Scanning electron microscopy of human lymphocyte-sheep erythrocyte rosettes.
Human lymphocytes of known B or T derivation were examined by scanning electron microscopy (SEM) before and after rosetting with SRBC. After collection of the cells onto silver membranes the samples were prepared for SEM by the critical point drying method. Sheep RBC frequently underwent sphero-echinocyte transformation and multiple projections extended from their surfaces. This was readily noticeable after storage of SRBC in the cold and washing in Hanks, but more prominent after rosetting. These erythrocyte surface alterations were less apparent when freshly withdrawn cells were used. Spontaneous sheep erythrocyte rosettes (E-R), a marker for human T lymphocytes, were prepared with normal peripheral blood lymphocytes (PBL), thymic cells, and cultured T cells. EAC-rosettes (EAC-R), used to identify B lymphocytes with complement receptors, were prepared with normal PBL and cultured B cells. The majority of rosetting T lymphocytes had generally smooth surfaces while about 20% had an intermediate number of microvilli and 15% were more villous and indistinguishable from villous B cells. Studies of rosetting thymocytes and cultured T cells however indicated that the surface of some T cells alters on rosetting, becoming more villous and thus account for the higher numbers of villous T cells seen in E-rosettes. Point to point contact sites between SRBC and T lymphocytes were more frequent than broad zones of attachment. The majority of rosetting B lymphocytes had multiple microvilli, about 25% had a moderate number of microvilli and less than 10% had smooth surfaces similar to those of most T cells. Areas of contact between EAC and B lymphocytes were frequently broad zones of attachment. The study confirms that in many cases B and T lymphocytes can be distinguished by their surface architecture as seen under the SEM; however, about 20% of rosetting B and T cells have similar surfaces with intermediate numbers of surface microvilli and cannot be distinguished by SEM without parallel immunologic identification.


A Comparative Study of the Adsorption of Transition Metals on Kaolinite.
Adsorption of Pb(II), Cu(II), Zn(II), Co(II), and Mn(II) to kaolinite was measured at 25 degrees C in the presence of 5 mM KNO(3). Adsorption edges (pH 3-10; total metal concentration 100 µM) for Pb(II) and Cu(II) were sigmoid, but those for Zn(II) and Co(II), and especially Mn(II), were characterized by distinct steps after about 40% adsorption. Adsorption isotherms (concentrations up to 60 µM; fixed pH) at pH 5.50 followed the simple Langmuir equation, but those at pH 7.50 (Zn(II), Co(II), and Mn(II)) required a two-site model. More protons were released during adsorption at the higher pH. All adsorption data, and the results of potentiometric titrations of kaolinite suspensions (alone and in the presence of metals at 100 µM), can be fitted closely by a constant-capacitance surface complexation model that incorporates two bidentate surface complexes. One involves electrostatic attraction between transition metal ions and the permanent, negatively charged sites on the silanol faces of kaolinite. The other is an inner-sphere complex at the variable-charge surface hydroxyl groups situated at the crystal edges and on the aluminol faces. Copyright 1999 Academic Press.


The Healthy Living Project: an individually tailored, multidimensional intervention for HIV-infected persons.
The NIMH Healthy Living Project (HLP), a randomized behavioral intervention trial for people living with HIV, enrolled 943 individuals, including women, heterosexual men, injection drug users, and men who have sex with men from Los Angeles, Milwaukee, New York, and San Francisco. The intervention, which is based on qualitative formative research and Ewart's Social Action Theory, addresses three interrelated aspects of living with HIV: stress and coping, transmission risk behavior, and medication adherence. Fifteen 90-minute structured sessions, divided into 3 modules of five sessions each, are delivered to individuals. Sessions are tailored to individuals within a structure that uses role-plays, problem solving, and goal setting techniques. A 'Life Project'--or overarching goal related to personal striving-provides continuity throughout sessions. Because this is an ongoing project with efficacy yet to be established, we do not report intervention outcomes. However, the intervention was designed to be useful for prevention case management, settings where repeated one-on-one contact is possible, and where a structured but highly individualized intervention approach is desired.


Laparoscopic adrenalectomy: where do we stand now?
Laparoscopic adrenalectomy (LA) has become the procedure of choice for the surgical removal of the vast majority of small sized adrenal tumors (<or= 6 cm), because of its significant and multiple advantages: reduced hospital stay and wound morbidity, decreased transfusion requirements, postoperative pain and complications. The role of LA in patients with large adrenal lesions or potential malignancy remains controversial. The aim of this article is to review the current and up-to-date surgical approaches for LA, which include: 1) transabdominal anterior or flank approach and 2) retroperitoneal technique with the patient in either lateral or prone position. Specific advantages and disadvantages are referred to for each of them. The choice of each of these techniques is determined particularly by the preference and the experience of the surgeon, but other objective criteria must be taken into consideration, such as the size of the adrenal and history of previous abdominal surgeries.


Evaluation of immunogenicity and safety of Genevac B: a new recombinant hepatitis B vaccine in comparison with Engerix B and Shanvac B in healthy adults.
Genevac B, a new indigenous recombinant hepatitis B vaccine was evaluated for its immunogenicity and safety in comparison with Engerix B (Smithkline Beecham Biologicals, Belgium) and Shanvac B (Shantha Biotechnics, India) in healthy adult volunteers. While 240 study subjects were included in the Genevac B group, 80 each were the subjects for Engerix B and Shanvac B. A three dose regimen of 0,1,2 months was adopted with 20 gm dosage uniformly in all the three groups. Vaccinees were assessed during prevaccination, followup and post vaccination periods for clinical, haematological, biochemical and immunological parameters for safety and immunogenicity. Successful follow-up in all parameters for four months could be achieved in 92.5% (222/240) for Genevac B study subjects and the same was 85% (68/80) and 80% (64/80) for Engerix B and Shanvac B respectively. While 100% seroconversion was observed in all the three groups, the rate of seroprotectivity was 99.5% by Genevac B, 98.5% by Engerix B and 98.4% for Shanvac B. However the difference was not statistically significant (p>0.05). The GMT values of anti HBs after one month of completion of the vaccination were 735.50, 718.23 and 662.20 mIU/mL respectively. No systemic reaction was either seen or reported by the volunteers during the vaccination process of Genevac B and other two vaccines. Clinical, haematological and biochemical safety parameters remained within normal limits throughout the study period. The study confirms that Genevac B, the new recombinant Hepatitis B vaccine has the acceptable international standards of safety and immunogenicity.


[An unusual case of investigation into the child's disputable descent complicated by manifestation of a rare genomic mutation (disomy)].
This investigation was carried out in the framework of a criminal case concerning substitution of a newborn infant. The subjects involved in the case were the child and its putative mother. Solution of the problem required typing two hypervariable mitochondrial DNA markers and 82 chromosomal markers. Moreover, we had to depart from the current norms according to which parentage can be excluded if two loci of the child contain alleles absent in the reputed parent. The present examination was complicated by the manifestation of a rare genomic mutation (unipaternal disomy) that necessitated extensive studies and taking non-trivial decisions. Details of this unusual case are highlighted and difficulties encountered in the course of investigation discussed to promote future analyses of chromosomal DNA mutations in parental gametes that hamper unambiguous interpretation of results of forensic examination.


Hippocampal place cell instability after lesions of the head direction cell network.
The occurrence of cells that encode spatial location (place cells) or head direction (HD cells) in the rat limbic system suggests that these cell types are important for spatial navigation. We sought to determine whether place fields of hippocampal CA1 place cells would be altered in animals receiving lesions of brain areas containing HD cells. Rats received bilateral lesions of anterodorsal thalamic nuclei (ADN), postsubiculum (PoS), or sham lesions, before place cell recording. Although place cells from lesioned animals did not differ from controls on many place-field characteristics, such as place-field size and infield firing rate, the signal was significantly degraded with respect to measures of outfield firing rate, spatial coherence, and information content. Surprisingly, place cells from lesioned animals were more likely modulated by the directional heading of the animal. Rotation of the landmark cue showed that place fields from PoS-lesioned animals were not controlled by the cue and shifted unpredictably between sessions. Although fields from ADN-lesioned animals tended to have less landmark control than fields from control animals, this impairment was mild compared with cells recorded from PoS-lesioned animals. Removal of the prominent visual cue also led to instability of place-field representations in PoS-lesioned, but not ADN-lesioned, animals. Together, these findings suggest that an intact HD system is not necessary for the maintenance of place fields, but lesions of brain areas that convey the HD signal can degrade this signal, and lesions of the PoS might lead to perceptual or mnemonic deficits, leading to place-field instability between sessions.


[Sanitary evaluation of microclimate conditions at the ore mining and alluvial pits sites].
The authors summarized results of hygienic research carried in pits of Transbaikal region, Yakutia. Tchukotka, Kazakhstan, Kirgizia, Krivoy Rog, European North and other areas. Microclimate parameters in winze of mining and alluvial pits appeared to vary significantly and to depend on certain specific factors (depth of mining, climate geographic zone of the enterprise, temperature of the ores treated, etc.). Considering degree of influence on workers' heat state, taking into account significance of clothes heat insulation required, the authors defined 4 types of microclimate at workplace. For operative selection of optimal special clothing set, the authors represent dependence of proper heat resistance of clothes for main and auxiliary occupations on microclimate conditions.


The Arabidopsis RPS4 bacterial-resistance gene is a member of the TIR-NBS-LRR family of disease-resistance genes.
Plant-disease resistance (R) genes mediate the specific recognition of invading pathogens carrying cognate avirulence (avr) determinants. RPS4 is a disease-resistance locus on chromosome 5 of Arabidopsis thaliana specifying resistance to strains of Pseudomonas syringae pv. tomato expressing avrRps4. We have isolated the RPS4 gene using a map-based cloning approach. RPS4 encodes a predicted protein of 1217 amino acids that contains an N-terminus with homology to the intracellular domains of the Drosophila Toll protein and the mammalian interleukin-1 receptor (TIR domain), a tripartite nucleotide-binding site (NBS), and leucine-rich repeats (LRR). Incomplete splicing of the RPS4 mRNA was observed, which may give rise to truncated protein products consisting mainly of the TIR and NBS domains. These features classify RPS4 as a member of the TIR-NBS-LRR R gene family founded by N, L6 and RPP5, which determine resistance to viral, fungal and oomycete pathogens, respectively. Previous work has shown that RPS4, like other Arabidopsis TIR-NBS-LRR R genes specifying resistance to oomycetes, is dependent on a functional EDS1 allele for disease-resistance signaling. The characterization of RPS4 presented here thus establishes a role for TIR-NBS-LRR R genes in resistance to bacterial pathogens, and provides evidence for the model that dependence of R genes on EDS1 is determined by R protein structure, and not by pathogen type. The cloning of RPS4 and the previous isolation of avrRps4 provide the molecular tools for a genetic and molecular dissection of the TIR-NBS-LRR R gene signaling pathway in Arabidopsis.


