Plain and complex flagella of Pseudomonas rhodos: analysis of fine structure and composition.
Cells of Pseudomonas rhodos 9-6 produce two morphologically distinct flagella termed plain and complex, respectively. Fine structure analyses by electron microscopy and optical diffraction showed that plain flagellar filaments are cylinders of 13-nm diameter composed of globular subunits like normal bacterial flagella. The structure comprises nine large-scale helical rows of subunits intersecting four small-scale helices of pitch angle 25 degrees . Complex filaments have a conspicuous helical sheath, 18-nm wide, of three close-fitting helical bands, each about 4.7-nm wide, separated by axial intervals, 4.7 nm wide, running at an angle of 27 degrees . The internal core has similar but not identical substructure to plain filaments. Unlike plain flagella, the complex species is fragile and does not aggregate in bundles. Mutants bearing only one of two types of flagellum were isolated. Cells with plain flagella showed normal translational motion, and cells with complex flagella showed rapid spinning. Isolated plain flagella consist of a 37,000-dalton subunit separable into two isoproteins. Complex filaments consist of a 55,000-dalton protein; a second 43,000-dalton protein was assigned to complex flagellar hooks. The results indicate that plain and complex flagella are entirely different in structure and composition and that the complex type represents a novel flagellar species. Its possible mode of action is discussed.


Kapitza-Dirac Blockade: A Universal Tool for the Deterministic Preparation of Non-Gaussian Oscillator States.
Harmonic oscillators count among the most fundamental quantum systems with important applications in molecular physics, nanoparticle trapping, and quantum information processing. Their equidistant energy level spacing is often a desired feature, but at the same time a challenge if the goal is to deterministically populate specific eigenstates. Here, we show how interference in the transition amplitudes in a bichromatic laser field can suppress the sequential climbing of harmonic oscillator states (Kapitza-Dirac blockade) and achieve selective excitation of energy eigenstates, cat states, and other non-Gaussian states. This technique can transform the harmonic oscillator into a coherent two-level system or be used to build a large-momentum-transfer beam splitter for matter waves. To illustrate the universality of the concept, we discuss feasible experiments that cover many orders of magnitude in mass, from single electrons over large molecules to dielectric nanoparticles.


Predictive chirality sensing via Schiff base formation.
Among the large number of chiroptical sensors that have been developed to date, few allow rational determination of the absolute configuration of chiral substrates together with quantitative ee analysis. We have prepared and tested stereodynamic N-aryl aminobenzaldehyde sensors that bind chiral amines via Schiff base formation. The covalent binding of the amine substrate generates a conformational bias in the chromophoric sensor moiety which results in characteristic CD signals. Computational analysis revealed that CD prediction of the sign of the Cotton effect and thus determination of the absolute configuration of the substrate becomes practical with a sterically crowded sensor design because the number of conformations to be considered is largely reduced and the chiroptical sensor response is less sensitive to conformational equilibria. The amplitude of the measured CD signal can be used for quantitative ee analysis of nonracemic amine samples with the help of a calibration curve.


Dendrocytoclasis in Henoch-Schönlein purpura.
We studied by immunohistochemistry the fate of factor XIIIa-positive dermal dendrocytes in Henoch-Schönlein purpura. We have observed apoptosis affecting most of the perivascular dendrocytes. Such an aspect of dendrocytoclasis has never previously been reported in inflammatory disorders in the absence of vasculitis.


Beta-tubulin epitope expression in normal and malignant epithelial cells.
The expression of a unique beta-tubulin isoform (class III) was monitored in squamous cell carcinoma (SCC) and normal epithelial cells using a monoclonal tubulin antibody called TuJ1. Whole tissue homogenates of SCC, normal tissue, SCC grown in nude mice, and SCC cultured cells were examined using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot. TuJ1 antibody localization was performed using peroxidase immunostaining on paraffin sections of SCC, normal tissue, nude mouse SCC, and immunofluorescent microscopy of SCC cultured cells. The malignant tissues examined stained positive with TuJ1 and a general beta-tubulin antibody, whereas the normal tissues stained positively only for the general beta-tubulin antibody. TuJ1 epitope expression may be a useful marker for SCCs and may assist in understanding differences between normal and malignant squamous cells.


Measuring earplug noise attenuation: A comparison of laboratory and field methods.
Hearing protection device (HPD) fit-testing is a recommended best practice for hearing conservation programs as it yields a metric of the amount of attenuation an individual achieves with an HPD. This metric, the personal attenuation rating (PAR), provides hearing health care, safety, and occupational health personnel the data needed to select the optimal hearing protection for the occupational environment in which the HPD will be worn. Although commercial-off-the-shelf equipment allows the professional to complete HPD fit tests in the field, a standard test methodology does not exist across HPD fit-test systems. The purpose of this study was to compare the amount of attenuation obtained using the "gold standard" laboratory test (i.e., real-ear attenuation at threshold [REAT]) and three commercially available HPD fit-test systems (i.e., Benson Computer Controlled Fit Test System [CCF-200] with narrowband noise stimuli, Benson CCF-200 with pure tone stimuli, and Michael and Associates FitCheck Solo). A total of 57 adults, aged 18 to 63, were enrolled in the study and tested up to seven earplugs each across all fit-test systems. Once fitted by a trained member of the research team, earplugs remained in the ear throughout testing across test systems. Results revealed a statistically significant difference in measured group noise attenuation between the laboratory and field HPD fit-test systems (p < .0001). The mean attenuation was statistically significantly different (Benson CCF-200 narrowband noise was +3.1 dB, Benson CCF-200 pure tone was +2.1 dB, and Michael and Associates FitCheck Solo was +2.5 dB) from the control laboratory method. However, the mean attenuation values across the three experimental HPD fit-test systems did not reach statistical significance and were within 1.0 dB of one another. These findings imply consistency across the evaluated HPD fit-test systems and agree with the control REAT test method. Therefore, the use of each is acceptable for obtaining individual PARs outside of a laboratory environment.


Jupyter and Galaxy: Easing entry barriers into complex data analyses for biomedical researchers.
What does it take to convert a heap of sequencing data into a publishable result? First, common tools are employed to reduce primary data (sequencing reads) to a form suitable for further analyses (i.e., the list of variable sites). The subsequent exploratory stage is much more ad hoc and requires the development of custom scripts and pipelines, making it problematic for biomedical researchers. Here, we describe a hybrid platform combining common analysis pathways with the ability to explore data interactively. It aims to fully encompass and simplify the "raw data-to-publication" pathway and make it reproducible.


A partially differentiated interior for (1) Ceres deduced from its gravity field and shape.
Remote observations of the asteroid (1) Ceres from ground- and space-based telescopes have provided its approximate density and shape, leading to a range of models for the interior of Ceres, from homogeneous to fully differentiated. A previously missing parameter that can place a strong constraint on the interior of Ceres is its moment of inertia, which requires the measurement of its gravitational variation together with either precession rate or a validated assumption of hydrostatic equilibrium. However, Earth-based remote observations cannot measure gravity variations and the magnitude of the precession rate is too small to be detected. Here we report gravity and shape measurements of Ceres obtained from the Dawn spacecraft, showing that it is in hydrostatic equilibrium with its inferred normalized mean moment of inertia of 0.37. These data show that Ceres is a partially differentiated body, with a rocky core overlaid by a volatile-rich shell, as predicted in some studies. Furthermore, we show that the gravity signal is strongly suppressed compared to that predicted by the topographic variation. This indicates that Ceres is isostatically compensated, such that topographic highs are supported by displacement of a denser interior. In contrast to the asteroid (4) Vesta, this strong compensation points to the presence of a lower-viscosity layer at depth, probably reflecting a thermal rather than compositional gradient. To further investigate the interior structure, we assume a two-layer model for the interior of Ceres with a core density of 2,460-2,900 kilograms per cubic metre (that is, composed of CI and CM chondrites), which yields an outer-shell thickness of 70-190 kilometres. The density of this outer shell is 1,680-1,950 kilograms per cubic metre, indicating a mixture of volatiles and denser materials such as silicates and salts. Although the gravity and shape data confirm that the interior of Ceres evolved thermally, its partially differentiated interior indicates an evolution more complex than has been envisioned for mid-sized (less than 1,000 kilometres across) ice-rich rocky bodies.


Oxygen Vacancy Linear Clustering in a Perovskite Oxide.
Oxygen vacancies have been implicitly assumed isolated ones, and understanding oxide materials possibly containing oxygen vacancies remains elusive within the scheme of the isolated vacancies, although the oxygen vacancies have been playing a decisive role in oxide materials. Here, we report the presence of oxygen vacancy linear clusters and their orientation along a specific crystallographic direction in SrTiO3, a representative of a perovskite oxide. The presence of the linear clusters and associated electron localization was revealed by an electronic structure represented in the increase in the Ti2+ valence state or corresponding Ti 3d2 electronic configuration along with divacancy cluster model analysis and transport measurement. The orientation of the linear clusters along the [001] direction in perovskite SrTiO3 was verified by further X-ray diffuse scattering analysis. Because SrTiO3 is an archetypical perovskite oxide, the vacancy linear clustering with the specific aligned direction and electron localization can be extended to a wide variety of the perovskite oxides.


Identification of a new pathogen-induced member of the subtilisin-like processing protease family from plants.
By using biochemical, immunological, and molecular strategies we have identified and cloned a cDNA encoding a protease from tomato (Lycopersicon esculentum) plants (P69B) that is part of a proteolytic system activated in the plant as a result of infection with citrus exocortis viroid. This new protease is closely related, in terms of amino acid sequence and structural organization, to the previously identified pathogenesis-related subtilisin-like protease (Tornero, P., Conejero, V., and Vera, P. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 6332-6337). The 745-residue amino acid sequence of P69B begins with a cleavable signal peptide, contains a prodomain and a 631-residue mature domain which is homologous to the catalytic modules of bacterial subtilisins and eukaryotic Kex2-like proteases. Within the catalytic domain, the essential Asp, His, and Ser residues that conform the catalytic triad of this family of proteases are conserved in P69B. Northern blot and reverse transcriptase-polymerase chain reaction analysis demonstrated widespread induced expression of the 2.5-kilobase hybridizing mRNA in plant tissues as a consequence of viroid infection. We propose that P69B is a member of a complex gene family of plant Kex2/subtilisin-like proteases presumably involved in a number of specific proteolytic events activated during pathogenesis in plants and that takes place in the extracellular matrix.


