Differential cytokine response in host defence mechanisms triggered by gram-negative and gram-positive bacteria, and the roles of gabexate mesilate, a synthetic protease inhibitor.
Bacterial infection results in the production of inflammatory mediators and may be involved in the pathogenesis of sepsis and/or systemic inflammatory response syndrome. The effect of lipopolysaccharide (LPS), a major component of the outer surface of Gram-negative bacteria, and Staphylococcal enterotoxin B (SEB), a superantigen of Gram-positive bacteria, on cytokine production in peripheral blood mononuclear cells (PBMCs) was examined. LPS significantly increased the production of proinflammatory and anti-inflammatory cytokines, and SEB enhanced the production of helper T lymphocyte type cytokines. These results illustrated the different responses to Gram-negative and Gram-positive bacterial infections. The effect of gabexate mesilate, a synthetic protease inhibitor, on cytokine production and expression of the toll-like receptor (TLR) was also examined. The results suggest that gabexate mesilate-induced inhibition of tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18) production in LPS-stimulated PBMCs is due to the inhibition of the nuclear factor-kappa B activation pathway and/or inhibition of the processing pathway of pro-TNF-alpha and pro-IL-18, not to down-regulation of TLR-2 or TLR-4.


[Endomyocardial biopsy should be performed in selected patients with suspected myocarditis].
Endomyocardial biopsy (EMB) is the gold standard for the diagnosis of myocarditis. Patients with clinical presentation consistent with myocarditis and acute heart failure should undergo EMB, in particular to exclude giant-cell myocarditis or necrotizing eosinophilic myocarditis that are life-threatening conditions. The indication for EMB is debatable in case of suspected myocarditis with infarct-like presentation and preserved left ventricular ejection fraction. In fact, in this group of patients the prognosis is fairly good, and the clinical advantage to reach a histological diagnosis by means of an invasive procedure with potential complications such as EMB is limited. In this article we discuss the indication for EMB in the light of current guidelines based on existing consensus documents.


Ascorbic acid prevents chloroquine-induced toxicity in inner glial cells.
Ototoxicity is a collateral effect of prolonged treatment with chloroquine which is a widely utilized as an anti-lupus and anti-malarial drug. Glial cells of inner ear are responsible for maintenance of neuronal cells homeostasis in auditory system. In the current study we have evaluated chloroquine-induced toxicity and protective effect of ascorbic acid treatment on Schwann glial cell cultures of inner ear. Glial cells were cultured from organ of Corti of mice cochlear structure. Purity of Schwann glial cell was confirmed by S100 protein staining. Cell viability was evaluated in control and cultures treated with different concentrations of chloroquine. Glutamate uptake and ROS production were measured by HPLC and DCFH-DA probe fluorescence, respectively. Results have shown that chloroquine treatment evoked concentration and time -dependent toxicity (LC50 = 70 μM) as well as significant decrease on glutamate uptake and high production of ROS in glial cell cultures. Co-treatment with ascorbic acid has prevented both chloroquine-induced ROS production and chloroquine toxicity on glial cell cultures. This pre-clinical study is the first one to demonstrate chloroquine-induced ROS production by glial cells of inner ear as well as the protective effect exerted by ascorbic acid on these cells.


Effects of generalized pooling on binocular disparity selectivity of neurons in the early visual cortex.
The key problem of stereoscopic vision is traditionally defined as accurately finding the positional shifts of corresponding object features between left and right images. Here, we demonstrate that the problem must be considered in a four-dimensional parameter space; with respect not only to shifts in space (X, Y), but also spatial frequency (SF) and orientation (OR). The proposed model sums outputs of binocular energy units linearly over the multi-dimensional V1 parameter space (X, Y, SF, OR). Theoretical analyses and physiological experiments show that many binocular neurons achieve sharp binocular tuning properties by pooling the output of multiple neurons with relatively broad tuning. Pooling in the space domain sharpens disparity-selective responses in the SF domain so that the responses to combinations of unmatched left-right SFs are attenuated. Conversely, pooling in the SF domain sharpens disparity selectivity in the space domain, reducing the possibility of false matches. Analogous effects are observed for the OR domain in that the spatial pooling sharpens the binocular tuning in the OR domain. Such neurons become selective to relative OR disparity. Therefore, pooling allows the visual system to refine binocular information into a form more desirable for stereopsis.This article is part of the themed issue 'Vision in our three-dimensional world'.


Regional and Sex Differences in the Prevalence and Awareness of Hypertension: An H3Africa AWI-Gen Study Across 6 Sites in Sub-Saharan Africa.
There is a high prevalence of hypertension and related cardiovascular diseases in sub-Saharan Africa, yet few large studies exploring hypertension in Africa are available. The actual burden of disease is poorly understood and awareness and treatment to control it is often suboptimal. The study sought to report the prevalence of measured hypertension and to assess awareness and control of blood pressure among older adults in rural and urban settings in 6 sites located in West, East, and Southern Africa. In addition, we examined regional, sex, and age differences related to hypertension. A population-based cross-sectional study was performed at 6 sites in 4 African countries: Burkina Faso (Nanoro), Ghana (Navrongo), Kenya (Nairobi), and South Africa (Agincourt, Dikgale, Soweto). Blood pressure measurements were taken using standardized procedures on 10,696 adults 40 to 60 years of age. Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or taking antihypertensive medication. The mean prevalence of hypertension ranged from 15.1% in Nanoro to 54.1% in Soweto. All 3 of the South African sites had a mean prevalence of hypertension of over 40.0%, significantly higher than in Nairobi (25.6%) and Navrongo (24.5%). Prevalence increased with age in both sexes and at all sites. A significantly higher prevalence of hypertension was observed in women in Agincourt, Dikgale, and Nairobi, whereas in Nanoro this trend was reversed. Within the hypertensive group the average proportion of participants who were aware of their blood pressure status was only 39.4% for men and 53.8% for women, and varied widely across sites. Our study demonstrates that the prevalence of hypertension and the level of disease awareness differ not only between but also within sub-Saharan African countries. Each nation must tailor their regional hypertension awareness and screening programs to match the characteristics of their local populations.


Alzheimer's disease: patterns of cognitive impairment at different levels of disease severity.
The aim of this study was to establish the presence and the consistency of different cognitive profiles in AD patients taking into consideration the severity of mental impairment. Therefore we stratified 679 neuropsychological observations on 119 probable AD patients followed longitudinally on the basis of overall degree of cognitive impairment. To compare performance on tests with different score ranges we transformed raw test scores into coefficients; to summarize our results in terms of language versus visuo-spatial performance we computed indices of prevalent impairment of performance (IPIP) by subtracting the coefficients for constructional praxis from coefficients for language-related tests. Finally, we converted these indices into z-scores for each level of mental decline to identify patients with generalized, language (L) or visuo-spatial (V) prevalent impairment. The latter, 30% of the sample, can be detected at all stages of dementia. There was a higher percentage of males among language impaired patients (P<0.05). Approximately half of patients with L/V prevalent impairment continued to show such a focality when followed longitudinally. The groups did not differ in the annual rate of cognitive decline.


Tocilizumab in systemic sclerosis treatment: a case report.
In the United States, tocilizumab was approved for the treatment of scleroderma and scleroderma-related interstitial lung disease because it inhibited the decrease in forced expiratory volume, so scleroderma treatment is entering a new era. A 44-year-old female patient with systemic scleroderma, diagnosed 6 years ago, presented with breathlessness over the last week. The modified Rodnan's score was 18. Tocilizumab 162 mg subcutaneously once every 2 weeks was prescribed. After 4 weeks, a decrease in Rodnan score was observed. Tocilizumab was stopped after 6 months without any side effects due to treatment. Treatment with tocilizumab may maintain lung function nearly unchanged. Its effect on perfecting skin fibrosis seems promising. Tocilizumab may be fairly safe to use. Tocilizumab may be effective and fairly safe to use. Further exploration is anticipated to advance a new period of systemic sclerosis treatment.


[Bradykinin and ventricular function].
Kinins are vasodilator peptides implicated in many physiological and physiopathological processes such as blood pressure regulation and that of the coronary circulation and inflammatory reactions. Kinins play an essential role in ventricular function as they counteract the effects of angiotensin II during myocardial ischaemia, ventricular remodelling and severe cardiac failure, emphasising the value of treatment favouring local endogenic production of bradykinin such as ACE inhibitors, neutral endopeptidase inhibitors and antagonists of AT1 receptors of angiotensin II.


Effects of Milk or Apple Juice Ingestion on the Pharmacokinetics of Elvitegravir and Cobicistat in Healthy Japanese Male Volunteers: A Randomized, Single-Dose, Three-Way Crossover Study.
Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) is specified in its package insert to be taken with food to obtain sufficient exposure of EVG. It has been reported that a nutritional protein-rich drink shows comparable pharmacokinetics (PK) of EVG to those with a standard breakfast. In this study, the PK profiles of EVG and COBI were evaluated by administration of a single dose of EVG/COBI/FTC/TAF, after ingestion of either a nutritional protein-rich drink, milk, or apple juice. The geometric means for Cmax and AUCinf of EVG following milk ingestion slightly decreased by 21% and 14%, respectively, and those following apple juice ingestion decreased by 67% and 61%, respectively, compared with a nutritional protein-rich drink. There were no differences in any PK parameters of COBI. Therefore, taking EVG/COBI/FTC/TAF after milk or apple juice ingestion appeared to be not appropriate. However, for plasma trough concentrations (Ctau ), it is known that Ctau is best correlated with the efficacy of EVG. The mean C24 of EVG after milk ingestion was 620.6 ng/mL, which was more than 10-fold the protein binding-adjusted 95% inhibitory concentration. With all the above considerations, it was concluded that taking EVG/COBI/FTC/TAF with milk could be an option to maintain sufficient plasma concentrations of EVG.


Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation.
Autosomal dominantly inherited spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders primarily affecting the cerebellum. Genetically, 26 different loci have been identified so far, although the corresponding gene has not yet been determined for 10 of them. Recently, mutations in the ATPase family gene 3-like 2 gene were presented to cause SCA type 28. To define the frequency of SCA28 mutations, we performed molecular genetic analyses in 140 unrelated familial cases with ataxia. Among other variations, we found a novel missense mutation at an evolutionarily conserved amino-acid position using a single-strand conformation polymorphism approach, followed by DNA sequencing. This amino-acid exchange p.E700K was detected in a four-generation German family and was not observed in a survey of 400 chromosomes from healthy control individuals.


