[Effect of Ju-Pi-Tang on Cisplatin-induced Emetic Model in Minks].
To study the antiemetic effect of Ju-Pi-Tang from Jin Kui Yao Lue on cisplatin-induced emetic model in minks, and to observe the immunoexpression of peripheral and central c-fos and substance P. The minks were randomly divided into blank control group, Ju-Pi-Tang blank control group, model group, ondansetron group, aprepitant group, Ju-Pi-Tang (in high-, mid-, and low-dose) groups. Every group was administered with the antiemetic agent or distilled water on 24 h before cisplatin injection. The antiemetic effect of drugs was investigated in the emetic model of minks induced by cisplatin in 72 h observation. Immunohistochemistry was used to compare the differences of c-fos and substance P expression in the area postrema of brain and distal ileum tissues. During observation period,compared with model group,the frequency cisplatin induced retching and vomiting was significantly reduced by Ju-Pi-Tang in high- and mid-dose groups, during the 0-24 h acute period, the number of retching of Ju-Pi-Tang in high-dose group was decreased more than aprepitant group, during the 24-72 h delayed period, the number of both retching and vomiting was decreased more than ondansetron group, after 72 h of cisplatin administration, compared with model group, the grey levels of c-fos and substance P expression in distal ileum and brain tissues of Ju-Pi-Tang groups were higher significantly. Ju-Pi-Tang has a good effect against cisplatin-induced emesis in minks.


Memory processes in delayed spatial discriminations: response intentions or response mediation?
Pigeons were trained on a pair-comparison task in which left versus right choices were reinforced following different sequences of two center-key stimuli. Choice accuracy was higher when retention intervals occurred after the entire sequence than when they separated the two stimuli comprising it, and this effect occurred independently of whether the initial and terminal stimuli came from the same or different dimensions. The initial stimulus from the prior trial was a source of proactive interference only in groups for which the retention interval separated the two sequence stimuli. By contrast, differential delay-interval behavior was observed only in groups for which the retention interval followed presentation of the entire sequence. These results indicate that coding processes in delayed discriminations are influenced by the location of the retention interval, and that response mediation affects retention performances if the reinforced choice can be determined prior to the interval.


The technique of endovascular intracranial revascularization.
Intracranial atherosclerosis was traditionally believed to carry a risk of stroke of 8% to 22% per annum. The annualized stroke rate in the recent stenting and aggressive medical management for preventing stroke in intracranial stenosis (SAMMPRIS) trial medical management arm was 12.2%. This trial was halted due to excessive periprocedural events in the stent arm. This stroke rate is still unacceptably, high and a treatment strategy is still needed. SAMMPRIS has no bearing on angioplasty alone. Angioplasty alone has always been our primary intervention for intracranial atherosclerosis and remains so to this day due to its relative simplicity, low complication rate, and efficacy. We have, however, made adjustments to our patient management regimen based on the results of SAMMPRIS. This paper outlines our current patient selection, procedural technique, and post-procedure management. The complications we have encountered while developing our technique are described along with how to avoid them and how to manage them. Our most recent results (since previous publications) are also discussed.


[Synthesis and antiulcer activity of 2-amino-8H-indeno[1,2-d]thiazole derivatives].
A series of 8H-indeno[1,2-d]thiazoles containing various N-substituted amino groups at the 2 position were synthesized by the reaction of 2-bromo-indanones and N-substituted thioureas. Their anti-ulcerous activity was evaluated. Alkylamino derivatives have a more potent inhibitory behavior on ethanol-induced gastric ulcers compared with arylamino derivatives. We also studied the effect of various substituents on the both benzene and pyridine ring of 2-pyridylamino derivatives on ethanol-induced gastric ulcers. However no clear effects were observed. Among 3-morpholinopropylamino derivatives, 5-isopropyl- (21) and 7-chloro-2-(3-morpholinopropyl)amino-8H-indeno[1,2-d]thiazole (25) showed a considerably stronger inhibitory behavior on hydrochloric acid-induced gastric ulcers than cetraxate hydrochloride. Furthermore, 3-morpholinopropylamino derivatives have potent inhibitory effects on gastric acid secretion in pylorus ligated rats.


Dominance and parent-of-origin effects of coding and non-coding alleles at the acylCoA-diacylglycerol-acyltransferase (DGAT1) gene on milk production traits in German Holstein cows.
Substantial gene substitution effects on milk production traits have formerly been reported for alleles at the K232A and the promoter VNTR loci in the bovine acylCoA-diacylglycerol-acyltransferase 1 (DGAT1) gene by using data sets including sires with accumulated phenotypic observations of daughters (breeding values, daughter yield deviations). However, these data sets prevented analyses with respect to dominance or parent-of-origin effects, although an increasing number of reports in the literature outlined the relevance of non-additive gene effects on quantitative traits. Based on a data set comprising German Holstein cows with direct trait measurements, we first confirmed the previously reported association of DGAT1 promoter VNTR alleles with milk production traits. We detected a dominant mode of effects for the DGAT1 K232A and promoter VNTR alleles. Namely, the contrasts between the effects of heterozygous individuals at the DGAT1 loci differed significantly from the midpoint between the effects for the two homozygous genotypes for several milk production traits, thus indicating the presence of dominance. Furthermore, we identified differences in the magnitude of effects between paternally and maternally inherited DGAT1 promoter VNTR - K232A haplotypes indicating parent-of-origin effects on milk production traits. Non-additive effects like those identified at the bovine DGAT1 locus have to be accounted for in more specific QTL detection models as well as in marker assisted selection schemes. The DGAT1 alleles in cattle will be a useful model for further investigations on the biological background of non-additive effects in mammals due to the magnitude and consistency of their effects on milk production traits.


Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein.
In the cell nucleus the NS1 protein of influenza A virus inhibits both pre-mRNA splicing and the nuclear export of mRNAs. Both the RNA-binding and effector domains of the protein are required for these nuclear functions. Here we demonstrate that the NS1 protein has a latent nuclear export signal (NES) that is located at the amino end of the effector domain. In uninfected, transfected cells the NS1 protein is localized in the nucleus because the NES is specifically inhibited by the adjacent amino acid sequence in the effector domain. Substitution of alanine residues for specific amino acids in the adjacent sequence abrogates its inhibitory activity, thereby unmasking the NES and causing the full-length NS1 protein to be localized to the cytoplasm. In contrast to uninfected cells, a substantial amount of the NS1 protein in influenza virus-infected cells is located in the cytoplasm. Consequently, the NES of these NS1 protein molecules is unmasked in infected cells, indicating that the NS1 protein most likely carries out functions in the cytoplasm as well as the nucleus. A dramatically different localization of the NS1 protein occurs in cells that are infected by a virus encoding an NS1 protein lacking the NES: the shortened NS1 protein molecules are almost totally in the nucleus. Because the NES of the full-length NS1 protein is unmasked in infected but not uninfected cells, it is likely that this unmasking results from a specific interaction of another virus-specific protein with the NS1 protein.


Cutaneous metastasis of extraskeletal osteosarcoma arising in the mediastinum.
Cutaneous metastases have been reported in 5%-10% of patients with internal malignancy. The most common clinical features are the sudden appearance of discrete, firm, and nontender nodules in a particular area of the body. The most frequent metastatic site of extraskeletal osteosarcoma (ESOS) is the lungs. Cutaneous metastasis of ESOS is rare. To our knowledge, only one case of ESOS has been reported with skin metastasis, histopathologically classified as the osteoblastic subtype. Here, we describe a case of chondroblastic ESOS arising in the mediastinum with metastasis to the skin. Our patient presented with a scalp nodule after diagnosis of primary ESOS at the mediastinum.


Genomic analyses of bacterial porin-cytochrome gene clusters.
The porin-cytochrome (Pcc) protein complex is responsible for trans-outer membrane electron transfer during extracellular reduction of Fe(III) by the dissimilatory metal-reducing bacterium Geobacter sulfurreducens PCA. The identified and characterized Pcc complex of G. sulfurreducens PCA consists of a porin-like outer-membrane protein, a periplasmic 8-heme c-type cytochrome (c-Cyt) and an outer-membrane 12-heme c-Cyt, and the genes encoding the Pcc proteins are clustered in the same regions of genome (i.e., the pcc gene clusters) of G. sulfurreducens PCA. A survey of additionally microbial genomes has identified the pcc gene clusters in all sequenced Geobacter spp. and other bacteria from six different phyla, including Anaeromyxobacter dehalogenans 2CP-1, A. dehalogenans 2CP-C, Anaeromyxobacter sp. K, Candidatus Kuenenia stuttgartiensis, Denitrovibrio acetiphilus DSM 12809, Desulfurispirillum indicum S5, Desulfurivibrio alkaliphilus AHT2, Desulfurobacterium thermolithotrophum DSM 11699, Desulfuromonas acetoxidans DSM 684, Ignavibacterium album JCM 16511, and Thermovibrio ammonificans HB-1. The numbers of genes in the pcc gene clusters vary, ranging from two to nine. Similar to the metal-reducing (Mtr) gene clusters of other Fe(III)-reducing bacteria, such as Shewanella spp., additional genes that encode putative c-Cyts with predicted cellular localizations at the cytoplasmic membrane, periplasm and outer membrane often associate with the pcc gene clusters. This suggests that the Pcc-associated c-Cyts may be part of the pathways for extracellular electron transfer reactions. The presence of pcc gene clusters in the microorganisms that do not reduce solid-phase Fe(III) and Mn(IV) oxides, such as D. alkaliphilus AHT2 and I. album JCM 16511, also suggests that some of the pcc gene clusters may be involved in extracellular electron transfer reactions with the substrates other than Fe(III) and Mn(IV) oxides.


