Use of the Ambu(®) aScope™ in 10 patients with predicted difficult intubation.
Fibreoptic intubation is the gold standard for patients with predicted difficult intubation. The Ambu(®) aScope™ is a single-use device for fibreoptic tracheal intubation. We assessed its performance in 10 patients with predicted difficult tracheal intubation. The procedure was easy and successful in nine patients. However, the limited time of use did not permit intubation in one patient who required three attempts with different size tracheal tubes. The limited image resolution that can be expected of a single-use fibreoptic system and the absence of a suction channel are other potential limitations. On the other hand, being single-use this device has the advantage of avoiding the risk of infectious disease transmission and is always ready to use.


Molecular phylogeny of the New World Dipsadidae (Serpentes: Colubroidea): a reappraisal.
We present a phylogenetic analysis of the New World dipsadids based on an expanded data matrix that includes 246 terminal taxa including 196 dipsadids. The species are sampled for eight genes (12S, 16S, cytb, nd2, nd4, bdnf, c-mos, rag2). The data are explored using two distinct optimality procedures-maximum parsimony and maximum likelihood-and two alignment strategies-dynamic homology and static homology. Two previously unsampled dipsadid genera, Sordellina and Rhachidelus, are now included in the analysis. The definitions of the genera, Erythrolamprus, Clelia, Hypsirhynchus, Philodryas and Phimophis, and the tribes Alsophiini, Echinantherini and Conophiini, are revised. In order to maintain monophyly, the genus Umbrivaga is synonymized with Erythrolamprus, and two new genera are erected to accommodate Phimophis iglesiasi and Clelia rustica, as well as their closely related species. The West Indian genera Schwartzophis, Darlingtonia, Antillophis and Ocyophis are resurrected. © The Willi Hennig Society 2012.


Current methods of burn reconstruction.
After reading this article, the participant should be able to: 1. Explain the present challenges in reconstructive burn surgery. 2. Describe the most appropriate treatment methods and techniques for specific burn injury types, including skin grafts, dermal substitutes, and a variety of flap options. 3. Identify the appropriate use, advantages, and disadvantages of specific flaps in the treatment of burn injuries, including local, regional, superthin, prefabricated, prelaminated, and free flaps. Victims of thermal burns often form heavy scars and develop contractures around joints, inhibiting movement. As burns can occur in all cutaneous areas of the body, a wide range of reconstructive options have been utilized. Each method has advantages and disadvantages that must be considered by both patients and surgeons. The authors reviewed the literature for burn reconstruction and focused their discussion on areas that have been recently developed. They reviewed the mechanism of burn injury and discussed how this relates to the pathophysiology of the burn injury. Surgeons now have a wide array of plastic surgical techniques that can be used to treat burn victims. These range from skin grafts and local flaps to free flaps, prefabricated flaps, superthin flaps, and dermal scaffolds. Recent advances in burn reconstruction provide methods to decrease scar tissue and joint contractures. In the future, the authors hope that further developments in burn treatment will foster the development of new technologies that will allow site-specific reconstruction with minimal donor-site morbidity.


Body composition in institutionalized elderly people in Granada (Spain). Relation with other nutritional parameters.
Anthropometric characteristics and body composition were assessed in a group of 93 institutionalized elderly people, mean age 80.9 +/- 7.6 years, in Granada (Spain). The body composition was measured by the bioelectrical impedance technique. The influence of dietary energy intake, lifestyle, physical activity and health data were studied. Forty-five per cent of the women and 17% of the men were obese (BMI > 30 kg/m2) and 78% of the women and 54% of the men were overweight (BMI > 25 kg/m2). Only 12% of men and 4% of women suffered from undernutrition (BMI < 20 kg/m2). No significant correlations (P > 0.05) were found between BMI or body fat percentage and energy intake. Lifestyle and health data do not affect the BMI or body composition, but a significant negative correlation (P < 0.05) was found between the physical handicap level and the energy intake in all the sample (r = -0.26) and in the women (r = -0.16).


Principal networks.
Graph representations of brain connectivity have attracted a lot of recent interest, but existing methods for dividing such graphs into connected subnetworks have a number of limitations in the context of neuroimaging. This is an important problem because most cognitive functions would be expected to involve some but not all brain regions. In this paper we outline a simple approach for decomposing graphs, which may be based on any measure of interregional association, into coherent "principal networks". The technique is based on an eigendecomposition of the association matrix, and is closely related to principal components analysis. We demonstrate the technique using cortical thickness and diffusion tractography data, showing that the subnetworks which emerge are stable, meaningful and reproducible. Graph-theoretic measures of network cost and efficiency may be calculated separately for each principal network. Unlike some other approaches, all available connectivity information is taken into account, and vertices may appear in none or several of the subnetworks. Subject-by-subject "scores" for each principal network may also be obtained, under certain circumstances, and related to demographic or cognitive variables of interest.


Decreased energy reserve in an animal model of dilated cardiomyopathy. Relationship to contractile performance.
An animal model was used to test the hypothesis that in heart failure the decrease in the ability to resynthesize ATP through the creatine kinase (CK) reaction (which we call energy reserve) contributes to the inability of the heart to maintain its normal function and contractile reserve. One-week-old turkey poults were fed furazolidone for 14 days to induce dilated cardiomyopathy. Isolated Langendorff-perfused hearts from these myopathic animals showed a 73% decrease in baseline isovolumic contractile performance. Neither increasing [Ca2+]o nor electrical pacing rate increased isovolumic contractile performance. Measured by 31P nuclear magnetic resonance magnetization transfer and chemical assay, ATP concentration was decreased by 23%, phosphocreatine concentration by 42%, CK enzyme activity by 34%, and the pseudo first-order rate constant for the CK reaction by 50%. Measured CK reaction velocity decreased by 71%. The reduced ability to increase cardiac performance in response to increasing [Ca2+]o in hearts with lower CK reaction velocity was reproduced in part by feeding a separate group of turkey poults beta-guanidino-propionic acid to specifically reduce CK reaction velocity by decreasing guanidino substrate concentration. These hearts had normal baseline performance but blunted contractile reserve. These observations provide further support for the hypothesis that a decrease in energy reserve via the CK system contributes to reduced cardiac function in the failing heart.


Enhancing Cultural Competency: A Phenomenological Study.
An increase of ethnic minorities in the United States heightens concerns for health disparities. International service-learning provides an immersion in a community to identify issues related to culture and health. This study reports nursing students' experiences related to participation in an international service-learning project. A qualitative phenomenological design was used. Twenty participants who immersed in the community for 9 days were interviewed. Two semistructured focus interviews were audio recorded, transcribed, and analyzed using thematic analysis. Four themes emerged: Value Communication, Appreciate Differences, Provide Education, and Accept Humanity. This experience highlights the needs of diverse communities and enhances participants' skills to deliver culturally competent care with better education, compassion, and communication. By exploring students' experiences, service-learning experiences may be better understood as a pedagogy for teaching cultural competency and improving health outcomes in diverse populations. [J Nurs Educ. 2020;59(9):485-492.].


