The solution structure of the periplasmic domain of the TonB system ExbD protein reveals an unexpected structural homology with siderophore-binding proteins.
The transport of iron complexes through outer membrane transporters from Gram-negative bacteria is highly dependent on the TonB system. Together, the three components of the system, TonB, ExbB and ExbD, energize the transport of iron complexes through the outer membrane by utilizing the proton motive force across the cytoplasmic membrane. The three-dimensional (3D) structure of the periplasmic domain of TonB has previously been determined. However, no detailed structural information for the other two components of the TonB system is currently available and their role in the iron-uptake process is not yet clearly understood. ExbD from Escherichia coli contains 141 residues distributed in three domains: a small N-terminal cytoplasmic region, a single transmembrane helix and a C-terminal periplasmic domain. Here we describe the first well-defined solution structure of the periplasmic domain of ExbD (residues 44-141) solved by multidimensional nuclear magnetic resonance (NMR) spectroscopy. The monomeric structure presents three clearly distinct regions: an N-terminal flexible tail (residues 44-63), a well-defined folded region (residues 64-133) followed by a small C-terminal flexible region (residues 134-141). The folded region is formed by two alpha-helices that are located on one side of a single beta-sheet. The central beta-sheet is composed of five beta-strands, with a mixed parallel and antiparallel arrangement. Unexpectedly, this fold closely resembles that found in the C-terminal lobe of the siderophore-binding proteins FhuD and CeuE. The ExbD periplasmic domain has a strong tendency to aggregate in vitro and 3D-TROSY (transverse relaxation optimized spectroscopy) NMR experiments of the deuterated protein indicate that the multimeric protein has nearly identical secondary structure to that of the monomeric form. Chemical shift perturbation studies suggest that the Glu-Pro region (residues 70-83) of TonB can bind weakly to the surface and the flexible C-terminal region of ExbD. At the same time the Lys-Pro region (residues 84-102) and the folded C-terminal domain (residues 150-239) of TonB do not show significant binding to ExbD, suggesting that the main interactions forming the TonB complex occur in the cytoplasmic membrane.


Expression of a testis-specific form of TBP-related factor 2 (TRF2) mRNA during mouse spermatogenesis.
The gene encoding TATA-binding protein-related factor 2 (TRF2/TLF/TLP/TRP), essential for the progress of spermiogenesis, is abundantly expressed in mammalian testis. A sequence database search revealed that mouse TRF2 is encoded by two mRNAs containing the same protein-coding region and different 5'-untranslated regions. Northern blot analysis using DNA probes specific for the 5'-untranslated regions demonstrated that these two mRNAs are distinguished from each other by the expression patterns: ubiquitous and testis-specific expression. The ubiquitously expressed form of TRF2 mRNA was present at a very low level throughout testicular development, whereas expression of the testis-specific form was first detectable in the 14-day-old testis, and the mRNA level abundantly increased at the later stages of testicular development. Western blot analysis indicated that the TRF2 level increases during testicular development, which is consistent with the expression pattern of the testicular form of TRF2 mRNA. Thus, the presence of the testis-specific form of TRF2 mRNA may account for overexpression of the TRF2 gene in the testis.


Long-term cytokine alterations following allogeneic blood transfusion.
Allogeneic blood transfusion is associated with an increased risk of infection and higher cancer recurrence rates. Previous research has shown that blood transfusion results in multiple immune effects, including cytokine alterations. The purpose of this study was to measure the long term kinetics of splenocyte cytokine production in transfused mice. Balb/c mice received either syngeneic transfusion (Syn-BT) or allogeneic transfusion (Allo-BT) from C3H-HeN mice. Splenocyte production of IL-2, IL-6, IL-10, and IFN-gamma was quantitated by ELISA on post-transfusion days 5, 10, 21, and 30. Both Allo-BT and Syn-BT produced significant alterations in cytokine production, but Allo-BT produced the most dramatic and enduring effects as summarized: IL-2: Production of IL-2 was suppressed at day 5, (p < 0.0001), but then rose, peaking at day 21, 30% greater than control values (p < 0.05). IL-6: Allo-BT mice showed suppression of IL-6 throughout the study period (p < 0.005 vs controls, each time point). IL-10: A 5-fold increase in IL-10 production was seen at day 5 after Allo-BT (p < 0.0001 vs control). Production of IL-10 was suppressed at days 10 and 21 (p < 0.001), but returned to control levels by day 30, gamma-IFN: At day 5 post Allo-BT, gamma-IFN was 4 x greater than controls (p < 0.0001). Gamma-IFN production was suppressed at day 10, but then rose at days 21 and 30 to nearly 3 x control levels (p < 0.0001). Allo-BT produced multiple cytokine alterations that were of prolonged duration. These results provide a theoretic explanation for the multiple, long-term immunomodulating effects seen in patients who have received transfusions.


Gene expression in the salivary complexes from Haementeria depressa leech through the generation of expressed sequence tags.
A survey of the transcriptional profile of Haementeria depressa Ringuelet, 1972 (Annelida, Hirudinea) salivary complexes was produced through expressed sequence tag (EST). Sequences from 898 independent clones were assembled in 555 clusters, representing the transcript profile of this tissue. The repertoire of possible proteins involved in feeding and host interaction processes of the leech corresponded to 10.6% of all identified transcripts (67 clusters), being the carbonic anhydrases (30%), several coagulation inhibitors (25%) and hemerythrin-like molecules (19%), the major components. Among the 387 clusters matching cellular proteins, the majority represents molecules involved in gene and protein expression, reflecting a high specialization of this tissue for protein synthesis. Our H. depressa dbEST was also compared to those from other blood-feeding organisms, providing evidences that among the secreted proteins, the coagulation inhibitors present a profile very characteristic of this animal class.


Tomatidine, a novel antiviral compound towards dengue virus.
Dengue is the most common arboviral disease worldwide with 96 million symptomatic cases annually. Despite its major impact on global human health and huge economic burden there is no antiviral drug available to treat the disease. The first tetravalent dengue virus vaccine was licensed in 2015 for individuals aged 9 to 45, however, most cases are reported in infants and young children. This, together with the limited efficacy of the vaccine to dengue virus (DENV) serotype 2, stresses the need to continue the search for compounds with antiviral activity to DENV. In this report, we describe tomatidine as a novel compound with potent antiviral properties towards all DENV serotypes and the related Zika virus. The strongest effect was observed for DENV-2 with an EC50 and EC90 value of 0.82 and 1.61 μM, respectively, following infection of Huh7 cells at multiplicity of infection of 1. The selectivity index is 97.7. Time-of-drug-addition experiments revealed that tomatidine inhibits virus particle production when added pre, during and up to 12 h post-infection. Subsequent experiments show that tomatidine predominantly acts at a step after virus-cell binding and membrane fusion but prior to the secretion of progeny virions. Tomatidine was found to control the expression of the cellular protein activating transcription factor 4 (ATF4), yet, this protein is not solely responsible for the observed antiviral effect. Here, we propose tomatidine as a candidate for the treatment of dengue given its potent antiviral activity.


Intravenous route of cell delivery for treatment of neurological disorders: a meta-analysis of preclinical results.
The last decade has been marked by a growing interest in an employment of intravenous cell delivery for treatment of neurological disorders. Numerous preclinical experimental studies have reported functional benefits, and have recently been followed by clinical trials. Some early clinical studies have indicated only modest positive effects, suggesting that the optimal conditions have not been defined yet. Thus, the evaluation of factors that influence outcomes, on the level of the whole population of preclinical studies by advanced statistical analysis, is warranted. PubMed search was conducted from the inception through 2006, and 60 preclinical studies were found and subjected to analysis. Categorical and continuous independent variables (IVs) were extracted. Three distinct outcomes of interest were selected as dependent variables (DVs) and named treatment effects: morphological, behavioral, and molecular, respectively. Mean outcomes, standard deviations (SDs), and animal numbers were retrieved and calculated by individual comparisons of experimental and control groups, based on the Hedges g formula, and were expressed as effect sizes (ESs) and variances. Publication bias and homogeneity were evaluated. The mainspring analyses were performed under a random effect model using Proc Mixed (SAS, version 9.2). A significant heterogeneity and publication bias were found. The ES pooling revealed large treatment effects. Univariate and multivariate meta-regression revealed that cell-related variables explained most of the heterogeneity. Cells retrieved from established lines and genetic modification of cells warrants the highest efficiency, in a dose-dependent manner. The stratified analysis of molecular effect measures revealed that apoptosis inhibition is the strongest brain tissue-positive change induced by cell therapy.


Writing long holographic diffraction gratings by use of a novel scanning method.
A novel method for writing holographic diffraction gratings is proposed in which the two interfering beams are moved together across the recording medium in such a way that the interference pattern at the medium is unchanged. The phase compensation is discussed both for an idealized setup and for a realistic experimental arrangement.


[Sinus-like tachycardias].
Various tachycardias presenting with positive P waves in the standard leads are described in this article. Sinus tachycardia may occur as a normal adaptation reaction to the environment or in the setting of autonomic dysregulation. It may also be mimicked by various arrhythmias which share the earliest depolarisation in the sinus node area. The authors expose a review of these mechanisms.


Recurrent polymyositis triggered by bronchiectasis-associated infections.
Polymyositis is a cell-mediated autoimmune disease and various systemic infections can trigger it. However, there have been only rare reports of recurrent polymyositis triggered by systemic infections. We report the case of a 69-year-old woman with recurrent polymyositis triggered by bronchiectasis-associated infections. This case indicates that recurrent polymyositis triggered by systemic infections suggests a non-specific autoimmune antigenic response of polymyositis.


Beryllium-free Rb3Al3B3O10F with reinforced interlayer bonding as a deep-ultraviolet nonlinear optical crystal.
A new beryllium-free borate Rb3Al3B3O10F has been synthesized and characterized by single-crystal X-ray diffraction. It features a framework structure consisting of alveolate [Al3(BO3)3OF]∞ layers tightly bound via Al-O and Al-F bridged bonds, with the in-layer [BO3](3-) groups in nearly coplanar and aligned arrangement. This compound is transparent down to 200 nm and is phase-matchable with a powder second-harmonic generation efficiency of 1.2 times that of KH2PO4. Remarkably, it exhibits a strong interlayer bonding which is about one order larger than that of the benchmark KBe2BO3F2, thus no layering tendency was observed during the crystal growth. In addition, it is nonhygroscopic and thermally stable up to ∼1462 K. These attributes make Rb3Al3B3O10F a promising nonlinear optical crystal in the deep-ultraviolet region. First-principles calculations, combined with the anionic group theory, were adopted to rationalize the optical properties.


