Endoscopic ultrasound-guided sampling of solid pancreatic masses: the fine needle aspiration or fine needle biopsy dilemma. Is the best needle yet to come?
Fine needle aspiration (FNA) is currently the standard of care for sampling pancreatic solid masses by using endoscopic ultrasound (EUS). The accuracy of the technique is reported to be high, especially if coupled with the rapid on site evaluation (ROSE), and it has a high safety profile. However, FNA presents some limitations, such as the small amount of tissue that can be collected and the inability of obtaining a core tissue with intact histological architecture, which is relevant to perform immunohistochemical analysis, molecular profiling and, therefore, targeted therapies. Moreover, the presence of the ROSE by an expert cytopathologist is very important to maximize the diagnostic yield of FNA technique; however, it is not widely available, especially in small centers. Hence, the introduction of EUS fine needle biopsy (FNB) with a new generation of needles, which show a high safety profile too and a satisfying diagnostic accuracy even in the absence of ROSE, could be the key to overcome the limitations of FNA. However, FNB has not yet shown diagnostic superiority over FNA. Considering all the technical aspects of FNA and FNB, the different types of needle currently available, comparisons in term of diagnostic yield, and the different techniques of sampling, a tailored approach should be used in order to determine the needle that is most appropriate for the different specific scenarios.


Formation and stability of small polarons at the lithium-terminated Li4Ti5O12 (LTO) (111) surface.
Zero strain insertion, high cycling stability, and a stable charge/discharge plateau are promising properties rendering Lithium Titanium Oxide (LTO) a possible candidate for an anode material in solid state Li ion batteries. However, the use of pristine LTO in batteries is rather limited due to its electronically insulating nature. In contrast, reduced LTO shows an electronic conductivity several orders of magnitude higher. Studying bulk reduced LTO, we could show recently that the formation of polaronic states can play a major role in explaining this improved conductivity. In this work, we extend our study toward the lithium-terminated LTO (111) surface. We investigate the formation of polarons by applying Hubbard-corrected density functional theory. Analyzing their relative stabilities reveals that positions with Li ions close by have the highest stability among the different localization patterns.


Live birth prevalence of atrioventricular septal defect after the implementation of new prenatal screening guidelines.
In 2004, the Danish Health Authority implemented a new guideline on prenatal screening, offering all pregnant women in Denmark a foetal diagnostic ultrasound scan in the first and second trimester of their pregnancy. One of the diagnoses that may be diagnosed prenatally is congenital heart defect including atrioventricular septal defect (AVSD). AVSD is often associated with Down syndrome (DS). After a prenatal diagnosis of AVSD, parents are offered counselling on the impact of the diagnosis on their child's life. The aim of this study was to describe the impact of changes in prenatal screening programmes on the live birth prevalence of AVSD on the island of Funen, Denmark. This was a registry-based descriptive analysis drawing on data from the EUROCAT Registry of Congenital Malformations for Funen County, Denmark. Cases of AVSD and DS from 1990 to 2018 were included. Out of 153,757 births, 60 cases of AVSD were registered, with a total prevalence at 3.9 per 10,000 births. Among all cases, 40% had an associated chromosomal diagnosis. The prenatal detection rate increased by 83% after implementation of the new screening programme. This was paralleled by an increase in the number of cases of termination of pregnancy following foetal anomaly (TOPFA) from 3% to 21% (p-value less-than 0.05) and a 21% reduction in live births among infants with AVSD. A significant increase in the rate of TOPFA was found, with no difference in the distribution of chromosomal or non-chromosomal status, leading to a 21% reduction in liveborn infants with AVSD. none. none.


[Influence of estradiol and testosterone on carbon tetrachloride-induced liver damage in the rat].
The aim of the study was to know influences of estrogen and testosterone on carbon tetrachloride-induced liver damage in male Wistar rats. One hundred and two rats were divided into following six groups on the basis of the treatment: olive oil as control (O), carbon tetrachloride (0.1 ml/100 g, C), estradiol benzoate (0.1 mg/100 g, E), testosterone propionate (5 mg/100 g, T), C + E and C + T, in which each drug was intraperitoneally injected twice per week for consecutive 12 weeks. In the C + E group, decreases in serum albumin level at the 4th week and total cholesterol level at the 8th week seemed to be suppressed. And fibrotic change and fatty change were weak on the histological observation. However, hepatocellular hyperplasia was observed in 40% cases after the 8th week. On the flow cytometry analysis of the liver at the 4th week, an enhancement of hepatocellular proliferation was shown. Survival rate of the C + E group rats was lower than C group rats. On the other hand, in the C + T group, liver injury occurred in the same grade as C group, and the survival rate was worst among all six groups. These results suggest that simultaneous administration of estrogen with carbon tetrachloride could reduce hepatic injury, though it might cause hepatocellular hyperplasia.


Long-term adaptation to high doses of morphine causes desensitization of mu-OR- and delta-OR-stimulated G-protein response in forebrain cortex but does not decrease the amount of G-protein alpha subunits.
The functional activity of trimeric guanine-nucleotide-binding proteins (G-proteins) represents an essential step in linking and regulation of the opioid receptor (mu-, delta- and kappa-OR)-initiated signaling pathways. Theoretical basis and/or molecular mechanism(s) of opioid tolerance and addiction proceeding in the central nervous system were not studied in the forebrain cortex of mammals with respect to quantitative analysis of opioid-stimulated trimeric G-protein activity. G-protein activity was measured in PercollR-purified plasma membranes (PM) isolated from the frontal brain cortex of control and morphine-treated rats by both high-affinity [32P]GTPase and [35S]GTPgammaS binding assays. Exposition to morphine was performed by intra-muscular application of this drug. Control animals were injected with sterile PBS. Both mu-OR (DAMGO)- and delta-OR (DADLE)-responses were clearly desensitized in PM isolated from morphine-treated rats; kappa-OR (U-69593)- and baclofen (GABAB-R)-stimulated [35S]GTPgammaS binding was unchanged, indicating the specificity of the morphine effect. Under such conditions, the amount of G-protein alpha subunits was unchanged. The order of efficacy DADLE>DAMGO>U-69593 was the same in control and morphine-treated PM. Behavioral tests indicated that morphine-treated animals were fully drug-dependent and developed tolerance to subsequent drug addition. Prolonged exposure of rats to high doses of morphine results in decrease of the over-all output of OR-stimulated G-protein activity in the forebrain cortex but does not decrease the amount of these regulatory proteins. These data support the view that the mechanism of the long-term adaptation to high doses of morphine is primarily based on desensitization of OR-response preferentially oriented to mu-OR and delta-OR.


Fulminant hepatic failure resulting from lamivudine-resistant hepatitis B virus in a renal transplant recipient: durable response after orthotopic liver transplantation on adefovir dipivoxil and hepatitis B immune globulin.
Mutations in the hepatitis B virus (HBV) genome may occur during therapy. We report an asymptomatic HBV carrier who underwent transplantation for end-stage renal disease. She developed an HBV flare 6 months after transplantation and was placed on lamivudine. After initial rapid improvement, she relapsed clinically and virologically. She decompensated with jaundice, peripheral edema, ascites, encephalopathy, coagulopathy, and hepatorenal syndrome. A liver biopsy specimen revealed submassive necrosis. Emergency liver transplantation was performed: lamivudine was discontinued. Hepatitis B immunoglobulin and adefovir dipivoxil were initiated. Sixteen months after orthotopic liver transplantation, she is HBV DNA seronegative with normal liver enzymes. Sequencing of HBV polymerase gene from preliver transplantation sera did not detect the usual lamivudine resistance mutations in the YMDD motif but instead two other mutations (F514-->L, L528-->M). Lamivudine resistance was demonstrated in vitro. Asymptomatic HBV carriers may reactivate following renal transplantation after immunosuppression. Resistance to lamivudine may result in severe hepatic damage in immunocompromised patients.


Lateral popliteal sciatic nerve block compared with ankle block for analgesia following foot surgery.
The purpose of this study was to compare postoperative analgesia after foot surgery in patients anaesthetised either with popliteal sciatic nerve block or ankle block. In a prospective study, 40 patients scheduled for foot surgery involving osteotomies were allocated randomly into one of two groups. Following induction of general anaesthesia, Group PS (n = 21) received a lateral popliteal sciatic nerve block and Group AB (n = 19) received an ankle block. Both groups received 20 ml bupivacaine 0.5% plain. In group PS 43% required morphine analgesia in the Post Anaesthetic Recovery Room (PAR) compared with 16% in group AB. Postoperative analgesia was assessed using VAS and a pain scale in the PAR and a questionnaire by telephone follow-up on the day after surgery. The ankle block appeared to be more reliable, providing more consistent analgesia in the PAR. Postoperative analgesia in Group PS lasted a median of 18.0 hr and in Group AB lasted 11.5 hr (P < 0.05). Both techniques provided effective analgesia after discharge home and high levels of patient satisfaction.


Paracoccus amoyensis sp. nov., isolated from the surface seawater along the coast of Xiamen Island, China.
Strain 11-3T was isolated from the surface seawater along the coast of Xiamen Island, China. Cells were Gram-stain-negative, oxidase- and catalase-positive, short and rod-shaped, nonmotile, 0.5-1.0 μm in width and 1.0-2.0 μm in length. Growth of strain 11-3T was at temperature of 15-37°C (optimum 28-35°C), at pH of 5.0-11.0 (optimum 7.0-9.0) and at salinity range of 0-10 (optimum 0.5-1). Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain 11-3T belonged to the genus Paracoccus and had the highest similarity with Paracoccus caeni MJ17T (98.1 %), followed by Paracoccus xiamenensis 12-3T (97.1 %), Paracoccus zeaxanthinifaciens ATCC 21588T (97.1 %), Paracoccus aestuarii DSM 19484T (97.0 %), Paracoccus liaowanqingii 2251T (97.0 %), Paracoccus fistulariae KCTC 22803T (97.0 %) and other species of the genus Paracoccus (95.2-96.8 %). The DNA-DNA hybridization values between strain 11-3T and the selected strains (P. caeni MJ17T, P. xiamenensis 12-3T, P. zeaxanthinifaciens ATCC 21588T, P. aestuarii DSM 19484T and P. liaowanqingii 2251T) were 19.4, 19.5, 21.6, 19.3 and 19.8 %, respectively. Corresponding, their ANI values were 77.53, 75.61, 75.36, 75.73 and 75.33 %, respectively. The major fatty acid was summed feature 8 (C18:1 ω6c/ω7c). The major respiratory quinone was Q10. The polar lipids included phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), unidentified glycolipid (GL) and unidentified aminolipid (AL). The DNA G+C content of strain 11-3T was 60.1 %. Based on results of the phylogenetic analysis, phenotypic and chemotaxonomic characteristics, strain 11-3T represents a novel species of the genus Paracoccus, for which the name Paracoccus amoyensis sp. nov. is proposed. The type strain is 11-3T (=MCCC 1A16380T=KCTC 72689T).