Properties of sympathetic reflexes elicited by natural vestibular stimulation: implications for cardiovascular control.
1. To study the properties of vestibulosympathetic reflexes we recorded outflow from the splanchnic nerve during natural vestibular stimulation in multiple vertical planes in decerebrate cats. Most of the animals were cerebellectomized, although some responses were recorded in cerebellum-intact preparations. Vestibular stimulation was produced by rotating the head in animals whose upper cervical dorsal roots were transected to remove inputs from neck receptors; a baroreceptor denervation and vagotomy were also performed to remove visceral inputs. 2. The plane of head rotation that produced maximal modulation of splanchnic nerve activity (response vector orientation) was measured at 0.2-0.5 Hz. The dynamics of the response were then studied with sinusoidal (0.05- to 1-Hz) stimuli aligned with this orientation. 3. Typically, maximal modulation of splanchnic nerve outflow was elicited by head rotations in a plane near pitch; nose-up rotations produced increased outflow and nose-down rotations reduced nerve discharges. The gains of the responses remained relatively constant across stimulus frequencies and the phases were consistently near stimulus position, like regularly firing otolith afferents. Similar response dynamics were recorded in cerebellectomized and cerebellum-intact animals. 4. The splanchnic nerve responses to head rotation could be abolished by microinjections of the excitotoxin kainic acid into the medial and inferior vestibular nuclei, which is concordant with the responses resulting from activation of vestibular receptors. 5. The properties fo vestibulosympathetic reflexes recorded from the splanchnic nerve support the hypothesis that the vestibular system participates in compensating for posturally related changes in blood pressure.


[Advanced abdominal cancer. Treatment of complications].
Gastrointestinal obstruction and fistulas are well known complications in advanced cancer. Complications are common after surgery. Two case-histories illustrate etiology and treatment. A small syringe driver enables subcutaneous infusion. Continuous support by means of antiemetic, analgetic and anticholinergic drugs can provide sufficient control of symptoms. Patients with severe gastrointestinal obstruction can be cared for in their homes during the final weeks and months of terminal disease. Only rarely is tube-feeding or parenteral-nutrition indicated.


Expanding the bounds of military psychiatry: three clinical encounters.
This paper deals with clinical situations frequently encountered in military psychiatry. Using three narratives of soldiers assessed at the Israeli Defence Forces (IDF) during a period of marked conflict between Israel and the Palestinian Authority, the author portrays ethical dilemmas generated during assessments for fitness to go to combat. When the focus of the assessment is the soldier's refusal to serve in the army, particularly during periods of increased conflict, the psychiatrist faces a dilemma because of double loyalties, to the army of which he is a part, and to the soldier and his right to live. Based on previous literature and experience, some cases of refusal to serve may be understood going beyond the boundaries imposed by the medical model. The author discusses these issues in the context of Israeli society. In Israel, conscription is universal, and the army is not professional. However, given the lack of social legitimacy in Israel for refusal to serve in the IDF due to conscientious objection, soldiers who are otherwise aware of the ethical dilemmas imposed upon them by the harsh Israeli reality are left with no option other than to get exempted from military duties on psychiatric grounds. The author discusses how social and historical factors contribute to the construction of psychiatric and psychological symptoms.


Increased Oxygen Saturation in Retinal Venules During Isometric Exercise Is Accompanied With Increased Peripheral Blood Flow in Normal Persons.
A recent study has shown that an increase in the arterial blood pressure of approximately 10 mm Hg in healthy persons can increase the oxygen saturation in venules from the retinal periphery but not from the macular area. The purpose of the present study was to investigate whether a higher increase in blood pressure has further effects on oxygen saturations and whether this is accompanied with changes in retinal blood flow. In 30 healthy persons, oxygen saturation, diameter, and blood flow were measured in arterioles to and venules from the retinal periphery and the macular area. The experiments were performed before and during an experimental increase in arterial blood pressure of (mean ± SD) 18.3 ± 6.2 mm Hg. A higher number of venules than arterioles branching from the temporal vascular arcades to the macular area was balanced by a smaller diameter of the venules. Isometric exercise induced significant contraction of both peripheral and macular arterioles (P < 0.01 for both comparisons) and significant increase in oxygen saturation in both peripheral and macular venules (P < 0.001 for both comparisons). This was accompanied with a significant increase in the blood flow in the peripheral arterioles and venules (P = 0.4 for both comparisons), but not in their macular counterparts (P > 0.06 for both comparisons). Increased systemic blood pressure leading to arterial contraction and increased venous oxygen saturation in the retina in normal persons can increase peripheral blood flow without significant effects on macular blood flow. This may contribute to explaining regional differences in the response pattern of retinal vascular disease.


Macroscopic Strain-Induced Transition from Quasi-infinite Gold Nanoparticle Chains to Defined Plasmonic Oligomers.
We investigate the formation of chains of few plasmonic nanoparticles-so-called plasmonic oligomers-by strain-induced fragmentation of linear particle assemblies. Detailed investigations of the fragmentation process are conducted by in situ atomic force microscopy and UV-vis-NIR spectroscopy. Based on these experimental results and mechanical simulations computed by the lattice spring model, we propose a formation mechanism that explains the observed decrease of chain polydispersity upon increasing strain and provides experimental guidelines for tailoring chain length distribution. By evaluation of the strain-dependent optical properties, we find a reversible, nonlinear shift of the dominant plasmonic resonance. We could quantitatively explain this feature based on simulations using generalized multiparticle Mie theory (GMMT). Both optical and morphological characterization show that the unstrained sample is dominated by chains with a length above the so-called infinite chain limit-above which optical properties show no dependency on chain length-while during deformation, the average chain length decrease below this limit and chain length distribution becomes more narrow. Since the formation mechanism results in a well-defined, parallel orientation of the oligomers on macroscopic areas, the effect of finite chain length can be studied even using conventional UV-vis-NIR spectroscopy. The scalable fabrication of oriented, linear plasmonic oligomers opens up additional opportunities for strain-dependent optical devices and mechanoplasmonic sensing.


Peritoneal dialysate IgG/C3 levels do not predict susceptibility to peritonitis.
To investigate the usefulness of dialysate IgG and C3 concentrations in predicting likelihood of developing peritonitis. Prospective, longitudinal, and comparative study. Single university teaching hospital dialysis unit and outpatient clinic. Thirty-four uremic patients were studied (20 males, 14 females: mean age 47.2, range 20-73 years). Monthly serum and overnight dialysate (eight- to eleven-hour dwell) samples were obtained for IgG and C3 estimations over the first six months of the study, and trimonthly samples were obtained thereafter. All patients performed exchanges using standard transfer sets (Baxter system II, Baxter Healthcare Ltd., Thetford, Norfolk, U.K.), used no hypertonic fluid (3.86%) for overnight exchanges, and were followed up for a minimum of 18 months. Dialysate and serum levels of IgG and C3; peritonitis episodes. Forty-five episodes of peritonitis occurred in 24 patients during the study period. We examined opsonin levels in the group as a whole, and then in two subgroups of patients: those who remained peritonitis-free throughout the study, and those who did not. There were no significant differences between IgG and C3 levels in the two groups at any time point, and large interpatient and intrapatient variation in levels were seen. Dialysate levels of IgG and C3 from the overnight dwell are not helpful in predicting the risk of developing continuous ambulatory peritoneal dialysis peritonitis in individual patients. No correlation was found between opsonin levels and onset of clinical peritonitis.


Time-course of changes in arm impairment after stroke: variables predicting motor recovery over 12 months.
To characterize the time-course of changes in motor recovery in the upper extremity of hemiparetic stroke survivors over a 1-year interval after stroke, and to use kinematic and kinetic recordings of elbow voluntary movement at 1 month to predict recovery over this 1-year period. Motor impairment was assessed using the Fugl-Meyer Assessment (FMA) of the upper extremity. The angular elbow movement trajectory and its derivatives were recorded. Limb kinetics were quantified using maximum voluntary contractions. Subjects were examined at 1, 2, 3, 6, and 12 months after stroke. The growth mixture model was used to characterize the recovery patterns of the FMA over 1 year, and a logistic regression analysis was used to predict these patterns with the kinematic and kinetic measures recorded at 1 month. A hospital-based laboratory with a movement testing system including position and torque sensors. Hemiparetic stroke survivors (N=20) with upper-extremity impairment recruited within 4 weeks poststroke. Not applicable. Kinematic parameters, including active range of motion, peak velocity, peak acceleration, movement smoothness, and movement speed; kinetic parameters, including isometric voluntary contraction of elbow extensors and flexors; and clinical measurement of motor impairment (FMA). We found 2 classes of recovery patterns. Class 1 subjects started with a low-level FMA score and then increased quickly before tapering off gradually. Conversely, class 2 subjects started with a high-level FMA score that remained constant or increased slightly. Using logistic regression, the impact of each kinematic and kinetic measure on class membership was characterized. The class assignment helped predict the recovery pattern of motor impairment for each subject. Using elbow kinematic and kinetic measures 1 month after stroke, we were able to predict accurately the recovery of arm impairment in subjects with hemiparetic stroke at different time points in the first year. This information is of potential value for planning targeted therapeutic interventions.


Synthesis and Catalytic Application of Two Mononuclear Complexes Bearing Diethylenetriamine Derivative Ligand.
Two mononuclear zero-dimensional Ni(II) and Zn(II) complexes bearing diethylenetriamine derivative ligand, namely [NiL(CH3COO)2(H2O)] (1) and [ZnL(CH3COO)2] (2) [L = N, N'-bis(2-hydroxybenzyl)diethylenetriamine], were synthesized under reflux conditions. The molecular composition and structure of the complexes were identified by IR, PXRD, elemental analyses, and single crystal X-ray diffraction. Complex 1 belongs to a monoclinic crystal system with the P21/n space group, and Complex 2 belongs to a monoclinic crystal system with the C2/c space group. The Henry reaction of nitromethane with aromatic aldehydes was explored with Complexes 1 and 2 as the catalyst. Results from the catalytic reaction revealed that the complexes displayed excellent catalytic activities under the optimized conditions and that the substrate scope of aromatic aldehydes could be extended to a certain extent. In addition, the possible catalytic mechanism of the Henry reaction was also deduced.