[Use of ultrasonic folliculometry and LH determination in artificial insemination with donor semen].
The results of ultrasonic determinations of follicular growth and determinations of serum LH-levels were analysed in 34 patients who were artificially inseminated using cryopreserved donor semen (AID). 22 of them became pregnant. The ultrasonic findings had contributed to perform AID optimally, where as the determinations of LH did not surely indicate ovulation in each case. Frequency of inseminations per cycle was reduced by means of ultrasonic observations of follicle. The chance of success of artificial insemination using cryopreserved spermatozoa was decreased by delay of maturity of follicle. A peak of LH-concentration in serum was not detectable in 27 per cent of patients by one estimation daily.


Oxidative status and histological changes in sea bass larvae muscle in response to high dietary content of docosahexaenoic acid DHA.
In previous studies, we observed dystrophic alterations in muscle of 48-day-old sea bass fed imbalanced docosahexaenoic acid (DHA) and vitamin E diets. To understand the whole pathological process associated with oxidative stress, a histological study was performed by feeding 14-day-old sea bass larvae with microdiets containing different ratios of DHA/vitamin E (1/150, 5/150 and 5/300) for a period of 21 days. Larvae fed diet 1/150 showed no lesions in contrast to larvae fed diets 5/150 and 5/300 where the highest incidence of muscle lesions and thiobarbituric acid reactive substances (TBARS) content was observed. Semithin sections revealed focal lesions consisting of degenerated fibres with hypercontracted myofilaments and extensive sarcoplasm vacuolization affecting both red and white muscle. Ultrathin sections of degenerating muscle fibres showed diffuse dilatation of sarcoplasmic reticulum, disorganized myofilaments and autophagic vacuoles containing myelin figures and dense bodies. Additionally, some macrophages were observed among injured fibres as numerous satellite cells. Results from the study agree with those obtained from previous work, proving the pathological potential of free radicals in sea bass larvae musculature. Moreover, high vitamin E inclusion could not completely protect cell membranes from free radicals action.


Botulinum toxin type A treatment of multiple upper facial sites: patient-reported outcomes.
Aesthetic treatment planning must address subjects' goals and include subject-reported outcomes. The objective was to compare the effect of botulinum neurotoxin type A (BoNTA) with placebo on subject-reported outcomes and to assess the utility of 64 U of BoNTA to treat the entire upper face. Forty female subjects were randomized to receive 64 U of BoNTA or identical placebo injections (double-masked) divided among 16 sites of the upper face and were followed for 12 weeks. Subjects unimproved at Week 4 were eligible for open-label BoNTA treatment and were followed through Week 16. Main outcome measures were scores on seven items of the Facial Line Outcomes Questionnaire (FLO-7) and results on the Self-Perception of Age (SPA) for assessing age of appearance relative to actual age. BoNTA treatment resulted in significant improvements on the FLO-7 scores that were maintained throughout the study. BoNTA treatment also reduced age of appearance in a majority of subjects. Placebo had no effects on any measure. No serious adverse events occurred. Sixty-four-unit BoNTA treatment of upper facial rhytids safely and significantly improves subject-reported outcomes, as measured by the FLO-7 and SPA, and results in a younger, more satisfying, relaxed appearance.


In-Hospital Pediatric Stroke Alert Activation.
Pediatric stroke alerts or "code strokes" allow for rapid evaluation, imaging, and treatment of children presenting with stroke-like symptoms. In a previous study of emergency department-initiated pediatric stroke alerts, 24% of children had confirmed strokes. The purpose of this study was to characterize in-hospital pediatric stroke alerts. Demographic and clinical information was obtained from a quality improvement database and medical records for children (zero to 20 years) at a single institution for whom a stroke alert was activated after hospital admission between April 2011 and December 2016. Stroke alert activation criteria included a new focal neurological defect occurring within 48 hours. A neurologist evaluated the patient within 15 minutes and rapid magnetic resonance imaging was available. Medical personnel activated in-hospital stroke alerts for 56 children (median age 6.5 years, interquartile range 1 to 13, 52% male). Stroke was the final diagnosis of 25 (45%), 72% ischemic, and 28% hemorrhagic strokes. Other diagnoses included neurological urgencies: seizure (21%), posterior reversible encephalopathy syndrome (7%), transient ischemic attack (5%), and acute disseminated encephalomyelitis (4%). Of the stroke diagnoses, 68% were stroke alerts called in the pediatric intensive care unit or pediatric cardiac intensive care unit. Rapid neuroimaging was completed in 91%; magnetic resonance imaging brain was the first image in 55%. Of in-hospital pediatric stroke alerts, 45% were stroke while 38% were other neurological conditions requiring urgent evaluation. In-hospital stroke alerts were commonly activated for children with complicated medical histories. Rapid neurological evaluation facilitated care. No child underwent thrombolysis or thrombectomy.


A Randomized Control Intervention Investigating the Effects of Acute Exercise on Emotional Regulation.
Exercise may help to cope with hectic or demanding events after a stressful situation occurs. Limited research has evaluated whether exercise, prior to a stressor, helps to facilitate subsequent emotional regulation. This pilot study addresses this novel paradigm. We employed a randomized controlled trial evaluating the effects of acute exercise on emotional regulation. Participants were randomly assigned to stretch (control group, N = 10), walk (N = 9), or jog (N = 8) for 15-minutes, after which they were exposed to a film clip intended to elicit a negative emotional response. Participants' emotions were monitored before and during exercise, as well as after the film clip. Emotional responses were evaluated using the Exercise Induced Feeling Inventory and Affective Circumplex Scale. A group x time splitplot interaction effect was significant for anger (p = .046) and anxiousness (p = .038). Follow-up analyses showed that only the stretching group (p = .048) had a significantly increased anger score from baseline to post-film clip, suggesting a protective emotional effect from walking and jogging. Exercise was effective in regulating anger and anxiousness after a stressful event. These findings provide evidence for potential preventive effects of exercise in facilitating emotional regulation.


Regulation of cholecystokinin octapeptide secretion by rat cerebral cortical cells in primary culture.
The regulation of cholecystokinin octapeptide (CCK-8) secretion was studied using a fetal cerebral cortical cell culture system. After 2-3 weeks in culture, the cells were utilized for short-term release experiments. CCK-8 was measured by RIA and its identity was confirmed by HPLC. Depolarization of the cells with K+ (6 x 10(-2) M) evoked CCK-8 release and this response was blocked by the Ca++ channel blocker verapamil (2 x 10(-5) M) and by Ca++ free medium. The Na+ channel opener veratridine (10(-4) M) stimulated CCK-8 release and was blocked by the Na+ channel blocker tetrodotoxin (10(-6) M) and by Ca++ free medium. The adenylate cyclase activator forskolin (10(-5) M) markedly increased CCK-8 secretion. No changes in CCK-8 release were induced by epinephrine, norepinephrine, dopamine, acetylcholine, or 5-hydroxytryptamine at 10(-5) and 10(-4) M, but gamma-aminobutyric acid (GABA) at 10(-4) M inhibited CCK-8 release. GABA inhibition was reversed by the GABA antagonist picrotoxin (10(-4) M). Both picrotoxin (10(-4) M) and bicuculline (10(-3) M), another GABA receptor antagonist, alone stimulated CCK-8 secretion. These data show that CCK-8 secretion by cerebral cortical cells 1) is stimulated by cell membrane depolarization in a calcium-dependent fashion, 2) is regulated by cAMP, 3) is unaffected by the neurotransmitters characteristic of corticopetal systems, 4) is tonically inhibited by GABA.


Infective endocarditis due to Bartonella quintana: a challenging diagnostic entity.
Bartonella quintana is a gram-negative microorganism, which may lead to infective endocarditis especially in compromised patients. The major concern about this pathogen is the diagnosis and detection. Furthermore, the treatment of the infection has been a challenge for physicians. In this report, we present a 71-year-old patient with Bartonella quintana aortic valve endocarditis from the view of diagnosis and treatment aspects.


[Methods of topographic presentation of the bioelectric activity of the brain].
Prerequisites for developing brain activity topographic mapping and its present status are given. Its advantages and disadvantages, use potentialities in the diagnostic practice of neurological and mental hospitals are discussed.


Electronic Structure and Photoluminescence Properties of Eu(η9-C9H9)2.
The electronic structure of Eu2+-compounds results from complex combination of strongly correlated electrons and relativistic effects as well as weak ligand-field interaction. There is a tremendous interest to calculate the electronic structure, as nowadays Eu2+ ion is becoming more and more crucial, for instance in lighting technologies. Recently, the interest on semi-empirical methods to qualitatively evaluate the electronic structure and to model the optical spectra has gained popularity, although the theoretical methods strongly rely upon empirical inputs, hindering their prediction capabilities. Besides, ab initio multireference models are computationally heavy and demand very elaborative theoretical background. Herein, application of the ligand-field density-functional theory (LFDFT) method that is recently available in the Amsterdam Modelling Suite is shown: (i) to elucidate the electronic structure properties on the basis of the multiplet energy levels of Eu configurations 4f7 and 4f65d1; and (ii) to model the optical spectra quite accurately if compared to the conventional time-dependent density-functional theory tool. We present the theoretical study of the molecular Eu(η9-C9H9)2 complex and its underlying photoluminescence properties with respect to the Eu 4f - 5d electron transitions. We model the excitation and emission spectra with good agreement with the experiments, opening up the possibility of modeling lanthanides in complex environment like nanomaterials by means of LFDFT at much-reduced computational resources and cost.


Synergistic induction of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying TRAIL.
Chemoresistance and side effects are considered as the major obstacles in cisplatin-based chemotherapy of various human malignant tumors. Conjugation with cancer-specific apoptotic stimuli TRAIL or typical viro-agent ONYX-015 has been extensively investigated to enhance the antitumor activity of cisplatin. In this study, we presented a novel chemo-gene-virotherapeutic strategy to further improve the toxic effects in cancer cells and reduce the damage in normal cells. Here, an oncolytic adenoviral vector (ZD55), with a deletion of E1B 55-kDa gene, was employed to express the therapeutic TRAIL gene by constructing a recombinant virus ZD55-TRAIL. Exogenous gene delivery efficacy was determined by both in vitro and in vivo experiments and enhanced cytotoxicity of combined treatment of ZD55-TRAIL with cisplatin was evaluated in several cancer cell lines. Moreover, negative effects on normal cells have been tested in both L-02 and MRC-5 cell lines by MTT assay and apoptotic cell staining. According to our observation, combination of ZD55-TRAIL with cisplatin exhibited an apparent synergistic cytotoxicity in cancer cells, yet significantly abolished the negative toxicity in normal cells by reducing the dosage. Thus, a novel chemo-gene-virotherapeutic strategy for cancer therapy was proposed.


