtained after 100 micrograms o-CRF intravenous administration in 7 voluntary normal men.


Suicide reconstruction by glue-lift of gunshot residue.
Based upon the recently developed glue-lift collection of gunshot residue particles for examination in the scanning electron microscope with energy dispersive X-rays, this laboratory has undertaken a research program to determine if reconstruction of gunshot deaths is feasible. Because undisturbed conditions of suicide victims may help in securing unambiguous results and high success rates, the program has been carried out to reconstruct suicides only. Data obtained from 13 firearms suicides and their laboratory reconstruction which involved primarily shotguns and handguns, indicate that reconstruction can be immensely useful to interpretation of the gunshot residue distributions on a suspect's or victim's hands. This reports outlines the basic experiments performed to relate the residue emission from the gun to the deposits found on the firing hand(s) and a description of the reconstruction technique that uses a target to simulate a human body. The technique can determine the specifics of a victim's hand position at the time of firing and which hand was used to pull the trigger. Because the technique is sensitive to the nature of the grasp of the firing hand and of the supporting hand, in the case of a shotgun, it has been possible in all cases to date, to determine which one of the potential eight hand positions existed at the time of shooting.


Influence of young adult cognitive ability and additional education on later-life cognition.
How and when education improves cognitive capacity is an issue of profound societal importance. Education and later-life education-related factors, such as occupational complexity and engagement in cognitive-intellectual activities, are frequently considered indices of cognitive reserve, but whether their effects are truly causal remains unclear. In this study, after accounting for general cognitive ability (GCA) at an average age of 20 y, additional education, occupational complexity, or engagement in cognitive-intellectual activities accounted for little variance in late midlife cognitive functioning in men age 56-66 (n = 1009). Age 20 GCA accounted for 40% of variance in the same measure in late midlife and approximately 10% of variance in each of seven cognitive domains. The other factors each accounted for <1% of the variance in cognitive outcomes. The impact of these other factors likely reflects reverse causation-namely, downstream effects of early adult GCA. Supporting that idea, age 20 GCA, but not education, was associated with late midlife cortical surface area (n = 367). In our view, the most parsimonious explanation of our results, a meta-analysis of the impact of education, and epidemiologic studies of the Flynn effect is that intellectual capacity gains due to education plateau in late adolescence/early adulthood. Longitudinal studies with multiple cognitive assessments before completion of education would be needed to confirm this speculation. If cognitive gains reach an asymptote by early adulthood, then strengthening cognitive reserve and reducing later-life cognitive decline and dementia risk may really begin with improving educational quality and access in childhood and adolescence.


Enhanced Thermoelectric Cooling through Introduction of Material Anisotropy in Transverse Thermoelectric Composites.
Transverse thermoelectric materials can achieve appreciable cooling power with minimal space requirement. Among all types of material candidates for transverse thermoelectric applications, composite materials have the best cooling performance. In this study, anisotropic material properties were applied to the component phase of transverse thermoelectric composites. A mathematical model was established for predicting the performance of fibrous transverse thermoelectric composites with anisotropic components. The mathematical model was then validated by finite element analysis. The thermoelectric performance of three types of composites are presented, each with the same set of component materials. For each type of component, both anisotropic single-crystal and isotropic polycrystal material properties were applied. The results showed that the cooling capacity of the system was improved by introducing material anisotropy in the component phase of composite. The results also indicated that the orientation of the anisotropic component's property axis, the anisotropic characteristic of a material, will significantly influence the thermoelectric performance of the composite. For a composite material consisting of Copper fiber and Bi2Te3 matrix, the maximum cooling capacity can vary as much as 50% at 300 K depending on the property axis alignment of Bi2Te3 in the composite. The composite with Copper and anisotropic SnSe single crystal had a 51% improvement in the maximum cooling capacity compared to the composite made of Copper and isotropic SnSe polycrystals.


In vitro studies of the modulatory effects of sensory neuropeptides on peripheral blood mononuclear leukocytes of normal and allergic subjects.
The purpose of the present study was to evaluate the modulatory effects of sensory neuropeptides on peripheral blood mononuclear leukocytes of normal and allergic subjects. Peripheral blood mononuclear leukocytes obtained from five normal subjects and from five patients with allergic rhinitis and asthma were incubated with morphine, ACTH, vasoactive intestinal peptide, or substance P at concentrations of 10(-9) M, 10(-7) M, 10(-6) M and suboptimal (0.0125 microgram/mL, 0.025 microgram/mL, and 0.05 microgram/mL) concentrations of PHA. Uptake of 3H-thymidine was evaluated at 72 hours of culture. An inhibitory effect was observed with morphine, ACTH, and substance P while stimulatory effects were seen with vasoactive intestinal peptide, both in normal and in allergic subjects. The results of these preliminary studies provide further evidence for a modulatory role of neuropeptides on the immune function in both normal and allergic subjects.