[Serum growth hormone and prolactin levels in neonates with hypoxic-ischemic encephalopathy].
To investigate the levels and roles of serum growth hormone (GH) and prolactin (PRL) in neonatal hypoxic-ischemic encephalopathy (HIE). Serum GH and PRL levels were measured by radioimmunoassay in 54 neonates with HIE (20 mild, 19 moderate and 15 severe HIE) at the acute and convalescence stages. Twenty normal neonates were used as controls. Serum GH levels were significantly lower, but PRL levels were significantly higher in moderate and severe HIE neonates at the acute stage compared with those of controls and mild HIE neonates (P < 0.01). There were noticeable differences in serum levels of GH and PRL between the moderate and severe HIE cases (P < 0.01). During the convalescence stage, serum GH levels increased and PRL levels decreased in moderate and severe HIE neonates compared with those at the acute stage (P < 0.01); serum GH and PRL levels in each sub-group of HIE restored to the levels of controls. There was a closely negative correlation between GH and PRL levels at the acute stage of HIE (r = -0.8759, P < 0.01). GH and PRL might be involved in the pathophysiological process of HIE. The levels of GH and PRL closely relate to the severity of HIE at the acute stage.


Psychiatric diagnoses in sexual harassment cases.
Forty-four women and three men who were plaintiffs in sexual harassment and sexual discrimination cases were evaluated by experts for the plaintiffs and by the author, an expert in these cases, for the defense. There were considerable differences in the diagnostic assessments. Some reasons for these differences and their implications for forensic evaluations are discussed.


Cadmium sorption, influx, and efflux at the mesophyll layer of leaves from ecotypes of the Zn/Cd hyperaccumulator Thlaspi caerulescens.
Differential sorption and transport characteristics of the leaf mesophyll layer of the Prayon and Ganges ecotypes of the hyperaccumulator Thlaspi caerulescens were examined. (109)Cd influx and efflux experiments were conducted with leaf sections, and X-ray absorption near edge structure (XANES) data were collected from leaves as a general comparison of in vivo cadmium (Cd) coordination. There were modest differences in cell wall sorption of Cd between ecotypes. There were obvious differences in time- and concentration-dependent Cd influx, including a greater V(MAX) for Prayon but a lower K(M) for Ganges for concentration-dependent Cd uptake and a notably greater Cd uptake by Ganges leaf sections at 1000 microm Cd. Leaf sections of Prayon had a greater Cd efflux than Ganges. The XANES spectra from the two ecotypes suggested differences in Cd coordination. The fundamental differences observed between the two ecotypes may reflect differential activity and/or expression of plasma membrane and tonoplast transporters. More detailed study of these transporters and the in vivo coordination of Cd are needed to determine the contribution of these processes to metal homeostasis and tolerance.


Diagnostics for generalized linear hierarchical models in network meta-analysis.
Network meta-analysis (NMA) combines direct and indirect evidence comparing more than 2 treatments. Inconsistency arises when these 2 information sources differ. Previous work focuses on inconsistency detection, but little has been done on how to proceed after identifying inconsistency. The key issue is whether inconsistency changes an NMA's substantive conclusions. In this paper, we examine such discrepancies from a diagnostic point of view. Our methods seek to detect influential and outlying observations in NMA at a trial-by-arm level. These observations may have a large effect on the parameter estimates in NMA, or they may deviate markedly from other observations. We develop formal diagnostics for a Bayesian hierarchical model to check the effect of deleting any observation. Diagnostics are specified for generalized linear hierarchical NMA models and investigated for both published and simulated datasets. Results from our example dataset using either contrast- or arm-based models and from the simulated datasets indicate that the sources of inconsistency in NMA tend not to be influential, though results from the example dataset suggest that they are likely to be outliers. This mimics a familiar result from linear model theory, in which outliers with low leverage are not influential. Future extensions include incorporating baseline covariates and individual-level patient data.


Maternal fish consumption during pregnancy and risks of wheezing and eczema in childhood: the Generation R Study.
Maternal fish consumption during pregnancy might influence the fetal immune system through anti-inflammatory effects of omega-3 fatty acids, and might affect the risks of childhood asthma and atopy. In Generation R, a prospective cohort study in the Netherlands, we examined the associations of first trimester fish consumption with childhood wheezing and eczema in the first 4 years of life. In total, 2976 mothers completed a 293-item semiquantitative food frequency questionnaire covering dietary intake in the first trimester. The occurrence of wheezing and eczema was yearly assessed by questionnaires. Median weekly fish consumption was 83 (95% range 0-316) grams per week. We observed no consistent associations of maternal total-, lean- or fatty-fish consumption during pregnancy with the risks of childhood wheezing. Maternal shellfish consumption of 1-13 g per week was associated with overall increased risks of childhood wheezing and eczema (OR 1.20 (1.04, 1.40) and OR 1.18 (1.01, 1.37), respectively). Maternal fatty fish consumption of 35-69 g per week was associated with increased overall risks of childhood eczema (OR 1.17 (1.00, 1.38)), but maternal total- or lean-fish consumption was not. During pregnancy, shellfish consumption was associated with increased risks of wheezing and eczema, while fatty fish consumption was associated with a higher risk of eczema only. Maternal total fish or lean fish consumption were not associated with wheezing or eczema. Further studies are needed to replicate these findings and to explore underlying mechanisms.


Organ weights in healthy and apparently healthy Danish infants.
The weights of brain, heart, liver, kidneys, spleen, lungs, and thymus were registered in 222 forensic autopsies of Danish infants aged 1 week to 0.99 year (137 males, 85 females), who prior to death were healthy or apparently healthy based on clinical evidence. Variability of organ weights was estimated, and the relationship between individual organ weights and age, body weight, and body length, and the sum of organ weights was evaluated in relation to age, body weight, and body length. No significant differences were found between males and females, and between the healthy and apparently healthy infants. There was a positive, significant correlation of the individual organ weights with age, body weight, and body length. It was most pronounced for the weight of the brain and least pronounced for the thymus. Am. J. Hum. Biol. 9:35-38 © 1997 Wiley-Liss, Inc.


Comparison of the fertilizing capability of spermatozoa from ejaculates, epididymal aspirates and testicular biopsies using intracytoplasmic sperm injection.
A prospective study was carried out to compare the fertilizing capability and pregnancy outcome following intracytoplasmic sperm injection (ICSI) using spermatozoa obtained from ejaculates, or surgically from epididymis or seminiferous tubules. A total of 77 ICSI cycles (one per patient) was included. In all, 28 patients had severe oligoasthenoteratozoospermia, 19 patients had obstructive azoospermia and 30 patients had non-obstructive azoospermia. The main outcome measures were fertilization rate per injected metaphase II oocyte and the clinical pregnancy rate per embryo transferred back to the female recipients. In patients with severe oligoasthenoteratozoospermia, the fertilization and pregnancy rates were 79 and 25 %. In patients with obstructive azoospermia, for whom epididymal spermatozoa were used, these were 75 and 28%, and in the non-obstructive group for which testicular spermatozoa were used for injection, they were 69 and 21% respectively. These rates were not significantly different in the three groups (P = 0.85 and P = 0.14 respectively), suggesting that spermatozoa from the ejaculates and epididymal or testicular biopsies are able to fertilize equally by using ICSI. Live birth per embryo transfer was significantly reduced in patients with non-obstructive azoospermia compared to the other two groups. The high abortion rate (50%) in the group in which testicular spermatozoa were used raises doubts about the developmental competence of such embryos.


The effects of novel vasodilator long chain acyl carnitine esters in the isolated perfused heart of the rat.
1. The effects of palmitoyl carnitine (PC) and novel derivatives were examined on the isolated Langendorff perfused heart of the rat. 2. Bolus injections of PC (1-300 nmol) produced coronary constriction accompanied by a cumulative irreversible depression of contractility. 3. Prior storage of PC in chloroform containing 2% ethanol in heat-sealed ampoules resulted in production of the ethyl ester of the compound (PCE). This compound was isolated and also synthesized (P1E). In contrast to PC, both PCE and P1E exhibited potent vasodilator activity. 4. Increasing the fatty acid chain length from palmitoyl to stearoyl resulted in a significant reduction in coronary dilator activity of the ester compound, whereas different ester groups did not affect the vasodilator action appreciably. Complete removal of the fatty acid chain abolished all vascular effects at the doses used. 5. The vasodilatation produced by these acyl carnitine esters was comparable to that produced by several known vasodilator drugs including verapamil, cromakalim, amyl nitrate and iloprost; however, the duration of the vasodilator response was more prolonged with the carnitate derivatives.


[Successful treatment with rituximab in two cases of IgM-monoclonal gammopathy of undetermined significance (MGUS) neuropathy].
A 66-year-old male was hospitalized with muscle weakness and gait disturbance. Examination revealed IgM 3,407 mg/dl (IgM, κ-type M protein) and he was diagnosed as having IgM-MGUS neuropathy. He suffered from paralysis of respiratory muscles and required a respirator support. Plasmapheresis and intravenous immunoglobulin were performed and he was weaned from the respirator. Rituximab given as 8 weekly infusions improved gait disturbance. A 71-year-old male was hospitalized with lumbago, numbness of lower extremities and gait disturbance. Examination revealed IgM 1,553 mg/dl (IgM, λ-type M protein) and he was diagnosed with IgM-MGUS neuropathy. Rituximab given as 8 weekly infusions improved gait disturbance. It was concluded that rituximab is a well-tolerated treatment that may be effective in some patients with IgM-MGUS neuropathy.


[Assessing Change of Depressive Symptoms and Severity of Depression in an Inpatient Setting : Performance of the HoNOS (Health of the Nation Outcome Scales)].
Objectives This study investigates the assessment of change of depressive symptoms and severity of depression with the "Health of the Nation Outcome Scales" (HoNOS) in an inpatient setting. Method Participants were 132 adults diagnosed with depressive disorder (F32: n=102; F33: n=30). Bivariate correlations were used to determine the correlation of the HoNOS with self-reported (BDI) and observer-rated depressive symptoms (HAMD). The predictive validity of the HoNOS was analysed with linear regression models. Results The HoNOS differentiated significantly between patients with moderate versus severe depression at baseline (p<0,05). It correlated with the HAMD change score (r=0,25, p<0,008), but not with the BDI change score (r=0,19, p>0,008).The HoNOS was not a significant predictor of observer-rated depression at discharge (β=0,03, p>0,05). Conclusion As the HoNOS only partially seems to assess the change and severity of depressive symptoms, it should only be used in combination with depression-specific instruments.