The limits of stability in patients with unilateral vestibulopathy.
To characterize the stability limits and region in patients with unilateral vestibulopathy according to the side of the lesion and determine if that imposes any bias. To analyze if the stability limits and region depend on the functional deficit as evaluated in the sensory organization test. Forty patients with chronic dizziness and without any vertigo spell for least 6 months prior to testing. In all of them, a unilateral vestibulopathy was diagnosed clinically and at vestibular testing. A computerized dynamic posturography system was used to test for the ability of patients and controls to displace their center of pressure (COP) to the corresponding LOS. The area was calculated and compared to other data from vestibular tests. The area of stability among patients shows a reduction to 35-62% of the expected total. That reduction was not found to be dependent on age. There is a symmetric reduction in the limits of stability (LOS) in patients with unilateral vestibulopathy who suffer chronic instability. None of the areas measured were correlated with the composite score of the sensory organization test and, as such, must be considered as an adjunct measure to characterize the postural limitations in those patients.


catena-Poly[[triphenyl-tin(IV)]-μ-2-(cyclo-hexyl-amino-carbon-yl)benzoato-κO:O].
In the title polymeric complex, [Sn(C(6)H(5))(3)(C(14)H(16)NO(3))](n), adjacent triphenyl-tin cations are bridged by the N-cyclo-hexyl-phthalamate anion through the carboxyl-ate and carbonyl O atoms, forming a helical chain running along the b axis. The amide N atom is a hydrogen-bond donor to the uncoordinated carboxyl-ate O atom. The geometry at the five-coordinate Sn atom is trans-C(3)SnO(2) trigonal-bipyramidal.


Community-acquired pneumonia: role of atypical organisms.
M. pneumoniae infection occurs world-wide and is the most common cause of community-acquired pneumonia (CAP) in the 5 to 20 year-old age group. The most reliable diagnostic test is enzyme immunoassay that allows immunoglobulin (Ig)G and IgM titration and presents 92% sensitivity and 95% specificity on paired samples. Potentially active drugs are tetracyclines, macrolides, ketolides, lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. The incidence of Legionella infection, in spite of its world-wide diffusion, is highly variable in different studies, ranging from 1% to 27% of CAP. The most likely mode of transmission is direct inhalation from Legionella-contaminated water-supply systems. Extrapulmonary manifestations are relatively common but nonspecific. However, some signs and symptoms may raise the suspicion of Legionella infection: a sputum Gram stain with a high number of neutrophils without any organism, hyponatremia, and diarrhea in a critically ill patient. Urinary radioimmunoassay (RIA) antigen detection is the method of choice for L. pneumophila serogroup 1. The best treatment regimen is a full three-week treatment with a macrolide (erythromycin, clarithromycin, azithromycin). An alternative treatment regimen may be the association of second generation fluoroquinolones with tetracyclines. A notable improvement in most of the new fluoroquinolones is their activity against Legionella, so that their use as single agent may be hypothesised even if clinical data are still insufficient for a definitive indication. Chlamydia pneumoniae account for 6-20% of CAP depending on several factors such as setting of the studied population, age group examined, and diagnostic methods used. The current gold standard for serological diagnosis of acute infection is microimmunofluorescence testing. Tetracyclines and erythromycin show good in vitro activity and so far have been the most commonly employed drugs in the treatment of C. pneumoniae infection. New macrolides, ketolides, and new fluoroquinolones are other potentially effective drugs.


Role of Patrick-FABER test in detecting sacroiliitis and diagnosing spondyloarthritis in subjects with low back pain.
To evaluate sensitivity, specificity, and predictive value of Patrick-FABER test in assessing magnetic resonance imaging (MRI) sacroiliitis and addressing the diagnosis of spondyloarthritis (SpA) in subjects with low back pain (LBP). Subjects with LBP were consecutively enrolled. The assessors were blinded to patients' clinical, laboratory, or imaging data. All subjects underwent sacroiliac joint MRI to detect presence of sacroiliac oedema or structural changes. One hundred and ten subjects were included in the study [males (61.8%); median age of 45 (21-69) years; LBP duration of 78 (3-240) months]. Patrick-FABER test sign's sensitivity was 76.2% (95% CI: 60.5-87.9%), specificity was 66.2% (95% CI: 53.6-77.2%), positive predictive value (PPV) was 58.1% (95% CI: 44.1-71.3%) and negative predictive value (NPV) was 81.8% (95% CI: 69.1-90.9%) for the diagnosis of sacroiliitis, with an overall diagnostic accuracy of 70%. At the univariate and multivariate analysis, Patrick-FABER test sign was associated with inflammatory lesions of sacroiliitis at MRI and SpA diagnosis. Univariate and multivariate analysis showed an association between smoking status (p=0.01), sacroiliitis, and SpA diagnosis. The odds of having sacroiliitis was 2.7 higher in smokers (OR: 2.7; 95% CI: 1.1-7) as compared to non-smokers and 6.3 higher in those with a positive Patrick-FABER test sign (OR: 6.3; 95%CI: 2.5-15.6) as compared to those with a negative sign. Our study shows that Patrick-FABER test positivity could represent a useful clinical test for addressing the use of sacroiliac joints MRI and SpA diagnosis in subjects with LBP. Further, smoking habit could represent an associate anamnestic element for addressing the use of sacroiliac MRI.


Actin--an inhibitor of eukaryotic elongation factor activities.
An inhibitor of diphtheria toxin- and endogenous transferase-dependent ADP-ribosylation of eukaryotic elongation factor 2 (eEF2) has been found in the cytoplasmic fraction from rat liver. We provide evidence that this cytoplasmic inhibitor corresponds to actin, which gives rise also to inhibition of polyphenylalanine (polyPhe) synthesis. Both globular monomeric (G-actin) and filamentous (F-actin) forms of actin appear to be inhibitory on the action of elongation factors 1 and 2 (eEF1 and eEF2) in polyPhe synthesis with the inhibitory effect of G-actin proving to be stronger. Some component(s) in the postribosomal supernatant (S-130) fraction and also DNase I prevent actin-promoted inhibition of polyPhe synthesis.


Why do Jordanian women stay in an abusive relationship: implications for health and social well-being.
The purpose of this study was to explore why Jordanian women stay with an abusive husband. The study used a qualitative approach to collect data from 28 abused women who were recruited through their community during the summer and fall of 2007. Data were collected using an open-ended question through one-on-one in-depth interviews. Results from analysis of the qualitative data revealed that abused Jordanian women identified five main reasons for staying with an abusive husband: the inherited social background, financial dependency, lack of family support, sacrificing self for the sake of the children, and the adverse social consequences of divorce. The results indicate that Jordanian women are strongly bound by traditions and cultural rules and lack all means of empowerment. Results of the study have implications for healthcare providers, social workers, policy makers, and educators to enhance the health and social well-being of Arab Muslim women in Jordan. The findings may also apply to Arab families immigrating to the United States, Canada, and Europe who tend to bring their cultural beliefs, values, and norms, and may help healthcare professionals dealing with violence against women in these countries. Healthcare professionals worldwide need to play an instrumental role in providing culture-specific and evidence-based care to empower women staying in abusive relationships, taking into consideration the influence of Arab Muslim culture.


Developmental profile of excitatory GABA(A) responses in cultured rat cerebellar granule cells.
GABA induced a transient increase in cytosolic free Ca2+ in cerebellar granule cells, which decreased from 3 to 8 days in vitro (DIV). Cytosolic Ca2+ changes induced by glutamate/glycine were comparable at 3 and 7 DIV. The GABA response was ascribed to GABA(A)-receptor mediated depolarization activating L-type Ca2+ channels since the response was inhibited by bicuculline or nifedipine. GABA-mediated Ca2+ rise at 4 DIV was potentiated by pentobarbital or by the neurosteroid 5beta-pregnan-3alpha-ol-20-one, or by decreasing the extracellular Cl- concentration. Neurons cultured for > 7 DIV showed no rise in intracellular Ca2+ in response to GABA regardless of the Cl- gradient. GABA(A) receptor-mediated cytosolic Ca2+ rise suggests an important role for the excitatory activity of GABA in developing cerebellar granule neurons.


Evaluation of the ABX Cobas Vega automated hematology analyzer and comparison with the Coulter STKS.
An evaluation of the new automated hematology analyzer was performed in comparison with the Coulter STKS on 1,694 blood samples coming from the different departments of Nice University Hospital. The Cobas Vega showed very satisfactory results in terms of repeatability, reproducibility and linearity. Correlation with the STKS was excellent with the exception of the following parameters: red blood cell distribution index and the absolute values for eosinophils and basophils. Two qualities were particularly appreciable: absence of leukocyte carryover, and stability of the complete blood count and leukocyte differential count over a long period. Analysis of qualitative flags showed that the overall blood smear review rate was 47% for the Cobas Vega, not forgetting that optical microscopy detects 37% of all abnormalities. The STKS's review rate was 49.5%. Flags commonly concerned the granulocytic lineage, 61% for the STKS and 48% for the Vega, with a false positive rate of 43.4% for the STKS compared with 22% for the Vega. The opposite phenomenon was observed with the flag for atypical lymphocytes which represented 11% of flags for the STKS and 25.6% for the Vega, with a false positive rate of 25.5% for the STKS and 34% for the Cobas Vega. This may be explained by the fact that lymphocyte abnormalities sometimes generated "granulocytic" flags on the STKS. Studies of the false negative rate carried out using light microscopy on 505 blood samples without flags on either system, detected the presence of a slight myelemia, and a few hyperbasophilic lymphocytes or plasmocytes in 18.6% of all cases. Finally, the Cobas Vega's practicality was greatly appreciated and there was no trouble with breakdowns throughout the whole period of its use.