[Study on anti-tumor activity of extracts from cultured cells of Taxus chinensis].
To analyze the cytotoxicity and inhibitory effect of extracts from cultured cells(from stems) of Taxus chinensis on cancer cell line SMMC-7721. MTT assay for cell viability and flow cytometry for cell cycle analysis. MTT results showed that the extact by dichloromethane was more effective than that by methanol on SMMC-7721, IC50 were 0.0834 mg DCW.ml-1 and 0.8002 mg DCW.ml-1 respectively. SMMC-7721 cells in G2-M stage increased with higher concentration of dichloromethane extracts from Taxus chinensis cells and longer incubation. Extracts from cultured cells of Taxus chinensis could have cytotoxic effect on SMMC-7721 and could induce apoptosis of cancer cells.


Hyperspectral photometric stereo for a single capture.
We present a single-capture photometric stereo method using a hyperspectral camera. A spectrally and spatially designed illumination enables a point-wise estimation of reflectance spectra and surface normals from a single hyperspectral image. The illumination works as a reflectance probe in wide spectral regions where reflectance spectra are measured, and the full spectra are estimated by interpolation. It also works as the resource for shadings in other spectral regions. The accuracy of estimation is evaluated in a simulation. Also, we prepare an experimental setup and demonstrate a surface reconstruction against a real scene.


Emergency department use of computed tomography in children with epilepsy and breakthrough seizure activity.
Children with epilepsy are frequently evaluated in the emergency department for breakthrough seizure activity. This population is at risk for undergoing repeated computed tomography (CT) scans. The long-term health risks associated with CT scans has been the subject of multiple articles in recent years. In 2002, the National Cancer Institute released a statement that focused on reducing long-term health risks by limiting children's exposure to CT radiation. A retrospective study that included 124 children (ages 2 months-16 years) who presented to our emergency department with epilepsy and breakthrough seizure activity was performed to determine whether the National Cancer Institute statement made an impact on the number of head CT scans ordered. Physician's compliance with the American Academy of Neurology guidelines for emergent head CT scans in patients with known seizure disorder and the diagnostic yield of the head CT scans was also assessed. There was a significant increase (P = .016) in the number of CT scans performed from the years 2000-2001 to the years 2003-2004. Of the 21 children who had CT scans, 15 (71%) children did not meet American Academy of Neurology guidelines for an emergent CT scan. None of the children had an acute finding on CT, and all were discharged from the emergency department. This finding suggests that the yield of emergent CT scans in children with epilepsy and breakthrough seizure activity is low. This study demonstrates the increasing utilization of CT scans in this population at our institution and that compliance with American Academy of Neurology guidelines is not optimal.


Homolysis of the Ln-N (Ln = Yb, Eu) bond. Synthesis, structural characterization and catalytic activity of ytterbium(II) and europium(II) complexes with methoxyethyl functionalized indenyl ligands.
The interaction of methoxyethyl functionalized indene compounds (C(9)H(6)-1-R-3-CH(2)CH(2)OMe, R =t-BuNHSiMe(2)(1), Me(3)Si (2), H (3)) with [(Me(3)Si)(2)N](3)Ln(mu-Cl)Li(THF)(3)(Ln=Yb (4), Eu (5)) produced a series of new ytterbium(II) and europium(II) complexes via tandem silylamine elimination/homolysis of the Ln-N (Ln=Yb, Eu) bond. Treatment of the lanthanide(III) amides [(Me(3)Si)(2)N](3)Ln(mu-Cl)Li(THF)(3)(Ln=Yb (4), Eu (5) with 2 equiv. of, 1,2 and 3, respectively, produced, after workup, the ytterbium(II) complexes [eta5:eta1-Me(2)Si(MeOCH(2)CH(2)C(9)H(5))(NHBu-t)](2)Yb(II) (6), (eta5:eta1-MeOCH(2)CH(2)C(9)H(5)SiMe(3))(2)Yb(II) (7), (eta5:eta1-MeOCH(2)CH(2)C(9)H(6))(2)Yb(II)(8) and the corresponding europium(II) complexes [eta5:eta1-Me(2)Si(MeOCH(2)CH(2)C(9)H(5))(NHBu-t)](2)Eu(II)(9), (eta5:eta1-MeOCH(2)CH(2)C(9)H(5)SiMe(3))(2)Eu(II)(10) and (eta5:eta1-MeOCH(2)CH(2)C(9)H(6))(2)Eu(II)(11) in moderate to good yield. In contrast, interaction of the corresponding indene compounds 1, 2 or 3 with the lanthanide amides [(Me(3)Si)(2)N](3)Ln (Ln = Yb, Eu) was not observed, while addition of 0.5 equiv. of anhydrous LiCl to the corresponding reaction mixture produced, after workup, the corresponding ytterbium(II) or europium(II) complexes. All the new compounds were fully characterized by spectroscopic and elemental analyses. The structures of complexes, and were determined by single-crystal X-ray analyses. The catalytic activity of all the ytterbium(II) and europium(II) complexes on MMA polymerization was examined. It was found that all the ytterbium(II) and europium(II) complexes can function as single-component MMA polymerization catalysts. The temperature, solvent and ligand effects on the catalytic activity were studied.


Degenerative spondylolisthesis.
A clinical study has been made of forty-three patients with symptoms arising from degenerative spondylolisthesis of the lumbar spine. Attention is drawn to the lower average level of the iliac crests in these patients, and to the high incidence of osteoarthritis of the hips. Many patients in this series had been referred specifically for operation and fourteen were so treated. The techniques of decompression and of spinal fusion are discussed. It is concluded that patients with back pain predominant are well treated by corsetry, only a minority needing fusion, and that patients with nerve root involvement or with symptoms of spinal stenosis need decompression. The place of spinal fusion is the main problem, but it seems reasonable, firstly, in younger patients with clear evidence of instability and degenerative change at a single level, and secondly, when radical decompression is judged to increase the risk of instability.


Effects of 1800 MHz RF-EMF exposure on DNA damage and cellular functions in primary cultured neurogenic cells.
To systematically evaluate the effects of 1800 MHz radiofrequency electromagnetic fields (RF-EMF) exposure on DNA damage and cellular functions in primary cultured neurogenic cells. The primary cultured astrocytes, microglia and cortical neurons were exposed to RF-EMF at a SAR of 4.0 W/kg. The DNA damage was evaluated by γH2AX foci formation assay. The secretions of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) in astrocytes and microglia, microglial phagocytic activity and neuronal development were examined by enzyme-linked immunosorbent assay, phagocytosis assay and immunofluorescent staining on microtubule-associated protein tau, microtubule-associated protein 2, postsynaptic density 95 and gephyrin, respectively. RF-EMF exposure did not significantly induce γH2AX foci formation in three primary cultured neurogenic cells. Furthermore, RF-EMF exposure did not significantly affect the secretion of cytokines in astrocytes and microglia, and the morphological indicators of dendrites or synapses of cortical neurons. However, the exposure significantly reduced the phagocytic activity of microglia and inhibited the axon branch length and branch number of cortical neurons. Our data demonstrated that exposure to RF-EMF did not elicit DNA damage but inhibited the phagocytic ability of microglia and the axon branch length and branch number of cortical neurons.


Standard and embedded solitons in nematic optical fibers.
A model for a non-Kerr cylindrical nematic fiber is presented. We use the multiple scales method to show the possibility of constructing different kinds of wave packets of transverse magnetic modes propagating through the fiber. This procedure allows us to generate different hierarchies of nonlinear partial differential equations which describe the propagation of optical pulses along the fiber. We go beyond the usual weakly nonlinear limit of a Kerr medium and derive a complex modified Korteweg-de Vries equation (CM KdV) which governs the dynamics for the amplitude of the wave packet. In this derivation the dispersion, self-focussing, and diffraction in the nematic fiber are taken into account. It is shown that this CM KdV equation has two-parameter families of bright and dark complex solitons. We show analytically that under certain conditions, the bright solitons are actually double-embedded solitons. We explain why these solitons do not radiate at all, even though their wave numbers are contained in the linear spectrum of the system. We study (numerically and analytically) the stability of these solitons. Our results show that these embedded solitons are stable solutions, which is an interesting property since in most systems the embedded solitons are weakly unstable solutions. Finally, we close the paper by making comments on the advantages as well as the limitations of our approach, and on further generalizations of the model and method presented.


Aging, food patterns and disability.
To lay the groundwork for devising, improving and implementing strategies to prevent or delay the onset of disability in the elderly, a systematic literature review was conducted of longitudinal studies published between 1985 and 2001 that reported statistical significant associations between individual baseline nutritional risk factors and subsequent functional status in community-living older persons. The review revealed that nutrition has been neglected in past research. Not more than three studies fulfilled the methodological criteria (e.g. control for baseline functional status, control for confounding or attrition rate). The association between increased and decreased body mass index and functional decline was high. This and other available information regarding the importance of nutrition for the disablement process underline how important adequate intakes of energy and nutrients today are for the ability to manage activities of daily living tomorrow. Vulnerable groups of elderly people can be identified by questions on number of meals a day, food group intake and assessment of weight change. Policy makers and health care professionals should put a joined effort in optimising the food intake of these vulnerable elderly people. On one hand by stimulating physical activity to animate food intake and on the other hand by facilitating the availability of attractive nutritious foods.


Using visual inquiry to reveal differences in nursing students' perception of case management.
An exploratory, qualitative study of 24 senior generic nursing students (GNSs) and 23 practicing registered nurse baccalaureate students (PRNSs) was conducted to evaluate students' perceptions about case management for community-based children with disabilities, and to examine the differences in the two student groups' perceptions utilizing the visual inquiry method. For a class project, the students used words and photographs to show how they solved one problem for a family caring for a child with a disability in the community. All students agreed on the overall theme, home environment; however, significant differences in each group's perception of this theme emerged. The GNSs described the home environment as a barrier, whereas the PRNSs described the home environment as being inside the home and outside the home. Moreover, two other themes emerged with the 23 PRNSs that were not perceived by the GNSs. The analysis of students' perceptions about case management of their clients was conducted from data analysis of the photographs. Though the literature does not support that differences in learning between the GNSs and PRNSs exist, this study demonstrates there are differences in perception about case management between the two groups.