Ignorance of family planning methods in India: an important constraint on use.
Interviews wih women in six villages in India and with educated, working women selected to be trained as interviewers in five states, and evidence from formal studies are discussed to support the conclusions that (1) the low overall rates of contraceptive use in India are at least partly due to low levels of knowledge about different methods of birth control, especially of the modern reversible methods; and (2) the low use of all methods except sterilization is a good proxy for lack of knowledge about these methods. It is suggested that, both in the interests of achieving demographic targets and in the interests of the clientele of the family planning program, much greater emphasis must be placed on spreading practical information about reversible contraception. The information dissemination activities of the program so far have tended to concentrate on the why of family planning and neglect the how, except in promoting sterilization.


Factors Associated With COVID-19 Hospitalizations and Deaths in French Nursing Homes.
To describe the clinical characteristics and management of residents in French nursing homes with suspected or confirmed coronavirus disease 2019 (COVID-19) and to determine the risk factors for COVID-19-related hospitalization and death in this population. A retrospective multicenter cohort study. Four hundred eighty nursing home residents with suspected or confirmed COVID-19 between March 1 and May 20, 2020, were enrolled and followed until June 2, 2020, in 15 nursing homes in Marseille's greater metropolitan area. Demographic, clinical, laboratory, treatment type, and clinical outcome data were collected from patients' medical records. Multivariable analysis was used to determine factors associated with COVID-19-related hospitalization and death. For the former, the competing risk analysis-based on Fine and Gray's model-took death into account. A total of 480 residents were included. Median age was 88 years (IQR 80-93), and 330 residents were women. A total of 371 residents were symptomatic (77.3%), the most common symptoms being asthenia (47.9%), fever or hypothermia (48.1%), and dyspnea (35.6%). One hundred twenty-three patients (25.6%) were hospitalized and 96 (20%) died. Male gender [specific hazard ratio (sHR) 1.63, 95% confidence interval (CI) 1.12-2.35], diabetes (sHR 1.69, 95% CI 1.15-2.50), an altered level of consciousness (sHR 2.36, 95% CI 1.40-3.98), and dyspnea (sHR 1.69, 95% CI 1.09-2.62) were all associated with a greater risk of COVID-19-related hospitalization. Male gender [odds ratio (OR) 6.63, 95% CI 1.04-42.39], thermal dysregulation (OR 2.64, 95% CI 1.60-4.38), falls (2.21 95% CI 1.02-4.75), and being aged >85 years (OR 2.36, 95% CI 1.32-4.24) were all associated with increased COVID-19-related mortality risk, whereas polymedication (OR 0.46, 95% CI 0.27-0.77) and preventive anticoagulation (OR 0.46, 95% CI 0.27-0.79) were protective prognostic factors. Male gender, being aged >85 years old, diabetes, dyspnea, thermal dysregulation, an altered level of consciousness, and falls must all be considered when identifying and protecting nursing home residents who are at greatest risk of COVID-19-related hospitalization and death.


Cross-platform gene expression signature of human spermatogenic failure reveals inflammatory-like response.
The molecular basis of human testicular dysfunction is largely unknown. Global gene expression profiling of testicular biopsies might reveal an expression signature of spermatogenic failure in azoospermic men. Sixty-nine individual testicular biopsy samples were analysed on two microarray platforms; selected genes were validated by quantitative real-time PCR and immunohistochemistry. A minimum of 188 transcripts were significantly increased on both platforms. Their levels increased with the severity of spermatogenic damage and reached maximum levels in samples with Sertoli-cell-only appearance, pointing to genes expressed in somatic testicular cells. Over-represented functional annotation terms were steroid metabolism, innate defence and immune response, focal adhesion, antigen processing and presentation and mitogen-activated protein kinase K signalling pathway. For a considerable proportion of genes included in the expression signature, individual transcript levels were in keeping with the individual mast cell numbers of the biopsies. When tested on three disparate microarray data sets, the gene expression signature was able to clearly distinguish normal from defective spermatogenesis. More than 90% of biopsy samples clustered correctly into the corresponding category, emphasizing the robustness of our data. A gene expression signature of human spermatogenic failure was revealed which comprised well-studied examples of inflammation-related genes also increased in other pathologies, including autoimmune diseases.