[Magnetic stimulation in the diagnosis of diseases of the central and peripheral nervous systems].
Magnetic stimulation of the cerebral cortex and roots CVI--CVII and LII--LIV was performed in 19 healthy subjects, 45 multiple sclerosis (MS), 21 lateral amyotrophic sclerosis and 24 demyelinating polyneuropathy patients. M-response of m. abductor digiti min (AdV) and m. tibialis ant. (TA) was registered. The difference of M-response latent time induced by the stimulation, CVI--CVII and LII--LIV determined the time of the impulse central conduction (ICC) to the corresponding roots. In healthy subjects ICC--C amounts to 8.28 +/- 1 ms (maximum 10.3 ms), ICC--S is equal to 14.6 +/- 1.46 ms (maximum 16.8 ms). In patients with the above affections increased ICC was a frequent finding which also occurred in subclinical pyramidal lesions.


Pulsatile secretion of gonadotrophins, ovarian steroids and ovarian oxytocin during the periovulatory phase of the oestrous cycle in the cow.
An injection of 500 micrograms prostaglandin (PG) analogue was given on Day 12 (mid-luteal phase) of the oestrous cycle to 8 cows. An LH surge occurred 59 +/- 2 h later. LH, FSH, prolactin, oestradiol-17 beta, progesterone and oxytocin concentrations were determined in blood samples collected from the caudal vena cava and/or the jugular vein at 20-min (5 cows) or 5-min (3 cows; only LH and FSH concentrations were determined) intervals for 24 h, beginning 48 h after the PG injection. Oxytocin concentrations were low and similar in the vena cava and the jugular vein. In blood samples collected every 5 min the interpulse interval for LH and FSH during the period before the LH surge was 38-40 min. In the 20-min samples the interpulse interval for oestradiol was similar to that for LH and FSH, but pulse amplitude and basal concentrations steadily increased to reach maximum concentrations 6-8 h before and again during the LH surge. A decrease in oestradiol concentrations, lasting at least 60 min, occurred just before the start of the LH surge. Progesterone concentrations also increased at the same time as the LH surge. The magnitude of the LH surges varied from 7 to 32 ng/ml, but all cows ovulated and had oestrous cycles of normal length. Distinct pulses of LH and FSH were observed throughout the LH and FSH surges. Pulsatile secretion of LH was not detected for a period of up to 6-12 h following the LH surge, but then low-amplitude pulses occurred. In contrast, the pulsatile secretion of FSH remained at a frequency similar to that observed during the descending phase of the FSH surge. Furthermore, a second increase in FSH concentrations occurred, beginning 4-12 h after the LH-surge. It is concluded that: (1) the frequent, high-amplitude pulses of oestradiol that occur before and during the LH surge are probably due to stimulation by pulses of LH; (2) the LH surge is the result of an increase in frequency and amplitude of the LH pulses; (3) the second increase in FSH that follows the LH and FSH surges appears to be the result of an increase in the amplitude (not frequency) of the FSH pulses; and (4) very little, if any, oxytocin is secreted from the ovary during the periovulatory phase of the oestrous cycle.


Unsuccessful/successful attempts to produce penta(heteroaryl)-phosphoranes/-arsoranes R5E (E = P, As; R = 2-furyl, 2-thienyl).
Tri(2-thienyl)phosphine (1) has been transformed into chlorotri(2-thienyl)phosphonium chloride (3) in the reaction with hexachloroethane, into tetra(2-thienyl)phosphonium bromide (4) in a NiBr2-catalyzed quaternization with 2-bromothiophene, and into the p-tolylsulfonyliminotri(2-thienyl)phosphorane (6) using "chloramine T". Attempts to generate the homoleptic penta(2-thienyl)phosphorane (2-C4H3S)5P (5) by treating 3, 4, 6 or the known (PhO)3P=NSO2C6H4-2-Me (9) with 2-thienyllithium were unsuccessful. Tri(2-furyl)phosphine (2) was converted into the related imine 7, but the reaction of 7 or of 9 with 2-furyllithium failed to give (2-C4H3O)5P (8). It was only with the strained phosphorane Ph(C12H8)P=NSO2C6H4-4-Me (C12H8= 2,2'-biphenylylene) (10) that with 2-C4H3OLi the corresponding phosphorane Ph(C12H8)P(C4H3O-2)2 (11) could be obtained (31P NMR: delta-106.7 ppm). In the arsenic series, tri(2-thienyl)- and tri(2-furyl)arsine (12, 13) were converted into the tosylimino compounds (14, 15) and successfully transformed into the homoleptic arsoranes with 2-C4H3E-Li: penta(2-thienyl)- (16) and penta(2-furyl)-arsorane (17) are stable colourless crystalline solids, the NMR spectra of which indicate rapid pseudo-rotation in solution. The single crystal structure analysis of 17 shows an only slightly distorted trigonal-bipyramidal configuration. In crystals of the phosphine 2 and the arsine 13 the molecules have a propeller configuration with approximate C3v symmetry for the former, but Cs symmetry for the latter. The crystal structures of the precursors or intermediates 3, 4, 6, 9, and 10 have also been determined.


Maintenance of reinforcement to address the chronic nature of drug addiction.
Drug addiction can be a chronic problem. Abstinence reinforcement can initiate drug abstinence, but as with other treatments many patients relapse after the intervention ends. Abstinence reinforcement can be maintained to promote long-term drug abstinence, but practical means of implementing long-term abstinence reinforcement are needed. We reviewed 8 clinical trials conducted in Baltimore, MD from 1996 through 2010 that evaluated the therapeutic workplace as a vehicle for maintaining reinforcement for the treatment of drug addiction. The therapeutic workplace uses employment-based reinforcement in which employees must provide objective evidence of drug abstinence or medication adherence to work and earn wages. Employment-based reinforcement can initiate (3 of 4 studies) and maintain (2 studies) cocaine abstinence in methadone patients, although relapse can occur even after long-term exposure to abstinence reinforcement (1 study). Employment-based reinforcement can also promote abstinence from alcohol in homeless alcohol dependent adults (1 study), and maintain adherence to extended-release naltrexone in opioid dependent adults (2 studies). Treatments should seek to promote life-long effects in patients. Therapeutic reinforcement may need to be maintained indefinitely to prevent relapse. Workplaces could be effective vehicles for the maintenance of therapeutic reinforcement contingencies for drug abstinence and adherence to addiction medications.


[Computerized sonographic imaging of tongue motility using pseudo-3 dimensional reconstruction].
A new method for analysis and documentation of tongue movements was used in 24 healthy volunteers. This method enables direct digitalization of the information obtained from sequences of B-Mode pictures. Besides of allowing to further digital evaluation of the findings, it offers the facility of "pseudo 3D"-reconstruction of the tongue movements occurring on swallowing. The method appears to be of particular value for therapy control in neurological and phoniatric patients.


Polylactide-Cholesterol Stereocomplex Micelle Encapsulating Chemotherapeutic Agent for Improved Antitumor Efficacy and Safety.
For efficient therapy, optimized polymer micelle drug delivery systems require stability during circulation, appropriate diameters for targeting, and controlled drug release at the lesion site. To enhance the stability, adjust the sizes, and improve the selectivity of drug release of micelles from polylactides and polypeptides, stereocomplex interaction has been introduced. Herein, the cholesterol (CHOL)-enhanced doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (CDM/DOX), poly(L-lactide)-based micelle (CLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric 4-armed poly(ethylene glycol)-polylactide copolymers were reported to enhance tumor cell uptake and control drug release for treatment of cervical carcinoma. The introduction of hydrophobic CHOL further upregulated the stability, drug-loading capability, and cell uptake of micelles. All these DOX-loaded micelles showed appropriate sizes of ∼100 nm for the enhanced permeability and retention (EPR) effect. Compared to CDM/DOX and CLM/DOX, SCM/DOX exhibited the highest cell uptake and the most efficient antitumor efficacy in vitro. For U14 cervical carcinoma mouse model, all of the DOX-loaded micelles, especially SCM/DOX, effectively inhibited the progression of cervical carcinoma, as demonstrated by nearly stagnant tumor growth and increased apoptosis and necrosis areas within tumor tissue. Furthermore, these DOX-loaded micelles effectively alleviated the systemic toxicity of DOX. All the above results suggest that the DOX-loaded micelles, especially SCM/DOX, are an ideal drug delivery system for combating cervical carcinoma.


Perception of pain among pediatric patients with sickle cell pain crisis.
Pain related to vasoocclusion is the most common reason for emergency department visits and hospital stays among pediatric patients with sickle cell disease. Using a prospective descriptive design, patients hospitalized with sickle cell pain were asked to complete the Adolescent Pediatric Pain Tool on each day of their hospital stay, providing data on the location, intensity, and quality of their pain. Data for 82 hospital stays were collected from 40 African American study participants. Mean age was 14.8 years, and mean length of stay (LOS) was 5.1 days. Mean LOS for 8 to 12 year olds (3.23 days; n = 22) was shorter than mean LOS for 13 to 19 year olds (5.85 days; n = 60). This LOS difference was significant (P = .004). Difference in LOS by gender was not significant. Higher initial number of body sites with pain was significantly associated with longer LOS (r = .39; P < .001). Higher initial pain intensity scores were significantly associated with longer LOS (r = .37; P = .001). Higher initial number of word descriptors was only weakly associated with longer LOS. Neither gender nor age differences were significant for Adolescent Pediatric Pain Tool data.


Medical Big Data for Research Use: Current Status and Related Issues.
Advances in the computerization of information and development of technology have mitigated restrictions on handling of a large amount of information. This has resulted in growth of expectations for the use of large-scale databases, or so-called "big data." This is also the case in the field of healthcare. Projects that involve building of the national receipt database (NDB) of medical fee bill (receipt) information and special health check-up information based on the Act on Assurance of Medical Care for Elderly People and the development of medical information databases have been pursued by the national government, and considerable attention has also been focused on researches conducted through the secondary uses of publicly collected data. Aside from these trends, there are numerous projects which collect diagnosis procedure combination (DPC) data to build large-scale databases for research purposes. Following to the ethics guidelines for epidemiologic studies, they collect and analyze anonymized DPC data from cooperating institutions. This communication concentrates on the use of DPC data, and outlines the scale of data currently available for research use. Examples on the use of DPC data will be shown for analysis on the current status of clinical practice from the microscopic perspective and macroscopic analysis of community medical care provision. Additionally, potential for extending studies to long-term outcomes research, limitations and issues related to the use of medical big data will also be discussed.