Selenoprotein W depletion in vitro might indicate that its main function is not as an antioxidative enzyme.
Examination of the antioxidative homeostasis in skeletal muscle cells in the presence or absence of selenoprotein W (SelW) is necessary to understand the importance of SelW in the antioxidative system. Depletion of SelW by RNA interference was achieved by introducing a synthetic small interfering RNA into the mouse skeletal muscle cell line C2C12 (C3H). Transfectant screening was performed by real-time reverse transcription-PCR, Western blotting, flow cytometry, fluorescence staining, cell viability, and glutathione assays. SelW expression and mRNA levels were downregulated by 62.1 and 72.4%, respectively. In addition, acute cytotoxicity and an apoptosis rate of approximately 36% in SelW-depleted cells demonstrated that RNA interference was successful. As compared with non-SelW-depleted cells, the enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase and total antioxidative capability and glutathione level increased by 47.6, 103.0, 31.0, 205.6, and 30.0%, respectively (P < 0.05). Thus, SelW is important for the antioxidative system of muscle cells. Depletion of SelW, however, could be compensated by other intracellular antioxidative enzymes because oxidative stress was not the causative factor for apoptosis in SelW-depleted cells. Thus, the main function of SelW in muscle cells is not in the antioxidative system.


[Small bowel carcinoid].
Tumors of the small intestine can be fatal from the oncologic point of view. Its quite sporadic incidence and absence of early clinical symptoms lead to its very difficult diagnosis. Carcinoid stays as the second most often tumor of the small intestine and it is qualified by some authors as semimalignant. The case report presented is aimed at that issue.


Role of probiotics, prebiotics and synbiotics in chemoprevention for colorectal cancer.
Colorectal cancer is the third most common form of cancer. Current treatments are all associated with a high risk of complications and a low success rate. Recently, synbiotics have been proposed as a new preventive and therapeutic option. There is no direct experimental evidence for cancer suppression in humans as a result of the consumption of pro-, pre- or synbiotics. However, there is a wealth of evidence emerging from laboratory studies. The mechanisms by which pro-, pre- and synbiotics may inhibit colon cancer are now beginning to be understood and will be addressed in the present review.


Involvement of the central catecholaminergic system in nicotine-induced tail-tremor in rats.
The effect of 6-hydroxydopamine on repeated nicotine-induced tail-tremor was investigated in rats. Tail-tremor induced by nicotine (0.5 mg/kg/day, subcutaneously) became more pronounced in intensity with daily administration for 9 days. Rats pretreated with 6-hydroxydopamine (250 micrograms, intracerebroventricularly) showed almost the maximum degree of tail-tremor during the whole experimental period. However, in rats pretreated with 6-hydroxydopamine plus desipramine, enhancement of tail-tremor was slight in the beginning but increased with the daily nicotine administration. Fourteen-day administration of nicotine did not result in significant changes in noradrenaline and dopamine levels in the cortex, hypothalamus, striatum and nucleus accumbens. These results suggest that nicotine-induced tail-tremor is associated with the supersensitivity of postsynaptic catecholaminergic receptors in the central nervous system, and that the noradrenergic system may be more important than the dopaminergic system in this phenomenon.


BEST-TROSY experiments for time-efficient sequential resonance assignment of large disordered proteins.
The characterization of the conformational properties of intrinsically disordered proteins (IDPs), and their interaction modes with physiological partners has recently become a major research topic for understanding biological function on the molecular level. Although multidimensional NMR spectroscopy is the technique of choice for the study of IDPs at atomic resolution, the intrinsically low resolution, and the large peak intensity variations often observed in NMR spectra of IDPs call for resolution- and sensitivity-optimized pulse schemes. We present here a set of amide proton-detected 3D BEST-TROSY correlation experiments that yield the required sensitivity and spectral resolution for time-efficient sequential resonance assignment of large IDPs. In addition, we introduce two proline-edited 2D experiments that allow unambiguous identification of residues adjacent to proline that is one of the most abundant amino acids in IDPs. The performance of these experiments, and the advantages of BEST-TROSY pulse schemes are discussed and illustrated for two IDPs of similar length (~270 residues) but with different conformational sampling properties.


Genome Sequence of a Urease-Positive Campylobacter lari Strain.
Campylobacter lari is frequently isolated from shore birds and can cause illness in humans. Here, we report the draft whole-genome sequence of a urease-positive strain of C. lari that was isolated in estuarial water on the coast of Delaware, USA.


The level of secretory IgA in saliva of patients with dental infections.
In this study the level of s-IgA in saliva of the patients with dental infections was measured. In the treatment only herbal drug was applied locally after the surgical procedures. The samples of saliva were taken three times: I--before treatment, II--after 3-4 days of the treatment and III--after the treatment. The level of s-IgA in saliva was measured according to ELISA method. Results were compared with 30-people control. Statistical analysis was done according to t-Student test. The level of s-IgA in saliva differed a lot between patients. Mean level of s-IgA in saliva of the patients was statistically higher before treatment and just after the treatment as compared to control (*p < 0.05, **p < 0.01). It was also shown that the level of s-IgA in women before treatment was higher as compared to man. The level of s-IgA was statistically higher in younger age group in comparison with older age group. The statistical differences between women treated and the control in measurements I and II were found (*p < 0.05; **p < 0.01).


Comparative proteomic analysis of outer membrane protein 43 (omp43)-deficient Bartonella henselae.
Outer membrane proteins (OMPs) of Gram-negative bacteria constitute the first line of defense protecting cells against environmental stresses including chemical, biophysical, and biological attacks. Although the 43-kDa OMP (OMP43) is major porin protein among Bartonella henselae-derived OMPs, its function remains unreported. In this study, OMP43-deficient mutant B. henselae (Δomp43) was generated to investigate OMP43 function. Interestingly, Δomp43 exhibited weaker proliferative ability than that of wild-type (WT) B. henselae. To study the differences in proteomic expression between WT and Δomp43, two-dimensional gel electrophoresis-based proteomic analysis was performed. Based on Clusters of Orthologus Groups functional assignments, 12 proteins were associated with metabolism, 7 proteins associated with information storage and processing, and 3 proteins associated with cellular processing and signaling. By semi-quantitative reverse transcriptase polymerase chain reaction, increases in tldD, efp, ntrX, pdhA, purB, and ATPA mRNA expression and decreases in Rho and yfeA mRNA expression were confirmed in Δomp43. In conclusion, this is the first report showing that a loss of OMP43 expression in B. henselae leads to retarded proliferation. Furthermore, our proteomic data provide useful information for the further investigation of mechanisms related to the growth of B. henselae.


From mirror self-recognition to the looking-glass self: exploring the Justification Hypothesis.
In his Tree of Knowledge (ToK) System, Henriques (2003) posits that the human ego or "self" has evolved because human beings are the only animals that have had to justify their behavior to others. This essay provides evidence for this Justification Hypothesis (JH) from everyday life sociology, starting with the work of George Herbert Mead and Charles Horton Cooley, and focuses on research related to the concept of the "looking-glass self." Special emphasis is given to the pragmatics of speech acts, the presentation of self in interaction rituals, the accounts given by actors in justification of their actions, and the role of social norms and conformity in the large-scale justification systems commonly called "culture."


Epidemiological characterization of newly recognized rat parvovirus, "rat orphan parvovirus".
Newly recognized rat parvovirus (rat orphan parvovirus: ROPV) was examined for viral excretion and persistence in infected rats, and also for infectivity to mice and hamsters. The virus appeared to replicate mainly in lymphoid or hematopoietic tissues, and was detected in feces, urine and oropharynx of the infected rats at 1 to 4 weeks postinfection. The infective virus was also detected in peripheral leukocytes and various tissues at an acute phase of infection, and decreased in every tissue at 8 weeks postinfection. Viral DNA, however, was persistent in lymphoid tissues at least up to 24 weeks postinfection. When the virus was inoculated to mice and hamsters, no evidence of viral production and antibody response was demonstrated. ROPV is assumed to be a variant of the known rat parvovirus which resulted to alter cell tropism and persist in lymphoid or hematopoietic tissues, in order to escape from host immune system.


Sternal dehiscence. Early detection by radiography.
A study was conducted to look for radiographic indicators that might provide a clue to threatened separation of the median sternotomy closure. To evaluate this problem, we studied two groups of patients. In group A the postoperative plain chest roentgenograms of 50 consecutive patients having cardiac operations were reviewed until the time of their complete recovery from the operation. Sternal problems were not identified in these patients clinically. However, chest roentgenograms showed that one patient had a displaced sternal wire and another had a classic sternal separation as judged by the change in wire topography. In the second series of patients, group B, 10 patients with clinical separation of the sternum were similarly evaluated. In seven of the 10 an early subtle change in position of one or more sternal wires preceded clinical detection of separation by 1 to 8 days, and a gross change in the sternal wire positions preceded clinical diagnosis in five patients by 1 to 6 days. The appearances of the wires by roentgenogram showed four common patterns. These findings indicate that thoracic surgeons and radiologists alike do not always carefully examine the appearance of the sternal wires on the postoperative roentgenograms. Subtle changes or gross changes in the position of the wires is an indicator of sternal separation. Therefore, the topography of the sternal wires should be scrutinized along with the other postoperative changes seen on roentgenograms after median sternotomy.


Post-mortem interaction between methidathion and human serum albumin in blood.
Methidathion [3-(dimethoxyphosphinothioylsulfanylmethyl)-5-methoxy-1,3,4-thiadiazol-2-one; hereinafter DMTP], one of the most widely used organophosphorus pesticides, has been detected in some clinical cases of accidental exposure and suicide in Japan. It has been reported that DMTP concentration is decreased in blood. In this study, it is difficult to recover DMTP in the free form because DMTP is bound to human serum albumin (HSA). We detected DMTP adducts in HSA by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). The mass spectra showed that DMTP was preferably bound to the lysine (K), tyrosine (Y), and cysteinylproline (CP) residues of HSA. The concentrations of K-adduct, DMTP-Y-adduct and DMTP-CP-adduct were increased in vitro in a dose-dependent fashion when DMTP concentration was lower than the lethal dose. Furthermore, the DMTP-Y-adduct and DMTP-CP-adduct were also detected in post-mortem blood of an autopsied subject who died by intentional DMTP ingestion. The results suggested that the DMTP-Y-adduct and DMTP-CP-adduct could be used as a biomarker of DMTP poisoning, and the decrease concentration of DMTP in blood after death could be determined on the basis of the concentration of the DMTP-CP-adduct in blood.


Calcified lymph node metastases in adenocarcinoma of the colon.
Radiologically demonstrable calcification has been described in a variety of primary tumours and metastatic deposits. Dystrophic calcification in retroperitoneal lymph nodes may occur in malignant lymphoma or metastatic carcinoma, most often after radiotherapy or chemotherapy. However, de novo calcification in retroperitoneal lymph node metastases from carcinoma are very rare. Such a case is presented here.


