Effects of nicardipine and diltiazem on alpha-adrenoceptor responses in canine saphenous veins.
The effects of calcium antagonists, diltiazem and nicardipine (-6.0 to -4.0 log mol/l), on the contractile responses to noradrenaline, methoxamine and BHT-920 in isolated canine saphenous vein rings, were studied with isometric tension recordings. Concentration-effect curves to the alpha-agonists were obtained in the control state and in the presence of diltiazem or nicardipine. Propranolol (-6.0 log mol/l) was present in the bath throughout. Diltiazem had no significant inhibitory effect on the responses mediated by all three agonists. Nicardipine (-5.0 and -4.0 log mol/l) produced a small but significant inhibitory effect on the responses to noradrenaline and methoxamine while it had no effect on the response to BHT-920. The effects of nicardipine were greatest on the responses to methoxamine. These calcium antagonists appeared to have only small post-synaptic inhibitory effects on the contractile responses to alpha-agonists in the canine saphenous vein with nicardipine exerting a greater inhibitory influence than diltiazem.


Development and lateralization of language in the presence of early brain lesions.
There is a broad consensus that language is, in most right-handers and in a substantial part of left-handers, controlled by the left hemisphere. This seems to be, at least in part, genetically determined, as neuroanatomical asymmetries have been observed already prenatally (e.g. a larger left planum temporale). Left hemisphere lesions in adolescents and adults accordingly lead to persistent language deficits. However, this is not the case in lesions acquired prenatally or in early childhood.


Effective identification of Lactobacillus casei group species: genome-based selection of the gene mutL as the target of a novel multiplex PCR assay.
Lactobacillus casei,Lactobacillus paracasei and Lactobacillusrhamnosus form a closely related taxonomic group (the L. casei group) within the facultatively heterofermentative lactobacilli. Strains of these species have been used for a long time as probiotics in a wide range of products, and they represent the dominant species of nonstarter lactic acid bacteria in ripened cheeses, where they contribute to flavour development. The close genetic relationship among those species, as well as the similarity of biochemical properties of the strains, hinders the development of an adequate selective method to identify these bacteria. Despite this being a hot topic, as demonstrated by the large amount of literature about it, the results of different proposed identification methods are often ambiguous and unsatisfactory. The aim of this study was to develop a more robust species-specific identification assay for differentiating the species of the L. casei group. A taxonomy-driven comparative genomic analysis was carried out to select the potential target genes whose similarity could better reflect genome-wide diversity. The gene mutL appeared to be the most promising one and, therefore, a novel species-specific multiplex PCR assay was developed to rapidly and effectively distinguish L. casei, L. paracasei and L. rhamnosus strains. The analysis of a collection of 76 wild dairy isolates, previously identified as members of the L. casei group combining the results of multiple approaches, revealed that the novel designed primers, especially in combination with already existing ones, were able to improve the discrimination power at the species level and reveal previously undiscovered intraspecific biodiversity.


A biomimetic strategy to access the silybins: total synthesis of (-)-isosilybin A.
We report the first asymmetric, total synthesis of (-)-isosilybin A. A late-stage catalytic biomimetic cyclization of a highly functionalized chalcone is employed to form the characteristic benzopyranone ring. A robust and flexible approach to this chalcone provides an entry to the preparation of the entire isomeric family of silybin natural products.


[Organizational principles in prophylaxis of stroke].
Modern system of insult prophylaxis intends development of 2 directions: population strategy and individual tactics. The effectiveness of population strategy depends on quality of health survey and of sanitarian-educational work. The effectiveness of individual tactics depends on intensity of clinical, laboratorial and instrumental checkup and elaborating an adequate correction of representative syndromes. Model of an individual prophylaxis of insult exists in the 2nd Central Military Clinical Hospital of P.V. Mandryka more then 15 years. According to the result of yearly health survey, therapist, in cooperation with cardiologist and neurologist, elaborates a "plan of health", which intends decrease of negative factor's influence and using medicinal substances, correcting the representative syndromes. High-technological algorithms of checkup include ultrasonics surveys of brachycephaly vessel and of the heart, an entire-day electrocardiogram monitoring or loading test, large bio-chemistry tests, directed to finding hyper-coagulation and dislipidemia. The experience of work demonstrates large capabilities in increasing of effectiveness of prophylaxis programs. These capabilities permit decrease sickness rate of insult--to the 30% during latter years.


Study of HLA antigens in patients with Hodgkin's disease.
This paper studies relations of 21 HLA antigens of the A and B loci to selected characteristics in a group of patients with Hodgkin's disease. The investigated characteristics are age, sex, histological patterns, clinical stage and symptomatology. The considered group consists of 68 patients, 37 males and 31 females aged from 19 to 66 years and from 26 to 63 yr, respectively. A comparison between antigen frequencies for patients and controls (301 unrelated blood donors) is carried out. The results confirm that there is no relation between HLA antigens and Hodgkin's disease. A significant increase of A11 is found for females under 40 yr. Certain HLA antigens show significant correlation neither with the patient age nor with clinical or histological stages. A significant increase of B5 is observed for 16 relapsed patients. For them, significant test characteristics are found in the presence of cross-reacting HLA-B5, B35.


Large-for-gestational-age newborns in women with insulin-treated gestational diabetes under strict metabolic control.
To assess the influence of strict metabolic control in women with insulin-treated gestational diabetes on the risk of large-for-gestational-age (LGA) newborns, the frequency of obstetrical complications and fetal outcome. In this prospective cohort study, 875 women were screened for gestational diabetes mellitus with a 75 g oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. The study group (n = 162) consisted of women with insulin-treated gestational diabetes mellitus (GDM) and the control group (n = 713) of women with normal glucose tolerance (NGT). In the women with diabetes, strict adjustments of fasting glucose levels to 90 mg/dl and 130 mg/dl postprandially were achieved with insulin administration. No increased risk for LGA newborns was observed in women with GDM and good metabolic control (16.7% vs. 12.3%; p = 0.1). In women with NGT, maternal prepregnancy BMI was significantly higher in those who delivered LGA newborns than in those who gave birth to newborns below the 90th percentile [27.2 kg/m(2) (5.0) vs. 24.4 kg/m(2) (5.6); p = 0.006], whereas there was no influence of maternal BMI on birth weight of newborns in women with GDM. There was no difference between the two groups with respect to maternal birth traumata and fetal outcome, except for plexus palsy which occurred in three GDM women with macrosomic newborns. Strict metabolic control and surveillance in women with insulin-treated GDM seems to attenuate the risk for LGA newborns, diabetic fetopathia, and the influence of maternal BMI on fetal growth.


[Usefulness of low-dose irinotecan for multiple lung metastases of cholangiocellular carcinoma after operation--a case report].
We treated a patient in whom low-dose irinotecan therapy was effective for the treatment of multiple lung metastases of cholangiocellular carcinoma after operation. The patient was a 50-year-old man. He underwent extended right hepatectomy for cholangiocellular carcinoma, and multiple lung metastases occurred 8 months after operation. For the treatment of lung metastases, low-dose irinotecan therapy (70 or 40 mg/week) was carried out. Eighteen months after the lung recurrence, he is still alive with a good quality of life, although the lung metastases have progressed. These results suggest that low-dose irinotecan therapy can be effective for lung metastases of cholangiocellular carcinoma.


Immunohistochemical staining patterns of type VI collagen in the normal, hyperplastic, and neoplastic adult male breast.
Ten cases of primary invasive male breast ductal carcinomas (N.O.S.), one case of male breast fibroadenoma, seven cases of pure florid gynecomastia and four cases of normal mammary glands were examined immunohistochemically for type VI collagen expression and distribution. In normal male breast type VI collagen was absent in the whole fibrous stroma. On the contrary this collagen was markedly expressed in the stroma of invasive carcinoma as well as fibroadenoma and gynecomastia. In all these proliferative diseases, type VI collagen gave a distinct basement membrane-like deposition at the epithelial-stromal junctions while organized a fibrillar network in the interstitium. Our immunohistochemical findings showed that type VI collagens is involved in the stromal response of benign and malignant male breast proliferative diseases.


Effects of a surfactant (FFD-6) on Scenedesmus morphology and growth under different nutrient conditions.
Surfactants are man-made compounds that are meanwhile omnipresent in the environment, but environmental concentrations of surfactants are such that they are thought to have little risk for aquatic systems. The major anionic surfactants currently on the global market are linear alkylbenzene sulfonates (LAS), a class where the commercially available FFD-6 belongs to. The hypothesis was tested that sublethal effects of FFD-6, i.e. the morphological effect of colony formation in the common test alga Scenedesmus obliquus, occurs at a concentration lower than the no-observed-effect concentrations for endpoints commonly used in regulatory toxicity testing with algae. The surfactant FFD-6 induced colonies in Scenedesmus at concentrations a few orders of magnitude lower (i.e. between 0.001 and 0.01 g l-1) than at which growth inhibition was observed (i.e. between 1 and 10g l -1). Growth rates were lowest for Scenedesmus grown in P-limited medium, intermediate for algae reared in N-limited medium and highest for algae cultured in non-limited standard medium. Growth inhibition due to FFD-6 was similar for non-limited and nutrient-limited Scenedesmus, but colony formation was stronger in non-limited Scenedesmus than in nutrient limited cultures. The colony inducing effect of the surfactant FFD-6 on Scenedesmus occurs at much lower concentrations than growth inhibition and might affect species interactions, the survival of species and the energy flow along the food chain.


Influence of limestone characteristics on mercury re-emission in WFGD systems.
This work evaluates the influence of the effect of the properties of limestones on their reactivity and the re-emission of mercury under typical wet scrubber conditions. The influence of the composition, particle size, and porosity of limestones on their reactivity and the effect of sorbent concentration, pH, redox potential, and the sulphite and iron content of the slurry on Hg(0) re-emission was assessed. A small particle size, a high porosity and a low magnesium content increased the high reactivity of the limestones. Moreover, it was found that the higher the reactivity of the sample the greater the amount of mercury captured in the scrubber. Although sulphite ions did not cause the re-emission of mercury from the suspensions of the gypsums, the limestones enriched in iron increased Hg(0) re-emission under low oxygen conditions. It was observed that the low pH values of the gypsum suspensions favored the cocapture of mercury because Fe(2+) formation was avoided. The partitioning of the mercury in the byproducts of the scrubber depended on the impurities of the limestones rather than on their particle size. No leaching of mercury from the gypsum samples occurred suggesting that mercury was either tightly bound to the impurities of the limestone or was transformed into insoluble mercury species.