Optimization of computation efficiency in underwater acoustic navigation system.
This paper presents a technique for the estimation of the relative bearing angle between the unmanned underwater vehicle (UUV) and the base station for the homing and docking operations. The key requirement of this project includes computation efficiency and estimation accuracy for direct implementation onto the UUV electronic hardware, subject to the extreme constraints of physical limitation of the hardware due to the size and dimension of the UUV housing, electric power consumption for the requirement of UUV survey duration and range coverage, and heat dissipation of the hardware. Subsequent to the design and development of the algorithm, two phases of experiments were conducted to illustrate the feasibility and capability of this technique. The presentation of this paper includes system modeling, mathematical analysis, and results from laboratory experiments and full-scale sea tests.


[Histamine-producing neuroendocrine tumor of the ampulla of Vater].
Neuroendocrine tumors of the ampulla of Vater are rare (less than 100 cases reported). We report here a new case characterized by histamine secretion, a hitherto unreported feature. Clinical presentation is similar to that of other tumors of the ampulla of Vater. In our observation, the patient had noticed urticaria on the right forearm for several months. Tumor of the ampulla was confirmed by endoscopic ultrasonography, while neuroendocrine characterization was assessed on biopsies after endoscopic sphincterotomy. Histamine concentration in blood was the only elevated neuroendocrine marker and returned to normal after surgical resection. Histology showed a neuroendocrine tumor with extension to lymph nodes. On immunohistochemical analysis, production of histamine was confirmed, and the diagnosis of mastocytoma was eliminated. In view of the literature, neuroendocrine tumors of the ampulla of Vater are associated with a good prognosis (5 year-survival rate: 90%) despite early lymph node involvement.


Suppression of Schistosoma bovis egg production in cattle by vaccination with either glutathione S-transferase or keyhole limpet haemocyanin.
Two of the antigens which have shown vaccine potential in animal experiments against Schistosoma mansoni are glutathione-S-transferase (GST) and GP38, protective epitopes of which are shared with keyhole limpet haemocyanin (KLH). We therefore tested S. bovis GST and KLH for vaccine efficacy against S. bovis in the natural Zebu cattle host. In a preliminary experiment three vaccinations with a total of 1.39 mg of native GSTs of S. bovis induced specific antibody at the time of challenge as detected by Western blotting and ELISA and mean faecal egg counts between weeks 6-10 post-challenge were reduced by 56.4 to 82.5% compared to non-vaccinated controls. Mean adult worm recoveries and tissue egg densities in large intestine and liver samples were also reduced in the vaccinated group, but these differences were not statistically significant. In a subsequent experiment one group of calves was vaccinated with a similar schedule to that used above; a second group of calves was given only two injections of GST (total 0.48 mg protein); a third group of calves was vaccinated twice with a total of 2.0 mg KLH in PBS. All three vaccination schedules induced specific antibody. Both GST vaccination schedules induced significant reductions in faecal egg counts compared to non-vaccinated controls and in this experiment tissue egg densities were also significantly reduced. A striking finding, however, was that adult worm counts were not reduced by vaccination. An essentially similar outcome resulted from KLH vaccination, since there were significant reductions in faecal and tissue egg counts in the absence of a reduction in adult worm numbers.(ABSTRACT TRUNCATED AT 250 WORDS)


Acetate metabolism and Escherichia coli biofilm: new approaches to an old problem.
Current antibiotics continue to lose effectiveness for infectious diseases, especially in cases where the bacteria from a biofilm. This review article summarizes control mechanisms for bacterial biofilm, with an emphasis on the modification of signal transduction pathways, such as quorum sensing and two-component signaling, by externally added metabolic intermediates. As a link between central metabolism and signal transduction, we discuss the activation of two-component response regulators by activated acetate intermediates in response to signals from the environment. These signals constitute 'nutrients' for the bacteria in most cases. Depending on the identity of the nutrient, biofilm amounts may be reduced. The nutrient may then be used for the development of both novel prevention and treatment options for biofilm-associated infectious diseases.


Catalytic regioselective construction of phenylthio- and phenoxyldifluoroalkyl tetrazoles from difluorodiazoketones.
Here we report the design and synthesis of two new difluoro-diazoketone reagents (difluorophenylthiol diazoketone and difluorophenoxyl diazoketone) and their [3+2] cycloaddition reactions with aryldiazonium salts under silver catalysis conditions. This protocol enables regioselective access to a broad scope of difluorophenylthiol- and difluorophenoxyl-substituted tetrazole-carbinols in a one-pot operation. Further synthetic derivatizations including dephenylthiolation and unexpected phenylthiol group migration/fluorination allow the efficient preparation of α-difluoromethyl tetrazole-carbinols and α-trifluoromethyl tetrazole-thioethers.


Self-organized pacemakers and bistability of pulses in an excitable medium.
Pattern formation in an excitable medium described by a three-component reaction-diffusion system is investigated. Our focus is on stable self-organized pacemakers which give rise to spatially extended target patterns. Bistability of pulse solutions in the excitable regime is also reported, and interactions of the different pulses with each other and the pacemaker are studied. Self-organized pacemakers are created by a suitable perturbation from the steady state or through interaction of pulses. Bound states of one-dimensional pacemakers and phase flips are also observed.


[Sensitivity and specificity of alpha-1-antitrypsin and acid alpha-1-glycoprotein in colorectal carcinoma].
In a group of 80 patients with colorectal cancer and a control group of 91 persons and in 15 patients with acute diverticulitis of the sigmoid colon acid alpha-1-glycoprotein (AGP) and alpha-1-antitrypsin (AAT) were measured. The median of AAT in the carcinoma group was 3.34 g/l, in the control group 2.39 g/l. AGP was in the carcinoma group 1.19 g/l, in the control group 0.79 g/l. Both differences are significant. The sensitivities of AGP and AAT were compared with the sensitivities of CEA and CA 19/9 using ROC-curves. AAT and AGP have a distinctly lower sensitivity than CEA, but only on the basis of a high specificity of 95%. In the region of lower specificities AAT has the highest sensitivity. Therefore, the sensitivity of CEA for colorectal carcinoma is not reached by AAT and AGP, when a high specificity of the test is required. The relevance of AAT and AGP determinations is further reduced because in the diverticulitis group the levels were as high as in the carcinoma group.


Dyspnea in interstitial lung disease.
Dyspnea is a common complication of interstitial lung disease, yet little is known about its cause and effective management. This review attempts to summarize the current state of the art in this area. Dyspnea is a near-universal finding in people with interstitial lung disease, predominantly due to neuromechanical abnormalities. Several well studied metrics exist for the measurement of dyspnea in this population, and its severity has been linked to quality of life and survival. The management of dyspnea in interstitial lung disease remains a challenge, with no proven pharmacological options. Pulmonary rehabilitation shows therapeutic promise, and aggressive treatment of physical and psychiatric comorbidities is important. Dyspnea remains a common and difficult to treat symptom for people with interstitial lung disease. More research is sorely needed.


NAD+ Levels Are Augmented in Aortic Tissue of ApoE-/- Mice by Dietary Omega-3 Fatty Acids.
Maintaining bioenergetic homeostasis provides a means to reduce the risk of cardiovascular events during chronological aging. Nicotinamide adenine dinucleotide (NAD+) acts as a signaling molecule, and its levels were used to govern several biological pathways, for example, promoting angiogenesis by SIRT1 (sirtuin 1)-mediated inhibition of Notch signaling to rejuvenate capillary density of old-aged mice. NAD+ modulation shows promise in the vascular remodeling of endothelial cells. However, NAD+ distribution in atherosclerotic regions remains uncharacterized. Omega-3 polyunsaturated fatty acids consumption, such as docosahexaenoic acid and eicosapentaenoic acid, might increase the abundance of cofactors in blood vessels due to omega-3 polyunsaturated fatty acids metabolism. Apolipoprotein E-deficient (ApoE-/-) mice were fed a Western diet, and the omega-3 polyunsaturated fatty acids-treated groups were supplemented with docosahexaenoic acid (1%, w/w) or eicosapentaenoic acid (1%, w/w) for 3 weeks. Desorption electrospray ionization mass spectrometry imaging was exploited to detect exogenous and endogenous NAD+ imaging. NAD+, NADH, NADP+, NADPH, FAD+, FADH, and nicotinic acid adenine dinucleotide of the aortic arches were detected higher in the omega-3 polyunsaturated fatty acids-treated mice than the nontreated control. Comparing the distribution in the outer and inner layers of the arterial walls, only NADPH was detected slightly higher in the outer part in eicosapentaenoic acid-treated mice. Supplementation of adding docosahexaenoic acid or eicosapentaenoic acid to the Western diet led to a higher NAD+, FAD+, and their metabolites in the aortic arch. Considering the pleiotropic roles of NAD+ in biology, this result serves as a beneficial therapeutic strategy in the animal model counter to pathological conditions.


Dental education in Queensland: II. Principles of curriculum design.
A modern dental curriculum must produce graduates who are competent to practise in a variety of settings immediately upon graduation; cognisant of community needs and the social milieu in which they serve their patients' health needs; able to anticipate and cope with changes following graduation; committed to self-improvement, willing to change to reflect best clinical practice; and equipped with skills for self-assessment and lifelong learning. This requires the appropriate balance of emphasis on educational content and educational process. This paper outlines the design considerations underlying the new BDSc curriculum at the University of Queensland. This curriculum uses an integrated rather than subject-based approach, with student-centred modes of learning as the principal learning style. Active learning strategies develop critical thinking and clinical problem-solving skills. Learning occurs in the context of a clinical situation (either overt or implied). Year 2 provides the major scientific foundations, and later years build upon this base, particularly through problem-based learning. Senior clinical staff involved in teaching in earlier parts of the course, help provide an overt clinical context to learning activities. The integrated curriculum model provides clinically relevant education in basic sciences and scientifically based education in clinical care. The curriculum has a focus on outcomes and on preparation for general practice. Importantly, it has an open and transparent structure, and each component is linked explicitly with the competencies expected of the new dental graduate.


