Human experience with transvenous biventricular defibrillation using an electrode in a left ventricular vein.
This study investigated the safety and feasibility of transvenous biventricular defibrillation in ICD patients. Some patients may have high DFTs due to weak shock field intensity on the LV. Animal studies showed a LV shocking electrode dramatically lowered DFTs. This approach might benefit heart failure patients already receiving a LV lead or conventional ICD patients with high DFTs. A modified guidewire was used as a temporary left venous access defibrillation electrode (LVA lead). In 24 patients receiving an ICD, the LVA lead was advanced through a guide catheter in the coronary sinus (CS) and into a randomized LV vein (anterior or posterior) using a venogram for guidance. Paired DFT testing compared a standard right ventricular defibrillation system to a biventricular defibrillation system. There were no complications or adverse events. As randomized, LVA lead insertion success was 87% and 71% for anterior and posterior veins, respectively, and 100% after crossover. Total insertion process time included venogram time (32.5 +/- 26.9 minutes, range 5-115, mode 15 minutes) and LVA lead insertion time (15 +/- 14 minutes, range 1-51, mode 7 minutes). An apical LVA lead position was achieved in 11 (45%) of 24 patients and 7 (64 %) of these 11 displayed a DFT reduction; however, mean DFTs were not statistically different. Transvenous biventricular defibrillation is feasible and was safe under the conditions tested. Additional clinical studies are justified to determine if optimized LV lead designs, lead placement, and shock configurations can yield the same large DFT reductions as observed in animals.


Occurrence of two plastidic ATP/ADP transporters in Arabidopsis thaliana L.--molecular characterisation and comparative structural analysis of similar ATP/ADP translocators from plastids and Rickettsia prowazekii.
Recently, we sequenced a cDNA clone from Arabidopsis thaliana L. encoding an ATP/ADP transporter protein (AATP1) located in the plastid envelope membrane. The deduced amino acid sequence of AATP1 exhibits a high degree of similarity (> 66%) to the ATP/ADP transporter from the obligate intracellular gram-negative bacterium Rickettsia prowazekii. Here we report a second plastidic ATP/ADP carrier from A. thaliana (AATP2). As deduced from the amino acid sequence, AATP2 exhibits 77.6% identity to AATP1 and 36% to the rickettsial protein. Hydropathy analysis indicates that all three translocators are highly hydrophobic membrane proteins, which exhibit marked similarities and differences. The AATP1 translocator lacks the sixth transmembrane domain that is present in AATP2 and the bacterial transporter in R. prowazekii. In contrast to AATP1 and the bacterial transport protein, only AATP2 exhibits a truncated C-terminal end. To compare the general biochemical properties of AATP2 with the known transport properties of AATP1 we cloned the entire AATP2 cDNA into plasmid pJT118, leading to the presence of an additional N-terminal histidine tag of 10 amino acids. For heterologous expression of His10-AATP2 we chose the Escherichia coli strain C43, which was reported recently to allow overproduction of eucaryotic membrane transport proteins. After transformation and subsequent induction by isopropylthio-2-D-galactopyranoside intact E. coli cells harbouring plasmid pJT118 showed import of radioactively labelled ATP and ADP. As deduced from a Lineweaver-Burk analysis His10-AATP2 exhibited apparent Km values for ATP and ADP of 22 microM and 20 microM, respectively. Import of ADP into His10-AATP2-expressing E. coli cells occurred at a rate of 24 nmol x mg protein(-1) x h(-1), which was about threefold faster than import of ATP. These biochemical characteristics are similar to transport properties of the heterologously expressed His10-AATP1 protein.


Tobacco craving and eyeblink startle modulation using 3D immersive environments: a pilot study.
Both the cue reactivity and startle reflex modulation paradigms have been used in addiction research to investigate the motivational mechanism of craving. However, while there is a growing body of literature that indicates the utility of 3D technology in addiction-relevant cue reactivity research, no study has been reported on its utility using the startle reflex modulation paradigm. The aim of the present study was to extend the 3D technology to research on tobacco craving using the startle reflex methodology. Participants were 32 university students who smoked more than 10 cigarettes daily. They participated in a psychophysiological testing to assess the modulation of the startle reflex induced by viewing pleasant, unpleasant, and tobacco-related 3D immersive environment stimuli (3D-IEs). Results confirmed that 3D-IEs were effective in inducing emotional states to modulate the startle response. Pleasant and unpleasant 3D-IEs modulated the startle response, as expected: The reflex was increased while viewing unpleasant stimuli and decreased while viewing pleasant ones. Tobacco-related 3D-IEs were similar to unpleasant stimuli in increasing the startle response. However, they were subjectively evaluated as positive, which suggests that the mechanism underlying craving coactivates both aversive and appetitive motivational tendencies.


Serine 129 phosphorylation reduces the ability of alpha-synuclein to regulate tyrosine hydroxylase and protein phosphatase 2A in vitro and in vivo.
Alpha-synuclein (a-Syn), a protein implicated in Parkinson disease, contributes significantly to dopamine metabolism. a-Syn binding inhibits the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Phosphorylation of TH stimulates its activity, an effect that is reversed by protein phosphatase 2A (PP2A). In cells, a-Syn overexpression activates PP2A. Here we demonstrate that a-Syn significantly inhibited TH activity in vitro and in vivo and that phosphorylation of a-Syn serine 129 (Ser-129) modulated this effect. In MN9D cells, a-Syn overexpression reduced TH serine 19 phosphorylation (Ser(P)-19). In dopaminergic tissues from mice overexpressing human a-Syn in catecholamine neurons only, TH-Ser-19 and TH-Ser-40 phosphorylation and activity were also reduced, whereas PP2A was more active. Cerebellum, which lacks excess a-Syn, had PP2A activity identical to controls. Conversely, a-Syn knock-out mice had elevated TH-Ser-19 phosphorylation and activity and less active PP2A in dopaminergic tissues. Using an a-Syn Ser-129 dephosphorylation mimic, with serine mutated to alanine, TH was more inhibited, whereas PP2A was more active in vitro and in vivo. Phosphorylation of a-Syn Ser-129 by Polo-like-kinase 2 in vitro reduced the ability of a-Syn to inhibit TH or activate PP2A, identifying a novel regulatory role for Ser-129 on a-Syn. These findings extend our understanding of normal a-Syn biology and have implications for the dopamine dysfunction of Parkinson disease.


Association of a positive direct antiglobulin test with chronic immune thrombocytopenia and use of second line therapies in children: A multi-institutional review.
Immune thrombocytopenia (ITP) is the most common autoimmune cytopenia in children. Approximately, 25% of patients develop chronic disease, which may be unpredictable and challenging to treat. It is not currently possible to predict at the time of presentation which patients will have chronic disease or will experience symptoms requiring second-line therapy defined as treatment beyond corticosteroids, intravenous immunoglobulin, or Rh immune globulin. A multi-institutional retrospective review of 311 pediatric patients with ITP was performed with the goal of identifying clinical characteristics associated with disease course. In a cohort of 216 patients tested and for whom disease status was known, a positive direct antiglobulin test (DAT) was associated with chronic ITP vs spontaneous resolution of disease (29.2% vs 8.1%, P < 0.001) as well as the need for treatment with second line agents (38.5% vs 11.4%, P < 0.001) in 241 patients. Controlling for the effect of Evans syndrome, defined as having two immune cytopenias, a positive DAT was independently associated with chronic ITP (OR = 2.7, 95% CI: 1.0-7.2, P = 0.041) and use of second-line agents (OR: 3.6, 95% CI: 1.7-7.7, P = 0.001) by multivariate logistic regression model. These findings demonstrate an association with positive DAT and chronic disease, as well as refractory disease requiring second-line agents.


Effects of trimebutine maleate (TM-906) on the spontaneous contraction of isolated guinea pig colon.
Effects of trimebutine maleate (TM-906) on the spontaneous contraction of isolated guinea pig colon were investigated. TM-906 in the concentrations of 10(-6) g/ml and 10(-5) g/ml increased the tone without affecting the amplitude of the spontaneous contraction in the preparations with low tone, whereas it decreased the tone and the amplitude of the spontaneous contraction in the preparations with high tone. At the higher concentration (10(-4) g/ml). TM-906 decreased the tone and finally abolished the spontaneous contraction in any preparation. The increase in tone induced by TM-906 was prevented by diltiazem and exposure to Ca++-free solution, but not by tetrodotoxin, atropine, phentolamine or propranolol, and depended on the extracellular concentration of CaCl2. On the other hand, the decrease in tone and amplitude of the spontaneous contraction produced by TM-906 were not prevented by tetrodotoxin, phentolamine or propranolol. TM-906 further increased the tone increased by 10 mM KCl, while it decreased the tone increased by 30 mM KCl. From results described above, it is suggested that TM-906 possesses both a relaxing effect and an excitatory effect which seem to be due to its direct action on the smooth muscle.


Immune-inflammatory cells in recurrent oral ulcers (ROU).
Tissue lesions from eight patients with recurrent oral ulcers (ROU) were subjected to detailed immunohistopathologic studies. In five patients, a specimen of an unaffected area from the opposite site was obtained. The main inflammatory cells in situ were CD3 positive T lymphocytes, with CD4 cells forming approximately half (range 30-60%) and CD8 cells 20% (range 10-30%) of all cells. CD19 positive B lymphocytes formed 5-12% of all cells. Furthermore, 45% (range 15-65%) of all lymphoid cells had signs of previous antigenous contact and had helper/inducer CDw29 type. Suppressor/inducer CD45R cells formed only about 20% (range 7-50%) of all cells. Although this observation suggests involvement of antigen as a causative and/or triggering stimulus, elements of a non-specific inflammatory response were observed as well. Endogenous peroxidase-positive neutrophils were present at the ulcer site, and were occasionally observed intravascularly and in the extracellular matrix in areas characterized by inflammatory mononuclear cell infiltrates. Although the proportion of endogenous peroxidase-positive, recently recruited monocytes was low, CD11b and nonspecific esterase-positive mature tissue macrophages formed about 14% (range 5-35%) of all inflammatory cells in situ, particularly at the periphery of the lymphoid cell infiltrates. Mast cells were also observed in all samples studied, forming 2-5% of inflammatory cells in the richly vascularized connective tissue beneath the basement membrane. In the specimens from clinically unaffected areas, inflammatory cells were rare. Our observations stress the multifaceted nature and participation of multiple effector systems in the local tissue pathogenesis of ROU.