Magnetic quantum tunneling: insights from simple molecule-based magnets.
This perspectives article takes a broad view of the current understanding of magnetic bistability and magnetic quantum tunneling in single-molecule magnets (SMMs), focusing on three families of relatively simple, low-nuclearity transition metal clusters: spin S = 4 Ni(II)(4), Mn(III)(3) (S = 2 and 6) and Mn(III)(6) (S = 4 and 12). The Mn(III) complexes are related by the fact that they contain triangular Mn(III)(3) units in which the exchange may be switched from antiferromagnetic to ferromagnetic without significantly altering the coordination around the Mn(III) centers, thereby leaving the single-ion physics more-or-less unaltered. This allows for a detailed and systematic study of the way in which the individual-ion anisotropies project onto the molecular spin ground state in otherwise identical low- and high-spin molecules, thus providing unique insights into the key factors that control the quantum dynamics of SMMs, namely: (i) the height of the kinetic barrier to magnetization relaxation; and (ii) the transverse interactions that cause tunneling through this barrier. Numerical calculations are supported by an unprecedented experimental data set (17 different compounds), including very detailed spectroscopic information obtained from high-frequency electron paramagnetic resonance and low-temperature hysteresis measurements. Comparisons are made between the giant spin and multi-spin phenomenologies. The giant spin approach assumes the ground state spin, S, to be exact, enabling implementation of simple anisotropy projection techniques. This methodology provides a basic understanding of the concept of anisotropy dilution whereby the cluster anisotropy decreases as the total spin increases, resulting in a barrier that depends weakly on S. This partly explains why the record barrier for a SMM (86 K for Mn(6)) has barely increased in the 15 years since the first studies of Mn(12)-acetate, and why the tiny Mn(3) molecule can have a barrier approaching 60% of this record. Ultimately, the giant spin approach fails to capture all of the key physics, although it works remarkably well for the purely ferromagnetic cases. Nevertheless, diagonalization of the multi-spin Hamiltonian matrix is necessary in order to fully capture the interplay between exchange and local anisotropy, and the resultant spin-state mixing which ultimately gives rise to the tunneling matrix elements in the high symmetry SMMs (ferromagnetic Mn(3) and Ni(4)). The simplicity (low-nuclearity, high-symmetry, weak disorder, etc.) of the molecules highlighted in this study proves to be of crucial importance. Not only that, these simple molecules may be considered among the best SMMs: Mn(6) possesses the record anisotropy barrier, and Mn(3) is the first SMM to exhibit quantum tunneling selection rules that reflect the intrinsic symmetry of the molecule.


A general scaling rule for the collision energy dependence of a rotationally inelastic differential cross-section and its application to NO(X) + He.
The quasi-quantum treatment (QQT) (Gijsbertsen et al., J. Am. Chem. Soc., 2006, 128, 8777) provides a physically compelling framework for the evaluation of rotationally inelastic scattering, including the differential cross sections (DCS). In this work the QQT framework is extended to treat the DCS in the classically forbidden region as well as the classically allowed region. Most importantly, the QQT is applied to the collision energy dependence of the angular distributions of these DCSs. This leads to an analytical formalism that reveals a scaling relationship between the DCS calculated at a particular collision energy and the DCS at other collision energies. This scaling is shown to be exact for QM calculated or experimental DCSs if the magnitude of the (kinematic apse frame) underlying scattering amplitude depends solely on the projection of the incoming momentum vector onto the kinematic apse vector. The QM DCSs of the NO(X)-He collision system were found to obey this scaling law nearly perfectly for energies above 63 meV. The mathematical derivation is accompanied by a mechanistic description of the Feynman paths that contribute to the scattering amplitude in the classically allowed and forbidden regions, and the nature of the momentum transfer during the collision process. This scaling relationship highlights the nature of (and limits to) the information that is obtainable from the collision-energy dependence of the DCS, and allows a description of the relevant angular range of the DCSs that embodies this information.


Effect of chronic experimental renal insufficiency on urate metabolism.
The rise in plasma uric acid (UA) in chronic renal failure (CRF) is quite limited. This may be due to either increased extrarenal excretion, diminished biosynthesis, and/or enhanced degradation of uric acid. The intestinal flux studies revealed a striking modification of urate transport from no net flux to a net secretory flux in the jejunum and from a basal net absorptive to a net secretory flux in the colon of CRF animals. In addition, CRF animals showed a marked reduction in hepatic, renal, and enteric tissue xanthine oxidase activity and no significant change in tissue uricase activity. The correction of anemia with erythropoietin did not significantly alter the plasma concentration or urinary excretion of urate. Thus, enhanced enteric excretion and depressed production of uric acid (reduced xanthine oxidase activity) may account for the lack of significant hyperuricemia in CRF.


[MR and CT patterns of neurocysticercosis].
MRI and CT manifestations were studied in five cases of neurocysticercosis. As demonstrated by long-term follow-ups the disease usually causes multiple lesions the morphology of which depends on the life cycle of the parasite. Tissue lesions consist of three main types: 1) vital cysticerci, 2) inflammatory parenchymatous reactions following degenerating cysts and 3) calcified granulomas. MRI provides all information that is given by CT except for small calcifications which are usually missed. Morphological details of vital cysticerci like cyst wall and scolex are better outlined by MRI. When i.v. contrast medium is applied, it leads to nodular or annular enhancement of inflamed tissue. The sensitivity of MRI towards edema caused by parasite exceeds that of CT by several weeks. CT and MRI are complementary methods providing at the present time the highest degree of specificity in diagnosing neurocysticercosis.


Anomalous nucleation of crystals within amorphous germanium nanowires during thermal annealing.
In this work, germanium nanowires rendered fully amorphous via xenon ion irradiation have been annealed within a transmission electron microscope to induce crystallization. During annealing crystallites appeared in some nanowires whilst others remained fully amorphous. Remarkably, even when nucleation occurred, large sections of the nanowires remained amorphous even though the few crystallites embedded in the amorphous phase were formed at a minimum of 200 °C above the temperature for epitaxial growth and 100 °C above the temperature for random nucleation and growth in bulk germanium. Furthermore, the presence of crystallites was observed to depend on the diameter of the nanowire. Indeed, the formation of crystallites occurred at a higher annealing temperature in thin nanowires compared with thicker ones. Additionally, nanowires with a diameter above 55 nm were made entirely crystalline when the annealing was performed at the temperature normally required for crystallization in germanium (i.e. 500 °C). It is proposed that oxygen atoms hinder both the formation and the growth of crystallites. Furthermore, as crystallites must reach a minimum size to survive and grow within the amorphous nanowires, the instability of crystallites may also play a limited role for the thinnest nanowires.


Compilation and analysis of sigma(54)-dependent promoter sequences.
Promoters recognized by the RNA-polymerase with the alternative sigma factor sigma(54) (Esigma54) are unique in having conserved positions around -24 and -12 nucleotides upstream from the transcriptional start site, instead of the typical -35 and -10 boxes. Here we compile 186 -24/-12 promoter sequences reported in the literature and generate an updated and extended consensus sequence. The use of the extended consensus increases the probability of identifying genuine -24/-12 promoters. The effect of several reported mutations at the -24/-12 elements on RNA-polymerase binding and promoter strength is discussed in the light of the updated consensus.


Effect of bezafibrate on the sequelae of acute experimental focal cerebral ischaemia.
The possibility that the ability of bezafibrate to lower the oxygen affinity of haemoglobin might lead to an increased oxygen delivery to ischaemic cerebral tissue was explored in preliminary studies in two animal models. The combined morbidity and mortality of unilateral carotid ligation in the gerbil appeared to be reduced at two hours in bezafibrate treated animals. By four hours and thereafter the outcome was unaffected. Two hours after MCA occlusion bezafibrate-treated rats showed a significantly reduced rise in tissue lactate concentration (p less than 0.01) suggesting less anaerobic metabolism had occurred in the ischaemic tissue.


Vitamin D deficiency increases risk of nephropathy and cardiovascular diseases in Type 2 diabetes mellitus patients.
Vitamin D (VD) deficiency is associated with insulin function and secretion. It is linked with diabetes mellitus (DM) progression, and complications were also recorded. Therefore, the current study aimed to investigate serum VD level in Type 2 DM (T2DM) patients and its association with diabetic nephropathy and cardiovascular diseases (CVD). In this cross-sectional study, 205 patients with Type 2 diabetes age ranged from 39 to 75 years old were enrolled. Serum VD, high-sensitivity C-reactive protein (hs-CRP), and hemoglobin A1c (HbA1c) were measured. In addition, urinary albumin:creatinine ratio (ACR) was estimated. Patients with Type 2 diabetes had a 78.5% VD level <30 ng/m. ACR and hs-CRP levels were significantly increased in patients with diabetes with VD <30 ng/m (P = 0.011 and P = 0.008, respectively). Female had significantly lower VD level than male P < 0.001. Patients exposed to sunlight had significantly higher VD level and lower hs-CRP levels compared with less-exposed, P value (0.001 and <0.001), respectively. Exercise significantly increased VD and decreased ACR levels in DM patients, P value (0.046 and 0.002), respectively. VD was positively associated with age (r = 0.355 P = 0.040) and negatively correlate with BMI (r = -0.502 P = 0.009), duration of disease (r = -0.498 P = 0.003), ACR (r = -0.384 P = 0.015), and HbA1c (r = -0.327 P = 0.032). The evidence from this study suggest that patients with Type 2 diabetes with VD deficiency are at higher risk for developing CVD and nephropathy.


Synthesis and biological activity of photostable and persistent abscisic acid analogs.
The plant hormone abscisic acid (ABA) plays a critical role in various environmental stress responses and has long been expected to be used in agriculture. However, the practical use of ABA has been limited, mainly because of its photoinstability and rapid biodegradation. We previously developed photostable ABA agonists, BP2A and Me 1',4'-trans-diol BP2A, in which the dienoic acid side chain of ABA was replaced with phenylacetic acid. This finding validated our structure-based approach in designing photostable agonists and provided a basis for developing a more potent or long-lasting ABA agonist. In this study, we synthesized novel BP2A analogs in which the cyclohexenone ring was modified to avoid catabolism by the ABA metabolic enzyme, ABA 8'-hydroxylase. All synthesized analogs showed higher photostability than BP2A under sunlight. In an Arabidopsis seed germination assay, (+)-compounds 5 and 6 with a tetralone ring displayed significantly stronger ABA agonist activity than (+)-BP2A. In contrast, in the in vitro phosphatase assays, both compounds showed comparable or weaker ABA receptor (PYL1) agonistic activity than (+)-BP2A, suggesting that the stronger ABA-like activity of (+)-5 and (+)-6 may arise from their metabolic stability in vivo. This study provides data relevant to designing photostable and persistent ABA agonists.