Relative transgene expression frequencies in homozygous versus hemizygous transgenic mice.
We have used a simple binomial model of stochastic transgene inactivation at the level of the chromosome or transgene, rather than the cellular level, for the analysis of two mouse transgenic lines that show variegated patterns of expression. This predicts the percentages of cells that express one, both or neither alleles of the transgene in homozygotes from the observed percentages of cells, which express the transgene in hemizygotes. It adequately explained the relationship between the numbers of cells expressing the transgene in hemizygous and homozygous mosaic 21OH/LacZ mouse adrenals and mosaic BLG/7 mouse mammary glands. The binomial model also predicted that a small proportion of cells in mosaic mammary glands of BLG/7 homozygotes would express both BLG/7 alleles but published data indicated that all cells expressing the transgene showed monoallelic expression. Although it didn't fit all of the BLG/7 data as precisely as a more complex model, which used several ad hoc assumptions to explain these results, the simple binomial model was able to explain the relationship in observed transgene expression frequencies between hemizygous and homozygous mosaic tissues for both 21OH/LacZ and BLG/7 mice. It may prove to be a useful general model for analysing other transgenic animals showing mosaic transgene expression.


SFRS7-mediated splicing of tau exon 10 is directly regulated by STOX1A in glial cells.
In this study, we performed a genome-wide search for effector genes bound by STOX1A, a winged helix transcription factor recently demonstrated to be involved in late onset Alzheimer's disease and affecting the amyloid processing pathway. Our results show that out of 218 genes bound by STOX1A as identified by chromatin-immunoprecipitation followed by sequencing (ChIP-Seq), the serine/arginine-rich splicing factor 7 (SFRS7) was found to be induced, both at the mRNA and protein levels, by STOX1A after stable transfection in glial cells. The increase in SFRS7 was followed by an increase in the 4R/3R ratios of the microtubule-associated protein tau (MAPT) by differential exon 10 splicing. Secondly, STOX1A also induced expression of total tau both at the mRNA and protein levels. Upregulation of total tau expression (SFRS7-independent) and tau exon 10 splicing (SFRS7-dependent), as shown in this study to be both affected by STOX1A, is known to have implications in neurodegeneration. Our data further supports the functional importance and central role of STOX1A in neurodegeneration.


Complications of pyloromyotomy for infantile hypertrophic pyloric stenosis.
Few references exist regarding contemporary complications of pyloromyotomy (PM) for infantile hypertrophic pyloric stenosis (IHPS). Therefore, we reviewed the frequency and outcome of patients with IHPS who developed complications from PM. A 25-year retrospective review was performed in two populations. The first group included all infants who had a PM for IHPS at two pediatric surgery centers. The second group included all infants referred from other institutions who developed complications following PM for IHPS. Between 1969 and 1994, 901 PMs were performed. Intraoperative complications occurred in 40 patients (4%), including 39 duodenal perforations and 1 difficult intubation requiring prolonged ventilation. No unrecognized duodenal perforations or incomplete PMs were found. Postoperative complications developed in 52 patients (6%). The wound infection rate was less than 1%. Postoperative vomiting occurred in 31 infants (3%). The mortality rate was 0.1%, with 1 death due to sepsis from delayed diagnosis of Hirschsprung's disease. During the same study period, 11 patients were referred from other hospitals for postoperative complications. Five had persistent vomiting treated successfully with expectant management. Six infants needed reoperation: 3 for persistent IHPS, 1 for gastric outlet obstruction, and 1 for small bowel obstruction secondary to adhesions; 1 required wound abscess drainage. Pyloromyotomy is not without complications. Duodenal perforation should be infrequent, but when it occurs, it can usually be readily recognized and treated with minimal morbidity. Postoperative vomiting can be managed nonoperatively, but if it persists longer than 5 days, radiologic evaluation should be performed. Incomplete PM is uncommon and should not occur. A second myotomy is needed when the diagnosis of incomplete myotomy is established. A single standard of care should be expected of all surgeons who perform PM for IHPS.


miRNAs in the alga Chlamydomonas reinhardtii are not phylogenetically conserved and play a limited role in responses to nutrient deprivation.
The unicellular alga Chlamydomonas reinhardtii contains many types of small RNAs (sRNAs) but the biological role(s) of bona fide microRNAs (miRNAs) remains unclear. To address their possible function(s) in responses to nutrient availability, we examined miRNA expression in cells cultured under different trophic conditions (mixotrophic in the presence of acetate or photoautotrophic in the presence or absence of nitrogen). We also reanalyzed miRNA expression data in Chlamydomonas subject to sulfur or phosphate deprivation. Several miRNAs were differentially expressed under the various trophic conditions. However, in transcriptome analyses, the majority of their predicted targets did not show expected changes in transcript abundance, suggesting that they are not subject to miRNA-mediated RNA degradation. Mutant strains, defective in sRNAs or in ARGONAUTE3 (a key component of sRNA-mediated gene silencing), did not display major phenotypic defects when grown under multiple nutritional regimes. Additionally, Chlamydomonas miRNAs were not conserved, even in algae of the closely related Volvocaceae family, and many showed features resembling those of recently evolved, species-specific miRNAs in the genus Arabidopsis. Our results suggest that, in C. reinhardtii, miRNAs might be subject to relatively fast evolution and have only a minor, largely modulatory role in gene regulation under diverse trophic states.


Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis.
Consumption of ponderosa pine needles causes late-term abortions in cattle and is a serious poisonous plant problem in foothill and mountain rangelands. Isocupressic acid (IA) is the component of pine needles responsible for the abortifacient effect, its abortifacient effect may be due to inhibition of steroidogenesis. To investigate the more detail molecular mechanism, we used MA-10 cell, which is wild used to investigate molecular mechanism of steroidogenesis, to characterize the molecular mechanisms underlying the actions of IA in more detail. In this report, we focus on the function of IA on important steroidogenic genes, including steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD). We found that IA does not affect enzyme activities of these genes but inhibits transcription of P450scc and translation of StAR and P450scc through attenuating cAMP-PKA signaling. Thus, steroid productions of cells were suppressed.


A straightforward genotyping of the relevant IL28B SNPs for the prediction of hepatitis C treatment outcome.
A sustained virological response is not achieved by a significant proportion of chronic hepatitis C patients treated with interferon-based regimens. Due to the associated side effects and high costs, therapy response markers have been thoroughly sought. Two Single Nucleotide Polymorphisms (SNPs), rs12979860 and rs8099917, which are located upstream from the IL28B gene, have been remarkably described to have a strong association with treatment efficacy. The aim of this study was to develop a straightforward method for genotyping such polymorphisms. A Polymerase Chain Reaction (PCR) followed by enzymatic restriction of amplicons was established for SNPs genotyping. Online computation resources were employed for retrieving reference sequences, such as the selection of oligonucleotides and restriction enzymes. Two pairs of primers were designed and validated for the amplification of segments encompassing rs12979860 (694bp) and rs8099917 (496bp) with common thermocycling parameters. The endonucleases Hpy166II and BsrDI were selected and used for allelic discrimination related to rs12979860 (C/T) and rs8099917 (T/G), respectively. The expected electropherotypes were confirmed for all possible genotypes in 75 blood samples. In addition, the results were validated by sequencing. The method constitutes a simple and reliable assay, which may be readily available for genotyping of rs12979860 and rs8099917 in laboratories that support hepatitis C treatment centers.


Estimating the 'consumer surplus' for branded versus standardised tobacco packaging.
Tobacco companies question whether standardised (or 'plain') packaging will change smokers' behaviour. We addressed this question by estimating how standardised packaging compared to a proven tobacco control intervention, price increases through excise taxes, thus providing a quantitative measure of standardised packaging's likely effect. We conducted an online study of 311 New Zealand smokers aged 18 years and above that comprised a willingness-to-pay task comparing a branded and a standardised pack at four different price levels, and a choice experiment. The latter used an alternative-specific design, where the alternatives were a branded pack or a standardised pack, with warning theme and price varied for each pack. Respondents had higher purchase likelihoods for the branded pack (with a 30% warning) than the standardised pack (with a 75% warning) at each price level tested, and, on average, were willing to pay approximately 5% more for a branded pack. The choice experiment produced a very similar estimate of 'consumer surplus' for a branded pack. However, the size of the 'consumer surplus' varied between warning themes and by respondents' demographic characteristics. These two experiments suggest standardised packaging and larger warning labels could have a similar overall effect on adult New Zealand smokers as a 5% tobacco price increase. The findings provide further evidence for the efficacy of standardised packaging, which focuses primarily on reducing youth initiation, and suggest this measure will also bring notable benefits to adult smokers.


The combined effect of haematoporphyrin derivative and light on the normal mouse retina.
Combined treatment with haematoporphyrin derivative (Hpd) and light irradiation has been reported to be an effective method of killing cancer cells. This would be a very suitable treatment of intraocular tumours because the light can be controlled by the refractive media of the eye. Light and electron microscopy of Hpd and light treated normal mouse retina showed that only the irradiated area was damaged. Tissue destruction increased with greater concentrations of Hpd and longer light exposure. The outer layers of the retina were most sensitive. Hpd was retained in the tissue for 6 days.


Determination of proliferating fractions in malignant melanomas by anti-PCNA/cyclin monoclonal antibody.
An immunohistochemical study of melanocytic tumours using 19A2, a monoclonal antibody against proliferating cell nuclear antigen (PCNA/cyclin), was performed on tissues routinely processed with formalin fixation and paraffin embedding. In normal skin, keratinocytes of the suprabasal region in epidermis, the papillae and outer root sheath of hair follicles and the basal cells lining the lobules of sebaceous glands were stained in the nucleus. Other skin components, including basal and follicular melanocytes, did not demonstrate nuclear labelling. In addition, expression of PCNA/cyclin in keratinocytes was higher in sun-exposed skin compared with unexposed skin. In melanocytic lesions, PCNA/cyclin positive tumour cells increased in number and staining intensity according to the following progression: common melanocytic naevi; dysplastic naevi; primary melanomas; and metastatic melanomas. Expression of PCNA/cyclin, therefore, provides a useful marker for proliferation and tumour progression in skin.


