Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia.
Phosphodiesterase 4D interacting protein (PDE4DIP) interacts with cAMP-specific phosphodiesterase 4D and its abnormal expression promotes the development of hematological malignancies, breast cancer, and pineal cell carcinoma. However, there is currently no systematic pan-cancer analysis of the association between PDE4DIP and various cancers. Thus, this study aimed to elucidate the potential functions of PDE4DIP in various cancers. Based on the multiple public databases and online websites, we conducted comprehensive analyses for PDE4DIP in various cancers, including differential expression, prognosis, genetic variation, DNA methylation, and immunity. We thoroughly analyzed the specific role of PDE4DIP in acute myeloid leukemia (LAML). The results indicated that there were differences in PDE4DIP expression in cancers, and in kidney chromophobe, LAML, pheochromocytoma and paraganglioma, thymoma, and uveal melanoma, PDE4DIP had potential prognostic value. PDE4DIP expression was also correlated with genetic variation, DNA methylation, immune cell infiltration, and immune-related genes in cancers. Functional enrichment analysis showed that PDE4DIP was mainly related to immune-related pathways in cancers, and in LAML, PDE4DIP was mainly related to immunoglobulin complexes, T-cell receptor complexes, and immune response regulatory signaling pathways. Our study systematically revealed for the first time the potential prognostic and immunotherapeutic value of PDE4DIP in various cancers, including LAML.


In vivo electroporation induces cell cycle reentry of myonuclei in rat skeletal muscle.
Adult urodele amphibians such as newts are capable of regenerating lost structures including their limbs. In these species, dedifferentiation of myofiber is essential for the regenerative process. Upon terminal differentiation, nuclei of myofiber (myonuclei) are withdrawn from cell cycle, but prior to dedifferentiation, myonuclei reenter the cell cycle. In contrast with urodele amphibians, it is generally accepted that mammalian myofibers are not able to dedifferentiate in response to muscle injury. A recent study has suggested that electroporation can induce dedifferentiation response of skeletal muscle in newt limbs. In the present study, we examined whether myonuclei of skeletal muscle of mammals are capable of reentering the cell cycle by means of electroporation. Electroporation was applied to tibialis anterior muscle of the rat with or without plasmid DNA. Histological analyses revealed that, while electroporation induces degenerative/regenerative responses in skeletal muscle irrespective of the presence of plasmid DNA, the expression of proliferating cell nuclear antigen (PCNA) in myonuclei was observed only in the presence of plasmid DNA. The present results indicate that myonuclei of skeletal muscle are capable of reentering the cell cycle and suggest that in vivo electroporation can induce dedifferentiation of mammalian skeletal muscle.


Relationship of fertility to day of insemination during the laying sequence.
Fertility among hens artificially inseminated (AI) at different stages of the laying sequence were compared in two experiments with broiler breed (Experiment 1) and egg-type hens (Experiment 2). The different stages of the laying sequence were prepause (PP)-oviposition without ovulation, pause (P)-no oviposition with or without ovulation, and nonpause (NP)-oviposition with ovulation. There were no significant differences among PP, P, and NP groups for duration or percent fertility in Experiment 1. Fertility and duration were significantly lower in PP than NP in Experiment 2. However, these differences were most likely caused by 36% of the PP hens ovipositing during the time of AI. Time of AI seems to be a more important factor in determining subsequent fertility than the day of AI during the laying sequence.


Mononucleosis and hepatic failure associated with diphenylhydantoin treatment in an infant.
Diphenylhydantoin-induced hepatitis and mononucleosis are uncommon in children. The occurrence of these two diseases in the same individual, with progression to hepatic failure is rare and has not been reported in infants. This report represents a 6-month-old male infant who developed an infectious mononucleosis-like syndrome and hepatic failure 16 days after diphenylhydantoin administration. He took this anticonvulsant for controlling seizures after a head injury. Fever, skin rash, hepatosplenomegaly, lymphadenopathy, and atypical lymphocytosis led to the initial diagnosis of infectious mononucleosis. However, negative heterophil antibody did not support the diagnosis. Jaundice ensued in the following course and became more and more profound. Meanwhile, physical examination showed shrinking in liver size. Negative virology studies, including Epstein-Barr virus, cytomegalovirus, and hepatitis B virus, excluded them as causative agents. The patient lapsed into a stage I hepatic coma, but gradually recovered clinically and biochemically after eight successive exchange transfusions and supportive care. Two liver biopsies were performed 20 and 50 days after the onset of disease, respectively. Remarkable hepatic parenchymal loss, cholestasis, and fatty change were found on histologic examination of the first biopsy specimen, and portal fibrosis was noted on the second.


Genetic Variants at BCL11A and HBS1L-MYB loci Influence Hb F Levels in Chinese Zhuang β-Thalassemia Intermedia Patients.
Increased Hb F levels can ameliorate the symptoms of β-thalassemia (β-thal). Due to the genetic heterogenicity of β-thal, the relationship between genetic variants in modifier genes and Hb F level has been studied in different populations. The Chinese Zhuang has the second largest population in China and has 6.78% prevalence of β-thal. However, the effects of these single nucleotide polymorphism (SNP) variants on the Hb F levels of β-thal intermedia (β-TI) patients in this population have not been reported. To explore the association between modifier loci (β-globin gene cluster, HBS1L-MYB intergenic region and BCL11A) and Hb F levels in Chinese Zhuang β-TI patients, 96 unrelated β-TI patients (50 males and 46 females) with different Hb F levels were recruited and genotyped by mass spectrometry. A total of 13 SNPs were confirmed to be in a significant relationship with Hb F levels in this population. Of these, high-risk genotypes of six Hb F-associated SNPs, rs9376090, rs7776054, rs9399137, rs9389268, rs9402685 in the HBS1L-MYB intergenic region and rs189984760 in the BCL11A locus, showed association with high Hb F levels, especially for SNPs in linkage disequilibrium. One novel Hb F-associated SNP, rs189984760, was identified in our study. Our findings will be of valuable reference for correlation between modifier genes and Hb F in Chinese Zhuang populations and may lead to better understand the modifying mechanisms for β-thal.


Effect of laminectomy and anesthesia upon spinal cord blood flow.
Spinal cord blood flow (SCBF) in 10 sheep subjected to laminectomy at L6-7, T6-7, and C7-T1 was compared to that of 10 control sheep subjected to anesthesia alone. Blood flow was measured using the radioactive microsphere technique, with the PaCO2 maintained at 40 +/- 2 mm Hg. Both laminectomy and control animals showed a decrease in SCBF at a rate of 7% to 16%/hr for the 3 hours following the first blood flow determination. When prelaminectomy and postlaminectomy SCBF values were compared to their counterparts in the control animals, there were no significant differences. Laminectomy does not appear to alter SCBF from control values. Spinal evoked potentials (SEP's) were elicited in the laminectomy group by direct cord stimulation at C-7 and L-7. No changes were noted in amplitude or latency of SEP's over time in either caudal or rostral conduction.


Synthesis and Functional Reconstitution of Light-Harvesting Complex II into Polymeric Membrane Architectures.
One of most important processes in nature is the harvesting and dissipation of solar energy with the help of light-harvesting complex II (LHCII). This protein, along with its associated pigments, is the main solar-energy collector in higher plants. We aimed to generate stable, highly controllable, and sustainable polymer-based membrane systems containing LHCII-pigment complexes ready for light harvesting. LHCII was produced by cell-free protein synthesis based on wheat-germ extract, and the successful integration of LHCII and its pigments into different membrane architectures was monitored. The unidirectionality of LHCII insertion was investigated by protease digestion assays. Fluorescence measurements indicated chlorophyll integration in the presence of LHCII in spherical as well as planar bilayer architectures. Surface plasmon enhanced fluorescence spectroscopy (SPFS) was used to reveal energy transfer from chlorophyll b to chlorophyll a, which indicates native folding of the LHCII proteins.


Computer- and robot-aided head surgery.
In this paper new methods and devices for computer and robot based head surgery are presented. A computer based planning system for CMF-surgery allows the surgeon to plan complex trajectories on the head of the patient for operations where bone segments were cut out and shifted. Different registration methods have been developed and tested. A surgical robot system for bone cutting on the head has been developed and evaluated at the patient in the operating theatre. In future, laser cutting of bones with a robot will be seen as a new powerful method for robot based surgery. A 3D augmented reality system will assist the surgeon in the future by augmenting virtual anatomical structure into the situs.


Levels of arginine-vasopressin in cerebrospinal fluid during passive avoidance behavior in rats.
The concentration of immunoreactive arginine-vasopressin (IR-AVP) was measured in the cerebrospinal fluid (CSF) during acquisition and retention of passive avoidance behavior. IR-AVP level in CSF of male Wistar rats immediately after the learning trial was increased; the rate of which was related to the intensity of the electric footshock during the learning trial and the avoidance latency as measured 1 day after the learning trial. Immediately after the 24 h retention test IR-AVP levels were significantly increased in rats subjected to the low (0.25 mA) shock intensity during the learning trial, but IR-AVP levels of rats exposed to the high shock (1.0 mA) were under the limit of detection. If the retention test was postponed till 5 days after the learning trial, the increase of IR-AVP level in the CSF was related to avoidance latencies which reflect the intensity of aversive stimulation (electric footshock). The results suggest an association between central AVP release and passive avoidance behavior and may be indicative of the role of this peptide in neuronal mechanisms underlying learning and memory processes.


Fungal surfaces: effects of interactions with phagocytic cells.
Fungal surfaces undergo profound changes during morphogenesis that modify host responses. For example, inhaled spores or conidia of Rhizopus or Aspergillus lose their surface hydrophobic outer layers, initially swell, and then germinate to form mycelia that may invade tissues. These various fungal forms not only elicit differing response from host phagocytic cells but also differ in their susceptibilities to cellular microbicidal mechanisms. In addition, studies comparing neutrophil activation responses to opsonized and unopsonized Candida hyphae indicate that the presence or absence of antibody or complement on fungal surfaces determines distinct patterns of the early responses of neutrophils to stimulation, such as membrane depolarization, cytosolic increase in calcium, and phosphoinositide turnover. These initial events in the neutrophil activation sequence are followed by release of both fungicidal granule constituents and oxidants from the respiratory burst. The quantity and specificity of delivery of these toxic neutrophil products ultimately determine the relative efficiency of fungicidal activity versus inflammatory cytotoxicity to host cells.