Serum 25-hydroxy vitamin D levels in Bulgarian patients with prostate cancer: a pilot study.
The antiproliferative effect of the active form of vitamin D on cancer cells and its ability to induce cell differentiation and suppression of tumor-induced angiogenesis in the last decade has provoked enormous research for the elucidation of its role in the prevention of different types of cancer and in slowing down the malignancy progression. The aim of the present pilot study was to determine the circulating 25-hydroxy vitamin D (25OHD) levels in Bulgarian prostate cancer (PCa) patients and to investigate their relationship with various determinants associated with the severity and progression of the disease. A total of 53 male patients (mean age 67.0 ± 7.1 years) with clinical suspicion for PCa were enrolled in the study. All patients were subjected to systemic transrectal ultrasound-guided tru-cut prostate biopsies (10 cores at least). Detected tumors were graded using the Gleason grading system. Prostate specific antigen (PSA) serum levels were measured immunochemically. The 25OHD assay was performed by a validated HPLC-UV method. Other covariates (BMI, age, family history of PCa) were collected by interview at the time of hospitalization. One-way ANOVA with Kruskal Wallis statistics was used for comparison of medians of different parameters. The level of significance was set at p < 0.05. Significantly lower 25OHD levels were detected in PCa patients compared to those with benign prostate hyperplasia (BPH) (p < 0.05). Patients with high grade tumors (Gleason score ≥ 7) showed significantly lower 25OHD levels, while those with low grade tumors (Gleason score < 7) revealed better 25OHD status (50.49 vs. 63.17 nmol/L, p < 0.05). A moderate negative correlation between 25OHD levels and the Gleason score was established (Spearman r = -0.46, p < 0.05). Significant seasonal variations in 25OHD levels, both for PCa and BPH patients, were detected (p < 0.01). This preliminary study shows an association between 25OHD status and classical markers characterizing the severity of PCa. The results might suggest a potential beneficial role of vitamin D for PCa patients. Further prospective studies are needed to strengthen the interrelationships between 25OHD levels and variables related with PCa and to test them for causality.


Sensivity to change of the Spanish validated Memorial Pain Assessment Card in cancer patients.
Pain intensity is a good parameter to assess effective treatment of cancer and palliative care. The Memorial Pain Assessment Card (MPAC) is a quick, easy and reliable measure of quality of life in cancer patients. The MPAC was validated in Spanish in 2004. This study evaluated the sensitivity to change Spanish version of the MPAC. An epidemiological, prospective, 1- month, multicentre study, conducted at 4 oncology services. Patients evaluated suffered chronic cancer pain and were in a susceptible situation of change. The MPAC was administrated at baseline, at one week and at one month, including the 4 subscales (pain relief [VASPR], pain intensity measured by VAS [VASPI] and by an 8-item descriptor [Tursky], and psychological distress [VASMOOD]). Satisfaction of patients and health-care professionals with the MPAC was also evaluated. A total of 54 patients were studied. All of the MPAC subscales showed sensitivity to change during the follow-up. The subscale values at visit 1 vs. visit 3 were: VASPR 4.5+/-1.9 vs. 6.3+/-2.3, VASPI 6.6+/-1.6 vs. 3.5+/-1.9 and VASMOOD 5.5+/-2.1 vs. 4.0+/-2.1). Patients and healthcare professionals agreed in the facility use MPAC card (63% and 71% of cases, respectively). The present study showed sensitivity to change among the different MPAC subscales of the Spanish version. Moreover, the MPAC Spanish version has proven to be a good tool accepted by health-care-professionals and patients. Due to its facility of administration, it may allow a useful and quick evaluation of cancer-related pain in the clinical practice.


Sudden death after pancreatic head resection: rupture of hepatic artery caused by clostridial infection.
Rupture of the hepatic artery caused by clostridial infection has not been reported before. Case report and literature review. A 75 year-old man was admitted to the hospital for resection of a cystic tumor of the head of the pancreas. A pylorus-preserving radical pancreaticoduodenectomy was performed. On the fifth postoperative day, he developed fever (38.2 degrees C), and computed tomography scanning revealed free air in the subhepatic area near the pancreaticojejunal anastomosis. On the ninth postoperative day, the patient died suddenly. Autopsy revealed a ruptured hepatic artery secondary to clostridial infection. Close monitoring and early recourse to invasive diagnostic and therapeutic procedures may be advisable in the presence of suspect findings after pancreatic surgery to prevent this fatal complication.


Check out that body: a community awareness campaign in New York City.
The authors evaluate the effectiveness of the small media campaign in raising community awareness about the importance of going for a health check up. Data were collected over time from 535 respondents ages 15-30 years using cross-sectional surveys in two low-income, predominantly African-American communities in New York city. Regression analyses indicated campaign material recognition at 15 months was significantly higher in the intervention community relative to the comparison community. There were no significant changes in social norms, attitudes, or beliefs. Media campaigns aimed at adolescents and young adults on a community-wide level are an effective means of gaining material recognition. Editors' Strategic Implications: This research illustrates the effect of a public health media campaign on awareness, but it also serves as a reminder to public health officials that awareness is not necessarily sufficient to promote attitudinal or behavioral health changes.


Successful and unsuccessful psychopaths: a neurobiological model.
Despite increasing interest in psychopathy research, surprisingly little is known about the etiology of non-incarcerated, successful psychopaths. This review provides an analysis of current knowledge on the similarities and differences between successful and unsuccessful psychopaths derived from five population sources: community samples, individuals from employment agencies, college students, industrial psychopaths, and serial killers. An initial neurobiological model of successful and unsuccessful psychopathy is outlined. It is hypothesized that successful psychopaths have intact or enhanced neurobiological functioning that underlies their normal or even superior cognitive functioning, which in turn helps them to achieve their goals using more covert and nonviolent methods. In contrast, in unsuccessful, caught psychopaths, brain structural and functional impairments together with autonomic nervous system dysfunction are hypothesized to underlie cognitive and emotional deficits and more overt violent offending.


[Experience of surgical resection of Bismuth-Corlette type I and II hilar cholangiocarcinoma].
To report the experience of surgical resection of Bismuth-Corlette type I and II hilar cholangiocarcinoma. From January 1998 and January 2008, 52 cases of Bismuth-Corlette type I and II hilar cholangiocarcinoma were operated on. The clinical data and long-term outcome of the patients was retrospectively analyzed. Of the 52 cases, 44 cases (84.6%) received operation, 28 patients underwent radical resection (63.6%) and 16 patients (36.4%) underwent palliative resection.Seven patients were resected on caudate lobe and other section and lobe of the liver; among them, 2 patients received combined portal vein resection and 4 underwent combined hepatic artery resection respectively. Eleven cases developed postoperative complications and another one died in hospital. The median survival was 33.2 months in radical resection group, and 1-, 3-, 5-year survival rate was 82.6%, 47.8%, 34.7%, respectively, which was significant greater than those in the palliative resection group (41.6%, 16.6%, 8.3%, respectively) (P < 0.05). The median survival was 16.7 months in the palliative resection group. The radical resection is still the best treatment for Bismuth-Corlette type I and II hilar cholangiocarcinoma. Intraoperative pathology for resection margin, and combined liver resection, portal vein resection and hepatic artery resection can help improve the radical resection rate.


Reconstitution of cell-free NADPH-oxidase from human monocytes and comparison with neutrophils.
A rapid centrifugal elutriation procedure was developed to prepare high amounts of pure human blood monocytes. After disruption by nitrogen cavitation, a cytosol and a membrane fraction were obtained by sucrose-Percoll density centrifugation. The plasma membrane fraction contained cytochrome b558 and was free of microsomal or mitochondrial cytochromes as determined by low-temperature absorbance spectroscopy. Cell-free NADPH-oxidase activity from monocytes and neutrophils was reconstituted with cytosol and membranes in the presence of sodium dodecyl sulphate. By comparison with neutrophils, the cell-free NADPH-oxidase from monocytes showed a two- to threefold lower specific activity. The NADPH-oxidase was reconstituted with neutrophil membranes and monocyte cytosol, and vice versa. The Km for NADPH was always lower when monocyte cytosol was used. These experiments indicate that the membrane-bound components of the NADPH-oxidase from neutrophils and monocyte are similar and that levels of NADPH-oxidase components in the cytosols differ. Interferon gamma-treatment of the monocytes had no effect on the specific activity of the cell-free NADPH-oxidase.


Acousto-optic modulation by pulsed optical excitation: implications to imaging in turbid media.
We show that the transient response of acoustically modulated optical flux in a turbid medium irradiated by a pulsed point source of light is delayed in time relative to the light-alone flux obtained in the absence of acoustic modulation. The time delay is shown to result from an initial phase of flux reversal, as determined by the time point of the input pulse onset with reference to the ultrasound cycle. Both the time delay and amplitude of modulation are shown to be dependent on the effective attenuation coefficient of the medium. Application of a periodic train of excitation pulses spaced at equal intervals at, or in multiples of, the ultrasound period enables a time-locked detection of the modulated light, without the deleterious effects caused by speckle artifacts.


[Clinical and experimental studies on clearing away stomach-heat purging fire and nourishing yin principle in treating patients of recurrent aphthae].
To observe the therapeutic effect of Kouchuangping granule (KCP) on recurrent aphthae and explore its mechanism. One hundred and forty-eight patients treated with KCP were observed and compared with 49 patients treated with tripterygii multiglycoside tablet as control in controlling relapse, prolonging intermittent period, improving local symptom and the influence on humoral and cellular immunity. In animal experiment, the effects of KCP on immunologic function, anti-exudation, anti-inflammation and analgesia were studied. The clinical markedly effective and cure rate of the KCP group was 62.8% and the total effective rate was 89.9%, which were significantly higher than those of the control group (40.8% and 75.5%, P < 0.01, P < 0.05). In the KCP group, the intermittent period of aphthous ulcer recurrence was prolonged to 6 months and the local symptoms were markedly improved, the differences were significant as compared with those before treatment and those in the control group (P < 0.01 or 0.05). The KCP showed effects in suppressing humoral immunity and enhancing cellular immunity. Results of experimental study showed that KCP could inhibit the supernormal reaction of cellular immunity to prevent and treat the hypersensitivity caused erosion and ulceration of mucosae, inhibit capillary permeability and WBC migration and abate the 5-hydroxytryptamine (5-HT) and histamine induced local swelling and pain. KCP has a significant effect in treating recurrent aphthae, the mechanism might be related with its effect on immunoregulation, anti-inflammation and anti-exudation.