Left ventricular assessment in myocardial infarction: the VALIANT registry.
How often echocardiography and cardiac catheterization are used to evaluate left ventricular (LV) function in patients with myocardial infarction (MI) and how they are associated with quality of care is unknown. Patients with MI in the Valsartan in Acute Myocardial Infarction (VALIANT) registry were divided into those with (n = 1423) and without (n = 3968) heart failure (HF), and the use of either echocardiography or cardiac catheterization for LV assessment in each group was compared along with associated baseline characteristics. We evaluated the association between LV assessment and discharge medications. Using a multivariable model with a propensity analysis, we evaluated the association of LV assessment with in-hospital outcomes. Of the patients with HF, 322 (22.6%) had no LV assessment. Patients with HF with LV assessment were discharged more frequently under treatment with aspirin (81.3% vs 70.0%; P<.001), beta-blockers (65.6% vs 56.4%; P = .008), clopidogrel (30.4% vs 14.0%; P<.001), and statins (45.9% vs 34.2%; P<.001). Patients without HF who underwent LV assessment were discharged more frequently under treatment with an angiotensin-converting enzyme inhibitor (53.8% vs 41.5%; P<.001). After adjustment for regional use, other covariates, and revascularization, LV assessment was associated with lower in-hospital mortality in patients with HF (adjusted odds ratio [OR], 0.45; P<.001) and in patients without HF (adjusted OR, 0.30; P<.001). After excluding deaths during the first 2 days, LV assessment remained associated with lower mortality in patients with HF (adjusted OR, 0.59; P = .03) and in patients without HF (adjusted OR, 0.41; P<.001). Left ventricular assessment was frequently not performed during the in-hospital stay of patients with acute MI, including those with clinical HF, and its use was associated with better quality of care.


Role of Chemical Signals in the Orientation Behavior of the Sea Star Asterias forbesi.
The importance of chemical signals as foraging and orientation cues has been demonstrated for many marine organisms. It is still unclear whether sea stars use chemical signals during orientation and whether chemoreception occurs in the absence of macroscale flow. To determine whether the sea star Asterias forbesi can perceive chemical signals in the absence of flow and what role such signals play in orientation and foraging behavior, we tested the orientation behavior of sea stars to prey and nonprey items under conditions of nondirectional flow. Prey items were whole and broken clams (Mercenaria mercenaria) and mussels (Mytilus edulis); the nonprey item was squid flesh. Asterias forbesi showed the ability to successfully locate odor sources irrespective of the type of odor. Only in trials with the broken clam did the animals reveal an initial directional choice towards the odor source. There were significant changes in the movement rates and heading angles during orientation for all three stimuli. In addition, orientation paths were different for each of the chemical stimuli tested. From these results, we conclude that sea stars can detect and respond to chemicals in the absence of macroscale flow. Orientation paths appear to be more of a taxis, in which heading is directly guided by the stimulus field.


Structure-Based Optimization and Biological Evaluation of Potent and Selective MMP-7 Inhibitors for Kidney Fibrosis.
Matrix metalloproteinase-7 (MMP-7) has been shown to play important roles in pathophysiological processes involved in the development/progression of diseases such as cancer and fibrosis. We discovered selective MMP-7 inhibitors composed of arylsulfonamide, carboxylate, and short peptides by a molecular hybridization approach. These compounds interacted with MMP-7 via multiple hydrogen bonds in the cocrystal structures. To obtain compounds for in vivo evaluation, we attempted structural optimization, particularly targeting Tyr167 at the S3 subsite through structure-based drug design, and identified compound 15 as showing improved MMP-7 potency and MMP subtype selectivity. A novel π-π stacking interaction with Tyr167 was achieved when 4-pyridylalanine was introduced as the P3 residue. Compound 15 suppressed the progression of kidney fibrosis in a dose-dependent manner in a mouse model of unilateral ureteral obstruction. Thus, we demonstrated, for the first time, that potent and selective MMP-7 inhibitors could prevent the progression of kidney fibrosis.


Evaluation of Point-of-Care ACT Coagulometers and Anti-Xa Activity During Cardiopulmonary Bypass.
The activated clotting time (ACT) is used worldwide to confirm safe heparin anticoagulation for cardiopulmonary bypass. For the present study, the performances of 2 commonly used ACT devices were compared with each other and with anti-Xa levels throughout the surgical procedure in order to understand whether they can be used interchangeably. Prospective study. Tertiary care center. The study comprised 33 elective adult cardiac surgical patients. Blood samples were taken at standard times throughout the surgery (after induction, after heparin bolus, 4 samples at 30-minute intervals during cardiopulmonary bypass, after protamine), and ACTs and anti-Xa levels were analyzed. Data were compared using receiver operating characteristics and LOESS regression. The correlation between anti-Xa levels and the Hemochron ACT (Instrumentation Laboratory, Bedford, MA) was acceptable (r = 0.82, 95% confidence interval [CI] 0.757-0.868; p < 0.0001), as was the correlation between anti-Xa levels and the i-STAT (Abbott Point of Care, Abbott Park, IL) (r = 0.81, 95% CI 0.738-0.858; p < 0.0001). The correlation between the 2 ACT methods was poorer (r = 0.77, 95% CI 0.707-0.828; p < 0.0001) than their correlation to anti-Xa levels. When compared with anti-Xa levels, the sensitivity and specificity were mediocre for both devices, although the i-STAT performed better than the Hemochron ACT. The Hemochron ACT read higher values than the i-STAT ACT throughout the course of the surgery. The correlation between the Hemochron ACT and i-STAT ACT is moderate, and they have different sensitivity and specificity when compared with anti-Xa levels. This suggests that ACT devices should not be used interchangeably, but cut-off values for safe anticoagulation during cardiopulmonary bypass should be determined for each type of device, particularly when switching supplier.


Pancreatitis-associated protein in patients with celiac disease: serum levels and immunocytochemical localization in small intestine.
Since PAP is a stress protein expressed in human pancreas during pancreatitis but also constitutively synthesized in the small intestine, we looked whether its expression would be altered in patients with celiac disease. Serum PAP concentrations were determined consecutively in 54 patients with celiac disease on a free diet (group A), in 47 patients with celiac disease on a gluten-free diet (group B), in 22 patients with other intestinal pathologies but with normal intestinal mucosa (group C), in 14 patients with retarded growth, no gastrointestinal disease and normal intestinal mucosa (group D), and in 17 controls (group E). Serum PAP levels (ng/ml) were significantly higher in group A (127.3 +/- 56.8) than in the other groups (B: 47.2 +/- 20.5; C: 51.5 +/- 32.2; D: 47 +/- 22.8; E: 27.6 +/- 9.0), which were not different from each other. In group A, a positive correlation was observed between serum PAP values and antigluten antibody levels (vs. AGA IgG r = 0.58, p < 0.001; vs. AGA IgA r = 0.66, p < 0.001). Furthermore, 12 patients from group A were evaluated after 10-12 months of gluten-free diet and in all of them PAP serum concentration had decreased (mean +/- SE before the diet 122.5 +/- 36.4, after the diet 48.7 +/- 13.7, p < 0.0001). In addition, we performed an immunocytochemical study to localize PAP in the intestinal mucosa of patients from all groups except E. PAP was localized to the Paneth cells and to some globet cells, in patients with mucosal atrophy as well as in those with normal mucosa with no obvious quantitative difference. We concluded that in patients with celiac disease the active phase of the disease was accompanied by an increased serum concentration of PAP. Further studies are necessary to understand the mechanism leading to PAP elevation in the serum of patients with celiac disease.


Morphological findings contributing to a failed Fontan procedure. Twelve-year experience.
A group of 37 patients (age range, 3 months to 29 years) who died after the modified Fontan procedure (within 2 months), representing 15% of the 245 patients undergoing this procedure from 1976 through 1988, was reviewed to determine the causes of death. The three morphological groups were 1) univentricular atrioventricular connection (n = 19), 2) tricuspid atresia (n = 9), and 3) other complex malformations (n = 9). Subaortic stenosis was present in 15 patients (40%) in this group compared with 31 of 208 early survivors (15%) (p = 0.008). Pulmonary artery banding, identified as a risk factor in our previous experience, was performed in 14 patients, nine of whom had subaortic stenosis. Nine palliative procedures for subaortic stenosis were performed in eight patients--before the Fontan procedure in three patients and concurrently with the Fontan procedure in five patients. Myocardial hypertrophy and signs of acute ischemic injury were common findings at autopsy (n = 25) and were particularly prominent in all patients with univentricular heart of left ventricular morphology associated with subaortic stenosis and previous pulmonary artery banding (n = 7). We conclude that the present majority of deaths occurring after the modified Fontan procedure are myocardial in nature and attributable to advanced myocardial hypertrophy that is potentiated by previous pulmonary artery banding and subaortic stenosis.


[Salmeterol and fluticason and mortality in COPD patients].
In this study 6,112 COPD patients were treated with salmeterol 50 microg bid, fluticason 500 microg bid, salmeterol/fluticason combination 50/500 microg bid (SFK) or placebo for 3 years. The primary effect parameter was mortality and 875 patients had died after 3 years. Hazard ratio for death for SFK compared with placebo was 0.825, 95% confidence interval 0.681-1.002, p=0.052, or an absolute risk reduction of 2.6%. Active treatment reduced exacerbations and improved quality of life and lung function. The risk of pneumonia was higher in the fluticason and SFK treated groups than in the placebo group.