Quality of life and supportive care in the treatment of NSCLC.
The definition of quality of life (QOL) for individual patients with non-small cell lung cancer (NSCLC) is unclear and its evaluation difficult because of the heterogeneity of the patients involved. More research is needed to determine the best means of routinely expressing and comparing QOL assessments and implementing the results of these studies into daily patient care. The role of broad supportive care in optimizing patient comfort and functionality is also an important issue. Because it incorporates not only specific palliative treatment, but also nontumor-specific measures and medical intervention, supportive care is relevant to all patients with NSCLC, whether terminally ill or suffering treatment-related toxic reactions. More education, research, and financial support are needed to optimize QOL and supportive care of patients.


Construction and Periplasmic Expression of the Anti-EGFRvIII ScFv Antibody Gene in Escherichia coli.
In the previous study, we constructed an expression vector carrying the anti-EGFRvIII scFv antibody gene with VH-linker-VL orientation. The proteins were successfully produced in the periplasmic space of Escherichia coli. In this study, we substituted the inserted DNA with VL-linker-VH orientation of the anti-EGFRvIII scFv gene and analyzed its expression in E. coli. The DNA fragment was amplified from its cloning vector (pTz-rscFv), subsequently cloned into a previous expression vector containing the pelB signal sequence and his-tag, and then transformed into E. coli TOP10. The recombinant plasmids were characterized by restriction, PCR, and DNA sequencing analyses. The new anti-EGFRvIII scFv antibody proteins have been successfully expressed in the periplasmic compartment of E. coli Nico21(DE3) using 0.1 mM final concentration of IPTG induction. Total proteins, soluble periplasmic and cytoplasmic proteins, solubilized inclusion bodies, and extracellular proteins were analyzed by SDS-PAGE and Western Blot analyses. The results showed that soluble scFv proteins were found in all fractions except from the cytoplasmic space.


Lenalidomide treatment of myelodysplastic syndromes with chromosome 5q deletion: Results from the National Registry of the Italian Drug Agency.
The most typical cytogenetic aberration in myelodysplastic syndromes is del(5q), which, when isolated, is associated with refractory anaemia and good prognosis. Based on high rates of erythroid response and transfusion independence, Lenalidomide (LEN) became the standard treatment. This multi-centre study was designed to supplement Italian Registry data on LEN by addressing prescription, administration appropriateness, haematological and cytogenetic responses and disease evolution. MORE study was an observational, non-interventional, multi-centre, retrospective and prospective study. Cases were recruited from 45 Haematological Centres throughout Italy. Data were collected from the Italian National Registry for Lenalidomide administration and supplemented by a MORE data form. Data from 190/213 patients were analysed. In all, 149 had been diagnosed by conventional cytogenetics (GROUP A) and 41 only by FISH (GROUP B). Overall erythroid response was obtained in 92.8% of cases. Overall cytogenetic remission was achieved in 22.6% of cases. Disease progression occurred in 15.6% of cases. Clonal cytogenetic evolution characterised progression to AML but not to higher risk MDS. Erythroid response to Lenalidomide was similar in MDS with isolated del(5q) and with del(5q) plus one anomaly. Progression to AML or higher risk MDS showed different cytogenetic features.


The effect of inhaled vasoactive intestinal peptide on bronchial reactivity to histamine in humans.
Nonadrenergic, noncholinergic nerves are the predominant inhibitory nervous pathway in human airway smooth muscle, and there is evidence in animals that the major neurotransmitter of this system is vasoactive intestinal peptide (VIP). We have investigated the effect of VIP on bronchomotor tone and bronchial responsiveness to inhaled histamine in 6 atopic asthmatic subjects. The VIP was given by inhalation to avoid any indirect effects on the airways that might arise from the potent cardiovascular actions of this peptide when given systemically. The VIP (100 micrograms) was compared with control solution (diluent: 1% human serum albumin in 2 ml 0.9% saline) and with beta 2-agonist (salbutamol, 200 micrograms) given double blind in random order on separate days. Specific airway conductance (SGaw) did not change after control or VIP inhalations, but it significantly increased after salbutamol inhalation. The provocation concentration of histamine causing a 35% fall in SGaw (PC35) did not change after control inhalation, but significantly increased after VIP (from 2.18 +/- 1.04 to 5.00 +/- 2.31 mg/ml histamine, mean +/- SE; p less than 0.05), and after salbutamol (from 1.71 +/- 0.83 to 15.6 +/- 4.2 mg/ml, p less than 0.01), the increase after salbutamol being significantly greater than after VIP. No changes in heart rate or blood pressure were found after any inhalation. We conclude that VIP protects against histamine-induced bronchoconstriction in human airways in vivo, and therefore has the capacity to be the neurotransmitter of nonadrenergic, noncholinergic inhibitory nerves in human airway smooth muscle.


[Elite controllers and the mechanisms behind spontaneous control of HIV].
Elite controlllers (EC) are a unique and rare group of HIV-positive patients who control viral replication to undetectable levels in the absence of antiretroviral treatment. They tend to maintain stable CD4 count, and do not progress to AIDS. While the mechanisms underlying elite control are currently under intensive investigation, research has revealed that a set of host genetic and acquired factors, as well as specific viral characteristics, contribute to viral containment. One of the central genetic markers consistently associated with control is specific class I HLA molecules, especially HLA-B5701, highlighting the role of potent cytotoxic T cell responses in eliminating HIV-infected cells and restricting the viral reservoir. A significant contribution was also attributed to T helper cells, regulatory T cells and several cell subsets of the innate immune system including natural killer (NK) cells. Studies characterizing viruses from EC found inconsistent results showing both highly mutated viruses with reduced fitness, and virulent, fully replication-competent viruses, leaving open the question of host-mediated control versus intrinsic viral attenuation as the cause for extremely low viral reservoirs in elite controllers. Further understanding of the mechanisms behind spontaneous control of HIV infection is imperative, and might prove important for efforts to develop a prophylactic and therapeutic HIV vaccine.


Protective effects of celery juice in treatments with Doxorubicin.
The aim of this work was to investigate possible protective effect of celery juice in doxorubicin treatment. The following biochemical parameters were determined: content of reduced glutathione, activities of catalase, xanthine oxidase, glutathione peroxidase, peroxidase, and lipid peroxidation intensity in liver homogenate and blood hemolysate. We examined influence of diluted pure celery leaves and roots juices and their combinations with doxorubicine on analyzed biochemical parameters. Celery roots and leaves juices influenced the examined biochemical parameters and showed protective effects when applied with doxorubicine.


A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors.
Indoleamine 2,3-dioxygenase (IDO) is an enzyme that tumors use to create a state of immunosuppression. Indoximod is an IDO pathway inhibitor. Preclinical studies demonstrated that indoximod combined with chemotherapy was synergistic in a mouse model of breast cancer. A phase I 3+3 trial was designed to study the combination of docetaxel and indoximod. Docetaxel was administered at 60 mg/m2 intravenously every 3 weeks dose levels 1-4 and 75 mg/m2 for dose level 5. Indoximod was given at 300, 600, 1000, 2000, and 1200 mg PO twice daily continuously for levels 1-5, respectively. Serum drug levels were measured. Twenty-seven patients were treated, with 22 evaluable for response. DLTs included grade 3 dehydration (level 1), hypotension(level 4), mucositis (level 4) and grade 5 enterocolitis (level 2). Dose level 5 is the recommended phase II dose. The most frequent adverse events were fatigue (58.6%), anemia (51.7%), hyperglycemia (48.3%), infection (44.8%), and nausea (41.4%). There were 4 partial responses (2 breast, 1 NSCLC, 1 thymic tumor). No drug-drug interactions were noted. Docetaxel plus indoximod was well tolerated with no increase in expected toxicities or pharmacokinetic interactions. It was active in a pretreated population of patients with metastatic solid tumors.


Accurate Single-Cell Clustering through Ensemble Similarity Learning.
Single-cell sequencing provides novel means to interpret the transcriptomic profiles of individual cells. To obtain in-depth analysis of single-cell sequencing, it requires effective computational methods to accurately predict single-cell clusters because single-cell sequencing techniques only provide the transcriptomic profiles of each cell. Although an accurate estimation of the cell-to-cell similarity is an essential first step to derive reliable single-cell clustering results, it is challenging to obtain the accurate similarity measurement because it highly depends on a selection of genes for similarity evaluations and the optimal set of genes for the accurate similarity estimation is typically unknown. Moreover, due to technical limitations, single-cell sequencing includes a larger number of artificial zeros, and the technical noise makes it difficult to develop effective single-cell clustering algorithms. Here, we describe a novel single-cell clustering algorithm that can accurately predict single-cell clusters in large-scale single-cell sequencing by effectively reducing the zero-inflated noise and accurately estimating the cell-to-cell similarities. First, we construct an ensemble similarity network based on different similarity estimates, and reduce the artificial noise using a random walk with restart framework. Finally, starting from a larger number small size but highly consistent clusters, we iteratively merge a pair of clusters with the maximum similarities until it reaches the predicted number of clusters. Extensive performance evaluation shows that the proposed single-cell clustering algorithm can yield the accurate single-cell clustering results and it can help deciphering the key messages underlying complex biological mechanisms.


Comparison Between Two Strategies of Topical Treatment in Tar Burn: A Case Report.
The management of tar burns presents a wide range of possible approaches, and several strategies can be used to reduce the damage regarding the removal of tar adhered to the patient's skin. Tar residues should preferably be emulsified with solvent solutions. Due to the low incidence of tar burns, it has not yet been possible to select the appropriate agent for the removal of the adhered tar. In this article, we reported a case of a 47-year-old man with a tar burn in his forehead region and his both upper limbs treated with two different approaches and the outcomes. In the right upper limb, the removal of tar with oil-based on essential fatty acids was attempted at the time of hospital admission, whereas in the left upper limb, he was treated with 1% silver sulfadiazine cream, sterile gauze, and bandage. On the right upper limb, the treatment was eventually performed with debridement and split-thickness skin grafting. On the left upper limb, there was complete re-epithelialization of the burns. The more conservative approach of keeping a dressing with 1% silver sulfadiazine on the tar itself, followed by removing the material in the dressing changes was considered better than the immediate removal of tar with an oily solution, especially about pain. Our impression was that the application of 1% silver sulfadiazine cream at the time of the admission, as well as in the following days, may be beneficial for the removal of the tar in close contact with the skin. Possibly, this approach leads to less trauma to the skin and, eventually, simplifies the treatment of burns by hot tar.