Angiopoietins and Tie2 in vascular inflammation.
As a subset of the organism-wide reaction to severe infection, the host vascular response has received increasing attention in recent years. The transformation that small blood vessels undergo to facilitate the clearance of pathogens may become harmful to the host if it occurs too broadly or if it is sustained too long. Adverse clinical manifestations of leaky and inflamed blood vessels include edema impairing the function of critical organs and circulatory shock. The study suggests that this host vascular response may be both measurable and potentially targetable. Tie2 is a receptor tyrosine kinase (RTK) heavily enriched in the vascular endothelium whose tonic signaling actively maintains vascular quiescence. When Tie2 becomes inactivated, important molecular brakes are released in the endothelium, which in turn potentiate inflammation and vascular leakage. The ligands of Tie2, Angiopoietin-1 and Angiopoietin-2, regulate its activation status. Genetic and molecular studies spanning thousands of humans link Tie2 and imbalance of the Angiopoietins to major adverse clinical events arising from bacterial sepsis, other severe infections, and even acute sterile inflammation. The Tie2 signaling axis may constitute a molecular switch in systemic inflammation that can be measured and manipulated to target the host vascular response therapeutically.


Electrophysiological investigation of the adaptive response of the 5-HT system to the administration of 5-HT1A receptor agonists.
The effects of acute and long-term administration of 5-HT1A agonists were studied in vivo in the rat brain. Unitary extracellular recordings were obtained from dorsal raphe 5-HT neurons and dorsal hippocampus pyramidal neurons. Gepirone and 8-OH-DPAT, two 5-HT1A agonists, when administered intravenously or applied by microiontophoresis, dose-dependently decreased the firing rate of these 5-HT neurons. Gepirone acted as a full agonist at the somatodendritic 5-HT autoreceptor, which is of the 5-HT1A subtype. Microiontophoretic application of gepirone also decreased the firing activity of postsynaptic hippocampus pyramidal neurons. At these postsynaptic 5-HT1A receptors, however, gepirone acted as a partial agonist. A 2-day treatment with gepirone markedly reduced the firing rate of 5-HT neurons; this was followed by a partial recovery after 7 days of treatment and a complete one after 14 days of treatment. This adaptation of 5-HT neurons was attributable to a desensitization of their somatodendritic 5-HT autoreceptors. The 14-day treatment with gepirone did not induce a desensitization of 5-HT1A receptors on postsynaptic pyramidal neurons. It is concluded that the sustained administration of a 5-HT1A agonist results in an enhanced tonic activation of postsynaptic 5-HT1A receptors in the forebrain. It can be presumed that the recovery of the firing activity of 5-HT neurons restores a normal release of endogenous 5-HT, upon which the agonistic action of the 5-HT1A agonist on normosensitive postsynaptic 5-HT receptors is superimposed.


Relationships between serum IGF1 levels, blood pressure, and glucose tolerance: an observational, exploratory study in 404 subjects.
In the general population, low IGF1 has been associated with higher prevalence of cardiovascular disease and mortality. To investigate the relationships between IGF1 levels, blood pressure (BP), and glucose tolerance (GT). Four-hundred and four subjects (200 men aged 18-80 years). personal history of pituitary or cardiovascular diseases; previous or current treatments with drugs interfering with BP, GT, or lipids, corticosteroids (>2 weeks), estrogens, or testosterone (>12 weeks); smoking of >15 cigarettes/day and alcohol abuse (>3 glasses of wine/day). Two hundred and ninety-six had normal BP (73.3%), 86 had mild (21.3%), and 22 had severe (5.4%) hypertension; 322 had normal GT (NGT (79.7%)), 53 had impaired glucose tolerance (IGT (13.1%)), 29 had diabetes mellitus (7.2%). Normotensive subjects had significantly higher IGF1 levels (0.11+/-0.94 SDS) than those with mild (-0.62+/-1.16 SDS, P<0.0001) or severe (-1.01+/-1.07 SDS, P<0.0001) hypertension. IGF1 SDS (t=-3.41, P=0.001) independently predicted systolic and diastolic BP (t=-2.77, P=0.006) values. NGT subjects had significantly higher IGF1 levels (0.13+/-0.90 SDS) than those with IGT (-0.86+/-1.14 SDS, P<0.0001) or diabetes mellitus (-1.31+/-1.13 SDS, P<0.0001). IGF1 SDS independently predicted fasting glucose (t=-3.49, P=0.0005) and homeostatic model assessment (HOMA)-R (t=-2.15, P=0.033) but not insulin (t=-1.92, P=0.055) and HOMA-beta (t=-0.19, P=0.85). IGF1 levels in the low normal range are associated with hypertension and diabetes in subjects without pituitary and cardiovascular diseases.


Pleiotropic effects of apolipoprotein C3 on HDL functionality and adipose tissue metabolic activity.
APOC3 is produced mainly by the liver and intestine and approximately half of plasma APOC3 associates with HDL. Though it was believed that APOC3 associates with HDL by simple binding to preexisting particles, recent data support that biogenesis of APOC3-containing HDL (APOC3-HDL) requires Abca1. Moreover, APOC3-HDL contributes to plasma triglyceride homeostasis by preventing APOC3 association with triglyceride-rich lipoproteins. Interestingly, APOC3-HDL also shows positive correlation with the morbidly obese phenotype. However, the roles of APOC3 in HDL functionality and adipose tissue metabolic activity remain unknown. Therefore, here we investigated the direct effects of APOC3 expression on HDL structure and function, as well as white adipose tissue (WAT) and brown adipose tissue (BAT) metabolic activity. C57BL/6 mice were infected with an adenovirus expressing human APOC3 or a recombinant attenuated control adenovirus expressing green fluorescent protein and blood and tissue samples were collected at 5 days postinfection. HDL was then analyzed for its apolipoprotein and lipid composition and particle functionality. Additionally, purified mitochondria from BAT and WAT were analyzed for uncoupling protein 1, cytochrome c (Cytc), and Cytc oxidase subunit 4 protein levels as an indirect measure of their metabolic activity. Serum metabolomic analysis was performed by NMR. Combined, our data show that APOC3 modulates HDL structure and function, while it selectively promotes BAT metabolic activation.


Investigations of the attenuation coefficient of a narrow-bandwidth pulsed laser beam in water.
The attenuation coefficient of a pulsed laser beam in water is investigated experimentally. It is found that the attenuation coefficient is dependent on the pulse energy and the linewidth of the laser, rather than a constant. The attenuation coefficient for a narrow linewidth laser can exceed that of a broad linewidth laser due to stimulated Brillouin scattering when the laser intensity is larger than a certain value. A theoretical analysis is provided.


Implementation of electronic scripts in South Africa.
The legal framework in South Africa (SA) provides for strict requirements regarding prescriptions. However, pharmacists are still confronted daily with illegible handwritten scripts, increasing the risk of medication errors. E-prescribing is being implemented in SA to overcome these disadvantages. The general regulations made in terms of the Medicines and Related Substances Act as well as the Electronic Communications and Transactions Act must be read conjointly for the purposes of understanding the legal framework of electronic prescriptions in SA.


Bioactive proteins in breast milk.
Human milk contains many proteins that have been shown to be bioactive, but it is still not known whether these activities are exerted in breast-fed infants. These bioactivities include enzyme activities, enhancement of nutrient absorption, growth stimulation, modulation of the immune system and defence against pathogens. The antimicrobial activities are very diverse, ranging from stimulation of beneficial microorganisms (i.e. prebiotic effects), killing or inhibition of growth of pathogens, to mechanisms preventing attachment or invasion of harmful microorganisms. Among the bioactive proteins are lactoferrin, lysozyme, secretory immunoglobulin A, haptocorrin, lactoperoxidase, α-lactalbumin, bile salt stimulated lipase, β- and κ-casein, and tumour growth factor β. Human milk proteins may be largely resistant against digestion in the gastrointestinal tract, be partially digested into bioactive peptides, or be more or less completely digested and utilised as a source of amino acids. These events can be studied using an in vitro digestion model, which is useful for predicting results in human infants. Some bovine milk proteins, for example, lactoferrin and tumour growth factor β, may also resist proteolysis and be capable of exerting bioactivities similar to those of human milk proteins.


L-arginine supplementation in pigs decreases liver protein turnover and increases hindquarter protein turnover both during and after endotoxemia.
Accumulating evidence suggests that L-arginine, under conditions of septicemia, not only enhances immune function but also improves protein metabolism. Because the effect of L-arginine administration on the protein metabolism of different organs is unknown, the aim of the study was to elucidate the effects of exogenous supplementation of L-arginine during endotoxemia on the in vivo protein metabolism of individual organs and at the whole-body level. Female pigs were cannulated with catheters in the aorta and the splenic, caval, portal, hepatic, and renal veins, enabling measurements across the hindquarter, portal-drained viscera, liver, and kidneys. Endotoxemia was induced by a 24-h continuous intravenous infusion of endotoxin (3 microg x kg body wt(-1) x h(-1)). At 8 h, an intravenous infusion of L-arginine was started (n = 8). Control pigs (n = 6) received L-alanine. At 24 h, blood was sampled. After cessation of the endotoxin infusion, L-arginine and L-alanine infusions were continued as a supplement in the enterally infused diet. At 48 h, blood samples were obtained during the postendotoxemic and nutritionally supported conditions. Stable isotopes were used to assess protein metabolism and phenylalanine hydroxylation. Both during and after the endotoxin challenge, L-arginine administration enhanced protein synthesis and degradation across the hindquarter and simultaneously reduced protein synthesis and degradation in the liver at equal rates. Protein turnover across the kidneys and portal-drained viscera remained unaffected. After endotoxemia, L-arginine infusion decreased whole-body protein turnover without affecting the net protein balance. L-Arginine administration affects protein turnover of the muscle area and the liver oppositely.


Cortical thickness and metabolite concentration in chronic stroke and the relationship with motor function.
Hemiparesis is one of the most prevalent chronic disabilities after stroke. Biochemical and structural magnetic resonance imaging approaches may be employed to study the neural substrates underpinning upper-extremity (UE) recovery after chronic stroke. The purposes of this study were to 1) quantify anatomical and metabolic differences in the precentral gyrus, and 2) test the relationships between anatomical and metabolic differences, and hemiparetic arm function in individuals in the chronic stage of stroke recovery. Our hypotheses were: 1) the Stroke group would exhibit reduced precentral gyrus cortical thickness and lower concentrations of total N-acetylaspartate (tNAA) and glutamate+glutamine (Glx) in the ipsilesional motor cortex; and 2) that each of these measures would be associated with UE motor function after stroke. Seventeen individuals with chronic (>6 months) subcortical ischemic stroke and eleven neurologically healthy controls were recruited. Single voxel proton magnetic resonance spectroscopy (H1MRS) was performed to measure metabolite concentrations of tNAA and Glx in the precentral gyrus in both ipsilesional and contralesional hemispheres. Surface-based cortical morphometry was used to quantify precentral gyral thickness. Upper-extremity motor function was assessed using the Wolf Motor Function Test (WMFT). Results demonstrated significantly lower ipsilesional tNAA and Glx concentrations and precentral gyrus thickness in the Stroke group. Ipsilesional tNAA and Glx concentration and precentral gyrus thickness was significantly lower in the ipsilesional hemisphere in the Stroke group. Parametric correlation analyses revealed a significant positive relationship between precentral gyrus thickness and tNAA concentration bilaterally. Multivariate regression analyses revealed that ipsilesional concentrations of tNAA and Glx predicted the largest amount of variance in WMFT scores. Cortical thickness measures alone did not predict a significant amount of variance in WMFT scores. While stroke impairs both structure and biochemistry in the ipsilesional hemisphere our data suggest that tNAA has the strongest relationship with motor function.