Beta-fibrinogen G-455A polymorphisms and recurrent miscarriage.
The aim of this study was to investigate whether differences could be detected in genotype and allele frequencies of β-fibrinogen G-455A in relation to recurrent miscarriage (RM). β-Fibrinogen G-455A polymorphism was investigated by sequencing analysis in 98 women with RM and 78 control women who had no history of miscarriage (controls). The frequency of the -455 A/A genotype of β-fibrinogen was significantly different in women with RM compared with control women. The A/A genotype was found in 8 women of Group 1 (8.2%), but was not detected in any woman of the control group. In contrast, no differences were found in the allele frequencies between RM and control women. Women with the A/A genotype could have an increased risk of RM. However, the allele frequencies were similar between women with recurrent pregnancy loss and control women, suggesting that the effect of β-fibrinogen polymorphisms on RM, if any, is actually very slight.


10-Gbps, 1-microm waveband photonic transmission with a harmonically mode-locked semiconductor laser.
To open up a 1-microm waveband for photonic transport systems, we developed a hybrid and harmonically mode-locked semiconductor laser (MLL) that can transmit return-to-zero (RZ) optical signals at data rates on the order of gigabits per second. A single-mode hole-assisted fiber (HAF) was also developed for use as a 1-microm waveband signal transmission line. A stable optical pulse train with a repetition rate of 9.953 GHz, pulse width of 22 ps, and low timing jitter of 120 fs was obtained from a 1035-nm harmonically MLL. With these devices, we successfully demonstrated 1-microm waveband error-free transmission of a high-speed 10-Gbps RZ signal over a long distance of 7 km.


Ex vivo effects of high-density lipoprotein exposure on the lipopolysaccharide-induced inflammatory response in patients with severe cirrhosis.
High-density lipoproteins (HDL) are known to neutralize lipopolysaccharide (LPS). Because patients with cirrhosis have lower HDL levels, this may contribute to LPS-induced ex vivo monocyte overproduction of proinflammatory cytokines. However, the effects of HDL on cytokine production by monocytes from patients with cirrhosis have never been studied. The aim of this study was to determine the effects of HDL on LPS-induced proinflammatory cytokine production in whole blood and isolated monocytes from patients with severe cirrhosis and controls. Plasma levels of HDL and cytokines were determined. The effects of reconstituted HDL (rHDL) on LPS-induced cytokine production in whole blood were assessed by cytokine array and on tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) production in isolated monocytes. Plasma HDL levels were significantly lower in patients with cirrhosis than in controls. Plasma levels of TNF-alpha and IL-6 were significantly higher in patients with cirrhosis than in controls. Incubation of rHDL with whole blood prevented LPS-induced TNF-alpha and IL-6 overproduction in patients with cirrhosis. LPS-induced TNF-alpha production and CD14 expression were significantly more marked in cirrhotic monocytes than in control monocytes, and both decreased significantly after rHDL incubation. LPS-induced down-regulation of scavenger receptor, class B, type I (SR-BI) expression was abolished in cirrhotic monocytes. This study shows that rHDL abolishes the LPS-induced overproduction of proinflammatory cytokines in whole blood from patients with severe cirrhosis. These results were confirmed in isolated monocytes from these patients. This suggests that administration of rHDL might be a useful strategy for the treatment of cirrhosis to limit LPS-induced cytokine overproduction.


UV Photochemical vapor generation sample introduction for determination of Ni, Fe, and Se in biological tissue by isotope dilution ICPMS.
A novel, sensitive method is described for the accurate determination of Ni, Se, and Fe in biological tissues by isotope dilution inductively coupled plasma mass spectrometry (ID ICPMS) based on sample introduction arising from online UV photochemical vapor generation (UV-PVG). Volatile species of Ni, Se, and Fe were liberated from a formic acid medium following exposure to a UV source. Sensitivities were enhanced 27- to 355-fold compared to those obtained using pneumatic nebulization sample introduction. Although precision was slightly degraded (a factor of 2) with ultraviolet photochemical mediated vapor generation (UV-PVG), limits of detection (LODs) of 0.18, 1.7, and 1.0 pg g(-1) for Ni, Se, and Fe, respectively, based on an external calibration, provided 28-, 150-, and 29-fold improvements over that realized with conventional pneumatic solution nebulization. Method validation was demonstrated by determination of Ni, Se, and Fe in biological tissue certified reference materials (CRMs) TORT-2 and DORM-3. Concentrations of 2.33 +/- 0.03, 5.80 +/- 0.28, and 109 +/- 2 microg g(-1) (1SD, n = 4) and 1.31 +/- 0.04, 3.35 +/- 0.18, and 353 +/- 5 microg g(-1) (1SD, n = 4) for Ni, Se, and Fe, respectively were obtained in TORT-2 and DORM-3, in good agreement with certified values.


Update on the role of R2R3-MYBs in the regulation of glucosinolates upon sulfur deficiency.
To balance the flux of sulfur (S) into glucosinolates (GSL) and primary metabolites plants exploit various regulatory mechanisms particularly important upon S deficiency (-S). The role of MYB34, MYB51 and MYB122 controlling the production of indolic glucosinolates (IGs) and MYB28, MYB29, and MYB76 regulating the biosynthesis of aliphatic glucosinolates (AGs) in Arabidopsis thaliana has not been fully addressed at -S conditions yet. We show that the decline in the concentrations of GSL during S depletion does not coincide with the globally decreased transcription of R2R3-MYBs. Whereas the levels of GSL are diminished, the expression of MYB34, MYB51, MYB122, and MYB28 is hardly changed in early phase of S limitation. Furthermore, the mRNA levels of these MYBs start to raise under prolonged S starvation. In parallel, we found that SLIM1 can downregulate the MYBs in vitro as demonstrated in trans-activation assays in cultured Arabidopsis cells with SLIM1 as effector and ProMYB51:uidA as a reporter construct. However, in vivo, only the mRNA of MYB29 and MYB76 correlated with the levels of GSL at -S. We propose that the negative effect of SLIM1 on GSL regulatory genes can be overridden by a "low GSL signal" inducing the transcription of MYBs in a feedback regulatory loop. In accordance with this hypothesis, the expression of MYB34, MYB51, MYB122, and CYP83B1 was further induced in cyp79b2 cyp79b3 mutant exposed to -S conditions vs. cyp79b2 cyp79b3 plants grown on control medium. In addition, the possible role of MYBs in the regulation of essential S assimilation enzymes, in the regulation of GSL biosynthesis upon accelerated termination of life cycles, in the mobilization of auxin and lateral root formation at S deficiency is discussed.


Incoherent method for rotation-invariant recognition.
An optodigital hybrid system using an incoherent circular correlator that has features suitable for space and industrial applications is introduced. The incoherent circular correlator uses a fiber-optics sampler and carries out the correlations in white light. The trade offs involved for efficient detection of objects are discussed. The system has been built, and experimental results on a real air photograph are presented.


Changes in Nitric Oxide Releases of the Contralateral Acupoint during and after Laser Acupuncture at Bilateral Same-Name Acupoints in Human.
The purpose of the study was to examine the effects of laser acupuncture (LA) at right Neiguan (RPC6)/left Neiguan (LPC6) acupoints on the releases of nitric oxide (NO) in the treated and contralateral/nontreated PC6, compared to the nonacupoint control area. 24 mW LA at RPC6, LPC6, and nonacupoint in 22 healthy subjects for 40 min: sterilized dialysis tube was taped to the nontreated PC6/nonacupoint during the treatment and immediately taped to the treated and nontreated PC6/nonacupoint after LA removal. NO-scavenging compound was injected into the tube for 40 min to absorb the molecular which was tested by spectrophotometry in a blinded fashion. LA-induced NO releases over PC6 acupoints for the nontreated and treated sides all significantly increased after LA removal, but for the nontreated acupoints they did not change during LA stimulation. LA at RPC6 induced the more release of the NO at contralateral side than stimulating LPC6, but not on nonacupoints. The results suggest that LA-induced NO release over contralateral acupoint and NO release resulting from the lateralized specificity all are different and specific to the acupoint within different time course. LA-evoked NO release over acupoints could improve the neurogenic, endothelial activity of the vessel wall to further facilitate microcirculation.


Exploiting online discussions to discover unrecognized drug side effects.
Drugs can treat human diseases through chemical interactions between the ingredients and intended targets in the human body. However, the ingredients could unexpectedly interact with off-targets, which may cause adverse drug side effects. Notifying patients and physicians of potential drug effects is an important step in improving healthcare quality and delivery. With the increasing popularity of Web 2.0 applications, more and more patients start discussing drug side effects in many online sources. These online discussions form a valuable source for mining interesting knowledge about side effects. The main goal of this paper is to investigate the feasibility of exploiting these discussions to discover unrecognized drug side effects. We propose methods that can 1) build a knowledge base for drug side effects by automatically integrating the information related to drug side effects from different sources; and 2) monitor online discussions about drugs and discover potential unrecognized drug side effects. Experiment results show that the online discussions indeed provide useful information discovering unrecognized drug side effects. We find that the integrated knowledge base contains more information than individual online sources. Moreover, both proposed detection methods can identify the side effects related to the four recently recalled drugs, and the information from online discussions makes it possible to make the detection much earlier than official announcements. Finally, the proposed generative modeling method is shown to be more effective than the discriminative method. We find that it is possible to monitor online discussions to detect unrecognized drug side effects. The developed system is expected to serve as a complementary tool for drug companies and FDA to receive feedbacks from the patients, and it has the potentials to expedite the discovery process of unrecognized drug side effects and to improve the quality of healthcare.


cDNA cloning, heat shock regulation and developmental expression of the hsp83 gene in the Mediterranean fruit fly Ceratitis capitata.
This report presents the cDNA cloning, heat shock regulation and developmental expression of the hsp90 gene homologue of the Mediterranean fruit fly Ceratitis capitata (medfly). The isolated cDNA contained the coding region, the 3'UTR and most of the 5'UTR of the medfly hsp90 homologue, which was named Cchsp83. The deduced CcHSP83 polypeptide contained all the highly conserved amino acid segments that characterize the cytosolic members of the HSP90 family. Genomic analysis showed that the Cchsp83 gene is unique and was mapped at the 94C division of the sixth polytene chromosome. The size of the Cchsp83 mRNA was found to be approximately 2.7 kb. The predicted molecular mass of the CcHSP83 protein was 81.4 kDa, while the apparent molecular weight estimated by SDS-PAGE was approximately 90 kDa. Phylogenetic analysis based on 14 insect HSP90 amino acid sequences was consistent with the known phylogeny at low taxonomic level. The Cchsp83 gene is constitutively expressed in all stages of medfly development and is induced from a low level to several-fold by heat, depending on the developmental stage. Heat shock induction begins at 30 degrees C, reaching a maximum between 35 and 41 degrees C. Cchsp83 RNA expression is highly regulated during embryonic development; however, the temporal fluctuations in RNA levels during embryogenesis were not followed by similar fluctuations in the levels of the protein.


