Heterogeneity of Nef proteins in cells infected with human immunodeficiency virus type 1.
Human T-lymphocytic cell line H9 infected with the HTLV-IIIB isolate of human immunodeficiency virus type 1 (HIV-1) synthesizes two forms of the Nef protein (p25 and p27) that differ both in molecular weight and charge. Different subpopulations of viruses were isolated from the HTLV-IIIB stock which induce expression of only p25 or p27. Cells infected with HIV-1 derived from the HXB3 clone of the HTLV-IIIB isolate made only the p25 species, whereas the 8E5/LAV cell line which harbors a single defective LAV provirus produces only the p27 species. These findings are consistent with the notion that the HTLV-IIIB isolate consists of at least two distinct variants with different nef genes, one specifying p25 and the other encoding p27. After a considerable number of passages in culture, H9 cells chronically infected with the HTLV-IIIB isolate produced high levels of p25 and lower levels of p27. Passages in culture appear to select for a subpopulation of virus variants that specify high levels of p25 Nef expression.


Ellagic Acid: A Logical Lead for Drug Development?
Naturally occurring polyphenols are the subject of increasing attention due to their potent antioxidant activity and their marked effects on the prevention of various oxidative stress-associated diseases such as cancer. Ellagic acid (EA) is an herbal polyphenol that is structurally a condensed dimer of gallic acid. This review aims to provide a comprehensive and updated overview on the biological activities of EA and potential therapeutic applications. EA is found in fruits and nuts, either in the combined form with hexahydroxydiphenic acid or in the bound form (ellagitannins). EA exhibits many biological properties such as antioxidant, anti-diabetic, anticancer and apoptosis-inducing activities. These biological and pharmacological properties are relevant to the treatment of several human diseases. Owing to its multiple mechanisms of action, EA represents a potential therapeutic agent against human diseases particularly cancer.


Descriptive study of intravenous immunoglobulin for the treatment of recurrent Clostridium difficile diarrhoea.
Clostridium difficile diarrhoea (CDD) cases treated with intravenous immunoglobulin during a 2 year period were reviewed to determine disease severity and response to treatment. Of 580 CD cytotoxin-positive patients, five received intravenous immunoglobulin because of protracted and/or recurrent CDD (median duration 50 days, range 45-64); two had biopsy- proven pseudomembranous colitis. The five patients received a median three non-CDD antibiotic courses (range 2-8). Indices of CDD severity included hypoalbuminaemia (n = 5, median 27 g/L, range 11-29), marked hypokalaemia (n = 3, range 1.9-2.7 mM), markedly raised peripheral white cell count (n = 3, 18-34 x 10(9) cells/L), abdominal signs (n = 3) and pyrexia (n = 1). The five cases received metronidazole for median 17 days (range 0-63) plus vancomycin for median 14 days (range 10-42) before intravenous immunoglobulin. One also received rifampicin plus vancomycin and one was given Saccharomyces boulardii. Intravenous immunoglobulin was given at a dosage of 300-500 mg/kg (most commonly 400 mg/kg) for one dose (two patients), two doses (two patients) and in one case for six doses. The latter patient died of intractable CDD, three had a good therapeutic response to intravenous immunoglobulin and CDD recurred within 6 weeks in one case. In the three successfully treated cases, CDD resolved within 11 days. Intravenous immunoglobulin is useful for the treatment of intractable and severe CDD. Controlled studies are needed to assess the true value of this and other forms of passive immunotherapy.


Synthesis and antiinflammatory activity of 2H-tetrazol-2-acetic acids, esters and amides.
A series of 5-(pyridyl)-2H-tetrazol-2-acetic acids (16-21), esters (10-15), and amides (22-27) was synthesized in order to investigate the effect of 5-substituents (R1 = 2-, 3- or 4-pyridyl) and alpha-substituents (R2 = H, Me) on anti-inflammatory activity. The point of attachment of the R1-pyridyl substituent influenced potency. The relative potencies in the acetic acid ester, acetic acid and acetamide classes of compounds were 2- and 4- greater than 3-pyr, 2- and 3- greater than 4-pyr, and 4- greater than 2- and 3-pyr, respectively. In the acetic acid ester and acetamide classes, compounds having a R2 hydrogen substituent were generally more potent than corresponding methyl substituted compounds, whereas, in the acetic acid class the reverse applied. The relative order of anti-inflammatory potency was generally amide greater than ester greater than acid. 2-[5-(4-Pyridyl)-2H-tetrazol-2-yl]acetamide (26) was the most effective antiinflammatory agent in the series, reducing inflammation by 53% at 3 and 5 hr after a 25 mg/kg po dose.


[Extracorporeal circulation in no-cardiac surgery: experience at the Clinica Universidad de Navarra].
Analyse the use of the Extra-Corporeal Circulation (ECC) in no-cardiac operations at the Clinica Universidad de Navarra. Between 1985 and 2009, the ECC has been involved in 28 operations for retroperitoneal tumour with inferior vena cava thrombus, in 43 isolated hyperthermic perfusion of a limb for locally advanced cancer and in 8 cases of chest mass with invasion of the pulmonary veins or bronchial carina. The intraoperative mortality for renal cancer has been of 7% while the 28% of patients showed a major complication. None patient died for the isolated hyperthermic perfusion and the 81% showed no toxicity. 1 patient out of 8 for chest mass died during the surgery for impossibility of weaning from the ECC. The ECC has been utilised in our experience mostly in cases of advanced cancer. It is an aggressive technique with a certain rate of complications. Nevertheless mid- and long-term results are encouraging. The ECC is the only technique in some advanced cancer in order to safely perform the mass removal. The precise co-ordination of the team is necessary to reduce the complication rate.


Pathology of traumatic brain injury.
Although traumatic brain injury (TBI) is frequently encountered in veterinary practice in companion animals, livestock and horses, inflicted head injury is a common method of euthanasia in domestic livestock, and malicious head trauma can lead to forensic investigation, the pathology of TBI has generally received little attention in the veterinary literature. This review highlights the pathology and pathogenesis of cerebral lesions produced by blunt, non-missile and penetrating, missile head injuries as an aid to the more accurate diagnosis of neurotrauma cases. If more cases of TBI in animals that result in fatality or euthanasia are subjected to rigorous neuropathological examination, this will lead to a better understanding of the nature and development of brain lesions in these species, rather than extrapolating data from human studies.


[Clinical spectrum and treatment strategy in anti-NMDA receptor encephalitis: current status and issues].
Anti-NMDA receptor encephalitis is a disorder caused by IgG antibodies to the extracellular conformal epitope of the NR1 subunits. This disorder predominantly affects young female with ovarian teratoma;however, any person of any age, unrelated to gender or the presence of tumor, can be affected. This disorder usually follows multistage beginning with prodromal symptoms, followed by psychiatric symptoms, unresponsive state accompanied by intractable dyskinesias, seizure and central hypoventilation. Diversity of clinical spectrum has recently been emphasized based on antibody detection in various disorders, including schizophrenia, epilepsy, CJD, neuromyelitis optica, and HSV encephalitis, but these data must be cautiously interpreted; low serum titers may be false positive or clinically not relevant. This disorder has been regarded as treatment-responsive; however, only a half of the patients respond to the first-line immunotherapy (corticosteroids, immunoglobulins or plasma exchange) or tumor removal, and 19 percent remain highly disabled at 24 months with an estimated morality rate of 7%. In refractory cases early initiation of the second-line immunotherapy (rituximab and/or cyclophosphamide) recommended; however, it is difficult to follow the recommendation due to many issues, among those, off-label use is the major reason that prevents initiation of the second-line immunotherapy in Japan.


Excited- and ground-state versions of the tri-pi-methane rearrangement: mechanistic and exploratory organic photochemistry.
The di-pi-methane rearrangement with two pi-groups bonded to a single carbon leading to pi-substituted cyclopropanes is now well established. The present research had as its goal the exploration of molecular systems having three pi-moieties attached to an sp(3)-hybridized atom in a search for a tri-pi-methane rearrangement. Indeed, it was found that such systems do rearrange photochemically to afford cyclopentenes. However, it was also established that vinylcyclopropanes ring-expand to cyclopentenes on direct irradiation. Since both three-ring and five-ring photoproducts often are found to be produced, it was important to establish that the observed photochemistry was really the result of a true single-step tri-pi-methane rearrangement and not the consequence of two sequential rearrangements, first to form a vinyl cyclopropane which subsequently ring expanded to the cyclopentene. The general situation has three species-A, B, and C-corresponding to tri-pi-methane reactant A, vinylcyclopropane photoproduct B, and cyclopentene photoproduct C. Three rate constants are involved, k(1) for A --> B, k(2) for A --> C, and k(3) for B --> C. The kinetics were applied to two examples with provision to avoid differential light absorption; this utilized singlet sensitization. It was determined that direct formation of the cyclopentene photoproduct proceeds more rapidly than the ring-expansion route. In contrast to the di-pi-methane rearrangement, the tri-pi-methane reaction was found to be preferred by the singlet, while in these sterically congested systems, the triplet led to di-pi-methane reactivity. Finally, a ground-state counterpart of the reaction was obtained.


Seizure-induced changes in energy metabolites and effects of N-tert-butyl-alpha-phenylnitrone (PNB) and vitamin E in rats.
Impaired energy metabolism may play a critical role in the neuronal injury caused by kainic acid (KA) induced status epilepticus (SE). Following an acute dose of KA (15 mg/kg, s.c.) rats developed SE within 1 h. Rats were sacrificed 1 or 72 h after the onset of SE using a head focused microwave technique and the brain regions (pyriform cortex, amygdala, and hippocampus) were assayed for energy metabolites: ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) using reversed-phase HPLC (RP-HPLC). Control values were significantly higher in cortex (23-32%) than in other brain regions. Within 1 h, SE caused a marked decline in ATP (44-56%), PCr (49-64%), total adenine nucleotides (TAN, 45-50%) and total creatine compounds (TCC, 32-51%). Within three days, the hippocampus showed the greatest recovery, as the reduced values returned to normal. Pretreatment of rats with an antioxidant (PBN, 200 mg/kg, i.p., 30 min prior to KA; or vitamin E (Vit-E), 100 mg/kg, i.p./day for 3 days), which did not prevent seizure activity, attenuated depletion of high-energy phosphates caused by KA. These findings suggest that the depletion of energy metabolites caused by KA-induced seizures may be linked to oxidative stress mediated toxicity.