Glucose homeostasis in the perinatal period: the critical role of pancreatic hormones and exogenous substrates in the rat.
Birth in most mammalian species is characterized by an abrupt change from a high carbohydrate and low fat diet to a high fat and low carbohydrate diet. As the supply of glucose from the milk is not sufficient to cover the glucose needs of several tissues (such as the brain and the red blood cells) and as liver glycogen stores are exhausted within 12 hours of delivery, the newborn rapidly becomes dependent on its capacity for efficient gluconeogenesis. Among the factors that control the appearance of gluconeogenesis in the liver of the neonate, the pancreatic hormones play a crucial role. Studies in the rat have shown that the rise in plasma glucagon and the fall in plasma insulin which occur immediately after birth are the main determinants of the appearance of liver phosphoenolpyruvate carboxykinase (GTP), the rate-limiting enzyme of glyconeogenesis in this species. However, when this enzyme has reached its adult values in the liver 12 to 24 hours after birth, other factors involved in the regulation of hepatic gluconeogenesis. In order for it to maintain a high rate of gluconeogenesis the liver of the neonate must be supplied with sufficient amounts of gluconeogenic precursors and of non-esterified fatty acids. Studies in the rat have shown that active fatty acid oxidation is necessary to support gluconeogenesis by providing essential cofactors such as acetyl-CoA and NADH. The relevance of these studies for the understanding of neonatal glucose homeostasis in man is discussed.


The molecular and supramolecular structures of four 1,5,6,10b-tetrahydropyrazolo[1,5-c]quinazolines.
The supramolecular structures of the title compounds, 2-phenyl-5-p-tolyl-1,5,6,10b-tetrahydropyrazolo[1,5-c]quinazoline, C(23)H(21)N(3), (I), 5-(4-bromophenyl)-2-phenyl-1,5,6,10b-tetrahydropyrazolo[1,5-c]quinazoline, C(22)H(18)BrN(3), (II), 2-(4-chlorophenyl)-5-phenyl-1,5,6,10b-tetrahydropyrazolo[1,5-c]quinazoline, C(22)H(18)ClN(3), (III), and 5-(4-bromophenyl)-2-(4-chlorophenyl)-1,5,6,10b-tetrahydropyrazolo[1,5-c]quinazoline, C(22)H(17)BrClN(3), (IV), are of two general types. Compounds (I), (II) and (III) form base-paired dimers via N-H.N hydrogen bonds, where (I) and (II) are isomorphous, while in (IV), there are no conventional hydrogen bonds.


Of Mice and Men: In Vivo and In Vitro Studies of Primordial Germ Cell Specification.
Specification of mouse primordial germ cells (PGCs), the precursors of sperm and eggs, involves three major molecular events: repression of the somatic program, reacquisition of pluripotency, and reprogramming to a unique epigenetic ground state. Gene knockout studies in mouse models, along with global transcriptome analyses, have revealed the key signaling pathways and transcription factors essential for PGC specification. Knowledge obtained from these studies has been utilized extensively to develop robust in vitro PGC induction models not only in mice but also in humans. These models have, in turn, formed the basis for a detailed understanding of the signaling pathways and epigenetic dynamics during in vivo PGC specification and development. Recapitulation of human PGC specification in culture is of tremendous significance for understanding the mechanisms of human germ cell development in normal and disease states and has implications for addressing germ-cell-based causes of infertility.


Clonidine decreases the dose of thiamylal required to induce anesthesia in children.
Clonidine is a useful drug to give preoperatively because it produces anxiolysis, sedation, and hemodynamic stability, and reduces intravenous and volatile anesthetic requirements. Several premedicants, including midazolam and diazepam, have been shown to reduce the induction dose of intravenous anesthetics, such as thiopental, ketamine, or propofol. A randomized, double-blind controlled study was conducted to evaluate the effect of premedication with oral clonidine on thiamylal requirement for the induction of anesthesia and on associated hemodynamic changes in children. Sixty children (ASA grades I-II, 7-12 yr old) were assigned randomly to receive one of three treatments (n = 20, for each group): placebo (control), clonidine 2 micrograms/kg, or clonidine 4 micrograms/kg 105 min before the induction of anesthesia. Thiamylal was injected at a dose of 1 mg/kg every 15 s until loss of the eyelash reflex and the dose was recorded. Blood pressure (BP), heart rate (HR), and arterial oxygen saturation were recorded every minute from the beginning of injection of thiamylal for 5 min. Significant decreases in thiamylal dose were observed in patients receiving clonidine. The induction dose of thiamylal (mean +/- SD) was 5.4 +/- 0.9, 4.5 +/- 1.1, and 3.4 +/- 0.9 mg/kg for patients receiving placebo, clonidine 2 micrograms/kg, and clonidine 4 micrograms/kg, respectively (P < 0.05). Systolic BP decreased by 6.8%, 5.6%, and 6.6% and HR increased by 5.7%, 4.8%, and 4.1% after administration of thiamylal in the control (placebo) group and the clonidine 2 micrograms/kg and clonidine 4 micrograms/kg groups, respectively (P > 0.05). Premedication with oral clonidine reduced the dose of intravenous thiamylal required for the induction of anesthesia in children.


Skeletal maturity of the hand and wrist of healthy Argentinian children aged 4-12 years, assessed by the TWII method.
One previously trained observer assessed skeletal maturity in a representative sample of 388 and 387 healthy girls and boys respectively from La Plata city, a predominantly university and administrative urban centre in Argentina. The staging system used was TWII and the scores were calculated from three sources: British, Spanish and Italian standards. Our sample showed a marked advancement in bone age with regard to chronological age when using British standards and, to a lesser extent, when applying the Spanish standards. Local mean bone ages were very similar to chronological ages when the Italian scores were used. Second-degree polynomials were adjusted to log10 scores for boys and girls, in order to obtain local values for bone age (BA) transformations. The same staging system should be used in clinical work in Argentina, with the corresponding changes in BA transformatons. A marked advancement of carpal BAs with regard to RUS BAs was found, from age 5 onwards, in both sexes. Mean differences and SD of RUS-minus-carpal BA were 1.28, SD 1.08 and 1.18, SD 1.09 years for girls and boys respectively. These differences have not been described before, and require further investigation.


All-regions tunable high harmonic enhancement by a periodic static electric field.
Simulations show that a static electric field periodically distributed in space can be used to control the production of coherent light by high-order harmonic generation in a wide spectral range covering extreme-ultraviolet and soft x-ray radiation. The radiation yield is selectively enhanced due to symmetry breaking induced by a static electric field on the interaction between the driving laser and the medium. The spectral position of the enhancement is tuned by varying the periodicity of the static electric field which matches twice the coherence length of the harmonics in the desired region. We find that the static electric field strength inducing enhancement decreases for shorter wavelengths and predict an increase of more than two orders of magnitude for harmonics in the water window spectral range with a static electric field as weak as 1.12 MV/cm.


Experimental and theoretical charge density distribution in two ternary cobalt(III) complexes of aromatic amino acids.
The experimental charge density distributions in two optically active isomers of a Co complex have been determined. The complexes are Delta-alpha-[Co(R,R-picchxn)(R-trp)](ClO4)2.H2O) (1) and Lambda-beta1-[Co(R,R-picchxn)(R-trp)](CF3SO3)2) (2), where picchxn is N,N'-bis(2-picolyl-1,2-diaminocyclohexane) and R-trp is the R-tryptophane anion. The molecular geometries of 1 and 2 are distinguished by the presence in complex 1 of intramolecular pi...pi stacking interactions and the presence in complex 2 of intramolecular hydrogen bonding. This pair of isomers therefore serves as an excellent model for studying noncovalent interactions and their effects on structure and electron density and the transferability of electron density properties between closely related molecules. For complex 2, a combination of X-ray and neutron diffraction data created the basis for a X-N charge density refinement. A topological analysis of the resulting density distribution using the atoms in molecules methodology is presented along with d-orbital populations, showing that the metal-ligand bonds are relatively unaltered by the geometry changes between 1 and 2. The experimental density has been supplemented by quantum chemical calculations on the cobalt complex cations: close agreement between theory and experiment is found in all cases. The energetics of the weak interactions are analyzed using both theory and experiment showing excellent quantitative agreement. In particular it is found that both methods correctly predict the stability of 2 over 1. The transferability between isomers of the charge density and derived parameters is investigated and found to be invalid for these structurally related systems.


Discretionary death: conditions, dilemmas, and normative regulation.
The author examines a major shift in the conceptualization and practices relating to death and dying in Western and other societies with advanced medicine. This shift is the result of socio-technical and cultural developments characterized by but not limited to the routine widespread application of life support technologies in the hospital together with notions of increased patient rights. It has resulted in a class of end-of-life situations, which the author defines as "discretionary death." The concept of discretionary death underscores the role of contextual and discretionary factors in end-of-life decision-making. The author identifies and discusses the necessary and complex process of norm formation that informs and regulates end-of-life medical practice and establishes societal consensus across society with respect to legitimizing "discretionary death."


Inhibition of growth hormone secretion in mild primary hyperparathyroidism.
Impairment in growth hormone (GH) secretion has been reported to occur in primary hyperparathyroidism (PHP) with strikingly elevated (>150 pg/ml) plasma PTH and free Ca levels. Patients with these characteristics are relatively few, whereas the great majority of patients with biochemically diagnosed PHP are asymptomatic and show borderline or slightly elevated plasma PTH and Ca levels. We wondered whether also patients in these latter conditions show a defective GH secretory pattern. In order to answer this question, 8 female subjects (mean age +/- SE: 44 +/- 1.3 years) were selected at the time of a checkup examination from a larger population of persons in fairly good clinical condition. Inclusion criteria were plasma PTH values slightly above the normal range (up to 50% higher than the maximum limit) with free Ca levels in the upper normal range or slightly higher (experimental group). Normal values in our laboratory are ionized calcium: 1.22-1.42 mmol/ml and plasma PTH: 12-72 pg/ml. A group of 15 age-matched healthy women with plasma PTH and Ca levels in the middle normal range and significantly lower than values found in the experimental group was also selected and used as control. Experimental and control groups were tested with arginine [0.5 mg/kg body weight (BW)] infused intravenously over 30 min and arginine plus GH-releasing hormone (GHRH; 1 microg/kg BW in an intravenous bolus injection). The GH responses to these challenging stimulations were compared between groups. Basal serum GH values were similar in all subjects. Both arginine and arginine plus GHRH induced a significant GH rise in both groups; however, the GH responses were significantly lower in the experimental than in the control group. Mean GH peak was 27.7 and 14.6 times higher than baseline after arginine and 57.5 and 26.6 times higher than baseline after arginine plus GHRH in the control and experimental group, respectively. No significant correlation was observed between PTH or Ca levels and the GH responses to challenging stimuli in any group. These data show that impairment in GH secretion is associated with slightly elevated levels of PTH in the presence of serum Ca values in the upper normal range. GH responses to stimulations were reduced by about 50% in our hyperparathyroid subjects. A long-time duration of this relatively small decline of GH secretory activity may be supposed to contribute to age-related catabolic processes in a large number of patients with mild primary hyperparathyroidism.