Innovative solutions: leading the way: an innovative approach to support nurses on general care units with an early nursing intervention team.
In an effort to improve patient outcomes, there has been a global initiative to prevent avoidable adverse events. The rapid response team or medical emergency team concept has been in existence for the past several years and there has been a significant improvement in patient outcomes. This article will describe one institution's success in taking this concept even further by rounding on general care units before patient problems are evident. The focus of this discussion will be on the remarkably positive nursing staff outcomes that have been achieved as a result of a program called the Early Nursing Intervention Team, a totally nurse-led program.


Crossed jet reactive scattering dynamics of F+H(2)O-->HF(v,J)+OH:HF(v,J) product quantum state distributions under single-collision conditions.
Reactive scattering dynamics of F+H(2)O-->HF+OH have been investigated under single-collision, crossed, supersonic jet conditions at 5.4(1.3) kcalmol, and nascent HF(v,J) rovibrational populations (v<or=2, J<or=17) have been observed via high resolution IR laser absorption methods. Vibrational populations are highly inverted, with 75(2)% and 21(5)% of the observed HF product formed in v=1 and 0, respectively. Small but finite branching [5(1)%] into the v=2 manifold is observed, which is accessible only via the additional center of mass collision energy in the crossed jets. Despite energy constraints associated with substantial vibrational excitation, the reaction dynamics also lead to rotationally hyperthermal HF, with populations observed up to near the energetic limit for each of the v=0,1,2 vibrational manifolds. The trends in these nascent product rovibrational distributions are interpreted in terms of ab initio predictions of a strongly bent, early-barrier transition state and long-range dipole-dipole interactions in the exit channel.


Influence of Paravertebral Muscle Quality on Treatment Efficacy of Epidural Steroid Infiltration or Surgical Decompression in Lumbar Spinal Stenosis-Analysis of the Lumbar Spinal Outcome Study (LSOS) Data: A Swiss Prospective Multicenter Cohort Study.
Prospective multicenter cohort study. To study the question whether paravertebral muscle quality may affect the clinical outcome of epidural steroid infiltration (ESI) or surgical decompression in patients with symptomatic lumbar spinal stenosis (LSS). To the present, the impact of paravertebral muscle quality on clinical outcome of ESI or surgical decompression in patients with LSS has not been clarified. The Lumbar Stenosis Outcome Study was used as database. Patients with symptomatic LSS who received an ESI (group I) or lumbar decompression surgery (group II), had a follow-up of at least 12 months and a pretreatment lumbar magnetic resonance imaging were included (n = 205). Paravertebral muscle quality was quantified by the degree of fatty degeneration (according to Goutallier) on the level L3. Clinical outcome was assessed using the Spinal Stenosis Measure, Numeric Rating Scale, Roland and Morris Disability Questionnaire, and EQ-5D-3L sum score. Reinfiltration, surgery following infiltration, or revision was defined as treatment failure. ESI (group I) and surgical treatment (group II) were associated with a failure rate of 60% and 12.7%, respectively. In group I, there was a tendency for the rate of reintervention to be less in patients with bad muscle quality (P = 0.22). In group II, improvements in the clinical outcomes up to 12 months did not differ between Goutallier stage ≤1 and ≥2. Patients with Goutallier stage ≤1 had more improvement in Spinal Stenosis Measure symptoms (P = 0.04). Relevant fatty degeneration of the paravertebral musculature, as a sign of low muscle quality, has low impact on clinical outcome and the high failure rates with conservative treatment by ESI compared to surgical decompression. Therefore fatty degeneration has no relevant prognostic value for LSS treatment. 2.


Complications of jejunoileal bypass for morbid obesity.
Fifty-two patients had jejunoileal bypass surgery. End-to-end (Scott) or end-to-side (Payne) shunts were randomly selected for each patient; 31 standard length shunts and 21 shortened bypasses were performed. Only 22 patients had an acceptable result, whereas 30 patients had inadequate weight loss (less than 2.3 kg [5 lb] per month per year) or had gastrointestinal tract, metabolic, or surgical complications judged severe enough to render the outcome less than adequate. There was one death, and four patients required reanastomosis of the bypass. The primary deteriminant of success was age, ie, younger patients had clearly better results than older patients. In general, shorter shunts produced more weight loss than standard bypass procedures, but were associated with an increased complication rate. Three new complications of jejunolieal bypass are reported: acute comonic dilation with necrosis, beriberi, and lupus erythematosus.


Development of Feasible Methods to Image the Eyelid Margin Using In Vivo Confocal Microscopy.
To develop a feasible method to image eyelid margin structures using in vivo confocal microscopy (IVCM) for use in clinical research. Second, to assess the association between IVCM and meibography images. IVCM was performed on the central upper eyelid margin of 13 healthy participants (31 ± 5 years). Overall morphology montages (1600 × 1600 μm) were created of 3 participants. Single frames (400 × 400 μm) of 10 participants were imaged to determine the feasibility of measuring eyelid features. Meibography was performed with EASYTEARview+ in the same 10 participants. ImageJ software was used to quantify image structures. In the montages, structures of rete ridges, meibomian gland openings, and the lid wiper region were observed. The maximum possible montage size, using multiple single frames, was approximately 5200 × 1500 × 150 μm in the X, Y, and Z directions, respectively. The mean number, density, area, perimeter, and shortest and longest diameters of rete ridges of the 9 nonoverlapped frames were 12 ± 2/frame, 73 ± 5/mm, 2504 ± 403 μm, 250 ± 33 μm, 40 ± 6 μm, and 84 ± 13 μm, respectively. Sampling analysis determined at least 5 nonoverlapped frames were necessary to accurately represent the parameters of the ridges. The mean areas of 3 meibomian openings were 785 ± 784 μm, 1036 ± 963 μm, 950 ± 1071 μm, 848 ± 954 μm, 737 ± 831 μm, 735 ± 743 μm, and from 30 μm to 130 μm at 20-μm depth intervals, respectively. No significant association between IVCM and meibography parameters (P = 0.53) was found. Imaging rete ridges with IVCM should include at least 5 nonoverlapping single frames in the upper eyelid margin. At least 3 openings imaged between 30 and 130 μm at 20-μm depth intervals are recommended to determine the opening area.


Does a relative perfusion measure predict cerebral infarct size?
MR perfusion-weighted imaging (PWI) has been extensively used to quantify cerebral perfusion deficits after the onset of focal ischemia. The present study tested whether a relative measure of cerebral blood flow such as is obtained with PWI is sufficient to predict irreversible tissue damage following focal cerebral ischemia and reperfusion in the rat suture model. In rats, the middle cerebral artery was occluded (MCAO) for 1 hour followed by 1-hour reperfusion. Microspheres labeled with different tracers were injected into the left ventricle to permit measurement of blood flow at different time points: before MCAO, 30 minutes post-MCAO and 30 minutes postreperfusion. Absolute cerebral blood flow (CBF) was determined and relative CBF was calculated by comparing absolute CBF at each time point to baseline values before MCAO (relative CBF(B)) or to corresponding contralateral areas in the noninfarcted hemisphere (relative CBF(C)). Infarct size was assessed by 2,3,5-triphenyltetrazolium chloride staining. Absolute CBF in vital tissue was 0.69 +/- 0.07 mL/g/min. In partially and completely necrotic tissue, absolute CBF was 0.39 +/- 0.05 mL/g/min and 0.30 +/- 0.09 mL/g/min, respectively. Although there was a close inverse correlation between infarct volume and absolute CBF (r = 0.79), the correlations between infarct volume and relative CBF(C) were poor (r = 0.21). The present study revealed that absolute CBF is superior to relative CBF in predicting irreversible tissue damage following ischemia and reperfusion.


Gene expression profile of the developing endosperm in durum wheat provides insight into starch biosynthesis.
Durum wheat (Triticum turgidum subsp. durum) is widely grown for pasta production, and more recently, is gaining additional interest due to its resilience to warm, dry climates and its use as an experimental model for wheat research. Like in bread wheat, the starch and protein accumulated in the endosperm during grain development are the primary contributors to the calorific value of durum grains. To enable further research into endosperm development and storage reserve synthesis, we generated a high-quality transcriptomics dataset from developing endosperms of variety Kronos, to complement the extensive mutant resources available for this variety. Endosperms were dissected from grains harvested at eight timepoints during grain development (6 to 30 days post anthesis (dpa)), then RNA sequencing was used to profile the transcriptome at each stage. The largest changes in gene expression profile were observed between the earlier timepoints, prior to 15 dpa. We detected a total of 29,925 genes that were significantly differentially expressed between at least two timepoints, and clustering analysis revealed nine distinct expression patterns. We demonstrate the potential of our dataset to provide new insights into key processes that occur during endosperm development, using starch metabolism as an example. We provide a valuable resource for studying endosperm development in this increasingly important crop species.


Probing the Electrophysiology of the Developing Heart.
Many diseases that result in dysfunction and dysmorphology of the heart originate in the embryo. However, the embryonic heart presents a challenging subject for study: especially challenging is its electrophysiology. Electrophysiological maturation of the embryonic heart without disturbing its physiological function requires the creation and deployment of novel technologies along with the use of classical techniques on a range of animal models. Each tool has its strengths and limitations and has contributed to making key discoveries to expand our understanding of cardiac development. Further progress in understanding the mechanisms that regulate the normal and abnormal development of the electrophysiology of the heart requires integration of this functional information with the more extensively elucidated structural and molecular changes.


Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.
Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.


Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study.
Despite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB). Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 months after the start of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen-stimulated cytokines was conducted to select potential biomarkers for further testing. Outcome was defined as persistent culture positivity at 2 months into treatment. Of 167 enrolled patients, 26 had persistent culture positivity. RANTES, IL-22, MMP-8, IL-18, MIG, and Granzyme A were selected as potential biomarkers. For predicting persistent culture positivity, receiver-operating characteristics (ROC) analysis showed that initial RANTES (AUC: 0.725 [0.624-0.827]) and 2-month MMP-8 (AUC: 0.632 [0.512-0.713]) had good discriminative ability. Using a logistic regression model, low initial RANTES level (< 440 pg/mL), initial smear positivity, and high 2-month MMP-8 level (> 3000 pg/mL) were associated with persistent culture positivity. Low initial RANTES level and initial smear positivity had a positive predictive value of 60% (12/20) for persistent culture positivity, compared with 4% (3/75) among patients with high RANTES level and smear negativity upon diagnosis. In the 72 patients with either low RANTES/smear negativity or high RANTES/smear positivity upon diagnosis, the 2-month MMP-8 level had a positive and negative predictive value of 24 and 94%, respectively, for 2-month culture status. Aside from an initial sputum smear status, serum RANTES level at diagnosis and MMP-8 level at 2 months of treatment may be used to stratify risk for culture persistence.


[Plastic surgery in the treatment of the outcome of intestinal bypass for obesity: a clinical case report].
The authors report the case of a 39-year old woman who had a fast and dramatic weight loss after an intestinal bypass performed elsewhere. The result was a generalized skin flakiness which caused dissatisfaction and psychological unbalance of the patient. Three plastic surgeries were therefore programmed and performed at different moments: mastopexy, abdominoplasty and upper thigh dermolipectomy. No immediate or late complications were observed, even after 2 years. The authors stress the importance of a correct planning of a plastic surgery as a solution to the generalized tissue flakiness in the formerly obese patient.


Association between anxiety and skin conductance according to the intensity of shaking of virtual reality images.
Despite the advantages of virtual reality (VR), cyber sickness makes it difficult to apply VR to those who are already anxious and in distress. Skin conductance (SC) is widely used as a bio-signal reflecting anxiety. It is positively correlated with anxiety. The objective of this study was to determine the association between SC and anxiety in VR. Healthy volunteers with moderate-to-high stress defined as a Perceived Stress Scale-10 (PSS-10) score ≥20 were enrolled. STAI-X-1 was used to measure anxiety, and galvanic skin response was used to measure SC. This study used an open, randomized, crossover design. In this study, 360° videos consisted of two types, namely, less dizzying video (G1) and more dizzying video (G2). We randomized subjects into two groups according to video exposure order: G1 after watching G2 (Order 1) and G2 after watching G1 (Order 2). Of 81 subjects, the average age (±SD) was 39.98 ± 10.94 years for the Order 1 group and 36.54 ± 12.44 years for the Order 2 group. Anxiety was significantly decreased in the Order 2 group (p < 0.035) after watching videos, whereas there was no significant change in anxiety in the Order 1 group. In both groups, SC was significantly increased after exposure to a dizzying video. Mean difference (SD) between the second VR video and baseline SC was 1.61 (1.07) (p < 0.0001) in the Order 1 group and 0.92 (0.90) (p < 0.0001) in the Order 2 group, showing a significant difference between the two groups (p < 0.003). However, there was no significant difference between the two groups (p < 0.077) after baseline correction. Anxiety was decreased significantly in the Order 2 group. The Order 1 group showed a high rate of change in skin conductivity. It is possible to reduce SC and anxiety by viewing a less dizzying VR video first and then viewing a more dizzying video later.


Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction.
We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR. During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression. There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2α: 0.92; p < 0.06). Within the IUGR group, no fetal gender-dependent differences were seen in placental PIGF gene expression (Ln2α: 0.72; p = 0.05). Placental PIGF gene activity was significantly lower in fetuses with more severe IUGR versus less severe cases (Ln2α: -1.49; p < 0.03). We found no difference in gene expression of PIGF in placental samples obtained from IUGR pregnancies versus normal pregnancy suggesting the absence of a direct role of PIGF gene activity in the development of defective angiogenesis in IUGR during the later stages of gestation. However, in more severe cases of intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.


Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats.
Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines. The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL). Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-alpha, IL-1beta and IL-6 were also assayed in plasma samples. In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p<0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p<0.05-p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment. Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.


Self-assembled photoresponsive amphiphilic diphenylaminofluorene-C60 conjugate vesicles in aqueous solution.
Water-soluble oligo(ethylene glycolated) derivatives of two-photon absorptive diphenylaminofluorenocarbonyl-methano[60]fullerene, denoted as C60(>DPAF-EG6), were synthesized with their molecular self-assembly characteristics in H2O studied. The formation of nano- to submicron-sized spherical hollow vesicles with a shell width of 15-20 nm was observed by transmission electron microscopy (TEM) micrographs. This shell width fits approximately with the length of a disordered bilayer-like molecular packing of C60(>DPAF-EG6), arising from strong intermolecular hydrophobic interactions of fullerene cages. Photoinduced intramolecular charge separation followed by charge recombination on the nanosecond time scale, from the DPAF moiety to the C60 cage in the vesicle structure, was detected via transient spectroscopic measurements.


Factors associated with elective Norplant removal in black and white women.
Premature removal of contraceptive implants (Norplant [levonorgestrel implants], Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) is a cause of a sizable national medical expenditure in the United States. Understanding the factors that influence the decision to remove the implants and being able to predict which users are likely to elect discontinuation prematurely could provide useful information for counseling patients as they are considering contraceptive implants so that potentially enormous long-term savings could be achieved. This study surveyed 98 women who had Norplant inserted and removed between January 1991 and December 1994. Data were collected from chart review, and when necessary, a questionnaire was used to extract information not found in the chart. The chi-squared statistic and t-test were used to compare demographic variables. All but one subject received comprehensive pre-implant counseling. The main reason given for electively removing the Norplant prematurely was irregular menstrual bleeding (60%). Pre-implant counseling did not influence the decision for removal. These results indicate the importance of clarifying patients' doubts regarding menstrual bleeding irregularities during follow-up visits rather than relying on the information patients received during preimplant counseling.


[Therapeutic attitude of kidney transplantation patients--initial results of a psychological test study].
After kidney transplantation the patient is subject to psychological stress due to problem situations. To date these problems have described only in very general clinical terms. Initial results of a psychological study on 26 kidney-transplant patients allow us to recognize factors which influence the patients' attitude to the disease and therapy. Such factors are: success of therapy, emotional tension, attitude towards the doctor and the self-confidence of the patient. The doctor-patient relation corresponds to the attitude towards therapy only in the immediate post-operative period and in patients with a negative attitude towards therapy. In the assessment of the doctor-patient relation it is only of medium importance whether the patient likes the doctor. The Study is being continued.


Emerging therapeutic targets for gastric cancer from a host-Helicobacter pylori interaction perspective.
Gastric cancer (GC) has the higher genetic, cytologic, and architectural heterogeneity compared to other gastrointestinal cancers. By inducing gastric inflammation, Helicobacter pylori (HP) may lead to GC through combining bacterial factors with host factors. In this regard, identification of the major therapeutic targets against the host-HP interactions plays a critical role in GC prevention, diagnosis, and treatment. This study offers new insights into the promising therapeutic targets against the angiogenesis, invasion, or metastasis of GC from a host-HP interaction perspective. To this end, MEDLINE, EMBASE, LILACS, AIM, and IndMed databases were searched for relevant articles since 1992. Wnt signaling and COX pathway have a well-documented history in the genesis of GC by HP and might be considered as the most promising targets for early GC treatment. Destroying HP may decrease the risk of GC, but it cannot fully hinder the GC development induced by HP infection. Therefore, targeting HP-activated pathways, especially COX-2/Wnt/beta-catenin/VEGF, TLR2/TLR9/COX-2, COX2-PGE2, and NF-κB/COX-2, as well as EPHA2, MMPs, and miR-543/SIRT1 axis, can be an effective measure in the early treatment of GC. However, different clinical trials and large, multi-center cohorts are required to validate these potentially effective targets for GC therapy.


Raman spectra of double-wall carbon nanotubes under extreme uniaxial stress.
We investigated the pressure dependence of the Raman frequencies and intensities of the D and G bands of double-wall carbon nanotubes under strong uniaxial conditions. Using moissanite anvils, we observed for the first time the evolution of the D band under extreme stress/pressure conditions. We find that the difference between D and G frequencies remains constant over the whole stress range. In addition, we observe that double-wall carbon nanotubes behave elastically up to the maximum uniaxial stress reached in our experiments, which is estimated to be about 12 GPa.


[Osteogenesis and chondrogenesis from a stem cell source].
Osteoblasts and chondrocytes are most useful cells for osteogenesis and chondrogenesis, respectively. Mesenchymal stem cells can also be used after in vitro induction or without any treatment. Meanwhile, ES cells, iPS cells and GS cells become alternative cells for osteogenesis and chondrogenesis. Cell sources for the regenerative medicine of bone and cartilage should be determined, based on "benefit" and "risk" balance in clinics.


Regulated Assembly of LPS, Its Structural Alterations and Cellular Response to LPS Defects.
Distinguishing feature of the outer membrane (OM) of Gram-negative bacteria is its asymmetry due to the presence of lipopolysaccharide (LPS) in the outer leaflet of the OM and phospholipids in the inner leaflet. Recent studies have revealed the existence of regulatory controls that ensure a balanced biosynthesis of LPS and phospholipids, both of which are essential for bacterial viability. LPS provides the essential permeability barrier function and act as a major virulence determinant. In Escherichia coli, more than 100 genes are required for LPS synthesis, its assembly at inner leaflet of the inner membrane (IM), extraction from the IM, translocation to the OM, and in its structural alterations in response to various environmental and stress signals. Although LPS are highly heterogeneous, they share common structural elements defining their most conserved hydrophobic lipid A part to which a core polysaccharide is attached, which is further extended in smooth bacteria by O-antigen. Defects or any imbalance in LPS biosynthesis cause major cellular defects, which elicit envelope responsive signal transduction controlled by RpoE sigma factor and two-component systems (TCS). RpoE regulon members and specific TCSs, including their non-coding arm, regulate incorporation of non-stoichiometric modifications of LPS, contributing to LPS heterogeneity and impacting antibiotic resistance.