Functional imaging of intrarenal blood flow using scintillation camera and computer.
In order to obtain spatial distribution of an index for regional blood flow at each element on a scintigraphic image of the kidney, we attempted the construction of the so-called functional image. After injecting a single bolus of 133Xe into a renal artery by means of a catheter, this objective was accomplished using digital computer processing for a sequence of scintillation camera recordings of the following washout process from the kidney. This is expressed in a form of matrix of disappearance rate constant. Calculation for the rate constant, the flow index of the functional image, was done using either the least squares (LS) method or height-over-area (H/A) method. Although the former method was considered to be theoretically suitable without undue participation of background activities, the latter was preferred because of stable results for image construction. On reviewing the functional image thus obtained from 22 patients representing a variety of renal diseases, the H/A gave specific information concerning regional distribution of the perfusion integrity mainly related to the cortical part of the kidney. This is often difficult to accomplish utilizing the conventional method of compartmental analysis of the xenon washout curve or selective renal angiography.


Prevalence of cryptosporidium in Rawalpindi/Islamabad a comparison of saline, iodine and stained preparations.
Three hundred stool samples for routine ova and parasite examination were examined as saline and iodine wet preparations, the results were then compared with the Zeihl-Neelsen-modified Acid Fast staining (MAFS), as the oocysts are acid fast in character. Examination with saline preparation was unable to detect any oocyst, while iodine preparation yielded three oocyst and stained smears with MAFS revealed five positive stool samples.


Subdural hematoma - a cause of death in the development of a prostatic adenocarcinoma with dural metastases: case report.
Non-traumatic subdural hematoma secondary to dural metastases is a rare complication. Dural metastases from a prostate adenocarcinoma occur in the advanced stages of this pathology and may sometimes be the first manifestation of a prostate carcinoma. Less than 40 cases of subdural hematoma are reported in the literature as a consequence of dural metastases from a prostate adenocarcinoma. The authors present the case of a male patient diagnosed with stage IV prostate adenocarcinoma with bone metastasis, who is admitted for left hemisphere subdural hematoma with right hemiparesis. The evolution of the patient is unfavorable, and the autopsy shows dural metastases and a collection of subdural coagulated blood. The chronic subdural hematoma with re-bleeding is a rare cause of death in the development of a prostate adenocarcinoma.


Highly efficient sky blue electroluminescence from ligand-activated copper iodide clusters: Overcoming the limitations of cluster light-emitting diodes.
Organic light-emitting diodes using cluster emitters have recently emerged as a flexible optoelectronic platform to extend their biological and optical applications. However, their inefficient cluster-centered excited states and deficient electrical properties limit device performance. Here, we introduce donor groups in organic ligands to form ligand-activated clusters, enabling the fabrication of the first cluster-based sky blue-emitting device with a record 30- and 8-fold increased luminance and external quantum efficiency up to ~7000 nits and ~8%, respectively. We show that the electron-donating effect of donor groups can enhance ligand-centered transitions and thoroughly eliminate cluster-centered excited states by delocalizing the molecular transition orbitals from the cluster unit to the ligand, leading to 13-fold increased photoluminescence quantum yield. In turn, the excellent rigidity and photostability of the cluster unit improve the color purity and efficiency stability of the devices. These results will motivate the further development of high-performance optoelectronic clusters by ligand engineering.


Effect of salicylic acid on morphological and biochemical attributes in cowpea.
Effects of salicylic acid (SA) on seed germination, seedling growth, flowering and biochemical activities were studied out in four cowpea (Vigna unguiculata) genotypes in control environments. The results revealed that both germination and seedling growth were negatively affected by 0.02%. SA application, however did not affect the size of full expanded buds, time of 50% flowering and date of flower initiation. A maximum increase in peroxidase (EC188.8.131.52) activity was observed in UPC 4200 over other genotypes. No significant change in the content of total soluble and intercellular fluid proteins was observed except in UPC 4200 genotype. SA induced accumulation of total soluble sugars more at flowering stage than at seed setting stage. It is evident from the present study that UPC 4200 genotype was more responsive to salicylic acid both in terms of increased peroxidase activity and less negative effect on morphological attributes, thus suggesting its wider use without negative impact on environment as salicylic acid has been reported in plants.


Polarized transport of docetaxel and vinblastine mediated by P-glycoprotein in human intestinal epithelial cell monolayers.
The expression of the multidrug transporter P-glycoprotein has been studied in two human intestinal epithelial cell lines. No functional expression of P-glycoprotein was found in the differentiated HT29-18-C1 cell line. The expression of P-glycoprotein in the Caco-2 cell line was very high, as judged by immunoblotting and by active efflux of vinblastine. The polarized transport of vinblastine in the basolateral to apical direction was temperature and energy dependent, and was reduced by P-glycoprotein inhibitors such as verapamil, chlorpromazine and reserpine. This adds further evidence that the polarized transport of vinblastine across Caco-2 monolayers is mediated by P-glycoprotein. The anticancer drug docetaxel (Taxotere) was transported in a polarized manner: basolateral to apical permeability was 20-fold higher than in the reverse direction. This polarized transport was inhibited by verapamil, chlorpromazine and reserpine, thus demonstrating that docetaxel is a substrate of P-glycoprotein. The implications of these results for the pharmacokinetics and toxicity of taxoids are discussed.


Mouse Lung Fibroblast Resistance to Fas-Mediated Apoptosis Is Dependent on the Baculoviral Inhibitor of Apoptosis Protein 4 and the Cellular FLICE-Inhibitory Protein.
A characteristic feature of idiopathic pulmonary fibrosis (IPF) is accumulation of apoptotic resistant fibroblasts/myofibroblasts in the fibroblastic foci. As caveolin (Cav)-null mice develop pulmonary fibrosis (PF), we hypothesized that the participating fibroblasts display an apoptosis-resistant phenotype. To test this hypothesis and identify the molecular mechanisms involved we isolated lung fibroblasts from Cav-null mice and examined the expression of several inhibitors of apoptosis (IAPs), of c-FLIP, of Bcl-2 proteins and of the death receptor CD95/Fas. We found significant increase in XIAP and c-FLIP constitutive protein expression with no alteration of Bcl-2 and lower levels of CD95/Fas. The isolated fibroblasts were then treated with the CD95/Fas ligand (FasL) to induce apoptosis. While the morphological and biochemical alterations induced by FasL were similar in wild-type (wt) and Cav-null mouse lung fibroblasts, the time course and the extent of the alterations were greater in the Cav-null fibroblasts. Several salient features of Cav-null fibroblasts response such as loss of membrane potential, fragmentation of the mitochondrial continuum concurrent with caspase-8 activation, and subsequent Bid cleavage, prior to caspase-3 activation were detected. Furthermore, M30 antigen formation, phosphatidylserine expression and DNA fragmentation were caspase-3 dependent. SiRNA-mediated silencing of XIAP and c-FLIP, individually or combined, enhanced the sensitivity of lung fibroblasts to FasL-induced apoptosis. Pharmacological inhibition of Bcl-2 had no effect. Together our findings support a mechanism in which CD95/Fas engagement activates caspase-8, inducing mitochondrial apoptosis through Bid cleavage. XIAP and c-FLIP fine tune this process in a cell-type specific manner.


[Comparative analysis of informative-diagnostic properties of mucosa immune-reactivity parameters].
Study the features of immune-reactivity expression in mucosa depending on their topicity and etiopathogenesis of the pathological process. Data from 30 clinically healthy children and 77 children with acute and recurrent diseases of respiratory tract: 51--with acute and 15--with chronic bronchitis; as well as 132 women: 41--with active stage of acute urogenital chlamydia infection, 29--with recurrent chronic process, 30--with non-recurrent form and 32 clinically healthy women were analyzed. Saline and urogenital tract mucosa discharge was analyzed for IgG, sIgA and secretory component, IL-1beta, 4, 6, 8, 9, 10, 12, IFNgamma, TNFalpha and GM-CSF, TLR-2, TLR-3, TLR-4, TLR-8 gene expression levels as well as content of lysozyme, total protein and leucocytes. Solidity, universality and practically single-stage triggering of mucosa immune reaction mechanisms to intervention by foreign agents regardless of their localization was confirmed. A dependence of immune-reactivity expression on the form of pathologic process, its localization and qualitative and quantitative characteristics of the infectious agents was clearly seen. The highest level of clinical-laboratory and immunological parameters is inherent for patients with acute processes in urogenital tract (cervical canal and urethra), especially cause by mixed infections. Immune diagnostic parameters of mucosa among which TLR system is especially notable have high information properties allowing not only diagnostics of inflammatory process but also differentiating its form and character our course.


Worse Health Status and Higher Incidence of Health Disorders in Rhesus Negative Subjects.
Rhesus-positive and Rhesus-negative persons differ in the presence-absence of highly immunogenic RhD protein on the erythrocyte membrane. The biological function of the RhD molecule is unknown. Its structure suggests that the molecular complex with RhD protein transports NH3 or CO2 molecules across the erythrocyte cell membrane. Some data indicate that RhD positive and RhD negative subjects differ in their tolerance to certain biological factors, including, Toxoplasma infection, aging and fatique. Present cross sectional study performed on 3,130 subjects) showed that Rhesus negative subjects differed in many indices of their health status, including incidences of many disorders. Rhesus negative subjects reported to have more frequent allergic, digestive, heart, hematological, immunity, mental health, and neurological problems. On the population level, a Rhesus-negativity-associated burden could be compensated for, for example, by the heterozygote advantage, but for Rhesus negative subjects this burden represents a serious problem.


Palliative care in patients with brain metastases.
With improvements in systemic therapy, central nervous system metastases have increased in incidence in patients with cancer. Patients with brain metastases from solid tumors often have a dismal prognosis, and supportive measures are often critical in improving patient outcome. They include treatments against vasogenic edema, seizures, symptomatic venous thrombosis, and pain, and the management of iatrogenic side effects. This article reviews all the supportive care measures in patients with brain metastases, with the exception of tumor-specific chemotherapy treatments that are also used in this patient population. Recently, improvement has been made in the management of the following complications of brain metastases: epilepsy and antiepileptic drug side effects, thromboembolic complications, fatigue and cognitive disorder of mixed (tumoral and/or iatrogenic) origin, pain, hematological side effects of chemotherapy, and steroids complications. Patients with brain metastases are particularly prone to develop severe side effects, increased fatigue, and cognitive deteriorations following apparently minor changes in symptomatic treatments. Palliative management of brain metastasis requires a multidisciplinary approach, and it is important to avoid any treatment that is useless or harmful or has a poor toxicity/efficacy ratio.