[Advances in synthesis methods and applications of microporous organic networks for sample preparation].
Sample pretreatment is an essential step in chromatographic analysis. Solid phase extraction (SPE) is a widely used sample pretreatment method. In SPE, the quality of the adsorbent directly affects the adsorption and enrichment efficiency of the target compounds as well as the sensitivity and selectivity of the pretreatment and subsequent analysis. Therefore, the selection and development of adsorbents has become a research hotspot. Microporous organic networks (MONs) are a novel type of covalent organic materials that are synthesized by the Sonogashira reaction of aromatic alkynes and aromatic halides. These networks have the advantages of modifiable structures, large specific surface areas, high porosity, and simple synthesis methods. This paper reviews the synthesis and functional modification methods of MONs, with an emphasis on their applications in sample pretreatment. Future development trends are also prospected. In terms of synthesis, the preparation methods for MON-based materials have progressed from reflux and solvothermal synthesis to room-temperature synthesis, the conditions of which tend to be milder and more efficient. In terms of functional modification, the introduction of macromolecules and active groups (including amino, hydroxyl, and carboxylic groups) can increase the selectivity and active sites of MON-based materials. The combination of MONs with Fe3O4, SiO2, and metal organic frameworks yields core-shell-structured MONs. Furtherly, they can be calcined and etched to form porous carbon structures or hollow multilayer materials. Functionalized MONs and their composite materials have multiple interaction mechanisms (e. g., hydrogen bonding, hydrophobic, electrostatic, and π-π interactions) with various target compounds, thereby realizing their efficient extraction. MONs can be used as adsorbent materials in SPE, Solid phase microextraction, dispersed solid phase extraction, magnetic solid phase extraction, and other pretreatment methods. When combined with chromatography and chromatography-mass spectrometry, MONs achieve good adsorption effects and high sensitivity, demonstrating the application potential of these materials in sample pretreatment.


Clinical exercise physiology students learning with older adults: an innovative simulation-based education programme.
In this paper, we report on a series of placements for clinical exercise physiology students in a simulation-based education environment with older, independent adults. The purpose of these placement opportunities was to help prepare students to work confidently and competently with older adults in primary healthcare settings. The effectiveness of these placements was measured through semi-structured interviews with the students, their supervisors and the volunteer patients, and also by analysing the content of the students' written reflection assignments. A combination of directed content analysis, informed by the research objectives and imposed upon the data, and conventional content analysis, in which codes were developed from themes emerging from the data, was adopted. Coding was based on units of meaning. Overall, the placement aims were met. Students reported increased confidence in communicating with older adults and in using the tools of their trade. This innovative simulation-based education experience helped students gain an understanding of their developing professional identities. However, the data show that some students still failed to recognise the value and importance of communication when working with older adults. The older adults reported that they enjoyed interacting with the students and believed that they had helped the students gain a positive impression of the cognitive and physical abilities of older adults. These older adults had also gained insight into the benefits of exercise physiology in terms of their own wellbeing. This paper demonstrates the benefits of engaging community support in developing healthcare workers and provides guidelines for replication of these innovative simulation-based education experiences. The paper is limited to reporting the social and community engagement benefits for older adults and the learning opportunities for the clinical exercise physiology students. Further research is needed to demonstrate the health gains for older adults who participate in such programmes.


Harmonic motion microwave Doppler imaging: a simulation study using a simple breast model.
A hybrid method for tissue imaging using dielectric and elastic properties is proposed and investigated with simple bi-layered breast model. In this method, local harmonic motion is generated in the tissue using a focused ultrasound probe. A narrow-band microwave signal is transmitted to the tissue. The Doppler component of the scattered signal, which depends on the dielectric and elastic properties of the vibrating region, is sensed. A plane-wave spectrum technique is used together with reciprocity theorem for calculating the response of a vibrating electrically small spherical tumor in breast tissue. The effects of operating frequency, antenna alignment and distance, and tumor depth on the received signal are presented. The effect of harmonic motion frequency on the vibration amplitude and displacement distribution is investigated with mechanical simulations using the finite element method. The safety of the method is analyzed in terms of microwave and ultrasound exposure of the breast tissue. The results show that the method has a potential in detecting tumors inside fibro-glandular breast tissue.


Metabolic processing of gangliosides by normal and Salla human fibroblasts in culture. A study performed by administering radioactive GM3 ganglioside.
Cultured fibroblasts from normal subjects and from subjects affected by Salla disease, characterized by the lack or misfunction of the membrane carrier responsible for the egress of sialic acid from lysosomes, were fed with ganglioside GM3 labeled at the sialic acid acetyl group, [Neu5Ac-3H]GM3, or at C-3 of sphingosine (Sph), [Sph-3H]GM3, or at C-1 of stearoyl chain, [stearoyl-14C]GM3. After a 15-h pulse the total amount of cell-bound GM3 corresponded to about 2% of the endogenous ganglioside content. Cells were then subjected to a 72-h chase, and the radioactive products from both ganglioside catabolism and salvage processes of catabolic fragments were measured. These data indicated that about 50% of the cell-bound ganglioside underwent metabolic processing, suggesting a ganglioside half-life of 2-3 days. [Neu5Ac-3H] formed from [Neu5Ac-3H]GM3 degradation was mostly re-cycled for the biosynthesis of gangliosides and sialoglycoproteins, only a minor part being degraded to [3H]water, which constituted only 1.6% of total metabolite linked radioactivity. [Sph-3H] from the [Sph-3H]GM3 degradation was partly re-cycled for the biosynthesis of gangliosides, neutral glycosphingolipids and sphingomyelin, and partly (about 20% of the total metabolite linked radioactivity) degraded to [3H]water. In Salla fibroblasts metabolic processing of [Neu5Ac-3H]GM3 produced large amounts of free [3H]Neu5Ac, and a reduced incorporation of radioactivity into glycoconjugates (as compared to normal cells). However, the accumulation of free Neu5Ac was not accompanied by an increase of tritiated water. LacCer and Cer from [stearoyl-14C]GM3 catabolism were found to accumulate in Salla fibroblasts, an indication that the enzymes of glycosphingolipid metabolism were affected by the impairment of Neu5Ac egress from lysosomes. Particularly relevant was the accumulation of ceramide which was hardly detectable in control cells.


Concomitant mutation and epimutation of the MLH1 gene in a Lynch syndrome family.
Lynch syndrome (LS) is an inherited predisposition cancer syndrome, typically caused by germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 and PMS2. In the last years, a role for epimutations of the same genes has also been reported. MLH1 promoter methylation is a well known mechanism of somatic inactivation in tumors, and more recently, several cases of constitutional methylation have been identified. In four subjects affected by multiple tumors and belonging to a suspected LS family, we detected a novel secondary MLH1 gene epimutation. The methylation of MLH1 promoter was always linked in cis with a 997 bp-deletion (c.-168_c.116+713del), that removed exon 1 and partially involved the promoter of the same gene. Differently from cases with constitutional primary MLH1 inactivation, this secondary methylation was allele-specific and CpGs of the residual promoter region were totally methylated, leading to complete allele silencing. In the colon tumor of the proband, MLH1 and PMS2 expression was completely lost as a consequence of a pathogenic somatic point mutation (MLH1 c.199G>A, p.Gly67Arg) that also abrogated local methylation by destroying a CpG site. The evidences obtained highlight how MLH1 mutations and epimutations can reciprocally influence each other and suggest that an altered structure of the MLH1 locus results in epigenetic alteration.


Identification of extracellular vesicles and characterization of miRNA expression profiles in human blastocoel fluid.
In this study, for the first time, we demonstrated the presence of microRNAs and extracellular vesicles in human blastocoel fluid. The bioinformatic and comparative analyses identified the biological function of blastocoel fluid microRNAs and suggested a potential role inside the human blastocyst. We found 89 microRNAs, expressed at different levels, able to regulate critical signaling pathways controlling embryo development, such as pluripotency, cell reprogramming, epigenetic modifications, intercellular communication, cell adhesion and cell fate. Blastocoel fluid microRNAs reflect the miRNome of embryonic cells and their presence, associated with the discovery of extracellular vesicles, inside blastocoel fluid, strongly suggests their important role in mediating cell communication among blastocyst cells. Their characterization is important to better understand the earliest stages of embryogenesis and the complex circuits regulating pluripotency. Moreover, blastocoel fluid microRNA profiles could be influenced by blastocyst quality, therefore, microRNAs might be used to assess embryo potential in IVF cycles.


The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia.
Several different mutations collaborate with the fusion proteins in core-binding factor acute myeloid leukemia (CBF-AML) to induce leukemogenesis, but their prognostic significance remains unclear. We screened 354 predominantly younger (<60 years) adults with t(8;21) (n=199) or inv(16) (n=155) entered into UK MRC trials for KIT, FLT3 tyrosine kinase domain (FLT3(TKD)), N-RAS, K-RAS and c-CBL mutations and FLT3 internal tandem duplications (FLT3(ITD)) and assessed the impact of relative mutant level on outcome. Overall, 28% had KIT, 6% FLT3(ITD), 10% FLT3(TKD), 27% RAS and 6% CBL mutations. Mutant levels for all genes/loci were highly variable. KIT mutations were associated with a higher cumulative incidence of relapse but in multivariate analysis this was only significant for cases with a higher mutant level of 25% or greater (95% confidence interval (CI)=1.01-1.52, P=0.04). Similarly, only FLT3(ITD-HIGH) was a significant adverse factor for overall survival (OS; CI=1.27-5.39, P=0.004). Conversely, FLT3(TKD-HIGH) and CBL(HIGH) were both favorable factors for OS (CI= 0.31-0.89, P=0.01 and CI=0.05-0.85, P=0.02, respectively). KIT mutations were frequently lost at relapse, which is relevant to minimal residual disease detection and the clinical use of KIT inhibitors. These results indicate that relative mutant level should be taken into account when evaluating the impact of mutations in CBF-AML.