Hormonal control of isoperoxidases in lentil embryonic axis.
Detachment of the cotyledons from the lentil (Lens culinaris Med.) embryonic axis causes in the latter an increase in total peroxidase activity which is shown to be due to enhancement of specific cathodic isoperoxidases. Kinetin treatment of attached or detached axes promotes activity of essentially the same cathodic isoperoxidases. In addition kinetin enhances the activity of two anodic peroxidases and represses specifically that of a cathodic one. Abscisic acid inhibits the production of all isoenzymes in the presence or absence of kinetin. Cytokinin and abscisic acid actions are discussed in relation to the nature of a wounding hormone and the role of natural inhibitors in cotyledons during germination. Indoleacetic acid stimulates the activity of certain isoenzymes which are also stimulated by kinetin, whereas in others the effects of the two hormones are different. Specific inverse effects of indoleacetic acid and kinetin are demonstrated on the two most cathodic isoperoxidases. Indoleacetic acid-kinetin interactions on the cathodic isoperoxidases have been found in the literature and are discussed as a possible mechanism for explaining interactions of the two regulators on growth and other physiological processes.


[Massive lower gastrointestinal hemorrhage after polypectomy due to a colon fistula of a pseudoaneurysm of the splenic artery caused by chronic pancreatitis].
A life-threatening lower gastrointestinal bleeding is a rare complication due to coloscopic polypectomy. The following case report deals with a severe bleeding that was caused by polypectomy of a villous adenoma in a patient with chronic pancreatitis causing a huge pseudoaneurysm of the splenic artery. After polypectomy a wide iatrogenic communication between the pseudoaneurysm and the colon existed causing massive arterial intraluminal bleeding. Although this was successfully managed by transcatheter arterial embolization via splenic artery, the patient died a few days later caused by disseminated intravasal anticoagulation and multi organ failure.


Reuse of the Materials Recycled from Renewable Resources in the Civil Engineering: Status, Achievements and Government's Initiatives in Taiwan.
Growing concerns about the circular economy and sustainable waste management for civil applications of non-hazardous mineral industrial waste have increased in recent years. Therefore, this study presents a trend analysis of industrial waste generation and treatment during the years of 2010-2020, and focused on promotion policies and regulatory measures for mandatory renewable resources from industrial sources in Taiwan, including reclaimed asphalt pavement (RAP) material, water-quenched blast furnace slag, and ilmenite chlorination furnace slag. According to the official database of the online reported statistics during the period of 2010-2020, approximately three million metric tons per year of renewable resources were totally reused in civil engineering or related cement products, reflecting a balanced supply chain in the domestic market. Among these, water-quenched blast furnace slag accounted for about 90% (about 2.7 million metric tons) in Taiwan. Currently, the legislative framework of sustainable waste management in Taiwan is based on the Waste Management Act and the Resource Recycling Act, but there are some problems with them. In order to effectively reduce environmental loadings and conserve natural resources to mitigate climate change, some recommendations are addressed from different points of view.


The changing face of SDS denaturation: Complexes of Thermomyces lanuginosus lipase with SDS at pH 4.0, 6.0 and 8.0.
Lipases are widely used in the detergent industry and must withstand harsh conditions involving both anionic and zwitterionic surfactants at alkaline pH. Thermomyces lanuginosus lipase (TlL) is often used and stays active at high concentrations of the anionic surfactant sodium dodecyl sulfate (SDS) at pH 8.0, but is sensitive to SDS at pH 6.0 and below. We propose that enhanced stability at pH 8.0 results from a structurally distinct complex formation with SDS. We use small-angle X-ray scattering (SAXS) to elucidate structures of TlL:SDS at pH 4.0, 6.0, and 8.0 and further investigate the complexes at pH 8.0 using hydrogen/deuterium exchange mass spectrometry (HDX-MS). At pH 4.0, large dense aggregates are formed at low [SDS], which become gradually less dense at higher [SDS], resulting in a core-shell structure. At pH 6.0, SDS induces a TlL dimer and forms a hemi-micelle along the side of the dimer. At higher [SDS], TlL adopts a core-shell structure. At pH 8.0, TlL forms a dimer with a SDS hemi-micelle but avoids a core-shell structure and maintains activity. Three helices are identified as SDS anchor points. This study provides important structural insight into the stability of TlL towards SDS under alkaline conditions.


Studies on eliminating interference by electromagnetic induction from power lines in ECG signals.
Power lines can interfere with the measurement of ECG signals through electromagnetic induction. Here we describe an inverse loop method for eliminating this interference. The conductive loop area is one factor that is known to affect power line interference. However, two other variables, i.e. effective body area and inverse loop area, must be also considered. This work describes the relationship among these variables. We show that electromagnetic induction can be reduced to a very small value by this method. Because this method is simple and effective, it is useful and valuable not only for ECG signals but also for other bio-potential signal recording systems.


Investigating widely available substances as vaginal microbicides.
Microbicides to protect women from HIV are urgently needed. Several potential pharmaceutical microbicides are now undergoing obligatory clinical trials to check safety, acceptability and efficacy before approval for use. Microbicides may have side-effects and, paradoxically, their use may increase the risk of acquiring HIV. Several widely available substances have been suggested as microbicides, including substances with a low pH such as lemon juice, vinegar, soft drinks and lactobacillus dairy products. Because of the potential for harm it is important that these substances are tested before their use is widely promoted. After small scale safety and acceptability studies, their promotion needs to be evaluated as a communication intervention.


Involvement of ZFR1 of Fusarium verticillioides in kernel colonization and the regulation of FST1, a putative sugar transporter gene required for fumonisin biosynthesis on maize kernels.
Fumonisins comprise a class of carcinogenic mycotoxins produced by Fusarium verticillioides during colonization of maize kernels. In previous work, we identified ZFR1, which is predicted to encode a Zn(II)2Cys6 zinc finger transcription factor required for fumonisin B(1) (FB(1)) production during growth on kernels. In this study, we characterized the role of ZFR1 in colonizing maize kernels and inducing FB(1) biosynthesis. The ZFR1 deletion strain (Deltazfr1) grew approximately 2.5-fold less than the wild-type on endosperm tissue and a variety of other carbon sources, including glucose and amylopectin. However, the Deltazfr1 strain displayed higher alpha-amylase activity and expression of genes involved in starch saccharification than the wild-type, thus indicating that the reduced growth of the Deltazfr1 strain was not due to inhibition of amylolytic enzymes. In the wild-type strain, expression of six genes encoding putative sugar transporters was significantly greater on endosperm tissue than on germ tissue, and expression of at least three of the six genes was negatively affected by disruption of ZFR1. Intriguingly, disruption of FST1 had no effect on growth, kernel colonization or kernel pH but decreased FB(1) production by approximately 82% on maize kernels. Based on these findings, we hypothesize that ZFR1 controls FB(1) biosynthesis by regulating genes involved in the perception or uptake of carbohydrates.