Efficacy and safety of early coronary stenting for unstable angina.
To determine the efficacy and safety of early coronary stenting for unstable angina, we studied 91 consecutive patients with unstable angina. Thirty-one patients underwent stenting 72 h or more after admission, and another 60 patients underwent stenting within 72 h of admission. The clinical and angiographic follow-up had been done for 6 mo. There were no differences between the baseline clinical and angiographic characteristics of both groups. The maximum balloon pressure was higher (14.1 +/- 1.2 vs. 12.6 +/- 0.9, P < 0.01) and the hospital stay was shorter (9.7 +/- 2.7 vs. 18.7 +/- 5.8 d, P < 0.0001) in the early stenting group. These two groups were similar in the clinical success rate (90.0% vs. 93.5%), without any abrupt closure, subacute thrombosis, death, myocardial infarction, or coronary bypass surgery. These findings indicate that early stenting can be useful in patients with unstable angina.


Bortezomib in the front-line treatment of multiple myeloma.
Front-line therapy for multiple myeloma is rapidly evolving with the development of new, highly active regimens based on novel agents such as bortezomib. Bortezomib-based regimens are demonstrating substantial efficacy both as induction prior to stem cell transplantation and as treatment for patients ineligible for transplant, offering rapid and durable responses with consistently high rates of complete response, a surrogate end point for improved overall survival. Combinations of bortezomib plus established and novel agents, such as melphalan-prednisone, dexamethasone, doxorubicin, thalidomide-dexamethasone and, most recently, lenalidomide-dexamethasone, are proving superior to or more promising than previous standards of care. Importantly, these regimens are demonstrating enhanced activity across the front-line population, including patients with renal impairment, high-risk cytogenetics and advanced bone disease. Impressive Phase 3 results with bortezomib-melphalan-prednisone, bortezomib-dexamethasone and bortezomib-thalidomide-dexamethasone should facilitate the establishment of these highly effective regimens as key therapies for newly diagnosed myeloma.


Lymphatic microvessels density, VEGF-C, and VEGFR-3 expression in 25 cases of breast invasive lobular carcinoma.
Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer, having distinct morphologically but also prognostic and therapeutic features. This type of breast cancer shows a higher rate of multiple metastases with a more frequent axillary-lymph-node involvement. Related to these dissemination and metastatic features, we aimed to study the immunohistochemical expression of D2-40, VEGF-C and VEGFR-3 in 25 cases of ILCs stratified according to the histopathological and molecular classification. Regardless of histopathological or molecular subtype, the statistical tests proved that for ILC, the highest D2-40 lymphatic microvessels density (LMVD) was in the peritumoral areas. In classical subtype, the LMVD values were positively correlated with the degree of tumor differentiation and pTNM clinical stages and when these cases were classified based on the molecular criteria the highest recorded values were found in the luminal B subtype. In addition, regardless of the histopathological and molecular subtypes, the D2-40 LMVD varied in the same direction for both VEGF-C and VEGFR-3 categories, with the highest LMVD values recorded in those cases with the highest VEGF-C and VEGFR-3 reactivity, especially in the peritumoral areas. Considering only the molecular luminal A and B subtypes, we have noted that VEGF-C and VEGFR-3 expression was significantly higher in luminal A subtype compared to luminal B. This immunoprofile suggests the existence of a tumor type-specific lymphangiogenesis that may have certain prognostic and therapeutic implications.


The public health burdens of sedentary living habits: theoretical but realistic estimates.
Quantitative estimates indicate that sedentary living is responsible for about one-third of deaths due to coronary heart disease, colon cancer, and diabetes--three diseases for which physical inactivity is an established causal factor. Presumably, if everyone were highly active the death rate from these three disease would be only two-thirds of the current rate. Not everyone will become highly active, however. Assuming smaller increases in physical activity practices, mortality from these three conditions combined could be reduced by as much as 5-6%, or 30,000-35,000 deaths per year. Overall mortality in the United States might be reduced about 1-1.5%. The greatest gains would accrue from strategies that encourage those who report no leisure-time physical activity to do some and that encourage those who are irregularly active to participate in 30 or more minutes of light to moderate activity for 5 or more d.wk-1. Mortality is only one aspect of public health burdens that would be reduced by greater participation in regular physical activity. Quality of life, which we have not attempted to quantify, would also improve.


An empirical analysis of eating disorders and anxiety disorders publications (1980-2000)--part II: Statistical hypothesis testing.
The current study compared the eating disorder literature and the anxiety disorder literature in terms of statistical hypothesis testing features in 1980, 1990, and 2000. Computer literature searches were conducted using PubMed and PsychInfo databases to identify relevant eating disorder and anxiety disorder articles published at each of the three time points. A total of 456 articles were randomly selected, including 228 articles each from the fields of eating disorders and anxiety disorders. Within each field, one third (76) of the articles were selected from each of the three time points. Two raters, from a team of eight trained raters, were randomly assigned to independently rate each article in terms of 75 separate methodologic features. In the current article, we will emphasize the findings about hypothesis testing and statistical analysis. Disagreements in ratings were resolved via consensus. Ratings were tabulated separately by field across the three time points. Few differences were observed between eating disorder and anxiety disorder publications in terms of statistical hypothesis testing features. Although increases were observed in both fields in a number of areas from 1980 to 2000, there remains a pervasive absence of many of the statistical hypothesis testing features recommended by the American Psychological Association Task Force on Statistical Inference. These results are discussed in terms of their implications for the fields of eating disorders and anxiety disorders, for researchers, for reviewers, and for professional journals and editorial boards.


[Physician-patient relations: a teaching art].
Teaching the relationship patient-physician: how to convince one's patient. To learn how to announce bad news. Role-playing is a precious asset in this important apprenticeship for the patient as well as for the physician.


Peptide protected gold clusters: chemical synthesis and biomedical applications.
Bridging the gap between atoms and nanoparticles, noble metal clusters with atomic precision continue to attract considerable attention due to their important applications in catalysis, energy transformation, biosensing and biomedicine. Greatly different to common chemical synthesis, a one-step biomimetic synthesis of peptide-conjugated metal clusters has been developed to meet the demand of emerging bioapplications. Under mild conditions, multifunctional peptides containing metal capturing, reactive and targeting groups are rationally designed and elaborately synthesized to fabricate atomically precise peptide protected metal clusters. Among them, peptide-protected Au Cs (peptide-Au Cs) possess a great deal of exceptional advantages such as nanometer dimensions, high photostability, good biocompatibility, accurate chemical formula and specific protein targeting capacity. In this review article, we focus on the recent advances in potential theranostic fields by introducing the rising progress of peptide-Au Cs for biological imaging, biological analysis and therapeutic applications. The interactions between Au Cs and biological systems as well as potential mechanisms are also our concerned theme. We expect that the rapidly growing interest in Au Cs-based theranostic applications will attract broader concerns across various disciplines.


Evaluation of the Relationships between Irisin Levels and Cognitive Functions in Individuals with Schizophrenia.
: Irisin is a myokine that is involved in neurogenesis, neuronal proliferation, and neuronal differentiation. Many research examine the relationship between irisin and schizophrenia. In this study, we aimed to evaluate the relationship between irisin levels and cognitive functions in individuals with schizophrenia. : Ninety-six individuals who were diagnosed with schizophrenia were included. The Brief Psychiatric Rating Scale (BPRS) was used to assess disease severity. To evaluate the cognitive functions of the patients, the trail-making test was evaluated with the A and B forms and the verbal memory processes scale. After a 12-hour night fast, samples of fasting blood were obtained from the participants. : There was no significant correlation between irisin, duration of disease, and BPRS total score. In the analysis performed, a positive correlation was found between the plasma irisin level and the error score of the trail-making test form B. Other than that, no correlation was found between irisin level and cognitive performance in schizophrenia patients. In addition, in subgroup analysis between genders, it was determined that the duration of the trail-making test B was longer in female schizophrenia patients. : In this study, there was a positive correlation between the trail-making test B-form error scores and the irisin levels. This relationship between impaired executive functions and irisin levels may suggest that the irisin level is increased as compensation for the impairment in executive functions. More research is needed to understand the role of irisin in cognitive impairment and schizophrenia.


Evaluating Shifts in Perception After a Pilot Trauma Quality Improvement Training Course in Cameroon.
Trauma is a major contributor to the global burden of disease, with low- and middle-income countries (LMICs) being disproportionately affected. Trauma Quality Improvement (QI) initiatives could potentially save an estimated two million lives each year. Successful trauma QI initiatives rely on adequate training and a culture of quality among hospital staff. This study evaluated the effect of a pilot trauma QI training course on participants' perceptions on leadership, medical errors, and the QI process in Cameroon. Study participants took part in a three-day, eight-module course training on trauma QI methods and applications. Perceptions on leadership, medical errors, and QI were assessed pre and post-course using a 15-item survey measured on a five-point Likert scale. Median pre- and post-course scores were compared using the Wilcoxon signed-rank test. Knowledge retention and course satisfaction were also evaluated in a post-course survey and evaluation. A majority of the 25 course participants completed pre-course (92%) and post-course (80%) surveys. Participants' perceptions of safety and comfort discussing medical errors at work significantly increased post-course (pre-median = 5, IQR [4-5]; post-median = 5, IQR [5-5]; P = 0.046). The belief that individuals responsible for medical error should be held accountable significantly decreased after the course (pre-median = 3, IQR [2-4]; post-median = 1, IQR [1-2]; P < 0.001). Overall satisfaction with the course was high with median scores ≥4. These initial results suggest that targeted trauma QI training effectively influences attitudes about QI. Further investigation of the effect of the trauma QI training on hospital staff in larger courses is warranted to assess reproducibility of these findings.