Circular Penile Skin Fasciocutaneous Ventral Onlay Flap Urethroplasty as an Alternative to Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Complex Long-Segment Urethral Stricture: A Retrospective Study.
Background A urethral stricture is the narrowing of the urethra that results in symptoms of obstruction. It can appear anywhere along the male urethra's length and has a variety of causes. The circular penile fasciocutaneous flap is employed in the successful single-stage reconstruction of long-segment complex anterior urethral strictures especially when the buccal mucosa is unavailable due to various reasons. The study has tried to identify a surgical technique that is more beneficial for the treatment of urethral strictures. Objective The objective of this research was to evaluate the outcomes of circular penile skin fasciocutaneous ventral onlay flap urethroplasty (group A) and the outcomes of dorsal onlay buccal mucosal graft urethroplasty (group B) in the management of complex long-segment penile urethral stricture. Methods In this retrospective study between December 2012 and December 2022, 60 patients with long-segment complex penile urethral stricture who underwent urethroplasty at our center were evaluated. Patients were divided into two groups according to the flap used (dorsal onlay buccal mucosal graft urethroplasty was used in 30 patients (group B), and circular penile fasciocutaneous flap (single stage) was used in 30 patients (group A)). The success rate and the mean peak flow rate were also calculated post-operation to identify the effectiveness of the surgical procedure used for urethral strictures. Results The study consisted of 60 patients in total. Group A's mean age was determined to be 51.2±16.2 years, whereas group B's mean age was determined to be 40.7±16.8 years. Preoperatively, the median urethral stricture length was 69 mm in group A (range: 20-100 mm) and 56 mm in group B (range: 30-110 mm). The intraoperative median length of the urethral stricture was 82 mm in group A (range: 20-120 mm) and 65 mm in group B (range: 40-140 mm). The mean peak flow rate was 30.9±6.8 mL/s in group A compared to 18.1±4.9 mL/s in group B. The success rate for group A was 89.7%, while the success rate for group B was 75.9%. Conclusion For complex long-segment urethral strictures, circular penile skin fasciocutaneous ventral onlay flap urethroplasty has a higher rate of success and fewer complications than dorsal onlay buccal mucosal graft urethroplasty. Along with success rate, it has a better mean peak flow rate and lower complications.


Diagnosis of post-traumatic complex regional pain syndrome of the hand: current role of sympathetic skin response and three-phase bone scintigraphy.
To evaluate the role of sympathetic skin response (SSR) and three-phase bone scintigraphy (TPBS) in the diagnosis of complex regional pain syndrome (CRPS). 60 patients with CRPS of the hand were recruited. TPBS was performed using a bolus injection of 20 mCi of Tc-99m methylene diphosphonate in an antecubital vein and blood flow (first phase) image, blood pool (second phase) image, and delayed (third phase) image obtained. Patients were considered to have CRPS when the blood pool and blood flow images showed diffuse asymmetric uptake, or when the delayed image indicated increased asymmetric periarticular uptake. SSR was measured simultaneously in the affected and unaffected hands. Standard surface electromyogram disc electrodes were applied to the palm and dorsum of both hands. Electrical stimuli were applied to the skin at the base of little and ring fingers of the unaffected hand. Patients were considered abnormal when response was absent or the peak-to-peak amplitude was <50% of the contralateral hand in at least 2 readings. The delayed phase of TPBS tested positive in all; the first and second phases tested positive in 54 (90%) and 56 (93%) of the patients, respectively. Four of the 6 patients with a negative first phase had had symptoms persisting for more than 6 months, and the other 2 for about 3 to 6 months. No patient presenting within 3 months had a negative scan. SSR was absent in 16 (27%) patients and normal in 44 (73%). 11 (79%) of 14 patients who presented more than 6 months after symptom onset displayed an abnormal SSR, while only 10% of those presenting within 3 to 6 months and 11% of those presenting within 3 months had an abnormal SSR. 12 (75%) of the 16 patients with abnormal SSR had associated decreased sweating, compared with 2 (4.5%) of the 44 patients with a normal SSR. TPBS is a very sensitive corroborative test to confirm the clinical suspicion of CRPS during the initial stages, but not in late cases. SSR can be used to document the sympathetic dysfunction in cases having an associated sweating abnormality and may have some diagnostic value in late cases of CRPS, when TPBS is less reliable.


Female gonadal hormone effects on microglial activation and functional outcomes in a mouse model of moderate traumatic brain injury.
To address the hypothesis that young, gonad-intact female mice have improved long-term recovery associated with decreased neuroinflammation compared to male mice. Eight to ten week-old male, female, and ovariectomized (OVX) mice underwent closed cranial impact. Gonad-intact female mice were injured only in estrus state. After injury, between group differences were assessed using complementary immunohistochemical staining for microglial cells at 1 h, mRNA polymerase chain reaction for inflammatory markers at 1 h after injury, Rotarod over days 1-7, and water maze on days 28-31 after injury. Male mice had a greater area of injury (P = 0.0063), F4/80-positive cells (P = 0.032), and up regulation of inflammatory genes compared to female mice. Male and OVX mice had higher mortality after injury when compared to female mice (P = 0.043). No group differences were demonstrated in Rotarod latencies (P = 0.62). OVX mice demonstrated decreased water maze latencies compared to other groups (P = 0.049). Differences in mortality, long-term neurological recovery, and markers of neuroinflammation exist between female and male mice after moderate traumatic brain injury (MTBI). Unexpectedly, OVX mice have decreased long term neurological function after MTBI when compared to gonad intact male and female mice. As such, it can be concluded that the presence of female gonadal hormones may influence behavioural outcomes after MTBI, though mechanisms involved are unclear.