Cervical length as a predictor of pre-term birth in twin gestations.
The aim of this study was to determine the predictive value of cervical length as a risk factor for spontaneous pre-term birth in twin gestations. A retrospective chart review was carried out on patients with twin pregnancies referred to our multiples' clinic. Cervical length was measured by transvaginal ultrasonography. Patients with an indicated pre-term delivery or intervention were excluded from the analysis. Outcomes included preterm delivery < 28 and < 35 weeks gestation. After extracting the data, 2 x 4 tables were constructed. Likelihood ratios were then generated for cervical lengths < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm. Because of the limited number of measurements taken < 25 weeks gestation, we elected to collapse the tables, thereby achieving more meaningful results. For measurements taken before 30 weeks gestation, a shorter cervix did predict delivery < 28 weeks gestation (likelihood ratios for cervical lengths < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm were 4.43, 1.94, 0.97, and 1.02, respectively). The probability of preterm delivery < 35 weeks gestation increased with decreasing cervical length (likelihood ratios for cervical length < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm were 2.58, 1.66, 1.38, and 0.81, respectively). A shorter cervix measured before 30 weeks gestation was a stronger predictor of preterm delivery < 28 weeks compared to < 35 weeks gestation. Cervical length was not predictive of preterm delivery if measured after 30 weeks. Cervical length is predictive of preterm delivery < 28 weeks and < 35 weeks gestation when measured before 30 weeks gestation. No trend was seen when measured after 30 weeks gestation. A prospective study is currently underway to confirm these results.


Scanning-electron microscopy studies of 'ground substance' in the cement lines, resting lines, hypercalcified rings and reversal lines of human cortical bone.
Adult human cortical bone was decalcified and stained with Harris's hematoxylin, which has a strong affinity for cement lines, resting lines, hypercalcified rings and reversal lines. Small pieces of bone tissue containing these morphological entities were then dissected and manipulated mechanically so as to disrupt them partially. Scanning electron microscopy of these regions of interest revealed the presence of relatively large concentrations of amorphous 'ground substance' which was morphologically distinguishable from the fibrous collagen fiber bundles located in the adjoining collagen-rich lamellae. The methodology used in this study confirms the existence of the above-mentioned regions as true morphological entities and also makes possible enzymatic studies designed to identify the major biochemical components constituting the observed 'ground substance'.


Anti-proliferative lichen compounds with inhibitory activity on 12(S)-HETE production in human platelets.
Several lichen compounds, i.e. lobaric acid (1), a beta-orcinol depsidone from Stereocaulon alpinum L., (+)-protolichesterinic acid (2), an aliphatic alpha-methylene-gamma-lactone from Cetraria islandica Laur. (Parmeliaceae), (+)-usnic acid (3), a dibenzofuran from Cladonia arbuscula (Wallr.) Rabenh. (Cladoniaceae), parietin (4), an anthraquinone from Xanthoria elegans (Link) Th. Fr. (Calaplacaceae) and baeomycesic acid (5), a beta-orcinol depside isolated from Thamnolia vermicularis (Sw.) Schaer. var. subuliformis (Ehrh.) Schaer. were tested for inhibitory activity on platelet-type 12(S)-lipoxygenase using a cell-based in vitro system in human platelets. Lobaric acid (1) and (+)-protolichesterinic acid (2) proved to be pronounced inhibitors of platelet-type 12(S)-lipoxygenase, whereas baeomycesic acid (5) showed only weak activity (inhibitory activity at a concentration of 100 microg/ml: (1) 93.4+/-6.62%, (2) 98,5+/-1.19%, 5 14.7+/-2.76%). Usnic acid (3) and parietin (4) were not active at this concentration. 1 and 2 showed a clear dose-response relationship in the range of 3.33-100 microg/ml. According to the calculated IC50 values the highest inhibitory activity was observed for the depsidone 1 (IC50 = 28.5 microM) followed by 2 (IC50 = 77.0 microM). The activity of 1 was comparable to that of the flavone baicalein, which is known as a selective 12(S)-lipoxygenase inhibitor (IC50 = 24.6 microM).


Identification of Entamoeba histolytica intracellular phospholipase A and lysophospholipase L1 activities.
Entamoeba histolytica phospholipase A and lysophospholipase activities from a vesicular subcellular fraction (P30) were analyzed. The products, obtained using specific substrates labeled with 14C or 3H, indicated the presence of phospholipase A1 and A2 as well as lysophospholipase L1 activities. The enzymes detected could participate in phospholipid metabolism and the alkaline phospholipase A2 may contribute to E. histolytica cytopathogenicity.


[Regional campaign promoting the use of sodium iodide: "a pinch of health"].
The regional campaign aimed at promoting consumer purchase and use of iodized salt was launched in 1988. The aim of this campaign has been to disseminate correct dietary information to regional consumers, guaranteeing at the same time the availability of iodine-enriched salt through the regional commercial distribution network. The main campaign target is to reach average consumption levels in the more developed countries. The regional campaign is a part of the world-wide WHO and UNICEF projects aimed at eradicating thyroid disorders due to an inadequate iodine intake. The campaign is to be further developed through health and consumer education programs in the school as well as a wider coverage of the issue in the mass-media.


Structure-activity relationship of parathyroid hormone: relative sensitivity of rabbit renal microvessel and tubule adenylate cyclases to oxidized PTH and PTH inhibitors.
It has been shown previously that secondary structural changes of bPTH-(1-34) (synthetic amino-terminal (1-34) fragment of bovine parathyroid hormone), obtained by oxidation of the methionines 8 and 18, abolished its hypotensive but not its hypercalcemic action. Hence, it has been postulated that the various physiological effects of the hormone are mediated by different receptors that require different regions or configurations of the peptide. To further examine this hypothesis the relative sensitivity of the PTH-responsive adenylate cyclase of microvessels and tubules isolated from rabbit kidney cortex, to oxidized PTH and PTH inhibitors, was examined. In the presence of GTP, bPTH-(1-34) stimulated both microvessel and tubule adenylate cyclase in a dose-dependent fashion and with analogous affinities (ED50 = 52 nM in the microvessels and 85 nM in the tubules). Hydrogen peroxide treatment of bPTH-(1-34) resulted in the loss of the adenylate cyclase stimulating potency in the microvessels while there was substantial enzyme activation (ED50 = 900 nM) in the tubules. Oxidized PTH inhibited the untreated PTH-stimulated adenylate cyclase, suggesting that oxidized PTH still retains an affinity for vascular receptor sites. Similar treatment of the sulfur-free PTH analog [Nle8,18, Tyr34]bPTH-(1-34)NH2, where methionines have been replaced by norleucine, had little or no effect in both fractions. In the microvessels the synthetic PTH antagonist analogs [Nle8,18, Tyr34]bPTH-(3-34)NH2 and [Tyr34]bPTH-(7-34)NH2, strongly inhibited the adenylate cyclase responses to bPTH-(1-34). No inhibition was seen in the tubules with the same molar ratios of inhibitor to native PTH. Together, these results suggest strongly that the differences in the adenylate cyclase response to various PTH fragments most likely represent a difference in the structural requirements for PTH actions between microvessels and tubules.


The role of n-3 polyunsaturated fatty acids in the prevention and treatment of cardiovascular disease.
Growing evidence has suggested an important role of n-3 polyunsaturated fatty acids in reducing risk of cardiovascular disease in the general population and patients with preexisting heart disease. In particular, several long-term epidemiologic studies have found an inverse association between fish consumption and risk of coronary heart disease or stroke. Two secondary prevention trials have found that increasing fish consumption or fish oil supplementation significantly reduced coronary death among patients with existing myocardial infarction. In addition, epidemiologic and clinical studies have suggested that alpha-linolenic acid (ALA), a short-chain n3-3 fatty acid from plant sources, may have similar cardiac benefits as long-chain n-3 fatty acids from fish. Potential mechanisms through which n-3 polyunsaturated fatty acids protect against CVD include their antiarrhythmic and antithrombotic effects, and improving insulin sensitivity and endothelial function. (c) 2001 Prous Science. All rights reserved.


The selective biomarker IL-8 identifies IFTA after kidney transplantation in blood cells.
Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers in blood cells and serum may serve as diagnostic tools but studies with high patient numbers and differential groups are rare. We validated the potential value of several markers on mRNA level in blood cells and serum protein level in 166 samples from kidney transplanted patients under standard immunosuppressive therapy (steroids±mycophenolic acid±calcineurin inhibitor) with stable graft function, urinary tract infection (UTI), IFTA, antibody-mediated rejection (ABMR), and T-cell-mediated rejection (TCMR) applying RT-PCR and ELISA. The mRNA expression of RANTES, granulysin, granzyme-B, IP-10, Mic-A and Interferon-γ in blood cells did not distinguish specifically between the different pathologies. We furthermore discovered that the mRNA expression of the chemokine IL-8 is significantly lower in samples from IFTA patients than in samples from patients with stable graft function (p<0.001), ABMR (p<0.001), Borderline (BL) TCMR (p<0.001), tubulo-interstitial TCMR (p<0.001) and vascular TCMR (p<0.01), but not with UTI. Serum protein concentrations of granzyme-B, Interferon-γ and IL-8 did not differ between the patient groups, RANTES concentration was significantly different when comparing UTI and ABMR (p<0.01), whereas granulysin, Mic-A and IP-10 measurement differentiated ongoing rejection or IFTA processes from stable graft function but not from each other. The measurement of IL-8 mRNA in blood cells distinguishes clearly between IFTA and other complication after kidney transplantation and could easily be used as diagnostic tool in the clinic.


Ultraviolet light treatment of a patient with pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease). A case report.
The purpose of this case report is to detail the physical therapy of a patient with pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease), a condition usually not encountered by physical therapists. Prolonged exposure to ultraviolet light was the effective mode of treatment.


Immortalization of cells from brains derived from a strain (MSM/MSfB6C3F1) of wild mouse.
Escape from cellular aging is the rate-limiting step of multistep carcinogenesis. While normal human cells invariably undergo cellular aging and almost never spontaneously immortalize, cells derived from rodents such as mice are relatively easily immortalized. In this experiment, we studied the immortalization patterns of cells obtained from brain tissues of an inbred strain (MSM/MSfB6C3F1) derived from wild mice. We established 12 cell strains derived from 12 mouse brains in order to investigate whether these cells show cellular aging in the same fashion as human cells or whether these cells are immortalized as easily as rodent cells reported previously. As a result, all cell strains were immortalized up to about 200 days in culture. One strain immortalized very early, in the first 50 days, four strains immortalized in the last 200 days, and the other seven strains became immortal between 150 and 200 days in culture. All immortalized cell strains showed varying amounts of chromosome abnormalities, numerically and structurally, but no specific changes related to immortalization were detected. Before immortalization, three types of cells, glial-like, polygonal flat-thin, and fibroblast-like cells, were observed in culture, but after immortalization most of the cultures became fibroblastic. From these results, we concluded that fibroblast-like cells derived from brains of these mice immortalized in like fashion to fibroblasts of other inbred mice.