Rheumatology out-patient workload increases inexorably.
Rheumatology out-patient consultations in the south-west of England from 1 to 30 November 1994 were recorded by standard methods and compared to 1988, 1990, 1991 and 1992. Historical records at one centre provided additional detailed information. There has been an overall increase of 31% in the number of patients seen (30% for follow-up cases, 36% for new referrals), but the mean waiting time for new patient consultations increased from 65 to 108 days. The proportion of new patient consultations with non-arthritic diseases increased by 8.2%, and those with rheumatoid arthritis and polyarthritis decreased by 9.0%. Variation in discharge rates and length of follow-up appointments occurred, but mostly in uncommon diagnostic categories. Referral rates have been rising faster since the introduction of National Health Service reforms than can be accommodated by the increased workload undertaken.


Sepsis during pregnancy.
To provide a current review of the literature regarding the assessment and management of sepsis during pregnancy. A comprehensive review of current English-language literature search was performed with Ovid MEDLINE using the Medical Subject Headings pregnancy and sepsis, with Medical Subject Headings or keywords seeking randomized controlled trials and clinical reports, and by reviewing the bibliographies of clinical practice guidelines. Sepsis-related maternal morbidity and mortality is a significant and persistent problem in the modern critical care obstetric unit. The management of sepsis during pregnancy is challenging. The obstetric intensivist must simultaneously discern the effect of maternal physiologic changes on fetal vulnerability and the effect of the fetus on maternal status throughout the various phases of pregnancy. Little direct evidence exists to validate the extrapolation of some sepsis treatment modalities from other nonpregnant patient populations. Nevertheless, early detection, accurate diagnosis, and aggressive appropriate treatment strategies may significantly improve outcome. Approaches like the Surviving Sepsis Campaign guidelines are unproven but seem reasonable and practical. Sepsis during pregnancy is uncommon yet potentially fatal. Diagnostic and therapeutic guidelines should predominantly pattern those currently utilized for nonpregnant patients.


Direct supplementation of diet is the most efficient way of enriching broiler meat with n-3 long-chain polyunsaturated fatty acids.
1. Concentrations of beneficial omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) in poultry meat can be improved by increasing the concentration of n-3 PUFA in poultry diets. 2. A decrease in flavour quality is, however, usually associated with the dietary supplementation with n-3 PUFA, which is due to the susceptibility of PUFA to oxidation. 3. This experiment was conducted to study the effects of introducing two different n-3 fatty acid sources (extruded linseed and DHA Gold™, a proprietary algal product rich in docosahexaenoic acid), either separately or together, on broiler productive performance, and meat quality, oxidative stability, sensory traits and LC-PUFA profile. 4. Birds given the algal product displayed better productive performances than animals from other groups. 5. The data revealed an improvement in the fatty acid nutritional value of meat from birds receiving the algal product and an inefficient conversion of α-linolenic acid (LNA) into LC-PUFA. 6. Metabolisation of LNA in vivo is not sufficient to improve meat quality in n-3 LC-PUFA and direct supplementation of the diet with n-3 LC-PUFA is a better alternative to modulate an increase in beneficial fatty acids of broiler meat. 7. The overall acceptability of meat was negatively affected by the dietary supplementation with 7.4% of DHA, in contrast to the supplementation with 3.7% of DHA, which showed to be efficient in improving LC-PUFA meat content without affecting its sensory properties.


Commentary. Transcranial Magnetic Stimulation: Does It Matter Where or What or Whom You Target?
Repetitive transcranial magnetic stimulation is a promising treatment for depression and possibly for other psychiatric disorders. Clinical trials show a small but significant benefit compared with sham treatment. Occasional patients respond dramatically, as witnessed in the 2 cases presented here of patients with depersonalization symptoms. The guest discussant, Dr Joshua Berman, analyzes the challenges of finding individualized treatment parameters that could make repetitive transcranial magnetic stimulation more predictably effective.


The acute effect of strength exercises at different intensities on intraocular pressure.
This study aimed to determine the effect of two basic strength exercises with progressive loads on intraocular pressure (IOP). Seventeen (out of 20 recruited) physically active male military officers (46 ± 4.77 years) performed the jump squat and the ballistic bench press exercises, in counterbalanced order, with four and five progressive loads, respectively. IOP was measured with a rebound tonometer before and after each of the corresponding loads. IOP linearly increases with heavier loads for the jump squat (r = 0.976) and the ballistic bench press (r = 0.991) exercises. A significant IOP elevation was observed during the jump squat test (p < 0.001), and Bonferroni-Holm correction revealed that ~75% of one repetition maximum (RM) was able to promote significant changes in IOP with respect to the other three loads (all corrected p values <0.05), whereas the load corresponding to ~65%RM and ~60%RM induced a significant IOP rise when compared with the load of ~50%RM (corrected p-values of 0.43 in both cases). For its part, IOP significantly increases with the bench press test (p < 0.001), and performing the ~50%RM load was enough to induce significant IOP changes (corrected p-value <0.01). Acute performance of jump squat and ballistic bench press lead to a significant increase of IOP, and 5 min of rest are enough to recover baseline IOP values. There is a strong linear association between the increase in load and the IOP rise for both exercises, and bench press execution produces a significantly higher IOP increase when compared with the jump squat for the same relative loads.


Human herpesvirus 8-related childhood mononucleosis: a series of three cases.
Human herpesvirus 8 has been implicated in the pathogenesis of a limited subset of lymphoproliferative disorders in adults, but its role in children is unclear. A prospective evaluation of children with atypical lymphocytosis residing in the Hualien area, where the incidence of adult Kaposi sarcoma is high, revealed 3 cases caused by human herpesvirus 8.


Neuromuscular, hormonal, and metabolic responses to different plyometric training volumes in rugby players.
The purpose of this study was to investigate the effect of different volumes of plyometric exercise (i.e., 100, 200, or 300 hurdle jumps) on acute strength and jump performance and on the acute hormonal and lactate responses in rugby players. Eleven young male elite rugby players (age, 23.5 ± 0.9 years; height, 173 ± 4.8 cm) volunteered for the study. Maximal isometric peak torque (PT), maximal rate of force development (RFD), squat jump (SJ), and drop jump (DJ) performance were assessed before and 5 minutes, 8 hours, and 24 hours after 100, 200, or 300 jumps. In addition, total testosterone (TT), cortisol (COR), and lactate were measured before and after the 3 different plyometric exercise volumes. There were significant decreases in the PT (p < 0.02) and maximal RFD (p < 0.001) 5 minutes, 8 hours, and 24 hours after 100, 200, and 300 jumps, with no differences between the exercise volumes. Additionally, there were significant decreases in the SJ (p < 0.001) and DJ (p < 0.01) performances 24 hours after 100, 200, and 300 jumps, with no differences between the exercise volumes. However, there were significant increases in the TT (p < 0.001), COR (p < 0.05), and lactate (p < 0.001) after 100, 200, and 300 jumps, with no differences between the exercise volumes. All plyometric exercise volumes (100, 200, and 300 jumps) resulted in similar neuromuscular, metabolic, and hormonal responses.


Efficacy of montelukast and loratadine as treatment for allergic rhinitis in children.
The objective of this study was to compare the effectiveness of montelukast combined with loratadine once daily to loratadine alone for a 2-week treatment course of allergic rhinitis in a randomized, double-blind placebo controlled trial which enrolled 115 children, 6- 15-years-old. The patients were randomly assigned to receive montelukast and loratadine (treatment group) or placebo and loratadine (control group). The primary outcome was the mean percent change of the total daytime nasal symptom scores (PDTS) and secondary outcomes were the mean percent changes of the nighttime nasal, daytime eye and composite symptom scores (PNTS, PES, PCS), as well as the nasal secretion, turbinate swelling and nasal congestion scores (PNSS, PTSS, PNCS). There were no significant differences in the PDTS of the 2 groups. The change in the night time nasal congestion score (PNTS-congestion) was higher in the treatment group, but not statistically significant (p = 0.077). Only the mean percent change in decreased turbinate swelling was significantly greater in the montelukast and loratadine group than the loratadine alone group (-22 +/- 7 vs. -1 +/- 5, p < 0.05).


Heretical thoughts into hepatic encephalopathy.
Clinical progress in the development of new diagnostic modalities and therapeutic strategies for the management of patients with hepatic encephalopathy has lagged behind the vast knowledge that has been generated from basic studies. In this article, we critically assess matters that should be revisited, such as definition, classification, diagnosis and grading of hepatic encephalopathy, which are difficult to apply reproducibly using the current criteria. Many lines of investigation have confirmed that hepatic encephalopathy is irreversible in many patients and suggest the need for further studies focussing on mechanisms of neuronal injury and death, to guide future drug development for these patients. The clinical evidence behind using lactulose for all severities of hepatic encephalopathy, which is currently considered the standard of care, is poor and placebo-controlled trials for hepatic encephalopathy should be considered ethically sound. This expert opinion identifies current challenges in hepatic encephalopathy and highlights areas which require further debate and investigation in order to help advance the field both scientifically and clinically.


CYP2A13 metabolizes the substrates of human CYP1A2, phenacetin, and theophylline.
Human cytochrome CYP2A13 shows overlapping substrate specificity with CYP2A6, catalyzing the metabolism of coumarin, nicotine, cotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Recently, it was found that CYP2A13 could catalyze the metabolic activations of 4-aminobiphenyl and aflatoxin B(1), which are known to be catalyzed by human CYP1A2. In the present study, we investigated the substrate specificity of CYP2A13. It was shown that CYP2A13 could catalyze ethoxyresorufin O-deethylation, methoxyresorufin O-demethylation, and phenacetin O-deethylation, which are used as marker activities for human CYP1A2. Although the intrinsic clearances (V(max)/K(m)) of the two former reactions by CYP2A13 were much lower than that of CYP1A2, the value of the last reaction by CYP2A13 was 2-fold higher than that of CYP1A2. Of particular interest was that CYP2A13 has higher affinity toward phenacetin than CYP1A2. In contrast, CYP2A6 hardly catalyzed these reactions, although the amino acid identity with CYP2A13 is as high as 93.5%. Furthermore, we found that CYP2A13 can catalyze theophylline 8-hydroxylation and 3-demethylation, which are known to be mainly catalyzed by human CYP1A2, although the intrinsic clearances were approximately one-tenth that of CYP1A2. CYP2A13 would not contribute to the systemic clearance of these drugs because CYP2A13 is hardly expressed in human liver. However, it may play a role in metabolism in local tissues such as lung or trachea. In conclusion, the results of the present study could extend our understanding of the substrate specificity of CYP2A13.