Synthesis, receptor binding and functional studies of mesoridazine stereoisomers.
The four stereoisomers of mesoridazine were synthesized and evaluated in D2, 5-HT1A, 5-HT2A, 5-HT2C, D1, and D3 receptor binding and functional assays. Two isomers demonstrated potent D2 receptor binding (Ki < 3 nM) and functional antagonism (IC50 < or = 10 nM) activities. These two isomers also showed moderate affinity for the 5-HT2A and D3 receptors. A third isomer was devoid of significant D2 receptor binding, but did have moderate affinity for the 5-HT2A and D3 receptors. The fourth isomer demonstrated poor affinity for all the receptors tested. Most significantly, the stereochemistry of the sulfoxide moiety played a dominant role in the observed structure-activity relationship (SAR).


Orodental manifestations of facial port-wine stains.
Patients with facial port-wine stains (PWS) often demonstrate oral manifestations of their disorder; however, the spectrum and prevalence of such findings among a cohort of patients with PWS has not been established. As a result, dermatologists and oral health specialists may be uncertain how to counsel their patients with PWS regarding oral hypervascularity, bony oral changes, and oral hygiene. We sought to identify physical findings and complications involving the teeth, oral cavity, and perioral structures in individuals with facial PWS. This was a cross-sectional study of 30 patients with facial PWS. Descriptive data were collected through anonymous paired surveys completed by patients and their dentists, and analyzed (Fisher exact test) for trends based on physical findings and stage of the PWS. The most common orodental manifestations according to patients were enlargement of the lip (53.3%), stained gums (46.7%), abnormal bite (30%), and spontaneous bleeding of the gums (26.7%). Staining of the gingiva correlated significantly with gingival hyperplasia (P = .006), maxillary hyperplasia (P = .014), and widened interdental spaces (P = .002), and in all cases gingival staining predated these findings. Lip hyperplasia was reported more frequently by patients than by their dentists (50% vs 18.2%, P = .008). Orodental manifestations were more common among patients with darker and thicker PWS. Hemorrhage after dental procedures was rare (4.5%). Modest sample size and difficulty recruiting control subjects are limitations. Facial PWS commonly affect the orodental structures, and intraoral staining may predict future complications.


Middle Pleistocene hominids from Olduvai Gorge, northern Tanzania.
Cranial, dental, and mandibular remains of eight Olduvai hominids are described in detail. Four individuals were recovered in situ in Beds II to IV, while three more are most probably derived from Bed IV, the Masek Beds and the Lower Ndutu Beds. One specimen is of uncertain provenance. Deposits from which the fossils were collected range from late Lower Pleistocene to Middle Pleistocene in age. Of particular interest are three fragmentary lower jaws, which can be compared to mandibles of Homo erectus known from localities in Northwest Africa and China. Olduvai hominid 22, a nearly complete half mandible with crowns of P3-M2 in place, shares many anatomical features with fossils from Ternifine and Choukoutien. This individual is also similar to a jaw from the Kapthurin Formation west of Lake Baringo, Kenya. How best to interpret these comparisons is not clear, but in view of marked similarities between specimens representing geographically diverse populations from different time periods, it may be unwise to rely on mandibular evidence alone to document the presence of regional lineages. Gradual change and continuity within a sequence of Northwest African Homo fossils has been endorsed by many workers, but such hypotheses cannot be tested adequately with the fragmentary jaws available.


[Vaginal birth after cesarean delivery: can the trial of labor be extended].
Based on a retrospective analysis of 1000 cases of scared uteri following cesarean section(s) (one cesarean, n = 857, 85.7%); two n = 129, 12.9%; three n = 14, 1.4%), we tried to answer two questions. Is trial of labor in case of low segment uterine-scar (excepting pelvic abnormalities, corporeal scar and more than two scars) free of risk for the mother and child? Can trial of labor be extended to cases of breech presentation, two previous cesarean sections, twin pregnancy and suspected macrosomia? In this series, the cesarean was indicated before labor in 138 cases (13.8%). Trial of labor was conducted in 862 cases (86.2%), and led to vaginal birth in 728 (84.5%). Successful trial of labor was observed in 75% of twin pregnancies, in 100% of breech presentations and in 69.6% of macrosomic infants. Uterine rupture occurred in 23 cases (2.7%), especially in cases with unknown corporeal scars (15 cases). No case of perinatal death related to uterine rupture was observed in this series.


Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis.
The mediobasal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that transient receptor potential canonical type 3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis. To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mouse models. Hypothalamic glucose detection was studied in vivo by measuring food intake and insulin secretion in response to increased brain glucose level. The role of TRPC3 in GE neuron response to glucose was studied by using in vitro calcium imaging on freshly dissociated MBH neurons. We found that whole-body and MBH TRPC3-deficient mice have increased body weight and food intake. The anorectic effect of intracerebroventricular glucose and the insulin secretory response to intracarotid glucose injection are blunted in TRPC3-deficient mice. TRPC3 loss of function or pharmacological inhibition blunts calcium responses to glucose in MBH neurons in vitro. Together, the results demonstrate that TRPC3 channels are required for the response to glucose of MBH GE neurons and the central effect of glucose on insulin secretion and food intake.


Gangliosides involved in activation of rat T lineage cells.
Gangliosides have long been known to be involved in T-cell activation. In our previous studies, a unique GMlb-derived ganglioside, GD1c(NeuGc,NeuGc), was shown to be the predominant ganglioside in rat thymocytes and T-cells. Upon the activation of the thymocytes, the amount of GD1c(NeuGc,NeuGc) increases remarkably, and additionally a novel species of GD1b, GD1b(NeuGc,NeuGc), appears as the other major ganglioside (Nohara, et al. (1993) J. Biol. Chem. 268, 24997-25000). In the present study, monoclonal antibodies (MAbs) against these two gangliosides have been generated. The MAb AC1 established by immunizing mice with purified GD1c(NeuGc,NeuGc) reacted strongly with GD1c(NeuGc,NeuGc) and weakly with GD1b(NeuGc,NeuGc) by enzyme-linked immunosorbent assay (ELISA). The other MAb AB1 obtained by immunization with GD1b(NeuGc,NeuGc) showed a strong binding activity to GD1b(NeuGc,NeuGc) and no reactivity to GDlc(NeuGc,NeuGc) by ELISA. Flow cytometry analyses using these MAbs have revealed that an AC1-positive subset exists in a portion of resting CD4+CD8- thymocytes and CD4+ splenic T-cells. When the thymocytes were activated with 12-O-tetradecanoylpholbol-13-acetate (TPA) and calcium ionophore A23187, the proportion of AC1+ cells increased remarkably and were detected not only in CD4+ cells but also in CD8+ cells. An increase in the proportion of AC1+ cells was also seen in activated T-cells. In contrast, AB1-positive cells were only detected in activated thymocytes, not in resting thymocytes, or resting or activated T-cells. These results implicate GD1c(NeuGc,NeuGc) in the activation of thymocytes as well as T-cells, whereas GD1b(NeuGc,NeuGc) appears to be specifically related to the activation of thymocytes.


Cloning and sequencing of porcine LH-hCG receptor cDNA: variants lacking transmembrane domain.
Complementary DNA clones, encoding the LH-hCG (luteinizing hormone-human choriogonadotropic hormone) receptor were isolated by screening a lambda gt11 library with monoclonal antibodies. The primary structure of the protein was deduced from the DNA sequence analysis; the protein contains 696 amino acids with a putative signal peptide of 27 amino acids. Hydropathy analysis suggests the existence of seven transmembrane domains that show homology with the corresponding regions of other G protein-coupled receptors. Three other types of clones corresponding to shorter proteins were observed, in which the putative transmembrane domain was absent. These probably arose through alternative splicing. RNA blot analysis showed similar patterns in testis and ovary with a major RNA of 4700 nucleotides and several minor species. The messenger RNA was expressed in COS-7 cells, yielding a protein that bound hCG with the same affinity as the testicular receptor.


Optimisation of glycogen quantification in mixed microbial cultures.
This study addressed the key factors affecting the extraction and quantification of glycogen from floccular and granular mixed microbial cultures collected from activated sludge, nutrient removal systems and photosynthetic consortiums: acid concentration, hydrolysis time and concentration of biomass in the hydrolysis. Response surface modelling indicated that 0.9 M HCl and a biomass concentration of 1 mg mL(-1) were optimal conditions for performing acid hydrolysis. Floccular samples only needed a 2-h hydrolysis time whereas granular samples required as much as 5 h. An intermediate 3 h yielded an error of 10% compared to the results obtained with the hydrolysis times specifically tailored to the type of biomass and can thus be recommended as a practical compromise.


Aggregatibacter actinomycetemcomitans LtxC is required for leukotoxin activity and initial interaction between toxin and host cells.
Aggregatibacter actinomycetemcomitans is a human pathogen that produces the RTX toxin (repeats in toxin), leukotoxin (LtxA). Based on other RTX toxin systems, the product of ltxC, the first gene of the ltx operon, is predicted to be involved in fatty acid modification of LtxA. To determine the function of ltxC in A. actinomycetemcomitans, we generated an ltxC mutation in the highly leukotoxic strain JP2N using random mutagenesis. The toxin from the ltxC mutant (LtxA(ltxC)) was expressed and secreted into the cell culture supernatant but could not lyse human leukocytes or erythrocytes. Mass spectrometric analysis of LtxA(ltxC) and LtxA from strain JP2N (LtxA(wt)) revealed two peptides that differed and this data suggests that two internal lysine residues of LtxA from the wild-type strain are modified. In blocking experiments, pre-treatment of cells with LtxA(ltxC) was unable to prevent LtxA(wt) from killing cells. Furthermore, in contrast to LtxA(wt), LtxA(ltxC) did not cause an increase in intracellular calcium levels in human leukocytes. Taken together, our data show that ltxC is required for full activity and modification of LtxA in A. actinomycetemcomitans and that modification is important for initial binding of toxin to host cells, as defined by an increase in intracellular calcium levels.