Comparison of multifactor scoring systems and single serum markers for the early prediction of the severity of acute pancreatitis.
The purpose of this study was to clarify whether the current scoring systems and single serum markers used in pancreatitis remain applicable for the early prediction of infected pancreatic necrosis (IPN) and the severity and mortality of acute pancreatitis (AP) in accordance with the revised Atlanta and determinant-based classifications. Demographic, clinical, and laboratory data from 708 consecutive patients with AP were prospectively collected between January 2011 and December 2012. The severity was classified using the revised Atlanta and determinant-based classification systems. The predictive accuracies for moderately severe AP (MSAP), severe AP (SAP), critically severe AP (CAP), IPN, and mortality were measured using area under the receiver operating characteristic curves. The receiver operating characteristic analysis showed that the multifactor scoring systems and single serum markers had a low predictive accuracy regarding moderately severe AP. The Acute Physiology and Chronic Health Evaluation (APACHE) II score had the highest accuracy in predicting SAP with area under the curve (AUC) values of 0.75 (95% CI = 0.71-0.79) and 0.77 (95% CI = 0.73-0.81) at 24 and 48 h after admission, respectively. Procalcitonin was the most accurate predictor for CAP and IPN, with respective AUCs of 0.86 (95% CI = 0.82-0.89) and 0.83 (95% CI = 0.78-0.87) at 48 h after admission. In predicting mortality, both the APACHE II score and blood urea nitrogen had the highest accuracy. The APACHE II score had the highest predictive accuracy for SAP and mortality as defined by the revised Atlanta classification, whereas procalcitonin was the most accurate predictor for CAP and IPN.


Multicellular Tumor Spheroids (MCTS) as a 3D In Vitro Evaluation Tool of Nanoparticles.
Multicellular tumor spheroid models (MCTS) are often coined as 3D in vitro models that can mimic the microenvironment of tissues. MCTS have gained increasing interest in the nano-biotechnology field as they can provide easily accessible information on the performance of nanoparticles without using animal models. Considering that many countries have put restrictions on animals testing, which will only tighten in the future as seen by the recent developments in the Netherlands, 3D models will become an even more valuable tool. Here, an overview on MCTS is provided, focusing on their use in cancer research as most nanoparticles are tested in MCTS for treatment of primary tumors. Thereafter, various types of nanoparticles-from self-assembled block copolymers to inorganic nanoparticles, are discussed. A range of physicochemical parameters including the size, shape, surface chemistry, ligands attachment, stability, and stiffness are found to influence nanoparticles in MCTS. Some of these studies are complemented by animal studies confirming that lessons from MCTS can in part predict the behaviour in vivo. In summary, MCTS are suitable models to gain additional information on nanoparticles. While not being able to replace in vivo studies, they can bridge the gap between traditional 2D in vitro studies and in vivo models.


Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia.
Dopaminergic dysregulation remains an empirical cornerstone for theories concerning the causation of schizophrenia. Evidence for a dopamine system dysfunction in schizophrenia includes the psychosis-inducing effects of dopaminergic agonists and the antipsychotic potency of dopaminergic antagonists. Here we use positron emission tomography (PET) to examine the regulatory role of dopamine on cortical function in normal subjects and unmedicated schizophrenic patients. Using a factorial experimental design, we compared the effect of dopaminergic manipulation with apomorphine on a neural response to a cognitive task. In the schizophrenic patients, relative to controls, an impaired cognitive activation of the anterior cingulate cortex was significantly modulated by a manipulation of dopaminergic neurotransmission. Thus, after apomorphine, the schizophrenic subjects displayed a significantly enhanced cognitive activation of the anterior cingulate cortex relative to the controls. These data provide in vivo evidence that an impaired cognitive-task-induced activation of the anterior cingulate cortex in schizophrenic patients can be significantly modulated by a dopaminergic manipulation.


Carotid stump syndrome: pathophysiology and endovascular treatment options.
Carotid stump syndrome is one of the recognised causes of recurrent ipsilateral cerebrovascular events after occlusion of the internal carotid artery. It is believed that microemboli arising from the stump of the occluded internal carotid artery or the ipsilateral external carotid artery can pass into the middle cerebral artery circulation as a result of patent external carotid-internal carotid anastomotic channels. Different pathophysiologic causes of this syndrome and endovascular options for treatment are discussed.


Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP levels in patients with heart failure.
Anaemia may affect B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels, but this has not been well described in heart failure (HF) patients without the exclusion of patients with renal dysfunction. To study the influence of both anaemia and renal function on BNP and NT-proBNP levels in a large group of hospitalised HF patients. We studied 541 patients hospitalised for HF (mean age 71+/-11 years, 62% male, and left ventricular ejection fraction 0.33+/-0.14). Of these patients, 30% (n=159) were anaemic (women: Hb<7.5 mmol/l, men: Hb<8.1 mmol/l). Of the 159 anaemic patients, 73% had renal dysfunction (eGFR<60 ml/min/1.73 m2) and of the non-anaemic patients, 57% had renal dysfunction. BNP and NT-proBNP levels were measured in all patients before discharge. In multivariable analyses both plasma haemoglobin and eGFR were independently related to the levels of BNP and NT-proBNP (standardised beta's of -0.16, -0.14 [BNP] and -0.19, -0.26 [NT-proBNP] respectively, P-values<0.01). Anaemia and renal dysfunction are related to increased BNP and NT-proBNP levels, independent of the severity of HF. These results indicate that both anaemia and renal dysfunction should be taken into consideration during the interpretation of BNP and NT-proBNP levels in HF patients.


Chemoselective hydrogenation catalysts: Pt on mesostructured CeO2 nanoparticles embedded within ultrathin layers of SiO2 binder.
Pt on mesostructured CeO(2) nanoparticles embedded within ultrathin layers of highly structured SiO(2) binder shows highest activity reported with 80% selectivity for the chemoselective hydrogenation of crotonaldehyde. Characterization by transmission electron microscopy (TEM), CO adsorption, and X-ray photoelectron spectroscopy (XPS) show the presence of small Pt metal particles, preferentially located on CeO(2) (70%) together with the formation of Pt-CeO(2-x) sites at the interface between Pt and CeO(2) (4 nm) nanoparticles. These sites are able to polarize the carbonyl group and facilitate the selective hydrogenation of this with respect to the double bond.


Pluripotency factor Nanog is tumorigenic by deregulating DNA damage response in somatic cells.
The pluripotency gene Nanog is not expressed in normal adult tissues but is overexpressed in some human cancers. However, the tumorigenic roles of Nanog remain unclear. The ectopic expression of Nanog is not sufficient to induce spontaneous tumors in mice but can promote metastasis of established tumors by activating the expression of metastatic genes. The expression of Nanog in mouse skin activates tumor suppressor p53, leading to the differentiation of epidermal stem cells. In the absence of p53, Nanog induces spontaneous squamous cell carcinoma, identifying a novel role of Nanog in tumorigenesis. Therefore, the induction of p53 and differentiation in Nanog-expressing skin suppresses the tumorigenic activities of Nanog, which include the induction of DNA double-stranded break damage. Notably, Nanog interacts with the KRAB-associated protein 1 (KAP1) and inhibits its sumoylation activity, impairing KAP1-mediated chromatin remodeling, which is important for efficiently activating DNA damage response. In summary, Nanog is an oncogene with multiple roles in promoting tumorigenesis and metastasis.


The human retinitis pigmentosa GTPase regulator gene variant database.
X-linked retinitis pigmentosa (XLRP) is a genetically heterogeneous retinal degeneration. The major subtype of XLRP is RP3, which accounts for 6 to 20% of all RP cases. Mutations in the RP3 gene, called RP GTPase regulator (RPGR), cause a number of different retinopathies. An RPGR database has been created using the Leiden Open Source Variation Database (LOVD) software system and has comprehensive search and analysis tools. This database is a central resource of RPGR sequence variant data for investigators and will facilitate the interpretation of new mutations, variants, and polymorphisms when these are identified in patients. The database is available on the Internet (http://rpgr.hgu.mrc.ac.uk).


A re-examination of seasonal variation in suicides in Australia and New Zealand.
To examine the seasonality of suicides in Australia and New Zealand during the period 1981 to 1993. A chi-square test and a harmonic analysis were used to detect the seasonality of the suicide data. The reduced amplitude and a smaller proportion of variance accounted for by seasonality suggested the seasonal effect on suicide is greatly diminished. The absence of biseasonal distribution of female suicides was also consistently found in the two countries. The finding was contrary to the reported results in seventies in many Western countries. The change in living condition, roles of males and females and communication pattern resulted in the reduction of climatic and environment effect in the seasonality of suicides were suggested. The results would be better if a longer series of suicide date were available.


A case of Proteus syndrome with severe spinal canal stenosis, scoliosis, and thoracic deformity associated with tethered cord.
Proteus syndrome is a rare, sporadic, hamartomatous disorder manifesting with multifocal overgrowth of tissue. The features seem to develop most often during childhood. Vertebral overgrowth with severe spinal canal stenosis is unusual, although scoliosis with abnormal vertebral bodies is one of the typical features of Proteus syndrome. We report a case of Proteus syndrome with severe spinal canal stenosis, scoliosis, cervical kyphosis, and thoracic deformity with airway obstruction because of asymmetrical overgrowth of vertebrae and ribs associated with a tethered cord, lipomas, strawberry hemangioma, flat nasal bridge, and bilateral hypoplasty of the first metatarsal bones with hyperplasty of soft tissue.


Confirmation of anatoxin-a(s), in the cyanobacterium Anabaena lemmermannii, as the cause of bird kills in Danish lakes.
Cyanobacterial blooms were implicated in bird kills at lakes in Denmark in July 1993 and June-July 1994. These blooms were dominated by Anabaena lemmermannii and were shown to contain a neurotoxin with anticholinesterase activity. In this study, the toxin was isolated by mouse lethality guided column chromatographies from the field sample collected at Lake Knud sø in 1993. Various spectroscopic data indicated that the toxin was anatoxin-a(s), an irreversible anticholinesterase, first reported in Anabaena flos-aquae. Chemical detection of the same toxin in cultured A. lemmermannii also confirmed this species as the cause of the deaths of the wild birds.