Hormone-independent in vitro erythroid colony formation by bone marrow cells from Rauscher virus-infected mice.
Bone marrow cells from BALB/c mice infected with Rauscher erythroblastosis virus produced five to twenty-five times more erythroid colonies in vitro in the absence of erythropoietin (EP) as compared to normal cells. A good correlation existed between the state of the disease and the number of hormone-independent erythroid colony-forming cells (CFU-E). A significant number of hormone-independent CFU-E was found as early as 3 days after infection. A linear relationship existed between the number of cells plated and the number of erythroid colonies formed in vitro. Addition of EP did not enhance colony formation, even at low cell concentrations. Feeder layer experiments demonstrated that EP-independent colony formation was not due to the production of endogenous EP. Repeated injections of phenylhydrazine into normal mice did not lead to the loss of EP responsiveness in vitro; this indicated that the hormone independency induced by the virus was not due to continuous erythropoietic stimulation in vivo. Besides hormone independency, the CFU-E from infected mice required less serum in the culture medium. Normal erythroid colonies regressed after 4 days of culture, but EP-independent colonies from infected mice persisted for more than 2 weeks. These three phenomena may be regarded as indicative for a physiologic transformation.


Optimal Quantum Interference Thermoelectric Heat Engine with Edge States.
We show theoretically that a thermoelectric heat engine, operating exclusively due to quantum-mechanical interference, can reach optimal linear-response performance. A chiral edge state implementation of a close-to-optimal heat engine is proposed in an electronic Mach-Zehnder interferometer with a mesoscopic capacitor coupled to one arm. We demonstrate that the maximum power and corresponding efficiency can reach 90% and 83%, respectively, of the theoretical maximum. The proposed heat engine can be realized with existing experimental techniques and has a performance robust against moderate dephasing.


Fluorescence measurement of intracellular sodium concentration in single Escherichia coli cells.
The energy-transducing cytoplasmic membrane of bacteria contains pumps and antiports maintaining the membrane potential and ion gradients. We have developed a method for rapid, single-cell measurement of the internal sodium concentration ([Na(+)](in)) in Escherichia coli using the sodium ion fluorescence indicator, Sodium Green. The bacterial flagellar motor is a molecular machine that couples the transmembrane flow of ions, either protons (H(+)) or sodium ions (Na(+)), to flagellar rotation. We used an E. coli strain containing a chimeric flagellar motor with H(+)- and Na(+)-driven components that functions as a sodium motor. Changing external sodium concentration ([Na(+)](ex)) in the range 1-85 mM resulted in changes in [Na(+)](in) between 5-14 mM, indicating a partial homeostasis of internal sodium concentration. There were significant intercell variations in the relationship between [Na(+)](in) and [Na(+)](ex), and the internal sodium concentration in cells not expressing chimeric flagellar motors was 2-3 times lower, indicating that the sodium flux through these motors is a significant fraction of the total sodium flux into the cell.


[Skiing over Greenland--physical and psychological changes].
Three Norwegian physicians crossed the inland glacier of Greenland on skis without any support. Body weight, fat and lean body mass was measured by dual X-ray absorptiometry scanning. Maximal oxygen uptake, lung capacity measurements, and various blood tests were recorded. Subjective health-related well-being and four transistory arousal states were also recorded (GHQ-30 and AD ACL, short form). One participant lost 1 kilo body weight, while the others gained 1 and 4 kilos, respectively, during the trip. Overall, lean body mass increased (1.2-4.0 kg), while body fat was reduced (0.4-2.7 kg). These changes reversed after four weeks. Bone mass, lung function and blood tests did not vary throughout the study period. The level of energy and calmness were high at baseline and even higher towards the end of the expedition, while the scores were low and stable for tiredness and tension. Subjective well-being increased for all participants towards the second half of the trip. We conclude that expeditions involving physical and mental strain can produce positive psychological changes. Catabolic conditions are avoidable. Changes in body mass composition revert quickly.


Big 'G' and Little 'g' Geriatrics Education for Physicians.
In the July 2016 issue of this journal, Dr. Mary Tinetti proposed that geriatric medicine abandon attempts to increase the numbers of board-certified geriatricians and change focus to the development of a "small elite workforce." What would be gained and what sacrificed by accepting this challenge? We agree that the best clinical use of a scarce resource, specialty trained geriatricians, is to care for frail, complex, severely ill elderly adults and to help design and study novel interventions in research, education, and care models to improve the care of all older adults, but for this to happen, all other providers must attain specific competency in the care of older adults. This article responds and discusses alternative pathways for teaching geriatrics care, training specialists, and geriatrics fellows.


[Information given orally. The position of the psychologist].
As important as a precise diagnosis and an appropriate treatment, the words which the doctor is going to tell to the sick child and his family will have a determining therapeutic effect on the evolution or the regression of the disease. The present article illustrates this comment through histories lived in an intensive care unit of a Paris hospital.


In vitro Anti-Leishmanial Activities of Methanol Extract of Brucea antidysenterica J.F. Mill Seeds and Its Solvent Fractions.
Leishmaniasis is one of the neglected tropical diseases, threatening lives of about 350 million people globally. Brucea antidysenterica seeds are used for the treatment of cutaneous leishmaniasis in the traditional medicine in Ethiopia. This study aimed to evaluate Brucea antidysenterica seeds' anti-leishmanial activity in vitro. The crude (80% methanol) extract of Brucea antidysenterica seeds and its fractions were evaluated for their anti-leishmanial activities against promastigotes and intracellular amastigotes of Leishmania donovani and Leishmania aethiopica, and for their cytotoxic effects against mammalian cells. The quantitative estimations of total phenolic compounds (TPCs), flavonoids (TFCs) and alkaloids (TACs) were determined, spectrophotometrically. Median inhibitory concentration (IC50) and median cytotoxic concentration (CC50) of the extract and its solvent fractions were calculated using GraphPad Prism 9.1.0 computer software. Data was presented as mean ± standard error of the mean (SEM). The crude extract and its hexane, ethyl acetate and butanol fractions showed anti-leishmanial activities, with IC50 values of 4.14-60.12 µg/mL against promastigotes, and 6.16-40.12 µg/mL against amastigotes of both Leishmania species. They showed moderate cytotoxicity against Vero cell lines and peritoneal mice macrophages, with CC50 values of 100-500 µg/mL, but >1600 µg/mL against red blood cells. Selectivity indices ranged from 7.97 to 30.97. The crude extract, and its ethyl acetate and hexane fractions possessed 54.78-127.72 mg of gallic acid equivalent TPC, 18.30-79.21 mg of quercetin equivalent TFC, and 27.62-97.22 mg of atropine equivalent TAC per gram of extracts. The seeds of the plant possessed anti-leishmanial activities against L. aethiopica and L. donovani that might provide a scientific justification for its use in the treatment of leishmaniasis by traditional healers. Future works are recommended to isolate, purify and identify the possible secondary metabolites attributed to the anti-leishmanial activity.


Antidiuresis and vasopressin release with hypoxemia and hypercapnia in conscious dogs.
To determine the effects of acute blood gas derangements on renal water and solute excretion and vasopressin secretion, six unanesthetized mongrel dogs were studied during 1) combined acute hypoxemia and hypercapnic acidosis [arterial O2 partial pressure (PaO2) 36 +/- 1 Torr, arterial CO2 partial pressure (PaCO2) 54 +/- 2 Torr, pH 7.18 +/- 0.01], 2) acute hypoxemia (PaO2 33 +/- 2 Torr, PaCO2 33 +/- 1 Torr, pH 7.34 +/- 0.01), and 3) acute hypercapnic acidosis (PaO2 83 +/- 3 Torr, PaCO2 53 +/- 1 Torr, pH 7.19 +/- 0.02). Combined acute hypoxemia and hypercapnic acidosis increased (P less than 0.05) mean arterial pressure, but renal hemodynamic function deteriorated with decreased (P less than 0.05) glomerular filtration rate and increased (P less than 0.05) renal vascular resistance. Moreover free water clearance became more negative (P less than 0.05) and urine osmolality increased (P less than 0.05). During acute hypoxemia or acute hypercapnic acidosis alone, mean arterial pressure and renal hemodynamic function were unchanged but free water clearance became more negative (P less than 0.05). During acute hypoxemia, urine osmolality increased (P less than 0.05) comparably with values observed during combined acute hypoxemia and hypercapnic acidosis. Plasma vasopressin concentrations increased profoundly (P less than 0.05) during combined hypoxemia and hypercapnic acidosis and during acute hypoxemia alone and were significantly elevated (P less than 0.05) above the increased plasma vasopressin concentrations observed during acute hypercapnic acidosis. We conclude that acute hypoxemia and hypercapnic acidosis result in impairment of renal water excretion, probably mediated through vasopressin secretion.


Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy.
The Oxford Classification E score (endocapillary hypercellularity) predicts renal functional decline in IgA nephropathy (IgAN) patients free from steroid/immunosuppressive (IS) therapy, but is poorly reproducible. We hypothesise that endocapillary hypercellularity reflects glomerular inflammation and that the presence of CD68-positive cells is a more robust marker of E score. CD68-positive cells were quantified in glomeruli and tubulointerstitium in biopsies from 118 IgAN patients, and cell counts were correlated with the criteria of the Oxford Classification, assigned on PAS-stained serial sections. There was a strong correlation between median glomerular CD68 count and the percentage of glomeruli showing endocapillary hypercellularity (r = 0.67; P < 0.001; r2 = 0.45), while there was no correlation between CD68-positive cells and mesangial hypercellularity, % segmental sclerosis, % of crescents and % tubular atrophy/interstitial fibrosis (TA/IF). ROC curve analysis demonstrated that a maximum glomerular CD68 count of 6 is the best cut-off for distinguishing E0 from E1 (sensitivity 94.1%, specificity 71%, area under the curve = 89%). Identification of biopsies with a maximum glomerular CD68-count >6 was reproducible (kappa score 0.8), and there was a strong correlation between glomerular CD68 counts obtained by conventional light microscopy and by image analysis (r = 0.80, r2 = 0.64, P < 0.0001). Digital image analysis revealed that tubulointerstitial CD68-positive cells correlated moderately with % TA/IF (r = 0.59, r2 = 0.35, P < 0.001) and GFR at the time of biopsy (r = 0.54, r2 = 0.29, P < 0.0001), but not with mesangial and endocapillary hypercellularity. While glomerular CD68-positive cells emerge as markers of endocapillary hypercellularity, their tubulointerstitial counterparts are associated with chronic damage.