Familial history of diabetes and clinical characteristics in Greek subjects with type 2 diabetes.
A lot of studies have showed an excess maternal transmission of type 2 diabetes (T2D). The aim, therefore, of the present study was to estimate the prevalence of familial history of T2D in Greek patients, and to evaluate its potential effect on the patient's metabolic control and the presence of diabetic complications. A total of 1,473 T2D patients were recruited. Those with diabetic mothers, diabetic fathers, diabetic relatives other than parents and no known diabetic relatives, were considered separately. The prevalence of diabetes in the mother, the father and relatives other than parents, was 27.7, 11.0 and 10.7%, respectively. Patients with paternal diabetes had a higher prevalence of hypertension (64.8 vs. 57.1%, P = 0.05) and lower LDL-cholesterol levels (115.12 +/- 39.76 vs. 127.13 +/- 46.53 mg/dl, P = 0.006) than patients with diabetes in the mother. Patients with familial diabetes were significantly younger (P < 0.001), with lower age at diabetes diagnosis (P < 0.001) than those without diabetic relatives. Patients with a diabetic parent had higher body mass index (BMI) (31.22 +/- 5.87 vs. 30.67 +/- 5.35 Kg/m2, P = 0.08), higher prevalence of dyslipidemia (49.8 vs. 44.6%, P = 0.06) and retinopathy (17.9 vs. 14.5%, P = 0.08) compared with patients with no diabetic relatives. No difference in the degree of metabolic control and the prevalence of chronic complications were observed. The present study showed an excess maternal transmission of T2D in a sample of Greek diabetic patients. However, no different influence was found between maternal and paternal diabetes on the clinical characteristics of diabetic patients except for LDL-cholesterol levels and presence of hypertension. The presence of a family history of diabetes resulted to an early onset of the disease to the offspring.


Degradation of postural control with aging.
Aging negatively impacts the ability to maintain postural stability due to degraded control systems. The entropic half-life, a non-linear variable that quantifies the transition of sample entropy with increasing time scales, quantifies the time that elapses before old positional information no longer influences, or is no longer related to, the control mechanisms that regulate the movement at the current center of pressure location. The entropic half-life provides a more representative and comprehendible way of detecting changes in complexity using measurement units of time. The purpose of this study was to determine the effects of aging on the magnitude and temporal structure of the center of pressure movement during quiet single-limb stance. Center of pressure data of 24 older and 24 younger subjects were analyzed. The complexity of the temporal structure of the center of pressure signal was quantified by calculating the entropic half-life of the center of pressure in the medio-lateral and anterior-posterior directions. The magnitude of movement was quantified using excursion of the center of pressure in the medio-lateral and anterior-posterior directions, the path length, and the 95% ellipse area of the center of pressure. The older subjects demonstrated a significantly shorter entropic half-life for the center of pressure in the anterior-posterior direction (p < 0.001), longer excursions of the center of pressure in the medio-lateral (p < 0.001) and anterior-posterior (p = 0.001) directions, increased center of pressure path lengths (p < 0.001), and increased 95% ellipse areas of the center of pressure (p < 0.001). The results from this study showed that even though older subjects demonstrated more frequent postural adjustments (shorter entropic half-life), this did not help to reduce the magnitude of movement of their center of pressure during quiet stance, thus indicating an impaired peripheral and/or central neuromuscular control mechanism.


Arabidopsis β-Amylase2 Is a K+-Requiring, Catalytic Tetramer with Sigmoidal Kinetics.
The Arabidopsis (Arabidopsis thaliana) genome contains nine β-amylase (BAM) genes, some of which play important roles in starch hydrolysis. However, little is known about BAM2, a plastid-localized enzyme reported to have extremely low catalytic activity. Using conservation of intron positions, we determined that the nine Arabidopsis BAM genes fall into two distinct subfamilies. A similar pattern was found in each major lineage of land plants, suggesting that these subfamilies diverged prior to the origin of land plants. Moreover, phylogenetic analysis indicated that BAM2 is the ancestral member of one of these subfamilies. This finding, along with the conservation of amino acids in the active site of BAM2, suggested that it might be catalytically active. We then identified KCl as necessary for BAM2 activity. Unlike BAM1, BAM3, and BAM5, three Arabidopsis BAMs that all exhibited hyperbolic kinetics, BAM2 exhibited sigmoidal kinetics with a Hill coefficient of over 3. Using multi-angle light scattering, we determined that BAM2 was a tetramer, whereas BAM5 was a monomer. Conserved residues from a diverse set of BAM2 orthologs were mapped onto a homology model of the protein, revealing a large, conserved surface away from the active site that we hypothesize is a secondary carbohydrate-binding site. Introduction of bulky methionine for glycine at two points on this surface reduced catalytic activity significantly without disrupting the tetrameric structure. Expression analysis indicated that BAM2 is more closely coexpressed with other starch degradation enzymes than any other BAM, suggesting that BAM2 may play an important role in starch degradation in plants.


Cotransfection of granulosa cells with simian virus 40 and Ha-RAS oncogene generates stable lines capable of induced steroidogenesis.
Cellular and viral oncogenes are usually defined on the basis of their ability to elicit neoplastic transformation. However, oncogene activity has also been implicated in the control of differentiation. We have tested whether transfection of primary cultured granulosa cells with various oncogenes can yield cell lines that maintain their differentiated properties. Primary granulosa cells were prepared from diethylstilbestrol-treated immature female rats and transfected with simian virus 40 (SV40) DNA or with SV40 plus activated human Ha-RAS oncogene. Transfection with SV40 plus Ha-RAS yielded cell lines that lost response to gonadotropins but, after 48 hr of stimulation with isoproterenol, cholera toxin, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), produced progesterone at levels comparable to those of differentiated primary cells. In contrast, cells transformed only by SV40 lost their ability to produce progesterone. Whereas in primary cell cultures progesterone production was already evident after a 3-hr incubation with 1 mM 8-Br-cAMP, in cotransfected cells progesterone production became evident only after 12 hr. All cotransformed cell lines produced SV40 large tumor antigen as well as human RAS p21 protein. The expression of the expected oncogenes in the various cell lines was confirmed by mRNA analysis. These results suggest that the expression of an activated RAS oncogene in granulosa cells can play a role in preserving inducible steroidogenesis.