Quantification of free water transport in peritoneal dialysis.
In peritoneal dialysis (PD) total net ultrafiltration (NUF) is dependent on transport through small pores and through water channels in the peritoneum. These channels are impermeable to solutes, and therefore, crystalloid osmotic-induced free water transport occurs through them. Several indirect methods to assess free water transport have been suggested. The difference in NUF between a 3.86% and a 1.36% solution gives a rough indication, but is very time consuming. The magnitude of the dip in dialysate/plasma (D/P) sodium in the initial phase of a 3.86% exchange is another way to estimate free water transport. In the present study, a method was applied to calculate free water transport by calculating sodium-associated water transport in one single 3.86% glucose dwell. Forty PD patients underwent one standard peritoneal permeability analysis (SPA) with a 1.36% glucose solution, and another with a 3.86% glucose solution. At different time points intraperitoneal volume and sodium concentration were assessed. This made it possible to calculate total sodium transport. By subtracting this transport (which must have occurred through the small pores) from the total fluid transport, free water transport remained. These results were compared with the other methods to estimate free water transport. For the 1.36% glucose dwell, total transcapillary ultrafiltration in the first hour (TCUF(0-60)) was 164 mL, transport through the small pores was 129 mL, and free water transport was 35 mL (21%). For the 3.86% glucose solution, total TCUF(0-60) was 404 mL, transport through the small pores was 269 mL, and free water transport was 135 mL (34%). The contribution of free water transport in the first minute (TCUF(0-1)) was 39% of the total fluid transport. From the 40 patients, 11 patients had ultrafiltration failure (NUF <400 mL after 4 hours). For these patients the contribution of free water to TCUF(0-1) was significantly lower than for those with normal ultrafiltration (20% vs. 48%, P < 0.05). A strong correlation was present between free water transport as a percentage of total fluid transport and the maximum dip in D/P sodium (r= 0.84). The correlation was not significant with the difference in net ultrafiltration of 3.86% and 1.36% solutions (r= 0.24, P= 0.3). The method applied here is the first direct quantification of free water transport, calculated from a single standard peritoneal function test. It offers a quick possibility to evaluate patients suffering from ultrafiltration failure. In these patients free water transport was impaired, but the origin of this impairment is still to be determined.


Disentangling the effects of promised and delivered inducements: relational and transactional contract elements and the mediating role of trust.
Psychological contracts contain both relational and transactional elements, each of which is associated with unique characteristics. In the present research, the authors drew on these distinct qualities to develop and test hypotheses regarding differential employee reactions to underfulfillment, fulfillment, and overfulfillment of relational and transactional promises. Further, the authors extended their test of the theoretical distinctions between relational and transactional contracts by assessing the relevance of trust as a key underlying mechanism of relational and transactional psychological contract breach effects. Participants in this 3-wave longitudinal study included 342 full-time temporary employees. In support of existing theoretical distinctions, results indicated that employees reacted differently to varying levels of fulfillment of their relational and transactional contracts and that trust is a more central mechanism of relational, as opposed to transactional, psychological contract breach effects. These findings underscore L.S. Lambert, J. R. Edwards, and D. M. Cable's (2003) recent recommendation that the traditional conceptualization and study of psychological contract breach requires expansion.


Bovine chromosomal regions affecting rheological traits in rennet-induced skim milk gels.
Optimizing cheese yield and quality is of central importance to cheese manufacturing. The yield is associated with the time it takes before the gel has an optimal consistency for further processing, and it is well known that gel formation differs between individual milk samples. By identifying genomic regions affecting traits related to rennet-induced gelation, the aim of this study was to identify potential candidate genes affecting these traits. Hence, rennet-induced gelation, including rennet coagulation time, gel strength, and yield stress, was measured in skim milk samples collected from 379 animals of the Swedish Red breed using low-amplitude oscillation measurements. All animals had genotypes for almost 621,000 segregating single nucleotide polymorphisms (SNP), identified using the Bovine HD SNPChip (Illumina Inc., San Diego, CA). The genome was scanned for associations, haplotypes based on SNP sets comprising highly associated SNP were inferred, and the effects of the 2 most common haplotypes within each region were analyzed using mixed models. Even though the number of animals was relatively small, a total of 21 regions were identified, with 4 regions showing association with more than one trait. A major quantitative trait locus for all traits was identified around the casein cluster explaining between 9.3 to 15.2% of the phenotypic variation of the different traits. In addition, 3 other possible candidate genes were identified; that is, UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 1 (GALNT1), playing a role in O-glycosylation of κ-casein, and 2 cathepsins, CTSZ and CTSC, possibly involved in proteolysis of milk proteins. We have shown that other genes than the casein genes themselves may be involved in the regulation of gelation traits. However, additional analysis is needed to confirm these results. To our knowledge, this is the first study identifying quantitative trait loci affecting rennet-induced gelation of skim milk through a high-density genome-wide association study.


Diagnostic approach to recurrent bacterial meningitis in children.
Recurrence of bacterial meningitis in children is not only potentially life-threatening, but also involves or induces psychological trauma to the patients through repeated hospitalization and multiple invasive investigations if the underlying cause remains undetected. Bacteria migration, along congenital or acquired pathways from the skull or spinal dural defects, gains entrance into the central nervous system (CNS) and should be taken into consideration when children face recurrent bacterial meningitis, however, symptoms and signs of cerebrospinal fluid (CSF) rhinorrhea or otorrhea are rare in such patients. Without evidence of CSF leakage, a cranial symptom/sign or coccygeal cutaneous stigmata may suggest the approximate lesion site, diagnosis and detection remains difficult. To detect an occult dural lesion along the craniospinal axis, such as basal encephalocele, dermal sinus tract, or neurenteric cyst, a detailed clinical evaluation and the use of the modern diagnostic imaging methods is necessary. Because of the possibility of concomitant occurrence of more than one malformation, both the frontal and the lateral skull base should be carefully evaluated. Precise localization of the dural lesion is a prerequisite for successful surgical repair. In addition, the bacteria specificity could leave significant clues: Pneumoccocus or Hemophilus suggests cranial dural defects, E. coli or other gram negative bacilli suggests spinal dural defects, and meningococci suggest immunologic deficiency. Asplenia or immunodeficiency such as complement or immunoglobulin deficiency rarely causes recurrent meningitis without a history of frequent infection of non-CNS areas. Salmonella meningitis or brain abscess should not be treated incompletely or inadequately and could lead to recrudescence, relapse or recurrence of bacterial meningitis. Antibiotic (penicillin or trimethoprim-sulfamethoxazole) induced meningitis may repetitively occur on occasion.


Functional materials of 3D bioprinting for wound dressings and skin tissue engineering applications: A review.
The skin plays an important role in vitamin D synthesis, humoral balance, temperature regulation, and waste excretion. Due to the complexity of the skin, fluids loss, bacterial infection, and other life-threatening secondary complications caused by skin defects often lead to the damage of skin functions. 3D bioprinting technology, as a customized and precise biomanufacturing platform, can manufacture dressings and tissue engineering scaffolds that accurately simulate tissue structure, which is more conducive to wound healing. In recent years, with the development of emerging technologies, an increasing number of 3D-bioprinted wound dressings and skin tissue engineering scaffolds with multiple functions, such as antibacterial, antiinflammatory, antioxidant, hemostatic, and antitumor properties, have significantly improved wound healing and skin treatment. In this article, we review the process of wound healing and summarize the classification of 3D bioprinting technology. Following this, we shift our focus on the functional materials for wound dressing and skin tissue engineering, and also highlight the research progress and development direction of 3D-bioprinted multifunctional wound healing materials.


Free energy and kinetics of conformational transitions from Voronoi tessellated milestoning with restraining potentials.
Milestoning is a method aimed at reconstructing the statistical properties of the long-time dynamics of a system by exploiting the crossing statistics of a set of hypersurfaces, called the "milestones", placed along the reaction coordinate [Faradjian and Elber, J. Chem. Phys.2004, 120, 10880]. Recently, Vanden-Eijnden and Venturoli [J. Chem. Phys.2009, 130, 194101] showed that when a complete Voronoi tessellation of the configurational space is available, milestoning can be reformulated to utilise the statistics from a series of independent simulations, each confined within a single cell via strict reflections at the boundaries. As a byproduct, this "Voronoi tessellated milestoning" method also permits to compute the free energy of the tessellation. Here, the method is extended to support the usage of differentiable restraining potentials to confine the trajectories within each cell.


Pregnancy and neonatal outcomes of SARS-CoV-2 infection discovered at the time of delivery: a tertiary center experience in North Italy.
Although the knowledge on SARS-CoV-2 infection in pregnancy has greatly improved, there is still a lack of information on its role in the later stages of gestation. The aim of this study is to investigate whether SARS-CoV-2 discovered at delivery is associated with any obstetric or neonatal complications. A retrospective case-control study was conducted at Department of Obstetrics, University Hospital Maggiore della Carità, Novara, Italy, from March 2020 to March 2023. Pregnant women admitted were tested for SARS-CoV-2. 168 women resulted positive at the time of delivery; the women were asymptomatic or paucisymptomatic. 170 negative women were selected as controls, selecting, for each SARS-CoV-2 positive patient, the patient who gave birth right before, if negative. Demographic and anamnestic characteristics, pregnancy, labor, and neonatal outcomes were evaluated. SARS-CoV-2 positive patients were more likely to have gestational diabetes (13.7 vs. 5.3 %) and required less frequently intrapartum analgesia (11.3 vs. 27 %) and labor augmentation (7.3 vs. 16.5 %). Post-partum hemorrhage rate was lower (13.7 vs. 22.9 %) and a shorter length of first and second stage of labor occurred. There were no statistically significant differences between the two groups regarding the mode of delivery and neonatal outcomes. SARS-CoV-2 positive patients have shorter labor length and a lower incidence of postpartum hemorrhage. Fewer obstetric interventions, as well as less use of intrapartum analgesia and oxytocin, could explain these findings. Moreover, gestational diabetes could increase susceptibility to infection. SARS-CoV-2 infection discovered at the time of delivery in asymptomatic or paucisymptomatic patients does not appear to increase the rate of cesarean delivery or other obstetric complications, and neonatal outcomes have not worsened.