Properties of red cell ghost preparations susceptible to invasion by malaria parasites.
Experimental procedures are described that lead to the formation of sealed red cell ghosts capable of efficient invasion by malaria parasites. Both human and monkey cells have been studied with respect to invasion by Plasmodium falciparum and P. knowlesi respectively. Resealed ghosts containing about half the normal concentration of haemoglobin are prepared by osmotic lysis and resealing at a haematocrit of 70%. When examined in the scanning electron microscope, populations of these ghosts contain few echinocytes, but have an abundance of stomatocytic forms. When undiluted haemolysate is substituted for the aqueous saline diluent, in which the cells are suspended for lysis and resealing, discocytes result, with a morphology very similar to that of the original cells. Invasion is somewhat, but not dramatically higher for this material. An investigation of the effect of intracellular potassium concentration revealed that this had no major effect on invasion. A small increase in invasion resulted from addition of 50 or 100 mg/ml of albumin to the medium in which the cells were resealed, but intra-erythrocytic protein content per se is evidently not a major factor in determining the efficiency of invasion. Augmentation of the cytoplasmic ATP concentration during lysis and resealing increased the level of parasitaemia significantly, and the parasites in these ghosts developed normally and gave rise to viable merozoites. It was found that albumin at certain concentrations passed freely into the lysed cells and reached equilibrium with that in the external medium. By contrast, the high molecular weight solute Blue Dextran 2000 was completely excluded from the lysed cells.


The impact of 27-hydroxycholesterol on endometrial cancer proliferation.
Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X receptor (LXR) and a selective oestrogen receptor modulator (SERM). Exposure to oestrogenic ligands increases risk of developing EC; however, the impact of 27HC on EC is unknown. Samples of stage 1 EC (n = 126) were collected from postmenopausal women undergoing hysterectomy. Expression of LXRs (NR1H3, LXRα; NR1H2, LXRβ) and enzymes required for the synthesis (CYP27A1) or breakdown (CYP7B1) of 27HC were detected in all grades of EC. Cell lines originating from well-, moderate- and poorly-differentiated ECs (Ishikawa, RL95, MFE 280 respectively) were used to assess the impact of 27HC or the LXR agonist GW3965 on proliferation or expression of a luciferase reporter gene under the control of LXR- or ER-dependent promoters (LXRE, ERE). Incubation with 27HC or GW3965 increased transcription via LXRE in Ishikawa, RL95 and MFE 280 cells (P < 0.01). 27HC selectively activated ER-dependent transcription (P < 0.001) in Ishikawa cells and promoted proliferation of both Ishikawa and RL95 cells (P < 0.001). In MFE 280 cells, 27HC did not alter proliferation but selective targeting of LXR with GW3965 significantly reduced cell proliferation (P < 0.0001). These novel results suggest that 27HC can contribute to risk of EC by promoting proliferation of endometrial cancer epithelial cells and highlight LXR as a potential therapeutic target in the treatment of advanced disease.


Characterization of Antagonistic Bacteria Paenibacillus polymyxa ZYPP18 and the Effects on Plant Growth.
Paenibacillus polymyxa is a plant growth-promoting rhizobacteria (PGPR) that has significant biocontrol properties. Wheat sheath blight caused by Rhizoctonia cerealis is a significant soil-borne disease of wheat that causes significant losses in wheat production, and the biological control against the disease has received extensive attention. P. polymyxa ZYPP18 was identified using morphological and molecular characterization. An antagonistic activity experiment verified that ZYPP18 inhibits the growth of R. cerealis on artificial growth media. A detached leaf assay verified that ZYPP18 inhibits the expansion of wheat sheath blight on the detached leaf. ZYPP18 has been found to possess plant growth-promoting properties, as well as the ability to solubilize phosphate and generate indole-3-acetic acid. Results from hydroponic experiments showed that wheat seedlings treated with ZYPP18 grew faster. Additionally, pot experiments and field experiments demonstrated that ZYPP18 effectively controls the occurrence of wheat sheath blight. ZYPP18 reduced the incidence of wheat sheath blight in wheat seedlings by 37.37% and 37.90%, respectively. The control effect of ZYPP18 on wheat sheath blight was 56.30% and 65.57%, respectively. These findings provide evidence that P. polymyxa ZYPP18 is an effective biological factor that can control disease and promote plant growth.


Discrimination between closely related synthetic cannabinoids by GC-Cold-EI-MS.
Gas chromatography thermal-electron ionization mass spectrometry (GC-EI-MS) is an established method for the identification of mind-altering substances and is routinely used by forensic laboratories. However, some commonly analyzed drugs of abuse, relating to the synthetic cannabinoids receptor agonist group (SCs), pose a challenge for this conventional technique. As the molecular cation radicals of many excited SCs are labile within the ion source, the relative abundance of the molecular ions obtained by the GC-EI-MS is often too small to allow discrimination of structurally related drugs. In contrast, the cold-electron ionization (cold-EI) method allows the enhancement and clear identification of the molecular ions, while maintaining the ability to compare unknown analytes with comprehensive mass spectrum libraries. This technique was explored for mass-spectrometric identification and unambiguous differentiation of 15 emerging synthetic cannabinoids found on the drug market in Israel and elsewhere. The current method was demonstrated to discriminate pairs of closely related SCs: FUB-PB-22 and FDU-PB-22, and 5F-PB-22 and NM-2201. In addition, the dependence of the molecular ion enhancement on the cold-EI parameters was examined. Finally, analysis of SCs from seized street samples provided by the Israeli police demonstrates the enhanced identification power of GC-cold-EI-MS.