The impact of prolonged storage of red blood cells on cancer survival.
The duration of storage of transfused red blood cells (RBC) has been associated with poor clinical outcomes in some studies. We sought to establish whether prolonged storage of transfused RBC in cancer patients influences overall survival (OS) or cancer recurrence. Patients diagnosed with cancer at The Ottawa Regional Cancer Centre between January 01, 2000 and December 31, 2005 were included (n = 27,591) where 1,929 (7.0%) received RBC transfusions within one year from diagnosis. Transfused RBC units were categorized as "new" if stored for less than 14 days, "intermediate" if stored between 14 and 28 days and "old" if stored for more than 28 days. Baseline characteristics between the comparative groups were compared by ANOVA test. Categorical variables and continuous variables were compared using Chi-squared and Wilcoxan rank-sum tests respectively. Overall survival was not associated with duration of storage of transfused RBC with a median survival of 1.2, 1.7, 1.1 years for only new, intermediate and old RBC units respectively (p = 0.36). Cancer recurrence was significantly higher in patients who received a RBC transfusion than those who did not (56.3% vs 33.0% respectively; p<0.0001) but was not affected by the duration of storage of transfused RBC (p = 0.06). In multivariate analysis, lung cancer, advanced stage, chemotherapy, radiation, cancer-related surgery and cancer recurrence were associated with inferior OS (p<0.05), while age, advanced stage, lung cancer, and more than 6 units of blood transfused were associated with cancer recurrence (p<0.05). The duration of storage of RBC before transfusion was not associated with OS or cancer recurrence in multivariate analysis. In patients diagnosed with cancer, the duration of storage of transfused RBC had no impact on OS or cancer recurrence. This suggests that our current RBC storage policy of providing RBC of variable duration of storage for patients with malignancy is safe.


Inhibition of Escherichia coli isoleucine biosynthesis by isoleucine tetrazole.
Growth of a derivative of Escherichia coli K-10 was strongly inhibited by 2 times 10(-4) M L-5(1-amino-2-methylbutyl)-tetrazole (isoleucine tetrazole). Growth inhibition was reversed by isoleucine, threonine, glycyl-L-isoleucine, or glycyl-L-threonine, and, in a valine-resistant mutant, by L-valine. Partial reversal of growth inhibiton was effected by L-leucine, L-methionine, or L-homoserine. The tetrazole inhibited the activity of the biosynthetic threonine deaminase (EC 220.127.116.11 L-threonine hydrolyase [deaminating]), the inhibition being relieved by L-valine. The tetrazole also inhibited isoleucyl-transfer ribonucleic acid (tRNA) synthetase (EC 220.127.116.11 L-isoleucine: tRNA ligase [adenosine monophosphate]), but was without effect on the activities of alpha-isopropylmalate synthetase or acetohydroxy acid synthetase. One class of isoleucine tetrazole-resistant mutants produced biosynthetic threonine deaminases which were no longer subject to feedback inhibition by either isoleucine or the tetrazole.


Application of vaccine technology to prevention of Pseudomonas aeruginosa infections.
Development of an effective vaccine against the multiple presentations of Pseudomonas aeruginosa infection, including nosocomial pneumonia, bloodstream infections, chronic lung infections in cystic fibrosis patients and potentially sight-threatening keratitis in users of contact lenses, is a high priority. As with vaccine development for any pathogen, key information about the most effective immunologic effectors of immunity and target antigens needs to be established. For P. aeruginosa, although there is a role for cell-mediated immunity in animals following active vaccination, the bulk of the data indicate that opsonically-active antibodies provide the most effective mediators of acquired immunity. Major target antigens include the lipopolysaccharide O-polysaccharides, cell-surface alginate, flagella, components of the Type III secretion apparatus and outer membrane proteins with a potentially additive effect achieved by including immune effectors to toxins and proteases. A variety of active vaccination approaches have the potential for efficacy such as vaccination with purified or recombinant antigens incorporating multiple epitopes, conjugate vaccines incorporating proteins and carbohydrate antigens, and live attenuated vaccines, including heterologous antigen delivery systems expressing immunogenic P. aeruginosa antigens. A diverse range of passive immunotherapeutic approaches are also candidates for effective immunity, with a variety of human monoclonal antibodies described over the years with good preclinical efficacy and some early Phase I and II studies in humans. Finding an effective active and/or passive vaccination strategy for P. aeruginosa infections could be realized in the next 5 to 10 years, but will require that advances are made in the understanding of antigen expression and immune effectors that work in different human tissues and clinical settings, and also require a means to validate that clinical outcomes achieved in Phase III trials represent meaningful advances in management and treatment of P. aeruginosa infections.


Epidemiological Trends of Anterior Cruciate Ligament Reconstruction in a Canadian Province.
To determine epidemiological trends of anterior cruciate ligament reconstruction (ACL-R) in a Canadian province, estimate the national incidence, and compare with internationally published data. Retrospective review. All hospitals that performed ACL reconstructions in Manitoba between 1980 and 2015. All patients that underwent ACL-R in Manitoba between 1980 and 2015. This is a retrospective review looking at deidentified, individual-level administrative records of health services used for the entire population of Manitoba (approximately 1.3 million). Codes for ACL and cruciate ligament reconstruction were searched from 1980 to 2015. Patient demographics included age, sex, geographic area of residence, and neighborhood income quintile. Trends of ACL reconstructions from 1980 to 2015. A total of 10 114 ACL-R were performed during the 36-year study period and patients were predominantly male (63.1%). The mean age at ACL-R was 29.5 years (SD 10.0) for males and 28.5 years (SD 11.9) for females, whereas age younger than 40 years accounted for 81.7% of all ACL-R. The incidence of ACL-R increased from 7.56/100 000 inhabitants in 1980 to 48.45/100 000 in 2015. The proportion of females undergoing ACL-R has increased from 29.3% in 1980% to 41.9% in 2015, and female patients now comprise the majority of ACL-R in the under-20 age category. The incidence of ACL-R has significantly increased since 1980; female patients now make up a greater proportion than males of the ACL-R population younger than 20 years. This information can be used to guide resource allocation planning and focus injury prevention initiatives.


Calcium, magnesium, and nitrate in drinking water and gastric cancer mortality.
The possible association between the risk of gastric cancer and the levels of calcium, magnesium, and nitrate in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Records of gastric cancer deaths among eligible residents in Taiwan from 1987 through 1991 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by sex, year-of-birth, and year-of-death. Each matched control was selected randomly from the set of possible controls for each case. Data on calcium, magnesium, and nitrate levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation. The municipality of residence of the cases and controls was assumed to be the source of the subject's calcium, magnesium, and nitrate exposure via drinking water. The subjects were divided into tertiles according to the levels of calcium, magnesium, and nitrate in their drinking water. The results of the present study show that there is a significant positive association between drinking water nitrate exposure and gastric cancer mortality. The present study also suggests that there was a significant protective effect of calcium intake from drinking water on the risk of gastric cancer. Magnesium also exerts a protective effect against gastric cancer, but only for the group with the highest levels.


SEM examination of the eggs of five British Aedes species.
Ultrastructure descriptions are given of the eggs of five British Aedes species, namely Aedes (Aedes) cinereus Meigen, Aedes (Ochlerotatus) cantans (Meigen), Aedes (Ochlerotatus) punctor (Kirby), Aedes (Ochlerotatus) detritus (Haliday), and Aedes (Ochlerotatus) rusticus (Rossi). Eggs of the first 4 species are broadly cigar/boat-shaped, with those of Ae. cinereus being characteristically long and narrow, in contrast to the overall shape of Ae. rusticus, which is quite distinct, being in profile almost subtriangular with rounded corners, and is completely species-diagnostic. In Ae. cantans, Ae. punctor, and Ae. rusticus there is usually a single large tubercle in each chorionic cell and there is little, if any, difference in the sculpturing of the ventral and dorsal surfaces, whereas in Ae. detritus each cell contains more than 20 tubercles, and in Ae. cinereus there are usually 6 tubercles per cell ventrally, but dorsally there are no tubercles or distinct cells but numerous cone-shaped papillae. All 5 species can be separated from each other by SEM examination of their chorionic patterns.


Polycomb repression regulates Schwann cell proliferation and axon regeneration after nerve injury.
The transition of differentiated Schwann cells to support of nerve repair after injury is accompanied by remodeling of the Schwann cell epigenome. The EED-containing polycomb repressive complex 2 (PRC2) catalyzes histone H3K27 methylation and represses key nerve repair genes such as Shh, Gdnf, and Bdnf, and their activation is accompanied by loss of H3K27 methylation. Analysis of nerve injury in mice with a Schwann cell-specific loss of EED showed the reversal of polycomb repression is required and a rate limiting step in the increased transcription of Neuregulin 1 (type I), which is required for efficient remyelination. However, mouse nerves with EED-deficient Schwann cells display slow axonal regeneration with significantly low expression of axon guidance genes, including Sema4f and Cntf. Finally, EED loss causes impaired Schwann cell proliferation after injury with significant induction of the Cdkn2a cell cycle inhibitor gene. Interestingly, PRC2 subunits and CDKN2A are commonly co-mutated in the transition from benign neurofibromas to malignant peripheral nerve sheath tumors (MPNST's). RNA-seq analysis of EED-deficient mice identified PRC2-regulated molecular pathways that may contribute to the transition to malignancy in neurofibromatosis.