Overexpression of KIAA0101 predicts high stage, early tumor recurrence, and poor prognosis of hepatocellular carcinoma.
KIAA0101 is a proliferating cell nuclear antigen-associated factor and involved in cell proliferation. This study is to elucidate its role in the progression, early tumor recurrence (ETR), and prognosis of hepatocellular carcinoma (HCC). KIAA0101 mRNA was measured by reverse transcription-PCR in 216 resected, unifocal, primary HCCs and its protein in 164 cases by immunohistochemistry. KIAA0101 mRNA was overexpressed in 131 (61%) HCCs, and protein was detected in 105 (64%). KIAA0101 mRNA overexpression correlated with higher tumor grade (P = 0.0001), higher tumor stage with vascular invasion and various extents of intrahepatic spread (P = 1 x 10(-8)), ETR (P = 1.8 x 10(-6)), and lower 5-year survival (P = 0.0026). Multivariate analysis confirmed that KIAA0101 overexpression was an independent risk factor associated with high-grade tumor (P = 0.0001), high-stage tumor (P < 0.0001), and ETR (P = 0.0052) and thus contributed to poor prognosis. KIAA0101 protein-positive tumor cells accumulated at the borders of tumor macro-trabeculae and were more abundant in tumor thrombi than in the main tumors. Hence, KIAA0101 may contribute to growth advantage and resistance to hypoxic insult. In this series, p53 mutation was detected in 93 of 184 (51%) HCCs. In both p53-mutated and non-p53-mutated HCCs, KIAA0101 overexpression correlated with higher vascular invasion (stages IIIA to IV; all Ps < 0.0001) and, accordingly, led to lower 5-year survival rates (P = 0.011 and 0.029, respectively). KIAA0101 correlates with enhanced metastatic potential and is a significant prognostic factor of HCC.


What is the prevalence of burnout amongst first contact physiotherapists working within primary care?
It has long been known general practitioners suffer with burnout. First contact physiotherapists (FCP's) are a new role to primary care. However, concerns have been raised around the longevity and sustainability of the role and the risk of clinician burnout. To assess the prevalence of burnout amongst the FCP workforce. A self-reporting online questionnaire was developed and captured key demographical data and burnout scores amongst FCP's between February 2022 and March 2022. The burnout assessment tool (BAT12) was used to assess clinician burnout. A total of 332 responses were collected. Overall, 13% of clinicians were burnt out, and 16% at risk. The BAT12 also found 43% of the clinicians are exhausted and a further 35% are at risk of exhaustion. Non-clinical hours were significantly associated with burnout score. Clinicians who had more non-clinical time per month were the least burnt out. Increased non-clinical hours was significant in reducing burnout score. This study found 13% of clinicians are suffering from burnout with a further 16% at risk. Worryingly 78% of clinicians are either exhausted or at risk of exhaustion. Non-clinical hours have a direct impact on burnout and every effort is needed by employers to increase non-clinical time. This study supports the release by the Chartered Society of Physiotherapy whereby they recommend sufficient time be allocated within job plans for appropriate supervision, training and continued professional development. Further research is needed to explore the association of non-clinical time and clinician burnout.


Evaluation of a cacao drink as a simple oral stimulus to assess gallbladder contraction.
Gallbladder contractility plays an important role in the pathogenesis of gallstones and in the course of cholelithiasis. Furthermore, a functioning gallbladder is an important condition for performing a successful disolution of gallstones by bile acids. Therefore, a reliable simple physiological test is desired to assess gallbladder contractility. In ten volunteers gallbladder contraction was stimulated by 50 g chocolate, 330 ml cacao drink or in comparison by intramuscular injection of 0.3 microgram/kg ceruletide. Gallbladder volume was measured sonographically and CCK in serum was determined by radioimmunoassay (RIA) after 0, 15, 30 and 45 min. Additionally gallbladder contraction was determined in 20 patients with symptomatic gallstones using cacao drink on ceruletide. In health volunteers remaining gallbladder volume after 30 min was 28% +/- 5% using ceruletide and 37% +/- 7% using cacao. Stimulation by chocolate resulted in a remaining volume of 59% +/- 12% after 45 min only. Simultaneously to gallbladder contraction an increase of CCK in serum was registered. 30 min after cacao CCK had increased from 0.9 to 3.3 pmol/l. Using chocolate an increase of CCK amounted to 2.1 pmol/l after 45 min only. In patients with gallstones the positive predictive value of the cacao test for a functioning gallbladder was 91% and the negative predictive value was 78% in comparison to the unphysiologic stimulation by ceruletide injection. Cacao test but not chocolate is suitable and reliable to assess gallbladder contraction in patients with symptomatic gallstones.


A stimulus-contingent positive feedback loop enables IFN-β dose-dependent activation of pro-inflammatory genes.
Type I interferons (IFN) induce powerful antiviral and innate immune responses via the transcription factor, IFN-stimulated gene factor (ISGF3). However, in some pathological contexts, type I IFNs are responsible for exacerbating inflammation. Here, we show that a high dose of IFN-β also activates an inflammatory gene expression program in contrast to IFN-λ3, a type III IFN, which elicits only the common antiviral gene program. We show that the inflammatory gene program depends on a second, potentiated phase in ISGF3 activation. Iterating between mathematical modeling and experimental analysis, we show that the ISGF3 activation network may engage a positive feedback loop with its subunits IRF9 and STAT2. This network motif mediates stimulus-specific ISGF3 dynamics that are dependent on ligand, dose, and duration of exposure, and when engaged activates the inflammatory gene expression program. Our results reveal a previously underappreciated dynamical control of the JAK-STAT/IRF signaling network that may produce distinct biological responses and suggest that studies of type I IFN dysregulation, and in turn therapeutic remedies, may focus on feedback regulators within it.


Molecular genetics of polycystic kidney disease.
Polycystic kidney disease (PKD) is a major, multigene disorder that is characterized by the growth of large, fluid-filled cysts from the nephrons and collecting ducts of affected kidneys. At least three different genes are thought to give rise to the autosomal dominant (ADPKD) form of PKD. Two of the genes (PKD1 and PKD2) have now been isolated and sequenced, and based on their predicted structures are thought to encode proteins (polycystin-1 and polycystin-2) that function together as part of a multi-component membrane-spanning complex involved in cell-cell or cell-matrix interactions. Most mutations identified in affected families appear to be inactivating for the PKD1 and PKD2 genes, and recent evidence has suggested that a two-hit mechanism, in which the normal PKD1 allele is also inactivated, may be required for cyst growth. The large number of genes showing abnormal expression in cystic kidneys in humans and rodent models suggests that cellular processes associated with signal transduction, transcriptional regulation, and cell-cycle control are involved in cyst formation and that the cellular defect in PKD directly affects the regulation of epithelial differentiation.


Rheumatology practice amidst the COVID-19 pandemic: a pragmatic view.
The coronavirus disease 2019 (COVID-19) pandemic has come with many challenges for healthcare providers and patients alike. In addition to the direct burden it has placed on societies and health systems, it had a significant impact in the care of patients with chronic diseases, as healthcare resources were deployed to fight the crisis, and major travel and social restrictions were adopted. In the field of rheumatology, this has required notable efforts from departments and clinicians to adapt to the novel status quo and assure the follow-up of patients with rheumatic and musculoskeletal diseases. In the present viewpoint, we provide a practical approach to tackle this reality. Key measures include setting up preventive team management strategies, optimising communication with patients and reorganising patient care in all its dimensions. We then anticipate the nuances of rheumatology practice as restrictive measures are progressively lifted, while an effective vaccine is still pending. This includes the need to reimpose the same strategy as further waves unfold. Finally, we look ahead and address the lessons we can incorporate into post-COVID-19 rheumatology.


The Telomeric Complex and Metabolic Disease.
The attrition of telomeres is believed to be a key event not only in mammalian aging, but also in disturbed nutrient sensing, which could lead to numerous metabolic dysfunctions. The current debate focuses mainly on the question whether telomere shortening, e.g., as a heritable trait, may act as a cause or rather represents a consequence of such chronic diseases. This review discusses the damaging events that ultimately may lead or contribute to telomere shortening and can be associated with metabolic diseases.


SD-OCT analysis of regional epithelial thickness profiles in keratoconus, postoperative corneal ectasia, and normal eyes.
To assess corneal microarchitecture and regional epithelial thickness profile in eyes with keratoconus, postoperative corneal ectasia (ectasia), and normal unoperated eyes (controls) using spectral-domain optical coherence tomography (SD-OCT). Regional corneal epithelial thickness profiles were measured with anterior segment SD-OCT (Optovue RTVue-100, Optovue Inc., Fremont, CA). Epithelial thickness was assessed at 21 points, 0.5 mm apart, across the central 6-mm of the corneal apex in the horizontal and vertical meridians. One hundred twenty eyes were evaluated, including 49 eyes from 29 patients with keratoconus, 32 eyes from 16 patients with ectasia, and 39 eyes from 21 control patients. Average epithelial thickness at the corneal apex was 41.18 ± 6.47 μm (range: 30 to 51 μm) for keratoconus, 46.5 ± 6.72 μm for ectasia (range: 34 to 60 μm), and 50.45 ± 3.92 μm for controls (range: 42 to 55 μm). Apical epithelial thickness was significantly thinner in eyes with keratoconus (P < .0001) and ectasia (P = .0007) than in controls. Epithelial thickness ranges in all other areas varied widely for keratoconus (range: 21 to 101 μm) and ectasia (range: 30 to 82 μm) compared to controls (range: 43 to 64) (P = .0063). SD-OCT demonstrated significant central and regional epithelial thickness profile differences between keratoconus, ectasia, and control eyes, with significant variability and unpredictability in ectatic eyes. This regional irregularity may necessitate direct epithelial thickness measurement for treatments where underlying stromal variations may be clinically relevant, including corneal collagen cross-linking or topography-guided ablations.


[Measurement of customer satisfaction and participation of citizens in improving the quality of healthcare services.].
Managing quality in health care whilst ensuring equity is a fundamental aspect of the provision of services by healthcare organizations. Measuring perceived quality of care is an important tool for evaluating the quality of healthcare delivery in that it allows the implementation of corrective actions to meet the healthcare needs of patients. The Rome B (ASL RMB) local health authority adopted the UNI EN 10006:2006 norms as a management tool, therefore introducing the evaluation of customer satisfaction as an opportunity to involve users in the creation of quality healthcare services with and for the citizens. This paper presents the activities implemented and the results achieved with regards to shared and integrated continuous improvement of services.