Lived experience of vulnerability from a Gypsy Roma Traveller perspective.
To describe the lived experience of vulnerability of individuals within a Gypsy Roma Travelling community. People experience vulnerability whenever their health or usual functioning is compromised. This may increase when they enter unfamiliar surroundings, situations or relationships. One's experience of vulnerability can also be heightened through interactions between the individual and the society within which they live. Gypsy Roma Travellers are often identified as vulnerable owing to increased morbidity and mortality as well as their marginalised status within society. Yet little is known of the experiences of vulnerability by the individuals themselves. Without their stories and experiences, health professionals cannot effectively develop services that meet their needs. This descriptive phenomenological study sought to explore the lived experience of vulnerability in a Gypsy Roma Travelling community. Seventeen Gypsy Roma Travellers were interviewed in 2013-2014 about their experiences of feeling vulnerable. This paper reports on the findings from the depth phase in which 13 individuals were interviewed. The interviews were conducted and analysed using Giorgi's descriptive phenomenological approach. Six constituents of the phenomenon of vulnerability were identified as feeling: defined and homogenised as a group; pressurised to conform to live in a particular way; split in one's identity; a loss of one's heritage; discriminated, persecuted and threatened; and powerlessness. There is a wealth of evidence that Gypsy Roma Travellers experience high levels of morbidity and mortality, which has led to them being identified by health professionals and policy makers as a vulnerable community. Exploring their lived experience of vulnerability presents a different perspective regarding this concept and can help explain why they may experience poorer levels of physical and mental health.


Burden of disease, research funding and innovation in the UK: Do new health technologies reflect research inputs and need?
New and emerging health technologies (innovation outputs) do not always reflect conditions representing the greatest disease burden. We examine the role of research and development (R&D) funding in this relationship, considering whether areas with fewer innovative outputs receive an appropriate share of funding relative to their disease burden. We report a retrospective observational study, comparing burden of disease with R&D funding and innovation output. UK disability-adjusted life years (DALYs) and deaths came from the World Health Organization (WHO) 2004 Global Burden of Disease estimates; funding estimates from the UK Clinical Research Collaboration's 2006 Health Research Analysis; and innovation output was estimated by the number of new and emerging technologies reported by the National Institute for Health Research (NIHR) Horizon Scanning Centre between 2000 and 2009. Disease areas representing the biggest burden were generally associated with the most funding and innovation output; cancer, neuropsychiatric conditions and cardiovascular disease together comprised approximately two-thirds of DALYs, funding and reported technologies. Compared with DALYs, funding and technologies were disproportionately high for cancer, and technologies alone were disproportionately high for musculoskeletal conditions and endocrine/metabolic diseases. Neuropsychiatric conditions had comparatively few technologies compared to both DALYs and funding. The relationship between DALYs and innovation output appeared to be mediated by R&D funding. The relationship between burden of disease and new and emerging health technologies for different disease areas is partly dependent on the associated level of R&D funding (input). Discrepancies among key groups may reflect differential focus of research funding across disease areas.


[Cytomorphology of the basic histological forms of thymus tumors (cytohistological parallels)].
Cytomorphology of various histological types of thymic tumours was studied on transthoracic punctures and scrapes from the operatively removed thymomas. Cytological material was stained by Pappenheim with hematoxylin and eosin, by modified Papanicolau' method as well as by means of luminescent and phase-contrast microscopy. Histological slides were stained with hematoxylin and eosin. Cytological diagnostics of thymomas is based on the detection of the two main types of cells--lymphoid and epithelial. Hassals' bodies are detectable very rarely in the material of lymphoid thymomas punctures. The cytological features characteristic of lymphoid, lymphoepithelial, epithelial, and spindle-cell thymoma are described. The identity of cell types in both cytological smears and histological slides is stated, taking into account their changes in these two research methods.


Pelvic inlet shape measured by three-dimensional pelvimetry is a predictor of the operative time in the anterior resection of rectal cancer.
We evaluated pelvic shape as a predictor of the surgical outcome of anterior resection in patients with rectal cancer. In total, 228 patients who had undergone anterior resection (R0 resection and double-stapling anastomosis) for rectal cancer from 2005 to 2014 were included in this study. The anteroposterior (AP) and transverse (T) diameters of the pelvic inlet and outlet and pelvic depth were analyzed on three-dimensional volume-rendered images, and the AP/T ratio was calculated. Univariate and multivariate analyses were performed to determine the predictive significance of the operative time and intraoperative blood loss as surgical outcomes. No difference was observed between the inlet AP/T and patient sex ratios, but the other pelvic dimensions were significantly shorter in males than in females. The univariate analysis revealed that the operative time was significantly correlated with the inlet T diameter and that it tended to be correlated with the outlet T diameter and the inlet AP/T ratio. A multivariate analysis adjusted for operation-related factors revealed that the inlet AP/T ratio was the only independent risk factor for an extended operative time (p = 0.036). None of the pelvic dimensions were independent risk factors for increased blood loss. The shape of the pelvic inlet may be useful for predicting the operative time.


[Gastrointestinal surgery and gastroenterology. XII. Care of stoma patient].
A stoma nurse provides information, counselling and care to patients with gastrointestinal and urological conditions such as a stoma, incontinence, fistulas or an ileoanal anastomosis with a pouch. The stoma nurse will provide the patient and his or her partner with pre-operative information, post-operative counselling, practical care and instruction as well as check-ups at the outpatients' clinic. Careful selection of the most suitable collection device is highly important. This stoma care has a positive effect on the quality of life of a patient with a stoma. The most common complication is peristomal dermatitis which, in combination with care problems, may lead to social restrictions. Providing the patient's physical and psychological health is not in danger, the stoma care nurse can treat or control these complications, thereby avoiding the need for further surgery.


[Myocardial fibroma. Apropos of a case followed for 11 years].
A case of myocardial fibroma of the left ventricle is described in a young girl. The association of recurrent ventricular tachycardia and radiological deformation of the cardiac silhouette suggested the diagnosis and it was confirmed by myocardial scintigraphy, echocardiography and coronary angiography. At surgery, the tumour was too extensive to be removed. After 11 years follow-up, control of the arrhythmias is satisfactory and there has been no apparent increase in the tumour size. A review of 116 cases in the literature confirms the poor prognosis of myocardial fibroma. The diagnosis was made at autopsy in 60 cases. The 56 remaining patients were operated. Total resection was possible in 37 cases and partial resection in 4 cases. The tumour could not be removed in 15 cases. Overall operative mortality was 35 p. 100 but the prognosis thereafter was good.


Recent Advances in Metallaaromatic Chemistry.
Metallaaromatics can be broadly defined as aromatic compounds in which one of the ring atoms is a transition metal. The metallabenzenes are one important class of these compounds that has undergone extensive study recently. Closely related species such as fused-ring metallabenzenes, heterometallabenzenes, π-coordinated metallabenzenes and metallabenzynes have also attracted considerable attention. Although many metallaaromatics can be considered as metalla-analogues of classic organic aromatic compounds, this is not always the case. Recent seminal studies have shown that metallapentalenes and metallapentalynes, which are metalla-analogues of the anti-aromatic compounds pentalene and pentalyne, are in fact aromatic and highly stable. Very unusual spiro-metallaaromatic compounds have also recently been isolated. In this concepts article, key features of all these intriguing metallaaromatic compounds are discussed with reference to the structural, spectroscopic, reactivity and theoretical studies that have been undertaken. These compounds continue to generate much interest, not only because of the contributions they make to fundamental chemical understanding, but also because of the promise of possible practical applications.


[Role of radiotherapy and chemotherapy in the treatment of colorectal cancer].
Surgery is the only curative therapy for cancer of the colon and rectum. On some occasions, however, radiotherapy and chemotherapy play an important role. In this paper these two methods of treatment, alone or in combination with surgery, are extensively reviewed and the advantages and disadvantages are analyzed.


Synthesis and biological evaluation of isoxazolo[4,5-d]pyridazin-4-(5H)-one analogues as potent anti-inflammatory agents.
In this study, eighteen new isoxazolo[4,5-d]pyridazin-4(5H)-one derivatives possessing either a 1,3,4-thiadiazole or a 1,2,4-triazole-5-thione moiety were synthesized and tested for anti-inflammatory activity in vitro (COX-1/COX-2, 5-LOX) and in vivo (rat paw edema assay). Compounds 15, 16, 25, 26 and 28-30 showed dual COX-2 (IC(50)'s in the 2.1-10.9 μM range), and 5-LOX (IC(50)'s in the 6.3-63.5 μM range) inhibitory activity. When administered orally to rats, dual COX-2/5-LOX inhibitors showed higher anti-inflammatory activity in vivo (30-45% reduction of the inflammatory response) than the reference drug ibuprofen (18%). Among dual COX-2/5-LOX inhibitors, the most potent compound (28) exhibited the best anti-inflammatory profile by inhibiting both COX-2 (IC(50)=2.1 μM) and 5-LOX (IC(50)=6.3 μM) enzymes. We investigated the binding interactions of compound 28 by an enzyme-ligand molecular modeling (docking) studies, which showed favorable binding interactions in both COX-2 and 5-LOX active sites. Furthermore, the dual acting COX-2/5-LOX compound 28 exhibited a superior gastrointestinal safety profile (ulcer index=0.25) compared to the reference drug ibuprofen (UI=7.0) when administered orally at the same molar dose. These observations suggest that isoxazolo[4,5-d]pyridazin-4(5H)-one analogs represent a new scaffold to design potent, effective, and safe anti-inflammatory agents possessing dual COX-2/5-LOX inhibitory activity.


[Air quality vs. morbidity to lung cancer in selected provinces and localities of the Silesian region].
The objective of the study was analysis of the relationship between the quality of ambient air and icidence of lung cancer based on the results of measurements of selected indicator substances and epidemiological data from the localities/provinces in the Silesian Region. The levels of pyrene, benzoanthracene, benzopyrene and dibenzo(a,h)anthracene were analysed, as well as the concentrations of PM10 fractions sampled on glass fibre filters at sampling stations in 5 localities and 8 provinces in the Silesian Region. The classification of morbidity to lung cancer for the localities and provinces in the study was presented based on the data from the Regional Silesian Cancer Registry. In the group of males a relationship was observed between an increased morbidity to lung cancer and an increasing concentration of pyrene and PM10 respirable dust fraction in ambient air. The preliminary analyses confirmed the strong effect of the quality of ambient air on incidence of lung cancer in the Silesian Region.


Mechanism of dietary modulation of calcitonin levels in Fischer rats.
Aging caused an increase in serum calcitonin that was markedly suppressed by food restriction. Food restriction had no significant effect on gut calcium absorption, urinary calcium excretion, serum 1,25(OH)2 vitamin D, blood ionized calcium, the clearance of calcitonin from plasma, and its rate of inactivation in vitro by the kidney and liver. In contrast, food restriction modulated an increase with age in calcitonin secreting C-cells, thyroidal calcitonin and thyroidal calcitonin mRNA pools. We conclude that the lowering of age-related increase in serum calcitonin levels by food restriction is likely because of lowered thyroid calcitonin pools rather than changes in the metabolism of calcium, which is the primary stimulus for calcitonin secretion. Our findings also suggest that food restriction decreases age-related increase in calcitonin levels, at least in part, by modulating the expression of the calcitonin gene.