Isoalantolactone induces apoptosis in human breast cancer cells via ROS-mediated mitochondrial pathway and downregulation of SIRT1.
Isoalantolactone possessed various biological activities. However, whether it could treat breast cancer and its underlying mechanism remained largely unknown. This study was designed to evaluate the anticancer effects of isoalantolactone on breast cancer and explored the molecular mechanism. Two human breast cancer cell lines (MDA-MB-231 and MCF-7) and one normal breast cell line (MCF-10A) were applied. Our data suggested that isoalantolactone decreased breast cancer cell viability in a dose-dependent manner, but showed almost no toxicity to MCF-10A cells. The anticancer effects of isoalantolactone were related to the overexpression of reactive oxygen species. Isoalantolactone significantly induced breast cancer cell apoptosis by activating caspase cascade, cleaving poly (ADP-ribose) polymerase. Increase of Bax/Bcl-2 ratio, depolarization of mitochondrial membrane potential, release of cytochrome c from mitochondria to cytoplasm and cell cycle arrest at G2/M phase were associated to the apoptosis induction. Additionally, isoalantolactone increased the protein expression of p38 MAPK and JNK. The apoptosis-induction of isoalantolactone could be abrogated by co-treatment with SB203580 (inhibitor of p38 MAPK) or SP600125 (inhibitor of JNK). Furthermore, isoalantolactone induced breast cancer cells apoptosis in a caspase-independent pathway, which was downregulation of SIRT1. Therefore, isoalantolactone may serve as a chemotherapeutic agent for the treatment of human breast cancer.


The Possible Role of Gut Microbiota and Microbial Translocation Profiling During Chemo-Free Treatment of Lymphoid Malignancies.
The crosstalk between gut microbiota (GM) and the immune system is intense and complex. When dysbiosis occurs, the resulting pro-inflammatory environment can lead to bacterial translocation, systemic immune activation, tissue damage, and cancerogenesis. GM composition seems to impact both the therapeutic activity and the side effects of anticancer treatment; in particular, robust evidence has shown that the GM modulates the response to immunotherapy in patients affected by metastatic melanoma. Despite accumulating knowledge supporting the role of GM composition in lymphomagenesis, unexplored areas still remain. No studies have been designed to investigate GM alteration in patients diagnosed with lymphoproliferative disorders and treated with chemo-free therapies, and the potential association between GM, therapy outcome, and immune-related adverse events has never been analyzed. Additional studies should be considered to create opportunities for a more tailored approach in this set of patients. In this review, we describe the possible role of the GM during chemo-free treatment of lymphoid malignancies.


Biological activity of cauliflower mosaic virus aphid transmission factor expressed in a heterologous system.
Aphid transmission factor (ATF) activity of cauliflower mosaic virus (CaMV) gene II product was recovered after expression of the gene by a baculovirus recombinant. The expression product, when first acquired by aphids through parafilm membrane, was able to mediate the transmission of two aphid nontransmissible isolates (CM1841, CM4-184) providing the first direct evidence that the product of the gene II is the CaMV ATF. The CaMV ATF in its active conformation has a strong tendency to aggregate and all attempts at solubilizing it resulted in the loss of the ATF activity. The CaMV ATF was also expressed in Escherichia coli, using the pGEX 3X plasmid vector, as a fusion protein to glutathione S-transferase (GST) and was purified. The fusion product (GST-P18), whether purified or not, was not able to complement the transmission of transmission-defective isolates. However, when GST-P18 was added to some extracts from a plant infected with an aphid-transmissible isolate (Cabb B-JI), the transmission was inhibited. This suggests that it could be possible to block the in vitro transmission of CaMV using a molecule analogous to the ATF.


Involvement of Nrf-2/HO-1 pathway in sevoflurane-induced cognitive improvement in rats with traumatic brain injury.
Traumatic brain injury (TBI) is an increasingly common emergency disease that usually leads to prolonged physical and cognitive impairments. In this study, we investigated if sevoflurane could induce cognitive improvement in TBI rats. Rats were subjected to head trauma induced by a fluid percussion device. A two-hour exposure to 3% sevoflurane was performed in a chamber immediately after TBI. Sevoflurane inhalation reduced the neurological and cognitive deficits induced by TBI with ameliorated synaptic injuries in the hippocampus. Moreover, after sevoflurane treatment, the expression of nuclear factor erythroid-2-related factor-2 (Nrf-2) and hemeoxygenase-1 (HO-1) in the hippocampus was enhanced 1 d after TBI and maintained at high levels 14 days later, and oxidative stress induced by TBI was inhibited. However, the HO-1 inhibitor, Zinc protoporphyrin (ZnPP), used to demonstrate the involvement of HO-1, suppressed the protective effect of sevoflurane. These results indicate that sevoflurane administered immediately after TBI may protect against TBI-induced synaptic and cognitive impairments by promoting the antioxidant Nrf-2/HO-1 pathway. Sevoflurane may be a promising anesthetic for patients with TBI.


[Clinical evaluation on the sensitivity test for anti-cancer agents in malignant bone and soft-tissue tumors].
We will report the result obtained from sensitivity tests on various anti-cancer agents for malignant bone and soft-tissue tumors based on SDI (Succinic Dehydrogenase Inhibition Test) method with the use of enzymic activities as marker since 1976. Our study comprised 27 cases altogether 15 cases of osteosarcoma, one case each of Ewing's sarcoma, malignant fibrous histiocytoma and malignant lymphoma, 3 cases of metastatic bone tumor and one case each of angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma, 2 cases of metastatic lung tumor among soft-tissue sarcomas. In all cases, sensitivity tests were done on the tumor tissues according to SDI method at the same time as biopsy for the determination of the appropriate medications. Four to six weeks of pre-operative intra-arterial infusion was done followed by radical operation. The results obtained are as follows. Observing the long-term results between subjects that applied anti-cancer agents decided by sensitivity test and those without sensitivity test. The 5 years cumulative survival rate jumped from 30.5% to 50.5%, showing a clear improvement.


Endocervical gland involvement by cervical intraepithelial neoplasia grade III. Predictive value for residual and/or recurrent disease.
The prognostic significance for residual or recurrent disease of cervical intraepithelial neoplasia Grade III in endocervical glands by cone biopsy was examined in 341 consecutive patients diagnosed from 1979 through 1983 and followed through 1988. Treatment by hysterectomy, within 8 weeks of cone biopsy, was done in 96 patients. The only variable that could predict residual disease at hysterectomy was positive margins (P = 0.059). However, both positive margins and positive glands were (independently of one another and after the effects of length of follow-up, hospital of admission, and age at time of first diagnosis were held constant) highly significant predictors of residual or recurrent disease in the 245 women who did not undergo a hysterectomy (P = 0.000 for each). The authors therefore conclude that information concerning gland involvement on cone biopsy specimens should influence patient management.


Geometric Models for Seed Shape Description and Quantification in the Cactaceae.
Seed shape in species of the Cactaceae is described by comparison with geometric models. Three new groups of models are presented, two for symmetric seeds, and a third group for asymmetric seeds. The first two groups correspond, respectively, to superellipses and the combined equations of two semi-ellipses. The third group contains models derived from the representation of polar equations of Archimedean spirals that define the shape of asymmetric seeds in genera of different subfamilies. Some of the new models are geometric curves, while others are composed with a part resulting from the average silhouettes of seeds. The application of models to seed shape quantification permits the analysis of variation in seed populations, as well as the comparison of shape between species. The embryos of the Cactaceae are of the peripheral type, strongly curved and in contact with the inner surface of the seed coat. A relationship is found between seed elongation and the models, in which the genera with elongated seeds are represented by models with longer trajectories of the spiral. The analysis of seed shape opens new opportunities for taxonomy and allows quantification of seed shape in species of the Cactaceae.