Presentation, management and outcomes of iliopsoas abscess at a University Teaching Hospital in Nepal.
Iliopsoas abscess (IPA) is an uncommon clinical disease and is often missed to diagnose due to vague clinical presentation. Early treatment with drainage and appropriate antibiotic therapy is necessary before sepsis sets in and become lethal. We conducted this study to evaluate clinical features, etiology, management strategies, and outcomes in patients with IPA from a University Teaching Hospital in Nepal. A retrospective analysis of 32 consecutive IPA cases managed at Tribhuvan University Teaching Hospital, Nepal for the period of January 2019 to February 2022 was carried out. The mean age was 42.5 ± 19.1 years (range, 19-75 years) and the male: female ratio was 2.2:1. Two-thirds or more patients presented with fever, limp, fixed flexion deformity and/or low back pain. Ultrasonography (US) was diagnostic in 27 (84.4%) patients. Eighteen (56.3%) patients had primary IPAs, and 14 (43.7%) had secondary IPAs. Thirty (93.7%) patients were managed with US guided percutaneous drainage (PCD) and 2 (6.2%) patients underwent open surgical drainage. Drainage procedures were combined with antibiotics in all patients. Pus culture showed Staphylococcus aureus growing in the majority of cases (10 of 23, 43.5%). The hospital stay was longer in patients treated via surgical drainage compared to those who received PCD: 13 days (range 12-14 days) vs. 6.6 days (range 4-13 days), respectively. Recurrence of abscess was seen in 4 (12.5%) cases and all were successfully managed via a second PCD. There was no mortality. Varying clinical presentation of iliopsoas abscess demand a high index of suspicion for early diagnosis. Initial imaging modality in suspected case of IPA is US. US-guided PCD along with the appropriate antibiotics is a successful frontline treatment of IPAs with shorter hospital stay.


Effective remission induction of refractory childhood acute nonlymphocytic leukemia by VP-16-213 plus azacitidine.
Thirty-eight children and young adults with advanced acute nonlymphocytic leukemia (ANLL) in relapse were treated with VP-16-213 plus azacitidine (5AZ). Each patient had previously received many chemotherapeutic drugs, including anthracyclines and cytarabine. Initially, 16 patients received a 5-day course of VP-16-213 (100 mg/m(2)) daily x 3 days and 5AZ 9150 mg/m(2)) daily x 2 days, repeated after 9-16 days. Since this treatment produced marrow hypoplasia and complete remission (CR) in only one of 16 patients, a more intensive regimen was devised: the remaining 22 patients received a course of VP-16-213 (200 mg/m(2)) daily x 3 days, followed by 5AZ (300 mg/Fm(2)) daily x 2 days, repeated after 1-2 days until the bone marrow became hypoplastic. After two to four courses, 18 patients had marrow hypoplasia and ten of these achieved CR. The proportion of patients achieving CR with the higher doses was significantly greater than that with the initial doses )P less than or equal to 0.05). The toxicity also increased with the higher doses, with major problems due to prolonged pancytopenia. Supportive therapy was required for severe bleeding and infections. We conclude that the intensive treatment with VP-16-213 plus 5AZ can effectively induce remission in patients with refractory advanced acute nonlymphocytic leukemia.


Loneliness and subjective health complaints among school-aged children.
The first aim of this study was to explore the prevalence of loneliness and subjective health complaints (SHCs) among school-aged children in Finland. The second aim was to analyse to what extent perceived loneliness explains any variance in SHCs among school-aged children. A representative sample of 5925 Finnish children and adolescents from grades 5 ( Mage=11.8 years), 7 ( Mage=13.8) and 9 ( Mage=15.8) completed the Health Behaviour in School-aged Children (HBSC) survey. Descriptive statistics were used to examine the prevalence of health complaints and loneliness. Structural equation modelling was used to test how strongly loneliness was associated with SHCs. The prevalence of loneliness and SHCs was higher among girls and increased with age. Loneliness was a significant predictor of health complaints, especially of psychological symptoms among girls and among ninth grade students. The findings indicate that loneliness is a major risk to the health and well-being of school-aged children. The strong association between loneliness and SHCs highlights the importance of active preventive actions to reduce loneliness.


Management of patients with pulmonary arterial hypertension due to congenital heart disease: recent advances and future directions.
Pulmonary arterial hypertension is a serious complication of adult congenital heart disease associated with systemic-to-pulmonary shunts. Although early shunt closure restricts development of pulmonary arterial hypertension, patients remain at risk even after repair. The development of pulmonary arterial hypertension is associated with a markedly increased morbidity and mortality. It is important to identify patients with a poor prognosis using disease specific markers. Echocardiography and biomarkers arise as practical tools to determine the risk of mortality. Although pulmonary arterial hypertension cannot be cured, four classes of disease-targeting therapies are currently available and several promising therapies are being studied. There is a shift in drug studies towards more clinically relevant endpoints such as time to clinical worsening and morbidity and mortality events.


Endotoxaemia as a cause of fever in immunosuppressed patients.
Using a recently developed chromogenic substrate assay sensitive to 10 pg/ml Escherichia coli endotoxin in plasma, systemic endotoxaemia was found in 52% of 21 episodes of fever in patients with a haematological malignancy who were infected. Endotoxaemia was also found in 27% of 22 episodes of fever of unknown origin. In 45 afebrile patients neither neutropenia nor cytotoxic chemotherapy was a cause of endotoxaemia. Passage of endotoxin from portal blood into the systemic circulation can contribute to unexplained fever in immunosuppressed patients.


Ultraslow Phase Transitions in an Anion-Anion Hydrogen-Bonded Ionic Liquid.
A Raman spectroscopy study of 1-ethyl-3-methylimidazolium hydrogen sulfate, [C2C1im][HSO4], as a function of temperature, has been performed to reveal the role played by anion-anion hydrogen bond on the phase transitions of this ionic liquid. Anion-anion hydrogen bonding implies high viscosity, good glass-forming ability, and also moderate fragility of [C2C1im][HSO4] in comparison with other ionic liquids. Heating [C2C1im][HSO4] from the glassy phase results in cold crystallization at ∼245 K. A solid-solid transition (crystal I → crystal II) is barely discernible in calorimetric measurements at typical heating rates, but it is clearly revealed by Raman spectroscopy and X-ray diffraction. Raman spectroscopy indicates that crystal I has extended ([HSO4]-)n chains of hydrogen-bonded anions but crystal II has not. Raman spectra recorded at isothermal condition show the ultraslow dynamics of cold crystallization, solid-solid transition, and continuous melting of [C2C1im][HSO4]. A brief comparison is also provided between [C2C1im][HSO4] and [C4C1im][HSO4], as Raman spectroscopy shows that the latter does not form the crystalline phase with extended anion-anion chains.


Metallic Oxide-Induced Self-Assembly of Block Copolymers to Form Polymeric Hybrid Micelles with Tunable Stability for Tumor Microenvironment-Responsive Drug Delivery.
Since block copolymers are able to self-assemble into various polymeric architectures, it is intriguing to explore a unique self-assembly strategy for polymers. Two different metallic oxides [manganese dioxide (MnO2) and zinc oxide (ZnO)] are displayed herein to demonstrate this self-assembly mechanism of polymers. In situ generation of metallic oxides induces self-assembly of block copolymers to form polymeric hybrid micelles with tunable stability in aqueous solutions. These final ZnO-cross-linked polymeric micelles exhibited a high drug loading capacity of 0.41 mg mg-1 toward doxorubicin (DOX), whereas DOX-loaded ZnO-cross-linked polymeric micelles could be broken down into Zn2+ and polymer scraps, which facilitated drug release in tumor microenvironments. Both in vitro and in vivo investigations showed that the drug-loaded ZnO-cross-linked polymeric micelles effectively suppressed tumor growth. Accordingly, the present study demonstrates a novel strategy of polymer self-assembly for fabricating polymeric architectures that can potentially provide insight for developing other polymeric architectures.


Immunocytochemical demonstration of the lysosomal enzyme alpha-glucosidase in the brush border of human intestinal epithelial cells.
In investigations on the intracellular transport route(s) of lysosomal enzymes in polarized epithelial cells, we used immunocytochemical methods to localize lysosomal alpha-glucosidase in human small-intestinal epithelial cells. Two monoclonal antibodies which can discriminate between different biosynthetic forms of this enzyme were used. One monoclonal antibody, 43D1, which recognizes all forms of the enzyme, showed labeling of the Golgi apparatus, the lysosomes and, unexpectedly, of the brush border of the cells. Multivesicular bodies were free of label. In contrast, monoclonal antibody 43G8, which recognizes all forms except the 110,000 Da precursor of alpha-glucosidase, showed labeling of the lysosomes only. This leads us to conclude that the 110,000 Da precursor form of alpha-glucosidase is present in the Golgi apparatus and the brush border of human small-intestinal epithelial cells. Moreover, biochemical experiments show that this precursor copurifies with sucrase, a typical brush-border marker, when a partially purified microvilli fraction is prepared.


RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.
To facilitate precision medicine and whole-genome annotation, we developed a machine-learning technique that scores how strongly genetic variants affect RNA splicing, whose alteration contributes to many diseases. Analysis of more than 650,000 intronic and exonic variants revealed widespread patterns of mutation-driven aberrant splicing. Intronic disease mutations that are more than 30 nucleotides from any splice site alter splicing nine times as often as common variants, and missense exonic disease mutations that have the least impact on protein function are five times as likely as others to alter splicing. We detected tens of thousands of disease-causing mutations, including those involved in cancers and spinal muscular atrophy. Examination of intronic and exonic variants found using whole-genome sequencing of individuals with autism revealed misspliced genes with neurodevelopmental phenotypes. Our approach provides evidence for causal variants and should enable new discoveries in precision medicine.