Metabolic tumor volume by 18F-FDG PET/CT is prognostic for stage IVB endometrial carcinoma.
The objective of this study was to evaluate the potential prognostic factors in patients with primary stage IVB endometrial carcinoma, incorporating parameters from (18)F-FDG PET/CT such as standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Patients with primary M1 endometrial carcinoma who received (18)F-FDG PET/CT before treatment were retrospectively analyzed. Histological type, histological grade, T stage, N stage, age, ECOG performance status, hormone receptor status, metastatic patterns, number of involved metastatic patterns, serum CA125 level, and (18)F-FDG PET/CT derived parameters including total body SUVmax, total body MTV, and total body TLG were considered as potential prognostic factors for overall survival. Cox proportional hazards regression model was used for statistical analysis. Fifteen patients were eligible with a median survival of 17 months. Total body MTV and total body TLG were highly collinear (Pearson's r=0.978) and were found to be significant prognosticators (P=0.010 and 0.011 respectively). Four patients with total body MTV above 450 mL (or total body TLG above 2700 g) had a median survival of two months, while the remaining patients had a median survival of 47 months. Total body MTV is a significant prognostic factor for overall survival in patients with stage IVB endometrial carcinoma. Patients with total body MTV above 450 mL had a very poor survival, while more aggressive therapy may be considered in the remaining patients in pursuit of prolonged survival.


Amperometric urea biosensor based on urease and electropolymerized toluidine blue dye as a pH-sensitive redox probe.
The electropolymerized toluidine blue film deposited on the glassy carbon electrode show amperometrically detectable pH sensitivity. This feature of polytoluidine blue (PTOB) film was used for a construction of an amperometric urea biosensor. We have observed a linear shift of the formal redox potential with increasing pH value between 4 and 8 giving the slope of 81 mV(Delta) pH(-1). Polytoluidine blue film has had a significantly increased stability and higher electrochemical activity compared to the adsorbed monomeric dye. The polytoluidine blue urea biosensor has been operating at a working potential of -200 mV vs. SCE. The sensitivity of the biosensor was 980 nA mM(-1) cm(-2). The biosensor showed linearity in concentration range up to 0.8 mM with the detection limit of 0.02 mM (S/N=3).


Small molecule inhibitors in children with malignant gliomas.
Pediatric high grade gliomas (HGG) remain difficult to cure despite recent advances in imaging, neurosurgery, and radiation. Current treatment modalities have demonstrated only modest survival benefit. Research utilizing molecular biologic techniques reveals that the phenotype of HGG is complex and results from dysregulation of numerous inter-related cellular pathways. Knowledge of potential molecular targets along dysregulated pathways has led to the development of novel and highly specific targeted therapies, which include small molecule inhibitors. This article will review small molecule inhibition of cellular pathways involved in gliomagenesis, challenges to small molecule therapy, and future directions in the use of this therapy.


Typologies of alcohol dependence. From Jellinek to genetics and beyond.
The goal of typology research is to identify subtypes of alcohol dependent (AD) patients sharing fundamental characteristics and try to match each subtype, with the most precise treatment strategy. This review provides a comprehensive history of the literature on alcohol dependent subtypes starting from the earliest attempt made by Jellinek. The binary models identified most closely with Cloninger and Babor as well as the successively more complex classifications are discussed. Typology classification potentially useful in guiding the treatment of AD patients, especially in the case of the serotonergic medications. Contrasting data suggests that other factors could influence the response to a medication and/or that more complex typologies should be identified. In summary, typology models may assist in the ascertainment criteria for clinical trials performed in behavioral and pharmacotherapeutic interventions. Greater emphasis, however, must be made to more clearly delineate this field of research, while moving toward more standardized typologies.


The count-mass distinction in typically developing and grammatically specifically language impaired children: new evidence on the role of syntax and semantics.
By the age of three, typically developing children can draw conceptual distinctions between "kinds of individual" and "kinds of stuff" on the basis of syntactic structures. They differ from adults only in the extent to which syntactic knowledge can be over-ridden by semantic properties of the referent. However, the relative roles of syntax and semantics in determining the nature of the count-mass distinction in language acquisition are still not well-understood. This paper contributes to this debate by studying novel noun acquisition in a subgroup of children, aged 8-15 years, with specific language impairment, whose core deficits are limited to within the grammatical system (G-SLI), We conducted two experiments: a production task and a word extension task. Such children might be expected to rely to a greater extent than their age-matched peers on semantic properties of referents in order to assign noun interpretations, since by hypothesis they have greater difficulty in accessing and utilizing syntactic category distinctions than typically developing children. In the production task, the Children with G-SLI demonstrated rigid over-application of a pluralization rule which masked even basic knowledge of semantic information about individuated objects versus non-individuated substances. Age-matched control children only performed in this way when all syntactic and conceptual/perceptual cues were neutralized. In the word extension task, which required a non-verbal response, the Children with G-SLI showed evidence of only very limited abilities to use syntactic or semantic information for word-learning. Thus, developmental deficits in the grammatical system can be seen to impact on lexical acquisition as well as syntactic development. As a result of this activity, the reader will be able to: (1) describe how syntactic (grammatical) impairment affects the ability to use syntactic cues for lexical acquisition, resulting in difficulties representing the structure of even simple phrases; (2) discuss the interaction between language components throughout development, and the cumulative impact of impairment in one or more aspect of language, which results in secondary impairments in other parts of the system; (3) consider the effects of an impairment in the ability to use syntactic cues for narrowing down word meanings, and how this can result in a much bigger problem affecting the subtle semantics of words and word classes.


[Epidemic of aseptic meningitis with echovirus type 7 in Gifu prefecture in 1986].
During the period from April to November in 1986, an epidemic of aseptic meningitis occurred in Gifu prefecture. Epidemiological, virological and serological investigations were performed. Cases involved ranged from 0 to 30 years of age, and 84.2% of them were under 7 years of age. Seven types of enteroviruses were isolated from 136 of 190 cases (71.6%), and echovirus type 7 was recovered from 121 cases (88.9%). With the cross neutralizing test between the prototype and isolated strains in 1986 of echovirus type 7, a remarkable antigenic variation could not be found. In the serological studies, the positive rates of neutralizing antibodies to echovirus type 7 in 1985, was lower than those in 1975. During the past 18 years before the 1986, echovirus type 7 was not isolated in Gifu prefecture, but in the serological studies, it was confirmed that the sporadic infection with echovirus type 7 had occurred in Gifu prefecture.


[The gas chromatographic determination of dichlorobutenes and trichlorobutenes in washings from the skin].
A sensitive selective method of unsaturated chlorated hydrocarbons detection by means of gas chromatography in skin was worked out. The limits are: for 3,4-dichlorobutene (DCB)-1-0.0024 mu g, for 1,3 DCB-2-0.0027 mu g, for 1,4-DCB-2 (cys)-0.0024 mu g, for 1,4-DCB-2 (trans)-0.0032 mu g, for 2,3,4 trichlorobutene (TCB)-1-0.0093 mu g in analysed volume. The method can be used for the sanitary control of the skin contamination in subjects exposed to DCB and TCB.


Polyclonal Antibodies in Microplates to Predict the Maximum Adsorption Activities of Enzyme/Mutants from Cell Lysates.
With microplate-immobilized polyclonal antibodies against a starting enzyme or its active mutant bearing consistent accessible epitopes, the maximum activity of an adsorbed enzyme/mutant (Vs) was predicted for comparison to recognize weakly-positive mutants. Rabbit antisera against Escherichia coli alkaline phosphatase (ECAP) were fractionated with 33% ammonium sulfate to yield crude polyclonal antibodies for conventional immobilization in 96-well microplates. The response curve of the activities of ECAP/mutant adsorbed by the immobilized polyclonal antibodies to protein quantities from a cell lysate was fit to an approximation model to predict Vs. With 0.4 μg crude polyclonal antibody for immobilization, Vs was consistent for ECAP in cell lysates bearing fourfold differences in its apparent specific activities when its abundance was greater than 0.9%. The ratio of Vs of the mutant R168K to that of ECAP was 1.5 ± 0.1 (n = 2), consistent with that of their specific activities after affinity purification. Unfortunately, the prediction of Vs with polyclonal antibodies that saturated microplate wells was ineffective to Pseudomonas aeruginosa arylsulfatase bearing less than 2% specific activity of ECAP. Therefore, with microplate-immobilized polyclonal antibodies to adsorb enzyme/mutants from cell lysates, high-throughput prediction of Vs was practical to recognize weakly-positive mutants of starting enzymes bearing fairly-high activities.


Professional identification: a study of female students at a medical college in India.
This paper explores female medical students' identification with their profession at a medical college in India by comparing it with that of male students. The professional identification is conceptualized as having three elements: career commitment, career-satisfaction and professional self-image, each elicited by a single question. Compared to males, females were found to perceive medicine as more satisfying, and yet they were less sure than males of pursuing a medical career throughout their lives. The female students' commitment to their career was basically conditional, whereas for the males, it was primarily categorical. Additionally, females expressed less professional ambition than males and preferred different specialties. The main thrust of this paper is that the professional identification of both males and females is qualitatively different. The reasons for these differences are sought in sex-role socialization, cultural norms and informal social pressures at home and at the college.


How soon can I be proficient in embryo transfer? Lessons from the cumulative summation test for learning curve (LC-CUSUM).
Embryo transfer, a crucial step for achieving pregnancy after in vitro fertilization, is an operator-dependent technique but the number of procedures required for a trainee to reach proficiency is unknown. We set out to evaluate the learning curve (LC) of embryo transfer using a specifically designed statistical tool. The first embryo transfers performed by five trainees were monitored by the cumulative summation test for learning curve (LC-CUSUM), a statistical tool designed to indicate when a process has reached a predefined level of performance. The main outcome measure was a positive hCG test. A 40% pregnancy rate (PR) per transfer was chosen to define adequate performance and a PR of 20% was considered inadequate. After the learning phase, standard CUSUM were implemented to ensure that performance was maintained. The same CUSUM parameters were also applied to monitor 241 consecutive embryo transfers performed by a senior gynaecologist. Between 11 and 99 embryo transfers were necessary for the trainees to reach the predefined level of performance. Simple and intuitive graphical representations of the LCs were generated. CUSUM tests confirmed that performance was maintained after the learning phase. The PR of the senior gynaecologist was 42.7% and the CUSUM showed that performance remained adequate throughout the 241 procedures. This study provides an exportable model for a quantitative monitoring of the LC of embryo transfer as well as a reference curve for continuous monitoring of performance in embryo transfer. The length of the LC of embryo transfer is highly variable, justifying a tailored training to learn this procedure.