[Cooling shell in renal transplantation. Thermometric evaluation of a prototype].
We have developed a cooling system for renal transplants designed to eliminate the second period of warm ischaemia corresponding to the vascular anastomosis phase of renal transplantation. This is an autonomous and independent system which forms a shell around the transplant. Following application of the system, cooling is achieved by refrigeration of a Multitherm sponge contained in the wall of the shell. The thermometric characteristics of a prototype were evaluated in vitro and in vivo in pigs. This system allows the kidney to be preserved at a temperature of less than 10 degrees C for 1 hour without inducing any risk of lesions of the renal surface. Human applications should be developed in the near future.


Public perceptions of the importance of prognosis in allocating transplantable livers to children.
The system to allocate scarce transplantable livers has been criticized for not giving enough weight to the prognoses of the patients receiving the transplants, but little research has been done looking at how the public weights the relative importances of efficacy and equity in distributing the organs. This study was an experimental survey of prospective jurors asked to distribute transplantable livers among transplant candidates grouped according to their prognoses. The relative prognoses of the transplant candidates were varied across survey versions. As the prognostic difference between transplant groups increased, the subjects became less likely to distribute the organs equally between them (p < 0.005). However, the subjects' willingness to base allocation on prognosis was moderated by a number of factors, including their understanding of how to use prognostic information and their attitudes toward using prognostic information for individuals versus groups. Thus, even when the relative prognoses of transplant groups differed by 60%, less than a fourth of the subjects were willing to give all the organs to the better-prognosis group. Many subjects feel that prognosis is an important consideration in allocating scarce livers. However, few are willing to base allocation purely on maximizing survival. Policies that base allocations purely on outcomes will violate the values of a significant portion of the public.


Nanomaterials: the next step in injectable bone cements.
Injectable bone cements (IBCs) are biocompatible materials that can be used as bone defect fillers in maxillofacial surgeries and in orthopedic fracture treatment in order to augment weakened bone due to osteoporosis. Current clinically available IBCs, such as polymethylmethacrylate and calcium phosphate cement, have certain advantages; however, they possess several drawbacks that prevent them from gaining universal acceptance. New gel-based injectable materials have also been developed, but these are too mechanically weak for load-bearing applications. Recent research has focused on improving various injectable materials using nanomaterials in order to render them suitable for bone tissue regeneration. This article outlines the requirements of IBCs, the advantages and limitations of currently available IBCs and the state-of-the-art developments that have demonstrated the effects of nanomaterials within injectable systems.


Cotinine reduces depressive-like behavior and hippocampal vascular endothelial growth factor downregulation after forced swim stress in mice.
Cotinine, the predominant metabolite of nicotine, appears to act as an antidepressant. We have previously shown that cotinine reduced immobile postures in Porsolt's forced swim (FS) and tail suspension tests while preserving the synaptic density in the hippocampus as well as prefrontal and entorhinal cortices of mice subjected to chronic restraint stress. In this study, we investigated the effect of daily oral cotinine (5 mg/kg) on depressive-like behavior induced by repeated, FS stress for 6 consecutive days in adult, male C57BL/6J mice. The results support our previous report that cotinine administration reduces depressive-like behavior in mice subjected or not to high salience stress. In addition, cotinine enhanced the expression of the vascular endothelial growth factor (VEGF) in the hippocampus of mice subjected to repetitive FS stress. Altogether, the results suggest that cotinine may be an effective antidepressant positively influencing mood through a mechanism involving the preservation of brain homeostasis and the expression of critical growth factors such as VEGF. (PsycINFO Database Record (c) 2014 APA, all rights reserved).


AlphaB-crystallin immunolocalization yields new insights into inclusion body myositis.
To study the expression of the small heat shock protein, alphaB-crystallin (alphaBC), in inclusion body myositis (IBM). In humans, alphaBC is constitutively expressed in the eye lens, muscle, and heart, but not in lymphoid tissues. Induced expression of alphaBC occurs under metabolic stress, in virus-infected lymphocytes, and in degenerative brain lesions, including neurofibrillary tangles and senile plaques in AD. The previously reported pathologic similarities between AD and IBM prompted us to study alphaBC expression in IBM. Immunolocalization of alphaBC in muscle of 11 patients with IBM, 50 patients with other muscle diseases, and 4 controls; and quantitative analysis of the frequency of fibers with 1) increased alphaBC expression in IBM and polymyositis and 2) structural abnormality (vacuolated, non-necrotic and invaded by mononuclear cells, Congo red-positive, SMI-31 positive, and ubiquitin positive) in IBM. We detected enhanced expression of alphaBC not only in all structurally abnormal IBM fibers, but also, and with severalfold higher frequency, in IBM fibers without significant structural abnormality (X fibers) (p values in paired t-tests < 0.001). We also found enhanced alphaBC in abnormal fibers in other diseases; X fibers, however, were extremely sparse or absent, except in two atypical cases of polymyositis refractory to immunotherapy. That the X fibers are much more frequent than the structurally abnormal fibers in IBM points to a pathogenic stressor acting upstream to the development of structural abnormalities. The identification of this stressor is now of paramount importance for deciphering the enigma of IBM.


Measuring Patient Trust in Public versus Private Physicians in the Kingdom of Saudi Arabia (KSA).
This study aims to assess and compare patient trust in public vs private physicians and to determine the factors that can affect the level of trust in the context of the KSA. A cross-sectional study was carried out in the KSA to assess patient trust in physicians. A questionnaire was administered in both Arabic and English to patients above 18 years of age via online channels. A statistically significant difference was found between the level of trust in public vs private physicians, where the public physicians showed higher patients' trust scores compared to private physicians, where the mean was 2.51 (SD=0.60) and 2.29 (SD=0.56), respectively, P-value<0.001. A statistically significant difference was also found between self-assessment health status (SAHS) groups (F(3)=11.429, P=0.010). Other factors were not significantly associated. This study found that public physicians engender a higher level of patient trust than private physicians. A further qualitative study should be conducted in the future to investigate the reasons behind the high trust in public physicians in the KSA. The results of this study open doors for new investigations that might result in the implementation of new interventions to promote patient trust in the healthcare journey in KSA.


Interstitial Lung Fibrosis Imaging Reporting and Data System: What Radiologist Wants to Know?
The aim of this work is to review interstitial lung fibrosis Imaging Reporting and Data System (ILF-RADS) that was designed for reporting of interstitial lung fibrosis (ILF). Findings include pulmonary and extrapulmonary findings and is subsequently designed into 4 categories. Pulmonary findings included lung volume, reticulations, traction bronchiectasis, honeycomb, nodules, cysts, ground glass, consolidation, mosaic attenuation and emphysema, and distribution of pulmonary lesions; axial (central, peripheral and diffuse), and zonal distribution (upper, middle, and lower zones). Complications in the form of acute infection, acute exacerbation, and malignancy were also assessed. Extrapulmonary findings included mediastinal, pleural, tracheal, and bone or soft tissue lesions. The lexicon of usual interstitial pneumonia (UIP) was classified into 4 categories designated as belonging in 1 of 4 categories. Lexicon of ILF-RADS-1 (typical UIP), ILF-RADS-2 (possible UIP), ILF-RADS-3 (indeterminate for UIP), and ILF-RADS-4 (inconsistent with UIP).


Diagnostic algorithm and management of immune-mediated complications associated with subcutaneous insulin therapy.
Immune mediated complications associated with subcutaneous insulin therapy such as insulin neutralizing antibodies and/or skin reactions are rare conditions since human insulin is in general use. Nevertheless, if it occurs, a stepwise diagnostic approach is essential for differential diagnosis and consecutive treatment of these complications. Here we suggest a diagnostic algorithm to deal with e.g. insulin antibody formation of the IgG and/or IgE type and/or severe skin reactions resulting in poor metabolic control and often "brittle diabetes" in affected patients. This diagnostic algorithm includes step 1: Intradermal skin testing with positive and negative controls, additives and different insulin preparations; step 2: Quantification of insulin specific IgG and IgE in the serum, and step 3: Analysis of the time dependent binding/dissociation curves of the insulin neutralizing antibodies in an ex vivo/in vitro assay to assess the clinical significance of these antibodies. Based on 158 insulin treated control subjects and four patients with typical symptoms and signs representing the spectrum of immune-mediated complications subsequent to subcutaneous insulin therapy we demonstrate that the proposed stepwise approach leads to a definite diagnosis as a prerequisite for individual and successful therapy.


Total synthesis of (-)-salicylihalamide A.
[see structure]. A 16-step synthesis of the novel cytotoxin salicylihalamide A (1E) has been achieved in 3.3% overall yield using ring closing metathesis to generate the macrolide and addition of (1Z,3Z)-hexadienylcuprate (2), which was generated in situ from ethylcuprate and acetylene, to alkenyl isocyanate 3 to form the side chain.


Differences in the impedance of cochlear implant devices within 24 hours of their implantation.
Cochlear implantation is a surgical procedure, which is performed on severely hearing-impaired patients. Impedance field telemetry is commonly used to determine the integrity of the cochlear implant device during and after surgery. At the Department of Otolaryngology, Cheng Hsin General Hospital (Taipei, Taiwan), the cochlear implant devices are switched on within 24 hours of their implantation. In the present study, the impedance changes of Advanced Bionics™ cochlear implant devices were compared with previous studies and other devices. The aim was to confirm previous hypotheses and to explore other potential associated factors that could influence impedance following cochlear implantation. The current study included 12 patients who underwent cochlear implantation at Cheng Hsin General Hospital with Advanced Bionics cochlear implant devices. The cochlear devices were all switched on within 24 hours of their implantation. The impedance was measured and compared across all contact channels of the electrode, both intra-operatively and post-operatively. The intra-operative impedance was compared with the switch-on impedance (within 24 hours of the cochlear implantation); the impedance was notably increased for all contact channels at switch-on. Of the 16 channels examined, 4 channels had a significant increase in impedance between the intra-operative measurement and the switch-on measurement. To the best of our knowledge, the impedance of a cochlear implant device can be affected by the diameter of the electrode, the position of the electrode arrays in the scala tympani, sheath formation and fibrosis surrounding the electrode after implantation and electrical stimulation during or after surgery. When the results of the current study were compared with previous studies, it was found that the impedance changes were opposite to that of Cochlear™ implant devices. This may be explained by the position of the electrode arrays, sheath formation, the blow-out effect and differences in electrical stimulation.