A CASE OF LITTRÉ'S HERNIA AT ZINDER NATIONAL HOSPITAL, ZINDER, NIGER.
The presence of a Meckel's diverticulum in a hernia sac is known as Littré's hernia. We report a case of Littré's hernia in an 18-year old young man because of the uncommon condition. An 18-year old young patient was admitted to the Emergency Surgical Department of Zinder National Hospital, Zinder, Niger with a painful inguinoscrotal swelling of three days duration. The diagnosis of strangulated right inguinoscrotal hernia was made. At surgery, a Meckel's diverticulum was found at the antimesenteric border of the ileum in the hernia sac, the bowel loop was not viable. Resection of the non-viable ileal loop with the Meckel's diverticulum attached to it was performed with an end-to-end ileal anastomosis. The hernia defect in the groin was repaired according to Bassini procedure. The postoperative recovery was uneventful and the patient was followed up for 5 months without symptoms. Littre hernia is uncommon and difficult to diagnose; it is often an incidental finding at surgery which should ensure complete resection of the Meckel's diverticulum in order to prevent future complications.


[Application of cardiovascular risk scales to identify carotid atherosclerosis in patients with rheumatoid arthritis].
To evaluate the cardiovascular risk (CVR) and analyze its relationship with detection of early carotid artery atherosclerotic lesion in patients with rheumatoid arthritis (RA). One hundred and nine RA patients aged 45 to 60 without established cardiovascular diseases (CVD) were included in the study. The median age was 52 [48; 54] years, duration of RA was 120 [36; 204] months, DAS28 was 4.7 [3.5; 5.6] points. CVD risk was calculated with mSCORE, Reynolds Risk Score (RRS), ASSIGN, QRISK3, ERS-RA scales and Carotid Artery Doppler Ultrasound Exam was performed for all patients. High risk was found in 5, 5, 14, 6, and 38% of patients according to mSCORE, RRS, ASSIGN, QRISK3, ERS-RA scales, respectively. Atherosclerotic plaques of carotid arteries were found in 30% of patients. It was found that carotid intima-media thickness is correlated to all CVR calculators, age, systolic and diastolic blood pressure, cholesterol, erythrocyte sedimentation rate, interleukin-6 levels. The sensitivity and specificity of the CVR algorithms in prognostication of atherosclerotic carotid artery lesions were 73 and 67% for mSCORE, 64 and 63% for RRS, 64 and 56% for ASSIGN, 73 and 49% for QRISK3, respectively, p0.05 in all cases, 67 and 50% for ERS-RA, p=0.06. RRS, mSCORE, ASSIGN, QRISK3 calculators equally predict atherosclerotic carotid artery damage in RA patients. The optimal ratio of specificity and sensitivity is shown for the mSCORE scale. Stratification of CVR in RA patients should include assessment of the carotid intima-media thickness. To identify CVR in RA patients, the most informative methods are mSCORE calculation and carotid intima-media thickness determination.


Human TAP1 polymorphisms detected by denaturing gradient gel electrophoresis.
Presentation of endogenous peptides by major histocompatibility complex class I (MHC) molecules is controlled, in part, by the Tap1 and Tap2 genes in the MHC class II region that encode a heterodimeric peptide transporter. Polymorphisms of human Tap1 in normal individuals have now been investigated systematically by denaturing gradient gel electrophoresis (DGGE) analysis of fragments of genomic DNA generated by the polymerase chain reaction. Polymorphisms identified by distinctive DGGE band patterns were confirmed by DNA sequencing. In addition to four previously described polymorphisms in the open reading frame, DGGE detected three new polymorphisms: a G-->T substitution in the promoter region, a 10-bp insert in intron 9, and a G-->T substitution 80-bp downstream of the translation termination codon.


Subsurface aeration mitigates organic material mulching-induced anaerobic stress via regulating hormone signaling in Phyllostachys praecox roots.
Organic material mulching has been used extensively to allow Phyllostachys praecox to promote growth and development of shoots. However, the bamboo forest always showed a significant degradation, probably due to anaerobic damage caused by the mulching after several years. Therefore, we have innovatively proposed an improvement measure to aerate the underground pipes for the first time. We investigated the role of subsurface pipe aeration in regulating root hypoxia to reduce the stress and to identify the degradation mechanism. Results showed that aeration increased oxygen concentration, shoot yield and root growth compared with mulching, and the aeration enhanced the concentration of indole-3-acetic acid (IAA) and the expression of Aux/IAAs (Aux1, Aux2, Aux3, and Aux4). Aeration reduced gibberellin (GA), ethylene (ETH), and abscisic acid (ABA) contents as well as anaerobic enzyme activities (alanine transaminase, AlaAT; alcohol dehydrogenase, ADH; pyruvate decarboxylase, PDC; and lactate dehydrogenase, LDH), which alleviated root damage in anoxic conditions. Furthermore, correlation showed that the activities of ADH, LDH, PDC, and AlaAT showed significant linear correlations with soil oxygen levels. RDA analyses showed that ABA, IAA, and ETH were found as the key driving hormones of Aux/IAAs in the root of the forest mulched with organic material. Here we show that subsurface aeration increases soil oxygen concentration, shoot yield, root growth and regulates phytohormone concentrations and Aux/IAAs expression, which reduces anaerobic enzyme activities. Consequently, subsurface pipe aeration is an effective measure to mitigate the degradation of bamboo forests caused by soil hypoxia that results from organic material mulching.


Sipple syndrome and pregnancy.
Sipple syndrome is an unusual entity during pregnancy. To our knowledge, this is the second case report of a pregnant patient with signs of Sipple syndrome. During pregnancy, this syndrome may present unusual complications, which require informed physician expertise for appropriate management. Our patient had a strong family history for Sipple syndrome, which is considered to be transmitted as an autosomal dominant. Thus, other family members, including the patient's offspring must be assessed frequently during their lifetime for any of the developing manifestations of this entity. Genetic counseling should be included in the management of all patients with Sipple syndrome.


Multi-QTL mapping for quantitative traits using epistatic distorted markers.
The interaction between segregation distortion loci (SDL) has been often observed in all kinds of mapping populations. However, little has been known about the effect of epistatic SDL on quantitative trait locus (QTL) mapping. Here we proposed a multi-QTL mapping approach using epistatic distorted markers. Using the corrected linkage groups, epistatic SDL was identified. Then, these SDL parameters were used to correct the conditional probabilities of QTL genotypes, and these corrections were further incorporated into the new QTL mapping approach. Finally, a set of simulated datasets and a real data in 304 mouse F2 individuals were used to validate the new method. As compared with the old method, the new one corrects genetic distance between distorted markers, and considers epistasis between two linked SDL. As a result, the power in the detection of QTL is higher for the new method than for the old one, and significant differences for estimates of QTL parameters between the two methods were observed, except for QTL position. Among two QTL for mouse weight, one significant difference for QTL additive effect between the above two methods was observed, because epistatic SDL between markers C66 and T93 exists (P = 2.94e-4).


Slice-push, formation of grooves and the scale effect in cutting.
Three separate aspects of cutting are investigated which complement other papers on the mechanics of separation processes presented at this interdisciplinary Theo Murphy meeting. They apply in all types of cutting whether blades are sharp or blunt, and whether the material being cut is 'hard, stiff and strong' or 'soft, compliant and weak'. The first topic discusses why it is easier to cut when there is motion along (parallel to) the blade as well motion across (perpendicular to) the cutting edge, and the analysis is applied to optimization of blade geometries to produce minimum cutting forces and hence minimum damage to cut surfaces. The second topic concerns cutting with more than one edge with particular application to the formation of grooves in surfaces by hard pointed tools. The mechanics are investigated and applied to the topic of abrasive wear by hard particles. Traditional analyses say that abrasive wear resistance increases monotonically with the hardness of the workpiece, but we show that the fracture toughness of the surface material is also important, and that behaviour is determined by the toughness-to-hardness ratio rather than hardness alone. Scaling forms the third subject. As cutting is a branch of elasto-plastic fracture mechanics, cube-square energy scaling applies in which the important length scale is (ER/k (2)), where E is Young's modulus, R is the fracture toughness and k is the shear yield strength. Whether, in cutting, material is removed as ductile ribbons, as semi-ductile discontinuous chips, or by brittle 'knocking lumps out' is shown to depend on the depth of cut relative to this characteristic length parameter. Scaling in biology is called allometry and its relationship with engineering scaling is discussed. Some speculative predictions are made in relation to the action of teeth on food.


The functional interaction between nicotinic acetylcholine receptors and Ly-6/neurotoxin proteins in Locusta migratoria.
Failures in expressing insect nAChRs (nicotinic acetylcholine receptors) limit the understanding of their functional properties, although insect nAChRs have been developed as insecticide targets for decades. Some accessory proteins can modulate nAChRs, but only a few have been identified in insects, including lynx from Ly-6/neurotoxin superfamily. Until now, only one to three lynx were identified in one insect species. Here, 11 lynx were identified in Locusta migratoria with common features of Ly-6/neurotoxin members. The effects of these lynx on seven hybrid nAChRs functionally constructed in Xenopus oocytes were tested, in which each nAChR subtype contained one L. migratoria α subunit plus rat β2 subunit. One lynx could selectively modulate several nAChR subtypes to significantly increase the amplitude of epibatidine-evoked currents, while Loc-lynx10 acted on all test nAChRs. Among nine lynx with obvious modulation effects to increase inward currents, only four significantly increased the specific [3H]epibatidine binding, and the binding increase existed in all modulated nAChRs by these lynx. The results indicated that the modulation mode was decided by the specific lynx and had nothing to do with nAChR subtypes. This study provides an approximate panorama for the functional interaction net between L. migratoria lynx and nAChRs, although some other nAChRs need further tests.


Human monocyte inflammatory mediator gene expression is selectively regulated by adherence substrates.
During the process of extravasation, monocytes transiently adhere to capillary endothelium and subsequently with a variety of extracellular matrix components. These early interactions are likely to serve as modifiers of transcriptional activity and serve to prime monocytes for rapid synthesis of mediators. We have previously reported that adherence to plastic rapidly induced or down-regulated steady-state mRNA levels of a number of monocyte inflammatory mediator genes. We now report that adherence to surfaces pretreated with fibronectin resulted in TNF-alpha and CSF-1 mRNA levels approximating adherence to plastic, whereas adherence to fibronectin, fibronectin/anti-fibronectin complexes, or collagen resulted in markedly decreased levels of CSF-1 induction and lysozyme down-regulation. In contrast, monocyte adherence to collagen induced the highest sustained levels of TNF-alpha expression. PMA, but not the chemotactic factor FMLP, stimulated non-adherent monocytes to express c-fos and TNF-alpha and down-regulate lysozyme mRNA. Although all donors responded to adherence, several failed to produce CSF-1 mRNA after PMA stimulation in the non-adherent state. These data demonstrate that monocyte mediator expression may be more dependent on the selectivity of signals induced by adherence to different substrates than the initial chemotactic response.