Controlled electrochemical growth of ultra-long gold nanoribbons.
This paper describes the electrochemical growth of branchless gold nanoribbons with ∼40 nm × ∼300 nm cross sections and >100 μm lengths (giving length-to-thickness aspect ratios of >103). These structures are useful for opto-electronic studies and as nanoscale electrodes. The 0.75-1.0 V voltage amplitude range is optimal for branchless ribbon growth. Reduced amplitudes induce no growth, possibly due to reversible redox chemistry of gold at reduced amplitudes, whereas elevated amplitudes, or excess electrical noise, induce significant side-branching. The inter-relatedness of voltage-amplitude, noise, and side-branching in electrochemical nanoribbon growth is demonstrated.


Relationship Between the Onset of Ménière's Disease and Sympathetic Hyperactivity.
The pathogenesis of Ménière's disease is still largely unknown; however, it is known to be strongly associated with stress. Excessive stress can cause hyperactivity of the sympathetic autonomic nervous system. With the aim of understanding changes in sympathetic hyperactivity before and after Ménière's disease, we compared autonomic nervous function in patients in a stable phase of Ménière's disease and that in healthy adults. We also gathered data over about 10 years on autonomic nervous function immediately before a Ménière's attack. Prospective study. Autonomic nervous function was analyzed in 129 patients in a stable phase of Ménière's disease 31 healthy adult volunteers. In nine patients, autonomic nervous function was also measured immediately before and after treatment of a vertigo attack. Power spectrum analysis of heart rate variability (HRV) of EEG/ECG and an infrared electronic pupillometer were used. Sympathetic and parasympathetic nervous function was measured. There were no statistically significant differences in autonomic nervous function determined by HRV and electronic pupillometry between patients in a stable phase of Ménière's disease and healthy adults. Sympathetic function as measured by electronic pupillometry parameters VD and T5 showed no difference between the affected and unaffected sides in the baseline data measured in the stable phase (VD: affected side is 31.02 ± 6.16 mm/sec, unaffected side is 29.25 ± 5.73 mm/sec; T5: affected side is 3.37 ± 0.43 msec, unaffected side is 3.25 ± 0.39 msec). In contrast, all nine patients whose HRV data had been obtained just before an attack showed marked suppression of the parasympathetic nervous system and activation of the sympathetic nervous system. Electronic pupillometry also revealed an overactivation of the sympathetic nervous system on the affected side, just before the attacks. Analysis of sequential changes after the onset of an attack revealed that overactivation on the affected side was reduced after treatment, and no difference between affected and unaffected sides was observed 3 days after treatment. Detailed analysis of autonomic nervous function showed that immediately before an attack of Ménière's disease, the sympathetic nervous system on the affected side was strongly overactivated.


Microwave Study of Field-Effect Devices Based on Graphene/Aluminum Nitride/Graphene Structures.
Metallic gate electrodes are often employed to control the conductivity of graphene based field effect devices. The lack of transparency of such electrodes in many optical applications is a key limiting factor. We demonstrate a working concept of a double layer graphene field effect device that utilizes a thin film of sputtered aluminum nitride as dielectric gate material. For this system, we show that the graphene resistance can be modified by a voltage between the two graphene layers. We study how a second gate voltage applied to the silicon back gate modifies the measured microwave transport data at around 8.7 GHz. As confirmed by numerical simulations based on the Boltzmann equation, this system resembles a parallel circuit of two graphene layers with different intrinsic doping levels. The obtained experimental results indicate that the graphene-aluminum nitride-graphene device concept presents a promising technology platform for terahertz- to- optical devices as well as radio-frequency acoustic devices where piezoelectricity in aluminum nitride can also be exploited.


Implications of the genetics revolution for health services research: pharmacogenomics and improvements in drug therapy.
To review the societal and economic implications of the use of genetic information to individualize drug therapies. Although studies have begun to address the ethical issues raised by the use of genetic information , few have examined the implications of pharmacogenomics f rom the perspective of health services research. We propose a research agenda for health services research in three areas: (1) to evaluate the effectiveness and cost-effectiveness of pharmacogenomics; (2) to evaluate the effect of pharmacogenomics from the perspective of patients, providers, insurers, industry, and government ; and (3) to evaluate the ethical and societal implications of pharmacogenomics. Throughout the article we use the example of HIV genotyping as an illustration of how genetic technology is disseminated and used. More research is needed on the societal and economic implications of pharmacogenomics to inform the clinical and policy decisions about its use that will be increasingly urgent in the future.