Cardiovascular safety of the dipetidyl peptidase-4 inhibitor alogliptin in type 2 diabetes mellitus.
As there have been concerns that some classes or agents for the treatment of type 2 diabetes may increase CV risk, we evaluated the cardiovascular profile of the dipeptidyl peptidase-4 inhibitor alogliptin. We evaluated the incidence of CV events in patients treated with alogliptin, placebo or comparator antihyperglycaemic drugs in the clinical trial database for alogliptin using the composite major adverse cardiovascular event (MACE) endpoints of CV death, non-fatal myocardial infarction and non-fatal stroke. The pooled analysis included 4168 patients exposed to alogliptin 12.5 and 25 mg daily for 2023 patient-years compared to 691 patients treated with placebo for 263 patient-years and 1169 patients treated with other antidiabetic agents (metformin, sulfonylureas and thiazolidinediones) for 703 patient-years. CV events were adjudicated by an expert endpoint committee blinded to treatment allocation. The incidence rates of the combined MACE were not significantly different between patients treated with alogliptin and comparator therapies (hazard ratio=0.635, 95% confidence interval, 0.0, 1.41). Additionally, other types of serious CV events were not significantly different between patients treated with alogliptin and comparator therapies. These analyses have not shown a signal of increased CV risk with alogliptin in patients with type 2 diabetes. Future results from the adequately powered EXAMINE trial will definitively assess the CV safety profile of aloglipin in patients with type 2 diabetes mellitus.


Developing quality measures for non-pharmacological prevention and rehabilitation in primary health care for chronic conditions: a consensus study.
Poor health-related behaviours are root causes of a large number of chronic conditions; however, this study is the first to develop guideline-based quality measures targeting health-related behaviours through generic non-pharmacological secondary prevention and rehabilitation in municipal primary health care for persons with chronic conditions. From January 2020 to September 2021, a consensus study was conducted in accordance with the current scientific recommendations for developing guideline-based quality measures. A clinical expert panel (n = 11) was established and included a patient representative, health care professionals, researchers, and key specialists. The process for developing quality measures was led by methodologists and encompassed a modified Research and Development/University of California at Los Angeles (RAND/UCLA) study to evaluate consensus in the expert panel. The consensus recommendations were directed to a steering group including the Danish Ministry of Health, the Danish Regions, and the Local Government Denmark. The expert panel rated 102 clinical practice recommendations. Consensus was demonstrated on 13 quality measures assessing whether the patients are offered participation in and adhere to: self-management, smoking cessation, physical exercise training, nutritional efforts, and preventive consultation on excessive alcohol consumption; whether the patients participate in a closing meeting, whether they are offered follow-up, and whether reasons for dropout are documented. The identified quality measures constitute a framework for assessing the quality of non-pharmacological prevention and rehabilitation in municipal primary health care for persons with chronic conditions. The next steps focus on field testing of the quality measures to refine measure criteria and assess implementation. A close link between clinical practice, the evidence and practice recommendations, the data infrastructure, economic considerations, and national priorities was a key to the consensus process.


The ribosomal P0 protein induces a spontaneous immune response in patients with head and neck advanced stage carcinoma that is not dependent on its overexpression in carcinomas.
A typical feature in systemic lupus erythemathosus patients is the presence of autoantibodies to the carboxyl-terminal homologous P proteins (P0, P1, P2) domain (C-22 P0 epitope). In this report we provide evidence for the in vivo immunogenicity of the P0 protein in head and neck cancer patients as well as overexpression by immunohistochemistry of the C-22 P0 epitope in invasive carcinomas (55/57). Overexpression of this epitope was also significantly associated with a number of pathological lesions arising in the head and neck stratified epithelium including acanthosis (8/8), benign tumors (11/11), dysplasia (23/25) and in situ carcinomas (9/9). Intermediate cell layer restricted epitope overexpression was observed in well differentiated carcinomas, while undifferentiated tumors showed overexpression throughout the cell layers. Employing recombinant P proteins, sera from 40 of the 57 carcinoma patients and 39 normal donors, were subjected to immunoblot analysis. Immunity to P0 protein (7/40) was associated with malignancy and with advanced disease stage, but it was not dependent on the C-22 P0 epitope overexpression, although it was the preferential autoantibody target in 4 patients. Increased expression of the C-22 P0 epitope on the surface of pharynx cancer cells following cellular stress in vitro, may imply P0 protein presentation as an in vivo autoantibody target in cancer patients. Evidence for immunity to the P0 protein, as well as overexpression in patients with head and neck carcinoma may be relevant for monitoring cancer progression, in planning immunotherapeutic strategies, and contribute to the understanding of immuno-biological behaviour of head and neck carcinomas.


[Chemical-toxicological analysis of butorphanol].
The conditions of butorphanol isolation from biological fluids were studied. The method of its extraction with the mix of organic solvents by pH 12 was proposed. How to identify butorphanol with the methods of thin-layer chromatography, ultraviolet spectrometry, high-performance liquid chromatography, gas chromatography with a detector of electron capture, chromato-mass spectrometry was developed. Possibility of use ultraviolet spectrometry for quantitative assessment of butorphanol was shown.


Feelings of being disabled as a prognostic factor for mortality in the drug-eluting stent era.
It remains unclear whether feelings of being disabled are a relevant psychological factor that determines outcome after percutaneous coronary intervention (PCI). Therefore, we evaluated "feelings of being disabled" as an independent risk factor for mortality 4 years post-PCI. As part of the Taxus-Stent Evaluated At Rotterdam Cardiology Hospital (T-SEARCH) Registry, 658 consecutive patients (age 63 years, 75% male) completed the subscale "feelings of being disabled" of the Heart Patients Psychological Questionnaire (HPPQ), within the first month after PCI. At 4-year follow-up, 8% of the patients (n=55) had died, 2% (n=16) underwent a myocardial infarction (MI), 13% (n=90) had a target-vessel revascularization (TVR), and 21% (n=137) had one or more major adverse cardiac events (MACE). One-third of the patients (32%) had high scores on "feelings of being disabled" at baseline. After adjusting for baseline characteristics, including symptoms of anxiety and depression, patients with a high score on "feelings of being disabled" had an increased risk for all cause mortality (HR=2.9, 95% CI=1.5-5.6), the composite end point mortality/MI (HR=2.4, 95% CI=1.3-4.4), and the occurrence of MACE (HR=1.7, 95% CI=1.1-2.7). Feelings of being disabled were an independent predictor of all-cause mortality, mortality/MI, and MACE 4 years post-PCI. These patients should be identified in clinical practice, as they warrant additional treatment, e.g., of a psychosocial nature, in addition to the standard medical treatment.


Computational prognostic indicators for breast cancer.
Breast cancer remains the leading cause of cancer-related mortality in women. Comprehensive genomics, proteomics, and metabolomics studies are emerging that offer an opportunity to model disease biology, prognosis, and response to specific therapies. Although many biomarkers have been identified through advances in data mining techniques, few have been applied broadly to make patient-specific decisions. Here, we review a selection of breast cancer prognostic indicators and their implications. Our goal is to provide clinicians with a general evaluation of emerging computational methodologies for outcome prediction.


Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies.
A continuing limitation and major challenge in the development and utilization of predictable stem cell therapies (SCTs) is the determination of the optimal dosages of stem cells. Herein, we report the quantification of stem cell fractions (SCF) of human mesenchymal stem cell (MSC) preparations derived from oral tissues. A novel computational methodology, kinetic stem cell (KSC) counting, was used to quantify the SCF and specific cell culture kinetics of stem cells in oral alveolar bone-derived MSC (aBMSCs) from eight patients. These analyses established, for the first time, that the SCF within these heterogeneous, mixed-cell populations differs significantly among donors, ranging from 7% to 77% (ANOVA p < 0.0001). Both the initial SCF of aBMSC preparations and changes in the level of the SCF with serial culture over time showed a high degree of inter-donor variation. Hence, it was revealed that the stability of the SCF of human aBMSC preparations during serial cell culture shows inter-donor variation, with some patient preparations exhibiting sufficient stability to support the long-term net expansion of stem cells. These findings provide important insights for the clinical-scale expansion and biomanufacturing of MSCs, which can facilitate establishing more effective and predictable outcomes in clinical trials and treatments employing SCT.


Potentiation of glucocorticoid activity in hypoxia through induction of the glucocorticoid receptor.
Tissue hypoxia is intimately associated with chronic inflammatory disease and may signal to the resolution of inflammatory processes. Glucocorticoid signaling through the glucocorticoid receptor (GR) represents a clinically important endogenous anti-inflammatory pathway. Microarray analysis reveals that the GR is transcriptionally up-regulated by hypoxia in human renal proximal tubular epithelial cells. Hypoxic up-regulation of the GR was confirmed at the level of promoter activity, mRNA, and protein expression. Furthermore, functional potentiation of glucocorticoid activity in hypoxia was observed as an enhancement of dexamethasone-induced glucocorticoid response element promoter activity and enhanced dexamethasone-mediated inhibition of IL-1beta-stimulated IL-8 expression and hypoxia-induced vascular endothelial growth factor expression. Knockdown of enhanced GR gene expression in hypoxia using specific GR small inhibitory RNA (siRNA) resulted in an attenuation of the enhanced glucocorticoid sensitivity. A role for the hypoxia-inducible transcription factor, HIF-1alpha, in the regulation of GR expression and the associated potentiation of glucocorticoid activity in hypoxia was also demonstrated. These results reveal a novel signaling aspect responsible for the incorporation of hypoxic and glucocorticoid stimuli, which we hypothesize to be an important co-operative pathway for the control of gene expression observed in complex tissue microenvironments in inflamed states.


G protein-coupled receptor microarrays for drug discovery.
The dominance of G protein-coupled receptors (GPCRs) as a drug target class, coupled with the increased pace of target identification and expansion of compound libraries, presents a compelling need to develop technologies to screen multiple GPCRs simultaneously. To address this need, GPCR microarrays that require the co-immobilization of lipid molecules and the probe receptors of interest have been fabricated, using conventional robotic printing technologies. Assays to screen compounds for their pharmacological properties (binding affinity, relative potency and selectivity) using GPCR microarrays are discussed.


Preparing for the unexpected: special considerations and complications after sugammadex administration.
Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.