Clinical Nursing Faculty Competence Inventory - development and psychometric testing.
This paper is a report of the development and psychometric testing of the Clinical Nursing Faculty Competence Inventory. Clinical faculty plays a vital role in nursing education. Highly competent clinical faculty is a prerequisite for graduating competent future nurses. Many studies have examined the effectiveness of clinical nursing teaching. Yet, translating this body of knowledge into accurate and comprehensive assessment tools for measuring the competence of nursing faculty remains a challenge. Thirty-one indicators of core competence of clinical nursing faculty were identified thorough literature review, expert consultation and a small sample pilot test. A total of 237 nursing faculty members, students and administrators from six advanced medical colleges in China were surveyed during 2007-2008. Using a five-point Likert-type scale, the respondents identified their level of agreement with statements addressing the components of clinical nursing faculty competence. Exploratory factor analysis was used to determine the factor structure of the inventory. Students and faculty members valued aspects of clinical nursing faculty competence differently. Exploratory factor analysis using varimax rotation determined construct validity of the inventory and 26 items were retained. Five important categories of clinical nursing faculty competence were revealed: leadership ability, problem solving ability, educational intelligence, general teaching ability and clinical nursing skills. The Cronbach's alpha level of the inventory was 0·91, with each domain ranging from 0·61 to 0·85. The inventory has good psychometric properties and can be used in training and evaluation of clinical nursing faculty.


[Occurrence and mortality of breast cancer in Norway. Can early diagnosis explain the different trends?].
A comparison is made between incidence rates of breast cancer 1956-85 and mortality rates for Norwegian women 1951-85. The trends are very different. While all age-specific incidence rates have increased steadily, mortality rates have remained stable in women younger than 70 years and have increased slowly among older women. Different explanations are discussed, with the focus on early diagnostic methods and possible implications for future mammographic screening.


The use of lactate dehydrogenase (LDH) release kinetics for the evaluation of death and growth of mammalian cells in perfusion reactors.
A general methodology is proposed to estimate the actual specific growth and death rate of mammalian cells in continuous perfusion reactors from the monitoring of the release of the cytoplasmic enzyme lactate dehydrogenase (LDH) in the culture medium. The procedure is illustrated on a perfusion culture of human tumor kidney cells growing on microcarriers and producing prourokinase (PUK). The intracellular LDH content of living attached cells is checked to be constant during the culture. However, cells detached from the microcarriers, and counted dead because of the uptake of trypan blue, have only released part of their intracellular LDH. In the culture medium, LDH is relatively stable as the loss of activity does not exceed 5% per day. The time variation of the LDH concentration in the medium is used to calculate the total amount of lysed and actually produced cells in the reactors, hence, the actual specific rates of cell growth and death. It is thus found that the stationary phase observed after 400 h of perfusion culture is the result of equal growth and death rates, with a daily renewal of living cells on the microcarriers near 10%. Moreover, for the cell line tested, the production of PUK is associated with cellular growth.


Priming of centromere for CENP-A recruitment by human hMis18alpha, hMis18beta, and M18BP1.
The centromere is the chromosomal site that joins to microtubules during mitosis for proper segregation. Determining the location of a centromere-specific histone H3 called CENP-A at the centromere is vital for understanding centromere structure and function. Here, we report the identification of three human proteins essential for centromere/kinetochore structure and function, hMis18alpha, hMis18beta, and M18BP1, the complex of which is accumulated specifically at the telophase-G1 centromere. We provide evidence that such centromeric localization of hMis18 is essential for the subsequent recruitment of de novo-synthesized CENP-A. If any of the three is knocked down by RNAi, centromere recruitment of newly synthesized CENP-A is rapidly abolished, followed by defects such as misaligned chromosomes, anaphase missegregation, and interphase micronuclei. Tricostatin A, an inhibitor to histone deacetylase, suppresses the loss of CENP-A recruitment to centromeres in hMis18alpha RNAi cells. Telophase centromere chromatin may be primed or licensed by the hMis18 complex and RbAp46/48 to recruit CENP-A through regulating the acetylation status in the centromere.


Drosophila canopy b is a cochaperone of glycoprotein 93.
Drosophila gp93 was identified as the ortholog of the mammalian endoplasmic reticulum-resident chaperone gp96. gp93 was found capable of rescuing gp96 client proteins, such as Toll-like receptors (TLRs) and integrins, in a gp96-deficient murine cell line. Mammalian gp96 was further found to require the cochaperone canopy 3 (CNPY3) for proper folding and expression of TLRs, but not integrins. In Drosophila, two possible CNPY family members have been identified but have not yet been characterized. Therefore, we sought to determine the role of Drosophila CNPYa and CNPYb in gp93 biology. Because of higher similarities between CNPY3 and CNPYb, we postulated that CNPYb would be a TLR-specific cochaperone of gp93. Indeed, CNPYb addition in gp93-expressing cells improved TLR expression. CNPYb and gp93 were further found to physically interact. Mutational analysis of cysteine residues in CNPYb identified differential dependence of these cysteines in chaperone function. Our study is the first to characterize Drosophila CNPY molecules. We further uncover more gp93 biology by identifying CNPYb as a cochaperone. A better understanding of this simpler Drosophila system will enable application to the mammalian system, such as has been done with Escherichia coli, yeast, and mammalian HSP90.


Effect of progesterone and FSH on testes of immature chickens.
The effect of progesterone (P), estradiol benzoate (EB) plus P, and FSH on the testicular weight, macromolecular content, and incorporation of 3H-leucine, 3H-uridine and 3H-thymidine into macromolecules was examined in the testes of immature chickens. Not P alone but EB plus P lowered the testicular weight, and content of protein and RNA in the tissues, whereas FSH brought about an increase in the weight, and content of the two macromolecular elements. The DNA content was not affected by any hormones used. P, EB plus P and FSH brought about a decrease in the incorporation of radioactive leucine, uridine and thymidine into the macromolecules in the testes, with the exception of no change in the incorporation of 3H-uridine after EB plus P treatment and 3H-thymidine after FSH treatment. These results suggest that P, alone or in combination with estrogen, and FSH cause several changes in metabolic activity in the testes of immature chickens.


Platelet involvement in the activated coagulation time of heparinized blood.
The activated coagulation time (ACT), commonly used during cardiopulmonary bypass (CPB), is assumed to measure only differences in heparin levels. Studies were undertaken to determine whether platelet activation/inhibition might also influence the test. When either the platelet inhibitor prostacyclin or the platelet activator adenosine diphosphate (ADP) was added to healthy donor blood containing 2 IU of heparin per ml, there was significant prolongation of the ACT (prostacyclin: mean prolongation, 60.6%; ADP: mean prolongation, 52.3%). In blood taken from the extracorporeal circuit of ten CPB cases, the prolongation with the platelet inhibitor carbacyclin, a prostacyclin analogue, was infinite. It is concluded that the ACT as used during CPB must be interpreted as a measure of both platelet procoagulant activity and heparin activity. Furthermore, this dual sensitivity, while fortuitous, is probably advantageous; patients with hyporeactive platelets will automatically receive less heparin.


Endocrine and behavioral response to a decline in habitat quality: effects of pond drying on the slider turtle, Trachemys scripta.
The effect of the simulated drying of a pond on the behavior and corticosterone secretion of Trachemys scripta was measured in a field situation. Slider turtles were held in experimental and control ponds (12 x 15 m) enclosed with a drift fence integrated with spring-triggered livetraps. The experimental pond water level was dropped 10 cm per day for 8 d, until water was completely drained. Slider turtles responded to the draining of the pond by the emigration of the majority (75%) of the experimental population. Emigrating turtles had significantly elevated corticosterone at Time 0 (blood sample within 10 min of handling=4.48 ng/mL+/-0.503SE) when compared with turtles captured in a control pond (Time 0=0.954 ng/mL+/-0.121SE), where conditions were held constant. Turtles emigrated during the final 72 hr of pond draining when ponds reached 30 cm depth and lower and water temperature was at least 30.8 degrees C or higher. Additionally, the effect of trapping using spring-activated livetraps was tested. Turtles held in livetraps (n=6) for 45-110 min showed a characteristic corticosterone response (Time 0=0.957 ng/mL+/-0.091SE; Time 30=2.85 ng/mL+/-0.131SE), indicating that this trapping technique alone does not stimulate corticosterone secretion. The findings of the study met our predictions that turtles would respond to the draining of the pond behaviorally by emigrating from the habitat concurrent with an elevated corticosterone concentration. This supports the view that corticosterone is involved in stress avoidance mechanisms that allow organisms to respond to environmental perturbations.


Reliability and determinants of retinal vessel oximetry measurements in healthy eyes.
To assess the reliability and determinants of retinal vessel oximetry measurements with the Oxymap T1 Retinal Oximeter in normal Asian eyes. Subjects older than 40 years without a history of stroke and heart disease were recruited from a community-based clinic. Subjects underwent standardized systemic and ocular examinations. Normal eyes were defined as eyes without major eye diseases such as age-related macular degeneration, glaucoma, or retinopathy. Retinal vessel oximetry levels were measured by using the Oxymap T1 Retinal Oximeter. Intra- and intergrader reliability of retinal vessel oximetry measurements were assessed by using 50 images. Intravisit repeatability of retinal vessel oximetry measurements was assessed by using 20 paired images. Univariable linear regression was performed to examine the associations between retinal vessel oximetry measurements and systemic determinants. A total of 118 retinal oximetry images were included in the final analysis. Intra- (intraclass correlation coefficient [ICC] values: 0.89-0.99) and intergrader (ICC values: 0.77-0.94) reliability, and intravisit (ICC values: 0.85-0.96) repeatability were both high. In the linear regression analysis, older age was associated with reduced overall retinal venular oximetry levels (β: -2.61%; 95% confidence interval [CI]: -4.92 to -0.29) and reduced inferior-nasal retinal venular oximetry levels (β: -3.53%; 95% CI: -6.07 to -0.99). The Oxymap Retinal Oximeter allows reliable and repeatable retinal vessel oximetry measurements. Age is the main factor that influences retinal venular oximetry levels and should be taken into account when retinal oximetry measurements are interpreted.