Metachronous Double Pituitary Adenoma with Altered Transcriptional Factor Profile: A Case Report and Literature Review.
Double pituitary adenomas (DPAs), especially metachronous DPAs, are extremely rare and there has been no report about DPAs with altered transcriptional factors. We describe the case of a 25-year-old man who presented with acromegaly 7 years after surgery for a non-functioning pituitary adenoma (NFPA). Before the initial surgery, endocrine evaluation confirmed NFPA or silent somatotroph pituitary adenoma (SPA) because of normal serum levels of insulin-like growth factor-1 (IGF-1) and insufficient suppression of growth hormone (GH) levels in the oral glucose tolerance test (OGTT). Immunohistochemistry of resected tissue obtained from gross total resection (GTR) with transsphenoidal surgery (TSS) was negative for follicle-stimulating hormone, luteinizing hormone, GH, and Pit-1 but positive for GATA3, which confirmed the gonadotroph pituitary adenoma (GPA) diagnosis. Seven years later, follow-up brain MRI revealed a 13.3 × 5.6 × 4.7 mm tumor within the sellar turcica. The endocrine evaluation confirmed acromegaly because of high serum levels of IGF-1 and insufficient suppression of GH levels upon OGTT. GTR with TSS was again performed, and immunohistochemistry was negative for GATA3 but positive for GH and Pit-1. Surprisingly, he showed altered transcription factor expressions between initial and recurrent surgery. Based on the overall clinical course and hormonal secretion findings, we speculated metachronous development of a DPA, i.e., SPA followed by GPA, wherein a few remaining cells of the SPA might have regrown after the initial surgery. We conducted a literature review of cases that documented altered hormone secretion at recurrence and emphasized the necessity of identifying a small adenoma when there is a discrepancy between pathological findings and hormone secretion tests.


A physiological analysis of hyponatremia: implications for patients on peritoneal dialysis.
The basis for hyponatremia is a negative balance for sodium (Na+) plus potassium (K+) and/or a positive balance for water. In patients with normal renal function, vasopressin is needed to prevent the excretion of electrolyte-free water. Vasopressin is not important when there is little residual renal function. If hyponatremia is accompanied by a quantitatively appropriate gain in weight, this implies that a gain of electrolyte-free water was the basis for hyponatremia. In the absence of this weight gain, a loss of salts is to be suspected. If the extracellular fluid (ECF) volume is obviously low, hyponatremia is due to a deficit of NaCl, unless there is a deficit of K+. With a KCl deficit and a contracted ECF volume, there should also be a large shift of Na+ into cells, so metabolic alkalosis would not be an expected finding. In contrast, those patients with no change in weight who have a normal or expanded ECF volume are subdivided into those with a gain of solutes restricted to the ECF compartment (glucose, mannitol), or those with a deficit of solutes of intracellular fluid origin, which implies that a catabolic state (malnutrition) may be present.


[Nutritional recommendations, supplementation, and physical activity program following Roux-en-Y gastric bypass for morbid obesity].
The number of gastric bypass operations (RYGB) needed worldwide is increasing annually due to the obesity epidemic.Yet the success of this treatment is only guaranteed if an appropriate exercise therapy, a corresponding change of diet, and an adequate supplementation take hold in the aftercare program.Subject to pre-existing musculoskeletal diseases, exercise therapy should start about 4 weeks after the operation and comprise alternating cardiovascular and connective tissue-restitution training. The required change of diet focuses on small portions of calorie-reduced as well as protein- and vitamin enriched food. The standard daily intake should be between 800 and 1,200 kcal. However, after RYGB, nutritive deficiencies have been registered for proteins in 1-3%, for iron in 45-52%,vitamin B12 in 33-37%, folic acid in about 35%, calcium in 10-12%, and vitamins in 10-45% of the patients. For this reason,laboratory analysis at regular intervals is necessary in the follow-up and an appropriate supplementation of minerals, vitamins,and trace elements must be implemented.


Effect of ritanserin, specific 5HT-2 antagonist, on PRL secretion in normal subjects and in different hyperprolactinaemic conditions.
The availability of a new specific anti 5HT-2 compound, ritanserin (RTS), led us to further investigate the role of serotonin in controlling PRL secretion. The drug was administered to normoprolactinaemic subjects and to patients with differing hyperprolactinaemic conditions. While RTS failed to modify PRL levels in normoprolactinaemic subjects and in patients with PRL-secreting pituitary adenomas, a marked decrease in the hormone was obtained in patients with functional and puerperal hyperprolactinaemia. The lack of effect of RTS in PRL-secreting pituitary adenomas suggests that the reported suppression of PRL by other antiserotoninergic drugs, such as metergoline, is probably due to their concomitant dopaminergic activity.


Reasoning about other people's beliefs: bilinguals have an advantage.
Bilingualism can have widespread cognitive effects. In this article we investigate whether bilingualism might have an effect on adults' abilities to reason about other people's beliefs. In particular, we tested whether bilingual adults might have an advantage over monolingual adults in false-belief reasoning analogous to the advantage that has been observed with bilingual children. Using a traditional false-belief task coupled with an eye-tracking technique, we found that adults in general suffer interference from their own perspective when reasoning about other people's beliefs. However, bilinguals are reliably less susceptible to this egocentric bias than are monolinguals. Moreover, performance on the false-belief task significantly correlated with performance on an executive control task. We argue that bilinguals' early sociolinguistic sensitivity and enhanced executive control may account for their advantage in false-belief reasoning.


Eye muscles surgery.
In the past year, experimental studies have analyzed instrument-induced measurement errors during strabismus surgery, investigated intraoperative variables pertinent to adjustable sutures, and investigated ways to prevent and create adhesions in animal models. Newer surgical techniques include coincident resection and recession of a rectus muscle, recession and resection without placement of scleral sutures, and modification of graded anterior transposition of the inferior obliques. Ocular motility problems related to thyroid ophthalmopathy, or lost muscles, as well as those occurring after surgery for retinal detachment remain a challenge. Patients may avoid the risks associated with the use of topical corticosteroids after strabismus surgery by using nonsteroidal anti-inflammatory drugs in their place. Recent contributions to the literature on these issues are reviewed here.


[Superoxide dismutase encapsulated erythrocytes used in the study of cerebral ischemia-reperfusion].
The possibility of using red blood cells (RBC) as the carrier of superoxide dismutase (SOD) was studied in this paper. SOD was encapsulated into rabbit erythrocytes (RBC-SOD), and was used in the study of cerebral ischemia-reperfusion (I-R). The effect of RBC-SOD on cerebral I-R was observed. The circulation half-life (T1/2) of RBC-SOD was determined in rabbits by 51Cr radiolabel. T1/2 was 13.4 +/- 1.5 days (n = 6) for RBC, and T1/2 was 13.7 +/- 1.0 days (n = 5) for RBC-SOD. The increase of lipid peroxidation (LPO) during cerebral I-R was inhibited by RBC-SOD. The maximum concentration of nitric oxide (NO) in plasma occurred in 10 minutes following reperfusion. The concentration of nitric oxide reduced gradually as reperfusion continued in both control and SOD groups, but it remained at a relatively high level continuous during the 4.5 hours of reperfusion in RBC-SOD group. These results indicate that intact RBC-SOD could scavenge superoxide anion (O2-.) produced during cerebral I-R.


Contribution of parental psychopathology to offspring smoking and nicotine dependence in a genetically informative design.
It is not known if parental psychiatric disorders have an independent effect on offspring smoking after controlling for genetic and environmental vulnerability to nicotine dependence. We tested if parental alcohol, drug, or conduct disorders; antisocial personality disorder; depression; and anxiety disorders remained significant predictors of offspring smoking initiation, regular smoking, and nicotine dependence before and after adjusting for genetic and environmental risk for nicotine dependence. Data were obtained via semi-structured interviews with 1,107 twin fathers, 1,919 offspring between the ages of 12 and 32, and 1,023 mothers. Genetic and environmental liability for smoking outcomes was defined by paternal and maternal nicotine dependence. Multinomial logistic regression models were computed to estimate the risk for offspring trying cigarettes, regular smoking, and the Fagerström Test for Nicotine Dependence (FTND) as a function of parental psychopathology and sociodemographics before and after adjusting for genetic and environmental vulnerability to nicotine dependence. Before adjusting for genetic and environmental risk for nicotine dependence, ever trying cigarettes was associated with maternal depression, regular smoking was associated with maternal alcohol dependence and maternal conduct disorder, and FTND was associated with paternal and maternal conduct disorder and antisocial personality disorder. No parental psychopathology remained significantly associated with regular smoking and FTND after adjusting for genetic and environmental vulnerability to nicotine dependence in a multivariate model. The association between parental psychopathology and offspring smoking outcomes is partly explained by genetic and environmental risk for nicotine dependence. Point estimates suggest a trend for an association between parental antisocial personality disorder and offspring regular smoking and nicotine dependence after adjusting for genetic and environmental vulnerability. Studies in larger samples are warranted.


cis,cis,cis-(Acetato-κ(2) O,O')bis-[1,2-bis-(diphenyl-phosphan-yl)ethane-κ(2) P,P']ruthenium(II) 0.75-trifluoro-methane-sulfonate 0.25-chloride.
In the title Ru(II) carboxyl-ate compound, [Ru(C2H3O2)(C26H24P2)2](CF3O3S)0.75Cl0.25, the distorted tris-bidentate octa-hedral stereochemistry about the Ru(II) atom in the complex cation comprises four P-atom donors from two 1,2-bis-(diphenyl-phosphan-yl)ethane ligands [Ru-P = 2.2881 (13)-2.3791 (13) Å] and two O-atom donors from the acetate ligand [Ru-O = 2.191 (3) and 2.202 (3) Å]. The disordered counter-anions are located on the same site in the structure in a 3:1 ratio, the expanded formula comprising four complex cations, three trifluoro-methane-sulfonate anions and one chloride anion, with two such formula units in the unit cell.