Altered lipid raft-associated proximal signaling and translocation of CD45 tyrosine phosphatase in B lymphocytes from patients with systemic lupus erythematosus.
B lymphocytes from patients with systemic lupus erythematosus (SLE) exhibit defective intracellular signaling, hyperactivity, and autoantibody production. Recent evidence indicates a reduced expression of Lyn kinase, a negative regulator of B cell signaling, and reduced translocation of Lyn into membrane signaling domains in SLE. The present study was undertaken to investigate the causes of this altered regulation of Lyn by assessing the expression levels of regulatory molecules and their translocation into the signaling domains of SLE B lymphocytes. Blood was obtained from 48 patients with SLE and 28 healthy controls for the assessment of B lymphocytes. Levels and intracellular distribution of Lyn, CD45, COOH-terminal Src kinase (Csk), and c-Cbl were studied by Western blotting, confocal microscopy, and flow cytometry. The kinetics of signaling molecule translocation to the B cell receptor (BCR)-antigen synapse were investigated by confocal microscopy. A profound alteration in the expression and translocation of regulatory signaling molecules in membrane domains of B cells from patients with SLE was observed. B lymphocytes from SLE patients, but not those from healthy controls, expressed a low molecular weight isoform of CD45 in lipid raft signaling microdomains. Kinetic studies revealed that translocation of Lyn, CD45, Csk, and c-Cbl led to increased recruitment and retention of Lyn and CD45 in the BCR-antigen synapse in SLE B cells. The results provide evidence of altered expression and translocation/interaction of kinases and phosphatases in membrane signaling microdomains of B cells from patients with SLE. Altered translocation of CD45 correlated with reduced expression of Lyn, indicating that Lyn is a key molecule in the regulation of BCR-mediated signaling.


Molecular insights into early hematopoiesis.
During embryogenesis, a pool of pluripotential, self-renewing hematopoietic stem cells is specified from undifferentiated ventral mesoderm. These cells proliferate and differentiate to yield all the peripheral blood lineages. Although the mechanisms involved in the commitment and differentiation of multipotential progenitors have been well documented, little focus has been directed to the molecular events underlying the formation of hematopoietic stem cells. In this review we discuss the recent advances made in defining a bone morphogenetic protein-responsive signal cascade that regulates the earliest phase of blood formation during embryogenesis.


Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships.
Synapses are fundamental units of communication in the brain. The prototypical synapse-organizing complex neurexin-neuroligin mediates synapse development and function and is central to a shared genetic risk pathway in autism and schizophrenia. Neurexin's role in synapse development is thought to be mediated purely by its protein domains, but we reveal a requirement for a rare glycan modification. Mice lacking heparan sulfate (HS) on neurexin-1 show reduced survival, as well as structural and functional deficits at central synapses. HS directly binds postsynaptic partners neuroligins and LRRTMs, revealing a dual binding mode involving intrinsic glycan and protein domains for canonical synapse-organizing complexes. Neurexin HS chains also bind novel ligands, potentially expanding the neurexin interactome to hundreds of HS-binding proteins. Because HS structure is heterogeneous, our findings indicate an additional dimension to neurexin diversity, provide a molecular basis for fine-tuning synaptic function, and open therapeutic directions targeting glycan-binding motifs critical for brain development.


Cutting Edge: Class II-like Structural Features and Strong Receptor Binding of the Nonclassical HLA-G2 Isoform Homodimer.
HLA-G is a natural tolerogenic molecule and has the following unique features: seven isoforms (HLA-G1 to HLA-G7), formation of disulfide-linked homodimers, and β2-microglobulin (β2m)-free forms. Interestingly, individuals null for the major isoform, HLA-G1, are healthy and expressed the α2 domain-deleted isoform, HLA-G2, which presumably compensates for HLA-G1 function. However, the molecular characteristics of HLA-G2 are largely unknown. In this study, we unexpectedly found that HLA-G2 naturally forms a β2m-free and nondisulfide-linked homodimer, which is in contrast to the disulfide-bonded β2m-associated HLA-G1 homodimer. Furthermore, single-particle analysis, using electron microscopy, revealed that the overall structure and domain organization of the HLA-G2 homodimer resemble those of the HLA class II heterodimer. The HLA-G2 homodimer binds to leukocyte Ig-like receptor B2 with slow dissociation and a significant avidity effect. These findings provide novel insights into leukocyte Ig-like receptor B2-mediated immune regulation by the HLA-G2 isoform, as well as the gene evolution of HLA classes.


Lymphocyte-induced corneal neovascularization: a morphologic assessment.
Lymphocytes obtained from mesenteric lymph nodes of rabbits were stimulated in vitro by concanavalin A and injected into the corneas of allogeneic hosts. Controls were nonstimulated, killed, or autogeneic lymphocytes injected into the contralateral corneas. The stimulated cells were significantly better inducers of neovascular growth. Histologic observations of the vascularized corneas showing marked mononuclear reactions at the limbus, coupled with the requirement of allogenicity, suggest that there was immunologic recognition of the implanted cells. Stimulated allogeneic blast cells may amplify this host recognition by their elaboration of lymphokines or enhanced antigenicity. The apparent importance of allogenicity for the induction of vessel growth in these experiments may be significant in the pathogenesis tumor-induced or graft-related corneal neovascularization.


Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function.
Skin integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. While interfollicular epidermal progenitors control normal homeostasis, hair follicle stem cells residing within the bulge provide regenerative potential during hair cycle and in response to wounding. The aryl hydrocarbon receptor (AhR) modulates cell plasticity and differentiation and its overactivation results in severe skin lesions in humans. However, its physiological role in skin homeostasis and hair growth is unknown. Reconstitution assays grafting primary keratinocytes and dermal fibroblasts into nude mice and 3-D epidermal equivalents revealed a positive role for AhR in skin regeneration, epidermal differentiation, and stem cell maintenance. Furthermore, lack of receptor expression in AhR-/- mice delayed morphogenesis and impaired hair regrowth with a phenotype closely correlating with a reduction in suprabasal bulge stem cells (α6low CD34+ ). Moreover, RNA-microarray and RT-qPCR analyses of fluorescence-activated cell sorting (FACS)-isolated bulge stem cells revealed that AhR depletion impaired transcriptional signatures typical of both epidermal progenitors and bulge stem cells but upregulated differentiation markers likely compromising their undifferentiated phenotype. Altogether, our findings support that AhR controls skin regeneration and homeostasis by ensuring epidermal stem cell identity and highlights this receptor as potential target for the treatment of cutaneous pathologies.


Psychological risks experienced by interpreters in the domestic violence cases: a systematic review.
Interpreters occupy a complex position in police interviews involving domestic violence cases-neutral but necessary parties to traumatic content. The following systematic review explores the relatively sparse scholarly literature on interpreters' psychological responses to being a party to domestic violence interviews in a policing context. This article aims to explore themes of relevant studies targeting interpreters' mental health in such cases, with nine articles emerging from a comprehensive search of eight databases supplemented with a Google Scholar search. Various themes involving interpreters emerged from the ensuing analysis, including intrinsic difficulties, misguided expectations, role requirements, psychological impacts, posttraumatic growth, coping strategies, and recommendations for future research and practice, with findings holding implications for interpreting in other traumatic domains.


Smooth muscle cells, interstitial cells and neurons in the gallbladder (GB): Functional syncytium of electrical rhythmicity and GB motility (Review).
The motility of the gallbladder (GB) involves the storage, concentration and delivery of bile. GB motor functions are controlled by multiple complex factors, such as extrinsic and intrinsic innervation, humoral factors and neuropeptides. GB emptying results from coordinated contractions of the muscular layers of the GB wall. Depolarization of GB smooth muscle (GBSM) depends on the activation of the regular depolarization‑repolarization potential, referred to as slow waves (SWs). These rhythmic SWs of GBSM contraction are mediated by several cell types, including smooth muscle cells (SMCs), GB neurons, telocytes (TC) and specialized pacemaker cells called interstitial cells of Cajal (ICC). The present article introduced a new GB motor unit, the SMC‑TC‑ICC‑neuron (STIN) syncytium. In GB, STIN cells provide pacemaker activity, propagation pathways for SWs, transduction of inputs from motor and sensory neurons and mechanosensitivity. The present review provided an overview of STIN cells, mechanisms generating GBSM contractile behavior and GB motility, and discussed alterations of STIN cell function under different disease conditions.


Metamorphosis of the quantum Hall ferromagnet at nu=2/5.
We report on the dramatic evolution of the quantum Hall ferromagnet in the fractional quantum Hall regime at nu=2/5 filling. A large enhancement in the characteristic time scale gives rise to a dynamical transition into a novel quantized Hall state. The observed Hall state is determined to be a zero-temperature phase distinct from the spin-polarized and spin-unpolarized nu=2/5 fractional quantum Hall states. It is characterized by a strong temperature dependence and puzzling correlation between temperature and time.


Signalling pathways in pemphigus vulgaris.
Acantholysis in pemphigus vulgaris is induced by binding of autoantibodies to desmoglein 3 (Dsg3). The roles of signalling pathways on development of acantholysis have recently been extensively studied. In the study by Sayar et al., recently published in Exp Dermatol, epidermal growth factor receptor (EGFR) signalling was activated in both in vivo and in vitro pemphigus vulgaris experimental models. However, while EGFR inhibitors suppressed activity of p38 mitogen-activated protein kinase (p38MAPK) linearly, they suppressed activity of c-Myc and acantholysis in a non-linear, V-shaped relationship. These findings indicated complicated interactions among EGFR, p38MAPK and c-Myc in pemphigus vulgaris pathology.


Cerebral air embolism after percutaneous kyphoplasty: a rare case report.
Cerebral air embolism (CAE) is considered as a rare complication during the routine medical procedures in the literature review. We reported a very rare complication of CAE after the percutaneous kyphoplasty (PKP) for the treatment of acute vertebral compression fracture.


Recent Developments in the Field of Tumor-Inhibiting Metal Complexes
25 years after the first approval of cisplatin in the clinic against a number of cancer diseases, cisplatin and related compounds continue to be among the most efficient anticancer drugs used so far. Efforts are focused to develop novel platinum- and non-platinum-based antitumor drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. In the field of non-platinum compounds exhibiting anticancer properties, ruthenium complexes are very promising, showing activity on tumors which developed resistance to cisplatin or in which cisplatin is inactive. Furthermore, general toxicity was found to be very low. The first ruthenium compound NAMI-A entered phase I clinical trials in 1999 as an antimetastatic drug, whereas the ruthenium complex KP1019 will enter phase I clinical trials in 2003 as an anticancer drug which is among others very active against colon carcinomas and their metastases. Remarkable progress is also seen in developing tumor inhibiting gallium compounds. One of them, KP46, will also enter phase I clinical trials in 2003. This article reviews briefly the achievements in the field of anticancer metal complexes focusing the discussion onto the impact of the group of Bioinorganic Chemistry at the Department of Inorganic Chemistry at the University of Vienna. The development of pH sensitive platinum prodrugs, platinum-based drug targeting strategies with low-molecular-weight carriers, kinetically inert platinum(IV) complexes, as well as tumor inhibiting non-platinum anticancer drugs based on ruthenium and gallium is covered in the following sections.