[Long-term results (5-year minimum) of the diet treatment of adult obesity. Elements of weight prognosis. Apropos of 138 patients].
One hundred and thirty-eight out of 250 obese patients admitted to hospitals between 1972 and 1976 for dietetic treatment comprising 1,000 calories and 100 g carbohydrates were recontacted with a minimum follow-up of 5 years. Seventy-five patients refused to answer the questionnaire or attend an outpatient appointment. Four patients were later excluded from the study. Finally, fifty-nine patients were reassessed. The percentage of good results at 5 years (defined as greater than or equal to 5 p. 100 loss of initial body weight) was 45.5 p. 100 of those reassessed, a minimum of 20 p. 100 of the total number recontacted. The course of obesity was not linear. During the follow-up period there were 45.5 p. 100 of secondary failures (regain of initial body weight after having lost at least 5 p. 100), but also 17 p. 100 of secondary successes. The prognosis was not related to the age of onset of obesity, its duration, sex, occupation, alleged trigger factors, apparent motivation, duration of hospital admission, or treatment before or after hospitalisation. The prognosis was better in patients under 30 or over 50 years of age at the time of treatment (P less than 0.01) and when the body weight had not varied +/- 5 kg in the years preceding treatment (P less than 0.01). The following factors may also play a favourable role (but not statistically significant): the degree of obesity (better results in major obesity greater than or equal to 50 p. 100 overweight), a positive family history, the detection of a physical factor (glucose intolerance) during investigation, and the repetition of medical check-ups after initial counselling.


[Not Available].
Underlying this issue of Nurse Researcher is a sense of continuity. Amidst new beginnings - new volume, new editor - the commitment to providing readers with the tools 'to evaluate and appreciate research work' that has driven the journal since its inception, remains the same.


The role of the physical state of lipopolysaccharides in the interaction with complement. High molecular weight as prerequisite for the expression of anti-complementary activity.
Lipopolysaccharides interact with complement only when they are present in a state of high aggregation with a high apparent molecular weight. Lipopolysaccharides in uniform salt forms prepared by electrodialysis and neutralization with different bases exhibited distinct differences in their anticomplementary activity which correlated with differences in their sedimentation coefficients. Conversion of smooth (S) form lipopolysaccharides into the low-molecular-weight triethylamine form completely abolished their anti-complementary activity while conversion into the high-molecular-weight sodium form increased their activity. In contrast, a similar treatment of highly defective Re and Rd rough (R) form lipopolysaccharides had no effect on their ability to interact with complement. Both the triethylamine and sodium forms were strongly anti-complementary despite large differences in their molecular weight. This was found to be due to the property of R lipopolysaccharides to reaggregate into a large-molecular-weight form through absorption of Mg2+ and Ca2+ present in the guinea pig serum used as complement source. Defective lipopolysaccharides derived from the Ra and Rb classes showed only negligible anti-complementary activity which did not increase by conversion into salt forms with high molecular weight.


LIFE HISTORY STUDIES OF THE LESSER SNOW GOOSE (ANSER CAERULESCENS CAERULESCENS). III. THE SELECTIVE VALUE OF PLUMAGE POLYMORPHISM: NET FECUNDITY.
Between 1969 and 1977 the frequency of the blue phenotype of the dimorphic Lesser Snow Goose (Anser caerulescens caerulescens) showed a steady increase at the La Pérouse Bay colony near Churchill, Manitoba. Cooch (1961, 1963) suggested the global increase resulted from selection pressures favoring blue individuals. The selection hypothesis was evaluated by examining phenotypic differences in net fecundity. We partitioned the reproductive cycle into a series of stages, each defined by a particular index of fecundity. Despite large samples we were unable to detect any significant differences between the two maternal phenotypes in those indices that could conceivably influence population dynamics. We cannot, however, dismiss selection as the mechanism of population change, nor as a contributor to the maintenance of the polymorphism without assessing potential phenotypic differences in viability, age of maturation, and breeding propensity. These attributes are examined in the following paper (Rockwell et al., 1985).


Selective labilization of specific granules in polymorphonuclear leukocytes by phorbol myristate acetate.
The action of phorbol myristate acetate (PMA), the active principle of croton oil, on polymorphonuclear leukocytes (PMNs) has been evaluated in this study. Small amounts of PMA caused the rapid development of vacuoles in neutrophils and the disappearance of specific granules. Histochemical and cytochemical studies revealed that alkaline phosphatase activity was transferred to vacuoles and disappeared from the cells, while myeloperoxidase activity remained associated with intact azurophilic lysosomes. Electron-dense tracers indicated that the vacuole membranes originated, at least in part, from the cell wall of the neutrophils. The results indicate that PMA stimulates events remarkably similar to those which take place when bacteria are engulfed by PMNs, except for the failure of azurophilic lysosomes to participate in PMA-induced vacuole formation. PMA appears to be the first chemical agent capable of inducing selective labilization of specific granules in the neutrophil.


Countrywide Spatial Variation of Potentially Toxic Element Contamination in Soils of Turkey and Assessment of Population Health Risks for Nondietary Ingestion.
Countrywide surface soil concentrations of potentially toxic elements (PTEs) in Turkey were reviewed in the Web of Science database. A total of 93 papers were investigated to compose a PTE dataset for determining spatial variations and estimating exposure and health risks. Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn were selected as PTEs in surface soil. A compiled PTE concentration dataset was used to estimate chronic toxic risks (CTRs) and carcinogenic risks (CRs) according to the deterministic and probabilistic approaches. While the CTR and CR levels of age and sex groups were estimated using a deterministic approach, population risks were estimated using a probabilistic approach. CTR and CR levels in lower age groups and female sex groups were estimated to be higher than those in higher age groups and associated male sex groups. The average CTR levels of the nondietary ingestion of As-containing soil in <11 year age groups were near/just above the threshold level, while As-associated average CR levels of adults and other age groups were estimated to be in the acceptable risk range (10-6 < CR < 10-5) and low priority risk range (10-5 < CR < 10-4), respectively. As-, Cr(VI)-, and Pb-associated upper-bound CR levels of the Turkish population were simulated to be 5.14 × 10-4, 6.23 × 10-5, and 2.34 × 10-6, respectively. Health risk models show the significance of As in both chronic toxic and carcinogenic effects.


The pathogenesis of interstitial pneumonitis induced by trehalose dimycolate. II. Reserpine prevents formation of lesions.
A single intraperitoneal injection of 10 micrograms of trehalose dimycolate (TDM) produced interstitial and hemorrhagic pneumonitis in C57BL/6 mice. As a part of an investigation of a possible role for cell-mediated immunity in the pathogenesis of this disorder, we found that reserpine, 3 mg/kg, given before, at the same time, or on Day 5 after administration of TDM, significantly reduced development of interstitial pneumonitis by Day 7. Smaller doses were less effective. Administration of reserpine, 3 or 2 mg/kg, 1 to 3 days after administration of TDM was lethal to most mice. Reserpine has been shown to inhibit expression of cell-mediated immune responses in mice, probably by causing intercellular release and degradation of vasoactive amines. Inhibition of pulmonary lesions by reserpine in TDM-treated mice suggests that a similar mechanism may be involved in the pathogenesis of TDM-induced lung injury.


[Conjunctival tumor...more than meet the eye].
The authors present the case of a patient diagnosed with a conjunctival tumor. Questions are being asked about the nature of the tumor--is there just a melanocitic conjunctival tumor or a scleral extension of a intraocular tumor (that also infiltrates the cornea). A minimally invasive surgical approach is decided, with excellent intra- and post-op results. There have been no complications during 1 year of combined ophthalmologist - oncologist surveillance.


Pesticide induced muscle necrosis: mechanisms and prevention.
The nerve agent soman, as well as other organophosphates such as paraoxon and phospholine in concentrations that caused cholinergic symptoms induced a progressive dose-related necrosis in rat skeletal muscle fibers. The severity of the myopathy depended on a critical decrease in activity and duration of acetylcholinesterase (AChE) inhibition. The number of muscle fibers affected was greatest with soman, followed by tertiary phospholine, paraxon , and quaternary phospholine. The necrotic nerve fibers were repaired within 1 week. Atropine and gentamycin in concentrations that do not block neuromuscular transmission, attenuate the necrotic action of the organophosphates by interacting with the presynaptic Ca2+ uptake mechanism. The half-time recovery rate of AChE after exposure to soman varied between 12 hr for sciatic nerve, 5-9 days for muscle, and 14 days for brain. AChE activity of peripheral nerve was minimally inhibited by soman and had recovered to control activity within 24 hr. The reason for this apparent insensitivity of the nerve AChE to soman may be due to the high activity of an enzyme that hydrolyzes soman. AChE at the neuromuscular junction in part has a protective and regulatory function through its control of free acetylcholine (ACh). By limiting the accumulation of ACh and the extent of its interaction with pre- and postsynaptic membranes, the morphological integrity of nerve terminals and muscle is preserved.


Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis.
Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target vaccination strategy depended on the inclusion of the herd protection effect. Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution.


Neutrophil Accumulation in the Small Intestine Contributes to Local Tissue Destruction Following Combined Radiation and Burn Injury.
The threat of nuclear disaster makes combined radiation and burn injury (CRI) a relevant topic when discussing modern trauma, as burn injuries are likely to occur with detonation of a conventional nuclear weapon. Previous studies in a murine model have shown that there is a breakdown of the gut epithelium and subsequent bacterial translocation into mesenteric lymph nodes after CRI. This study examines the early innate immune response of the small intestine after CRI. Using a previously established murine model of 5 to 5.5 Gy total body irradiation combined with 15% TBSA burn, the injury response of the small intestine was examined at 24, 48, and 72 hours by visual assessment, myeloperoxidase, and cytokine measurement. At 24 hours, intestinal damage as measured by villus blunting, crypt debris, and decreased mitosis, was apparent in all injury groups but the derangements persisted out to 72 hours only with CRI. The prolonged intestinal damage in CRI was accompanied by a 2-fold (P < .05) elevation in myeloperoxidase activity over sham animals at 48 hours and persisted as a 3-fold (P < .05) elevation at 72 hours after injury. Corresponding levels of KC were 8-fold (P < .05) higher than sham at 48 hours with persistent elevation at 72 hours. An enhanced innate immune response, partially mediated by the influx of neutrophils into the gastrointestinal tract is contributing to the hyperinflammatory state seen after CRI. Attenuation of the local gastrointestinal inflammatory response may play a major role in managing victims after nuclear disaster.