[Postprandial hypotension in patients with compression of the celiac trunk].
One of the causes of the development of postprandial hypotension is thought to be impaired vegetative nervous regulation of arterial pressure. Patients with the syndrome of the celiac trunk compression also have signs of dysautonomy. The investigation performed has shown that syndrome of the celiac trunk compression is often combined with postprandial hypotension. Patients with such combination much more often have complains associated with asthenia and dysfunction of the autonomous nervous system. After operative treatment of patients with the celiac trunk compression (decompression of the celiac trunk) the frequency of symptoms of postprandial hypotension and clinical manifestations of asthenia and dysautonomy become less often in such patients.


Chloride channels in physiological volume regulation of human spermatozoa.
As with other mammalian species, human spermatozoa experience a decrease in extracellular osmolarity in cervical mucus upon ejaculation, which requires the efflux of osmolytes and water to counteract swelling that hinders mucus penetration. Recent evidence for the operation of K+ channels in the process of volume regulation suggests parallel involvement of Cl-/anion channels for electro-neutrality as in somatic cells. This was studied using ejaculated spermatozoa washed at seminal osmolality and incubated for 30 min in a medium of mucus osmolality in the presence of Cl- channel blockers. Increases in cell size measured as laser forward-scatter by flow cytometry were detected in the presence of 100 microM 5-nitro-2(3-phenylpropylamino) benzoic acid, 400 microM diisothiocyanato-stilbene-2,2'-disulphonic acid, and 20 microM tamoxifen. No volume changes were found with 400 microM 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulphonic acid, 200 microM verapamil, or niflumic acid, whereas 1 mM niflumic acid induced shrinkage. Among the candidate channel proteins, Western blotting revealed the presence of ClC-3 (CLCN3) at 87 kDa, but the absence of ClC-2 (CLCN2) from sperm proteins in all samples tested. ICln (CLNS1A) was found in only one of eight samples. Immunocytochemistry localized CLCN3 to the sperm tail. To confirm molecular identities, sperm mRNA was extracted and checked for quality by the presence of protamine 2 transcripts and the absence of sperm DNA and leukocyte mRNA using reverse transcription-polymerase chain reaction. Transcripts of Clcn3 were found in all samples and that of Clns1a in some but not all samples. Clcn3 was therefore considered the most likely candidate of Cl- channel involved in volume regulation of human sperm.


The use of the Periotest value as the initial success criteria of an implant: 8-year report.
Osseointegration is a histometric process that occurs gradually over a period of time. The load that an implant is able to bear depends upon, among other parameters, the quality of the bone-implant contact. For 8 years the damping capacity of 1,182 Brånemark implants inserted consecutively in 315 patients was measured using the Periotest method. The following clinical observations were made: (1) a relationship was found between implants with a specific Periotest value range that, at the moment of the transepithelial connection, were considered to be clinically stable, asymptomatic, and whose radiograph image was not radiolucent; (2) a relationship was found between clinically nonintegrated implants with a different Periotest value range; (3) variations in the Periotest value were related to the type of bone in which the implant was placed; (4) a small percentage of borderline implants with a Periotest value between the osseointegrated and the nonosseointegrated Periotest values was detected; (5) the percentage of secondary failures was related to an initial Periotest value corresponding to a borderline implant; (6) the healing time of each implant was individualized in accordance with the successively obtained Periotest value; (7) the load and the design of the prosthesis were individualized; (8) early detection of failing implants before fabrication of prostheses is possible; (9) communication was improved between the surgeon and the prosthodontist; and (10) variations in Periotest value were related to bone remodeling. The sensitivity of the principal clinical test in evaluating osseointegration is discussed regarding the moment of its application. The use of Periotest values as an initial success criteria of an implant is proposed.


Metabolism of neuropeptides. Hydrolysis of the angiotensins, bradykinin, substance P and oxytocin by pig kidney microvillar membranes.
Microvillar membranes derived from the brush border of the renal proximal tubule are very rich in peptidases. Pig kidney microvilli contain endopeptidase-24.11 associated with a battery of exopeptidases. The manner by which some neuropeptides are degraded by the combined attack of the peptidases of this membrane has been investigated. The contribution of individual peptidases was assessed by including inhibitors (phosphoramidon, captopril, amastatin and di-isopropyl fluorophosphate) with the membrane fraction when incubated with the peptides. Substance P, bradykinin and angiotensins I, II and III and insulin B-chain were rapidly hydrolysed by kidney microvilli. Oxytocin was hydrolysed much more slowly, but no products were detected from [Arg8]vasopressin or insulin under the conditions used for other peptides. The peptide bonds hydrolysed were identified and the contributions of the different peptidases were quantified. For each of the susceptible peptides, the main contribution came from endopeptidase-24.11 (inhibited by phosphoramidon). Peptidyl dipeptidase A (angiotensin-I-converting enzyme) was of less importance, even in respect of angiotensin I and bradykinin. When [2,3-Pro3,4-3H]bradykinin was also investigated at a lower concentration (20 nM), the conclusions in regard to the contributions of the two peptidases were unchanged. The possibility that endopeptidase-24.11 might attack within the six-residue disulphide-bridged rings of oxytocin and vasopressin was examined by dansyl(5-dimethylaminonaphthalene-1-sulphonyl)ation and by reduction and carboxymethylation of the products after incubation. Additional peptides were only observed after prolonged incubation, consistent with hydrolysis at the Tyr2-Ile3 and Tyr2-Phe3 bonds respectively. These results show that a range of neuropeptides are efficiently degraded by microvillar membranes and that endopeptidase-24.11 plays a key role in this process.


Distributed collaborative CAD system based on Web Service.
This paper presents a novel Web Service based distributed collaborative CAD system employing feature as its collaborative design element and uses XML to define feature operations and communication protocol between the server and the client. To reduce network load and increase response ability of the system, the feature information is updated incrementally on the client. The system supports collaborative designing on heterogeneous platforms. Its framework and communication protocols are analyzed in detail. The experimental results from the developed prototype system showed that it can effectively support collaborative design under the distributed environment.


Regression of organ damage following renal denervation in resistant hypertension: a meta-analysis.
Prospective observational studies have suggested that renal denervation (RDN) is associated with target organ damage (TOD) regression. Our aim is to review and meta-analyze the available evidence for the effect of RDN on TOD. We searched literature for studies with eligible content and performed random-effect meta-analyses for the following outcomes: left ventricular mass index (LVMI), left atrial volume index (LAVI), E to A wave velocities of trans-mitral inflow (E/A) and E wave velocity to Em velocity from tissue Doppler imaging (E/Em), central augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV). Seventeen studies (n = 698 patients) were incorporated in the present meta-analysis. RDN led to a regression of LVMI by 14.17 g/m (95% CI -18.33 to -10.01, P < 0.001) and by 4.75 g/m (95% CI -7.83 to -1.67, P = 0.003) for echocardiography and cardiac magnetic resonance, respectively. The pooled effect of RDN to E/A was not significant [0.04 (95% CI -0.03 to 0.12, P = 0.252)], whereas a decline of E/Em [-0.73 (95% CI -1.38 to -0.08, P = 0.03)] was observed. The pooled effect to LAVI [-1.67 ml/m (95% CI -4.60 to 1.27, P = 0.266)] reached statistical significance only in sensitivity analysis. RDN had beneficial effects in both AIx [-7.05 (95% CI -9.12 to -4.98, P < 0.001)] and PWV [1.54 m/s (95% CI -2.16 to -0.92, P < 0.001)]. Metaregression analysis revealed an independent effect of RDN on TOD regarding baseline blood pressure and blood pressure reduction. Catheter-based RDN can favorably affect TOD.


An introduction to metabolomics and its potential application in veterinary science.
Metabolomics has been found to be applicable to a wide range of fields, including the study of gene function, toxicology, plant sciences, environmental analysis, clinical diagnostics, nutrition, and the discrimination of organism genotypes. This approach combines high-throughput sample analysis with computer-assisted multivariate pattern-recognition techniques. It is increasingly being deployed in toxico- and pharmacokinetic studies in the pharmaceutical industry, especially during the safety assessment of candidate drugs in human medicine. However, despite the potential of this technique to reduce both costs and the numbers of animals used for research, examples of the application of metabolomics in veterinary research are, thus far, rare. Here we give an introduction to metabolomics and discuss its potential in the field of veterinary science.


Intrapartum magnesium sulfate is associated with neuroprotection in growth-restricted fetuses.
Intrapartum magnesium sulfate administration is recommended for fetal neuroprotection in women with imminent very preterm birth. However, previous studies have not included or separately analyzed the outcomes of pregnancies with fetal growth restriction that were treated with intrapartum magnesium sulfate. We sought to evaluate the neonatal and neurodevelopmental outcomes of growth-restricted fetuses born <29 weeks' gestation and exposed to maternal intrapartum magnesium sulfate. We conducted a retrospective cohort study of infants born <29 weeks' gestation from 2010 through 2011, admitted to participating Canadian Neonatal Network units, and followed by the Canadian Neonatal Follow-up Network centers. Growth restriction was defined either as estimated fetal or actual neonatal birthweight <10th percentile according to fetal or neonatal growth standards for gestational age and sex, respectively. Infants exposed to intrapartum magnesium sulfate were compared with unexposed infants. The primary outcome was composite of death or significant neurodevelopmental impairment at 18-36 months' corrected age. Secondary outcomes were death or any neurodevelopmental impairment at 18-36 months' corrected age. Neonatal morbidities were also compared. Of the 336 growth-restricted fetuses, 112 (33%) received magnesium sulfate and of the 177 growth-restricted infants, 61 (34%) received magnesium sulfate. Administration of magnesium sulfate was at the discretion of the treating physician. Intrapartum magnesium sulfate was associated with reduced odds of composite of death or significant neurodevelopmental impairment for infants classified according to both fetal standards (adjusted odds ratio, 0.42; 95% confidence interval, 0.22-0.80) and neonatal standards (adjusted odds ratio, 0.44; 95% confidence interval, 0.20-0.98). Intrapartum administration of magnesium sulfate to women with growth-restricted fetuses born <29 weeks' gestation was associated with reduced odds of composite of death or significant neurodevelopmental impairment.