Exertional heat stroke in the marathon.
Exertional heat stroke (EHS) during or following a marathon race can be fatal if not promptly recognised and treated. EHS is a true medical emergency and immediate cooling markedly improves the outcomes. It is critical to recognise EHS and stop the cell damage before the cascade of heat-induced tissue changes becomes irreversible. The goal is to keep the area that is >40.5 degrees C under the body temperature versus time curve at <60 degree-minutes. Measuring the rectal temperature is the only precise estimate of core temperature available for field use. The field treatment of EHS is immediate, total-body cooling with ice-water tub immersion or rapidly rotating ice-water towels to the trunk, extremities and head, combined with ice packing of the neck, axillae and groin. Any combination of delayed recognition or cooling increases the potential for morbidity and mortality. For optimal outcomes, it is best to treat immediately with on-site whole-body cooling if cardiorespiratory status is 'stable' and then to transfer the runner for additional evaluation and care.


Direct observation of quantum tunnelling charge transfers between molecules and semiconductors for SERS.
We used high-quality ZnO nanostructures/graphene substrates for understanding the mechanisms of charge transfer (CT) that take place under nonplasmonic conditions. As the optimal conditions for CT processes are found, we studied the range of CT normal to the ZnO surface that is coated with nanoscale HfO2 layers with different thicknesses. We could observe that CT decays over a few nanometers. In addition, we also observed a unique oscillation of the SERS intensity in the atomically thin oxide layers, which reflects the quantum tunneling effects of CT electrons across the oxide layers. To the best of our knowledge, this is the first direct observation of SERS-active charge transport and measurement of a CT span with atomic-scale accuracy.


[Investigation of lung cancer patients with cardiovascular disease].
According to the aging in Japan, surgery of lung cancer with cardiovascular disease is increasing. Among them, the merger of the heart and large blood vessel disease would be expected to be directly linked to the perioperative management. We conducted a retrospective analysis of 1,005 patients who had undergone surgical resection of primary lung adenocarcinoma between January 1997 and June 2014 at Hokkaido University Hospital. Among them, 81 patients had more than one cardiovascular disease. The median age was 71 years old. Men are 62 cases(76%). 64 cases (79%)had smoking history. Ischemic heart disease( IHD) was 29 cases(33%), followed by atrial fibrillation(Af), arrhythmia other than Af, valve disease and macrovascular disease. Anticoagulant or antiplatelet therapy were preoperatively done in 41% of IHD cases, 39% of Af cases. Thirty four% of IHD, 50% of vascular disease received the treatment other than medication. Video-assisted thoracic surgery was performed in 67 cases(83%). Lobectomy, sublobectomy were performed for 59 cases(73%), 19 cases(23%), respectively. Postoperative complications were occurred in 32 cases(40%). Two patients(2.5%)died in hospital without discharge. Univariate analysis revealed tumor size, pStage, lymph node dissection, operation time or blood loss were correlated with postoperative complication. For the patients with cardiovascular disease, careful evaluation of surgical indication, perioperative management is required.


Appropriate indications for positron emission tomography/computed tomography: College of Nuclear Physicians of the Colleges of Medicine of South Africa.
Individualised patient treatment approaches demand precise determination of initial disease extent combined with early, accurate assessment of response to treatment, which is made possible by positron emission tomography/computed tomography (PET/CT). PET is a non-invasive tool that provides tomographic images and quantitative parameters of perfusion, cell viability, and proliferation and/or metabolic activity of tissues. Fusion of the functional information with the morphological detail provided by CT as PET/CT can provide clinicians with a sensitive and accurate one-step whole-body diagnostic and prognostic tool, which directs and changes patient management. Three large-scale national studies published by the National Oncologic PET Registry in the USA have shown that imaging with PET changes the intended patient management strategy in 36.5% to 49% of cases, with consistent results across all cancer types. The proven clinical effectiveness and growing importance of PET/CT have prompted the College of Nuclear Physicians of South Africa, in collaboration with university hospitals, to develop a list of recommendations on the appropriate use of fluorine-18-fluorodeoxyglucose (18F-FDG) and non-18F-FDG PET/CT in oncology, cardiology, neurology and infection/inflammation. It is expected that other clinical situations will be added to these recommendations, provided that they are based upon solid clinical evidence. These recommendations are intended to offer advice regarding contemporary applications of PET/CT, as well as indicating novel developments and potential future indications. The CNP believes that these recommendations will serve an important and relevant role in advising referring physicians on the appropriate use of 18F-FDG and non-18F-FDG PET/CT. More promising clinical applications will be possible in the future, as newer PET tracers become more readily available.


Evaluating the effect of childbirth education class: a mixed-method study.
To examine Chinese women's satisfaction with and the perceived effect of childbirth education class on their labour experience. Attending childbirth education classes is a common activity for pregnant women. Nonetheless, evidence reveals that evaluation of the effects of childbirth education classes is inconsistent. Moreover, women's perceived effect of these classes has not been systematically examined. This two-phase study adopted a mixed-method design with Donadedian's model as the theoretical framework. In Phase One, a random sample of 40 Chinese women was invited to complete a questionnaire after attending a childbirth education class. The questionnaire was focused on their satisfaction with specific aspects of the class. Descriptive statistics were performed to summarize participants' response. In Phase Two, six of the original 40 women were purposely selected for a semi-structured interview pertaining to the perceived effect of the childbirth education class on their labour experience. Thematic analysis was conducted on the interview data. The participants expressed overall satisfaction with the class. The area that satisfied them the most was the performance of the midwife. The areas that satisfied them the least were the date, length, size and time of the class. Three themes emerged from the interview data, namely, 'learning about labour', 'contributing to a smooth labour process' and 'coping with uncertainty and handling anxiety. This study supports using a mixed-method approach to evaluate client education activity, and highlights the importance of cultivating positive coping measures among the Chinese women after attending childbirth education class when facing childbirth-related anxiety.


Comparative proteomic analysis of seedling leaves of different salt tolerant soybean genotypes.
Salinity is one of the major environmental constraints limiting yield of crop plants in many semi-arid and arid regions around the world. To understand responses in soybean seedling to salt stress at proteomic level, the extracted proteins from seedling leaves of salt-sensitive genotype Jackson and salt-tolerant genotype Lee 68 under 150 mM NaCl stress for 1, 12, 72 and 144 h, respectively, were analyzed by 2-DE. Approximately 800 protein spots were detected on 2-DE gels. Among them, 91 were found to be differently expressed, with 78 being successfully identified by MALDI-TOF-TOF. The identified proteins were involved in 14 metabolic pathways and cellular processes. Based on most of the 78 salt-responsive proteins, a salt stress-responsive protein network was proposed. This network consisted of several functional components, including balancing between ROS production and scavenging, accelerated proteolysis and reduced biosynthesis of proteins, impaired photosynthesis, abundant energy supply and enhanced biosynthesis of ethylene. Salt-tolerant genotype Lee 68 possessed the ability of higher ROS scavenging, more abundant energy supply and ethylene production, and stronger photosynthesis than salt-sensitive genotype Jackson under salt stress, which may be the major reasons why it is more salt-tolerant than Jackson.


Positive interactions between human interferon and cyclophosphamide or adriamycin in a human tumor model system.
Human lymphoblastoid interferon strongly increased the anti-tumor activity of suboptimal doses of two commonly used anti-cancer drugs, cyclophosphamide and Adriamycin, on a human breast tumor xenograft growing in nude mice. A combination of human lymphoblastoid interferon with either of these agents caused regression and in some cases total disappearance of tumors at doses of drug and interferon that, used singly, were capable only of inhibiting tumor growth. The combined therapy also resulted in a greatly increased survival. Studies with interferon and cyclophosphamide indicated that the antitumor activity was greatest when the two agents were administered simultaneously rather than sequentially.


Dysentery in calves caused by an atypical strain of Escherichia coli (S102-9).
Dysentery lasting 4-8 days was produced in five 4-day-old colostrum-fed calves, after inoculation with an atypical strain of Escherichia coli S102-9; peak excretion of S102-9 occurred during the period of dysentery. Two calves were killed when clinical signs were most severe and bacteria were seen attached to the surfaces of enterocytes in the large intestine; microscopic lesions were seen in these areas. The lesions were identical to those previously reported in a natural outbreak of dysentery in calves, from which E. coli S102-9 was isolated, and to those seen in gnotobiotic calves experimentally infected with S102-9. Reinfection of the three surviving calves 16-20 days later with S102-9 and primary infection of two calves aged 24 and 51 days did not cause dysentery. Four of 659 coliforms isolated from field outbreaks of calf diarrhoea resembled the atypical strain S102-9. These four isolates and S102-9 did not produce heat-stable enterotoxin, but all produced a toxin cytopathic for Vero and HeLa cells. Two of the four isolates were inoculated alone into 4-day-old gnotobiotic calves deprived of colostrum; neither calf developed dysentery but microscopic lesions identical to those produced by S102-9 were detected in the large intestines of both animals.


Anti-HTLV-III testing of blood donors: reproducibility and confirmability of commercial test kits.
Since 2% of the cases of Acquired Immune Deficiency Syndrome (AIDS) have been attributed to transfusions of blood and blood products, licensed tests to detect antibody to the human T-lymphotropic virus type III (anti-HTLV-III) have been put into practice to reduce the risk of transfusion associated AIDS. Two commercial ELISA kits (Abbott and ENI) were used to test for anti-HTLV-III in 100 coded samples from individuals with AIDS, at high risk for AIDS, or with low risk for AIDS and in 1280 unlinked blood donor serums. From the 100 coded samples, both Abbott and ENI tests identified 51 of 52 coded samples with anti-HTLV-III which were confirmable with Western blot analysis. Initial testing of the donor serums by Abbott's test revealed 20 reactives, of which 5 were repeatably reactive; initial testing by ENI's test revealed 25 reactives, of which 14 were repeatably reactive. However, only 3 donor serums were repeatably reactive by both test kits, out of 17 repeatable reactive by either, and no ELISA positive samples were confirmed by Western blot or IFA. Before a blood donor is notified of "anti-HTLV-III reactivity", tests demonstrating this should be both reproducible and confirmable by at least one additional test.