Validation of commercially available infrared thermometers for measuring skin surface temperature associated with deep and surrounding wound infection.
Increased local skin temperature is a classic sign of wound infection, repetitive trauma, and deep inflammation. Noncontact infrared thermometers can help to detect increases in skin surface temperatures; however, most scientifically tested devices are far too expensive for everyday wound care providers to use in routine clinical practice. This noninferiority study was conducted in an attempt to determine whether 4 less expensive, commercially available noncontact infrared thermometers have a similar level of accuracy as the scientifically accepted Exergen DermaTemp 1001 (Exergen Products, Watertown, Massachusetts). Using an observational study design, participants with open wounds were randomly selected from a chronic wound clinic (n = 108). Demographic data and wound location were documented for all participants. Skin temperatures were recorded using 5 noncontact infrared thermometers under consistent environmental conditions. The thermometer brands were as follows: Exergen DermaTemp, Mastercool MSC52224-A (Mastercool Inc, Randolph, New Jersey), ATD Tools 70001 Infrared Thermometer (ATD Tools Inc, Wentzville, Missouri), Mastercraft Digital Temperature Reader (Mastercraft Canada, Toronto, Ontario, Canada), and Pro Point Infrared Thermometer (Princess Auto, Winnipeg, Manitoba, Canada). Data analysis was based on the skin surface temperature difference (ΔT in degrees Fahrenheit) between the wound site and an equivalent contralateral control site. One-way analysis of variance was used to compare the mean ΔT values for all the 5 thermometers, followed by post hoc analysis. Demographic data were analyzed using descriptive statistics. Interrater reliability was assessed for consistency using the intraclass correlation coefficient. No statistical difference was reported between the ΔT values for the 5 different thermometers (F4,514 = 0.339, P = .852). Post hoc analysis showed no significant difference when the thermometers were compared with the Exergen DermaTemp 1001, and Mastercool MSC52224-A (P = .987), ATD Tools 70001 Infrared Thermometer (P = .985), Mastercraft Digital Temperature Reader (P = .972), and Pro Point Infrared Thermometer (P = .774). The results for intraclass correlation demonstrated a high reliability and agreement between raters, as the intraclass correlation coefficient values for all thermometers were greater than 0.95. The results of this study demonstrate that less expensive, industrial-grade noncontact infrared thermometers have reliable temperature readings to identify and quantify the temperature gradients that along with other signs may be associated with deep and surrounding wound infection or tissue injury due to repeated microtrauma.


[Primary inoperable breast cancer].
2-5% of breast cancers are locally advanced (LABC). The standard treatment is neoadjuvant chemotherapy (NC) with an anthracycline-based regimen followed by surgery and adjuvant therapy. Pathological complete response (pCR) to NC is correlated to survival. However, only a small percentage of patients achieve pCR and the prognosis is poor. Addition of paclitaxel or docetaxel increases clinical and pathologic response rates. In addition trastuzumab seems effective. Prediction of treatment response may be guided by novel biotechnological approaches.


Polyoxygenated sterols from the Formosan soft coral Sinularia gibberosa.
Chemical investigation on the dichloromethane-soluble fraction from the EtOH extract of Sinularia gibberosa Tixier-Durivault has led to the isolation of three new polyoxygenated sterols, gibberoketosterols B (1) and C (2) and gibberoepoxysterol (3), along with two known steroids, gibberoketosterol (4) and 24-methylenecholest-5-en-3beta-ol (5). These cholestane-type sterols possessing a 22,24(28)-conjugated diene (1 and 2) in the side chain or a 5alpha,6alpha-epoxide in the B-ring (3) were isolated for the first time from marine sources. Compound 4 showed significant inhibition against the up-regulation of the pro-inflammatory iNOS and COX-2 proteins of LPS-stimulated RAW264.7 macrophage cells, while 1 was found to be inactive. The cytotoxicity of 1-4 toward a limited panel of cancer cell lines is also reported.


Antigen challenge of sensitized rats increases airway responsiveness to methacholine.
We measured airway responsiveness to methacholine (MCh) of highly inbred rats before and after six inhalational challenges with antigen. Ten Brown-Norway rats (130-216 g) that were actively sensitized to ovalbumin (OA) received six challenges with OA at 5-day intervals beginning 19 days after sensitization. An aerosol of OA (5% wt/vol) was inhaled for 1, 2, 5, and 10 min or until pulmonary resistance (RL) increased by at least 50%. Challenges with aerosolized MCh were performed immediately before and 14 days after sensitization, 2 days after the 3rd OA exposure, and 2, 7, 12, and 17 days after the 6th OA challenge. Four unsensitized rats underwent inhalational challenges with MCh over an equivalent time period. Responsiveness to MCh was calculated as the concentration of MCh required to increase RL to 200% of the control value (EC200RL). Seven out of 10 rats in the experimental group reacted to the first OA challenge with an immediate increase in RL of greater than 50% of control (range 70-550%). Three animals were unreactive to OA. Base-line EC200RL for all rats undergoing sensitization was 2.13 mg/ml (geometric mean), and it did not change significantly after sensitization (2.05 mg/ml). However, EC200RL of the rats that reacted to OA (n = 7) decreased significantly after 3 (1.11 mg/ml; P less than 0.005) and 6 OA exposures (0.96 mg/ml; P less than 0.005). The increase in responsiveness to inhaled MCh was present 17 days after the last OA exposure (EC200RL = 1.40 mg/ml; P less than 0.05). EC200RL of neither the unreactive sensitized rats (n = 3) nor the control rats (n = 4) changed after OA challenges.(ABSTRACT TRUNCATED AT 250 WORDS)


Vascular endothelial growth factor haplotypes are associated with severe ischaemic complications in giant cell arteritis regardless of the disease phenotype.
To determine whether functional vascular endothelial growth factor (VEGF) polymorphisms influence the expression of the clinical phenotype of giant cell arteritis (GCA). We also evaluated whether VEGF polymorphism is associated with the development of severe ischaemic manifestations in patients with GCA regardless of the clinical phenotype, classic cranial GCA or predominantly extracranial GCA large vessel vasculitis (LVV). VEGF rs833061 T/C, rs2010963 G/C and rs3025039 C/T polymorphisms were genotyped in 185 patients with biopsy-proven cranial GCA, 105 with extracranial LVV-GCA and 490 healthy controls. Allelic combinations (haplotypes) of VEGF were carried out. Comparisons were performed between patients with GCA and healthy controls as well as between patients with GCA stratified according to the clinical phenotype and the presence of severe ischaemic manifestations. No significant differences in genotype, allele, and haplotype frequencies of VEGF were found between patients with GCA and healthy controls as well as between GCA patients with the classic cranial pattern and the extracranial LVV-GCA pattern of the disease. However, the VEGF CGC haplotype (OR= 1.63 [1.05-2.53]) and the CGT haplotype (OR= 2.55 [1.10-5.91]) were significantly more frequent in GCA patients with severe ischaemic complications compared to those patients without these complications. VEGF haplotypes seem to play a role in the development of severe ischaemic manifestations in GCA patients, regardless of the clinical phenotype of expression of the disease.


Designing Atomically Dispersed Au on Tensile-Strained Pd for Efficient CO2 Electroreduction to Formate.
Pd is one of the most effective catalysts for the electrochemical reduction of CO2 to formate, a valuable liquid product, at low overpotential. However, the intrinsically high CO affinity of Pd makes the surface vulnerable to CO poisoning, resulting in rapid catalyst deactivation during CO2 electroreduction. Herein, we utilize the interaction between metals and metal-organic frameworks to synthesize atomically dispersed Au on tensile-strained Pd nanoparticles showing significantly improved formate production activity, selectivity, and stability with high CO tolerance. We found that the tensile strain stabilizes all reaction intermediates on the Pd surface, whereas the atomically dispersed Au selectively destabilizes CO* without affecting other adsorbates. As a result, the conventional COOH* versus CO* scaling relation is broken, and our catalyst exhibits 26- and 31-fold enhancement in partial current density and mass activity toward electrocatalytic formate production with over 99% faradaic efficiency, compared to Pd/C at -0.25 V versus RHE.


Comparison between urea removal in hemodialysis and continuous ambulatory peritoneal dialysis using a mathematical kinetic model.
Urea removal by continuous ambulatory peritoneal dialysis (CAPD) was compared with that by hemodialysis (HD) using a mathematical kinetic model. The time-averaged urea-nitrogen concentration (TAC) in the blood of a patient on maintenance HD was calculated by the model. Clearance with HD giving a TAC value equal to the constant urea-nitrogen concentration in the blood of a patient on CAPD was obtained, leading to the relation of equivalent clearances between HD and CAPD on the assumption that the urea-generation rate of the patient on CAPD was equal to that of the patient on HD.


Air entrapment in pressure monitoring lines.
Less than 1 ml of air/24 h was entrapped in the transducer dome attached to each of 4 commercially available pressurized continuous-infusion flush devices. If entrained into the circulation, this amount is less than the volume of gas associated with significant morbidity in most experimental animal studies. The amount was not increased by periodic fast flushing but was further reduced with the addition of an air-eliminating filter between the flush reservoir and the dome. Other methods to further reduce bubble formation in this flush-dome-patient (FDP) system are discussed.


Influence of soot on hydrophobic organic contaminant desorption and assimilation efficiency.
Soot, soot-amended sediment, and unamended sediment spiked with hydrophobic organic contaminants (HOC) were subjected to laboratory desorption and assimilation efficiency experiments in an effort to assess and compare the importance of soot in controlling HOC desorption and deposit-feeder assimilation efficiency. Three contaminants, naphthalene (NAP), benzo[a]pyrene (BaP), and hexachlorobenzene (HCB) were sorbed to sediments, sediments amended with soot (2-4% dry wt), and soot for a period of 34 d. Desorption of all three contaminants into seawater from the three prepared sorbates was then monitored, and Nereis succinea assimilation efficiency experiments on the BaP- and HCB-contaminated sorbates were conducted. Both NAP and BaP desorption rates for soot and soot-amended sediments were reduced by at least a factor of two relative to unamended sediment. Hexachlorobenzene desorption rates were similar for both the soot-amended and the unamended sediments. Results of N. succinea assimilation efficiency experiments indicate a trend similar to the desorption experiments: higher assimilation of BaP from unamended relative to soot-amended sediment and little difference in assimilation between treatments for HCB. However, soot was more effective in reducing BaP desorption than assimilation efficiency, which would be consistent with the hypothesis that the gut fluid dissolution by deposit feeders may partially decouple biological availability from chemical availability.