Effects of sex, sexual orientation, infidelity expectations, and love on distress related to emotional and sexual infidelity.
The purpose of this study was to investigate the influence of participant sex, sexual orientation, infidelity expectations, and love on emotional responses to emotional and sexual infidelity. Participants (72 lesbian women, 114 heterosexual women, 53 gay men, and 57 heterosexual men) completed a demographic form, continuous emotion ratings in response to hypothetical infidelity scenarios, the Infidelity Expectations Questionnaire (IEQ), and the Triangular Love Scale. Sex, sexual orientation, and commitment and intimacy among partners were significant predictors of various emotional responses to sexual and emotional infidelity. Alternatively, passion among partners and expectations about a partner's likelihood of committing infidelity were not significant predictors of emotional reactions to infidelity. Across participants, sexual infidelity elicited more distressing feelings than emotional infidelity. Group differences were also found, with women responding with stronger emotions to emotional and sexual infidelity than men, and heterosexuals rating emotional and sexual infidelity as more emotionally distressing than lesbian and gay individuals. Sex and sexual orientation differences emerged regarding the degree to which specific emotions were reported in response to sexual and emotional infidelity. Clinical implications are offered, including how mental health professionals might use these findings to help clients cope with the negative effects of infidelity on romantic relationships.


Risk Factors for Death from Psychiatric Hospital-acquired Pneumonia.
Objectives Pneumonia is a major cause of death among inpatients at psychiatric hospitals. Psychiatric hospital-acquired pneumonia (PHAP) is defined as pneumonia developed in inpatients at psychiatric hospitals. PHAP is a type of nursing and healthcare-associated pneumonia (NHCAP). The purpose of this study was to clarify the risk factors for mortality among PHAP patients. Methods We retrospectively reviewed the clinical files of patients transferred to Tokyo Metropolitan Matsuzawa Hospital from psychiatric hospitals for PHAP treatment during the 10-year period from September 2007 to August 2017. We analyzed the clinical differences between the survivors and non-survivors and assessed the usefulness of severity classifications (A-DROP, I-ROAD, and PSI) in predicting the prognosis of PHAP. Results This study included a total of 409 PHAP patients, 87 (21.3%) of whom expired and 322 (78.7%) of whom survived. The mortality rates, according to the A-DROP classifications, were 4.9% in the mild cases, 21.6% in the moderate cases, 40.7% in the severe cases, and 47.6% in the very severe cases. The mortality rates, according to the I-ROAD classifications, were 9.5% in group A, 34.7% in group B, and 36.2% in group C. The mortality rates, according to the PSI classifications, were 0% in class II and III, 23.1% in class IV, and 44.9% in class V. The mortality rate increased as the severity increased. We identified 3 factors (age ≥65 years, body mass index ≤18.5 kg/m2, and bilateral pneumonic infiltration) as significant predictors of mortality. We therefore added two factors (body mass index ≤18.5 kg/m2 and bilateral pneumonic infiltration) to the A-DROP classification and established a modified A-DROP classification with a range of 0 to 7. The area under the receiver operation characteristic curves for predicting mortality were 0.699 for the A-DROP classification and 0.807 for the modified A-DROP classification. Conclusion The mortality rate in PHAP patients tended to increase with increasing classifications of severity. The modified A-DROP classification may be useful for predicting the prognosis of PHAP patients.


Aqueous ion channels.
The purpose of this paper is to describe models of ion channels in membranes which are built around a central core of ordered water. The calculated characteristics of such channels will be described and compared when possible with the measured properties of real ion channels. The approach is descriptive with reference when necessary to more detailed calculations contained in two previous papers (Edmonds, 1979, 1980). To place in perspective the problems of designing realistic model mechanisms for the translocation of ions across lipid membranes, the electrostatic self energy of a charged particle is introduced at the start. The severe limitations this energy places upon the environment that an ion must experience in traversing the lipid bilayer are briefly discussed.


Hereditary vascular anomalies: new insights into their pathogenesis.
Increased understanding of the mechanisms of angiogenesis and lymphangiogenesis has provided a glimpse at some of the molecules involved in the pathophysiology of hemangiomas and vascular malformations. This review focuses on recent advances in our understanding of the mechanisms of angiogenesis/lymphangiogenesis and the differentiation of arterial, venous, and lymphatic vessels. We integrate this knowledge with new data obtained from genetic studies in humans, which have revealed a number of heretofore-unsuspected candidates involved in the development of familial vascular anomalies. We present a common infantile vascular tumor, hemangioma, and then focus on hereditary familial vascular and lymphatic malformations. We also summarize transgenic mouse models for some of these malformations. It seems reasonable to believe that novel therapeutic strategies will soon emerge for the treatment of hemangiomas and vascular malformations.


Magnetic Fe3O4 nanoparticle heaters in smart porous membrane valves.
The application of magnetic nanoparticles (NPs) in membrane technology is still very new and combinations of such NPs and separation membranes are essentially unexplored. By the integration of NPs into polymeric membranes it is possible to create new functionalities based on the synergies of the materials. Here nanoparticle polymer hybrid membranes were created by immobilizing (super)paramagnetic Fe3O4 NPs on the walls of track-etched polyethylene terephthalate pores and further functionalization with poly(N-isopropylacryl amide) (PNIPAAm). The hybrid system can be controlled via local heat generation by the NPs induced by an external high frequency electromagnetic field, i.e., effective membrane pore size can be switched by the magnetic field due to the synergy between the nanoparticle functionality and the temperature-responsive properties of PNIPAAm. Analytical characterizations showed a successful and stable NP integration and the feasibility of functionalization with grafted PNIPAAm in the presence of immobilized NPs on the membrane pore surface. The valve function of the nanoparticle polymer hybrid materials with an external control via a high frequency electromagnetic field was demonstrated in water permeability experiments, but such systems will have significant potential for other applications such as drug release or mass separation.


Ambient Coarse Particulate Matter and the Right Ventricle: The Multi-Ethnic Study of Atherosclerosis.
Coarse particulate matter (P10-2.5) is primarily mechanically generated and includes crustal material, brake and tire wear, and biological particles. PM10-2.5 is associated with pulmonary disease, which can lead to right ventricular (RV) dysfunction. Although RV characteristics have been associated with combustion-related pollutants, relationships with PM10-2.5 remain unknown. To quantify cross-sectional associations between RV dysfunction and PM10-2.5 mass and components among older adults and susceptible populations. We used baseline cardiac magnetic resonance images from 1,490 participants (45-84 y old) from the Multi-Ethnic Study of Atherosclerosis and assigned 5-y residential concentrations of PM10-2.5 mass, copper, zinc, phosphorus, silicon, and endotoxin, using land-use regression models. We quantified associations with RV mass, end-diastolic volume, and ejection fraction after control for risk factors and copollutants using linear regression. We further examined personal susceptibility. We found positive associations of RV mass and, to a lesser extent, end diastolic volume with PM10-2.5 mass among susceptible populations including smokers and persons with emphysema. After adjustment for copollutants, an interquartile range increase in PM10-2.5 mass (2.2 μg/m3) was associated with 0.5 g (95% CI: 0.0, 1.0), 0.9 g (95% CI: 0.1, 1.7), and 1.4 g (95% CI: 0.4, 2.5) larger RV mass among former smokers, current smokers, and persons with emphysema, respectively. No associations were found with healthy individuals or with ejection fraction. Alterations to RV structure may represent a mechanism by which long-term PM10-2.5 exposure increases risks for adverse respiratory and cardiovascular outcomes, especially among certain susceptible populations. https://doi.org/10.1289/EHP658.


Clinical Report: Clinician Feedback on the Magnetic Levator Prosthesis.
Stakeholder engagement has been identified by national health organizations as a crucial step to successful translation of new health care treatments. In this clinical report, clinician-stakeholder feedback is presented for the magnetic levator prosthesis (MLP), a promising noninvasive spectacle device that restores eyelid motility with magnetic force. This study aimed to evaluate MLP clinical need and translational barriers. Ten vision rehabilitation optometrists who attended an educational presentation on the MLP and participated in a hands-on workshop in the fitting of a patient were invited to complete an anonymous online survey. Ten multiple-choice items gathered data on estimated patient need, current approaches, main barriers to MLP, temporary versus chronic use, cost barriers, and need for insurance coverage. Open fields allowed for additional comments. Nine of 10 specialists completed the survey. Of those, seven answered that they could potentially see at least 1 to 5 patients for ptosis management within a year. The most common ptosis management options reported were the ptosis crutch, taping the eyelid open, and oxymetazoline drops, all with six responses each. Seven clinicians indicated that cost was a main concern. If cost to patient was not a barrier, all indicated they would be at least somewhat likely to try the MLP (1) for temporary management of ptosis, (2) as a pre-surgical trial, and (3) for long-term management of ptosis, with more selecting extremely likely and very likely than somewhat likely. Main comments were expressing enthusiasm for the technology and that it would be more appealing for patients if covered by insurance. This clinical report suggests that the main barriers to clinical success of the MLP may be cost and insurance coverage, appearance of the device, and self-application. Possible solutions are cost-benefit analysis research, engineering efforts to reduce spectacle magnet size and improve the ease of eyelid magnet application.


Artificial Intelligence Surgery: How Do We Get to Autonomous Actions in Surgery?
Most surgeons are skeptical as to the feasibility of autonomous actions in surgery. Interestingly, many examples of autonomous actions already exist and have been around for years. Since the beginning of this millennium, the field of artificial intelligence (AI) has grown exponentially with the development of machine learning (ML), deep learning (DL), computer vision (CV) and natural language processing (NLP). All of these facets of AI will be fundamental to the development of more autonomous actions in surgery, unfortunately, only a limited number of surgeons have or seek expertise in this rapidly evolving field. As opposed to AI in medicine, AI surgery (AIS) involves autonomous movements. Fortuitously, as the field of robotics in surgery has improved, more surgeons are becoming interested in technology and the potential of autonomous actions in procedures such as interventional radiology, endoscopy and surgery. The lack of haptics, or the sensation of touch, has hindered the wider adoption of robotics by many surgeons; however, now that the true potential of robotics can be comprehended, the embracing of AI by the surgical community is more important than ever before. Although current complete surgical systems are mainly only examples of tele-manipulation, for surgeons to get to more autonomously functioning robots, haptics is perhaps not the most important aspect. If the goal is for robots to ultimately become more and more independent, perhaps research should not focus on the concept of haptics as it is perceived by humans, and the focus should be on haptics as it is perceived by robots/computers. This article will discuss aspects of ML, DL, CV and NLP as they pertain to the modern practice of surgery, with a focus on current AI issues and advances that will enable us to get to more autonomous actions in surgery. Ultimately, there may be a paradigm shift that needs to occur in the surgical community as more surgeons with expertise in AI may be needed to fully unlock the potential of AIS in a safe, efficacious and timely manner.