PLC gamma 1 Src homology domain induces mitogenesis in quiescent NIH 3T3 fibroblasts.
Previously, we demonstrated that microinjection of phosphoinositide-specific phospholipase C gamma 1 (PLC gamma 1) and lipase-defective mutants of PLC gamma 1 induced G(0) growth arrested NIH 3T3 fibroblasts to enter S phase of the cell cycle. These experiments suggested that regions other than the catalytic domain of PLC gamma 1 may be responsible for inducing mitogenesis. To test other regions of PLC gamma 1 for DNA synthesis inducing activity, cDNA fragments encoding Src homology (SH) and pleckstrin homology (PH) domains were subcloned into the bacterial expression plasmid pGEX-2TK, and the GST fusion proteins were purified. The complete PLC gamma l SH domain peptide was found to induce DNA synthesis after microinjection into growth arrested fibroblasts. Peptides containing a single SH3 domain or two SH2 domains induced a partial response that was restored to full activity if they were co-injected. The PH domain peptide did not induce DNA synthesis. Thus, both SH3 and SH2 activity combine to give maximum DNA synthesis induction, demonstrating that non-catalytic structural domains of PLC gamma 1 have pronounced effects on mitogenic signaling pathways.


A serological survey of canine respiratory coronavirus in New Zealand.
Aims: To determine the seroprevalence of canine respiratory coronavirus (CRCoV) in New Zealand dogs, and to explore associations with age, sex, breed, month, and geographical region of sampling and reported presence of clinical signs suggestive of respiratory disease.Methods: A total of 1,015 canine serum samples were randomly selected from submissions to a diagnostic laboratory between March and December 2014, and were analysed for CRCoV antibodies using a competitive ELISA. Logistic regression analysis was used to determine associations between seroprevalence of CRCoV and breed category, age, sex, sampling month, region, and reported health status of dogs.Results: Overall, 538/1,015 (53.0%) samples were seropositive for CRCoV, with 492/921 (53.4%) positive dogs in the North Island and 46/94 (49%) in the South Island. Age of dog, sampling month, region, and presence of abnormal respiratory signs were included in the initial logistic regression model. Seroprevalence was higher in dogs aged ≥3 compared with ≤2 years (p < 0.01). The lowest seroprevalence was observed in July (30/105; 28.5%) and August (32/100; 32%), and the highest in June (74/100; 74%). Seroprevalence in dogs from Auckland was higher than in dogs from the Hawkes Bay, Manawatu, Marlborough, and Waikato regions (p < 0.05). Abnormal respiratory signs (coughing, nasal discharge, or sneezing) were reported for 28/1,015 (2.8%) dogs sampled. Seroprevalence for CRCoV tended to be higher among dogs with respiratory signs (67.9 (95% CI = 47.6-83.4)%) than dogs with no reported respiratory signs (52.6 (95% CI = 49.5-55.7)%).Conclusions: Serological evidence of infection with CRCoV was present in more than half of the dogs tested from throughout New Zealand. Differences in CRCoV seroprevalence between regions and lack of seasonal pattern indicate that factors other than external temperatures may be important in the epidemiology of CRCoV in New Zealand.Clinical relevance: Our data suggest that CRCoV should be included in investigations of cases of infectious canine tracheobronchitis, particularly if these occur among dogs vaccinated with current vaccines, which do not include CRCoV antigens.


Five-year experience with Crossfire highly cross-linked polyethylene.
Our purpose was to compare the clinical wear performance of highly cross-linked (Crossfire) polyethylene with conventional (N2Vac) polyethylene total hip bearings. We implanted 56 hips (47 patients) with Crossfire acetabular bearing liners and compared their wear performance with 53 conventional polyethylene inserts. Wear and clinical data were collected retrospectively at a minimum 4-year and average 5-year followup. The linear femoral head penetration rate measured from plain radiographs was 0.055 mm/year +/- 0.022 mm/year for the Crossfire polyethylene and 0.138 mm/year +/- 0.073 mm/year for the control, a reduction of 60% for the Crossfire components. Calculated annual wear was 0.036 mm/year for the Crossfire components and 0.131 mm/year for the controls, a reduction of 72%. Radiographic review at most recent followup showed a reduction in erosive osteolytic lesions of the proximal femur for the Crossfire components compared with controls, also suggesting a reduction in debris release for the Crossfire components. Complications leading to revision were not seen in the Crossfire or control groups. These clinical findings suggest that this particular highly cross-linked polyethylene can provide wear reduction and an alternate bearing surface for active patient populations. Therapeutic study, Level III (retrospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.


[HCV+ patients on the waiting list for kidney transplantation. Retrospective analysis of data on the patient population with hepatitis C on the waiting list for kidney transplantation in the setting of the AIRT].
HCV infection in hemodialysis is still a matter of debate from an epidemiological and clinical point of view. Evaluation criteria for HCV-infected patients as transplant candidates are still not adequately standardized. Aims of the present study were to investigate: 1. the percentage of HCV positive patients on the waiting list of three Italian regions belonging to the Associazione InterRegionale Trapianti (AIRT); 2. to analyze the clinical approach in the evaluation of these patients in the attempt to define national guidelines for their pre- and post-transplant management. We evaluated 2045 uremic patients on the waiting lists of four transplant centers (Bari, Bologna, Modena, Novara) belonging to AIRT at 31/12/2002. The overall prevalence of HCV positive patients was 14.2%, with a peak in the Puglia waiting list. The most common screening tests were AST and ALT serum levels and viral load (HCV RNA). Although there is a clear evidence that histological parameters are the main diagnostic and prognostic markers, a liver biopsy was performed in only 9.5% of patients. An even smaller percentage of HCV-infected patients underwent anti-viral therapy. Our retrospective analysis evidenced the need to improve common clinical strategies in approaching HCV-infected canditates to renal transplantation in the attempt to improve their post-transplant outcome.


Inhibition of human bone marrow progenitors by the synthetic tetrapeptide AcSDKP.
The purpose of this work was to study the effects of a tetrapeptide, acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of spleen colony-forming unit (CFU-S) entry into DNA synthesis, on human progenitor cells. Normal human mononuclear cells were incubated with concentrations of the synthetic tetrapeptide ranging from 10(-12) to 10(-7) M for 1.5 and 24 h and then plated in methylcellulose in the presence of human placenta-conditioned medium and recombinant human erythropoietin. The proportion of progenitors in DNA synthesis was determined by the thymidine suicide assay. Incubation with AcSDKP for 24 h leads to a significant inhibition of granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth and in some cases of erythroid colony-forming unit (CFU-E) growth. The inhibition, which was never greater than 50%, was obtained with 10(-10)-10(-9) M AcSDKP, whereas no effect was seen at higher concentrations. The percentage of CFU-GM, BFU-E, and CFU-E in DNA synthesis was significantly reduced in five consecutive patients after incubation of cells for 24 h with inhibitory doses of the peptide, indicating that it is active on cycling cells. Therefore, these studies provide the first evidence that the tetrapeptide AcSDKP, originally obtained from bovine marrow and now chemically synthesized, is able to inhibit the in vitro growth of human progenitors and to decrease their proportion in cell cycle.


Listening to patients with cancer: using a literary-based research method to understand patient-focused care.
In spite of considerable attention, patients diagnosed with cancer continue to report poor experiences of care. The root causes of this remain unclear. This exploratory study aimed to investigate new ways of understanding the experience of patients with cancer, using a literary-based research approach. Interviews were undertaken with four patients diagnosed with high-grade brain cancers at least 6 months from diagnosis and with people (n=5) identified by the patients as important in their care pathway. Interview transcripts were analysed by humanities academics as pieces of literature, where each patient's story was told from more than one person's perspective. The academics then came together in a facilitated workshop to agree major themes within the patient experiences. The themes were presented at a patient and carer event involving 70 participants to test the validity of the insights. Insights into the key issues for patients with cancer could be grouped into six themes: accountability; identity; life context; time; language; rigour and emotion. Patients often held a different perspective to the traditionally held medical views of what constitutes good care. For example, patients did not see any conflict between a doctor having scientific rigour and portraying emotion. One key feature of the approach was its comparative nature: patients often held different views from those traditionally held by physicians of what constitutes health and good outcomes. This revealed aspects that may be considered by healthcare professionals when designing improvements. Proposals for further testing are discussed, with a particular emphasis on the need for sensitivity to individual differences in experiences.


Yeast-derived recombinant DG42 protein of Xenopus can synthesize hyaluronan in vitro.
We demonstrate in this report that the Xenopus DG42 gene product made in the yeast Saccharomyces cerevisiae can synthesize authentic high molecular weight hyaluronan (hyaluronic acid; HA) in vitro. Saccharomyces are eukaryotes that do not naturally produce HA or any other molecules known to contain glucuronic acid. Therefore bakers' yeast is a good model system to determine the enzymatic activity of the DG42 protein, which is the topic of recent debate. Membrane extracts prepared from cells expressing DG42 encoded on a plasmid incorporated [14C]glucuronic acid and N-[3H]acetylglucosamine from exogenously supplied UDP-sugar nucleotides into a high molecular mass (10(6) to 10(7) Da) polymer in the presence of magnesium ions. Both sugar precursors were simultaneously required for elongation. Control extracts prepared from cells with the vector plasmid alone or the DG42 cDNA in the antisense orientation did not display this activity. The double-labeled polysaccharide product synthesized in vitro was deemed to be HA by enzymatic analyses; specific HA lyase could degrade the polymer, but it was unaffected by protease or chitinase treatments. The fragments generated by HA lyase were identical to fragments derived from authentic vertebrate HA as compared by high performance liquid chromatography. We conclude that DG42 is a membrane-associated HA synthase capable of transferring both glucuronic acid and N-acetylglucosamine groups.