Sugar transport systems of Bifidobacterium longum NCC2705.
Here we present the complement of the carbohydrate uptake systems of the strictly anaerobic probiotic Bifidobacterium longum NCC2705. The genome analysis of this bacterium predicts that it has 19 permeases for the uptake of diverse carbohydrates. The majority belongs to the ATP-binding cassette transporter family with 13 systems identified. Among them are permeases for lactose, maltose, raffinose, and fructooligosaccharides, a commonly used prebiotic additive. We found genes that encode a complete phosphotransferase system (PTS) and genes for three permeases of the major facilitator superfamily. These systems could serve for the import of glucose, galactose, lactose, and sucrose. Growth analysis of NCC2705 cells combined with biochemical characterization and microarray data showed that the predicted substrates are consumed and that the corresponding transport and catabolic genes are expressed. Biochemical analysis of the PTS, in which proteins are central in regulation of carbon metabolism in many bacteria, revealed that B. longum has a glucose-specific PTS, while two other species (Bifidobacterium lactis and Bifidobacterium bifidum) have a fructose-6-phosphate-forming fructose-PTS instead. It became obvious that most carbohydrate systems are closely related to those from other actinomycetes, with a few exceptions. We hope that this report on B. longum carbohydrate transporter systems will serve as a guide for further in-depth analyses on the nutritional lifestyle of this beneficial bacterium.


Molecular mechanisms of neuroinvasion by monocytes-macrophages in HIV-1 infection.
HIV associated neurocognitive disorders and their histopathological correlates largely depend on the continuous seeding of the central nervous system with immune activated leukocytes, mainly monocytes/macrophages from the periphery. The blood-brain-barrier plays a critical role in this never stopping neuroinvasion, although it appears unaltered until the late stage of HIV encephalitis. HIV flux that moves toward the brain thus relies on hijacking and exacerbating the physiological mechanisms that govern blood brain barrier crossing rather than barrier disruption. This review will summarize the recent data describing neuroinvasion by HIV with a focus on the molecular mechanisms involved.


Fungicide Sensitivity Shifting of Zymoseptoria tritici in the Finnish-Baltic Region and a Novel Insertion in the MFS1 Promoter.
Septoria tritici blotch (STB) is caused by the ascomycete Zymoseptoria tritici and one of the predominating diseases in wheat (Triticum aestivum) in Europe. The control of STB is highly reliant on frequent fungicide applications. The primary objective of this study was to assess sensitivity levels of Z. tritici to different fungicide groups. The fungicides included in this study were epoxiconazole, prothioconazole-desthio, tebuconazole, and fluxapyroxad. A panel of 63 isolates from Estonia, Latvia, and Lithuania, and 10 isolates from Finland were tested. Fungicide sensitivity testing was carried out as a bioassay analyzing single pycnidium isolates on different fungicide concentrations. The average EC50 value in Baltic countries and Finland to epoxiconazole was high ranging from 1.04 to 2.19 ppm. For prothioconazole-desthio and tebuconazole, EC50 varied from 0.01 to 0.24 ppm, and 1.25 to 18.23 ppm, respectively. The average EC50 value for fluxapyroxad varied from 0.07 to 0.33 ppm. To explain the range of sensitivity, the samples were analyzed for CYP51 and Sdh mutations, as well as cytb G143A, CYP51 overexpression, and multidrug resistance (MDR). Frequencies of ZtCYP51 mutations D134G, V136A/C, A379G, I381V, and S524T in the Finnish-Baltic region were lower than in other European countries, but have increased compared to previous years. The frequency of cytb G143A conferring strobilurin resistance also augmented to 50-70% in the Z. tritici populations from Estonia, Finland, Latvia, and Lithuania. No Sdh mutations were found in this study, and neither strains of MDR phenotypes. However, we found a strain harboring a previously unknown transposon insertion in the promoter of the MFS1 gene, involved in drug efflux and multi-drug resistance. This new insert, however, does not confer an MDR phenotype to the strain.


Change in pattern of skin disease in Kaduna, north-central Nigeria.
We report our experience on the pattern of skin disease in Kaduna, north-central Nigeria over a 6-year period, and compare it with a similar survey conducted in the same area 30 years ago and with surveys from Nigeria and from other parts of Africa. The medical records of new patients attending the dermatology outpatient clinics of Barau Dikko Specialist Hospital and Habbat Medical Center from March 2000 to December 2005 were retrieved. Demographic data (age and sex) and the diagnoses of skin disease were extracted and analyzed. A total of 5982 cases was seen. Forty-nine per cent were males and 51% were females. One-third of the patients were aged under 20 years, and three quarters were aged below 40 years. Eczematous dermatitis was the most common skin disorder seen, making up 35% of cases, and had replaced dermatophyte infections and scabies, which were the most dominant skin diseases 30 years previously (now constituting 6% and 1.4% of cases, respectively). Atopic dermatitis had more than doubled in frequency (13.8% vs. 5.2%), and contact dermatitis had tripled in frequency (5.8% vs. 1.8%). Acne vulgaris (6.7%), pigmentary disorders (3.9%), urticaria (3.6%), papular urticaria (3.6%), hair disorders (3.3%), lichen simplex chronicus (3%), viral warts (2.9%), and drug eruptions (2.7%) had also increased. Human immunodeficiency virus-related skin disease constituted 4.3% of cases, with pruritic papular eruption being the most common condition. These changes in skin disease can be attributed mainly to an increase in urbanization and improved socio-economic conditions.


Diseases associated with growth hormone-releasing hormone receptor (GHRHR) mutations.
The growth hormone (GH)-releasing hormone (GHRH) receptor (GHRHR) belongs to the G protein-coupled receptors family. It is expressed almost exclusively in the anterior pituitary, where it is necessary for somatotroph cells proliferation and for GH synthesis and secretion. Mutations in the human GHRHR gene (GHRHR) can impair ligand binding and signal transduction, and have been estimated to cause about 10% of autosomal recessive familial isolated growth hormone deficiency (IGHD). Mutations reported to date include five splice donor site mutations, two microdeletions, two nonsense mutations, seven missense mutations, and one mutation in the promoter. These mutations have an autosomal recessive mode of inheritance, and heterozygous individuals do not show signs of IGHD, although the presence of an intermediate phenotype has been hypothesized. Conversely, patients with biallelic mutations have low serum insulin-like growth factor-1 and GH levels (with absent or reduced GH response to exogenous stimuli), resulting--if not treated--in proportionate dwarfism. This chapter reviews the biology of the GHRHR, the mutations that affect its gene and their effects in homozygous and heterozygous individuals.


A survey of mangiferin and hydroxycinnamic acid ester accumulation in coffee (Coffea) leaves: biological implications and uses.
The phenolic composition of Coffea leaves has barely been studied, and therefore this study conducts the first detailed survey, focusing on mangiferin and hydroxycinnamic acid esters (HCEs). Using HPLC, including a new technique allowing quantification of feruloylquinic acid together with mangiferin, and histochemical methods, mangiferin content and tissue localization were compared in leaves and fruits of C. pseudozanguebariae, C. arabica and C. canephora. The HCE and mangiferin content of leaves was evaluated for 23 species native to Africa or Madagascar. Using various statistical methods, data were assessed in relation to distribution, ecology, phylogeny and use. Seven of the 23 species accumulated mangiferin in their leaves. Mangiferin leaf-accumulating species also contain mangiferin in the fruits, but only in the outer (sporophytic) parts. In both leaves and fruit, mangiferin accumulation decreases with ageing. A relationship between mangiferin accumulation and UV levels is posited, owing to localization with photosynthetic tissues, and systematic distribution in high altitude clades and species with high altitude representatives. Analyses of mangiferin and HCE content showed that there are significant differences between species, and that samples can be grouped into species, with few exceptions. These data also provide independent support for various Coffea lineages, as proposed by molecular phylogenetic analyses. Sampling of the hybrids C. arabica and C. heterocalyx cf. indicates that mangiferin and HCE accumulation may be under independent parental influence. This survey of the phenolic composition in Coffea leaves shows that mangiferin and HCE accumulation corresponds to lineage recognition and species delimitation, respectively. Knowledge of the spectrum of phenolic accumulation within species and populations could be of considerable significance for adaptation to specific environments. The potential health benefits of coffee-leaf tea, and beverages and masticatory products made from the fleshy parts of Coffea fruits, are supported by our phenolic quantification.


Streptomyces mimosae sp. nov., an endophytic actinomycete isolated from the root of Mimosa pudica in Thailand.
An endophytic actinomycete, strain 3MP-10T, isolated from the root of Mimosa pudica was taxonomically studied based upon polyphasic approaches. This strain formed spiral spore chains on aerial mycelia. ll-Diaminopimelic acid, glucose and ribose were found in the whole-cell hydrolysates. It belonged to the genus Streptomyces and was closely related to Streptomyces zhaozhouensis DSM 42101T (98.9 %) and Streptomyces sedi JCM 16909T (98.6 %) based on 16S rRNA gene sequence analysis results. The major menaquinones were MK-10(H8), MK-10(H6) and MK-9(H8). The predominant cellular fatty acids were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The detected phospholipids were diphosphatidylglycerol, phosphatidylinositol mannoside, phosphatidylinositol, phosphatidylethanolamine and phosphatidylglycerol. Strain 3MP-10T had a genome size of 7.2 Mb with a genome G+C content of 73.4 mol%. Results of in silico genome-based similarity analysis revealed ANIb values of 84.94 and 84.77 %, ANIm values of 88.01 and 87.92 %, and dDDH values of 29.9 and 29.6 % when compared with S. zhaozhouensis DSM 42101T and S. sedi JCM 16909T, respectively. Based on the polyphasic approach, digital DNA-DNA relatedness and average nucleotide identity, we propose that the novel actinomycete represents a novel species, Streptomyces mimosae, with type strain 3MP-10T (=JCM 33328T=TISTR 2646T).


Acknowledging Anti-Blackness, Overlooking Anti-Asian Racism: Missed Developmental Opportunities for Chinese American Youth.
This paper explores the pathways and barriers to critical consciousness development for Chinese American youth. Thirty-five interviews conducted in 2020 with high-school-aged students in Chicago were analyzed to better understand young people's experiences developing an understanding of anti-Asian racism and anti-Blackness. Results indicated that participants overwhelmingly engaged in sustained conversations about Black Lives Matter and/or made efforts to address anti-Blackness within their families, but engaged in limited conversations about anti-Asian racism. Furthermore, conversations at home and school often failed to contextualize anti-Asian racism, specifically in relation to the experiences of other oppressed groups. Findings highlight a need for research on and practice with Chinese American adolescents to recognize the unique racial positioning of Asian Americans under White supremacy.