A health promotion program at a Japanese newspaper undergoing restructuring.
Occupational health activities based on a health promotion philosophy and focused on primary and secondary prevention were introduced at a Japanese newspaper company where restructuring had occurred. Japanese metabolic syndrome diagnostic standards were used to determine changes in certain lifestyle disease risk factors over 10 years. The amount of change from 1998 to 2007 was determined, and two groups (i.e., 1998 and 2007) were compared using paired t-tests. Results suggested that the occupational health activities focused on primary prevention had been effective. The authors concluded that, in situations where industrial change and corporate restructuring are occurring, occupational health activities based on a health promotion philosophy and focused on primary and secondary prevention are more effective than diagnostic activities and other types of health management focused on tertiary prevention.


A clinical study: Melaleuca, Manuka, Calendula and green tea mouth rinse.
A novel mouthrinse (IND 61,164) containing essential oils and extracts from four plant species (Melaleuca alternifolia, Leptospermum scoparium, Calendula officinalis and Camellia sinensis) were tested. This study aimed to evaluate the safety, palatability and preliminary efficacy of the rinse. Fifteen subjects completed the Phase I safety study. Seventeen subjects completed the Phase II randomized placebo-controlled study. Plaque was collected, gingival and plaque indices were recorded (baseline, 6 weeks, and 12 weeks). The relative abundance of two periodontal pathogens (Actinobacillus actinomycetemcomitans, Tanerella forsythensis) was determined utilizing digoxigenin-labeled DNA probes. ANCOVA was used at the p = 0.05 level of significance. Two subjects reported a minor adverse event. One subject withdrew from the study. Several subjects objected to the taste of the test rinse but continued treatment. Differences between gingival index, plaque index or relative abundance of either bacterial species did not reach statistical significance when comparing nine placebo subjects with eight test rinse subjects. Subjects exposed to the test rinse experienced no abnormal oral lesions, altered vital signs, changes in liver, kidney, or bone marrow function. Larger scale studies would be necessary to determine the efficacy and oral health benefits of the test rinse.


Micropuncture studies of the sweat formation in cystic fibrosis patients.
In order to determine whether the precursor solution of sweat is abnormal in cystic fibrosis, osmolality and concentrations of sodium and chloride were measured in fluid obtained by micropuncture from the sweat gland coil of the nail fold of patients with this disease. Osmolality was 323+/-4.8 SE (mOsm/kg of water), sodium concentration was 151+/-1.1 SE (mEq/liter), and chloride concentration was 124+/-6.0 SE (mEq/liter). The sweat:plasma ratio for osmolality averaged 1.1+/-0.015 SE. These values are not significantly different from the corresponding ones obtained previously in normal individuals. It is concluded therefore that the disturbance of sweat gland function as far as electrolytes are concerned is restricted to the excretory ducts. In a second series of experiments the stop-flow pressure which is generated by sweat glands during secretion was measured. Values up to 500 mm Hg were found in both patients and normals. According to van't Hoff's law (DeltaP = RTDeltaC) hydrostatic pressure differences of this magnitude can be generated by the osmotic difference of 27 mOsm/kg of water observed between precursor sweat and plasma in the present experiments. With respect to the mechanism of sweat secretion this finding supports the hypothesis that active solute transport creates an osmotic gradient which causes osmotic water flux.


Multilayer microcapsules as anti-cancer drug delivery vehicle: deposition, Sustained release, and in vitro bioactivity.
A drug delivery system based on spontaneous deposition of soluble, low-molecular-weight therapeutic agents has been developed for the purpose of sustaining drug release. Layer-by-layer assembly of oppositely charged polyelectrolytes onto melamine formaldehyde (MF) colloidal particles, followed by removal of the cores at low pH has yielded intact hollow microcapsules having the ability to induce deposition of various water-soluble substances. Dynamic observation by confocal laser scanning microscopy provided direct evidence of such deposition. Dependence of loading rate on molecular weight was investigated. Efficient loading of an anti-cancer drug, daunorubicin (DNR), was confirmed by transmission electron microscopy (TEM). Its release was quantified by fluorometry. The results indicated that loading, and subsequent release, could be tuned by factors such as feeding concentrations, temperature, and salt concentrations. The intrinsic mechanism of loading and release was discussed taking into account the interaction between the drugs and the poly(styrene sulfonate)/MF complex existing in the hollow capsules. With culture of the HL-60 cell line, a kind of human leukemia cell, the presence of DNR-loaded capsules was seen to steadily decrease the cyto-viability. Fluorescence intensity averaged from inside the circles as a function of incubation time.


Ultrastructural morphometric analysis of GABA-immunoreactive terminals in the ventrocaudal periaqueductal grey: analysis of the relationship of GABA terminals and the GABAA receptor to periaqueductal grey-raphe magnus projection neurons.
The periaqueductal grey (PAG) plays an important role in the descending modulation of nociception. Inhibitory influences of GABAergic terminals, located within the periaqueductal grey, are thought to play a role in antinociception by influencing the activity of neurons that project to the nucleus raphe magnus and adjacent reticular nuclei. The present study utilized electron microscopic immunocytochemistry to quantitate the normal neuronal associations of GABA-immunoreactive terminals, and to visualize the neuronal distribution of the GABAA receptor in the ventrolateral periaqueductal grey of the rat. Of particular interest was a quantitative description of the interaction between GABA-immunoreactive axon terminals and periaqueductal grey neurons that were retrogradely-labelled from the nucleus raphe magnus and adjacent medullary reticular nuclei. Most terminals were observed to be immediately apposed only to two or three dendrites, although axonal and perikaryal associations were also observed. In the ventrolateral periaqueductal grey, 37.5% of all GABA-immunoreactive terminals were adjacent to periaqueductal grey-nucleus raphe magnus and periaqueductal grey-reticular nucleus projection neurons. Symmetrical synapses with these retrogradely-labelled neurons were formed by 17% of GABA-immunoreactive terminals in the ventrolateral periaqueductal grey. We also noted that 13.2% of the GABA-immunoreactive terminals formed symmetrical synapses with GABA-immunoreactive dendrites in the periaqueductal grey, and occasionally those dendrites were retrogradely labelled. Only 0.8% of the GABA-immunoreactive terminals formed putative symmetrical synapses with other GABA-immunoreactive terminals. Consistent with these findings, GABAA receptor immunoreactivity was only associated with dendrites and perikarya in neurons of the ventrolateral PAG. These results are consistent with an inhibitory role for GABA on PAG neurons, a configuration required by hypothetical models for opoid disinhibitory circuitry within the PAG. In addition, the data further suggest that other kinds of GABAergic connections may be important in descending antinociception, and that a population of GABAergic PAG projection neurons exists that may be inhibitory within nucleus raphe magnus and the adjacent reticular nuclei.