A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression.
Neuropsychological studies of bipolar disorder reveal deficits in a variety of domains, including affective processing, memory, and sustained attention. These findings are difficult to interpret due to the potential confounding effects of mood-stabilizing medications. The present study aims to compare the cognitive performance of medicated and unmedicated subjects with bipolar depression to healthy control subjects. Unmedicated subjects with bipolar depression (UBD, n = 32), subjects with bipolar depression on therapeutic doses of lithium or valproic acid (MBD, n = 33), and healthy control subjects (HC, n = 52) performed neuropsychological tasks measuring affective processing, visual memory, and sustained attention. Performance measures were covaried with age and mood ratings, where applicable. With regard to affective processing, the MBD group exhibited greater response latency than the UBD and HC groups. For the same task, the MBD group made more omission errors during the happy condition than in the sad condition. On a task of sustained attention, the MBD group made more errors than the HC group. There were no significant group differences on measures of visual memory. Deficits in affective processing were found in the medicated group, while unmedicated subjects appear to be unaffected. In particular, the MBD group made more errors during happy conditions, indicating a potential attentional bias in subjects with bipolar depression on mood-stabilizing medications. The present study also implicates impairment in sustained attention for medicated subjects with bipolar disorder, particularly those with the type II variety.


Evaluating the effectiveness of a participatory ergonomics approach in reducing the risk and severity of injuries from manual handling.
Manual handling is the greatest contributor to non-fatal injury and disease in the workplace, commonly accounting for one-third of national injury counts. Interventional strategies that have focused on selecting or modifying the worker have been ineffective in reducing injury risk. In recent times, participatory ergonomics has been widely adopted as a process to reduce the risk of injury from manual handling but it is not well validated as an intervention. This study evaluated the effectiveness of a participatory ergonomics risk assessment approach in reducing the rate and severity of injuries from manual and non-manual handling sustained by a cohort of 137 cleaners within a hospital setting. The date of injury and the workers' compensation claim cost and hours lost from work were obtained for each injury incurred during the 4-year pre-intervention and 3-year intervention period. The age, gender and hours worked were ascertained for every cleaner whether injured or not. Using generalized linear mixed modelling analysis, reductions of rate of injury by two-thirds, workers' compensation claim costs by 62% and hours lost by 35% for manual handling injuries were found to be associated with the intervention period. Although the cleaners experienced a significant intervention period reduction in non-manual handling injury rate, the corresponding changes in severity of injury were not significant. The success of the intervention supports the adoption of a participatory ergonomics approach in reducing the rate and consequence of injuries in the workplace.


Structure and function of steroid receptor AF1 transactivation domains: induction of active conformations.
Steroid hormones are important endocrine signalling molecules controlling reproduction, development, metabolism, salt balance and specialized cellular responses, such as inflammation and immunity. They are lipophilic in character and act by binding to intracellular receptor proteins. These receptors function as ligand-activated transcription factors, switching on or off networks of genes in response to a specific hormone signal. The receptor proteins have a conserved domain organization, comprising a C-terminal LBD (ligand-binding domain), a hinge region, a central DBD (DNA-binding domain) and a highly variable NTD (N-terminal domain). The NTD is structurally flexible and contains surfaces for both activation and repression of gene transcription, and the strength of the transactivation response has been correlated with protein length. Recent evidence supports a structural and functional model for the NTD that involves induced folding, possibly involving alpha-helix structure, in response to protein-protein interactions and structure-stabilizing solutes.


Examining the perceived impact of the COVID-19 pandemic on cervical cancer screening practices among clinicians practicing in Federally Qualified Health Centers: A mixed methods study.
The COVID-19 pandemic led to reductions in cervical cancer screening and colposcopy. Therefore, in this mixed methods study we explored perceived pandemic-related practice changes to cervical cancer screenings in federally qualified health centers (FQHCs). Between October 2021 and June 2022, we conducted a national web survey of clinicians (physicians and advanced practice providers) who performed cervical cancer screening in FQHCs in the United States during the post-acute phase of the COVID-19 pandemic, along with a sub-set of qualitative interviews via video conference, to examine perceived changes in cervical cancer screening practices during the pandemic. A total of 148 clinicians completed surveys; a subset (n=13) completed qualitative interviews. Most (86%) reported reduced cervical cancer screening early in the pandemic, and 28% reported continued reduction in services at the time of survey completion (October 2021- July 2022). Nearly half (45%) reported staff shortages impacting their ability to screen or track patients. Compared to clinicians in Obstetrics/Gynecology/Women's health, those in family medicine and other specialties more often reported reduced screening compared to pre-pandemic. Most (92%) felt that screening using HPV self-sampling would be very or somewhat helpful to address screening backlogs. Qualitative interviews highlighted the impacts of staff shortages and strategies for improvement. Findings highlight that in late 2021 and early 2022, many clinicians in FQHCs reported reduced cervical cancer screening and of pandemic-related staffing shortages impacting screening and follow-up. If not addressed, reduced screenings among underserved populations could worsen cervical cancer disparities in the future. This study was funded by the American Cancer Society, who had no role in the study's design, conduct, or reporting.


Safety and Efficacy of Megakaryocytes Induced from Hematopoietic Stem Cells in Murine and Nonhuman Primate Models.
Because of a lack of platelet supply and a U.S. Food and Drug Administration-approved platelet growth factor, megakaryocytes have emerged as an effective substitute for alleviating thrombocytopenia. Here, we report the development of an efficient two-stage culture system that is free of stroma, animal components, and genetic manipulations for the production of functional megakaryocytes from hematopoietic stem cells. Safety and functional studies were performed in murine and nonhuman primate models. One human cryopreserved cord blood CD34+ cell could be induced ex vivo to produce up to 1.0 × 104 megakaryocytes that included CD41a+ and CD42b+ cells at 82.4% ± 6.1% and 73.3% ± 8.5% (mean ± SD), respectively, yielding approximately 650-fold higher cell numbers than reported previously. Induced human megakaryocytic cells were capable of engrafting and producing functional platelets in the murine xenotransplantation model. In the nonhuman primate model, transplantation of primate megakaryocytic progenitors increased platelet count nadir and enhanced hemostatic function with no adverse effects. In addition, primate platelets were released in vivo as early as 3 hours after transplantation with autologous or allogeneic mature megakaryocytes and lasted for more than 48 hours. These results strongly suggest that large-scale induction of functional megakaryocytic cells is applicable for treating thrombocytopenic blood diseases in the clinic. Stem Cells Translational Medicine 2017;6:897-909.


Earlier continuous renal replacement therapy is associated with reduced mortality in rhabdomyolysis patients.
Continuous renal replacement therapy (CRRT) is commonly employed for rhabdomyolysis (RM) patients. However, the optimal initiation timing of CRRT and prognostic factors were not well evaluated for patients with RM. We aimed to investigate the efficacy of CRRT timing on mortality and the risk factors for death in RM patients who received CRRT. RM patients who received CRRT between 1 May 2010 and 31 May 2021 in our center were retrospectively included. Univariate and multivariate logistic analyses were performed to identify the risk factors for primary outcome (90-day mortality). A total of 134 patients were included in our study. The 90-day mortality rate was 38.06%. The median time from CRRT initiation to peak CK occurrence was 4.8 h (IQR -16, 14), 67 patients received CRRT before 4.8 h after peak CK occurrence (early CRRT), and 67 patients received CRRT beyond 4.8 h after peak CK occurrence (late CRRT). Multivariate logistic regression analysis showed that the time from CRRT initiation to the peak CK (per 1 h, OR 1.026, 95% CI 1.004-1.049, p = 0.023), late CRRT (OR 3.082, 95% CI 1.072-8.859, p = 0.037), elevated serum cardiac troponin I (cTnI) (per 1 ng/mL, OR 1.218, 95% CI 1.011-1.468, p = 0.038), older age (per 1 year, OR 1.042, 95% CI 1.003-1.081, p = 0.032), and need of mechanical ventilation support (OR 4.632, 95% CI 1.292-16.61, p = 0.019) were independent risk factors for 90-day mortality. Earlier CRRT initiation before 4.8 h after peak CK occurrence was associated with lower 90-day patient mortality.


Design on semiconductor coupled SAW convolver.
This paper presents results of a design study on a semiconductor coupled surface acoustic wave (SAW) convolver in which bi-directionally propagating SAWs, on a piezoelectric substrate with a high coupling coefficient, couple with bonded semiconductor diodes through multistrips. To obtain convolution signals with a high efficiency, we adopted a diode-balanced bridge structure for the non-linear operation. We also found that the tapping pitches of the multi-strip electrodes have robustness against operation frequency variation and temperature-dependent variation on the delay of the SAW. We verified the effectiveness of the device in a circuit simulation and an experiment on a test circuit, which was fabricated by using an epitaxial lift-off film-bonding process.


Does Size Really Matter? A Review on How to Determine the Optimal Umbilical Size During an Abdominoplasty.
The umbilicus has historical significance regarding health and beauty principles. The visually pleasing aesthetic of the umbilicus has become a vital standard for the perceived success of an abdominoplasty procedure. While the ideal position and shape of the umbilicus have been studied extensively in literature, less is known about the optimal size. Herein, the authors provide a comprehensive literature review to help determine the ideal umbilical size. A computerized search in the PubMed database was performed to identify articles that discussed ideal umbilical size. The review was performed in July 2022. A total of 21 articles were initially identified, only 6 of which discussed umbilical size. References from the included articles were also evaluated for relevance and resulted in 10 additional articles in the final review. Most of the articles indicated that a smaller umbilicus was found to be aesthetically pleasing, but a numerical range of values were not specified. Although the literature on the ideal umbilical size is sparse, the consensus is toward a smaller, vertically oriented umbilicus.


MR-safe personal radiation dosimeters.
Magnetic resonance imaging (MRI) is being rapidly integrated for cancer treatments-such systems are referred to as MRI-guided radiation therapy (MRIgRT). As the magnet of an MRI scanner is always on, the presence of a strong static magnetic field from the MRI scanner during radiotherapy delivery presents new challenges. One of the challenges is that a personal radiation dosimeter used to estimate the radiation dose deposited in an individual wearing the device must be MR-safe. No such devices, however, are currently available. In this work we first modified an existing personal dosimeter (by removing a metal clip) to make it MR-safe and then investigated potential effects of magnetic field on dosimeter readings, i.e., optically stimulated luminescent dosimeter (OSLD) readings. We found that the effect of magnetic field on OSLD sensitivity was within radiation protection tolerance levels. OSLD personal dosimeters can be directly used in conjunction with MRIgRT radiation protection purposes.