Release of inflammatory mediators from guinea pig trachea by electrical field stimulation: lack of neuronal involvement.
Electrical field stimulation (EFS; 5-10 V, 1 ms, 20 Hz for 1 min) of isolated guinea pig trachea resulted in a rapid increase in tone that is blocked by either atropine or tetrodotoxin (TTX). EFS of tracheal spirals also caused large increases in the release of certain prostanoids with release of prostaglandin (PG)D2, PGE2 and PGF2 alpha (16.5-, 3.0- and 4.1-fold, respectively). In contrast to the smooth muscle response, however, EFS-induced release of prostanoids was not significantly altered in the presence of TTX. Removal of the epithelium reduced the amount of prostanoids released by EFS. Thus, EFS-induced production of PGD2, PGE2 and PGF2 alpha was significantly reduced by about 30%, 70% and 80% in epithelium-denuded tissues, respectively. Direct vagal stimulation caused a rapid contraction of the trachealis but failed to elicit increases in the release of histamine or arachidonic acid metabolites. Furthermore, the selective stimulant of C-type sensory fibers capsaicin (3 microM) or exogenously applied substance P (1 microM) or neurokinin A (1 microM) failed to induce histamine, leukotriene or prostanoid release from guinea pig tracheal rings. Although, the mechanism involved in stimulation of arachidonic acid metabolism by EFS is unclear, this effect in part involves the epithelium but apparently is not mediated by airway elements sensitive to TTX, direct vagal stimulation or tachykinins.


Sodium acetate ameliorates doxorubicin-induced cardiac injury via upregulation of Nrf2/HO-1 signaling and downregulation of NFkB-mediated apoptotic signaling in Wistar rats.
Despite the effectiveness of doxorubicin (DOX) in the management of a wide range of cancers, a major challenge is its cardio-toxic effect. Oxidative stress, inflammation, and apoptosis are major pathways for the cardiotoxic effect of DOX. On the other hand, acetate reportedly exerts antioxidant, anti-inflammatory, and anti-apoptotic activities. This particular research assessed the impact of acetate on cardiotoxicity induced by DOX. Mechanistically, acetate dramatically inhibited DOX-induced upregulation of xanthine oxidase and uric acid pathway as well as downregulation of Nrf2/HO-1 signaling and its upstream proteins (reduced glutathione peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione, and catalase, glutathione reductase). In addition, acetate markedly attenuated DOX-driven rise inTNF-α, NFkB IL-6 and IL-1β expression, and myeloperoxidase activity. Furthermore, acetate significantly ameliorated DOX-led suppression of Bcl-2 and Ca2+-ATPase activity and upregulation of Bax, caspase 3, and caspase 9 actions. Improved body weight, heart structural integrity, and cardiac function as depicted by cardiac injury markers convoyed these cascades of events. Summarily, the present study demonstrated that acetate protects against DOX-induced cardiotoxicity by upregulating Nrf2/HO-1 signaling and downregulating NFkB-mediated activation of Bax/Bcl-2 and caspase signaling.


Maternal anxiety and depression, poverty and marital relationship factors during early childhood as predictors of anxiety and depressive symptoms in adolescence.
This paper examines the degree to which symptoms of anxiety and depression at age 14 years are associated with early childhood experience of maternal anxiety and depression, poverty, and mother's marital relationship distress and break-up. In a longitudinal study, 4434 families were followed-up from infancy to adolescence. Maternal anxiety and depression during early childhood were found to have small, but significant, influences upon the development of high anxiety-depression symptoms at age 14, after controlling for the effects of poverty and marital relationship factors. This effect was greater with repeated exposure to high maternal anxiety and depression. Poverty, distressed marital relationship and marital break-up during the child's first five years also produced small, but significant, increases in risk of high anxiety and depression symptoms in adolescence. Stable, single-parent status was not found to be a risk factor. There was no evidence of marked gender differences in risk factors, other than poverty, which had a stronger impact for girls than boys. Overall, the results suggest that maternal anxiety and depression, poverty, parent relationship conflict and marital break-up during early childhood are associated with small, but significant, increased risk of anxiety-depression symptoms in adolescence.


Catalytic transfer hydrogenation of azobenzene by low-valent nickel complexes: a route to 1,2-disubstituted benzimidazoles and 2,4,5-trisubstituted imidazolines.
The one-pot synthesis of 1,2-disubstituted benzimidazoles by the transfer hydrogenation of azobenzene, using benzylamine as a hydrogen donor, sequential rearrangement of hydrazobenzene to semidine and further condensation with N-benzylideneamine is reported, catalyzed by 2 mol% of [Ni(COD)2] : dippe. The N2 substitution on benzimidazole can be controlled by the selection of different azobenzenes and C2 substitution will only depend on the chosen benzylamine. The current methodology avoids the addition of external oxidants, which are needed in the classical benzimidazole synthesis. In addition, the byproduct, N-benzylideneamine, obtained from dehydrogenation of benzylamine produced 2,4,5-trisubstituted imidazolines by cyclization and C-H functionalization, and this route was optimized with the use of 2 mol% of [Ni(COD)2] : 2PPh3.


Home visit effectiveness for peritoneal dialysis patients.
Medicare regulations require follow-up home visits to home dialysis patients, yet routine home visits require a lot of personnel time. The effectiveness of home visits was evaluated by a nurse, dietitian and social worker using a questionnaire. Thirty-six patients were evaluated during an 18-month period. Collectively the team documented an average of 10 pertinent observations per visit and made an average of 4 recommendations for change. Staff members gained new information about the patient as indicated by the fact that they changed their rankings on 5 of 15 parameters following the home visit. The home visit policy that recommended an annual home visit was revised to recommend a single home visit for each new peritoneal dialysis patient. Further visits are performed only if significant problems are identified.


Phosphaplatin Anti-tumor Effect Enhanced by Liposomes Partly via an Up-regulation of PEDF in Breast Cancer.
Phosphaplatin platinum (IV) (RRD4) complex has exceptional antitumor properties. The aim of this study was to investigate the effects and the mechanism of action of free and liposome-encapsulated RRD4 in breast cancer. Liposome-encapsulated RRD4 prepared by thin-film dehydration: hydration and free RRD4 were tested in vivo and in vitro against 4T1 breast cancer cells. Cell proliferation, migration and viability were determined. Tissue and cell production and expression of pigment epithelium-derived factor (PEDF) were assessed by ELISA and western blot. 4T1 cells treated with PEDF siRNA were evaluated for viability and apoptosis. RRD4 inhibited tumor growth and prevented distant metastasis. Liposome formulation enhanced this therapeutic benefit without increasing toxicity and prolonged RRD4 retention in tumor tissues. In vitro, RRD4 induced 4T1 apoptosis through up-regulation of FAS, BAX, and PUMA, and down-regulation of BCL2. RRD4 facilitates a FAS-intrinsic signaling mechanism. PEDF up-regulation represents another antitumor mechanism associated with this phosphaplatin compound. Free RRD4 or formulated into liposomes, are excellent candidates for adjuvant therapy against breast tumor growth and metastasis.


[Never ignore the therapeutic principles during the procedure of laparoscopic gastrectomy for gastric cancer].
In recent years, minimally invasive surgery has been adopted and widely used in Japan and Korea for early gastric cancer with low risk of lymph node metastasis, since laparoscopy-assisted distal gastrectomy (LADG) with lymph node dissection was first reported in 1994 by Kitano. The purposes of laparoscopic surgery for gastric cancer are to minimize surgical insults and to maximize patient's quality of life, while not compromising the oncologic clearance. As laparoscopic experience has accumulated, the indications for laparoscopic gastrectomy (LG) have been broadened to patients with advanced gastric cancer. However, the role of LG remains controversial, because studies of the long-term outcomes of LG are insufficient. Therefore, in order to make sure the same effectiveness of LG as conventional open operation, there are some basic principles should be strictly followed while performing LG, such as properly selected patients, sufficient surgical margins, standardized D2 lymphadenectomy, no-touch technique and so on.


Controllable Ion Channel Expression through Inducible Transient Transfection.
Transfection, the delivery of foreign nucleic acids into a cell, is a powerful tool in protein research. Through this method, ion channels can be investigated through electrophysiological analysis, biochemical characterization, mutational studies, and their effects on cellular processes. Transient transfections offer a simple protocol in which the protein becomes available for analysis within a few hours to days. Although this method presents a relatively straightforward and time efficient protocol, one of the critical components is calibrating the expression of the gene of interest to physiological relevant levels or levels that are suitable for analysis. To this end, many different approaches that offer the ability to control the expression of the gene of interest have emerged. Several stable cell transfection protocols provide a way to permanently introduce a gene of interest into the cellular genome under the regulation of a tetracycline-controlled transcriptional activation. While this technique produces reliable expression levels, each gene of interest requires a few weeks of skilled work including calibration of a killing curve, selection of cell colonies, and overall more resources. Here we present a protocol that uses transient transfection of the Transient Receptor Potential cation channel subfamily V member 1 (TRPV1) gene in an inducible system as an efficient way to express a protein in a controlled manner which is essential in ion channel analysis. We demonstrate that using this technique, we are able to perform calcium imaging, whole cell, and single channel analysis with controlled channel levels required for each type of data collection with a single transfection. Overall, this provides a replicable technique that can be used to study ion channels structure and function.


The future of teaching physiology: an international viewpoint.
The discipline of physiology is challenging to teach. It has ill-defined boundaries and no agreed sequence for learning; students' needs depend on the goals of the specific degree programs in which they are enrolled. Internationally, it is taught under many different conditions, using a range of strategies, to a wide variety of groups. All teachers are subject to local constraints and the availability of resources. Newer educational methods emphasizing active and integrated learning provide novel challenges. Computer-based educational strategies offer promise but do not represent easy solutions, particularly when they are unaffordable in many parts of the world. Particular difficulties in teaching arise for some when they are not themselves broadly educated in physiology and related disciplines and for others when they have only limited access to up-to-date knowledge and resources. Sessions and workshops on modern physiology and educational issues should be included in national, regional, and international conferences at which the participation of teachers is encouraged and supported.


Human insulin gene enhancer-binding proteins in pancreatic alpha and beta cell lines.
Electrophoretic mobility shift assays were performed using oligonucleotides corresponding to known protein binding sites within the human insulin gene enhancer and nuclear extracts from mouse pancreatic alpha and beta cell lines. The results demonstrate that a previously described factor, IUF-1, binds to three sites at -82 (the CT1 box), -215 (the CT2 box), and -319 (the CT3 box) in the human insulin gene enhancer. IUF-1 was present only in beta but not in alpha cells, while all other DNA-binding proteins were present in both cell lines. IUF-1 may therefore be an important determinant of insulin gene beta cell-specific expression.