Effect of jet stretch and particle load on cellulose nanocrystal-alginate nanocomposite fibers.
Alginate fibers have found many applications such as the preparation of dressings to treat exuding wounds, drug delivery, enzyme immobilization, etc.; however, their use is limited due to poor mechanical properties. Cellulose nanocrystals (CNCs) were isolated from cotton and introduced into calcium alginate fibers with the goal of improving their strength and modulus. The isolated CNCs are elongated nanoparticles of crystalline cellulose with an average length of 130 nm with a standard deviation (s) of 63 nm, an average width of 20.4 nm (s = 7.8 nm), and an average height of 6.8 nm (s = 3.3 nm). The CNCs were mixed with an aqueous sodium alginate dope solution and wet spun into a CaCl(2) bath to form fibers. It was found that if the apparent jet stretch (ratio of the fiber draw velocity to extrusion velocity) is kept constant, addition of the nanocrystals reduces the tensile strength and modulus of the material; however, a small concentration of CNCs in the dope solution increases the tensile energy to break and enables an increase in the fiber spinning apparent jet stretch ratio by nearly 2-fold at up to 25% CNCs load; the maximum ratio of 4.6 is observed at 25 wt % CNC loading as compared to a maximum of 2.4 for the native alginate. Mechanical testing showed a 38% increase in tenacity and a 123% increase in tensile modulus with 10 wt % CNCs loading and an apparent jet stretch of 4.2. The data suggest that alignment of the nanocrystals in the composites is a key factor influencing the mechanical properties. CNCs have potential to become a biocompatible, renewable, and cost-effective solution to reinforce alginate fibers.


New drug targets for the treatment of gout arthritis: what's new?
Gout arthritis (GA) is an intermittent inflammatory disease affecting approximately 10% of the worldwide population. Symptomatic phases (acute flares) are timely spaced by asymptomatic periods. During an acute attack, redness, joint swelling, limited movement, and excruciating pain are common symptoms. However, the current available therapies are not fully effective in reducing symptoms and offer numerous side effects. Therefore, unveiling new drug targets and effector molecules are required in developing novel GA therapeutics. This review discusses the pathophysiological mechanisms of GA and explores potential pharmacological targets to ameliorate disease outcome. In addition, we listed promising pre-clinical studies demonstrating effector molecules with therapeutical potential. Among those, we emphasized the importance of natural products, including traditional Chinese medicine formulas and their multitarget mechanisms of action. In our search, we observed that there is a massive gap between pre-clinical and clinical knowledge. Only a minority (4.4%) of clinical trials aimed to intervene by applying natural products or current hot targets described herein. In this sense, we envisage four possibilities for GA therapeutics, which include the repurposing of existing therapies, ALX/FPR2 agonism for improvement in disease outcome, the use of multitarget drugs (e.g. natural products), and targeting the neuroinflammatory component of GA.


Clinical study on effect of wrist-ankle acupuncture on incidence of hypertension after intubation during induction of general anesthesia.
To observe the effect of wrist-ankle acupuncture on the incidence of hypertension after tracheal intubation during induction of general anesthesia. 200 patients receiving selective surgery under tracheal intubation and general anesthesia in our Hospital were selected and divided into control group and wrist-ankle acupuncture group using the random number table method, with 100 patients in each group. Sufentanil, cisatracurium besilate, remifentanil, etomidate and lidocaine hydrochloride were used for anesthesia induction, and intravenously injected according to the onset time of drugs, successively. The wrist-ankle acupuncture group was needled in bilateral upper 1, 2 and 3 areas, while the control group was treated with false acupuncture.Blood pressure and related blood biochemical indexes were measured and observed at different stages in each group. The incidence of blood pressure exceeding 20% and 30% of basal blood pressure within 5 minutes after intubation was as follows:wrist-ankle acupuncture group 11.83% and 6.45%; control group 29.79% and 22.34%, The incidence in the study group was lower than that in the control group. Norepinephrine concentration in the wrist-ankle acupuncture group was significantly lower than that before induction (P < .05), and plasma Norepinephrine concentration in the wrist-ankle acupuncture group was significantly lower than that in the control group after intubation (P < .05). The plasma Norepinephrine concentration in the wrist-ankle acupuncture group was significantly lower than that in the control group after intubation (P < .05). wrist-ankle acupuncture can prevent hypertension after intubation during anesthesia induction. Moreover, it is safe, effective, minimally invasive. Therefore, it is easy to be popularized in clinical practice.


Influence of peripheral and motivational cues on rigid-flexible functioning: Perceptual, behavioral, and cognitive aspects.
Recent research has shown that performing approach versus avoidance behaviors (arm flexion vs. extension) effectively influences cognitive functioning. In another area, lateralized peripheral activations (left vs. right side) of the motivational systems of approach versus avoidance were linked to various performances in cognitive tasks. By combining these 2 avenues of research, the influence of motor behaviors on flexible thinking was examined through the use of lateralized approach or/and avoidance behaviors. In 5 experiments reported in this article, a combination of the laterality and arm flexion versus extension variables successfully determined flexibility-rigidity functioning, consistent with the motor congruence hypothesis (J. Cretenet & V. Dru, 2004). Through these experiments, this result has been replicated with perceptual, behavioral, and cognitive aspects of flexibility, contributing to a better understanding of the relationships between bodily components, affect, and cognition.


The efficacy and pharmacokinetics of terbinafine against the frog-killing fungus (Batrachochytrium dendrobatidis).
Captive and wild amphibians are under threat of extinction from the deadly fungal pathogen Batrachochytrium dendrobatidis (Bd). The antifungal drug terbinafine (TBF) is used by pet owners to treat Bd-infected frogs; however, it is not widely used in academic or zoological institutions due to limited veterinary clinical trials. To assess TBF's efficacy, we undertook treatment trials and pharmacokinetic studies to investigate drug absorption and persistence in frog skin; and then we correlated these data to the minimal lethal concentrations (MLC) against Bd. Despite an initial reduction in zoospore load, the recommended treatment (five daily 5 min 0.01% TBF baths) was unable to cure experimentally infected alpine tree frogs and naturally infected common eastern froglets. In vitro and in vivo pharmacokinetics showed that absorbed TBF accumulates in frog skin with increased exposure, indicating its suitability for treating cutaneous pathogens via direct application. The MLC of TBF for zoosporangia was 100 μg/ml for 2 h, while the minimal inhibitory concentration was 2 μg/ml, suggesting that the drug concentration absorbed during 5 min treatments is not sufficient to cure high Bd burdens. With longer treatments of five daily 30 min baths, Bd clearance improved from 12.5% to 50%. A higher dose of 0.02% TBF resulted in 78% of animals cured; however, clearance was not achieved in all individuals due to low TBF skin persistence, as the half-life was less than 2 h. Therefore, the current TBF regime is not recommended as a universal treatment against Bd until protocols are optimized, such as with increased exposure frequency.