Type II benign osteopetrosis (Albers-Schönberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations.
A 16-year-old male patient with type II autosomal dominant benign osteopetrosis (ADO) was genotyped and found to harbor a novel mutation in exon 25 of the gene encoding for the osteoclast-specific chloride channel, CLCN7, inherited from the father, who was asymptomatic. The patient had normal biochemical findings and acid-base balance, except for increased serum levels of creatine kinase, lactic dehydrogenase, and the bone formation markers bone alkaline phosphatase isoenzyme, osteocalcin and N-terminal type I collagen telopeptide/creatinine ratio. Unusual generalized osteosclerosis was observed together with a canonical increase in vertebral and pelvis bone mass. An affected first grade cousin presented with normal biochemical findings and a milder osteosclerotic pattern of the pelvis. At the cellular level, cultured osteoclasts from the patient showed increased motility, with lamellipodia, membrane ruffling and motile pattern of podosome distribution, all of which could have contributed to functional impairment of bone resorption. The present report documents a novel mutation of the CLCN7 gene causing osteopetrosis in a radiologically uncertain form of the diseases, with apparent incomplete penetrance.


Transforming growth factor-beta and IL-4 cause helper T cell precursors to develop into distinct effector helper cells that differ in lymphokine secretion pattern and cell surface phenotype.
We have investigated the effects of TGF-beta on the in vitro development of different subsets of Th cells and find that addition of TGF-beta results in the generation of cell populations with distinct characteristics that resemble those of memory cells. Resting, short-lived CD4+ precursor T cells can be induced by mitogen stimulation to proliferate and differentiate in in vitro cultures and after 4 to 7 days will generate a population of cells that, when restimulated, synthesize and secrete high titers of a wide variety of lymphokines. It has been previously reported that the presence of the lymphokine IL-4 during in vitro culture results in the generation of a population of "effector" cells that can be rapidly induced by mitogen to synthesize and secrete high titers of IL-4, IL-5, IL-3, IFN-gamma, and granulocyte-macrophage-CSF. We find that TGF-beta added to CD4+ precursors, suppresses the development of IL-4/IL-5 secreting effectors and results instead in the development of cells secreting IL-2 and IFN-gamma. CD4 T cells generated in the presence of TGF-beta show little or no expression of CD45RB, in contrast to those developed in IL-4 (or in IL-2 alone) that express high surface densities of CD45RB. The kinetics of cell recovery also differs when TGF-beta rather than IL-4 is present during culture. Cultures of effectors generated in TGF-beta, initially have low cell recoveries but cells expand dramatically between 4 to 7 days in the presence of IL-2 whereas IL-4 induces optimum cell recovery at day 4 and cell recoveries decrease with further culture. The properties of cells grown in TGF-beta thus show several attributes in common with memory or highly differentiated CD4+ cells, i.e., IL-2 as a predominant cytokine, easy propagation and low expression of CD45RB. Therefore, we propose the hypothesis that TGF-beta favors the development of a population(s) of Th cells that is likely to give rise to memory cells although IL-4 favors development of a short-lived effector population that secretes Th2 lymphokines.


[CADASIL: 2 case reports of hereditary multi-infarct dementia].
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary stroke disease linked to chromosome 19 q 12. We report on two families affected by this disease, which is characterised by recurrent subcortical ischaemic strokes, progressive pseudobulbar palsy, and presenile dementia. Neuroimaging revealed multiple deep infarcts and diffuse leukoencephalopathy. Diagnosis of CADASIL based on the typical clinical feature without vascular risk factors, the neuroradiological signs of extensive leukoencephalopathy, and the autosomal dominant pattern of inheritance. CADASIL might be an underestimated cause of familial stroke and should be considered in the differential diagnosis of hereditary stroke.


[Comparative analysis of Fourier-transform infrared spectra in normal and malignant stomach tissues].
New data have been reported on Fourier-transform infrared spectra in 97 samples of resected material taken from normal and malignant tissues of the human stomach. Malignant tissues revealed a significant drop in peak intensity of vsPO2 bands (approximately 1089 cm-1) of nucleic acids characterized by the prevalence of high-frequency vCH3/ vCH2 protein and lipid fragments, the narrowing of vC=O bands of phospholipids, the simultaneous growth and narrowing of amide-I and amide-II bands, an increased homogeneity of the spectra, etc. Statistical data on the differences in normal and malignant tissue samples and diagnostically relevant criteria are presented.


Pt Nanoparticles Densely Coated on SnO2-Covered Multiwalled Carbon Nanotubes with Excellent Electrocatalytic Activity and Stability for Methanol Oxidation.
A new electrocatalyst exhibiting enhanced activity and stability is designed from SnO2-covered multiwalled carbon nanotubes coated with 85 wt % ratio Pt nanoparticles (NPs). This catalyst showed a mass activity 6.2 times as active as that of the commercial Pt/C for methanol oxidation, owing to the unique one-dimensional structure. Moreover, the durability and antipoisoning ability were also improved greatly. The enhanced intrinsic performance was ascribed to the densely connected networks of Pt NPs on the SnO2 NPs.


Protection of dopaminergic cells by urate requires its accumulation in astrocytes.
Urate is the end product of purine metabolism and a major antioxidant circulating in humans. Recent data link higher levels of urate with a reduced risk of developing Parkinson's disease and with a slower rate of its progression. In this study, we investigated the role of astrocytes in urate-induced protection of dopaminergic cells in a cellular model of Parkinson's disease. In mixed cultures of dopaminergic cells and astrocytes oxidative stress-induced cell death and protein damage were reduced by urate. By contrast, urate was not protective in pure dopaminergic cell cultures. Physical contact between dopaminergic cells and astrocytes was not required for astrocyte-dependent rescue as shown by conditioned medium experiments. Urate accumulation in dopaminergic cells and astrocytes was blocked by pharmacological inhibitors of urate transporters expressed differentially in these cells. The ability of a urate transport blocker to prevent urate accumulation into astroglial (but not dopaminergic) cells predicted its ability to prevent dopaminergic cell death. Transgenic expression of uricase reduced urate accumulation in astrocytes and attenuated the protective influence of urate on dopaminergic cells. These data indicate that urate might act within astrocytes to trigger release of molecule(s) that are protective for dopaminergic cells.


The management of birth-related posterior fossa hematomas in neonates.
Symptomatic posterior fossa hematoma in the term newborn is rare. To report on the management and outcome of posterior fossa subdural hematoma (PFSDH) in neonates. A retrospective analysis of the department database and clinical notes of neonates admitted since 1985 with a PFSDH was performed together with a literature review of similar case series. Sixteen patients were included. The median gestational age was 40 weeks with a high proportion of primiparous mothers (n = 9) and forceps delivery (n = 9). Nine neonates had symptoms of brainstem dysfunction within the first 24 hours of life, whereas the other 7 had a delayed presentation (median 4 days) with signs of raised intracranial pressure due to hydrocephalus. Each patient had a cranial ultrasound followed by computed tomography scan that showed the PFSDH. Eleven neonates required surgical evacuation of the PFSDH, whereas hydrocephalus was managed by transient external ventricular drainage in 2 further patients. Eventually, 2 neonates required a permanent ventriculoperitoneal shunt. Five neonates had no operative intervention. With a mean follow-up of 7.8 years, 2 patients had mild developmental delay and 1 had severe developmental delay. The 13 other patients had a normal development. In neonates with a PFSDH, surgery can be safely performed in those who have clinical and radiological signs of brainstem compression or hydrocephalus. A small number of neonates require a ventriculoperitoneal shunt in the long term. Initial aggressive resuscitation should be performed even in cases of initial severe brainstem dysfunction because of the good long-term neurological outcome.


Adult human pancreatic endocrine cells in culture. Insulin and glucagon release and influence of cold storage.
Adult human pancreatic tissue was minced and digested with collagenase. Resulting cell clusters, including both exocrine and endocrine components, were suspended in the medium and inoculated into 35 mm Petri dishes. Viable cell clusters became spherical 4 or 5 hr after inoculation and attached to the bottom of the dish within 24 hr. They spread out to form a pavementlike epithelial cell sheet by the seventh day of culture. Insulin and glucagon release were determined on the culture day 3. Insulin release stimulated by 500 mg/dl glucose, 10 mM theophylline, and 200 micrograms/ml tolbutamide was increased 1.5- to 3.7-fold in comparison with that stimulated by 100 mg/dl glucose. A 20 mM arginine concentration did not affect insulin release. Glucagon release, stimulated by 10 mM theophylline and 20 mM arginine, showed 1.7- to 2.7-fold increase and was suppressed significantly by 500 mg/dl glucose. Tolbutamide did not affect glucagon release significantly. Ultrastructural studies demonstrated that islet cells were preserved excellently. Chopped pancreatic tissue could be stored at 4 degrees C for at least 12 hr, with retention of normal following subsequent in vitro culture of islet cells.


Triclocarban and Triclosan Inhibit Human Aromatase via Different Mechanisms.
Human aromatase (CYP19A1) is an important enzyme, which produces estrogen from androgen for maintaining the female reproductive function and pregnancy. Triclocarban and triclosan are antimicrobial chemicals added to personal care, household, and industrial products. They could be endocrine disruptors and may disrupt human CYP19A1 activity. In the present study, we investigated the effects of triclocarban and triclosan on estradiol production and human CYP19A1 activity in JEG-3 cells. Triclocarban and triclosan reduced estradiol production in JEG-3 cells. Triclocarban and triclosan inhibited human CYP19A1 with IC50 values of 15.81 and 6.26 μM, respectively. Triclosan competitively inhibited CYP19A1, while triclocarban noncompetitively inhibited this enzyme. Docking study showed that triclosan bound to the steroid-binding pocket of CYP19A1, while triclocarban was off this target, suggesting a different mechanism. In conclusion, triclocarban and triclosan are inhibitors of human CYP19A1.