Is sacral instrumentation mandatory to address pelvic obliquity in neuromuscular thoracolumbar scoliosis due to myelomeningocele?
Prospective study. To evaluate the functional outcome of two-stage anterior and posterior instrumented fusion without fixation to the sacrum on 11 patients with neuromuscular scoliosis from thoracolumbar myelomeningocele. To our knowledge, there are no published results of combined anterior and posterior correction and fusion without inclusion of the sacrum in neuromuscular scoliosis from thoracolumbar myelomeningocele. In this article we present our experience and critically evaluate the functional outcome on 11 patients with neuromuscular scoliosis. From July 1, 1992 through June 30, 1995, 11 consecutive patients with severe thoracolumbar scoliosis were admitted at our hospital. The mean age at operation was 12 years 9 months (range 9 years 9 months to 14 years 6 months). All patients underwent a two-stage anterior and posterior spinal reconstruction. The patients were evaluated before surgery and after surgery. All patients were observed for a mean of 4 years 11 months (range 42-88 months) from the time of second stage procedure. Before treatment the mean scoliosis was 81 degrees (range 55-110 degrees ); this was reduced to a mean of 31 degrees (range 8-70 degrees ), and at the final follow-up the correction had deteriorated slightly to a mean of 35 degrees (range 12-80 degrees ). No patient had increased neurologic deficit or showed other major complication. Pelvic obliquity in thoracolumbar neuromuscular scoliosis from lumbosacral myelomeningocele spontaneously corrected when the scoliotic deformity is adequately addressed with instrumented fusion without inclusion of the sacrum. The correction obtained remained stable at follow-up. In the absence of a control group we believe that sparing lumbar segments from primary fusion offers these patients a better freedom of mobility.


[A case of primary pulmonary malignant lymphoma associated with autoimmune hemolytic anemia].
A 74-year-old man who had been treated for autoimmune hemolytic anemia was admitted to our hospital for dry cough and shortness of breath. Chest X-ray revealed multiple round opacities. The pathological examination of a percutaneous biopsy specimen revealed B-cell malignant lymphoma of the diffuse large-cell type. Gallium scintigraphy showed positive accumulation only in the lungs, and thus a diagnosis of primary pulmonary lymphoma was made. He received several courses of R-CHOP therapy and achieved partial remission. Primary pulmonary malignant lymphoma associated with autoimmune hemolytic anemia is extremely rare. Although the underlying mechanism remains to be clarified, it is likely that Epskin-Barr virus infection leads to the development of malignant lymphomas in some cases.


Activated Fps/Fes tyrosine kinase regulates erythroid differentiation and survival.
A substantial body of evidence implicates the cytoplasmic protein tyrosine kinase Fps/Fes in regulation of myeloid differentiation and survival. In this study we wished to determine if Fps/Fes also plays a role in the regulation of erythropoiesis. Mice tissue-specifically expressing a "gain-of-function" mutant fps/fes transgene (fps(MF)) encoding an activated variant of Fps/Fes (MFps), were used to explore the in vivo biological role of Fps/Fes. Erythropoiesis in these mice was assessed by hematological analysis, lineage marker analysis, bone-marrow colony assays, and biochemical approaches. fps(MF) mice displayed reductions in peripheral red cell counts. However, there was an accumulation of immature erythroid precursors, which displayed increased survival. Fps/Fes and the related Fer kinase were both detected in early erythroid progenitors/blasts and in mature red cells. Fps/Fes was also activated in response to erythropoietin (EPO) and stem cell factor (SCF), two critical factors in erythroid development. In addition, increased Stat5A/B activation and reduced Erk1/2 phosphorylation was observed in fps(MF) primary erythroid cells in response to EPO or SCF, respectively. These data support a role for Fps/Fes in regulating the survival and differentiation of erythroid cells through modulation of Stat5A/B and Erk kinase pathways induced by EPO and SCF. The increased numbers and survival of erythroid progenitors from fps(MF) mice, and their differential responsiveness to SCF and EPO, implicates Fps/Fes in the commitment of multilineage progenitors to the erythroid lineage. The anemic phenotype in fps(MF) mice suggests that downregulation of Fps/Fes activity might be required for terminal erythroid differentiation.


Subtle genotypic changes can be observed soon after diagnosis in Mycobacterium tuberculosis infection.
Clonal variants of Mycobacterium tuberculosis (MTB) coexist in specific patients, although the dynamics of their emergence is unknown. We used MIRU-VNTR to detect microevolution leading to variants of MTB in 3 out of 19 patients (15%) soon after diagnosis (61-85days). Most harbored SNPs and for some of them a potential functional role was suggested. Microevolution in tuberculosis seems to occur sooner and more often than expected and could affect tracking of transmission.


Indications and outcome of colonoscopy in the middle of Nile delta of Egypt.
In Egypt, few data are available on the outcome of colonoscopy. Epidemiologic studies have shown that inflammatory bowel disease (IBD) tends to increase. Endoscopists have reported an increasing incidence of IBD and colorectal cancer (CRC). This may be explained by an increasing index of suspicion and the availability of endoscopy. Population-based studies are lacking. The aim of our study was to retrospectively evaluate the patient characteristics and final diagnosis in patients subjected to colonoscopy in Tanta University Hospital and affiliated hospitals at the middle of Nile delta of Egypt, which is one of the most densely populated regions in the country. This study was done at the endoscopy units of Tanta University Hospital and affiliated hospitals (all units of colonoscopy at Gharbia governorate) from June 2008 to June 2009. A total of 864 patients presented with different indications for colonoscopy. All findings were recorded, analyzed, and discussed. Colonoscopy revealed a diagnosis of ulcerative colitis (UC) in 22%, hemorrhoids in 18%, CRC in 15%, benign colorectal polyps in 9%, Crohn's disease (CD) in 3%, diverticulosis in 2%, and anal fissures in 2% of patients. No organic colonic disease was found in 28% of patients. Complications occurred in less than 1% of the cases. In Egyptian patients subjected to colonoscopy, the most frequent diagnoses were UC, followed by hemorrhoids, CRC, benign polyps, and CD. This may represent an increasing incidence of UC and CRC. Colonoscopy was safe and few complications were recorded. Prospective population-based studies are needed in order to measure the incidence, prevalence, and risk factors of various diseases of the colon in Egypt.


Fouling of reverse osmosis and nanofiltration membranes by dairy industry effluents.
Fouling experiments of nanofiltration (NF) and reverse osmosis (RO) are reported for treatment of the effluent of chemical-biological treatment plant and the original effluent of dairy industry respectively. In the experiments, a thin film composite type of spiral wound was used and fitted with flowmeters and pressure sensors. The feed water was stored into a feed tank and passed a fine filter and was pumped to membrane. Brine and permeate were recirculated back to the feed tank. Membrane fouling was investigated with 16 and 30% water recovery of a single membrane at different pressures and flowrates for RO and NF membranes respectively. Fouling is evaluated with a relationship between relative flux (J/Jo) which is the ratio of the flux at any time during the fouling test to the initial flux and relative resistance (Rf/Rm) which is the ratio of fouling (cake) layer resistance to clean membrane resistance. Turbidity, conductivity, chemical oxygen demand (COD), total suspended solids (TSS) and total hardness were measured in the feed and permeate side of each membrane. The effluent total hardness concentrations of chemical-biological treatment plant were found greater than the influents. The results are presented in terms of the relative flux as a function of time related to hydrodynamic conditions and pollution characteristics of wastewater. The permeate water flux of RO membrane decreases more rapidly than NF membrane, the relative flux decreases with increasing the fouling layer resistance, Rf onto membrane surface. 50% the drop of permeate flux was observed for RO and NF membranes after 50 h and 80 h of operation, respectively. The fouling rate increases with an increase in the concentration of the wastewater constituents in the dairy industry. The relative flux decreased 10 and 20% with increasing chemical oxygen demand (COD) from 5,000 mgl-1 to 10,000 mgl-1 and from 45 mgl-1 to 450 mgl-1 for RO and NF membranes, respectively after 45 h of time. Fouling of membranes resulted in 100% increase of specific energy consumption as the relative permeate fluxes of NF and RO membranes decreased 30 and 40% respectively. The average of specific energy consumption was obtained at 6 and 10 kWhm-3; consequently, operational costs were estimated at U.S. $0.45 m-3 and U.S. $0.75 m-3 for NF and RO units respectively. Also, operational cost for chemical-biological treatment was found at U.S. $0.30 m-3.


The mechanism of action of phenformin in starved rats.
The ability of phenformin to lower the blood glucose concentration after an intraperitoneal glucose load, with a concomitant increase in blood lactate concentration, indicated that the drug was increasing the rate of anaerobic glycolysis. The results of experiments in which glucose and gluconeogenic precursors were given to starved rats were explained by a hypothesis for the mechanism of action of phenformin involving inhibition of certain NAD+-dependent dehydrogenases. Substrates with NAD+-linked oxidations could be discriminated from those, like succinate, with FAD-linked oxidations, and succinate may be of use in the treatment of clinical lacticacidosis caused by biguanide drugs.


Respiratory circuits: development, function and models.
Breathing is a rhythmic motor behavior generated and controlled by hindbrain neuronal networks. Respiratory motor output arises from two distinct, but functionally interacting, rhythmogenic networks: the pre-Bötzinger complex (preBötC) and the retrotrapezoïd nucleus/parafacial respiratory group (RTN/pFRG). This review outlines recent advances in delineating the genetic specification of the neuronal constituents of these two rhythmogenic networks, their respective roles in respiratory function and how they interact to constitute a functional respiratory circuit ensemble. The often lethal consequences of disruption to these networks found in naturally occurring developmental disorders, transgenic animals, and highly specific lesion studies are described. In addition, we discuss how recent computational models enhance our understanding of how respiratory networks generate and regulate respiratory behavior.


Solution of the Hodgkin-Huxley and cable equations on an array processor.
This paper presents a method for the solution of equations for membrane ionic currents and the cable equation which describes the interaction of various segments in a compartmentalized model of the neuron. The method embodies some innovations which would speed calculation of propagating action potentials in any computing environment, but were specifically designed to permit the use of a relatively inexpensive array processor. The array processor produces an improvement in speed of calculation which permits exploration of a wider range of neuronal phenomena than has been previously feasible.


Laryngeal cleft type I: a novel method of repair using Bioplastique.
The authors report a novel treatment of a case of type I laryngeal cleft diagnosed in an adult. They describe a technique of endoscopic obliteration of the posterior commissure defect. Initially, a test implant of starch and adrenaline was used, followed by permanent staged injections of Bioplastique to the posterior commissure. This rare congenital anomaly usually presents in childhood but late presentation should be considered when adults present with lifelong dysphonia especially when associated with gastro-oesophageal reflux disease.


Declining prevalence of antibodies to hepatitis A virus infection in Iceland.
The prevalence of antibodies to hepatitis A virus (anti-HAV) was investigated in 445 outpatients in Iceland in 1987. No difference in anti-HAV prevalence according to sex or residence was found. The prevalence rates were low in persons less than 50 years with a sharp increase in persons greater than or equal to 50 years. The prevalence of anti-HAV was now significantly lower in the age groups of 40-49 years and 50-59 years than in 1979 indicating a cohort effect. These findings correspond to a marked decrease in notified cases of hepatitis (epidemic jaundice) after 1950 in Iceland.