[Hepatitis B virus integration and oncogene activation].
In hepatitis B virus (HBV) related hepatoma samples there is a high frequency of HBV-DNA integration into the chromosome, but the frequency of integration in the early-stage of carcinogenesis is expected to be even higher. Structural an analysis of integrated HBV-DNA and chromosomal flanking DNAs disclosed that the marked rearrangement of chromosomal DNA is not directly linked to carcinogenesis. HBV-DNA integration and chromosomal DNA depletion occur even in chronic hepatitis tissues. Integration is, therefore, thought to trigger a series of reactions which lead to carcinogenesis. However, the oncogene is not detected within the HBV genome, and the HBV integration site in the chromosome is variable. As one approach to clarifying the cause and effect relationship between HBV-DNA integration and liver carcinogenesis DNA transfection experiments were conducted using mouse NIH3T3 cells to detect hepatoma-related oncogenes. As a result, the well-known N-ras gene and an unknown oncogene were independently isolated from different hepatoma tissues.


Rational Design, Synthesis, and Biological Evaluation of Novel S1PR2 Antagonists for Reversing 5-FU-Resistance in Colorectal Cancer.
Resistance to 5-FU reduces its clinical efficacy for the treatment of colorectal cancer. Sphingosine-1-phosphate receptor 2 (S1PR2) has emerged as a potential target to reverse 5-FU-resistance by inhibiting the expression of dihydropyrimidine dehydrogenase (DPD). In this study, 38 novel S1PR2 antagonists based on aryl urea structure were designed and synthesized, and the structure-activity relationship was investigated based on the S1PR2 binding assay. Representative compound 43 potently interacts with S1PR2 with a KD value of 0.73 nM. It displays potent 5-FU resensitizing activity in multiple 5-FU-resistant tumor cell lines, particularly in SW620/5-FU (EC50 = 1.99 ± 0.03 μM) but shows no cytotoxicity in the normal colon cell line NCM460 up to 1000 μM. Moreover, 43 significantly enhances the antitumor efficacy of 5-FU in the SW620/5-FU animal model. These data suggest that 43 could be a novel lead compound for developing a 5-FU resensitizing agent.


Discrepancy between patients' perspectives, staff's documentation and reflections on basic nursing care.
In recent years, Denmark has witnessed an increasing written and oral debate concerning the quality of basic nursing care. The present study is an attempt to characterize basic nursing care in a Danish hospital by collecting data on patient perceptions of their main somatic problems in seven pre-set categories. These data include documentation of patient problems in corresponding problem categories, and the staff's additional knowledge about patient problems. Triangulation of methods was used. Data were collected on 120 patients and from 22 nurses. The patients had 2.3 problems on average: pain (58%) and sleep (43%) were the problems cited most frequently. Only 31% of patients' experienced problems were documented in the nursing records. The nursing staff had more knowledge than was registered in the nursing records. However, one-third of the patients' problems was totally unknown to the nursing staff. From the patients' point of view, essential aspects of basic nursing care are overlooked in daily clinical practice. The findings show that the method employed is suitable for integration of the patients' perspective.


IVC diameter in patients with chronic heart failure: relationships and prognostic significance.
The aim of this study was to assess the relation between inferior vena cava (IVC) diameter, clinical variables, and outcome in patients with chronic heart failure (HF). The IVC distends as right atrial pressure rises. Therefore it might represent an index of HF severity independent of left ventricular ejection fraction (LVEF). The relation between IVC diameter and other clinical variables and its prognostic significance in patients with HF has not been explored. Outpatients attending a community HF service between 2008 and 2010 were enrolled. Heart failure was defined as the presence of relevant symptoms and signs and objective evidence of cardiac dysfunction: either LVEF <45% or the combination of both left atrial dilation (≥4 cm) and raised amino-terminal pro-brain natriuretic peptide (NT-proBNP) ≥400 pg/ml. Patients were followed for a median of 567 (interquartile range: 413 to 736) days. The primary composite endpoint was cardiovascular death and HF hospitalization. Among the 693 patients enrolled, median age was 73 years, 33% were women, and 568 had HF. Patients with HF in the highest tertile of IVC diameter were older; had lower body mass index; were more likely to have atrial fibrillation and to be treated with diuretics; and had larger left atrial volumes, higher pulmonary pressures, and less negative values for global longitudinal strain. The LVEF and systolic blood pressure were similar across tertiles of IVC diameter. The IVC diameter and log [NT-proBNP] were correlated (r = 0.55, p < 0.001). During follow-up, 158 patients reached a primary endpoint. In a multivariable Cox regression model, including NT-proBNP, only increasing IVC diameter, urea, and the trans-tricuspid systolic gradient independently predicted a poor outcome. Neither global longitudinal strain nor LVEF were adverse predictors. In patients with chronic HF with or without a reduced LVEF, increasing IVC diameter identifies patients with an adverse outcome.


Determining the amount of waste plastics in the feed of Austrian waste-to-energy facilities.
Although thermal recovery of waste plastics is widely practiced in many European countries, reliable information on the amount of waste plastics in the feed of waste-to-energy plants is rare. In most cases the amount of plastics present in commingled waste, such as municipal solid waste, commercial, or industrial waste, is estimated based on a few waste sorting campaigns, which are of limited significance with regard to the characterisation of plastic flows. In the present study, an alternative approach, the so-called Balance Method, is used to determine the total amount of plastics thermally recovered in Austria's waste incineration facilities in 2014. The results indicate that the plastics content in the waste feed may vary considerably among different plants but also over time. Monthly averages determined range between 8 and 26 wt% of waste plastics. The study reveals an average waste plastics content in the feed of Austria's waste-to-energy plants of 16.5 wt%, which is considerably above findings from sorting campaigns conducted in Austria. In total, about 385 kt of waste plastics were thermally recovered in all Austrian waste-to-energy plants in 2014, which equals to 45 kg plastics cap-1. In addition, the amount of plastics co-combusted in industrial plants yields a total thermal utilisation rate of 70 kg cap-1 a-1 for Austria. This is significantly above published rates, for example, in Germany reported rates for 2013 are in the range of only 40 kg of waste plastics combusted per capita.


Aggressive behaviour in immature captive Nile crocodiles, Crocodylus niloticus, in relation to feeding.
This study presents five aspects of aggressive behaviour in juvenile Nile crocodiles, Crocodylus niloticus, as observed in five cohorts of 6-18 month-old animals. During this period, the animals grew from a range of 35-55 cm, to a range of 65-115 cm. 1) Stock density related to aggression: decrease in density resulted in significant decrease in the frequency of agonistic events, with 0.64 events/100 crocodiles/min observed in a density of 6.7 crocodiles/m2, compared to 0.26 events/100 crocodiles/min observed in a density of 4.7 crocodiles/m2. 2) Aggression during feeding: in all five groups, there was a significantly higher level of aggression during feeding times. 3) Aggression related to body size: the largest crocodiles were the most aggressive group in agonistic events, mainly against the smallest ones. The largest group, the medium sized, was the least involved in agonistic events. 4) Aggression related to food preference: crocodile food preference was live fish > live chicks > dead fish > ground meat. Except for one food type (live chicks), a significant (p < 0.05) correlation was found between food preference and feeding related aggression in the prey diet groups. 5) Aggression related to an artificial selection for size: removal of the largest crocodiles (which formed 30% of the stock) from the population caused a dramatic decrease in all forms of aggressive behaviour.


Stages of Larval Development and Stem Cell Population Changes During Metamorphosis of a Hydrozoan Planula.
Scanning electron microscopy and light histology were used to reveal the changes in overall morphology and in stem cell differentiation and distribution that occur as a free-swimming, solid hydrozoan planula larva is transformed into a sessile, hollow adult polyp. Eight stages of development are described: young 10-hour planula, mature 48-hour planula, attaching planula, disc, pawn, crown, immature polyp, and primary adult polyp. The larval interstitial stem cell population (interstitial cells, nematocytes, ganglion cells) undergoes dramatic changes during metamorphosis: (1) distribution patterns change, (2) certain larval derivatives disappear, (3) new types of derivatives differentiate, and (4) migration patterns become more complex. This study is the first to examine how a stem cell system develops in an organism that goes from embryo to larva to adult.


New Insights Into the Metabolism and Role of Cytokinin N-Glucosides in Plants.
Cytokinin (CK) N-glucosides are the most abundant group of CK metabolites in many species; however, their physiological role in planta was for a long time perceived as irreversible storage CK forms only. Recently, a comprehensive screen showed that only vascular plants form CK N-glucosides in contrast to mosses, algae, and fungi. The formation of CK N-glucosides as biologically inactive CK conjugates thus represents an evolutionarily young mechanism for deactivation of CK bases. Even though CK N-glucosides are not biologically active themselves due to their inability to activate the CK perception system, new data on CK N-glucoside metabolism show that trans-zeatin (tZ) N7- and N9-glucosides are metabolized in vivo, efficiently releasing free CK bases that are most probably responsible for the biological activities observed in a number of bioassays. Moreover, CK N-glucosides' subcellular localization as well as their abundance in xylem both point to their possible plasma membrane transport and indicate a role also as CK transport forms. Identification of the enzyme(s) responsible for the hydrolysis of tZ N7- and N9-glucosides, as well as the discovery of putative CK N-glucoside plasma membrane transporter, would unveil important parts of the overall picture of CK metabolic interconversions and their physiological importance.


Regulatory processes, risk, and resilience in adolescent development.
This article highlights the potential of developmental psychopathology as a useful integrative perspective for the challenging task of linking the study of brain development and adolescent behavior in context; it considers clues from behavioral research on resilience on the nature of regulatory processes as risks and assets, or vulnerabilities and protective factors for the development of competence and psychopathology in adolescence; and it advocates more integrative neurobehavioral research on risk and resilience in adolescent development.


Recent Advances in Genetic Technique of Microbial Report Cells and Their Applications in Cell Arrays.
Microbial cell arrays have attracted consistent attention for their ability to provide unique global data on target analytes at low cost, their capacity for readily detectable and robust cell growth in diverse environments, their high degree of convenience, and their capacity for multiplexing via incorporation of molecularly tailored reporter cells. To highlight recent progress in the field of microbial cell arrays, this review discusses research on genetic engineering of reporter cells, technologies for patterning live cells on solid surfaces, cellular immobilization in different polymers, and studies on their application in environmental monitoring, disease diagnostics, and other related fields. On the basis of these results, we discuss current challenges and future prospects for novel microbial cell arrays, which show promise for use as potent tools for unraveling complex biological processes.