Cascade Energy Transfer and White-Light Emission in Chirality-Controlled Crystallization-Driven Two-Dimensional Co-assemblies from Donor and Acceptor Dye-Conjugated Polylactides.
Achieving predictable and programmable two-dimensional (2D) structures with specific functions from exclusively organic soft materials remains a scientific challenge. This article unravels stereocomplex crystallization-driven self-assembly as a facile method for producing thermally robust discrete 2D-platelets of diamond shape from biodegradable semicrystalline polylactide (PLA) scaffolds. The method involves co-assembling two PLA stereoisomers, namely, PY-PDLA and NMI-PLLA, which form stereocomplex (SC)-crystals in isopropanol. By conjugating a well-known Förster resonance energy transfer (FRET) donor and acceptor dye, namely, pyrene (PY) and naphthalene monoimide (NMI), respectively, to the chain termini of these two interacting stereoisomers, a thermally robust FRET process can be stimulated from the 2D array of the co-assembled dyes on the thermally resilient SC-PLA crystal surfaces. Uniquely, by decorating the surface of the SC-PLA crystals with an externally immobilized guest dye, Rhodamine-B, similar diamond-shaped structures could be produced that exhibit pure white-light emission through a surface-induced two-step cascade energy transfer process. The FRET response in these systems displays remarkable dependence on the intrinsic crystalline packing, which could be modulated by the chirality of the co-assembling PLA chains. This is supported by comparing the properties of similar 2D platelets generated from two homochiral PLLAs (PY-PLLA and NMI-PLLA) labeled with the same FRET pair.


Conversion of carbazole carboxamide based reversible inhibitors of Bruton's tyrosine kinase (BTK) into potent, selective irreversible inhibitors in the carbazole, tetrahydrocarbazole, and a new 2,3-dimethylindole series.
Incorporation of a suitably-placed electrophilic group transformed a series of reversible BTK inhibitors based on carbazole-1-carboxamide and tetrahydrocarbazole-1-carboxamide into potent, irreversible inhibitors. Removal of one ring from the core of these compounds provided a potent irreversible series of 2,3-dimethylindole-7-carboxamides having excellent potency and improved selectivity, with the additional advantages of reduced lipophilicity and molecular weight.


Interferon-α induces neurotoxicity through activation of the type I receptor and the GluN2A subunit of the NMDA receptor.
Elevated levels of interferon-alpha (IFNα) in the central nervous system (CNS) are linked to cognitive dysfunction in patients with inflammatory CNS diseases such as HIV-associated neurocognitive disorders (HAND). Increased CNS IFNα has also been found to be associated with cognitive dysfunction in a HAND mouse model. Here, we corroborate previous studies showing a dose-dependent decrease in dendritic branching and length caused by IFNα treatment and extend those studies. Because both direct and indirect mechanisms of IFNα-induced neurotoxicity are likely involved, the cell signaling pathway involving the IFNα receptor (IFNAR) was initially evaluated. Rat neuronal cultures exposed to IFNα demonstrate increased phosphorylation of STAT1 and increased interferon stimulating gene 15 (ISG15) expression, indicators of IFNAR engagement. However, specific blocking antibodies to the IFNAR were found to only partially protect neurons from IFNα-induced neurotoxicity. Additionally, inhibiting the GluN2A subunit of N-methyl-D-asparate receptor (NMDAR) was also found to be partially protective against IFNα-induced neurotoxicity compared with the GluN2B subunit. Neurotoxicity is evident in neurons extracted from IFNAR KO mice treated with IFNα as well, further indicating that IFNAR signaling is not required for IFNα neurotoxicity. The neurotoxic actions of IFNα are mediated through both the IFNAR as well as the GluN2A subunit of the NMDAR to reduce dendritic arborization in neurons. Complete protection from IFNα-induced neurotoxicity was demonstrated when both pathways were blocked. Blocking these pathways could lead to potential therapies for cognitive dysfunction during neuroinflammation and specifically lead to better treatments for HAND.


Platinum(II)-Crosslinked Single-Chain Nanoparticles: An Approach towards Recyclable Homogeneous Catalysts.
We introduce the synthesis and in-depth characterization of platinum(II)-crosslinked single-chain nanoparticles (PtII -SCNPs) to demonstrate their application as a recyclable homogeneous catalyst. Specifically, a linear precursor copolymer of styrene and 4-(diphenylphosphino)styrene was synthesized via nitroxide-mediated polymerization. The triarylphosphine ligand moieties along the backbone allowed for the intramolecular crosslinking of single chains via the addition of [Pt(1,5-cyclooctadiene)Cl2 ] in dilute solution. The successful formation of well-defined PtII -SCNPs was evidenced by size exclusion chromatography, dynamic light scattering, nuclear magnetic resonance (1 H, 31 P{1 H}, 195 Pt), and diffusion-ordered spectroscopy. Finally, the activity of the PtII -SCNPs as homogeneous, yet recyclable catalyst was successfully demonstrated using the example of the amination of allyl alcohol.


PFG-NMR measurements of the self-diffusion coefficients of water in equilibrium poly(HEMA-co-THFMA) hydrogels.
The self-diffusion coefficients for water in a series of copolymers of 2-hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA, swollen with water to their equilibrium states have been studied at 310 K using PFG-NMR. The self-diffusion coefficients calculated from the Stejskal-Tanner equation, D(obs), for all of the hydrated polymers were found to be dependent on the NMR storage time, as a result of spin exchange between the proton reservoirs of the water and the polymers, reaching an equilibrium plateau value at long storage times. The true values of the diffusion coefficients were calculated from the values of D(obs) in the plateau regions by applying a correction for the fraction of water protons present, obtained from the equilibrium water contents of the gels. The true self-diffusion coefficient for water in polyHEMA obtained at 310 K by this method was 5.5 x 10(-10) m(2)s-1. For the copolymers containing 20% HEMA or more a single value of the self-diffusion coefficient was found, which was somewhat larger than the corresponding values obtained for the macroscopic diffusion coefficient from sorption measurements. For polyTHFMA and copolymers containing less than 20% HEMA, the PFG-NMR stimulated echo attenuation decay curves and the log-attenuation plots were characteristic of the presence of two diffusing water species. The self-diffusion coefficients of water in the equilibrium-hydrated copolymers were found to be dependent on the copolymer composition, decreasing with increasing THFMA content.


What is the Role of Hyaluronic Acid Ester in Myringoplasty? Systematic Review and Meta-Analysis.
To reveal odds of tympanic membrane closure and postoperative hearing outcomes for myringoplasty utilizing hyaluronic acid ester via systematic review and meta-analysis. 1) Search of English articles in PubMed/Medline, Embase, and Cochrane databases published between January 1, 1998 and March 31, 2018. Inclusion criteria: 1) English language; 2) clinical studies; 3) reported posttreatment perforation status, hearing outcomes, or complications. hyaluronic acid used for middle ear packing or topical application of hyaluronic acid solution. Number of patients, surgical technique, mean age, overall rate of tympanic membrane closure, success rate based on size of perforation, mean air-bone gap improvement, and postoperative speech scores and complications. Ten studies encompassing 531 patients met criteria. Reported success rates for closure of chronic perforation ranged from 70.0 to 92.7% (mean, 85.21%). Smaller perforation predicted success in complete closure. Mean air-bone gap closure was 10.6 dB (4-24 dB). There were five complications reported. Meta-analysis was performed on five studies. No difference was noted in the success rates between hyaluronic acid ester myringoplasty and conventional tympanoplasty using fascia or perichondrium, with an overall closure rates of 89.8 and 89.4%, respectively (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.59-1.82, p = 0.896). A higher closure rate was seen in hyaluronic acid ester myringoplasty (87.9%) when compared with fat graft myringoplasty (70.8%), (OR 3.01, 95% CI 1.42-6.35, p = 0.004). Hyaluronic acid (HA) ester myringoplasty appears to be safe and effective at attaining complete closure of tympanic membrane perforation, although there exists significant selection bias and inconsistent reporting among existing papers.


Comparative Analysis of the Extracellular Matrix Composition in Proliferating and Involuted Infantile Hemangiomas.
Changes in the composition of the extracellular matrix (ECM) occur between the proliferating and involuted phases of infantile hemangiomas (IH), and are associated with angiogenic growth. We examined the composition of the ECM in proliferating and involuted IHs and assessed correlations between the composition of the ECM and whether the IH was in the proliferating or the involuted phase. We evaluated IH samples from a cohort of patients who had five proliferating IHs and five involuted IHs. The following ECM molecules were analyzed using enzyme-linked immunosorbent assays and immunohistochemistry: laminin, fibronectin, collagen type I, collagen type II, and collagen type III. The involuted IHs had higher levels of deposition of collagen type III than the proliferating IHs. The median values (interquartile ranges) were 1.135 (0.946-1.486) and 1.008 (0.780-1.166) (P=0.019), respectively. The level of laminin was higher in involuted IHs than in proliferating IHs, with median values (interquartile ranges) of 3.191 (2.945-3.191) and 2.479 (1.699-3.284) (P=0.047), respectively. Abundant collagen type III staining was found in involuted IHs. Laminin α4 chain staining was clearly present within the basement membrane adjacent to the blood vessels, and was significantly more intense in involuted IHs than in proliferative IHs. Involuted hemangiomas showed extensive deposition of collagen III and laminin, suggesting that differences in the composition of the ECM reflect stages of the development of IHs. This pattern may be due to the rapid senescence of IHs.


Food pathogens as the most common cause of bacterial food poisoning.
The aim of the paper was to characterize the food borne microorganisms, which are the most common causes of bacterial food poisonings in humans. Furthermore, the dietary recommendations in acute gastro-intestinal disorders were presented.