Biochemical characteristics and water exchange in the surface layer of human joint cartilage.
We compared the contents of collagen, glycosaminoglycans, and various forms of water in the surface layer and whole tissue of joint cartilages of different localization. It was found that the surface layer is characterized by reduced content of glycosaminoglycans compared to the whole tissue and higher water-holding capacity due high content of bound water.


Status report of the heavy ions source research and development for Spiral2.
The physics background requiring a very intense multicharged heavy ion source for Spiral2 is explained. The new Spiral2 low energy beam line dedicated to the heavy ions production and equipped with PHOENIX V2 ECRIS is presented. A status of the A-PHOENIX commissioning at 18 GHz is summarized. A new hybrid ECRIS concept with a cryogenic permanent magnet hexapole is proposed as an improvement of A-PHOENIX technology.


[Smooth muscle tumor of uncertain malignant potential (STUMP)--clinico-pathomorphological analysis of the cases and literature review].
This retrospective study was designed to evaluate the clinical and pathological features and outcomes of patients diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP). Ten patients diagnosed with uterine STUMP and seen between 2008 and 2011 at the Memorial Cancer Center--Institute of Oncology in Warsaw were identified using the institution databases. Variables of interest included histopathological details, age at diagnosis, types of treatment and recurrence rate. The mean age at diagnosis was 41 years (range 25-56 years). The mean follow-up time was 16 months (range 4-29 months). Diameter of the tumors ranged from 3 to 29 cm. Uterine bleeding was the second most frequent symptom observed in this cohort In three cases conservative procedure was performed, whereas in other patients hysterectomy was performed. No recurrence was observed during the follow-up period. In all tumors mitoses were less than 10 per 10/hpf, atypia of middle or severe type, and in 3 cases necrosis was observed. In half of the tumors expression of TP53 was found, and value of MIB 1 was estimated at 2-35%. STUMP should be diagnosed by experienced pathologists due to the fact that they are often misdiagnosed as leiomyosarcomas. Clinical behavior of these tumors allows to consider a conservative management in patients wishing to preserve fertility


Mitochondrial and nuclear mutagenicity of ellipticine and derivatives in the yeast Saccharomyces cerevisiae.
Haploid strains of the yeast Saccharomyces cerevisiae were tested for their sensitivity to ellipticine and nine derivatives; some of them exhibiting antitumor properties. Different mutagenic properties of ellipticines are described. Charged ellipticines, which were ineffective in Ames' bacterial assay, were found to be potent inducers of the mitochondrial p- mutation: induction proceeded even in the absence of growth. Uncharged ellipticines increased mitochondrial antibiotic resistance mutations, whereas charged derivatives decreased them. Ellipticine derivatives enhanced, reduced, or did not change the reversion frequencies of nuclear auxotrophic markers. The result depended on the strain being tested: no structure-effect relationship existed. As some ellipticine derivatives were mutagenic in Saccharomyces cerevisiae despite being ineffective in Ames' assay, multiple tests should be used to check that chemotherapeutic drugs are devoid of mutagenic properties.


Evaluation of the effect of storage condition on cell extraction and flow cytometric analysis from intestinal biopsies.
Flow cytometric (FC) analysis of intestinal tissue biopsies requires prompt cell isolation and processing to prevent cell death and generate valid data. We examined the effect of storage conditions prior to cell isolation and FC on viable cell yield and the proportions of immune cell phenotypes from intestinal biopsies. Biopsies (N = 224) from inflamed or non-inflamed ileal and/or colonic tissue from three patients with Crohn's disease were processed and analyzed immediately in duplicate, or stored under different conditions. Cells were isolated and stained for specific markers, followed by FC. Decreased mean live CD45+ cell counts were observed after storage of biopsies at -80 °C dimethyl sulfoxide (DMSO)/citrate buffer compared with immediate processing (1794.3 vs. 19,672.7; p = 0.006]). A non-significant decrease in CD45+ live cell count occurred after storage at -20 °C in DMSO/citrate buffer and cell yield was adequate for subsequent analysis. CD3+ cell proportions were significantly lower after storage at 4 °C in complete medium for 48 h compared with immediate analysis. Mean CD14+ cell proportions were significantly higher after storage of biopsies at -80 °C in DMSO/citrate buffer compared with immediate analysis (2.61% vs. 1.31%, p = 0.007). CD4+, CD8+ and CD4+/CD8+ cell proportions were unaffected by storage condition. Storage of intestinal tissue biopsies at -20 °C in DMSO/citrate buffer for up to 48 h resulted in sufficient viable cell yield for FC analysis without affecting subsequent marker-positive cell proportions. These findings support the potential shipping and storage of intestinal biopsies for centralized FC analysis in multicenter clinical trials.


Performance-Based Adaptive Fuzzy Tracking Control for Networked Industrial Processes.
In this paper, the performance-based control design problem for double-layer networked industrial processes is investigated. At the device layer, the prescribed performance functions are first given to describe the output tracking performance, and then by using backstepping technique, new adaptive fuzzy controllers are designed to guarantee the tracking performance under the effects of input dead-zone and the constraint of prescribed tracking performance functions. At operation layer, by considering the stochastic disturbance, actual index value, target index value, and index prediction simultaneously, an adaptive inverse optimal controller in discrete-time form is designed to optimize the overall performance and stabilize the overall nonlinear system. Finally, a simulation example of continuous stirred tank reactor system is presented to show the effectiveness of the proposed control method.


'The buck stops here': accepting responsibility for learning and actions after graduation from a problem-based learning nursing education curriculum.
Despite the increased attention that problem-based learning has received as an appropriate pedagogical technique for educating adults for professional practice, reports that evaluate the process are rare and usually relate to professions other than nursing. A study was undertaken in order to discover the graduates' own perceptions of a problem-based learning programme and its effectiveness in preparing them for the reality of their chosen profession. Twelve practising graduate nurses who had completed the programme were interviewed according to the ethnographic method. Three categories were identified from the data: 'and all of a sudden...', which describes the transition from PBL student to staff nurse; 'not an unthinking assistant', where the characteristics that the PBL graduates believe make them different from traditionally trained nurses are described; and 'the buck stops here', which describes the sense of personal responsibility that the graduates experience in terms of their learning and actions.


[Cellular transplants for Parkinson's disease].
In rats with a lesion of the dopaminergic nigrostriatal pathway induced by 6-hydroxydopamine (6-OHDA), the histologic and functional viability of the striatal implant of fetal mesencephalic substantia nigra has been demonstrated. In the same model, the implant of adrenal medulla is also effective but less lasting. In monkeys with parkinsonism induced by MPTP there are suggestions of effectiveness of the fetal mesencephalic implant and also of other tissues such as placenta and sympathetic ganglion or sural nerve. Now the possibility of a better functional recovery by acting on the neuronal growth factors is being evaluated. In patients with Parkinson's disease, the accumulated experience indicates that 32% are improved with adrenal medulla implant, but the best candidates are those who also benefit from the available drug therapy without the risks of surgery. The implant of fetal tissue has been carried out in about 90 patients, with very variable results. In the most thoroughly investigated patients the improvement has been moderate. The future research points to the identification of the factors that control and regulate striatal reinnervation and the use of genetically determined cells. That would permit a more precise reposition of the biochemical deficiency in Parkinson's disease, without the ethical and practical problems derived from the use of fetal tissue.


[On the problem of venous strokes].
Two cases of venous strokes diagnosed on autopsy of fixed brain are described, one in a 54-years-old female with diabetes and hypertension, and another in a 78-years-old female. In both cases the course of the disease was very dramatic and in both thrombosis of the vena cerebri magna was found.


Sonography of Wrist Ganglion Cysts: Which Location Is Most Common?
The literature states that wrist ganglion cysts are most commonly dorsal; however, our experience suggests a volar location is more common. The purpose of this study was to identify the locations of ganglion cysts of the wrist as imaged with sonography. After Institutional Review Board approval with informed consent waived, retrospective review of wrist sonography reports from January to April 2016 was completed. Only patients who had a comprehensive evaluation that included the dorsal and volar wrist were included. Ultrasound images were reviewed to characterize wrist ganglion cysts. The study group consisted of 98 subjects (78% female, 22% male) (median age, 51 years; range 13-79) with 124 wrist ganglion cysts, where 69% (86 of 124) were volar and 31% (38 of 124) were dorsal. Ganglion cysts were located between the radial artery and flexor carpi radialis in 63% (78 of 124), followed by a dorsal location superficial to the scapholunate ligament in 20% (25 of 124), other dorsal locations in 11% (13 of 124), and other volar locations in 6% (8 of 124). With dorsal ganglion cysts, the scapholunate ligament when imaged appeared normal in 91% (20 of 22). Ganglion cysts were multilocular/multilobular in all subjects. The most common location for wrist ganglion cysts is in the volar wrist, particularly between the radial artery and flexor carpi radialis tendon, appearing multilocular or multilobular with a mean largest dimension of 1.0 cm. Given the propensity of ganglion cysts to occur at this site, attention to this area when imaging the wrist with sonography or magnetic resonance imaging should be considered.


Categorizing natural color distributions.
The natural objects that we are surrounded with virtually always contain many different shades of color, yet the visual system usually categorizes them into a single color category. We examined various image statistics and their role in categorizing the color of leaves. Our subjects categorized photographs of autumn leaves and versions that were manipulated, including: randomly repositioned pixels, leaves uniformly colored with their mean color, leaves that were made by reflecting the original leaves' chromaticity distribution about their mean ("flipped leaves"), and simple patches colored with the mean colors of the original leaves. We trained a linear classifier with a set of image statistics in order to predict the category that each object was assigned to. Our results show that the mean hue of an object is highly predictive of the natural object's color category (>90% accuracy) and observers' choices are consistent with their use of unique yellow as a decision boundary for classification. The flipped leaves produced consistent changes in color categorization that are possibly explained by an interaction between the color distributions and the texture of the leaves.


Brain damage following severe acute normovolemic hemodilution in combination with controlled hypotension in rats.
The reduced oxygen content and perfusion pressure during acute normovolemic hemodilution (ANH) and controlled hypotension (CH) raise concerns about hypoperfusion and ischemic injury to the brain. In this study on rats, we examined the brain damage following four different degrees of ANH combined with CH. Forty rats were randomly assigned to receive a sham operation or CH and ANH [with a hematocrit (Hct) of 30, 25, 20 or 15%]. ANH was performed after baseline physiological parameters had been monitored for 20 min; 30 min later, CH was induced using sodium nitroprusside, and the mean arterial blood pressure was maintained at 50-60 mmHg for 1 h. Rats were killed 3.5 h after hemodilution. Ultrastructural alterations in the CA1 region of the rat hippocampus were observed, and serum concentrations of S100B and neuron-specific enolase (NSE) were measured before and after ANH. The serum S100B concentration increased significantly in the Hct 20% + CH and Hct 15% + CH groups. However, there were no significant differences in the serum levels of NSE between the groups. In the CA1 region of the rat hippocampus, marked ultrastructural alterations, such as mitochondrial denaturalization and nucleus distortion, were observed in the Hct 20% + CH and Hct 15% + CH groups. Severe ANH (Hct < or = 20%) combined with CH may induce cerebral damage, as confirmed by marked ultrastructural alterations in the CA1 region of the rat hippocampus and significantly increased serum levels of S100B, and should be avoided.