A standardised terminology of the embryonic envelopes and associated developmental stages of tapeworms (Platyhelminthes: Cestoda).
Over the past 40 years, much has been published on the ultrastructure and cellular development of embryonic structures in a wide range of cestodes. However, the literature contains many discrepancies in both terminology and interpretations because of the facts that these organisms are phylogenetically diverse within their respective orders and families, the habitats that affect embryonic envelope structure are diverse, and the work has been done in various laboratories around the world. This review and synthesis was initiated by a working group of biologists from around the world convened at the Fifth International Workshop on Cestode Systematics and Phylogeny in Ceské Budejovice, at the Institute of Parasitology of the Biology Centre, Academy of Sciences of the Czech Republic. It brings together the data from published work and establishes a uniform terminology and interpretation based on the data as they are presented. A consensus was reached for standardised definitions of the oncosphere, hexacanth, coracidium, embryonic envelopes, outer envelope, inner envelope, embryophore, vitelline capsule, shell, and outer coat. All of these are defined as components of the embryo or its vitellocyte-derived or uterine-derived coatings.


[The concept of disease in Galen].
Galen was, with no doubt, a great authority in ancient medicine rivalled only with "the father of medicine" Hippocrates. His medicine inherited not only Hippocratic tradition, which is characterized by dynamic pathology, but also Alexandrian medicine, which made a great contribution to anatomy. He did not generalize all the pathological phenomena according to one dogmatic theory. His medicine was open to all kinds of medicine, but he was quite selective in receiving different medical traditions.Galen defined disease as impairment of bodily activities. Whatever that impairs the bodily activities is the cause of disease. Galen' s pathology is built upon two heterogeneous medical traditions: 1) Dynamic pathology of the Hippocratic medicine, but which ignored anatomy 2) Anatomical pathology of Alexandrian medicine. Galen integrated these two different traditions by his concept of disease. His definition of disease, impairment of bodily activities, made it possible to harmorize these two different traditions otherwise which would have been conflictual. It is Galen' s great contribution to Western medicine to have laid a foundation of pathology by combining physiological and anatomical point of view .


Human spastin has multiple microtubule-related functions.
Hereditary spastic paraplegias (HSPs) are neurodegenerative diseases caused by mutations in more than 20 genes, which lead to progressive spasticity and weakness of the lower limbs. The most frequently mutated gene causing autosomal dominant HSP is SPG4, which encodes spastin, a protein that belongs to the family of ATPases associated with various cellular activities (AAAs). A number of studies have suggested that spastin regulates microtubule dynamics. We have studied the ATPase activity of recombinant human spastin and examined the effect of taxol-stabilized microtubules on this activity. We used spastin translated from the second ATG and provide evidence that this is the physiologically relevant form. We showed that microtubules enhance the ATPase activity of the protein, a property also described for katanin, an AAA of the same spastin subgroup. Furthermore, we demonstrated that human spastin has a microtubule-destabilizing activity and can bundle microtubules in vitro, providing new insights into the molecular pathogenesis of HSP.


Modulation of colony stimulating factor-induced murine myeloid colony formation by S-peptido-lipoxygenase products.
Prompted by the observation that the selective blockade of lipoxygenase pathway by known inhibitors of this pathway inhibited the colony stimulating factor (CSF)-induced colony formation in both mouse and human marrow cells and the fact that this inhibitory effect could be reversed by a crude total lipoxygenase extract from an incubation of rat peritoneal neutrophils and arachidonic acid, we investigated which of the two major classes of lipoxygenase products, mono- and dihydroxy fatty acids (5S-hydroxyeicosatetraenoic acid and 5S-, 12R-dihydroxyeicosatetraenoic acid) and the S-peptidohydroxy fatty acids (leukotrienes C4 and D4), is involved in the modulation of CSF-induced colony formation by mouse marrow cells. Data from incubations with synthetic lipoxygenase products revealed that (a) the culture of mouse marrow cells in the presence of varying amounts of purified CSF-I (Mia PaCa 2) with a low concentration (5 micrograms/ml) of nordihydroguaretic acid consistently suppressed CSF-induced colony formation by approximately 40-50%. This concentration of nordihydroguaretic acid selectively inhibits only the lipoxygenase pathway; (b) additions of two S-peptido-hydroxy fatty acids [5S-hydroxy-6R-S-glutathionyl-7,9,11,14-(E,E,Z,Z)-eicosatetraenoic acid and 5S-hydroxy-6R-S-cysteinglycyl-7,9,11,14-(E,E,Z,Z)-eicosatetraenoic acid] to these partially suppressed colonies restored the CSF-induced colony formation to control levels in a dose-dependent manner; and (c) additions of two mono- and dihydroxy acids, 5S-hydroxyeicosatetraenoic acid and 5S-12R-dihydroxyeicosatetraenoic acid [5S, 12R-dihydroxy-6,8,10,14-(Z,E,E,Z)-eicosatetraenoic acid], failed to restore the nordihydroguaretic acid inhibited colony formation. These novel observations underscore the importance of these peptido-5-hydroxy fatty acids and the lipoxygenase pathway in the mechanism of CSF-induced colony formation in mouse marrow cells.


Quantitative severity of stress thallium-201 myocardial perfusion single-photon emission computed tomography defects in one-vessel coronary artery disease.
The relation between the quantitative myocardial perfusion defect severity of exercise thallium-201 single-photon emission computed tomography (SPECT) and the quantitative degree of coronary stenosis was examined in 18 patients with 1-vessel disease (> or = 50% diameter stenosis), and abnormal thallium-201 SPECT. A total of 26 vessels were analyzed. Thallium-201 SPECT quantitative defect severity score was derived by summing the number of pixels in a coronary territory in which counts fell below the normal mean and multiplied by the number of SDs by which they fell below the normal mean. The thallium-201 defect severity score was significantly (p < 0.001) related to the maximal percent luminal diameter narrowing (r = 0.93), percent area narrowing (r = 0.89), absolute stenotic area (r = 0.79), and absolute stenotic diameter (r = 0.81). As expected, the strongest relation between thallium-201 defect severity and quantitative angiographic indexes was in the low and high ranges of coronary stenosis, with more variability and lower correlation coefficients (percent diameter: r = 0.75, p < 0.02, percent area stenosis: r = 0.63, p < 0.05) in the middle ranges (50 to 80% diameter stenosis). This observation is likely to be due to the complex flow characteristics across stenotic lesions. The findings suggest that in a select population, thallium-201 defect severity is potentially useful for noninvasive characterization of the functional severity of coronary artery stenosis and may complement coronary angiography in predicting functionally significant stenosis.


Soy protein with or without isoflavones, soy germ and soy germ extract, and daidzein lessen plasma cholesterol levels in golden Syrian hamsters.
Dietary isolated soy protein (ISP, containing approximately equal amounts of daidzein and genistein), ethanol-extracted ISP (ISP (-)), soygerm or soygerm extract (containing large amounts of daidzein and glycitein and little genistein) and the isoflavone, daidzein, were hypothesized to lessen plasma cholesterol in comparison with casein. Sixty male and 60 female golden Syrian hamsters (6-8 weeks of age) were randomly assigned to six treatments fed for 10 weeks. Four of the experimental diets (ISP, daidzein, soygerm, and soygerm extract) contained 1.3 mmol total isoflavones/kg. The ISP (-) diet contained 0.013 mmol isoflavone/kg, whereas the casein diet contained no isoflavones. Hamsters fed ISP, ISP (-), daidzein, soygerm, and soygerm extract had significantly less plasma total cholesterol (by 16%-28%), less non-HDL cholesterol (by 15%-50%) and less non-HDL/HDL cholesterol ratios compared with hamsters fed casein (P < 0.01). For male hamsters, there were no differences among treatments in plasma HDL concentrations. Female hamsters fed ISP (-) had significantly greater HDL levels (P < 0.01) than females fed casein or daidzein. Triglyceride concentration was significantly less in hamsters fed ISP (-) compared with the casein-fed females. Because soy protein with or without isoflavones, soygerm and soygerm extract, and daidzein lessened plasma cholesterol to an approximately equal extent, soy protein alone, varying mixtures of isoflavones, and other extractable components of soy are responsible for cholesterol-lessening effects of soy foods, mainly due to their effects to lessen LDL cholesterol.


Broadband Plasmonic Polarization Filter Based on Photonic Crystal Fiber with Dual-Ring Gold Layer.
Polarization filter is a very important optical device with extinction characteristics. Due to the design flexibility of photonic crystal fibers and the high excitation losses of the gold layer, the polarization filter based on the photonic crystal fiber and surface plasmonic resonance effect is widely studied. Considering these, we present a simple and high-performance polarization filter using the finite element method. Numerical simulations show that there is a large difference in energy between the two polarization directions by reasonable adjustment of the structural parameters, the confinement loss in the x-pol direction is less than that in the y-pol direction, which is suitable to realize a broadband polarization filter. When the fiber length is 2 mm, the extinction ratio peak can reach -478 dB, and the bandwidth with the extinction ratio better than -20 dB is 750 nm, which covers communication wavelengths of 1.31 μm and 1.55 μm (1.05-1.8 μm). It also has a low insertion loss of 0.11 dB at 1.31 μm and 0.04 dB at 1.55 μm. In addition, our design has high feasibility in fabrication and better tolerance. The proposed filter with compactness, high extinction ratio, broad bandwidth, and low insertion loss would play an important role in the sensing detection, bio-medical, and telecommunication field.


APC: the toll road to continued high quality communication.
In this article we briefly review the reasons and advantages that underly our publisher's decision to introduce article-processing charges (APC) for manuscripts submitted to Cell Communication and Signaling. The charge is an attempt to develop a new business model for distributing biomedical information and has been accepted in a number of other journals. APCs will enable BioMed Central to continue to provide their excellent service and will help to establish our journal.