Cytologic diagnosis of ciliated hepatic foregut cyst.
Ciliated hepatic foregut cyst (CHFC) is a rare, benign, solitary cyst occurring most often in the left lobe of the liver. CHFCs are typically found incidentally during radiologic imaging, surgical exploration, or autopsy. Only six cases of CHFC diagnosed by fine needle aspiration have been reported in the literature. We describe a CHFC diagnosed by aspiration in a 70-yr-old woman who presented with a 2-yr history of abdominal discomfort. The radiologically benign-appearing lesion was located in the subcapsular area of segment IV of the liver. The aspirate contained benign ciliated columnar cells and goblet cells suspended in mucoid material. Sections from a cell block demonstrated pseudo-stratified bronchial-type epithelium with mucin secreting cells and an absence of cartilage, characteristic of CHFC. Mucin-containing goblet cells stained with alcian blue. The neuroendocrine cells within the bronchial-type epithelium stained for calcitonin and synaptophysin. On follow-up, a computed tomography (CT) demonstrated the cyst to be unchanged, but as the patient continued to have pain, sclerosis of the cyst was planned. The diagnosis of CHFC by fine needle aspiration and its distinction from other solitary cysts of the liver may prevent unnecessary surgical exploration and excision.


Reticulocyte hemoglobin measurement--comparison of two methods in the diagnosis of iron-restricted erythropoiesis.
The aims of this study were to diagnose iron-restricted erythropoiesis (functional iron deficiency) in patients with classic iron deficiency (ID), anemia of chronic disease (ACD) and the combined state of ID/ACD with the use of two hematological methods for the measurement of reticulocyte hemoglobinization. In comparison, the biochemical markers of iron status were determined. We studied 474 anemic patients admitted to hospital with a broad spectrum of diseases. We measured indicators of reticulocyte hemoglobinization. CHr was determined on an Advia 120 hematology analyzer. A Sysmex XE-2100 hematology analyzer was used to determine RET-Y, the forward scatter of fluorescence-labeled reticulocytes, which can also be expressed as the reticulocyte hemoglobin equivalent (RET-H(e)), as well as RBC-Y, the forward scatter of fluorescence-labeled erythrocytes, which can be expressed as the erythrocyte hemoglobin equivalent. Ferritin, soluble transferrin receptor (sTfR) and the sTfR/log ferritin ratio (sTfR-F index) were used as biochemical markers. The comparison of RET-Y with CHr demonstrated an excellent curvilinear relationship between the two parameters. The normal reference range for Ret-Y was 1630-1860 arbitrary units (AU); mathematical transformation to RET-H(e) gave a range of 28.2-35.7 pg. Correlations of biochemical iron markers with RET-H(e) were as weak as with CHr in patients with ACD and acute phase response. In a diagnostic plot to identify iron status, RET-H(e) could replace CHr without any loss of sensitivity or specificity. Patient mismatch analysis between RET-H(e) and CHr in the diagnostic plot demonstrated agreement for 449 of 474 patients (94.4%). Patient specific anemia mismatches were 2.9-6.2%. According to our results, the indicators of reticulocyte hemoglobinization, RET-H(e) and CHr, measure the same phenomenon. RET-H(e) is as valuable as CHr for the diagnosis of iron-restricted erythropoiesis. The combination of RET-H(e) and the sTfR-F index in a diagnostic plot offers an attractive tool for the evaluation of iron status and identification of the progression of ID.


Genetically encoded stress indicator for noninvasively imaging endogenous corticosterone in living mice.
Physical and emotional stress is one of the major controllers of physiological reactions and homeostasis in living animals. A stress hormone, corticosterone, is secreted from the adrenal cortex into the blood vessels when animals sense the stress. The quantitative evaluation of corticosterone in living animals has been limited because of the unavailability of suitable methods in vivo. For a noninvasive molecular imaging of the stress, we developed a method for detecting physiological increases in the endogenous corticosterone caused by exo- and endogenous stress in living animals. We constructed a pair of genetically encoded indicators composed of cDNAs of glucocorticoid receptor (GR), split Renilla luciferase (RLuc), and a Synechocystis sp. DnaE intein. The GR fused with C-terminal halves of RLuc and DnaE is localized in the cytosol, whereas a fusion protein of N-terminal halves of RLuc and DnaE is localized in the nucleus. If corticosterone induces GR translocation into the nucleus, the C-terminal RLuc meets the N-terminal one in the nucleus, and full-length RLuc is reconstituted by protein splicing with DnaE. Cell-based methods provided a quantitative bioluminescence assay of the extent of GR translocation into the nucleus. We further demonstrated that the indicator enabled noninvasive imaging against two different types of imposed stress: a forced swimming and metabolic perturbation caused by 2-deoxy-D-glucose. This stress indicator should be valuable for screening pharmacological compounds and for tools to study the mechanism of physiological stress.


Mental health literacy of school nurses in the United Arab Emirates.
To support promotion, prevention and early intervention for mental illness school nurses need to be mental health literate. Three hundred and thirty-nine school nurses employed in government and private schools from three Emirates in the UAE were surveyed. A culturally adapted Mental Health Literacy questionnaire comprising three vignettes of fictional characters meeting diagnostic criteria for the target conditions along with the Kessler Psychological Distress Scale (K10) was administered to ascertain school nurses' ability to correctly identify the conditions and to elicit beliefs about helpfulness of treatment interventions and of health care providers for these conditions. Less than 50% of the respondents correctly identified the disorders presented, while accurate identification of evidence-based interventions was also limited. Correlations between level of psychological distress and level of inaccurate survey responses was also revealed, respondents who correctly identified the correct diagnosis of the vignette and the most appropriate interventions were those who had a significantly lower K10 score. Low levels of mental health literacy amongst respondents in combination with potential religious and cultural factors as reported in the literature, highlight the need for curriculum enhancements for future health professionals and a targeted program of culturally appropriate professional development focused on mental health promotion for those in clinical practice. The level of psychological distress noted in this cohort also signals a need to ensure that appropriate supports are available for clinical staff employed in schools.


Training meals on wheels volunteers as health literacy coaches for older adults.
Homebound older adults constitute a "hardly reached" population with respect to health communication. Older adults also typically suffer from health literacy challenges, which put them at increased risk of adverse health outcomes. Suboptimal interactions with providers are one such challenge. Interventions to improve interactive health literacy focus on training consumers/patients in question preparation and asking. Meals on Wheels volunteers are uniquely suited to coach their clients in such interaction strategies. Seventy-three Meals on Wheels volunteers participated in workshops to train as health literacy coaches. The 3- to 4-hour workshops included units on communicating with older adults, on the nature of health literacy, and on the process of interactive health literacy coaching. Participants viewed and discussed videos that modeled the targeted communication behaviors for older adult patients interacting with physicians. They role-played the coaching process. After 9 months, coaches participated in a "booster" session that included videos of ideal coaching practices. Evaluation questionnaires revealed that participants had favorable reactions to the workshops with respect to utility and interest. They especially appreciated learning communication skills and seeing realistic videos. A measure of knowledge about the workshop material revealed a significant increment at posttest. Fidelity of coaching practices with respect to workshop curriculum was confirmed. This training in interactive health literacy for community-based lay volunteers constitutes one way to implement the National Action Plan to Improve Health Literacy for one "hardly reached" population. An online tool kit containing all workshop materials is available.


Employees' Job Satisfaction: A Test of the Job Characteristics Model Among Social Work Practitioners.
The present article describes an investigation of the Job Characteristics Model (JCM) by Hackman and Oldham (1976) for the prediction of job satisfaction of employees in social work areas. While there is considerable evidence for the JCM with respect to profit-oriented organizations, it was tested whether it can also be applied to the non-profit sector. The present study surveyed 734 holders of jobs in social work in Germany in order to assess their job satisfaction and the core variables of the JCM (i.e., the five job characteristics and the three psychological states). Regression and mediation analyses were used to examine the relations between these variables. The results showed that the expected relations were remarkably in accordance with the findings from the for-profit sector. All model variables correlated positively with job satisfaction, with the psychological states showing higher coefficients than the job characteristics. In addition, the influence of job characteristics on job satisfaction was significantly mediated through the psychological states. These findings were supported by a replication study. Implications of the JCM for practice, in particular for assessment and interventions in social work organizations, are discussed.


Management of acute heart failure.
Acute heart failure may be defined as the failure of the circulation to supply the demands of metabolising tissues due to acute cardiac dysfunction. First aid measures aimed at reducing symptomatology should be chosen with respect to their ability to improve cardiac function. The use of diuretics in acute heart failure does not sit well with the principle of improving cardiac function whereas the use of vasodilators does. As with any circulatory disturbance treatment must be guided by appropriate monitoring and the demands of metabolizing tissues must be reduced. Inotropes should be reserved for severe cases where other treatments have failed. This is to avoid the increased myocardial oxygen demand as a result of inotrope use.


Inhibition of (-)-trans-(1S,2S)-U50488 hydrochloride by its enantiomer in white mice -- a placebo-controlled, randomized study.
Previous studies have been performed to see if toxicity of optically active compounds may be inhibited by potentized preparations of their enantiomers. The present study is based on the hypothesis that the toxic effects of an optical isomer may be counteracted or reversed by the administration of a potentized preparation of one of its stereoisomers and in particular the enantiomer (patent applied for). The design was prospective, blind, randomized, and placebo-controlled. 210 ICR conventional mice were used. 105 mice were administered a mixture of (+)-U50488 hydrochloride homeopathic potencies prior to and during the experiment, and the other 105 were administered indistinguishable placebo. The first 52 mice were used to establish an LD(50) of intraperitoneally administered (-)-U50488 hydrochloride under the conditions of this experiment. The estimated LD(50) was 25 mg/kg. The remaining 158 mice were then administered this LD(50) of (-)-U50488 HCl intraperitoneally. One mouse from the placebo group was excluded from the analysis because it died immediately after the possibly intravenous injection of (-)-U50488 HCl. 67% of homeopathy mice survived compared with 47% of placebo mice. The end point for statistical analysis was the difference in survival between the placebo and homeopathy mice. The analysis was adjusted for mouse weight using a logistic regression (LR) model. The LR treatment odds ratio for survival of treatment mice relative to placebo mice was 2.301 and the LR treatment chi-square was 6.2030 (1 degree of freedom), which has a p-value of 0.0128. Consequently, we reject the null hypothesis of no treatment effect on survival. We conclude that toxicity of intraperitoneal injection of (-)-U50488 hydrochloride may be inhibited by administration of a mixture of potencies of its enantiomer.