[Exercise induces increased CLUT4 gene expression and protein content in diabetic rats].
To investigate the effects of exercise on insulin receptor, glucose transporter 4 (GLUT4) gene expression and protein content in skeletal muscle cells of streptozotocin-induced diabetic rats. All rats were randomized into three groups: normal, diabetic and diabetic exercise groups. Diabetic exercise rats were swim-trained for 6 weeks. The GLUT4 mRNA of skeletal muscle was determined with dot blot and GLUT4 protein was detected by Western blotting. After 6 weeks of exercise training, plasma glucose level of diabetic rats decreased from 18.5 mmol/L +/- 1.9 mmol/L to 14.0 mmol/L +/- 3.3 mmol/L (P < 0.01). The dot blot revealed that GLUT4 mRNA decreased by 54.9% in skeletal muscle cells of diabetic rats compared with the normal rats. The Western blotting showed that GLUT4 protein of skeletal muscle cell in diabetic rats decreased by 30.7% compared with the control rats. GLUT4 mRNA and the protein of skeletal muscle in diabetic exercise group increased by 56% and 60.8% respectively as compared with the diabetic rats. However, the maximum binding of insulin receptor of skeletal muscle cells in diabetic exercise group decreased significantly compared with diabetic group. The weaker expression of GLUT4 gene and the lower level of GLUT4 protein may be one of the causes of hyperglycemia in diabetic rats. Exercise training may raise the GLUT4 gene expression and the amount of GLUT4 protein in diabetic rats, contributing to the main mechanism of improved post-receptor insulin resistance and decreased hyperglycemia in diabetic rats.


Sextortion of Minors: Characteristics and Dynamics.
Sextortion (threats to expose sexual images to coerce victims to provide additional pictures, sex, or other favors) has been identified as an emerging online threat to youth, but research is scarce. We describe sextortion incidents from a large sample of victims (n = 1,385) and examine whether incidents occurring to minors (n = 572) are more or less serious than those experienced by young adults (n = 813). We ran advertising campaigns on Facebook to recruit victims of sextortion, ages 18-25, for an online survey. We use cross tabulations and logistic regression to analyze incidents that began when 18- and 19-year-old respondents were minors (ages 17 and younger) and compare them with incidents that began at ages 18-25 years. Most minor victims were female (91%) and aged 16 or 17 when incidents started (75%). Almost 60% of respondents who were minors when sextortion occurred knew perpetrators in person, often as romantic partners. Most knowingly provided images to perpetrators (75%), but also felt pressured to do so (67%). About one-third were threatened with physical assaults and menaced for >6 months. Half did not disclose incidents, and few reported to police or websites. Perpetrators against minors (vs. adults) were more likely to pressure victims into producing initial sexual images, demand additional images, threaten victims for >6 months, and urge victims to harm themselves. Sextortion incidents were serious victimizations, and often co-occurred with teen dating violence. We describe resources so that practitioners can help victims find support and legal advice and remove posted images.


Salvage chemotherapy using a combination of fludarabine and cyclophosphamide for refractory or relapsing indolent and aggressive non-Hodgkin's lymphomas.
The prognosis of patients with refractory or relapsing non-Hodgkin's lymphoma (NHL) after primary therapy is poor and multi-drug salvage treatments are associated with less than 60% response rates, usually of short duration. Here we report the results of a phase II study using a fludarabine-cyclophosphamide (FAMP-Cy) combination as a salvage failure regimen in refractory and relapsing low-grade (6) and intermediate-grade (9) NHL patients. Fifteen patients, who had received up to 4 regimens prior to therapy with FAMP-Cy were treated with fludarabine (25 mg/m2) and cyclophosphamide (300 mg/m2) for 3 consecutive days followed by G-CSF (5 microg/kg). The overall response was 74%, 4 achieving complete responses (CR) and 7 partial responses (PR). All patients with low-grade NHL responded (4 CR, 2 PR); 5 patients with intermediate-grade NHL achieved PR lasting for a median of 5 months. The main toxicity encountered was moderate myelosuppression. Three patients had febrile neutropenia, one had drug-induced fever and a single patient developed severe neurotoxicity. Opportunistic infections due to lymphopenia were not seen. The combination of fludarabine and cyclophosphamide used as a salvage regimen showed an impressive response in a small group of heavily pretreated low-grade NHL patients who had previously received a large number of prior regimens. FAMP-Cy had limited effect in a similar group of intermediate-grade NHL patients. Results with this "failure" regimen are encouraging, however further studies are needed in order to confirm these observations in a larger series of patients.


Boseongazepines A-C, pyrrolobenzodiazepine derivatives from a Streptomyces sp. 11A057.
Three new pyrrolobenzodiazepine derivatives, boseongazepines A-C (1-3), were isolated from a culture broth of Streptomyces sp. 11A057, together with the known compound usabamycin B (4). The structures of 1-4 were determined through the analysis of spectroscopic data including extensive 1D-, 2D-NMR, and MS techniques. Cell growth inhibition effects of these compounds were evaluated against Jurkat, K-562, HL-60, and HepG2 cell lines.


Dopamine receptor subtypes in the human coronary vessels of healthy subjects.
Dopamine D(1)-D(5) receptors subtypes were studied in human coronary vessels of healthy subjects to assess their localization and their expression. Samples of intraparenchymal and extraparenchymal branches of human coronary arteries and veins were harvested from four normal native hearts explanted from four young brain dead heart donors in case of orthoptic transplant, not carried out for technical reasons. In all the samples morphological, biochemical, immunochemical, and morphometrical studies were performed including quantitative analysis of images and evaluation of data. Microanatomical section showed healthy coronary vessels, which expressed all dopamine receptors (from D(1) to D(5)) with a different pattern of distribution between the different layers, in the intra and in the extraparenchymal branches.D(1) and D(5) (with a prevalence D(1) over D(5)) were distributed in the adventitia and to a lesser extent in the outer media but they were absent in arterioles, capillaries and venules. Endothelial and the middle layer showed D(2), D(3) and D(4) receptors, with a greater expression of D(2). Immunoblot analysis of dopamine monoclonal antibodies and dopamine receptors showed a different migration band for each receptor: D(1) (45 KDa); D(2) (43 KDa); D(3) (42 kDa); D(4) (40-42 KDa); D(5) (38-40 KDa) These findings demonstrate the presence of all dopamine receptor subtypes in the wall of human coronary vessels of healthy subjects. Dopamine D(1) and D(2) receptor subtypes are the most expressed, suggesting their prominent role in the coronary vasoactivity.


[The "tuning" mechanism of the segmental apparatus before voluntary movement].
The probability of motor unit discharges and changes in the inter-spike interval duration before the voluntary contraction were studied on m. soleus of human beings. A strong motoneuron facilitation was revealed 15-20 ms before the burst of potentials in EMG and only in some experiments a weak facilitation took place earlier (30-50 ms before the burst). So, "tuning" (H-reflex increasing) 60 ms before the voluntary contraction may be regarded as a result of H-reflex presynaptic disinhibition.


Solid gastric emptying mediated by the serotonin (5-HT)3 receptor in mice is a simple marker to predict emesis.
Nausea and emesis are often observed as side effects with many medicines and may lead to poor treatment compliance. In the present study, we aimed to establish simple methods for predicting nausea and/or emesis in mice, which do not vomit, using drugs and chemicals known to evoke nausea and/or emesis. The gastrointestinal transit test, the liquid gastric emptying by phenol red solution (Phenol red method) and the solid gastric emptying by resin beads (Beads method) were used and the effects of antispasmogenics (atropine, 0.1-3 mg/kg i.p.; salmon calcitonin, 1-30 units/kg i.m.), nauseants (copper sulfate, 1-30 mg/kg p.o.; apomorphine, 0.01-0.3 mg/kg s.c.) and chemotherapeutics (cisplatin, 0.3-10 mg/kg i.v.; doxorubicin, 0.3-10 mg/kg i.v.) were evaluated. In addition, the effects of ondansetron, a serotonin (5-HT)(3) receptor antagonist, on the inhibition of solid gastric emptying induced by salmon calcitonin, copper sulfate, cisplatin and doxorubicin were also assessed. Only the solid gastric emptying method could detect changes of gastric emptying by all drugs and chemicals. We also found that the inhibition of solid gastric emptying induced by cisplatin and doxorubicin was dose-dependently antagonized by ondansetron. However, ondansetron failed to antagonize the salmon calcitonin-induced delay, but exerted only very weak effects with copper sulfate. Solid gastric emptying may be more suitable than gastrointestinal intestinal transit or liquid gastric emptying in mice to predict nausea and/or emesis. Our results also suggest that chemotherapeutic-induced delay of solid gastric emptying mediated via 5-HT(3) receptors in mice could also be useful for prediction purposes.


Septal flash: At the heart of cardiac dyssynchrony.
Cardiac resynchronization therapy (CRT) has been a major step in the treatment of heart failure patients and intraventricular conduction delay. As a considerable number of patients do not respond adequately to CRT, echocardiographic dyssynchrony selection criteria have been proposed to improve CRT response, but these parameters eventually failed to provide superior selection of CRT candidates. In the last decade, an echo-dyssynchrony parameter called "septal flash" was been reported by several investigators and opinion leaders in the field of CRT. This parameter has a strong pathophysiological rationale and was shown to be a robust and predominant predictor of CRT response in recent observational and retrospective studies. We here provide a comprehensive and balanced overview of septal flash and address several important aspects, questions and potential future implications of septal flash in cardiomyopathy and CRT.