A convolutional neural network algorithm for breast tumor detection with magnetic detection electrical impedance tomography.
Breast cancer is a malignant tumor disease for which early detection, diagnosis, and treatment are of paramount significance in prolonging the life of patients. Magnetic Detection Electrical Impedance Tomography (MDEIT) based on the Convolutional Neural Network (CNN), which aims to realize non-invasive, high resolution detection of breast tumors, is proposed. First, the MDEIT forward problem of the coronal and horizontal planes of the breast was simulated and solved using the Finite Element Method to obtain sample datasets of different lesions. Then, the CNN was built and trained to predict the conductivity distribution in different orientations of the breast model. Finally, noise and phantom experiments were performed in order to assess the anti-noise performance of the CNN algorithm and its feasibility of detecting breast tumors in practical applications. The simulation results showed that the reconstruction relative error with the CNN algorithm can be reduced to 10%, in comparison with the truncated singular value decomposition algorithm and back propagation algorithm. The CNN algorithm had better stability in the anti-noise performance test. When the noise of 60 dB was added, the shape of the breast tumor could still be restored by the CNN algorithm. The phantom experimental results showed that through the CNN based reconstruction algorithm, the reconstruction conductivity distribution image was legible and the position of the breast tumor could be determined. It is reasonable to conclude that the MDEIT reconstruction method proposed in this study has practical importance for the early and non-invasive detection of breast tumors.


Influence of heart rate and age on Q-Korotkoff sound intervals.
The Korotkoff sound appearance time (QK intervals) was measured in 224 normal subjects of both sexes between the age of 6 and 79 years. The sex difference was not obvious except for the diastolic values of the intervals (QKd) in the sixth decade. Although the QK intervals remained almost unchanged between the third and the fifth decade, both the systolic (QKs) and the diastolic values were significantly smaller in the young subjects under the age of 20. On the other hand, QKs was significantly decreased and QKd and the difference between the systolic and diastolic values (QKs-d) were significantly increased in the elderly subjects. The short QK interval in the young subjects was considered to be mainly attributable to the short preejection period, while the increased pulse wave velocity was postulated to be the main responsible factor for the shortening of QKd in the elderly subjects. A statistically significant negative correlation was demonstrated between QKd and the heart rate in both sexes, while QKs and QKs-d were not significantly correlated with the heart rate.


Developing the random phase approximation into a practical post-Kohn-Sham correlation model.
The random phase approximation (RPA) to the density functional correlation energy systematically improves upon many limitations of present semilocal functionals, but was considered too computationally expensive for widespread use in the past. Here a physically appealing reformulation of the RPA correlation model is developed that substantially reduces its computational complexity. The density functional RPA correlation energy is shown to equal one-half times the difference of all RPA electronic excitation energies computed at full and first order coupling. Thus, the RPA correlation energy may be considered as a difference of electronic zero point vibrational energies, where each eigenmode corresponds to an electronic excitation. This surprisingly simple result is intimately related to plasma theories of electron correlation. Differences to electron pair correlation models underlying popular correlated wave function methods are discussed. The RPA correlation energy is further transformed into an explicit functional of the Kohn-Sham orbitals. The only nontrivial ingredient to this functional is the sign function of the response operator. A stable iterative algorithm to evaluate this sign function based on the Newton-Schulz iteration is presented. Integral direct implementations scale as the fifth power of the system size, similar to second order Moller-Plesset calculations. With these improvements, RPA may become the long-sought robust and efficient zero order post-Kohn-Sham correlation model.


Frequency Of Different Risk Factors Associated With Recurrent Urinary Tract Infection Among Postmenopausal Women.
Urinary Tract Infection is one of the most common infections encountered by women. These infections have the tendency to recur. In order to identify women at risk of recurrence there is a need to identify risk factors associated with it. Among women, factors predisposing to recurrent infections are not much explored. The study was done with an objective to determine different risk factors associated with recurrent UTI among postmenopausal women. This was a cross sectional study conducted at the Out Patient Department of Nephrology in Shifa International Hospital Islamabad over a period of six months, June 6th to December 5th 2012. Information regarding demographics and risk factors were recorded on a predesigned pro forma. A descriptive analysis was done for quantitative variables like age and qualitative variables like marital status and frequency of different risk factors. Stratification of risk factors according to age was also done. Hundred females were enrolled into the study after informed consent. The mean age of the study population was 64.4±9.48. 97% of the population was married. Out of 100 patients, 42 had high post-void volume, 35 had urinary incontinence and 17 patients were having cystocele. According to age stratification, most frequently affected age group was between 51-60 years (38%), followed by 61-70 years (36%), then 25% in more than 70 years, whereas only 1% was between 41-50 years. Recurrent UTI in postmenopausal females is most frequently associated with high post void volume and most frequently affected age group is between 51-60 years.


Abnormal presentation of pregnancy and postpartum initial-onset systemic lupus erythematosus combined with diffuse alveolar hemorrhage: A case report.
Systemic lupus erythematosus (SLE) is an autoimmune disease that most commonly occurs in women of childbearing age. However, cases of SLE with abnormal pregnancy as the initial manifestation, involving the development of diffuse alveolar hemorrhage (DAH), have rarely been reported. Herein, we report the case of a young woman who underwent a cesarean section for fetal distress and growth restriction at 35 + 1 weeks' gestation. Following discharge, she experienced progressive worsening of anemia and chest tightness, which was later diagnosed as SLE complicated by DAH.


The therapeutic effect and mechanism of melatonin on osteoarthritis: From the perspective of non-coding RNAs.
Osteoarthritis (OA) is a slowly progressing and irreversible joint disease. The existing non-surgical treatment can only delay its progress, making the early treatment of OA a research hotspot in recent years. Melatonin, a neurohormone mainly secreted by the pineal gland, has a variety of regulatory functions in different organs, and numerous studies have confirmed its therapeutic effect on OA. Non-coding RNAs (ncRNAs) constitute the majority of the human transcribed genome. Various ncRNAs show significant differentially expressed between healthy people and OA patients. ncRNAs play diverse roles in many cellular processes and have been implicated in many pathological conditions, especially OA. Interestingly, the latest research found a close interaction between ncRNAs and melatonin in regulating the pathogenesis of OA. This review discusses the current understanding of the melatonin-mediated modulation of ncRNAs in the early stage of OA. We also delineate the potential link between rhythm genes and ncRNAs in chondrocytes. This review will serve as a solid foundation to formulate ideas for future mechanistic studies on the therapeutic potential of melatonin and ncRNAs in OA and better explore the emerging functions of the ncRNAs.


It Takes Two to Tango! Protein-Protein Interactions behind cAMP-Mediated CFTR Regulation.
Over the last fifteen years, with the approval of the first molecular treatments, a breakthrough era has begun for patients with cystic fibrosis (CF), the rare genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These molecules, known as CFTR modulators, have led to unprecedented improvements in the lung function and quality of life of most CF patients. However, the efficacy of these drugs is still suboptimal, and the clinical response is highly variable even among individuals bearing the same mutation. Furthermore, not all patients carrying rare CFTR mutations are eligible for CFTR modulator therapies, indicating the need for alternative and/or add-on therapeutic approaches. Because the second messenger 3',5'-cyclic adenosine monophosphate (cAMP) represents the primary trigger for CFTR activation and a major regulator of different steps of the life cycle of the channel, there is growing interest in devising ways to fine-tune the cAMP signaling pathway for therapeutic purposes. This review article summarizes current knowledge regarding the role of cAMP signalosomes, i.e., multiprotein complexes bringing together key enzymes of the cAMP pathway, in the regulation of CFTR function, and discusses how modulating this signaling cascade could be leveraged for therapeutic intervention in CF.


Simultaneous determination of glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid mono-glucuronide in Shakuyaku-kanzo-to incubated with rat feces by semi-micro high-performance liquid chromatography.
A method for semi-micro high-performance liquid chromatography (HPLC) has been established for the simultaneous determination of glycyrrhizin (GL), glycyrrhetic acid (GA) and glycyrrhetic acid mono-glucuronide (GAMG) in incubation mixtures of rat feces with Shakuyaku-kanzo-to decoction (combination of licorice root and peony root). The analysis could be accomplished within 20 min with a TSKgel ODS-80TsQA (150 x 2.0 mm i.d.) column by linear gradient elution using a mobile phase containing aqueous phosphoric acid and acetonitrile at a flow rate of 0.2 ml x min(-1), a thermostatic oven at 25 degrees C, and detection at 254 nm. The detection limits of these compounds were 0.1-0.85 pmol per injection (5 microl). The concentrations of GL and its metabolites in the incubation mixture after continuous consumption of Shakuyaku-kanzo-to were significantly different compared with those of untreated control. GL-hydrolysis of rat feces was enhanced by pre-consumption of Shakuyaku-kanzo-to.


Anti-inflammatory effects of low-level laser therapy (LLLT) with two different red wavelengths (660 nm and 684 nm) in carrageenan-induced rat paw edema.
It has been suggested that low-level laser therapy (LLLT) can modulate inflammatory processes. The aim of this experiment was to investigate what effects red laser irradiation with two different wavelengths (660 nm and 684 nm) on carrageenan-induced rat paw edema and histology. Thirty two male Wistar rats were randomly divided into four groups. One group received a sterile saline injection, while inflammation was induced by a sub-plantar injection of carrageenan (1 mg/paw) in the three other groups. After 1 h, LLLT was administered to the paw in two of the carrageenan-injected groups. Continuous wave 660 nm and 684 nm red lasers respectively with mean optical outputs of 30 mW and doses of 7.5 J/cm(2) were used. The 660 nm and 684 nm laser groups developed significantly (p<0.01) less edema (0.58 ml [SE+/-0.17] ml and 0.76 ml [SE+/-0.10] respectively) than the control group (1.67 ml [SE+/-0.19]) at 4h after injections. Similarly, both laser groups showed a significantly lower number of inflammatory cells in the muscular and conjunctive sub-plantar tissues than the control group. We conclude that both 660 nm and 684 nm red wavelengths of LLLT are effective in reducing edema formation and inflammatory cell migration when a dose of 7.5 J/cm(2) is used.


Increased soluble interleukin 2 receptor levels in autoimmune thyroid disease.
We measured soluble interleukin 2 receptor, a part of the Tac protein (p55), in peripheral blood to study the immunological condition of the T cell in autoimmune thyroid disease. In 26 patients with untreated Graves' disease and 7 hyperthyroid patients with Hashimoto's thyroiditis, the mean levels of soluble IL-2 receptor were both significantly higher than in normal controls (1497 +/- 649 (mean +/- SD), 641 +/- 137 vs 221 +/- 63 10(3) U/l, p less than 0.001). There was good correlation between soluble IL-2 receptor levels and blood thyroxine levels (r = 0.684, p less than 0.001) in patients with untreated Graves' disease, but no correlation of soluble IL-2 receptor with TSH-inhibitory immunoglobulins, TS-ab, thyroidal autoantibodies to thyroglobulin and thyroidal microsomal antigen was found. We thought that the level of soluble IL-2 receptor is not dependent only on immunological conditions, but also on thyroid hormone status. When T3 was administered to subjects in remission from Graves' disease and in normal controls, the soluble IL-2 receptor levels significantly increased. Moreover, the mean level of soluble IL-2 receptor in patients with toxic multinodular goitre was also significantly higher than in normal controls (411 +/- 148 vs 221 +/- 63 10(3)U/l, p less than 0.05). We conclude that the soluble IL-2 receptor levels are higher in sera of subjects with elevated levels of thyroid hormone.