Detection of ultra-low levels of DNA changes by drinking water: epidemiologically important finding.
The safety of drinking water is essential to our health. In this context, the mutagenicity of water needs to be checked strictly. However, from the methodological limit, the lower concentration (less than parts per million) of mutagenicity could not be detected, though there have been of interest in the effect of less concentration mutagens. Here, we describe a highly sensitive mutation assay that detects mutagens at the ppb level, termed genome profiling-based mutation assay (GPMA). This consists of two steps; (i) Escherichia coli culture in the medium with/without mutagens and (ii) Genome profiling (GP) method (an integrated method of random PCR, temperature gradient gel electrophoresis and computer-aided normalization). Owing to high sensitivity of this method, very low concentration of mutagens in tap water could be directly detected without introducing burdensome concentration processes, enabling rapid measurement of low concentration samples. Less expectedly, all of the tap waters tested (22 samples) were shown to be significantly mutagenic while mineral waters were not. Resultantly, this article informs two facts that the GPMA method is competent to measure the mutagenicity of waters directly and the experimental results supported the former reports that the city tap waters contain very low level of mutagenicity reagent trihalomethanes.


Examining the organization and quality of the psychiatric consultative service in Norway.
Patients admitted to somatic departments may face psychiatric challenges, such as suicidal behavior, substance abuse, crisis reactions, or somatoform disorders. Mental disorders can complicate the diagnosis and treatment of a somatic disorder. The Consultation-Liaison Psychiatry Service (CLP) can provide advice and guidance to attending staff in somatic departments. CLP in Norwegian hospitals was last reviewed in 1997. There is insufficient awareness of the service as it currently stands. This specialist field is expanding, and there is a need to examine how the service is organized at present and how it works. A study of the scope, quality, availability, content, and organization of the psychiatric consultative service was conducted in February-March 2016. The study also examined whether service users and providers were satisfied with the service, the content of the service, and whether they considered the service to be adequate. Although CLP has expanded over the last three years, somatic and psychiatric departments wish for its further expansion. The service provision is at an acceptable level during the daytime, but not during weekends and holidays. We found that 20% of all referrals are rejected and that 80-90% of all physicians wanted outpatient services for short-term follow-up and for help with undiagnosed, unclear, unexplained, (indeterminate) conditions. The service works satisfactorily during ordinary working hours. There is a need to establish outpatient services and to strengthen the services outside these hours. Collaborative research should be further developed.


The role of inflammatory mediators in the development of prostatic hyperplasia and prostate cancer.
Benign prostatic hyperplasia and prostate cancer remain the most prevalent urologic health concerns affecting elderly men in their lifetime. Only 20% of benign prostatic hyperplasia and prostate cancer cases coexist in the same zone of the prostate and require a long time for initiation and progression. While the pathogenesis of both diseases is not fully understood, benign prostatic hyperplasia and prostate cancer are thought to have a multifactorial etiology, their incidence and prevalence are indeed affected by age and hormones, and they are associated with chronic prostatic inflammation. At least 20% of all human malignancies arise in a tissue microenvironment dominated by chronic or recurrent inflammation. In prostate malignancy, chronic inflammation is an extremely common histopathologic finding; its origin remains a subject of debate and may in fact be multifactorial. Emerging insights suggest that prostate epithelium damage potentially inflicted by multiple environmental factors such as infectious agents, dietary carcinogens, and hormones triggers procarcinogenic inflammatory processes and promotes cell transformation and disease development. Also, the coincidence of chronic inflammation and tumorigenesis in the peripheral zone has recently been linked by studies identifying so-called proliferative inflammatory atrophy as a possible precursor of prostatic intraepithelial neoplasia and prostate cancer. This paper will discuss the available evidence suggesting that chronic inflammation may be involved in the development and progression of chronic prostatic disease, although a direct causal role for chronic inflammation or infection in prostatic carcinogenesis has yet to be established in humans. Further basic and clinical research in the area, trying to understand the etiology of prostatic inflammation and its signaling pathway may help to identify new therapeutic targets and novel preventive strategies for reducing the risk of developing benign and malignant tumors of the prostate.


Use of honey in wound care: an update.
The therapeutic use of honey in wound care has been used since ancient times. Honey has been shown to have antibacterial properties in vitro and animal studies have demonstrated accelerated wound healing with the use of honey. In human trials, there is currently not enough strong evidence to fully support the use of honey in wound care; however, use in minor burns and prevention of radiation mucositis appear to be 2 areas where honey shows therapeutic promise.


Long term effects of boron on layer bone strength and production parameters.
1. The effects of dietary boron (0, 50, 100, 200, and 400 mg/kg) on bone strength characteristics and egg production of white leghorn layers were investigated. 2. The shear fracture energy increased in the tibia and radius at 72 weeks for birds started on the 200 mg/kg supplement at 32 weeks of age. 3. The shear force, stress, and fracture energy of the tibia and radius increased for the non-egg producing birds at 72 weeks. 4. Bird body weight, food consumption, egg weight, and egg production all decreased at 400 mg/kg boron. 5. Boron concentrations in the breast, liver, thigh and bone tissue increased with increasing concentrations of supplemental boron.