Aerotactic responses in bacteria to photoreleased oxygen.
Bacterial aerotaxis is a rapid response towards or away from oxygen. Here we report on the use of computer-assisted motion analysis coupled to flash photolysis of caged oxygen to quantify aerotactic responses in bacteria. The caged compound (mu-peroxo)(mu-hydroxo)bis[bis(bipyridyl) cobalt(III)] perchlorate liberates molecular oxygen upon irradiation with near-UV light. A mixture of cells and the caged oxygen compound was placed in a capillary tube and challenged by discrete stimuli of molecular oxygen produced by photolysis. We then recorded the rate of change of direction (rcd) as an estimate of tumble frequency in response to liberated oxygen and measured the signal processing (excitation) times in Bacillus subtilis, Bacillus halodurans and Escherichia coli. This computer-assisted caged oxygen assay gives a unique physiological profile of different aerotaxis transducers in bacteria.


Grape seed extract neutralizes the effects of Cerastes cerastes cerastes post-synaptic neurotoxin in mouse diaphragm.
This work was undertaken to investigate the toxic activity of the post-synaptic neurotoxic fraction isolated from the venom of the Egyptian sand viper (Cerastes cerastes cerastes), and the ability of grape seed extract to antagonize this effect produced in sublethally intoxicated mice, with an emphasis on ultrastructural features. Light and transmission electron microscopy of diaphragms of intoxicated mice showed myonecrosis, myofiber hypercontraction, sarcomere disorganization, and mitochondrial damage. Alterations in motor neurons and axon terminals were also observed. The toxic activities of C. cerastes cerastes neurotoxin were inhibited by administrating grape seed extract, either before or after intoxication, showing that grape seed extract has protective and therapeutic potential to be used as antivenom.


PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β Signaling Induced by Resveratrol.
Protein arginine methyltransferase 5 (PRMT5) is implicated in various types of human cancer and tumor development, especially in lung cancer. Nevertheless, it is still unclear whether suppression of PRMT5 could promote lung cancer cell apoptosis and chemosensitivity induced by resveratrol, and the underlying molecular mechanism remains completely unknown. Here, we showed that PRMT5 was overexpressed in human lung cancer tissues and different types of lung cancer cell lines. Moreover, we constructed PRMT5 stable knockdown cell lines (A549 and ASCT-a-1) and investigated the roles of PRMT5 and the related signaling pathway in lung cancer cell apoptosis induced by resveratrol. Our results indicated that inhibition or down-regulation of PRMT5 by GSK591, a PRMT5-specific inhibitor, or shRNAs markedly enhanced cell apoptosis and chemosensitivity stimulated by resveratrol. Further investigation showed that inhibition or down-regulation of PRMT5 further reduced Akt/GSK3β phosphorylation and the downstream targets cyclin D1 and E1 expression upon resveratrol treatment. Our findings suggest that PRMT5 is a pivotal mediator for human lung cancer cell death induced by resveratrol, which also reveals that PRMT5 may serve as a new therapeutic target for the treatment of human lung cancer.


[Cardiac multidetector-row CT: first clinical results of retrospectively ECG-gated spiral with optimized temporal and spatial resolution].
The significantly improved temporal and spatial resolution of Multidetector-Row CT opens up new possibilities for cardiac imaging. A method with retrospectively ECG-gated spiral acquisition is presented. A total of 10 patients underwent cardiac CT on a fast multi-slice CT system with 4 simultaneously acquired slices and 0.5 s rotation time (Siemens Somatom Volume Zoom). Continuous spiral data of the entire heart volume (5 studies precontrast for calcium scoring, 5 studies with contrast) were acquired together with the patient's ECG and reconstructed with dedicated spiral algorithms providing 250 ms temporal resolution. Three-dimensional image data sets were built up from overlapping slices that were reconstructed in an arbitrary, user-defined phase of the heart cycle (e.g., diastolic phase). To evaluate the capability of the method for functional imaging, complete image volumes were reconstructed from the same spiral data set in different phases of the heart cycle. Within a single breath-hold, a spiral data set of the entire heart volume could be acquired. Typical scan times for standard examinations with 3-mm slice width were 12-17 s, and for high-resolution CT angiographies of the coronary arteries with 1.25-mm slice width about 25-35 s. Motion-free reconstruction of the heart and coronary arteries with high spatial resolution were possible in the diastolic phase of the heart cycle. Multiphase reconstructions from the same spiral scan data set were possible. Fast multi-slice spiral CT with retrospectively ECG-gated spiral reconstruction is well suited for three-dimensional and functional imaging of the heart, especially for high-resolution imaging of calcified coronary plaques and CT-angiography of the coronary arteries.


Adoption of ICT by Elderly with Hip Fracture After a Fall.
The purpose of this study is to investigate the adoption of Information and Communication Technologies (ICTs) of elderly with hip fracture after a fall. Demographic and clinical data using a general questionnaire were obtained from 67 elderly patients with a hip fracture after fall and compared with 67 gender-age matched elderly healthy controls regarding their knowledge and use of ICT-based devices. Univariate and multivariate analyses were conducted at p=0.05. 25.4% of the patients vs 10.5% of the controls uses ICT-based devices (p=0.024). Among patients, the demographic factors significantly associated with the use of ICT-based devices included area of residence, educational level and financial status (p<0.001 to p=0.045). In conclusion, based on a small sample, it seems that the adoption of ICT by the elderly vulnerable populations is limited.


Interactions of blood proteins with poly(isobutylcyanoacrylate) nanoparticles decorated with a polysaccharidic brush.
The aim of this work was to examine the in vitro interactions of core-shell poly(isobutylcyanoacrylate)-polysaccharide nanoparticles (NP) with blood proteins. The particles were prepared by initiating the emulsion polymerization of isobutylcyanoacrylate (IBCA) in the presence of dextran 71 or 15 kDa, heparin, a blend of dextran 71 and heparin, or dextran sulphate in aqueous medium at pH 1. The mechanisms of polymerisation were redox radical (Rad) or anionic (An), resulting in differences in the spatial arrangement of the polysaccharide chains at the NP surface, i.e. "loops" and "trains" by anionic polymerization, "brush" by radical polymerization. Surface composition of NPs was determined by X-ray photo-electron spectroscopy (XPS) and surface charge by zeta potential measurements. In the presence of citrated blood plasma, efficacy of the steric repulsive effect of the NP dextran shell towards protein adsorption decreased in the order: Dex71-Rad > Dex15-Rad > Dex71-AnDex15-An. Dextran-coated NPs adsorbed ApoA-I and fibrinogen from plasma. Concerning activation of complement in serum, the effect was sharp: Dex71-Rad was a very low activator whereas Dex15-An, Dex15-Rad and Dex71-An were strong activators. In citrated plasma, the steric repulsive effects of Hep-Rad and Dex-Hep-Rad NPs were similar to Dex71-An, and Dex-Sulph-Rad NPs adsorbed twice more proteins than Hep-Rad. Hep-Rad, Dex-Hep-Rad and Dex-Sulph-Rad NPs adsorbed IgG and fibrinogen. Complement was not activated in serum in the presence of Hep-Rad and Dex-Hep-Rad and a slight adsorption of C3 was noted. C3 was completely adsorbed on Dex-Sulph-Rad. The exquisite sensitivity of blood proteins to differences in the nature and outermost structure of the polysaccharides-coated NPs is highlighted by the present results.


Regression to the mean: a potential source of error in clinical pharmacological studies.
The design and interpretation of clinical trials in clinical pharmacology must avoid certain pitfalls to be useful in guiding drug therapy decisions. Here, we discuss one important problem in clinical trial design, the problem of regression to the mean. Because certain disease states tend to wax and wane in severity and because patients tend to present for treatment when disease activity is high, the expected course of the disease is improvement. Therefore, any treatment begun will appear to lessen disease activity. We give four examples of diseases where improper and inadequate recommendations for drug therapy have been made based on clinical trials that ignored the problem of regression to the mean: vasospastic angina, rheumatoid arthritis, chronic congestive heart failure, and renal stones. Studies of drug therapy in diseases such as these should be conducted with concurrent placebo controls rather than having each patient serve as his own control.


Site directed mutagenesis: a tool for enzyme mechanism dissection.
Protein engineering has become the principle means of examining the active site of an enzyme to identify and quantify the roles of specific residues in ligand binding, specificity and catalysis. Site-specific mutagenesis has extended our knowledge gained from X-ray crystallography, and has provided striking proof that the intricate active-site geometry is supported by the remainder of the protein infrastructure for maximum catalytic efficiency.


Ribotyping differentiates relapse from reinfection in the treatment failures of Escherichia coli urinary tract infections in children.
Analysis of restriction fragment-length polymorphism of ribosomal DNA regions (ribotypes) was used as an epidemiologic tool to compare 25 pre- and posttreatment strains obtained from 12 patients treated with either cefpodoxime proxetil or amoxicillin-clavulanic acid. Ribotyping is a promising method to differentiate relapse from reinfection in the treatment failures of Escherichia coli urinary tract infections.


Two-year-old girl with impacted ureteral stone successfully treated with a single session of combined percutaneous nephrostomy and ureteroscopy.
Impacted stones frequently cause changes in the ureter, including edema of the ureteral wall, stone embedding in the ureteral mucosa or ureteral bending, which often preclude spontaneous passing of the stone and increase the risk of complications during surgery. When stone impaction is suspected preoperatively, management should be adapted accordingly. However, surgical treatment strategies remain controversial in pediatric patients because of the scarcity of cases reported. We describe the case of a 2-year-old girl with a right impacted ureteral stone who presented with gross hematuria and pyuria, but no metabolic risk factors or hematological abnormalities. Ureteroscopy was carried out in the presence of a percutaneous nephrostomy catheter. At the 7-month follow up, hydronephrosis had improved from grade 3 to grade 1, and the ureter was free from residual or recurrent stones. No complications were noted. We believe that percutaneous nephrostomy before the lithotripsy facilitates treatment for impacted stones in pediatric patients.