Predictors of time to death after terminal withdrawal of mechanical ventilation in the ICU.
Little information exists about the expected time to death after terminal withdrawal of mechanical ventilation. We sought to determine the independent predictors of time to death after withdrawal of mechanical ventilation. We conducted a secondary analysis from a cluster randomized trial of an end-of-life care intervention. We studied 1,505 adult patients in 14 hospitals in Washington State who died within or shortly after discharge from an ICU following terminal withdrawal of mechanical ventilation (August 2003 to February 2008). Time to death and its predictors were abstracted from the patients' charts and death certificates. Predictors included demographics, proxies of severity of illness, life-sustaining therapies, and International Classification of Diseases, 9th ed., Clinical Modification codes. The median (interquartile range [IQR]) age of the cohort was 71 years (58-80 years), and 44% were women. The median (IQR) time to death after withdrawal of ventilation was 0.93 hours (0.25-5.5 hours). Using Cox regression, the independent predictors of a shorter time to death were nonwhite race (hazard ratio [HR], 1.17; 95% CI, 1.01-1.35), number of organ failures (per-organ HR, 1.11; 95% CI, 1.04-1.19), vasopressors (HR, 1.67; 95% CI, 1.49-1.88), IV fluids (HR, 1.16; 95% CI, 1.01-1.32), and surgical vs medical service (HR, 1.29; 95% CI, 1.06-1.56). Predictors of longer time to death were older age (per-decade HR, 0.95; 95% CI, 0.90-0.99) and female sex (HR, 0.86; 95% CI, 0.77-0.97). Time to death after withdrawal of mechanical ventilation varies widely, yet the majority of patients die within 24 hours. Subsequent validation of these predictors may help to inform family counseling at the end of life.


[Culture, purification and biological characters of olfactory ensheathing cells from adult transgenic mice].
Several studies have demonstrated the potential of olfactory ensheathing cells (OECs) for the repair of central and peripheral nerve injury. In this work, ensheathing cells that express the receptor gene coding for enhanced green fluorescent protein (eGFP) from adult mice were isolated and purified, and then, its biological characters were examined in vitro. The work was based on combinations of fluorescence confocal, phase contrast, cell proliferation assay and immunolabeling identification. The results showed that (1) two major morphologically and immunohistochemically distinct types of cells were present after 15 days in the primary cultures of adult transgenic mice olfactory nerves and glomerular layers of the olfactory bulb. One cell type was bipolar or multipolar OECs and strained positively for P75 low affinity neurotrophic receptor (P75N), S100, and glial fibrillary acidic protein(GFAP). The other type was fibroblasts with flat or endothelial-like shape, and reacted with antibody against Thy1.1. (2) A simple, inexpensive method for purifying ensheathing cells, in which various harvested cell types showed different rates of attachment to the uncoated culture ware, was developed. This technique neither binds any antibodies nor requires any costly equipment, and yields a large number of highly purified cells. (3) In sequential observations over 22 days in culture, the population of purified cells was maintained and continued to proliferate for longer. This experiment not only supported and advanced the ensheathing cell research but also offered ideal materials of in vivo transplantation for the repair of CNS injury.


Small bowel injury as a complication of lumbar microdiscectomy : case report and literature review.
Small bowel injury resulting from unforeseen penetration of the anterior annulus fibrosus and longitudinal ligament is a rare complication of lumbar microdiscectomy. The patient complained of abdominal tenderness and distention immediately after microdiscectomy for L4-5 and L5-S1 disc herniation. Using abdominal computed tomography, we found several foci of air overlying the anterior aspect of the vertebral body at the L5-S1 level. Segmental resection of the small bowel including small tears and primary anastomosis of the jejunum were performed. Here, we present a case of intestinal perforation after lumbar microdiscectomy and discuss technical methods to prevent this complication with a review of literature.


Mechanism of formation of the ester linkage between heme and Glu310 of CYP4B1: 18O protein labeling studies.
Cytochrome P450s in the CYP4 family covalently bind their heme prosthetic group to a conserved acidic I-helix residue via an autocatalytic oxidation. This study was designed to evaluate the source of oxygen atoms in the covalent ester link in CYP4B1 enzymes labeled with [18O]glutamate and [18O]aspartate. The fate of the heavy isotope was then traced into wild-type CYP4B1 or the E310D mutant-derived 5-hydroxyhemes. Glutamate-containing tryptic peptides of wild-type CYP4B1 were found labeled to a level of 11-13% 18O. Base hydrolysis of labeled protein released 5-hydroxyheme which contained 12.8 +/- 1.9% 18O. Aspartate-containing peptides of the E310D mutant were labeled with 6.0-6.5% 18O, but as expected, no label was transmitted to recovered 5-hydroxyheme. These data demonstrate that the oxygen atom in 5-hydroxyheme derived from wild-type CYP4B1 originates in Glu310. Stoichiometric incorporation of the heavy isotope from the wild-type enzyme supports a perferryl-initiated carbocation mechanism for covalent heme formation in CYP4B1.


Long-term effects of acute low-dose ionizing radiation on the neonatal mouse heart: a proteomic study.
Epidemiological studies establish that children and young adults are especially susceptible to radiation-induced cardiovascular disease (CVD). The biological mechanisms behind the elevated CVD risk following exposure at young age remain unknown. The present study aims to elucidate the long-term effects of ionizing radiation by studying the murine cardiac proteome after exposure to low and moderate radiation doses. NMRI mice received single doses of total body (60)Co gamma-irradiation on postnatal day 10 and were sacrificed 7 months later. Changes in cardiac protein expression were quantified using isotope-coded protein label and tandem mass spectrometry. We identified 32, 31, 66, and 34 significantly deregulated proteins after doses of 0.02, 0.1, 0.5, and 1.0 Gy, respectively. The four doses shared 9 deregulated proteins. Bioinformatics analysis showed that most of the deregulated proteins belonged to a limited set of biological categories, including metabolic processes, inflammatory response, and cytoskeletal structure. The transcription factor peroxisome proliferator-activated receptor alpha was predicted as a common upstream regulator of several deregulated proteins. This study indicates that both adaptive and maladaptive responses to the initial radiation damage persist well into adulthood. It will contribute to the understanding of the long-term consequences of radiation-induced injury and developmental alterations in the neonatal heart.


Femoral rotational asymmetry is a common anatomical variant.
The sulcus line (SL) is a three-dimensional landmark that corrects for individual variation in the coronal alignment of the trochlear groove in contrast to the traditional Whiteside's line (WL). Femoral rotational asymmetry (FRA) is an anatomical variation in which the posterior condyles and trochlear groove are not perpendicular to each other. This study aims to measure the SL and assess its reliability relative to WL, in addition to measuring and classifying the FRA. A retrospective analysis of a series of 191 CT scans of nonarthritic knees was performed. Measurements were taken of rotational landmarks in three-dimensional reconstructions. The variability and outlier rate of SL was less than WL (P < 0.05), however, it was also greater than the posterior condylar line (PC) (P < 0.05). Averaging the PC + 3° and the SL did not change the rate of femoral malrotation relative to the surgical epicondylar axis (SEA) (P > 0.05), however it decreased the rate of change of the rotational alignment of the trochlear groove between the native knee and the prosthetic knee from 31% to 5% (P < 0.05). FRA was classified and was >5° in 56/191 (29%) of cases. The SL technique is more accurate than WL for determining the rotational alignment of the trochlear groove. Nonarthritic femora have a high rate of rotational asymmetry. Identifying and classifying FRA in individual cases allows the femoral component to be inserted in a position which gives the best possible match to both the native posterior condyles and trochlear groove. Clin. Anat. 31:551-559, 2018. © 2018 Wiley Periodicals, Inc.


Abnormally expanded CD8+/Leu-7+ lymphocytes persisting in long-term bone marrow-transplanted patients are resting pre-cytotoxic T-lymphocytes.
We analyzed the functional status of the small CD8+/Leu-7+ T-lymphocytes that circulate in increased proportions in the blood of many allogeneic bone marrow transplant (BMT) patients. Purified CD8+/Leu-7+ T cells were tested for their effect on T-cell proliferative responses. In contrast to CD8+/Leu-7-T-lymphocytes, such cells behaved as suppressor cells for lectin-induced mitogenic responses of the donor's peripheral blood lymphocytes. However, they did not interfere with the in vitro responsiveness to specific stimuli such as protein purified derivative (PPD) or alloantigens. We demonstrate that CD8+/Leu-7+ T cells are resting pre-cytotoxic T-lymphocytes (CTL) that can be induced by mitogenic lectins to express their cytolytic program in a non-specific, non-major histocompatibility complex-restricted manner against phytohemagglutinin-treated lymphoblasts or K562 target cells. The lectin-triggered cytotoxicity was achieved within a few days, together with limited cell division. Our results suggest that circulating CD8+/Leu-7+ T cells from BMT recipients are in vivo primed CTL awaiting cellular activation.


Management of Locally Advanced Cutaneous Squamous Cell Carcinoma of the Scalp: A Case Report and Literature Review.
Cutaneous squamous cell carcinoma (cSCC) is a common malignancy in the head and neck region. Although rarely metastatic, it has the potential to become locally aggressive and invade surrounding structures. The involvement of the scalp with cSCC presents a unique surgical challenge given its proximity to vital structures. We present a case of locally advanced cutaneous scalp squamous cell carcinoma with involvement of the skull and dural involvement not previously demonstrated on imaging. This case required complex multidisciplinary surgical management from both neurosurgery and head and neck surgery for treatment, preservation of essential tissues, and cosmesis.