Cross-sectional study of the use of antimicrobials following common infections by rural residents in Anhui, China.
To describe help seeking behaviour from a medical doctor and antimicrobial use for common infections among rural residents of Anhui province, China. A cross-sectional retrospective household survey. 12 administrative villages from rural Anhui, China. 2760 rural residents selected through cluster-randomised sampling using an interviewer administered questionnaire. Logistic regression models were used to estimate associations between exposures (health insurance and antimicrobial-related knowledge), adjusted for confounders (sex, age and education), and help-seeking behaviour from a medical doctor and antimicrobial use following common infections, including acute respiratory tract infections (ARTIs), gastrointestinal tract infections (GTIs) and urinary tract infections (UTIs). In total 2611 (94.6%) rural residents completed the questionnaire. Help seeking from a medical doctor was highest for ARTIs (59.4%) followed by GTIs (42.1%), and UTIs (27.8%). Around two-thirds (82.3% for ARTIs, 87.0% for GTIs and 66.0% for UTIs) of respondents sought help within 3 days following symptom onset and over three quarters (88% for ARTIs, 98% for GTIs and 77% for UTIs) reported complete recovery within 7 days. Of the help-seeking respondents, 94.5% with ARTI symptoms recalled being prescribed either oral or intravenous antimicrobials (GTIs 81.7% and UTIs 70.4%). Use of antimicrobials bought from medicine shops without prescriptions ranged from 8.8% for GTIs to 17.2% for ARTIs; while use of antimicrobials leftover from previous illnesses or given by a relative ranged from 7.6% for UTIs to 13.4% for ARTIs. Multivariate logistic regression analysis revealed that respondents with a higher antimicrobial-related knowledge score and lack of insurance were associated with lower levels of help-seeking for ARTIs; while respondents with a higher antimicrobial-related knowledge score were less likely to be prescribed either oral or intravenous antimicrobials. Excessive antimicrobial use in the studied primary care settings is still prevalent.


[Percutaneous ethanol injection therapy for hepatocellular carcinoma in hepatic dome directly under right diaphragma--the trial of artificial ascites method].
We tried to infuse 40 approximately 100 ml saline solution into abdominal cavity (artificial ascites method) in case of percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC) in hepatic dome directly under right diaphragma (hepatic dome) which is considered as dead space on ultrasonography. Consequently broad visual field was acquired on ultrasonogram and puncture to HCC in hepatic dome was able to be performed very easily. There were no side effects such as difficult hemostasis and peritoneal dissemination. It was concluded that artificial ascites method is very useful to widen visual field of hepatic dome on ultrasonogram and therefore dead space on PEIT disappeared by this method.


Mental health and quality of life outcomes in family members of patients with chronic critical illness admitted to the intensive care units of two Brazilian hospitals serving the extremes of the socioeconomic spectrum.
Chronic critical illness (CCI) is a relevant clinical, social and financial health issue. The aim of this study was to compare the mental outcomes (symptoms of anxiety and depression) and quality of life outcomes of the family members of patients with CCI from different socioeconomic backgrounds who were admitted to one of the intensive care units (ICUs) in two Brazilian hospitals, one private and one public. It is a prospective study involving a public hospital that serves a low-income population and a tertiary private hospital that serves a high-income population. Family members of patients with CCI answered the Hospital Anxiety and Depression Scale (HADS) and The World Health Organization Quality of Life-WHOQOL-bref questionnaires. They responded to the European Quality of life Five Dimension three Level (EuroQol-5D-3L) and the Activities of Daily Living (ADL) questionnaires on behalf of the patients at three time points: during the ICU stay, 30 and 90 days after the patient was discharged. We used logistic regression models to evaluate the main predictors of a binary outcome regarding symptoms of anxiety and depression. We enrolled 186 patients with CCI. Many patients from public hospitals who were independent became dependent for their ADLs at 90 days (41.7% versus 14.3%, p = 0.03). At 30 days, family members from public hospital had worse impact on all domains of WHOQOL-bref compared with families from private hospital. At 90-days, the difference persists in the physical domain, worse for families from public hospital (p = 0.006). The symptoms of depression at 30-days (p = 0.008) and at 90-days (p = 0.013) were worse in the public hospital. CCIs affected quality of life and the emotional condition of family members, especially in families with fewer resources when the patients became more dependent. Family members with higher education were more likely to experience depression, while depression was associated with cohabiting with the patient in low-income families.


Understanding structures and hydrogen bonds of ionic liquids at the electronic level.
Due to their unique properties, ionic liquids (ILs) have attracted the academic and industrial attentions. However, recent controversies have focused on what are the main forces to determine the behaviors of ILs. In this work, a detailed DFT calculation was carried out to investigate the intermolecular interactions in two typical ILs, [Emim][BF(4)] and [Bmim][PF(6)]. The results indicate that hydrogen bonds (H-bonds) are the major intermolecular structural feature between cations and anions. Although the electrostatic force remains the major noncovalent force (70% of the total energy by energy decomposition calculation), the interaction energies calculated at different theoretical levels indicate that H-bond and van der Waals interactions cannot be ignored. However, the H-bonded capacities from natural bond orbital (NBO) delocalization energies do not show the consistent changes in the total interaction energies and number of H-bonds. Based on the canonical orbitals analysis, it is found that the σ-type orbital overlap and the partial charges transfer between anion and cation, finally, result in the significant energy reduction and rationalize the preferable location of anion, which is an essential understanding for the interaction and structure in the ion pair. Additionally, the strong agreement between the experimental IR spectra and the calculated vibrations implies that the structures of the larger ion clusters provide a reasonable depiction for bulk ILs at room temperature condition.


P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin.
Digoxin is a drug with a narrow therapeutic index, which is substrate of the ATP-dependent efflux pump P-glycoprotein. Increased or decreased digoxin plasma concentrations occur in humans due to inhibition or induction of this drug transporter in organs with excretory function such as small intestine, liver and kidneys. Whereas particle size, dissolution rate and lipophilic properties have been identified as determinants for absorption of digitalis glycosides, little is known about P-glycoprotein transport characteristics of digitalis glycosides such as digitoxin, alpha-methyldigoxin, beta-acetyldigoxin and ouabain. Using polarized P-glycoprotein-expressing cell lines we therefore studied whether these compounds are substrates of P-glycoprotein. Polarized transport of digitalis glycosides was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells (LLC-PK1 cells stably transfected with the human MDR1 P-glycoprotein). Inhibition of P-glycoprotein-mediated transport of these compounds in Caco-2 cells was determined using the cyclosporine analogue PSC-833 (valspodar) as inhibitor of P-glycoprotein. No polarized transport was observed for ouabain. However, basal-to-apical transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin was greater than apical-to-basal transport in Caco-2 and L-MDR1 cells. In Caco-2 cells net transport rates of these compounds were similar to those of digoxin (digoxin: 16.0+/-4.4%, digitoxin: 15.0+/-3.3%, beta-acetyldigoxin: 16.2+/-1.6%, alpha-methyldigoxin: 13.5+/-4.8%). Furthermore, polarized transport of these compounds could be completely inhibited by 1 microM PSC-833. In summary, these data provide evidence that not only digoxin, but also digitoxin, alpha-methyldigoxin and beta-acetyldigoxin are substrates of P-glycoprotein.


Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk.
Transcriptomics data have been integrated with genome-wide association studies (GWASs) to help understand disease/trait molecular mechanisms. The utility of metabolomics, integrated with transcriptomics and disease GWASs, to understand molecular mechanisms for metabolite levels or diseases has not been thoroughly evaluated. We performed probabilistic transcriptome-wide association and locus-level colocalization analyses to integrate transcriptomics results for 49 tissues in 706 individuals from the GTEx project, metabolomics results for 1,391 plasma metabolites in 6,136 Finnish men from the METSIM study, and GWAS results for 2,861 disease traits in 260,405 Finnish individuals from the FinnGen study. We found that genetic variants that regulate metabolite levels were more likely to influence gene expression and disease risk compared to the ones that do not. Integrating transcriptomics with metabolomics results prioritized 397 genes for 521 metabolites, including 496 previously identified gene-metabolite pairs with strong functional connections and suggested 33.3% of such gene-metabolite pairs shared the same causal variants with genetic associations of gene expression. Integrating transcriptomics and metabolomics individually with FinnGen GWAS results identified 1,597 genes for 790 disease traits. Integrating transcriptomics and metabolomics jointly with FinnGen GWAS results helped pinpoint metabolic pathways from genes to diseases. We identified putative causal effects of UGT1A1/UGT1A4 expression on gallbladder disorders through regulating plasma (E,E)-bilirubin levels, of SLC22A5 expression on nasal polyps and plasma carnitine levels through distinct pathways, and of LIPC expression on age-related macular degeneration through glycerophospholipid metabolic pathways. Our study highlights the power of integrating multiple sets of molecular traits and GWAS results to deepen understanding of disease pathophysiology.


Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer.
The presence of circulating DNA in plasma of patients with malignant neoplasm has been a known fact for over 30 years. Since then, the concentration of free circulating plasma DNA has been studied as well as the genetic alterations and epigenetic alterations of tumour DNA of patients that suffer from various types of tumours. The analysis of circulating plasma DNA may be a useful marker to get an early diagnosis on malignant neoplasms. This study has been specifically designed to validate the quantification of circulating DNA in order to design a test useful for the early identification of non-small cell lung cancer patients and the monitoring of lung cancer progression. A second aim of this work is the sensibility and specificity evaluation of such method for future applications. The quantity of plasma DNA was determined using quantitative Real-Time PCR with amplification of the human telomerase reverse transcriptase (hTERT) gene in 151 patients that suffer from lung cancer and 79 healthy controls. The performance of the test was evaluated with a ROC curve. The relationship between the DNA concentration and main demographic, clinical and pathological variables was examined with logistic regression models as well as multiple linear regression models. The concentration of circulating plasma DNA was about four times higher in patients with lung cancer with respect to the controls (12.8 vs 2.9 ng/mL). The area under the ROC curve was 0.79 (95% CI, 0.710-0.83). The concentration of circulating DNA proved to be an important risk factor for the presence of the illness and a prognostic index in the follow-up. The use of quantitative Real-Time PCR revealed that higher values of circulating DNA can be found in patients with lung neoplasm compared to the healthy controls. This could have practical implications such as the use in screening programs and a possible prognostic significance in the follow-up.