Pathophysiological Consequences of Neuronal α-Synuclein Overexpression: Impacts on Ion Homeostasis, Stress Signaling, Mitochondrial Integrity, and Electrical Activity.
α-Synuclein (α-Syn) is intimately linked to the etiology of Parkinson's Disease, as mutations and even subtle increases in gene dosage result in early onset of the disease. However, how this protein causes neuronal dysfunction and neurodegeneration is incompletely understood. We thus examined a comprehensive range of physiological parameters in cultured rat primary neurons overexpressing α-Syn at levels causing a slowly progressive neurodegeneration. In contradiction to earlier reports from non-neuronal assay systems we demonstrate that α-Syn does not interfere with essential ion handling capacities, mitochondrial capability of ATP production or basic electro-physiological properties like resting membrane potential or the general ability to generate action potentials. α-Syn also does not activate canonical stress kinase Signaling converging on SAPK/Jun, p38 MAPK or Erk kinases. Causative for α-Syn-induced neurodegeneration are mitochondrial thiol oxidation and activation of caspases downstream of mitochondrial outer membrane permeabilization, leading to apoptosis-like cell death execution with some unusual aspects. We also aimed to elucidate neuroprotective strategies counteracting the pathophysiological processes caused by α-Syn. Neurotrophic factors, calpain inhibition and increased lysosomal protease capacity showed no protective effects against α-Syn overexpression. In contrast, the major watchdog of outer mitochondrial membrane integrity, Bcl-Xl, was capable of almost completely preventing neuron death, but did not prevent mitochondrial thiol oxidation. Importantly, independent from the quite mono-causal induction of neurotoxicity, α-Syn causes diminished excitability of neurons by external stimuli and robust impairments in endogenous neuronal network activity by decreasing the frequency of action potentials generated without external stimulation. This latter finding suggests that α-Syn can induce neuronal dysfunction independent from its induction of neurotoxicity and might serve as an explanation for functional deficits that precede neuronal cell loss in synucleopathies like Parkinson's disease or dementia with Lewy bodies.


AIRWAY MANAGEMENT WITH DIRECT LARYNGOSCOPY IN A CHILD WITH GOLDENHAR SYNDROME.
Goldenhar syndrome, also known as oculoauriculovertebral dysplasia, is a rare congenital condition characterized by facial, cranial, vertebral, ocular, auricular and cardiac abnormalities. This syndrome is associated with hemifacial microsomia due to inadequate growth of the mandible and vertebral anomaly of the cervical part of the spine. For anesthesiologists, airway management is of great interest because of facial and oral abnormalities such as mandibular hypoplasia and limitation of neck movement. Considering different conditions of Goldenhar syndrome, every patient should be preoperatively evaluated in order to make the plan for the anticipated difficult airway management. We report a case of a 2.5-year-old boy undergoing palatoplasty, who required general anesthesia and orotracheal intubation. Our decision to intubate with direct laryngoscopy and with slight external pressure on the larynx proved successful.


Size Matters a Lot: Drought-Affected Italian Oaks Are Smaller and Show Lower Growth Prior to Tree Death.
Hydraulic theory suggests that tall trees are at greater risk of drought-triggered death caused by hydraulic failure than small trees. In addition the drop in growth, observed in several tree species prior to death, is often interpreted as an early-warning signal of impending death. We test these hypotheses by comparing size, growth, and wood-anatomy patterns of living and now-dead trees in two Italian oak forests showing recent mortality episodes. The mortality probability of trees is modeled as a function of recent growth and tree size. Drift-diffusion-jump (DDJ) metrics are used to detect early-warning signals. We found that the tallest trees of the anisohydric Italian oak better survived drought contrary to what was predicted by the theory. Dead trees were characterized by a lower height and radial-growth trend than living trees in both study sites. The growth reduction of now-dead trees started about 10 years prior to their death and after two severe spring droughts during the early 2000s. This critical transition in growth was detected by DDJ metrics in the most affected site. Dead trees were also more sensitive to drought stress in this site indicating different susceptibility to water shortage between trees. Dead trees did not form earlywood vessels with smaller lumen diameter than surviving trees but tended to form wider latewood vessels with a higher percentage of vessel area. Since living and dead trees showed similar competition we did not expect that moderate thinning and a reduction in tree density would increase the short-term survival probability of trees.


The structure of oleamide films at the aluminum/oil interface and aluminum/air interface studied by Sum Frequency Generation (SFG) vibrational spectroscopy and Reflection Absorption Infrared Spectroscopy (RAIRS).
The structure of oleamide (cis-9-octadecenamide) films on aluminum has been investigated by sum frequency generation vibrational spectroscopy (SFG) and reflection absorption infrared spectroscopy (RAIRS). Three different film deposition strategies were investigated: (i) films formed by equilibrium adsorption from oleamide solutions in oil, (ii) Langmuir-Blodgett films cast at 1 and 25 mN m(-1), (iii) thick spin-cast films. Both L-B and spin-cast films were examined in air and under oil. The adsorbate formed in the 1 mN m(-1) film in air showed little orientational order. For this film, the spectroscopic results and the ellipsometric thickness point to a relatively conformationally disordered monolayer that is oriented principally in the plane of the interface. Direct adsorption to the metal interface from oil results in SFG spectra of oleamide that are comparable to those observed for the 1 mN m(-1) L-B film in air. In contrast, SFG and RAIRS results for the 25 mN m(-1) film in air and SFG spectra of the spin-cast film in air both show strong conformational ordering and orientational alignment normal to the interface. The 25 mN m(-1) film has an ellipsometric thickness almost twice that of the 1 mN m(-1) L-B film. Taken in combination with the spectroscopic results, this is indicative of a well packed monolayer in air in which the hydrocarbon chain is in an essentially defect-free extended conformation with the methyl terminus oriented away from the surface. A similar structure is also deduced for the surface of the spin-cast film in air. Upon immersion of the 25 mN m(-1) L-B film in oil the SFG spectra show that this film rapidly adopts a relatively disordered structure similar to that seen for the 1 mN m(-1) L-B film in air. Immersion of the spin-cast film in oil results in the gradual disordering of the amide film over a period of several days until the observed spectra become essentially identical to those observed for direct adsorption of oleamide from oil.


Evaluation of an in vitro cell culture assay for the potency assessment of recombinant human erythropoietin.
Recombinant human erythropoietin is a sialoglycoprotein that stimulates erythropoiesis. To assess potency of human erythropoietin produced by recombinant technology, we investigated an in vitro TF-1 cell proliferation assay, which was applied in conjunction with a reversed-phase liquid chromatography method for the determination of the content of sialic acids. The results obtained, which were higher than 126.8ng/μg, were compared with those obtained with the in vivo normocythaemic mouse bioassay. The in vitro assay resulted in a non-significant lower mean difference of the estimated potencies (0.61% ± 0.026, p > 0.05). The use of this combination of methods represents an advance toward the establishment of alternative in vitro approaches, in the context of the Three Rs, for the potency assessment of biotechnology-derived medicines.


Lesbian intra-partner oocyte donation: a possible shake-up in the Garden of Eden?
Treatment of same-sex couples using infertility therapies has become more acceptable over the years, but remains controversial. In December 2005, two law changes came into force in the UK that impact same-sex couples. Firstly, the Civil Partnership Act 2004 acknowledged legal relationships between same-sex couples; and secondly, the Adoption and Children Act 2002 allowed same-sex couples to adopt. In view of these law changes, it is timely to consider procreation in same-sex couples and, particularly, the possibility of intra-partner oocyte donation within a lesbian relationship. Such treatment would require one female partner to provide the oocyte and the other female partner to act as embryo recipient. The embryo(s) could be created using IVF with registered anonymous donor sperm. The novelty of allowing a lesbian couple to cause a pregnancy in this way could allow the recipient to give birth to a baby that was genetically related to her partner. If society finds this acceptable, intra-partner oocyte donation using donor sperm for IVF could successfully provide a family for lesbian couples, offering an alternative to individual donor insemination. The ethical aspects of the treatment are discussed.


Fuzzy Recurrence Exponents of Subcellular-Nanostructure Dynamics in Time-Lapse Confocal Imaging.
Studying the dynamics of nanostructures in the intracellular space is important because it allows gaining insights into the mechanism of complex biological functions of organelles. Understanding such dynamical processes can contribute to the development of nanomedicine for the diagnosis and treatment of many diseases caused by the interaction of multiple genes and environmental factors. Here a quantitative measure of spatial-temporal dynamics of nanostructures within a cell line in the context of nonlinear dynamics is introduced, where early endosomes, late endosomes, and lysosomes recorded by time-lapse confocal imaging are examined. The mathematical derivation of the proposed technique is based on the concept of recurrence dynamics and sequential rate of change over time. The quantification introduced as fuzzy recurrence exponents can be generalized for characterizing the dynamics of experimental evolutions in other nanostructures of living cells captured under the optical microscope.