Down-regulation of guanylate binding protein 1 causes mitochondrial dysfunction and cellular senescence in macrophages.
Macrophage polarization is tightly associated with its metabolic reprograming and immune dysfunction. However, the intracellular molecules/pathways that connect these alterations in inflammatory macrophages remain largely unidentified. Herein, we explored the role of guanylate binding protein 1 (Gbp1), an intracellular anti-microbial protein, in regulating polarization, metabolic reprogramming, and cellular aging of macrophages. We showed that Gbp1 expression in inguinal white adipose tissue is significantly decreased in high-fat diet -fed and aged mice. Gbp1 expression is significantly induced by IFNγ and LPS in macrophages but not adipocytes. Downregulation of Gbp1 expression causes macrophage polarization towards a pro-inflammatory phenotype. Gbp1 knockdown (Kd) macrophages have impaired mitochondrial respiratory function, which is further supported by down-regulation of genes encoding electron transport chain components and genes involved in fatty acid oxidation and mitochondrial function. Moreover, we observed Gbp1 is localized in both cytosol and mitochondrial fraction, and Gbp1 Kd macrophages display decreased mitophagy activity. More interestingly, Gbp1 Kd macrophages undergo senescence as evidenced by increased activation of AMPK-p53 pathway and positive staining of β-galactosidase. These observations suggest that Gbp1 may play an important role in protecting against mitochondrial dysfunction and preserving immune function of macrophages during inflammatory stress and aging.


Asbestos exposure and gastrointestinal malignancy review and meta-analysis.
The epidemiologic literature linking asbestos exposure with gastrointestinal malignancy is reviewed. Problems in comparing studies are discussed, appropriate strategies for comparison are developed, and study results are pooled using a model which accounts for both intrastudy and interstudy variability. Stratification of cohorts by dose reveals that significant asbestos exposure, as indicated by a lung cancer standardized mortality ratio (SMR) of at least 200, is associated with an elevated gastrointestinal cancer of SMR for five of six points examined [corrected].


Shared medical appointments in a residency clinic: an exploratory study among Hispanics with diabetes.
To assess the feasibility and effectiveness of shared medical appointments (SMAs) among Hispanic patients with diabetes mellitus attending a family medicine residency clinic. Exploratory and descriptive study. Hispanic patients having diabetes with poor glycemic control (glycated hemoglobin level, >7%) attending a family medicine residency clinic were randomized to an SMA group (n = 50) or a control group (n = 53).The main outcome was glycated hemoglobin level. Secondary outcomes were quality of life and diabetes knowledge. When comparing pre-post measures, there were mean decreases in glycated hemoglobin level of 1.19% for the SMA group (P <.01) and 0.67% for the control group (P = .02).In the SMA group, quality-of-life and diabetes knowledge scores increased by 5 and 1.5 points, respectively (P <.01). Implementing SMAs is feasible and effective among Hispanic patients with diabetes attending a family medicine residency clinic.Health plan managers and policy makers can work with family medicine residents to encourage the use of this model as an alternative approach or in addition to conventional one-on-one interactions with patients.


Rhabdoid choroid plexus carcinoma: a rare histological type.
Primary central nervous system atypical teratoid/rhabdoid tumors mostly occur during early childhood and are almost invariably fatal. These tumors show similar histological and radiological features to primitive neuroectodermal tumor, medulloblastoma and choroid plexus carcinoma, but present different biological behaviors. We present the case of an 18 year-old man who presented headache, vomiting and ataxia. CT-scan and MRI revealed a posterior fossa tumor. A gross total resection was performed. An intraoperative study showed papillary-like tumors with large cells and mitotic features. Histological examination showed two different main growth patterns: solid sheets of undifferentiated polygonal cells with papillary features and rhabdoid cells. Immunohistochemically, these rhabdoid cells were positive for vimentin, epithelial membrane antigen, smooth-muscle actin, cytokeratin, S-100 protein, and glial fibrillary acidic protein. Electro-microscopically, the typical rhabdoid cells contained whorled bundles of intermediate filaments in their cytoplasm. A rhabdoid tumor is a clinical-pathological entity and emphasizes the necessity to distinguish this unique tumor from other pediatric central nervous system neoplasms. Cytopathological features, immunohistochemistry and electro-microscopy differential diagnoses are discussed.


Acute allograft rejection in liver transplant recipients: lack of correlation with loss of hepatic artery diastolic flow.
Eighty hepatic artery Doppler ultrasound (US) examinations performed in 49 patients after liver transplantation were retrospectively analyzed to determine if loss of diastolic flow correlated with pathologic evidence of acute allograft rejection. All 80 Doppler examinations were performed within 7 days of hepatic needle biopsy. Forty-three Doppler waveforms from 27 patients showed normal diastolic flow. Seventeen Doppler studies in 17 patients showed complete absence of diastolic flow. Review of biopsy results for each group showed no significant difference in the proportion of acute allograft rejection present (42% for the normal group and 46% for the group lacking diastolic flow). The data from 53 US and biopsy examinations performed 2 days apart in 37 patients confirmed the lack of correlation between absent hepatic artery diastolic blood flow and rejection. The authors conclude that the loss of hepatic artery diastolic flow has no apparent clinical application for the diagnosis of acute hepatic allograft rejection.


Atherothrombosis: plaque instability and thrombogenesis.
Hemostasis involves a carefully regulated balance between circulating and endothelium-derived prothrombotic and antithrombotic factors. The unstable or vulnerable plaque facilitates thrombosis, clinically manifest as an acute coronary syndrome (ACS), by creating an environment that favors thrombus formation over prevention of lysis. Endothelial cell dysfunction is integral to both the development of the atherosclerotic lesion as well as its destabilization. The transformation of a stable plaque to an unstable one involves complex interactions among T lymphocytes, macrophages, endothelial cells, and smooth muscle cells. Degradation of the fibrous cap of the atherosclerotic lesion as well as the overexpression of prothrombotic and underexpression of antithrombotic factors by cells within the plaque precede thrombus formation. Accordingly, pharmacological interventions for the treatment of ACS are directed against the initiation and propagation of thrombosis, as well as toward improvement of endothelial function.


Effect of acute peritonitis on rocuronium-induced intraperitoneal pressure reduction and the uptake function of the sarcoplasmic reticulum.
Previous studies have reported the incomplete relaxation effect of neuromuscular blockers on skeletal muscles in acute peritonitis (AP) and other inflammatory processes; however, the underlying mechanisms responsible for this effect have not yet been satisfactorily identified. The impaired removal of cytosolic Ca2+ through sarcoendoplasmic Ca2+-ATPase (SERCA) and defects in sarcoplasmic reticulum (SR) Ca2+ uptake are the major contributing factors to diastolic dysfunction. Previous studies on the effects of neuromuscular blockers have primarily focused on neuromuscular transmission. Because of the reduced calcium uptake in the SR itself, even when neuromuscular transmission is fully blocked, the muscle is not able to relax effectively. In the present study, the impact of AP on rocuronium-induced intraperitoneal pressure reduction and rectus abdominal muscle relaxation, and SERCA uptake function was investigated. AP was induced via gastric perforation and changes in the intraperitoneal pressure before and after the administration of rocuronium were recorded. Muscle contractile properties, uptake and release functions and SERCA activity in the rectus abdominal muscles of AP model rats were measured. The half-relaxation time in the AP group was significantly prolonged compared with that in the control group (P<0.01). The peak rate of SR Ca2+ uptake for whole muscle homogenates was significantly reduced (P<0.05) in AP model rats without reduction of the rate of Ca2+ release evoked through AgNO3. In conclusion, gastric perforation-induced AP attenuates the intraperitoneal pressure-reducing effect of rocuronium, and AP induces diastolic dysfunction of the rectus abdominal muscle. The SR Ca2+-ATPase uptake rate was also reduced by AP.


Identifying and avoiding singularity-induced local traps over control landscapes of spin chain systems.
The wide success of quantum optimal control in experiments and simulations is attributed to the properties of the control landscape, defined by the objective value as a functional of the controls. Prior analysis has shown that on satisfaction of some underlying assumptions, the landscapes are free of suboptimal traps that could halt the search for a global optimum with gradient-based algorithms. However, violation of one particular assumption can give rise to a so-called singular control, possibly bringing about local traps on the corresponding landscapes in some particular situations. This paper theoretically and experimentally demonstrates the existence of singular traps on the landscape in linear spin-1/2 chains with Ising couplings between nearest neighbors and with certain field components set to zero. The results in a two-spin example show how a trap influences the search trajectories passing by it, and how to avoid encountering such traps in practice by choosing sufficiently strong initial control fields. The findings are also discussed in the context of the generally observed success of quantum control.


A review of municipal solid waste composition in the United Kingdom.
The move from landfill-based to resource-based waste management systems requires a greater knowledge of the composition of municipal solid waste. This paper draws together the findings of municipal solid waste (MSW) compositional surveys undertaken in the United Kingdom. The results from recent surveys show a good agreement over the composition of household-collected waste, but less agreement over civic amenity site waste composition. There is insufficient data to allow comparisons of the commercial waste element of municipal waste or of the other components, and further work is necessary to produce more reliable estimates of the composition of these streams. The use of questionnaire surveys and analysis of the results suggests that the size and age profile of a household influence the generation of household-collected waste. Some research suggests that the waste container provided by the local authority and the socio-economic classification of a household also influence household-collected waste generation, but other studies failed to find this link. Further research is required to investigate this by surveying all of the waste disposal routes available to specific households.


Conveying hope in consultations with patients with life-threatening diseases: the balance between supporting and challenging the patient.
There is limited knowledge about the communication of hope and denial in consultations with patients with life-threatening diseases on a practical level. In this study, we explored a real-life medical consultation between a doctor and a patient with incurable cancer, focusing on conveying hope. We found one consultation especially suited for illustrating how a physician can convey and reinforce hope without attaching it to curative treatment. The consultation was analysed using a method for discourse analysis, where we took as a point of departure that discourse means language in use. The doctor communicated in a recognising manner, expressing respect for the patient as a subject and an authority of his own experiences. The doctor and patient succeeded in creating a good working alliance characterised by warmth and trust. Within this context, there was room for the doctor to challenge the patient's views and communicate disagreement. The doctor succeeds in conveying and maintaining hope. Within a good working alliance with the patient the doctor can convey hope by balancing between supporting and challenging him. Exploring and grasping the patient's real concerns is essential for being able to relieve and comfort him and convey hope.


Anesthesiology in the Belgian health care environment.
This article focuses on anesthesiology practice in the context of Belgian health care. The first part describes the organization of Belgian health care, the role of private and public initiatives, the division of responsibilities between the different health authorities, the financing mechanisms, and the central role of the compulsory social health care insurance. Quantitative information on the evolution of expenditures, services, providers, and facilities is presented. The second part of the article deals more specifically with anesthesiology and contains information on current practice. The emphasis, however, concerns recent developments in training and accreditation.