Localization of transforming growth factor beta 1 and beta 2 during testicular development in the rat.
The transforming growth factor beta s (TGF beta s) affect the metabolic activities of the somatic cells of the testis. Sertoli cells, peritubular/myoid cells, and germ cells contain mRNA for TGF beta 1 and/or TGF beta 2. We have used immunohistochemical techniques to determine, in vivo, when TGF beta 1 and TGF beta 2 are present in the rat testis during development and have identified the precise localization of these growth factors. The most pronounced changes in TGF beta immunoreactivity occurred during spermatogenesis. TGF beta 1 predominated in spermatocytes and early round spermatids, but as the spermatids elongated around stages VIII-IX of the cycle, the TGF beta 1 levels declined. TGF beta 2 was undetectable in spermatocytes and early round spermatids, but as spermiogenesis progressed, around stages V-VI, the spermatids rapidly acquired TGF beta 2. The intense staining for TGF beta 2 was maintained as the spermatids elongated. TGF beta 1 immunoreactivity was detected in Sertoli cells throughout testicular development. TGF beta 2 was found in fetal Sertoli cells, but became undetectable rapidly after birth. In fetal animals the Leydig cells contained TGF beta 1 and TGF beta 2; after birth TGF beta 1 persisted whereas TGF beta 2 became undetectable in the Leydig cells. Prior to puberty, TGF beta 1 and TGF beta 2 were absent in a portion of the Leydig cells; when the adult stage was reached, TGF beta 1 was no longer detectable and TGF beta 2 staining was faint to absent. In conclusion, our novel findings show that TGF beta 1 and TGF beta 2 are present in vivo in testicular cells at clearly defined stages of their differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)


The unusual and dynamic character of PX-DNA.
PX-DNA is a four-stranded DNA structure that has been implicated in the recognition of homology, either continuously, or in an every-other-half-turn fashion. Some of the structural features of the molecule have been noted previously, but the structure requires further characterization. Here, we report atomic force microscopic characterization of PX molecules that contain periodically placed biotin groups, enabling the molecule to be labeled by streptavidin molecules at these sites. In comparison with conventional double stranded DNA and with antiparallel DNA double crossover molecules, it is clear that PX-DNA is a more dynamic structure. Furthermore, the spacing between the nucleotide pairs along the helix axis is shorter, suggesting a mixed B/A structure. Circular dichroism spectroscopy indicates unusual features in the PX molecule that are absent in both the molecules to which it is compared.


One macrocyclic ligand, four oxidation states: A 16-atom ringed dianionic tetra-NHC macrocycle and its Cr(II) through Cr(V) complexes.
Despite chromium being among the first transition metals ever reported to bind to an NHC, chromium NHC complexes, especially in mid and high oxidation states, have received scant attention. Herein, the synthesis, characterization, and reactivity of a series of Cr(II) to Cr(V) complexes bearing a 16-atom ringed dianionic tetra-NHC macrocycle are reported. The Cr(II) dimer is diamagnetic and displays a very short Cr-Cr quadruple bond, unprecedented for Cr-NHC complexes to date. Oxidative cleavage of the Cr-Cr bond leads to the formation of a highly stable diamagnetic Cr(IV) oxo complex. Similar reactions with organic azides lead to paramagnetic Cr(IV) imide complexes. Notably, the Cr(IV) oxo can be oxidized in a reversible reaction to yield a Cr(V) cationic oxo complex, which is a very rare high oxidation state Cr-NHC-compound. This Cr(V) oxo undergoes stoichiometric oxygen atom transfer. Similar reactions were attempted with molybdenum and tungsten to form macrocyclic NHC complexes, but only a molybdenum dimer could be isolated.


Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET Alteration: A Systematic Review and Meta-Analysis.
Crizotinib has been approved for the treatment of non-small-cell lung cancer (NSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion. This drug has also been granted breakthrough designation for NSCLCs with MET exon 14 alterations. This systematic review and meta-analysis aimed to investigate the efficacy and safety of crizotinib in patients with these diseases. We searched PubMed and Web of Science for relevant studies. Meta-analysis of proportions was conducted to calculate the pooled rate of complete response, partial response, stable disease, progressive disease, disease control rate (DCR), objective response rate (ORR), and drug adverse effects (AEs) of crizotinib in NSCLCs with ROS1 rearrangement or MET alterations. A total of 20 studies were included for meta-analysis. Among patients with ROS1-positive NSCLC, crizotinib exhibited a pooled DCR of 93.2% (95% confidence interval [CI] 90.8-95.5) and a pooled ORR of 77.4% (95% CI 72.8-82.1). The median progression-free survival (PFS) and overall survival (OS) of patients in this group was 14.5 and 32.6 months, respectively. For NSCLC with MET alterations, crizotinib was associated with a lower efficacy (DCR 78.9% [95% CI 70.3-87.4] and ORR 40.6% [95% CI 28.3-53.0]). The median PFS was 5.2 months, and median OS was 12.7 months. The most common drug AEs were vision impairment (43.7%), edema (42.9%), and fatigue (40.1%). Our study highlighted and confirmed the efficacy of crizotinib in patients with NSCLC with ROS1 or MET genetic alterations. Crizotinib had remarkable effects on advanced NSCLC with ROS1 fusion, as previously reported. However, the role of this targeted therapy in MET-altered NSCLC remains investigational.


IFN-gamma potentiates the release of TNF-alpha and MIP-1alpha by alveolar macrophages during allergic reactions.
Viral infections play an important role in the exacerbation of asthma. The production of interferons (IFNs) is well known to limit viral spread, but IFN-gamma can also prime alveolar macrophages to release more inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha). Given the importance of these cytokines, we have investigated the effect of IFN-gamma on their release by alveolar macrophages during stimulation by immunoglobulin (Ig)E/anti-IgE. Alveolar macrophages from normal or Nippostrongylus brasiliensis-infected rats, the latter having increased numbers of low-affinity receptors for IgE (Fcepsilon RII) on their alveolar macrophages, were treated with IgE for 2 h and stimulated with anti-IgE for 18 h. The increase of TNF-alpha release (153 +/- 48 pg/10(6) cells) by IgE/anti-IgE occurred only with alveolar macrophages from infected rats. The messenger RNA level for TNF-alpha in rat alveolar macrophages was also increased by stimulation with IgE/anti-IgE. Treatment with IFN-gamma prior to stimulation with IgE/anti-IgE showed a time- and concentration-dependent increase of TNF-alpha release. Interestingly, IgE/anti-IgE treatment did not stimulate the release of MIP-1alpha (15 +/- 5 pg/10(6) cells), but IFN-gamma treatment alone and with IgE /anti-IgE significantly increased and potentiated MIP-1alpha release (98 +/- 40 pg/10(6) cells) by alveolar macrophages, respectively. These results suggest that IFN-gamma produced at times such as during viral infections primes alveolar macrophages for enhanced release of inflammatory mediators during allergic reactions, thereby contributing to the inflammatory process.