Young Adult ADHD Symptoms in the General Population and Neurocognitive Impairment.
Neurocognitive impairments are associated with child and adult ADHD in clinical settings. However, it is unknown whether adult ADHD symptoms in the general population are associated with the same pattern of cognitive impairment. We examined this using a prospective, population-based cohort spanning birth to age 25 years. We examined associations between self-reported adult ADHD symptoms and cognitive task performance (attention and response inhibition) in adulthood and childhood. Self-rated ADHD symptoms at age 25 were associated with poorer performance in age 25 cognitive tasks capturing ADHD-related functioning (attention B = -0.03, 95% CI [0.05, -0.01], p = .005; response inhibition B = -0.03, 95% CI [-0.05, -0.01], p = .002). Neurocognitive impairments linked to adult ADHD symptoms in the general population, are similar to those found in people with childhood ADHD symptoms and are consistent with findings in adult ADHD clinical samples.


Technical note: Validation of a semi-automated software tool to determine gait-cycle variables in dairy cows.
This paper presents the validation of a software tool called Cow-Gait-Analyzer (University of Bern, Switzerland) to determine gait-cycle variables in lame and non-lame dairy cows using features derived from low-cost, stand-alone 3-dimensional accelerometers (400 Hz). The Cow-Gait-Analyzer automatically extracts the relevant gait events of foot load and toe off, which characterize gait-cycle duration, stance phase, and swing phase during walking. A nonautomatic step is visual inspection of the pedograms. If the software does not automatically choose the right peaks according to pedogram definitions, peaks can be manually chosen. We validated the algorithms by comparing the accelerometer data (pedogram) with the synchronized video data, which we used as a gold standard. We carried out the measurements at the metatarsal level of paired hind limbs during walking. We included 12 non-lame cows and 5 lame cows and expressed overall differences between the Cow-Gait-Analyzer and the gold standard as relative measurement error (RME). We analyzed 34 hind limbs with a mean of 9 gait cycles. The median RME for gait-cycle duration and stance phases were 0 and 1.69%, respectively. The peaks of gait-cycle variables showed RME of 0.67 and 0.24% for foot load and toe off, respectively. The semi-automated Cow-Gait-Analyzer can accurately determine gait-cycle variables in both lame and non-lame cows, and could be used to assess gait patterns in routine clinical and research practice focusing on individual cows.


Gastrointestinal stromal tumour lacking mutations in the KIT and PDGFRA genes in a cat.
Molecular subtyping in gastrointestinal stromal tumours is a useful method for predicting the efficacy of treatment using tyrosine kinase inhibitors in humans. However, owing to the paucity of reports on mutational analyses, the association between genetic mutations and the therapeutic response to tyrosine kinase inhibitors remains unclear in feline gastrointestinal stromal tumours. In this report, we describe the case of a cat with a gastrointestinal stromal tumour which was unresponsive to tyrosine kinase inhibitors. A mutational analysis revealed that the cat lacked mutations in both the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes. Our findings are consistent with the fact that KIT/PDGFRA wild-type gastrointestinal stromal tumours are less responsive to tyrosine kinase inhibitors in humans. This signifies the need for further evaluation and possibly individualised treatment for gastrointestinal stromal tumours in cats on the basis of mutational analyses.


Nuclear Factor κB/MicroRNA-155 Upregulates the Expression Pattern of Cytokines in Regulating the Relapse of Chronic Sinusitis with Nasal Polyps and the Underlying Mechanism of Glucocorticoid.
BACKGROUND The aim of this study was to explore the upregulated nuclear factor kappaB (NF-kappaB)/microRNA-155 (miR-155) in regulating inflammatory responses and relapse of chronic rhinosinusitis (CRS) with nasal polyps (NP), which underlies the molecular mechanism of glucocorticoid treatment. MATERIAL AND METHODS The study recruited 25 patients with eosinophilic (Eos) CRSwNP, 25 patients with Non-Eos CRSwNP, 25 patients with CRS without NP (CRSsNP) and 30 patients with nasal septum deviation (control group). The expression of NF-kappaB/miR-155 and inflammatory cytokines was detected in epithelial tissue specimens. Additionally, a mouse model of Eos CRSwNP was established, and the mice were treated by NF-kappaB inhibitor, miR-155 antagomir, or dexamethasone (DEX) to explore the role of NF-kB/miR-155 and the anti-inflammatory effects of glucocorticoid treatment. RESULTS Results showed that the expression level of NF-kappaB/miR-155 was significantly elevated in the Eos CRSwNP group, accompanied by the upregulation of cytokines: tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-4, IL-5 (P<0.05) compared with the control group, the CRSsNP group or the Non-Eos CRSwNP group. The upregulation of NF-kappaB/miR-155 increased inflammatory mediator cyclooxygenase2 (COX2) while decreasing anti-inflammatory mediator Src homology-2 domain-containing inositol 5-phosphatase 1 (SOCS1), which resulted in the aberrant expression pattern of cytokines in the mice model. DEX treatment inhibited the expression of cytokines and decreased the relapse rate of Eos CRSwNP via inhibiting NF-kappaB/miR-155 (P<0.05). CONCLUSIONS The upregulation of NF-kappaB/miR-155 was crucial in mediating the aberrant expression of inflammatory cytokines in Eos CRSwNP. This molecular mechanism is a concern with the high relapse rate of Eos CRSwNP. However, glucocorticoid treatment inhibited the relapse of CRSwNP via downregulation of NF-kappaB/miR-155.


Identification of the Differential Effect of City-Level on the Gini Coefficient of Health Service Delivery in Online Health Community.
Inequality of health services for different specialty categories not only occurs in different areas in the world, but also happens in the online service platform. In the online health community (OHC), health services often display inequality for different specialty categories, including both online views and medical consultations for offline registered services. Moreover, how the city-level factors impact the inequality of health services in OHC is still unknown. We designed a causal inference study with data on distributions of serviced patients and online views in over 100 distinct specialty categories on one of the largest OHCs in China. To derive the causal effect of the city-levels (two levels inducing 1 and 0) on the Gini coefficient, we matched the focus cases in cities with rich healthcare resources with the potential control cities. For each of the specialty categories, we first estimated the average treatment effect of the specialty category's Gini coefficient (SCGini) with the balanced covariates. For the Gini coefficient of online views, the average treatment effect of level-1 cities is 0.573, which is 0.016 higher than that of the matched group. Similarly, for the Gini coefficient of serviced patients, the average treatment effect of level-1 cities is 0.470, which is 0.029 higher than that of the matched group. The results support the argument that the total Gini coefficient of the doctors in OHCs shows that the inequality in health services is still very serious. This study contributes to the development of a theoretically grounded understanding of the causal effect of city-level factors on the inequality of health services in an online to offline health service setting. In the future, heterogeneous results should be considered for distinct groups of doctors who provide different combinations of online contributions and online attendance.


Social Cognitive Theory Predictors of Human Papillomavirus Vaccination Intentions of College Men at a Southeastern University.
The purpose of this study was to use social cognitive theory to predict human papillomavirus (HPV) vaccination intentions of college men attending a large, southeastern university. Data collection comprised two phases. Phase I established face and content validity of the instrument by a panel of six experts. Phase II assessed internal consistency reliability using Cronbach's alpha and predicted behavioral intentions applying multiple linear regression. HPV knowledge, expectations, self-efficacy to get HPV vaccine, situational perception, self-efficacy in overcoming barriers to get HPV vaccine, and self-control to get HPV vaccine were regressed on behavioral intentions. Situational perception and self-control to get HPV vaccine were significant predictors, accounting for 22% of variance in behavioral intentions to get vaccinated within the next 6 months. Overall, college men reported low behavioral intentions to getting vaccinated. Future interventions should target situational perception and self-control to increase HPV vaccination intentions.


In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity.
The purpose of this study was to evaluate in vitro interactions of commercially obtained pure herbal constituents with p-glycoprotein P-gp and cytochrome P-450 3A4 (CYP3A4) activities, which can further modulate the transcellular transport and metabolism kinetics of orally administered drugs. Caco-2 cells grown in the presence of 0.25 micromol/L 1alpha,25-dihydroxy vitamin D3 and multidrug-resistant 1 (MDR1) transfected MDCK cells were used as models to evaluate the effect of purified herbal constituents (quercetin, hypericin, hyperforin from St. John's wort, kaempferol from ginseng, silibinin from milk thistle, and allicin from garlic) on P-gp-mediated efflux of the human immunodeficiency virus (HIV) protease inhibitor ritonavir. In addition, the inhibitory effect of these constituents on CYP3A4-mediated metabolism was determined by using cortisol as a model compound. Silibinin and hyperforin did not significantly alter cellular uptake of H-ritonavir in Caco-2 cells. A similar result was also observed for silibinin when tested in MDR1-MDCK cells. Quercetin, hypericin, and kaempferol exhibited a remarkable inhibition of P-gp-mediated efflux of ritonavir by increasing its cellular uptake in these models. These values were also comparable with the inhibitory effect of quinidine in Caco-2 cells, a well-known inhibitor of P-gp, on ritonavir efflux from Caco-2 cells. Allicin exhibited a concentration-dependent inhibition of ritonavir efflux when tested on MDR1-MDCK cells. There was a significant decrease in the Apical to Basal/Basal to Apical (AP-BL/BL-AP) transport ratio of ritonavir in presence of hypericin, kaempferol, and quercetin. These herbal constituents inhibited the CYP3A4 activity when tested with the Vivid CYP3A4 assay kit, whereas silibinin did not alter cortisol metabolism. Hypericin showed a significant inhibition in reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent metabolism of cortisol with 64.6% of intact drug at the end of a 1-hour study. Similarly, kaempferol and quercetin also caused substantial inhibition of cortisol metabolism with 89.7% and 90.1% of intact cortisol, respectively, compared with 45.9% in the control. Prolonged exposure of quercetin resulted in significant increase of mRNA expression of both MDR1 and CYP3A4 levels in Caco-2 cells. However, hyperforin caused upregulation of CYP3A4 and downregulation of MDR1, whereas the effect of silibinin and kaempferol remained inconclusive on these gene expressions. Hypericin, kaempferol, quercetin, and allicin inhibit the efflux and CYP3A4-mediated metabolism of xenobiotics in vitro. Hence, this study warns against the use of herbal constituents along with prescribed HIV protease inhibitors that are substrates for P-gp and/or CYP3A4.