Effects of intraoperative colloid administration on outcome in a population-based general surgical cohort: a propensity score analysis.
Many studies on colloids have recently been retracted, leaving us with uncertain evidence of their safety. We aimed to analyze whether intraoperative colloid administration is associated with postoperative complications. The prospectively compiled database of the ARISCAT study of a large, representative cohort of general surgical patients was reanalyzed to compare outcomes according to whether intraoperative colloids were administered or not; a propensity score was used to adjust for potential confounders. The primary outcomes were major postoperative complications. Secondary outcomes were postoperative hospital-free days within 90 days and mortality at 30 and 90 days. In a retrospective survey we asked each center's data collectors to estimate the proportions of the different colloids administered during the study period. Of 2462 patients analyzed, 556 (22.6%) received some type of colloid intraoperatively. The median (25th-75th percentile) of total fluids administered was significantly higher in patients receiving colloids (10.0 [6.9-14.1] mL·kg-1·h-1 vs. 8.8 [6.0-12.8] mL·kg-1·h-1 for patients not receiving colloids; P<0.01). The median volume of colloids administered was 7.5 (6.3-10.4) mL·kg-1. An estimated 75.7% of the patients received third-generation hydroxyethyl starches (130/0.4). Significantly associated complications, after propensity score adjustment, were atelectasis, respiratory infection, bronchospasm, arrhythmia, sepsis, paralytic ileum, and hyperglycemia. Patients receiving colloids had 1.9 fewer postoperative hospital-free days (P<0.006). There were no significant differences in 30- and 90-day mortality. Our study suggests an association of intraoperative colloid administration, mainly of 130/0.4 hydroxyethyl starches, with diverse major postoperative complications and longer hospital stay. Controlled studies are urgently needed to assess the safety profile of colloid use in surgical patients.


[Anxiety disorders in children and adolescents. Psychotherapeutic interventions].
Anxiety disorders are among the most prevalent mental health problems in childhood and adolescence. In this article authors share their experience working with anxiety disorders in inpatient department. Fifty four case histories were analyzed. Authors present, which part of psychiatric disorders takes the anxiety disorders and how they distribute according to ICD-10 diagnostic categories. Anxiety disorders' risk factors, main clinical symptoms and psychotherapeutic methods are discussed.


Nursing in the People's Republic of China.
In June, 1994 Dr. Grayce Roessler led a group of nurses to China to attend and present at international nursing conferences in Beijing and Shanghai. Dr. Roessler, an internationally known transcultural nursing leader, has traveled extensively in China (some 36 trips over 20 years). Her first trip to China, focused on nursing, took place in the fall of 1981 as a member of the American Nurses Association (ANA). The ANA group was invited to China by the Chinese government and the Chinese Nurses Association (CNA). Subsequent to that visit, she became involved in working with the Chinese Ministry of Health, the Chinese Nurses Association, and several of the CNAs in various cities throughout China. In an effort to assist in the preparation of Chinese nurses as teachers and administrators in the evolving health care system, Dr. Roessler facilitated a one year (1985-86) study program in the United States (Golden West College, Huntington Beach, California) for a group of 20 Chinese nurses. It was the first time in history that a number of Chinese nurses had studied at one institution with American nurses in the United States. Dr. Roessler has since coordinated several international conferences in China and arranged for American nurse experts in various fields to present at these meetings. In addition, she has traveled independently as a teacher and consultant and has taken numerous nursing study tour groups to many countries as part of continuing educational experiences. In this issue of the Journal of Transcultural Nursing, Dr. Roessler presents her reflections on nursing in China from a historical and transcultural nursing leader's perspective.


Damage control for new corporate ventures.
In the aggregate, corporations lose billions on new ventures. Here's a venture cost management program that can save fortunes by keeping the cost of losers down while accelerating the success of the winners.


The impact of publication of Australian treatment recommendations for DCIS on clinical practice: A population-based, "before-after" study.
Clinical practice guidelines/recommendations have been promoted as a mechanism for ensuring evidence-based medicine. We examine the impact of the publication of Australian treatment recommendations (ATR) for ductal carcinoma in situ (DCIS) on clinical practice and surgeons' attitudes to the ATR. All new cases of DCIS diagnosed in the 12-months immediately before the ATR release (pre-ATR: September 2002 to August 2003) and three years later (post-ATR: September 2006 to August 2007) were identified from the state of Victoria's population cancer registry. Treatment information, extracted for each case by treating surgeon or study manager, was available for 342 of 353 (97%) tumours pre-ATR and 371 of 378 (98%) tumours post-ATR. Sixty-three surgeons (58% response) completed a survey on awareness and attitudes to the ATR. The proportion of cases undergoing image-guided biopsy, or breast conservation surgery (BCS) did not change between surveys nor did extent of surgical margins. Compared to the pre-ATR period, more BCS cases were referred to a radiation oncologist (67% versus 58%) and more received radiotherapy (53% versus 44%) post-ATR. Tumours greater than 20 mm, of intermediate grade and moderate necrosis were more likely to receive radiotherapy post-ATR. While surgeons agreed with most recommendations, items reflecting radiotherapy recommendations generated most disagreement. With the possible exception of adjuvant radiotherapy, most DCIS cases were treated according to treatment recommendations before the ATR's release. The lack of change in radiotherapy for low grade, smaller tumours may reflect surgeon's uncertainty regarding this therapy for all BCS treated cases.


Censuses of population and housing in Africa: some issues and problems.
"A census of population and housing, which contributes immensely to the development of social statistics and national statistical services in general, has been carried out at least once in every African country except Chad. The common issues and widespread practices of design, implementation, processing, and evaluation of this census are reviewed. Also reviewed are the problems that arise at each of these stages of conducting the census; problems arising as a result of the socio-economic and physical peculiarities of African conditions."


When is bacterial vaginosis not bacterial vaginosis?--a case of cervical carcinoma presenting as recurrent vaginal anaerobic infection.
Vaginal anaerobic infection is the most common cause of vaginal discharge in women. We present a case of recurrent vaginal anaerobic infection and cervical carcinoma and discuss the association of the two conditions. More frequent cytology/colposcopy may be indicated in women who give a history of recurrent or persistent vaginal anaerobic infection.


Antibodies to native and denatured deoxyribonucleic acid in systemic lupus erythematosus.
The relative reactivities with native and denatured DNA of 35 lupus sera were investigated by quantitative complement fixation and precipitin studies and showed great variations. The use of purified native DNA demonstrated that, in at least 22 of these 35 sera, the anti-DNA antibodies reacted with the native form, independently of denatured contaminants. Systemic lupus sera were shown to contain three main types of DNA antibodies: those reacting only with denatured DNA, those reacting to the same extent with both forms of DNA, and those reacting preferentially with native DNA. In some instances, the latter antibodies fix complement and precipitate only with native DNA but are inhibited by the denatured form. This finding points to the importance of conformation in the antigenic structure of DNA. The simultaneous occurrence of different varieties of DNA antibodies was demonstrated in several sera. Evidence was obtained that some of these human antibodies to DNA can belong to the IgM class. Thus, DNA antibodies from systemic lupus patients differ in many respects from most of the experimentally produced antibodies capable of reacting with DNA.


First evidence of laccase activity in the Pacific oyster Crassostrea gigas.
Phenoloxidases (POs) are a family of enzymes including tyrosinases, catecholases and laccases, which play an important role in immune defence mechanisms in various invertebrates. The aim of this study was to thoroughly identify the PO-like activity present in the hemolymph of the Pacific oyster Crassostrea gigas, by using different substrates (i.e. dopamine and p-phenylenediamine, PPD) and different PO inhibitors. In order to go deeper in this analysis, we considered separately plasma and hemocyte lysate supernatant (HLS). In crude plasma, oxygraphic assays confirmed the presence of true oxidase activities. Moreover, the involvement of peroxidase(s) was excluded. In contrast to other molluscs, no tyrosinase-like activity was detected. With dopamine as substrate, PO-like activity was inhibited by the PO inhibitors tropolone, phenylthiourea (PTU), salicylhydroxamic acid and diethyldithio-carbamic acid, by a specific inhibitor of tyrosinases and catecholases, i.e. 4-hexylresorcinol (4-HR), and by a specific inhibitor of laccases, i.e. cetyltrimethylammonium bromide (CTAB). With PPD as substrate, PO-like activity was inhibited by PTU and CTAB. In precipitated protein fractions from plasma, and with dopamine and PPD as substrates, PTU and 4-HR, and PTU and CTAB inhibited PO-like activity, respectively. In precipitated protein fractions from hemocyte lysate supernatant, PTU and CTAB inhibited PO-like activity, independently of the substrate. Taken together, these results suggest the presence of both catecholase- and laccase-like activities in plasma, and the presence of a laccase-like activity in HLS. To the best of our knowledge, this is the first time that a laccase-like activity is identified in a mollusc by using specific substrates and inhibitors for laccase, opening new perspectives for studying the implication of this enzyme in immune defence mechanisms of molluscs of high economic value such as C. gigas.


Intakes of minerals from diets and foods: is there a need for concern?
Continuous monitoring of the food supply through the Total Diet Studies allows for the identification of changes and trends in the mineral content of foods resulting from agricultural or manufacturing practices. The studies also allow for the estimation of average daily intakes of minerals and a comparison of these intakes with Recommended Dietary Allowances. The Total Diet Studies use a small number of foods (core foods) to represent the U.S. food supply. The core foods are purchased four times per year, prepared for consumption, and analyzed for 11 nutritional minerals. The food composition data are then merged with food consumption data from national surveys to provide estimates of daily intakes of minerals for selected age-sex groups. Results of the 1982-1991 Total Diet Studies indicated that average intakes of potassium, phosphorus, selenium, iodine and manganese were adequate. Sodium could not be adequately assessed because the studies did not include discretionary salt. Intakes of calcium, magnesium, iron, zinc and copper were below recommended intakes for some age-sex groups. Studies based on clinical and biochemical measurements confirm that calcium, iron and zinc are of concern for segments of the U.S. population. There are conflicting opinions about the need for concern for copper and magnesium.


The obesity-diabetes association: what is different in indians?
There is a growing epidemic of obesity and type 2 diabetes in the world, more than 75% of the patients are in the developing countries. India is facing a twin burden of under-nutrition and over-nutrition: it figures prominently both in the hunger map of the world as well as being the world's capital of diabetes. Indians are susceptible to diabetes at a younger age and at a relatively lower BMI compared to the white Caucasians. This is partly explained by the fact that the thin-looking Indians are quite adipose (higher body fat percent). Intrauterine epigenetic regulation could explain the thin-fat Indian body composition. A combination of maternal one carbon metabolism derangement (influenced by vitamin B12 and Folate nutrition) and hyperglycemia appear to be major drivers. Persistent micronutrient abnormalities and rapid economic development seem to contribute to the intergenerational amplification of the diabetes-adiposity epidemic in Indians. Effective curtailment of the growing epidemic may lie in the realm of maternal and child health and nutrition.