Electrical disconnection versus anatomical isolation of the pulmonary veins: two sides of the same treatment for atrial fibrillation?
There are currently two techniques for percutaneous electrical isolation of the pulmonary veins (PV): anatomical isolation and electrical disconnection. The aim of the present study was to assess the continuity and circumferential extension of the radiofrequency applications necessary for PV electrical disconnection in order to evaluate the differences between this technique and anatomical isolation. We studied 9 patients with paroxysmal atrial fibrillation who underwent PV electrical disconnection. The electrophysiologic study was performed with a decapolar circular catheter (Lasso) introduced in the PV ostia and a mapping and ablation catheter (CARTO). Ablation was performed following the activation sequence of PV potentials. Using the CARTO system we evaluated the number of applications, their distribution in quadrants, and the maximum distance between contiguous and opposite RF applications. We assessed the number of veins with circumferential applications. The number of applications and maximum distance between contiguous applications were compared to the maximum distance between opposite applications. A total of 26 PV were isolated, including 9 right superior, 5 right inferior, 6 left superior and 6 left inferior. On average more than 10 applications were necessary, with a heterogeneous distribution. In 80.8% of the PVs the maximum distance between contiguous application was less than 1 cm and maximum distance between opposite application were highest in the right superior PV and lowest in the right inferior PV. The applications were circumferential in 80.8% of the disconnections. The number of RF applications was significantly higher in PVs with greater distances between opposite applications (correlation coefficient 0.51; p=0.008). No relation was found between maximum distances in contiguous and opposite applications (correlation coefficient r=0.13; p=NS). Electrical disconnection was achieved in the great majority of cases with circumferential applications, similarly to anatomical isolation. However, the heterogeneous distribution of the applications implies the existence of areas that need a greater number of applications and that can only be identified during electrophysiologic study. Therefore, rather than two aspects of the same treatment for atrial fibrillation, electrical disconnection and anatomical isolation complement each other in the achievement of effective PV isolation.


[On a comparison between the theory of movement and the theory of Karma in Vaiśesika system in ancient India].
The action of a human body is composed of a series of momentary movements caused by a volitional effort on the human in the Vaiśesika system. According to the theory of Karma in the Vaiśesika system, when an action is done by a person, it leaves an ethical potency, so called karmā'saya on one's mind. When the potency, karmā'saya is accompanied with the other potency, affliction so called kle'sa in one's mind, it grows up as the seed of a plant and bears the fruit of it. Any person who has the fruit of karmā'saya in one's mind, is made to experience joy or sorrow in the future in accordance with the judgement of the Creator about the fruit of karmā'saya. The affliction is the emotional potency caused by ignorance, e.g. avarice. On the other hand, the first movement of matter is produced by the movement of a mover through the special contact, so called nodana. The first movement produces the vega (the power of motion) in the moved matter. Through nodana, the movement and the vega are correlatively increased. The nodana is impulsive contact, acting between a mover and the moved matter. As I have shown in my paper, "On the theory of movement in Vaiśesika system iin ancient India (II)", the above process of movements of matter through nodana is very similar to the mental process of remembrance of a person. The growing process of the ethical potency, karmā'saya in a person's mind is, however, different to the above process of movements of matter. The intensity of the vega is "temporarily" increased through the contact, nodana, but the karmā'saya is "perpetually" grown by the potency, affliction until the karmā'saya bears the fruit of it.


Very high-power short-duration catheter ablation for treatment of cardiac arrhythmias: Insights from the FAST and FURIOUS study series.
The QDOT MICRO™ Catheter is a novel open-irrigated contact force-sensing radiofrequency ablation catheter. It offers very high-power short-duration (vHPSD) ablation with 90 W for 4 s to improve safety and efficacy of catheter ablation procedures. Although the QDOT MICRO™ Catheter was mainly designed for pulmonary vein isolation (PVI) its versatility to treat atrial fibrillation (AF) and other types of arrhythmias was recently evaluated by the FAST and FURIOUS study series and other studies and will be presented in this article. Available study and registry data as well as case reports concerning utilization of the QDOT MICRO™ Catheter for the treatment of cardiac arrhythmias including AF, focal and macroreentry atrial tachycardia, typical atrial flutter by cavotricuspid isthmus block, premature ventricular contractions, and accessory pathways were reviewed and summarized. In summary, the QDOT MICRO™ Catheter showed safety and efficacy for PVI and is able to treat also other types of arrhythmias as is was recently evaluated by case reports and the FAST and FURIOUS studies.


[Comprehensive management of residual tumor in patients with an advanced testicular tumor].
Treatment for metastatic testicular tumors is based on risk stratification according to International Germ Cell Cancer Collaborative Group classification and consists of cisplatin-based chemotherapy and resection of residual tumors. The indication of residual tumor resection is sometimes controversial. The residual tumor is under surveillance without resection after chemotherapy of pure seminoma, but the residual tumor is resected after chemotherapy in most cases of nonseminomatous tumors. The Japanese Urological Association has established guidelines on testicular tumor useful for the evidence-based treatment in Japan. The indication and surgical techniques for retroperitoneal residual tumor resection after chemotherapy are discussed.


Mechanisms of UV-induced signal transduction.
Ultraviolet radiation (UV) causes a variety of biological effects that can be either beneficial or harmful for human health. To exert these effects on a cellular basis, UV uses a variety of signaling pathways. DNA is the major chromophore for UVB. Thus, nuclear DNA damage has been detected to be a major mediator of numerous UVB effects, and experimental reduction of DNA damage is associated with a loss of these effects. On the other hand, UV has been found to utilize molecular components within the cytoplasm or at the cell membrane for signaling. UV can directly activate cell surface receptors, kinases, and transcription factors. The nuclear and extranuclear signaling pathways are generated independently and have been recently recognized to be not mutually exclusive but to contribute to various UV effects in an independent and additive way. Further knowledge of how these signaling pathways relate to each other will certainly increase our understanding of how UV acts as a pathogen. The following review will briefly discuss current aspects of the mechanisms involved in UV-induced signal transduction.


Analysis and glycosyl composition of the exopolysaccharide isolated from the floc-forming wastewater bacterium Thauera sp. MZ1T.
Conditions were developed for the reproducible production, isolation and characterization of a novel microbial extracellular polysaccharide believed to be involved in transient viscous bulking at an industrial wastewater treatment plant. The exopolysaccharide was extracted from cell-free culture supernatants of Thauera sp. strain MZ1T grown on a minimal medium with succinate. The purified polymer was found to be approximately 260 kDa in size by gel-permeation chromatography. The GC-MS analysis of the alditol acetate and per-O-trimethylsilyl methyl glycoside derivatives revealed that the exopolysaccharide was composed of four monosaccharides including: rhamnose, galacturonic acid, N-acetylglucosamine and N-acetylfucosamine. Glucose, which also appeared at low levels, is most likely from a co-eluting glucan. The FTIR and NMR spectroscopic analyses further revealed the presence of esterified component groups on the polymer. These results represent the first published description of a polysaccharide from a member of the genus Thauera, and lay the foundation for a deeper understanding of the factors potentially involved in zoogloeal cluster formation and viscous bulking.


Knowledge Translation Interventions to Improve the Timing of Dialysis Initiation: Protocol for a Cluster Randomized Trial.
Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney function) has risen rapidly in the past 2 decades in Canada and internationally, despite absence of established health benefits and higher costs. In 2014, a Canadian guideline on the timing of dialysis initiation, recommending an intent-to-defer approach, was published. The objective of this study is to evaluate the efficacy and safety of a knowledge translation intervention to promote the intent-to-defer approach in clinical practice. This study is a multicenter, 2-arm parallel, cluster randomized trial. The study involves 55 advanced chronic kidney disease clinics across Canada. Patients older than 18 years who are managed by nephrologists for more than 3 months, and initiate dialysis in the follow-up period are included in the study. Outcomes will be measured at the patient-level and enumerated within a cluster. Data on characteristics of each dialysis start will be determined by linkages with the Canadian Organ Replacement Register. Primary outcomes include the proportion of patients who start dialysis early with an estimated glomerular filtration rate greater than 10.5 mL/min/1.73 m2 and start dialysis in hospital as inpatients or in an emergency room setting. Secondary outcomes include the rate of change in early dialysis starts; rates of hospitalizations, deaths, and cost of predialysis care (wherever available); quarterly proportion of new starts; and acceptability of the knowledge translation materials. We randomized 55 multidisciplinary chronic disease clinics (clusters) in Canada to receive either an active knowledge translation intervention or no intervention for the uptake of the guideline on the timing of dialysis initiation. The active knowledge translation intervention consists of audit and feedback as well as patient- and provider-directed educational tools delivered at a comprehensive in-person medical detailing visit. Control clinics are only exposed to guideline release without active dissemination. We hypothesize that the clinics randomized to the intervention group will have a lower proportion of early dialysis starts. Limitations include passive dissemination of the guideline through publication, and lead-time and survivor bias, which favors delayed dialysis initiation. If successful, this active knowledge translation intervention will reduce early dialysis starts, lead to health and economic benefits, and provide a successful framework for evaluating and disseminating future guidelines. ClinicalTrials.gov, NCT02183987.


Current and emerging biologic and small molecule therapies for atopic dermatitis.
Atopic dermatitis (AD) is the most common inflammatory skin disease, yet until recently there were no safe systemic therapies approved for the long-term management of AD in adult patients. A deeper understanding of disease pathogenesis and identification of molecular and cellular changes has resulted in a rapidly evolving pipeline of therapeutics that holds promise for safer long-term control. In this review, we highlight the growing arsenal of biologic and small molecule antagonists that target pathways implicated in AD pathogenesis. Evidence that AD is driven by multiple immune axes extending beyond the Th2 polarization has resulted in therapies targeting additional pathways, including the Th22, Th17/IL-23, and JAK-STAT pathways. Pruritus, a hallmark of AD, has been linked to multiple mechanisms and various therapeutics have emerged in response to alternative hypotheses. Despite the assumption that AD has a common disease mechanism, recent studies indicate that the disorder is characterized by several phenotypes and therapy may need to be tailored to the unique immune traits of specific phenotypes. Targeted therapy should complement and expand our molecular map of AD across the various phenotypic iterations and help push AD pharmacotherapy into a new era of personalized medicine.