[Effect of percutaneous transluminal mitral commissurotomy on pulmonary function and on the pulmonary vasculature].
We evaluated the therapeutic effect of percutaneous transluminal mitral commissurotomy (PTMC) on pulmonary function, and the damage caused to pulmonary vasculature by transient occlusion of the mitral valve during PTMC in patients with mild mitral stenosis. Pulmonary function tests were done and serum thrombomodulin was measured in 6 patients before and after PTMC. The mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure decreased significantly from the control values, and the decreases were proportional to the increase in the area of the mitral valve. VC, %VC, and DLco were in the normal range before and after PTMC but PEFR, FEV1%, FEV1, V50, V25, and V50/V25 were significantly higher after PTMC. Change in the area of the mitral valve correlated with the changes in FEV1% (r = 0.841), in V50 (r = 0.624), and in V25 (r = 0.697). The serum thrombomodulin levels before and after PTMC did not differ. We conclude that pulmonary dysfunction in patients with mild mitral stenosis MS is mainly due to an obstructive ventilatory defect, and that PTMC can correct this dysfunction without damaging the pulmonary vasculature.


Establishment and use of surgical rat models for assessment of organ specific in vivo clearance.
Knowledge of clearance plays a key role in the development of new drug entities, especially in the development of improved analogues for treatment of chronic conditions. Improved pharmacokinetic properties can be used to increase dosing interval and thereby improve patient compliance. This will lead to improved treatment outcome or decreased risk of treatment failure when treating chronic conditions. Therefore, animal models for assessment of organ-specific clearance are of great value in preclinical drug development. These models can be used to obtain insights into the relative importance of a clearance organ and thereby guide drug design of new analogues in early drug discovery. The current PhD project was undertaken to explore surgical in vivo models, which could be used in the assessment of the relative importance of major clearance organs. It was the aim of the PhD project to establish and validate both a nephrectomy model and a hepatectomy model as tools to investigate relative importance of renal and hepatic clearance. Furthermore, the project aim was to investigate renal clearance of rFVIIa and rhGH using a nephrectomy model in rats. The thesis is composed of a short theoretical background, a literature review, two papers based on experimental work as well as experimental work not included in the papers. Chapter one is an introduction with the specific aims and hypotheses. The chapters from two to five contain theoretical background of the clearance concept, anatomical and physiological description of clearance organs and a brief overview of potential clearance models including in vivo models. Chapters six through nine highlight the experimental work with the results obtained during the PhD project. Lastly, the chapters from ten to twelve contain a general discussion, conclusion and perspectives of the current thesis. Paper I "Nephrectomized and hepatectomized animal models as tools in preclinical pharmacokinetics" provides a literature review of animal models previously used as tools to investigate renal and hepatic clearance. An overview of the surgical procedures previously described for establishment of in vivo nephrectomy and hepatectomy models is given. Many different surgical methods have been employed in the attempt to make anephric or anhepatic in vivo models. The overall conclusion of the literature review was that a suitable clearance model would require only one surgical procedure. Furthermore, the clearance studies should be conducted immediately after completed surgery to decrease the impact on other clearance pathways and physiology in general. Paper II "The kidneys play an important role in the clearance of rFVIIa in rats" describes the establishment, validation and use of an in vivo model for assessment of renal clearance. The model employed was a rat nephrectomy model and the compounds investigated were inulin and rFVIIa. General physiology was assumed to be close to normal as rectal temperature, oxygen saturation and pulse were within normal range during the pharmacokinetic studies. Nephrectomy significantly reduced clearance of rFVIIa and almost completely abolished clearance of inulin. Thus, it was concluded that the nephrectomy model could be used in assessment of the relative importance of the kidneys in the clearance of rFVIIa and the data obtained indicate that renal clearance accounts for 50% of total body clearance of rFVIIa. Paper III "The kidneys play a central role in the clearance of rhGH in rats" addresses renal clearance of rhGH. The in vivo model established in Paper II was used in a pharmacokinetic study of rhGH to assess the relative importance of the kidneys in the clearance of rhGH. The conclusion drawn based on this study was that the kidneys account for 90% of total body clearance of rhGH in anaesthetized rats. Furthermore, it was noted that anaesthesia reduced clearance of rhGH by 36% compared to non-anaesthetized rats. In conclusion, establishment, validation and use of a rat nephrectomy model as a tool to investigate renal clearance was successful, but an in vivo rat model of hepatic clearance model was not successfully established.


Association between hypertension and stroke in US adults in the National Health and Nutrition Examination Surveys (NHANES) 2007 to 2018.
Hypertension is associated with stroke events. The purpose of this study was to analyze the correlation between hypertension and stroke in American adults from 2007 to 2018 in National health and Nutrition Examination Survey (NHANES) database. 28528 individuals in the NHANES from 2007 to 2018 were included in the cross-sectional analysis. The independent variable was blood pressure (BP) and the outcome variable was stroke. Multivariate linear regression model was used to study the correlation between BP and stroke. In each multivariate linear regression model, BP level was positively correlated with stroke, and this positive correlation was stable in both men and women (man OR: 1.36, 95% CI: 0.95 to 1.69; woman OR: 1.45, 95% CI: 1.12 to 1.78). Our results show that there is a significant positive correlation between BP and stroke. When the systolic blood pressure (SBP) is about 140 mmHg, the risk of stroke is the lowest; Male patients with diastolic blood pressure (DBP) of about 80 mmHg have a lower risk of stroke.