Diseases of oxidative phosphorylation due to mtDNA mutations.
Mitochondrial encephalomyopathies are disorders due to biochemical defects in the respiratory chain, which is under dual genetic control: 13 proteins are encoded by mitochondrial DNA (mtDNA), while all others are encoded by nuclear DNA. In the past 12 years, the small circle of mtDNA has proven to be a Pandora's box of pathogenic mutations, associated with a bewildering variety of multisystemic or tissue-specific disorders. After summarizing the principles of mitochondrial genetics, we attempt to provide general principles and practical clues to the diagnosis of mtDNA-related disorders by reviewing sequentially clinical presentation, family history, laboratory data, neuroradiology, exercise physiology, muscle morphology, muscle biochemistry, and molecular genetics.


Wave-like Patterns of Plant Phenology Determine Ungulate Movement Tactics.
Animals exhibit a diversity of movement tactics [1]. Tracking resources that change across space and time is predicted to be a fundamental driver of animal movement [2]. For example, some migratory ungulates (i.e., hooved mammals) closely track the progression of highly nutritious plant green-up, a phenomenon called "green-wave surfing" [3-5]. Yet general principles describing how the dynamic nature of resources determine movement tactics are lacking [6]. We tested an emerging theory that predicts surfing and the existence of migratory behavior will be favored in environments where green-up is fleeting and moves sequentially across large landscapes (i.e., wave-like green-up) [7]. Landscapes exhibiting wave-like patterns of green-up facilitated surfing and explained the existence of migratory behavior across 61 populations of four ungulate species on two continents (n = 1,696 individuals). At the species level, foraging benefits were equivalent between tactics, suggesting that each movement tactic is fine-tuned to local patterns of plant phenology. For decades, ecologists have sought to understand how animals move to select habitat, commonly defining habitat as a set of static patches [8, 9]. Our findings indicate that animal movement tactics emerge as a function of the flux of resources across space and time, underscoring the need to redefine habitat to include its dynamic attributes. As global habitats continue to be modified by anthropogenic disturbance and climate change [10], our synthesis provides a generalizable framework to understand how animal movement will be influenced by altered patterns of resource phenology.


Rational design and asymmetric synthesis of potent and neurotrophic ligands for FK506-binding proteins (FKBPs).
To create highly efficient inhibitors for FK506-binding proteins, a new asymmetric synthesis for pro-(S)-C(5) -branched [4.3.1] aza-amide bicycles was developed. The key step of the synthesis is an HF-driven N-acyliminium cyclization. Functionalization of the C(5) moiety resulted in novel protein contacts with the psychiatric risk factor FKBP51, which led to a more than 280-fold enhancement in affinity. The most potent ligands facilitated the differentiation of N2a neuroblastoma cells with low nanomolar potency.


Impaired Autophagic Flux in Glucose-Deprived Cells: An Outcome of Lysosomal Acidification Failure Exacerbated by Mitophagy Dysfunction.
Autophagy dysfunction is associated with human diseases and conditions including neurodegenerative diseases, metabolic issues, and chronic infections. Additionally, the decline in autophagic activity contributes to tissue and organ dysfunction and aging-related diseases. Several factors, such as down-regulation of autophagy components and activators, oxidative damage, microinflammation, and impaired autophagy flux, are linked to autophagy decline. An autophagy flux impairment (AFI) has been implicated in neurological disorders and in certain other pathological conditions. Here, to enhance our understanding of AFI, we conducted a comprehensive literature review of findings derived from two well-studied cellular stress models: glucose deprivation and replicative senescence. Glucose deprivation is a condition in which cells heavily rely on oxidative phosphorylation for ATP generation. Autophagy is activated, but its flux is hindered at the autolysis step, primarily due to an impairment of lysosomal acidity. Cells undergoing replicative senescence also experience AFI, which is also known to be caused by lysosomal acidity failure. Both glucose deprivation and replicative senescence elevate levels of reactive oxygen species (ROS), affecting lysosomal acidification. Mitochondrial alterations play a crucial role in elevating ROS generation and reducing lysosomal acidity, highlighting their association with autophagy dysfunction and disease conditions. This paper delves into the underlying molecular and cellular pathways of AFI in glucose-deprived cells, providing insights into potential strategies for managing AFI that is driven by lysosomal acidity failure. Furthermore, the investigation on the roles of mitochondrial dysfunction sheds light on the potential effectiveness of modulating mitochondrial function to overcome AFI, offering new possibilities for therapeutic interventions.


Distracted cervical spinal fusion for management of caudal cervical spondylomyelopathy in large-breed dogs.
Using an autogenous bone graft (obtained from the iliac crest), 4-mm cancellous bone screws, and polymethylmethacrylate, a distracted cervical spinal fusion technique was performed on 10 dogs with myelographic evidence of caudal cervical spondylomyelopathy. All dogs had evidence of dynamic soft tissue spinal cord compression, as indicated by flexion, extension, and traction myelographic views. Of the 10 dogs, 4 previously had undergone surgery by use of ventral slot or cervical disk fenestration techniques, and their neurologic status had deteriorated after the original surgery. Preoperative neurologic status of the 10 dogs included nonambulatory tetraparesis (n = 5), severe ataxia with conscious proprioceptive deficits (n = 2), and mild ambulatory ataxia with conscious proprioceptive deficits (n = 3). Five dogs had signs of various degrees of cervical pain. Clinical improvement was observed in 8 of 10 dogs--either improved neurologic status or elimination of cervical pain. Implant loosening developed in 3 dogs; 2 of them were euthanatized because of lack of neurologic improvement. Radiographic evidence of bony cervical fusion was observed during a 9- to 24-week period in 6 of the 8 surviving dogs. The distracted cervical fusion technique appears to be a valid surgical procedure to manage cervical spondylomyelopathy in those dogs in which the lesions are limited to one cervical intervertebral disk space.


Rapid increase in the incidence of type 1 diabetes in Polish children from 1989 to 2004, and predictions for 2010 to 2025.
We analysed the temporal changes in the incidence of childhood type 1 diabetes and its demographic determinants in Poland from 1989 to 2004, validating the model with data from 1970 to 1989. We also estimated a predictive model of the trends in childhood diabetes incidence for the near future. Children under 15 years with newly diagnosed type 1 diabetes mellitus and drawn from seven regional registries in Poland were ascertained prospectively using the Epidemiology and Prevention of Diabetes study (EURODIAB) criteria. The type 1 diabetes incidence rates (IRs) were analysed in dependency of age, sex, seasonality, geographical region and population density. Time trends in IR were modelled using several approaches. The average incidence, standardised by age and sex, for 1989 to 2004 was 10.2 per 100,000 persons per year and increased from 5.4 to 17.7. No difference was found between boys and girls, or between urban and rural regions. In children above 4 years, IR was significantly higher in the population of northern Poland than in that of the country's southern part, as well as in the autumn-winter season, this finding being independent of child sex. Based on the trend model obtained, almost 1,600 Polish children aged 0 to 14 years are expected to develop type 1 diabetes in 2010, rising to more than 4,800 in 2025. The estimates suggest at least a fourfold increase of IR between 2005 and 2025, with the highest dynamics of this increment in younger children. These estimates show that Poland will have to face a twofold higher increase in childhood type 1 diabetes than predicted for the whole European population. The dramatic increase could have real downstream effects on Poland's healthcare system.


Rheumatoid factors: good or bad for you?
Rheumatoid factors (RFs) are autoantibodies associated with rheumatoid arthritis. They can be detected in normal individuals, although transiently. This dichotomy has led to questions about the origins and types of RFs. Recently it has been shown that B cells that produce RFs only do so when activated by two signals, one from engagement of the B-cell receptor and the other from recognition of a pathogen-associated molecular pattern through a Toll-like receptor (TLR). These autoantibodies thus link the innate and acquired immune responses. Through a review of the literature, an examination of the current knowledge of RF induction is presented. The focus is on a discussion of a beneficial or detrimental role for RFs in normal individuals and in those with chronic disease. What makes RF 'good' in some cases and 'bad' in others may reflect the type of RF produced. Low-affinity polyreactive IgM RFs are probably beneficial as they aid in the clearance of immune complexes that are more efficiently cleared, and the RF B cell can act as an antigen-presenting cell and stimulate host defense. However, large amounts of high-affinity RFs found in patients with chronic disease may be harmful by participation in a vicious cycle of autoantibody production by stimulation of self lymphocytes, and/or deposition in blood vessels thus causing vasculitis. Whether RFs are beneficial or detrimental depends on the context in which they are expressed, the type and amount of RF produced, whether the response is perpetuated by TLR ligation and whether other cells are stimulated either directly or indirectly by RF-positive B cells.


IDENTIFICATION OF QTLs ON CHROMOSOME 1B FOR GRAIN QUALITY TRAITS IN BREAD WHEAT (TRITICUM AESTIVUM L.).
The present study was designed considering the importance of grain quality traits, genetic diversity and marker-trait association analysis in wheat. A significant amount of genetic diversity was found for various seed traits though the genotypes included in the study were found structured. The extent of polymorphism was high with a range of 2-13 alleles and average of 6.5 alleles per locus. Population structure was detected with 30 unlinked SSRs that divided the population of 92 genotypes in three sub-populations. Extensive LD extent was found on chromosome 1B with 42 SSRs specific for 1B chromosome. Marker-trait associations were determined using mixed linear model, where, population structure and kinship calculated on the basis of unlinked markers were covariated with 1B specific markers and traits data. Eight QTLs for five traits including protein, gluten contents, test weight bread and chapati making quality. Protein content, test weight, bread quality and Glu-B1 were found significantly associated with primers WMC419 (32 cM); WMC128 (30 cM), WMC419 (32 cM); WMC818 (17 cM) and WMC416 (44 cM), respectively.


Dietary polyunsaturated fatty acids decrease fat deposition in separable fat depots but not in the remainder carcass.
Two experiments were conducted in order to determine the effect of dietary fatty acid profile on deposition of body fat, carcass fat, and separable fat depots. Diets with four types of fat (tallow, olive, sunflower, and linseed oils) at an inclusion level of 10% were administered to female broiler chickens. In Experiment 1, total body fat, carcass fat (total body fat minus abdominal fat), and abdominal fat (AF) were determined. In Experiment 2, several separable fat depots (abdominal, neck, sartorial, and mesenteric fat) were removed and weighed. In general, the analyzed separable fat depots were reduced in broilers fed sunflower or linseed oils with respect to those fed tallow or olive oil (P < 0.05). Percentages of body and carcass fat were also slightly reduced in birds fed sunflower or linseed oil, with respect to those fed tallow; however, the differences were not statistically significant. Regression analysis showed that body fat, carcass fat, and fat depots variability were closely correlated with AF (R2 = 0.69, 0.56, and 0.81, respectively), except for birds fed tallow, in which abdominal and mesenteric fat showed a different growth pattern with respect to the other treatments and to the other fat depots. These results suggest that polyunsaturated fatty acids reduce fat deposition in separable fat depots with respect to monounsaturated and saturated fats but not in the rest of the body fat depots. The growth pattern of fat depots can be modified by dietary fatty acid profile. Broilers fed saturated fat tend to deposit more fat in abdominal and mesenteric depots.