Nutrient and Rainfall Additions Shift Phylogenetically Estimated Traits of Soil Microbial Communities.
Microbial traits related to ecological responses and functions could provide a common currency facilitating synthesis and prediction; however, such traits are difficult to measure directly for all taxa in environmental samples. Past efforts to estimate trait values based on phylogenetic relationships have not always distinguished between traits with high and low phylogenetic conservatism, limiting reliability, especially in poorly known environments, such as soil. Using updated reference trees and phylogenetic relationships, we estimated two phylogenetically conserved traits hypothesized to be ecologically important from DNA sequences of the 16S rRNA gene from soil bacterial and archaeal communities. We sampled these communities from an environmental change experiment in California grassland applying factorial addition of late-season precipitation and soil nutrients to multiple soil types for 3 years prior to sampling. Estimated traits were rRNA gene copy number, which contributes to how rapidly a microbe can respond to an increase in resources and may be related to its maximum growth rate, and genome size, which suggests the breadth of environmental and substrate conditions in which a microbe can thrive. Nutrient addition increased community-weighted mean estimated rRNA gene copy number and marginally increased estimated genome size, whereas precipitation addition decreased these community means for both estimated traits. The effects of both treatments on both traits were associated with soil properties, such as ammonium, available phosphorus, and pH. Estimated trait responses within several phyla were opposite to the community mean response, indicating that microbial responses, although largely consistent among soil types, were not uniform across the tree of life. Our results show that phylogenetic estimation of microbial traits can provide insight into how microbial ecological strategies interact with environmental changes. The method could easily be applied to any of the thousands of existing 16S rRNA sequence data sets and offers potential to improve our understanding of how microbial communities mediate ecosystem function responses to global changes.


Food selection and guidance for physically active people.
The everyday nutritional goals of athletes and physically active people reflect the special, and often increased, nutrient requirements arising from the commitment to regular exercise, as well as the practical challenges of achieving these goals in a busy lifestyle. Issues include achieving and maintaining a body weight and body fat level that is appropriate for optimal sports performance and health, as well as meeting increased requirements for protein and some micronutrients such as iron and calcium. While inadequate intakes of vitamins will impair exercise importance, the current view is that additional vitamin supplementation will not improve exercise performance. Attention to fluid and carbohydrate intake will be an important factor in exercise performance and recovery from exercise, particularly high intensity exercise which is carried out in hot conditions for prolonged periods. Guidelines to promote optimal fuel and fluid status include strategies before, during and after exercise. The dietary guidelines of many developed countries which emphasise dietary variety, based on high-carbohydrate, reduced-fat eating, provide an appropriate blue-print for the athletes diet'. Since sportspeople are well recognised and often hero-worshipped within the community, they provide a worthy example of the potential benefits of a well-chosen diet.


Expression of the leucocyte integrin LFA-1 (CD11a/CD18) and its ligand ICAM-1 (CD54) in lymphoid malignancies is related to lineage derivation and stage of differentiation but not to tumor grade.
The leucocyte adhesion molecule LFA-1 (CD11a/CD18) and its counter structure ICAM-1 (CD54) play a pivotal role in cell-cell interactions in the immune system and hence their expression on malignant cells might play an important role in determining the biological behavior of lymphoid malignancies. This study examined the LFA-1 (CD11a/CD18) and ICAM-1 (CD54) expression profiles of a large series of non-Hodgkin's lymphomas (NHL, n = 220) and lymphoid leukemias (LL, n = 48), which, by their differentiation-antigen phenotype represented essentially all stages of lymphoid development from stem cell to mature activated T- and B-lymphocyte. It was found that NHL and LL differentially express LFA-1 and ICAM-1 molecules according to their lineage derivation, stage of differentiation, and growth pattern. Specifically: (a) T-cell neoplasms nearly always express LFA-1 whereas B-cell tumors are often LFA-1 low/negative; (b) ICAM-1 expression is largely confined to tumors with a mature or activated T- or B-cell phenotype; (c) neoplasms with a leukemic dissemination pattern are either ICAM-1 low or negative. Importantly, neither LFA-1 nor ICAM-1 expression was related to tumor grade.


Nitric oxide as an inflammatory mediator of radiation pneumonitis in rats.
Radiation pneumonitis is a major complication of radiation therapy. To elucidate the mechanisms of radiation-induced pneumonitis, we studied nitric oxide (NO) produced from lung tissues using a model of unilaterally irradiated rats. Our results demonstrated that alveolar macrophages (AM) produced NO after irradiation, and the expression of inducible NO synthase (NOS) in both AM and alveolar epithelial cells was increased. Furthermore, the progression of radiation pneumonitis was reduced with the in vivo treatment of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). The effect of L-NAME was further confirmed by the inhibition of mRNA expression for procollagen-alpha1 type III of the lung. With these results, NO produced from AM and alveolar epithelial cells after irradiation may be an important mediator in the progression of radiation pneumonitis.


Pointers to the diagnosis of gastric lymphoma on computed tomography.
The computed tomographic features of 12 patients with primary gastric non-Hodgkin's lymphoma and a further seven patients with gastric involvement by disseminated non-Hodgkin's lymphoma have been reviewed. In eight of these 19 patients there were clefts within the area of gastric wall involved by lymphoma where oral contrast medium passed to within 2 mm of the serosal surface in and amongst areas of gastric wall thickening (maximal thickness ranging from 18 to 40 mm). In three of these patients some clefts extended beyond the expected margin of the stomach to enter into, and be contained by, a composite soft tissue mass of stomach, spleen and splenic hilar nodes. Awareness of these features, which are in keeping with the known range of macroscopic pathological appearances in non-Hodgkin's lymphoma, may help the radiologist to recognize this potentially curable disease.


Ultrastructural and immunohistochemical study of epithelioid hemangioendothelioma of bone: coexpression of epithelial and endothelial markers.
Four cases of epithelioid hemangioendothelioma of bone--a borderline malignant tumor of vascular origin--were studied ultrastructurally and immunohistochemically. The epithelioid tumor cells were positive for vimentin, polyclonal and monoclonal cytokeratins, and the endothelial markers factor VIII-related antigen (FVIII:RAg) and Ulex europaeus agglutinin I. The coexpression of polyclonal cytokeratin and FVIII:RAg was demonstrated by means of step sections in the same tumor cells. The endothelial origin of epithelioid tumor cells was supported ultrastructurally by identification of Weibel-Palade bodies.


Benchmarking time-series data discretization on inference methods.
The rapid development in quantitatively measuring DNA, RNA and protein has generated a great interest in the development of reverse-engineering methods, that is, data-driven approaches to infer the network structure or dynamical model of the system. Many reverse-engineering methods require discrete quantitative data as input, while many experimental data are continuous. Some studies have started to reveal the impact that the choice of data discretization has on the performance of reverse-engineering methods. However, more comprehensive studies are still greatly needed to systematically and quantitatively understand the impact that discretization methods have on inference methods. Furthermore, there is an urgent need for systematic comparative methods that can help select between discretization methods. In this work, we consider four published intracellular networks inferred with their respective time-series datasets. We discretized the data using different discretization methods. Across all datasets, changing the data discretization to a more appropriate one improved the reverse-engineering methods' performance. We observed no universal best discretization method across different time-series datasets. Thus, we propose DiscreeTest, a two-step evaluation metric for ranking discretization methods for time-series data. The underlying assumption of DiscreeTest is that an optimal discretization method should preserve the dynamic patterns observed in the original data across all variables. We used the same datasets and networks to show that DiscreeTest is able to identify an appropriate discretization among several candidate methods. To our knowledge, this is the first time that a method for benchmarking and selecting an appropriate discretization method for time-series data has been proposed. All the datasets, reverse-engineering methods and source code used in this paper are available in Vera-Licona's lab Github repository: https://github.com/VeraLiconaResearchGroup/Benchmarking_TSDiscretizations. Supplementary data are available at Bioinformatics online.


Factors responsible for mortality variation in the United States: A latent variable analysis.
Factors including smoking, drinking, substance abuse, obesity, and health care have all been shown to affect health and longevity. The relative importance of each of these factors is disputed in the literature, and has been assessed through a number of methods. This paper uses a novel approach to identify factors responsible for interstate mortality variation. It identifies factors through their imprint on mortality patterns and can therefore identify factors that are difficult or impossible to measure directly, such as sensitive health behaviors. The analysis calculates age-standardized death rates by cause of death from 2000-2009 for white men and women separately. Only premature deaths between ages 20-64 are included. Latent variables responsible for mortality variation are then identified through a factor analysis conducted on a death-rate-by-state matrix. These unobserved latent variables are inferred from observed mortality data and interpreted based on their correlations with individual causes of death. Smoking and obesity, substance abuse, and rural/urban residence are the three factors that make the largest contributions to state-level mortality variation among males. The same factors are at work for women but are less vividly revealed. The identification of factors is supported by a review of epidemiologic studies and strengthened by correlations with observable behavioral variables. Results are not sensitive to the choice of factor-analytic method used. The majority of interstate variation in mortality among white working-age adults in the United States is associated with a combination of smoking and obesity, substance abuse and rural/urban residence.


Continuous Heterogeneous Photocatalysis in Serial Micro-Batch Reactors.
Solid reagents, leaching catalysts, and heterogeneous photocatalysts are commonly employed in batch processes but are ill-suited for continuous-flow chemistry. Heterogeneous catalysts for thermal reactions are typically used in packed-bed reactors, which cannot be penetrated by light and thus are not suitable for photocatalytic reactions involving solids. We demonstrate that serial micro-batch reactors (SMBRs) allow for the continuous utilization of solid materials together with liquids and gases in flow. This technology was utilized to develop selective and efficient fluorination reactions using a modified graphitic carbon nitride heterogeneous catalyst instead of costly homogeneous metal polypyridyl complexes. The merger of this inexpensive, recyclable catalyst and the SMBR approach enables sustainable and scalable photocatalysis.


Different adsorption structures of pyridine on Si(001) and Ge(001) surfaces.
The adsorption and reaction of pyridine on the Si(001) and Ge(001) surfaces are investigated by first-principles density-functional calculations within the generalized gradient approximation. On both surfaces the N atom of pyridine initially reacts with the down atom of the dimer, forming a single bond between the N atom and the down atom. On Ge(001) such an adsorption configuration is most favorable, but on Si(001) a further reaction with a neighboring dimer occurs, resulting in formation of a bridge-type configuration. Especially we find that on Ge(001) the bridge-type configuration is less stable than the gas phase. Our results provide an explanation for a subtle difference in the adsorption structures of pyridine on Si(001) and Ge(001), which was observed from recent scanning tunneling microscopy experiments.