Genome of Xanthomonas oryzae bacteriophage Xp10: an odd T-odd phage.
Xp10 is a lytic bacteriophage of the phytopathogenic bacterium Xanthomonas oryzae. Though morphologically Xp10 belongs to the Syphoviridae family, it encodes its own single-subunit RNA polymerase characteristic of T7-like phages of the Podoviridae family. Here, we report the determination and analysis of the 44,373 bp sequence of the Xp10 genome. The genome is a linear, double-stranded DNA molecule with 3' cohesive overhangs and no terminal repeats or redundancies. Half of the Xp10 genome contains genes coding for structural proteins and host lysis functions in an arrangement typical for temperate dairy phages that are related to the Escherichia coli lambda phage. The other half of the Xp10 genome contains genes coding for factors of host gene expression shut-off, enzymes of viral genome replication and expression. The two groups of genes are transcribed divergently and separated by a regulatory region, which contains divergent promoters recognized by the host RNA polymerase. Xp10 has apparently arisen through a recombination between genomes of widely different phages. Further evidence of extensive gene flux in the evolution of Xp10 includes a high fraction (10%) of genes derived from an HNH-family endonuclease, and a DNA-dependent DNA polymerase that is closer to a homolog from Leishmania than to DNA polymerases from other phages or bacteria.


Chemical modification improves the stability of the DNA aptamer GBI-10 and its affinity towards tenascin-C.
Aptamers are useful tools in molecular imaging due to their numerous attractive properties, such as excellent affinity and selectivity to diverse types of target molecules and biocompatibility. We carried out structure-activity relationship studies with the tenascin-C (TN-C) binding aptamer GBI-10, which is a promising candidate in tumor imaging. To increase the tumor targeting ability and nuclease resistance under physiological conditions, systematic modifications of GBI-10 with single and multiple 2'-deoxyinosine (2'-dI) or d-/l-isonucleoside (d-/l-isoNA) were performed. Results indicated that sector 3 of the proposed secondary structure is the most important region for specific binding with TN-C. By correlating the affinity of eighty-four GBI-10 derivatives with their predicted secondary structure by Zuker Mfold, we first validated the preferred secondary structure at 37 °C. We found that d-/l-isoNA modified GBI-10 derivatives exhibited improved affinity to the target as well as plasma stability. Affinity measurement and confocal imaging analysis highlighted one potent compound: 4AL/26TL/32TL, which possessed a significantly increased targeting ability to tumor cells. These results revealed the types of modified nucleotides, and the position and number of substituents in GBI-10 that were critical to the TN-C binding ability. Stabilized TN-C-binding DNA aptamers were prepared and they could be further developed for tumor imaging. Our strategy to introduce 2'-dI and d-/l-isoNA modifications after the selection process is likely to be generally applicable to improve the in vivo stability of aptamers without compromising their binding ability.


Differences between neurosurgeons and orthopedic surgeons in classifying cervical dislocation injuries and making assessment and treatment decisions: a multicenter reliability study.
Variability exists in the management of cervical spinal injuries. The goal of this study was to assess the effect of training specialty (orthopedic surgery vs neurosurgery) on management of cervical dislocations. Twenty-nine spine surgeons reviewed 10 cases of cervical dislocation injuries. For each of the 10 cases, the surgeons evaluated 3 clinical scenarios, which included a neurologically intact patient, a patient with an incomplete spinal cord injury (SCI), and a patient with complete SCI. Surgeons determined whether a unilateral or bilateral facet dislocation was present and whether pretreatment magnetic resonance imaging (MRI) or immediate closed reduction was indicated. Management decisions were re-assessed after review of MRIs. While spine surgeons may agree on what they see on MRI and how they classify certain cervical injuries irrespective of training, significant differences of opinion continue to exist regarding the therapeutic implications of this information, specifically, whether to order a pretreatment MRI and how to manage the injury.


Carbon monoxide in firemen before and after exposure to smoke.
A statistically significant difference was found between the mean baseline carboxyhemoglobin of non-smoking firemen (COHb 2.53, sd = 1.05, n = 32) and smoking firemen (COHb 5.54, sd = 2.61, n = 26). A consistent increase in mean COHb levels after exposure to smoke was seen in both non-smoking (4.41 sd = 2.95, n = 7) and smoking men (8.74, sd = 5.66, n = 11), but the mean increase in these two groups was statistically significant only at the 90 percent level (t = 1.85, df = 16, p less than 0.1).


Giant arteriovenous malformation of the floor of the mouth presenting with dysarthria and difficulty in swallowing.
Arteriovenous malformation (AVM) is a vascular abnormality resulting in the development of abnormal connection between an artery and vein without capillary connections. An AVM develops mainly intracranially. Extracranial AVMs are rarely seen. Cheek, ear, nose, auricle, and forehead are the more common sites in the extracranial involvement. They cause cosmetic problems when located in the head and neck region. We report a case of a giant AVM in the floor of the mouth, which has not been specified and has not been reported until now. The lesion, in an elderly man, was supplied by multiple vessels and caused difficulty in speaking and swallowing. The lesion was totally excised after embolization of feeding vessels.


Gene transfer and cloning of flanking chromosomal regions using the medaka fish Tol2 transposable element.
For the ultimate purpose of developing genetic tools using the medaka fish Tol2 transposable element, we examined whether it can transfer a marker gene into the fish genome and also be applied for cloning of chromosomal regions adjacent to insertion points. An internal region of Tol2 was removed and replaced with the green fluorescent protein (GFP) gene and a bacterial plasmid replication origin. This modified Tol2 clone was microinjected into fertilized eggs together with messenger RNA for the Tol2 transposase. The GFP gene was found to be integrated into chromosomes and transmitted to subsequent generations. Restriction enzyme digestion of genomic DNA of a transformant fish, followed by ligation and introduction into bacteria, produced a plasmid containing the entire element and flanking chromosomal regions. Sequencing analysis of this clone demonstrated transposition of the element in the germline of the first generation. Thus, the basic requirements for a gene transfer vector and gene tagging system were fulfilled.


Which nicotine products are gateways to regular use? First-tried tobacco and current use in college students.
The potential for emerging tobacco products (ETPs) to be gateway products for further tobacco use among youth is of significant concern. To examine use of various nicotine-containing products on a tobacco-free college campus and whether the first product tried predicts subsequent tobacco use. Undergraduate students (N=1,304) at a large university completed an online survey of past/current use of cigarettes; smokeless tobacco (SLT); hookah; ETPs (dissolvables, snus, and electronic cigarettes); and nicotine replacement therapy (NRT). Data were collected from September 2012 to May 2013 and analyses were conducted from June to September 2013. Students were classified as single, dual, or poly tobacco users. The sample consisted of 79.5% non-users, 13.8% single, 4.4% dual, and 1.5% poly users. Overall, 49.4% of participants reported trying a tobacco product. Hookah was the most tried product (38%), but cigarettes were most often the first product ever tried (51%). First product tried did not predict current tobacco use and non-use, but individuals who first tried SLT or cigarettes (rather than hookah or ETPs) were more likely to be poly tobacco users. Current tobacco users who first tried ETPs or hookah were largely non-daily users of hookah; current tobacco users who first tried cigarettes or SLT were largely non-daily or daily users of cigarettes/SLT. Hookah and ETPs are increasingly becoming the first tobacco product ever tried by youth; however, uptake of ETPs is poor, unlike cigarettes and SLT, and does not appear to lead to significant daily/non-daily use of cigarettes and SLT.


[Urinary tract carcinomas in gas industry employees (author's transl)].
Arising from a retrospective investigation of the causes of death in active and pensioned employees from the author's sphere of observation, the increased occurence of urinary tract carcinoma in furnace battery and pipe system workers in the gas industry is pointed out. Statistical studies suggest a causal connection between exposure to tar in these jobs and the urinary tract carcinomas. The necessity for industrial medical precautions is commented on.


Comparison of continous-wave Doppler ultrasound monitor and echocardiography to assess cardiac output in intensive care patients.
Continuous-wave Doppler (CWD) ultrasound through the left ventricular outflow tract is one modality used for non-invasive cardiac output measurement. The ultrasonic cardiac output monitor (USCOM) is a relatively new monitor which uses a small, transcutaneous ultrasound probe to measure cardiac output with CWD via the suprasternal window. It is faster and less complex to train new users than conventional echocardiography. In addition to stroke volume (SV), the USCOM can calculate stroke volume variation (SVV) and the Smith-Madigan inotropy index (SMII), which is an estimate of the pre-load independent contractility of the myocardium. To assess the level of agreement between cardiac output measured with conventional echocardiography and with USCOM. A prospective, observational, multicentre trial of patients admitted to the intensive care units of two hospitals. After excluding patients with aortic stenosis, any patient undergoing a clinically indicated echocardiogram also underwent a subsequent USCOM study for comparison. We enrolled 121 patients in the study, with aortic stenosis the main reason for patient exclusion. Of the study patients, 63% were mechanically ventilated, 84% were in sinus rhythm, and the mean age of the study cohort was 66 years (SD, 17 years). There was a very strong correlation between SV as measured by the USCOM and by echocardiography. The mean difference in SV was 0.33 mL (SD, 5.62 mL), r2 = 0.956, and Bland-Altman analysis confirmed no significant bias with acceptable limits of agreement between the methods. Patients who were fluid responsive had an SVV cut point on the receiver operating characteristic curve of 21%, and sensitivity and specificity of 95%. A low SMII (< 1.1 watts/m2) calculated with the USCOM did not correlate well with low cardiac output status, with a sensitivity of only 69%. SV (and thus cardiac output) measured using the USCOM correlated well with echocardiographic cardiac output measurement, which suggests that the USCOM could be a valuable haemodynamic tool for assessment of cardiac output and fluid responsiveness in critically ill patients if patients with aortic stenosis are excluded. Inotropy, as a parameter of low cardiac output, was not useful in this cohort of patients.


Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review.
Cell targeting peptides (CTP) are small peptides which have high affinity and specificity to a cell or tissue targets. They are typically identified by using phage display and chemical synthetic peptide library methods. CTPs have attracted considerable attention as a new class of ligands to delivery specifically therapeutic and diagnostic agents, because of the fact they have several advantages including easy synthesis, smaller physical sizes, lower immunogenicity and cytotoxicity and their simple and better conjugation to nano-carriers and therapeutic or diagnostic agents compared to conventional antibodies. In this systematic review, we will focus on the basic concepts concerning the use of cell-targeting peptides (CTPs), following the approaches of selecting them from peptide libraries. We discuss several developed strategies for cell-specific delivery of different cargos by CTPs, which are designed for drug delivery and diagnostic applications.


A cytotoxic carotenoid from the marine sponge Prianos osiros.
Investigations of the marine sponge Prianos osiros, collected in Pohnpei, gave a new cytotoxic acetylenic carotenoid, (3R,3'R,5S)-3,3',5,19'-tetrahydroxy-7',8'-didehydro-gamma,epsilon-carotene-8-one. The absolute configuration of this carotenoid was solved by interpretation of IR, MS, and 2D NMR spectra and application of the modified Mosher's method. Compound 1 is cytotoxic toward cultured human colon tumor cells, HCT 116 (IC(50) 4.38 microg/mL).