Enterovesical Fistula After Enteric Conversion of a Bladder-Drained Pancreatic Allograft: A Case Report.
Since the inception of pancreas transplant as a treatment for type 1 diabetes mellitus, there has been considerable debate about the best way to manage exocrine secretions and monitor patients for graft rejection. For patients who undergo bladder exocrine drainage of a pancreatic allograft, a bladder-to-enteric drainage conversion can serve as a rescue procedure in case of anastomotic leaks or other complications. However, this procedure is associated with its own complications, including a rarely described enterovesical fistula. Here we report on a 45-year-old man who underwent a simultaneous kidney and pancreas transplant with bladder drainage to the latter. He developed a pancreatic allograft duodenal leak (duodenal-vesical anastomosis) requiring a bladder-to-enteric drainage conversion. The patient returned 2 weeks after discharge with an enterovesical fistula. He was treated nonsurgically with intravenous antibiotics, bowel rest, and parenteral nutrition, and the fistula successfully closed in approximately 2 weeks. Overall, enterovesical fistula formation is a rare but treatable complication that can occur after a bladder-to-enteric drainage conversion of a pancreatic transplant allograft. It can be managed nonsurgically, which is preferable in these immunocompromised patients.


Effect of mechanical stimulation on mucociliary clearance of chicken sinus.
The hypothesis that homeostatic control mechanisms control mucociliary function in ciliated mucous membranes was induced artificially by means of mechanical stimulation. The edge of right palatine cleft was stimulated mechanically by gentle touching with a dissecting needle, and sinus clearance time was recorded as soon as mechanical stimulation was initiated. Mechanical stimulation caused acceleration of mucociliary flow of the sinus; sinus clearance time was accelerated on the side adjacent to the mechanically stimulated side of the palatine cleft, but not on the opposite side. Therefore, the reflex may be effective only on the stimulated side. We investigated the effect of nerve blockers on mechanical stimulation. Mucociliary clearance in the chicken sinus was not affected by parasympatholytic agents, but was decelerated by the beta-adrenergic blocker. The effect of nerve blockers on the mechanical stimulation showed that parasympatholytic agents blocked mechanical stimulation, while sympatholytic agents did not completely block the response. These data suggest that mucociliary clearance may be regulated by the reflex of parasympathetic and partially sympathetic nerve fibers.


Multilevel ossification of the posterior longitudinal ligament causing cervical myelopathy: An observational series of North American patients.
Few studies regarding ossification of the posterior longitudinal ligament (OPLL) outside of Asia currently exist in the literature. A set of patients with multilevel cervical OPLL causing symptomatic myelopathy or radiculopathy from a North American sample is analyzed. The objective of this study was to describe the demographics, radiographic findings, and surgical outcomes of a cohort of North American patients with degenerative spondylosis presenting for operative management of multilevel (>3 segments) cervical OPLL. Forty-three patients diagnosed with multilevel cervical OPLL and degenerative spondylosis presenting with symptomatic cervical myelopathy or radiculopathy were surgically treated over a 9-year period at a single tertiary care academic medical center. Radiographic measurements were performed on preoperative computed tomography and magnetic resonance imaging images of the cervical spine. Clinical outcomes included pre- and postoperative Nurick scores, 90-day readmission, complication, and revision surgery rates. The mean age was 66.1 ± 10.9 years with a mean latest follow-up time of 32.7 ± 16.4 months. Most patients had previous diagnoses of obesity (70.7%) and hypertension (55.8%). At least one-quarter of patients were diagnosed with type 2 diabetes (34.9%), hyperlipidemia (41.9%), cardiovascular disease (25.6%), or chronic kidney disease (25.3%). The most common OPLL subtype was segmental (39.5%) and spanned a mean of 3.54 ± 1.48 segments. Myelopathic symptoms were present in 88.4% of patients. All patients experienced significant neurologic improvement at 3-week and latest follow-up (P < 0.001 for both). Obesity, diabetes, and other metabolic derangements in patients with existing cervical spondylosis may be risk factors for a particularly aggressive form of multilevel OPLL. Various operative approaches may be employed to achieve adequate neurologic recovery. Further workup for OPLL in patients with these risk factors may prove beneficial to ensure appropriate operative management.


Indications for cerebral revascularization for patients with atherosclerotic carotid occlusion.
Patients with complete carotid occlusion and recent ischemic symptoms are at high risk for subsequent stroke, particularly those with evidence of severe hemodynamic impairment due to poor collateral flow. Treatment options for these patients include direct extracranial to intracranial arterial bypass, or interventions aimed at improving collateral sources of flow such as endarterectomy or angioplasty and stenting of the ipsilateral external carotid artery, the contralateral carotid artery, or the vertebral arteries. The evidence supporting the use of these procedures for patients with complete occlusion of the carotid artery will be the focus of this article. The use of physiologic imaging to select subgroups of patients at high risk due to hemodynamic factors will also be discussed.