[Anthropometric measurements as indicators of nutritional status of the elderly].
This review contains details on anthropometric measurements required for assessment of nutritional status in the elderly. These measurements provide indicators of fat tissue content or body composition and evaluate trends in nutritional status. Anthropometric measurements in the elderly are similar to these in other groups of population but they have to be adopted according to changes in constitution and posture of elderly and disabled people. The following measurements are presented: stature, weight, skinfold thickness and mid upper-arm, waist and hip circumferences. Derived measurements and indices of nutritional status are also discussed.


Atrial natriuretic factor and vasopressin during dehydration and rehydration in rats.
To determine the effect of water deprivation (mixed volume and osmotic stimulus) on the secretion of atrial natriuretic factor (ANF) and arginine vasopressin (AVP), plasma immunoreactive ANF (IR-ANF), and plasma AVP were measured in normal conscious Sprague-Dawley rats. IR-ANF was decreased to 19.9 +/- 3.6 pg/ml (24 h dehydration), 9.8 +/- 2.5 pg/ml (48 h dehydration), and undetectable level (72 h dehydration) from the control level of 62.4 +/- 2.4 pg/ml. These decreases were accompanied by significant increase in plasma AVP, serum Na+, osmolality (osm), and hematocrit (Hct). In animals deprived of water for 3 days the secretion of ANF and AVP was monitored at seven time points during the 1st h after voluntary rehydration with tap water. After rehydration, IR-ANF was elevated dramatically within 3 min and gradually for up to 1 h after water was offered; AVP decreased within 3 min of rehydration and stayed at the water-repleted level during the next 1 h. Na+, osm, and Hct did not change until 15, 9, and 30 min after rehydration, respectively. The rapid modifications in plasma IR-ANF and AVP were accompanied by a transient but significant increase in arterial blood pressure for up to 15 min after water consumption. These results indicate that oropharyngeal-gastric stimuli contribute to the release of both ANF and AVP.


Development of Microneedle Patch Loaded with Bacopa monnieri Solid Lipid Nanoparticles for the Effective Management of Parkinson's Disease.
The demand for drug delivery systems (DDS) to treat Parkinson's disease (PD) is still high, and microneedle (MN) assisted transdermal DDS offers enormous potential. Herbal products for PD have been shown to have antioxidant effects in reducing dopaminergic neurons from degeneration. Here, we attempted to incorporate solid lipid nanoparticles (SLNs) of Bacopa monnieri into dissolvable microneedle arrays and evaluate its neuroprotective activity. The bloodless and painless microneedle arrays through the transdermal route deliver the drug across the blood-brain barrier at the desired concentration. The quality by design (QbD) approach was employed for optimizing the SLNs formulations. The mechanical strength, in vitro release studies, ex-vivo permeation investigation, skin irritation test, histopathological studies, biochemical studies, and behavioural tests SLNs loaded microneedle arrays were performed. The microneedle patches obtained were shown to be mechanically robust and were also found to be nonirritant with a decreased degree of bradykinesia, high motor coordination, and balance ability. Compared to systemic delivery systems, such an MN method can achieve a considerably lower effective dose and allow long-term home-based treatment.


Rat renal peritubular transport and metabolism of plasma [35S]glutathione.
More than 80% of the plasma glutathione is extracted during a single pass through the kidney. The peritubular component of this extraction was characterized by in situ arterial infusion of [35S]glutathione and [3H]inulin. The peak of 35S-labeled material recovered in the renal venous effluent was delayed approximately 10 S compared with the peak of [3H]inulin. As a result, the initial fractions exhibited a decreased 35S/3H ratio, indicating that 35S-labeled material is transported out of the postglomerular peritubular capillaries. Later fractions exhibited a normalized 35S/3H ratio greater than 1, consistent with the subsequent addition of a 35S-labeled metabolite to the venous circulation. An identical profile was observed when perfusion experiments were repeated using gamma-[35S]glutamyl-S-methylcysteine and [3H]inulin. Renal venous plasma samples obtained from a rat perfused with [35S]glutathione were reduced with sodium borohydride, reacted with monobromobimane, and analyzed by high-pressure liquid chromatography. More than 70% of the recovered 35S-labeled material was identified as cysteine and 20% was recovered as unmetabolized glutathione. Pretreatment of rats with a single injection of AT-125 resulted in 96% inactivation of renal gamma-glutamyltranspeptidase. Under these conditions, the percent of glutathione converted to cysteine (35%) was significantly less than the observed level of renal extraction (61%). Two injections of AT-125 caused a complete inhibition of cysteine formation. However, the residual level of renal extraction (41%) was still significantly greater than the filtration fraction (26%). The peritubular transport of glutathione is stimulated by prior depletion of renal glutathione with buthionine-L-sulfoximine and is competitively inhibited by simultaneous infusion of gamma-glutamylcysteine.(ABSTRACT TRUNCATED AT 250 WORDS)


Heart rate variability interventions for concussion and rehabilitation.
The study of heart rate variability (HRV) has emerged as an essential component of cardiovascular health, as well as a physiological mechanism by which one can increase the interactive communication between the cardiac and the neurocognitive systems (i.e., the body and the brain). It is well-established that lack of HRV implies cardiopathology, morbidity, reduced quality-of-life, and precipitous mortality. On the positive, optimal HRV has been associated with good cardiovascular health, autonomic nervous system (ANS) control, emotional regulation, and enhanced neurocognitive processing. In addition to health benefits, optimal HRV has been shown to improve neurocognitive performance by enhancing focus, visual acuity and readiness, and by promoting emotional regulation needed for peak performance. In concussed athletes and soldiers, concussions not only alter brain connectivity, but also alter cardiac functioning and impair cardiovascular performance upon exertion. Altered sympathetic and parasympathetic balance in the ANS has been postulated as a critical factor in refractory post concussive syndrome (PCS). This article will review both the pathological aspects of reduced HRV on athletic performance, as well as the cardiovascular and cerebrovascular components of concussion and PCS. Additionally, this article will review interventions with HRV biofeedback (HRV BFB) training as a promising and underutilized treatment for sports and military-related concussion. Finally, this article will review research and promising case studies pertaining to use of HRV BFB for enhancement of cognition and performance, with applicability to concussion rehabilitation.


Performance of 3DOSEM and MAP algorithms for reconstructing low count SPECT acquisitions.
Low count single photon emission computed tomography (SPECT) is becoming more important in view of whole body SPECT and reduction of radiation dose. In this study, we investigated the performance of several 3D ordered subset expectation maximization (3DOSEM) and maximum a posteriori (MAP) algorithms for reconstructing low count SPECT images. Phantom experiments were conducted using the National Electrical Manufacturers Association (NEMA) NU2 image quality (IQ) phantom. The background compartment of the phantom was filled with varying concentrations of pertechnetate and indiumchloride, simulating various clinical imaging conditions. Images were acquired using a hybrid SPECT/CT scanner and reconstructed with 3DOSEM and MAP reconstruction algorithms implemented in Siemens Syngo MI.SPECT (Flash3D) and Hermes Hybrid Recon Oncology (Hyrid Recon 3DOSEM and MAP). Image analysis was performed by calculating the contrast recovery coefficient (CRC),percentage background variability (N%), and contrast-to-noise ratio (CNR), defined as the ratio between CRC and N%. Furthermore, image distortion is characterized by calculating the aspect ratio (AR) of ellipses fitted to the hot spheres. Additionally, the performance of these algorithms to reconstruct clinical images was investigated. Images reconstructed with 3DOSEM algorithms demonstrated superior image quality in terms of contrast and resolution recovery when compared to images reconstructed with filtered-back-projection (FBP), OSEM and 2DOSEM. However, occurrence of correlated noise patterns and image distortions significantly deteriorated the quality of 3DOSEM reconstructed images. The mean AR for the 37, 28, 22, and 17mm spheres was 1.3, 1.3, 1.6, and 1.7 respectively. The mean N% increase in high and low count Flash3D and Hybrid Recon 3DOSEM from 5.9% and 4.0% to 11.1% and 9.0%, respectively. Similarly, the mean CNR decreased in high and low count Flash3D and Hybrid Recon 3DOSEM from 8.7 and 8.8 to 3.6 and 4.2, respectively. Regularization with smoothing priors could suppress these noise patterns at the cost of reduced image contrast. The mean N% was 6.4% and 6.8% for low count QSP and MRP MAP reconstructed images. Alternatively, regularization with an anatomical Bowhser prior resulted in sharp images with high contrast, limited image distortion, and low N% of 8.3% in low count images, although some image artifacts did occur. Analysis of clinical images suggested that the same effects occur in clinical imaging. Image quality of low count SPECT acquisitions reconstructed with modern 3DOSEM algorithms is deteriorated by the occurrence of correlated noise patterns and image distortions. The artifacts observed in the phantom experiments can also occur in clinical imaging.


[Expression of p63, p40 and CK5/6 in small cell lung cancer].
To study the expression of squamous cell markers p63, p40 and CK5/6 in small cell carcinoma of lung (SCLC). Immunohistochemical study for squamous cell markers (p63, p40 and CK5/6), neuroendocrine markers (chromogranin A, synaptophysin and CD56) and TTF1 was carried out in 283 cases of SCLC. The diagnostic value of these markers was evaluated. The expression rate of p63, p40 and CK5/6 were 20.7% (54/261), 7.9% (5/63) and 0.5% (1/221), respectively in the cases of SCLC studied. Amongst the squamous cell markers, CK5/6 had the lowest rate of positivity (P < 0.01). On the other hand, chromogranin A, synaptophysin and CD56 were positive in 61.8% (170/275), 85.5% (242/283) and 89.2% (248/278), respectively. The positivity rate for chromogranin A was lower than that for synaptophysin and CD56 (P < 0.01). TTF1 was expressed in 77.2% (217/281). p63 and p40 are expressed in a subset of SCLC. In contrast, CK5/6 is rarely positive in SCLC. An immunohistochemical panel of CK5/6, synaptophysin and CD56 is recommended for differential diagnosis of SCLC.