Patient and Practice Trends in Total Ankle Replacement and Tibiotalar Arthrodesis in the United States From 2007 to 2013.
Both total ankle replacement (TAR) and tibiotalar arthrodesis (TTA) are used in the surgical management of ankle arthritis. Over the past decade, TAR instrumentation, techniques, and implants have improved, making the procedure more reliable and reproducible, thus making TAR more common. The Nationwide Inpatient Sample database from 2007 to 2013 was used to obtain data on patients elder than 50 years who underwent either TAR or TTA. Differences in temporal, demographic, and diagnosis trends between TAR and TTA were analyzed. Between 2007 and 2013, 15,060 patients underwent TAR and 35,096 underwent TTA. Patients undergoing TTA had significantly more comorbidities (2.17 versus 1.55; P < 0.001). The share of TAR performed increased significantly from 2007 (14%) to 2013 (45%) (P < 0.001). From 2007 to 2013, we found a 12-fold increase in the odds of having a TAR for patients with posttraumatic osteoarthritis (P < 0.001), a 4.9-fold increase for those with primary osteoarthritis, and a 3.1-fold increase for patients with rheumatoid arthritis (P < 0.001). Over the past decade, the frequency of TAR has increased, particularly in patients with posttraumatic arthritis and osteoarthritis. Surgeons still perform TAR in healthier patients compared with TTA; however, because surgeons become more experienced with the technique, patients are undergoing TAR at a markedly higher rate. Level III: retrospective comparative study.


Seroepidemiology of spotted fever group rickettsial infections in humans in Zimbabwe.
In sera collected throughout Zimbabwe the prevalence of antibodies reactive with Rickettsia conorii (Kenya) and a Zimbabwean spotted fever group rickettsia (ZSFR) was investigated using an indirect immunofluorescence assay (IFA). A random sample of these sera was also tested using a commercial IFA test. There was close agreement between IFA titres using the African rickettsial antigens and the commercial antigen slides. When differences in titre were detected, these were rarely greater than a twofold serum dilution. In Western blot immunoassays, IFA positive human sera detected immunogens of ZSFR and R. conorii (Kenya) that could also be demonstrated with homologous mouse antisera. The overall seroprevalence was 52% to R. conorii (Kenya) and 55% to ZSFR. For both antigens the highest seroprevalence was recorded from the south of the country, where the highest incidence of clinical tick-bite fever was reported in a questionnaire survey to medical practitioners. No difference was found between the seroprevalence in males and females, but high titres of antibody were common in samples from young people.


Role of glutamate receptor subtypes in the differential release of somatostatin, neuropeptide Y, and substance P in primary serum-free cultures of striatal neurons.
The spiny and aspiny neuronal populations of the striatum display differential vulnerability to the toxic effects of glutamatergic agonists. Substance P-containing spiny neurons appear to be more vulnerable to NMDA-receptor-mediated toxicity and less susceptible to kainate toxicity than the somatostatin- and neuropeptide Y (NPY)-containing aspiny population. We studied whether selective glutamatergic agonists might have similar differential effects on neuropeptide release from the substance P- and somatostatin/NPY-containing neuronal populations. After collection of a baseline sample, striatal neurons in primary culture were treated with one of the following: phosphate-buffered saline, 56 mM potassium chloride (KCl), 100 microM N-methyl-D-aspartate (NMDA), 100 microM quisqualate, 100 microM kainate, or 100 microM glutamate. Baseline and treatment samples were measured by radioimmunoassay for somatostatin, NPY, and substance P. KCl and kainate provoked a selective release of somatostatin and NPY, whereas substance P measured in the same samples showed no response. By contrast, NMDA elicited a selective release of substance P without a similar increase of either somatostatin or NPY. Quisqualate evoked comparable responses in the three peptides. These results indicate that the glutamatergic regulation of somatostatin and NPY release from aspiny striatal neurons in primary culture is preferentially mediated by the kainate receptor, whereas substance P release is selectively mediated by the NMDA receptor. These findings suggest a preferential expression of functional kainate receptors on the aspiny somatostatin/NPY neurons and of NMDA receptors on the substance-P-containing spiny neurons.


Patagonfibrase modifies protein expression of tissue factor and protein disulfide isomerase in rat skin.
Patagonfibrase is a hemorrhagic metalloproteinase isolated from the venom of the South American rear-fanged snake Philodryas patagoniensis, and is an important contributor to local lesions inflicted by this species. The tissue factor (TF)-factor VIIa complex, besides triggering the coagulation cascade, has been demonstrated to be involved in inflammatory events. Our aim was to determine whether patagonfibrase affects the expression of TF and protein disulfide isomerase (PDI), an enzyme that controls TF biological activity, at the site of patagonfibrase injection, and thus if they may play a role in hemostatic and inflammatory events induced by snake venoms. Patagonfibrase (60 μg/kg) was administered s.c. to rats, and after 3 h blood was collected to evaluate hemostasis parameters, and skin fragments close to the site of injection were taken to assess TF and PDI expression. Patagonfibrase did not alter blood cell counts, plasma fibrinogen levels, or levels of TF activity in plasma. However, by semiquantitative Western blotting, patagonfibrase increased TF expression by 2-fold, and decreased PDI expression by 3-fold in skin samples. In agreement, by immunohistochemical analyses, prominent TF expression was observed in the subcutaneous tissue. Thus, patagonfibrase affects the local expression of TF and PDI without inducing any systemic hemostatic disturbance, although that they may be involved in the local inflammatory events induced by hemorrhagic metalloproteinases. Once antivenom therapy is not totally effective to treat the local injury induced by snake venoms, modulation of the activity and expression of TF and/or PDI might become a strategy for treating snake envenomation.


Development of an adolescent risk-taking instrument.
The purpose of this research study was to estimate the reliability and content validity of an instrument designed to measure risk-taking in adolescents. Six subscales containing 69 items were developed to measure the adolescent's perception of risk-taking. Subjects consisted of 75 male and female adolescents enrolled in a vocational training program. Support for reliability was obtained by the use of Chronbach's alpha correlation coefficient for the subscales and the Risk-Taking Instrument.


The properties of small fullerenol cluster (C60(OH)24)7: computer simulation.
The nanosystem composed of only as few as seven fullerenols C(60)(OH)(24) molecules was studied using the molecular dynamics (MD) technique. The interaction was taken to be the full site-site pairwise additive Lennard-Jones (LJ) potential, which generates both translational and anisotropic rotational motions of each fullerenol. The radial distribution function, the mean square displacement, the Lindemann index, the translational and angular velocity correlation functions of fullerenol have been calculated for several energies of the nanosystem. We provide also the in-depth evidence of the solid-liquid phase transition in the investigated cluster. The comparison with the properties of pure fullerene cluster (C(60))(7) is provided. The study are motivated by the expected diverse biological applications of water-soluble fullerenols.


Opiate antagonists: a role in the treatment of hypovolemic shock.
The opiate antagonist naloxone has been used to treat shock following acute blood loss in conscious rats. Naloxone treatment rapidly increased mean arterial pressure and pulse pressure in this new shock model. More importantly, these blood pressure changes were sustained and survival was significantly increased with maloxone as compared with placebo treatment. From these findings, it may be inferred that endorphins may play a role in the pathophysiology of hypovolemic shock. It is suggested that narcotic antagonists may prove to be of therapeutic value in the treatment of shock.


Suppression of experimental autoimmune uveoretinitis by Anti-IL-17 antibody.
To determine whether treatment with anti-IL-17 antibody could suppress the intraocular inflammation of experimental autoimmune uveoretinitis (EAU) in rats. Rats were immunized with interphotoreceptor retinoid binding protein (IRBP) R16 peptide and were treated with anti-IL-17 antibody. Clinical signs of inflammation and ocular histological sections were observed and graded. Cytokine levels of supernatants of cells from draining lymph nodes were measured by enzyme-linked immunosorbent assay (ELISA). Delayed-type hypersensitivity (DTH) and lymphocyte proliferation assay (LPA) were detected. Treatment of EAU with anti-IL-17 antibody delayed the onset of ocular inflammation and markedly inhibited the development of EAU. Antigen-specific DTH and LPA were suppressed, whereas the level of interferon (IFN)-gamma produced by draining lymph node cells was increased after treatment with anti-IL-17 antibody. There was no significant change of IL-5 level as compared with control rats. These findings demonstrate that blockade of endogenous IL-17 activity by treatment with anti-IL-17 antibody attenuates EAU in rats. IL-17 rather than IFN-gamma plays a crucial role in the development of EAU, and that antagonism of IL-17 could be useful for the treatment of human intraocular autoimmune diseases.


N-acetyl cysteine add-on treatment for bipolar II disorder: a subgroup analysis of a randomized placebo-controlled trial.
The evidence base for the pharmacological treatment of bipolar II disorder is limited. In bipolar disorder, there is evidence for glutathione depletion and increased oxidative stress, as well as dysregulation of glutamate; N-acetyl cysteine (NAC) has effects on both of these systems. Add-on NAC has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial. In this report, we explore the effects of this compound in a subset of patients with bipolar II disorder from that trial. Individuals were randomized to NAC or placebo in addition to treatment as usual, in a double-blind fashion. Mood and functional outcomes were assessed up to 24 weeks of treatment. Fourteen individuals were available for this report, seven in each group. Six people achieved full remission of both depressive and manic symptoms in the NAC group; this was true for only two people in the placebo group (χ(2)=4.67, p=0.031). Subgroup analyses in a small subsample of patients. Not all participants had elevated depression scores at baseline. Notwithstanding all the limitations that subgroup analysis of trials carry, this data could serve as a hypothesis-generating stimulus for further clinical trials of pharmacologic treatment for bipolar II depression.


The (oxalato)aluminate complex as an antimicrobial substance protecting the "shiro" of Tricholoma matsutake from soil micro-organisms.
Tricholoma matsutake, a basidiomycete, forms ectomycorrhizas with Pinus densiflora as the host tree. Its fruiting body, "matsutake" in Japanese, is an edible and highly prized mushroom, and it grows in a circle called a fairy ring. Beneath the fairy ring of T. matsutake, a whitish mycelium-soil aggregated zone, called "shiro" in Japanese, develops. The front of the shiro, an active mycorrhizal zone, functions to gather nutrients from the soil and roots to nourish the fairy ring. Bacteria and sporulating fungi decrease from the shiro front, whereas they increase inside and outside the shiro front. Ohara demonstrated that the shiro front exhibited antimicrobial activity, but the antimicrobial substance has remained unidentified for 50 years. We have identified the antimicrobial substance as the (oxalato)aluminate complex, known as a reaction product of oxalic acid and aluminum phosphate to release soluble phosphorus. The complex protects the shiro from micro-organisms, and contributes to its development.