Methotrexate analogues. 23. Synthesis, dihydrofolate reductase affinity, cytotoxicity, and in vivo antitumor activity of some putative degradation products of methotrexate-poly(L-lysine) conjugates.
Derivatives of methotrexate (MTX) in which the gamma-carboxyl group is joined to the epsilon-amino group of L-lysine, L-lysyl-L-lysine, or L-lysyl-L-lysyl-L-lysine, respectively, were prepared for evaluation of their dihydrofolate reductase (DHFR) affinity, their ability to retard cell growth in culture, and their antitumor activity in vivo. These small lysine derivatives of MTX are of interest as putative breakdown products of MTX-poly(L-lysine). Inhibition of DHFR in a cell-free assay was decreased only 3-fold relative to MTX, indicating that gamma-substitution by up to three lysines is well tolerated for binding. On the other hand, toxicity toward L1210 murine leukemia cells in culture decreased up to 120-fold relative to MTX as the lysines increased in number from one to three, suggesting that uptake across the cell membrane becomes difficult when positively charged lysines are at the gamma-position. Growth inhibition of H35 rat hepatoma cells was decreased 40- to 60-fold relative to MTX, but in H35R0.3 cells, which have normal DHFR content but are 180-fold MTX resistant by virtue of a transport defect, the lysine derivatives were only 3- to 7-fold less toxic than MTX. When the adducts were given to L1210 leukemic mice by twice-daily injection for 10 days, an increase in life span (ILS) of 80-100% was observed at 40 mg/kg (equivalent to 20-30 mg/kg of MTX). MTX itself, on the same schedule, gave a 100% ILS at 0.5 mg/kg. The low in vivo activity of the mono-, di-, and trilysine adducts suggests minimal systemic hydrolysis to free MTX.


A case study of Primary Progressive Aphasia: improvement on verbs after rTMS treatment.
This case-report shows that high frequency repetitive Transcranial Magnetic Stimulation (hf-rTMS), applied to the left prefrontal cortex, may improve the linguistic skills in Primary Progressive Aphasia (PPA). The patient's performance was evaluated on a battery of language production and memory span tasks, before and after two hf-rTMS treatments and one SHAM treatment. We observed a significant and lasting improvement of the patient's performance on verb production following the application of hf-rTMS versus Baseline and SHAM conditions. This finding suggests that hf-rTMS may directly strengthen the neural connections within an area of metabolic dysfunction and encourages the use of rTMS as an alternative therapeutic tool for neurodegenerative forms of aphasia.


Intoeing: a developmental norm.
Intoeing, often referred to as pigeon-toes, is a frequent reason for referral to the pediatric orthopaedic surgeon's practice. Parents and grandparents are concerned about the appearance of the legs and a history of frequent tripping and falling. Many of the "abnormalities" that these children present with are variations of normal development of the lower extremities and include flat footedness, and torsional or angular "deformity." The approach of the specialist team is to identify the source of the intoeing, to rule out neuromuscular dysfunction or other serious conditions, and to counsel the family on anticipatory guidance of the natural history of intoeing. The focus of this article is intoeing, associated examination techniques, and nursing considerations of education and treatment. An understanding of musculoskeletal developmental norms, the clinical examination for intoeing, and the current recommendations for treatment will enable the provider to educate and accurately inform families.


Descriptions of two new stick insect species of Cnipsomorpha Hennemann, Conle, Zhang & Liu (Phasmatodea) from China based on integrative taxonomy.
Accurate taxonomical identification is an extremely important basis for stick insect research, including evolutionary biology but also applied biology such as pest control. In addition, genetic methods are a valuable identification auxiliary technology at present. Therefore, this paper used morphological and molecular data to investigate five stick insect specimens from the genus Cnipsomorpha in Yunnan, successfully identifying two new species: Cnipsomorphayunnanensis Xu, Jiang & Yang, sp. nov. and C.yuxiensis Xu, Jiang & Yang, sp. nov. A phylogenetic tree was constructed through their 28S and COI genes in order to infer the phylogenetic position of the two new species. Photographs of the new species and a key to all known Cnipsomorpha species are provided.


The maltreatment of children: some unresolved problems.
Evidence suggests that physical results may be the least important criterion of successful management of maltreated children. Emotional, social, intellectual and personality development results should receive equal attention. The maltreated child may himself be a potential child-batterer and separation from his parents may not alter this prognosis. Professional ignorance, denial and collusion are all barriers to successful management, as are inadequate treatment facilities and a cumbersome legal system whose inappropriate priorities may readily produce tragedy.


Naturally occurring recombination in ferret coronaviruses revealed by complete genome characterization.
Ferret coronaviruses (FRCoVs) exist as an enteric and a systemic pathotype, of which the latter is highly lethal to ferrets. To our knowledge, this study provides the first full genome sequence of a FRCoV, tentatively called FRCoV-NL-2010, which was detected in 2010 in ferrets in The Netherlands. Phylogenetic analysis showed that FRCoV-NL-2010 is most closely related to mink CoV, forming a separate clade of mustelid alphacoronavirus that split off early from other alphacoronaviruses. Based on sequence homology of the complete genome, we propose that these mustelid coronaviruses may be assigned to a new species. Comparison of FRCoV-NL-2010 with the partially sequenced ferret systemic coronavirus MSU-1 and ferret enteric coronavirus MSU-2 revealed that recombination in the spike, 3c and envelope genes occurred between different FRCoVs.


Digital pressure in haemodialysis patients with brachial arteriovenous fistula.
: The pathophysiological mechanisms involved in distal pressure changes following arteriovenous fistula (AVF) creation in patients with end-stage renal disease (ESRD) are not completely understood. This study was aimed to assess digital pressure changes post-AVF creation and to identify the factors that might influence these changes in ESRD patients. : In this prospective study, 41 patients with ESRD underwent AVF creation. Basal digital pressure (BDP), digital brachial index (DBI), calcium, phosphorus and blood urea levels were assessed preoperatively. BDP, DBI, vein and artery diameters, and AVF blood flow were also evaluated at one and two month(s) post-AVF creation. : Mean BDP significantly decreased from 131.64±25.86 mmHg (baseline) to 93.15±32.14 and 94.53±32.90 mmHg at one and two months post-AVF creation, respectively (P <0.001). Mean DBI significantly decreased one month post-AVF creation versus baseline (0.70±0.18 vs. 0.89±0.17 mm, P <0.001) and remained similar at two versus one month(s) postoperatively (0.70±0.23 vs. 0.70±0.18 mm). At both postoperative timepoints, no correlation between DBI decrease and increased artery and vein diameters or fistula blood flow was observed. Mean DBI difference between patients with previous ipsilateral access versus those without was not significant from pre to one month postoperatively. No correlation was observed between baseline phosphorus, calcium and blood urea nitrogen and DBI changes. : Our findings suggest that decrease in distal pressure following AVF creation may not be influenced by the arterial remodelling degree, vein diameter or fistula flow. In uraemic patients, those with low calcium and/or increased phosphorus, no association between these parameters and DBI changes could be observed.


Mycophenolate mofetil (RS-61443): preclinical, clinical, and three-year experience in heart transplantation.
Mycophenolate mofetil (formerly known as RS-61443) is a morpholinoethyl ester of mycophenolic acid. Mycophenolic acid is a unique immunosuppressive agent because of its mechanism of action. By inhibiting the de novo pathway of purine synthesis, mycophenolic acid suppresses lymphocyte function much more than that of neutrophil, erythrocyte, and other rapidly dividing cell lines which can use the salvage purine synthesis pathway. Mycophenolate mofetil has been shown to be an effective immunosuppressive agent in both animal models and early human trials. This article describes the history, biochemistry, pharmacology, in vitro and in vivo effects, and clinical trials of myophenolate mofetil. In addition, previously unpublished 3-year follow-up of heart transplant recipients receiving mycophenolate mofetil is reported.


Involvement of the cellular vacuolar system with the cytotoxicity of bleomycin-like agents.
The role of acidic cellular organelles in regulating the toxicity of selected antitumor drugs was studied with L1210 cells using modifiers of vesicular pH or function. A 1 hr exposure to a non-toxic concentration of the acidotropic weak base ammonium chloride increased the lethality of bleomycin A2 (BLM A2), demethyl BLM A2, peplomycin, and talisomycin S10b to L1210 cells grown in culture. Enhanced BLM lethality was also seen with the lysosomal disruptive agents verapamil and diltiazem. The increased lethality with verapamil and BLM A2 was schedule dependent, being seen only when cells were exposed to the drugs simultaneously or to BLM A2 first and then verapamil. Non-toxic concentrations of the monovalent cationic ionophore monensin also increased the cytotoxicity of BLM A2 and talisomycin S10b but not doxorubicin. This enhanced cytotoxicity seen with monensin occurred without an increase in either cell associated BLM A2 or single-strand DNA damage as measured by alkaline elution. We propose that acidic cellular organelles or their contents participate in controlling the cytotoxicity of the BLM class of antitumor agents.


Single-Operator Ultrasound-Guided Central Venous Catheter Insertion Verifies Proper Tip Placement.
To evaluate whether a single-operator ultrasound-guided, right-sided, central venous catheter insertion verifies proper placement and shortens time to catheter utilization. Prospective observational study with historical controls. Adult ICUs. Sixty-four consecutive patients undergoing ultrasound-assisted right-sided central venous catheterization compared with 92 serial historic controls who had unassisted central catheter insertion at the same sites. Subcostal transthoracic echocardiography during catheter insertion. The primary outcome was the correct placement of the catheter tip determined by postprocedural chest radiography. The subclavian site was used in 41 patients (64%) (inserted without ultrasound guidance) in the ultrasound-assisted group and 62 (67%) in the control group, whereas the jugular vein was used in the remaining patients. The tip was accurately positioned in 59 of 68 patients (86.7%) in the ultrasound-assisted group compared with 51 of 94 (54.8%) in the control group (p < 0.001). The median time from end of the procedure to catheter utilization after chest radiography approval was 2.4 hours. A single-operator ultrasound-guided central venous catheter insertion is effective in verifying proper tip placement and shortens time to catheter utilization.