Pseudoaneurysm of the inferior epigastric artery.
Abdominal wound closure with safety retention sutures can cause intestinal obstruction, fistula, skin necrosis and rarely pseudoaneurysms of the inferior epigastric artery (IEA) (1, 2, 3). We report the case of a man presenting with a pseudoaneurysm of the IEA after traumatic extraction of retention sutures, successfully treated by surgical ligation of the feeding vessels. The importance of contrast enhanced CT and duplex colour Doppler sonography in differential diagnosis of postoperative abdominal wall masses is discussed, as well as possibilities and risks in the treatment of false aneurysms of the IEA.


Carbohydrate Targets for CAR T Cells in Solid Childhood Cancers.
Application of the CAR targeting strategy in solid tumors is challenged by the need for adequate target antigens. As a consequence of their tissue origin, embryonal cancers can aberrantly express membrane-anchored gangliosides. These are carbohydrate molecules consisting of a glycosphingolipid linked to sialic acids residues. The best-known example is the abundant expression of ganglioside GD2 on the cell surface of neuroblastomas which derive from GD2-positive neuroectoderm. Gangliosides are involved in various cellular functions, including signal transduction, cell proliferation, differentiation, adhesion and cell death. In addition, transformation of human cells to cancer cells can be associated with distinct glycosylation profiles which provide advantages for tumor growth and dissemination and can serve as immune targets. Both gangliosides and aberrant glycosylation of proteins escape the direct molecular and proteomic screening strategies currently applied to identify further immune targets in cancers. Due to their highly restricted expression and their functional roles in the malignant behavior, they are attractive targets for immune engineering strategies. GD2-redirected CAR T cells have shown activity in clinical phase I/II trials in neuroblastoma and next-generation studies are ongoing. Further carbohydrate targets for CAR T cells in preclinical development are O-acetyl-GD2, NeuGc-GM3 (N-glycolyl GM3), GD3, SSEA-4, and oncofetal glycosylation variants. This review summarizes knowledge on the role and function of some membrane-expressed non-protein antigens, including gangliosides and abnormal protein glycosylation patterns, and discusses their potential to serve as a CAR targets in pediatric solid cancers.


Phenelzine causes an increase in brain ornithine that is prevented by prior monoamine oxidase inhibition.
Phenelzine (PLZ), a nonselective irreversible inhibitor of monoamine oxidase (MAO), also inhibits GABA-transaminase (GABA-T), markedly increasing brain GABA levels. PLZ is also a substrate for MAO, and studies suggest that a metabolite formed by the action of this enzyme on PLZ may be responsible for the increase in GABA observed. We have recently found that PLZ also elevates brain ornithine (ORN), an amino acid precursor to both glutamate (and GABA) and the polyamines, and have conducted dose- and time-response studies on this effect. Rats were treated with vehicle or PLZ doses (7.5, 15 or 30 mg/kg i.p.), and brains were collected 3 h later. In the time-response study, animals were treated with vehicle or PLZ (15 mg/kg i.p.) and brains were collected 1-24 h later. To determine whether a metabolite formed by the action of MAO on PLZ may be responsible for the elevation in brain ORN observed, animals were pretreated with vehicle or the MAO inhibitor tranylcypromine (TCP) before vehicle or PLZ (15 mg/kg), and brains collected 3 h later. ORN levels (measured by an HPLC procedure) were dose- and time-dependently increased in PLZ-treated animals, with levels reaching approximately 650% of control at 6 and 12 h. Pretreatment with TCP completely abolished the PLZ-induced increase in brain ORN, suggesting, as with GABA, that a metabolite of PLZ formed by the action of MAO is responsible for the elevation of brain ORN observed. The possible contribution of increased ORN to therapeutic and/or neuroprotective properties of PLZ is discussed.


Apigenin inhibits HeLa sphere-forming cells through inactivation of casein kinase 2α.
The protein kinase casein kinase 2 (CK2) has been implicated in stem cell maintenance and its aberrant activation has been demonstrated in several types of cancer, including cervical cancer. In the present study, it was demonstrated that the sphere-forming cells (SFCs) of HeLa cell lines exhibited self-renewal capacity, indicating that they possessed the properties of cervical cancer stem-like cells. HeLa-derived SFCs exhibited a higher level of CK2α protein, compared with the parental cells. Apigenin, a dietary flavonoid, led to a dose-dependent inhibition of the self-renewal capacity and the protein expression of CK2α in HeLa-derived SFCs. Furthermore, forced overexpression of CK2α resulted in a decrease in the inhibition of CK2α expression and the self-renewal capacity induced by apigenin in HeLa-derived SFCs. These results suggested that apigenin inhibits the self-renewal capacity of HeLa-derived SFCs through downregulation of CK2α expression.


Anthropological Research in Light of Research-Ethics Review: Canadian Master's Theses, 1995-2004.
DESPITE CLAIMS THAT RESEARCH-ETHICS review is changing or discouraging social research, there are no studies that have tested this assumption. Examining Canadian Master's theses in anthropology between 1995 and 2004, this paper explores the extent to which the theses represent a change in number, topic, or methodology in relation to formal ethicsreview guidelines that came into force in Canada in 2001. ProQuest Digital Dissertations reveals that the number of theses has increased, and that there has not been a noticeable shift from research involving humans to research based on archival data, or theoretical or review theses. However, there has been a very significant increase in research that is called ethnography, but that relies exclusively on interviews. Possible reasons for the halving of percent of ethnographic or participantobservation research are explored.


Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized and observational studies.
Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with significant morbidity and mortality. Controversy exists regarding whether an off-pump technique can reduce post-CABG renal injury. Systematic review and meta-analysis. Adult patients undergoing CABG. MEDLINE, EMBASE, Cochrane Renal Library, and Google Scholar were searched in May 2008 for randomized controlled trials (RCTs) and observational studies comparing off-pump CABG (OPCAB) with conventional CABG (CAB) for renal outcomes. Studies involving patients on long-term renal replacement therapy (RRT) were excluded. OPCAB. Primary outcomes were overall AKI and AKI requiring RRT. 22 studies (6 RCTs and 16 observational studies) comprising 27,806 patients met the inclusion criteria. The pooled effect from both study cohorts showed a significant reduction in overall AKI (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.43 to 0.76; P for effect < 0.001; I(2) = 67%; P for heterogeneity < 0.001) and AKI requiring RRT (OR, 0.55; 95% CI, 0.43 to 0.71; P for effect < 0.001; I(2) = 0%; P for heterogeneity = 0.5) in the OPCAB group compared with the CAB group. In RCTs, overall AKI was significantly reduced in the OPCAB group (OR, 0.27; 95% CI, 0.13 to 0.54); however, no statistically significant difference was noted in AKI requiring RRT (OR, 0.31; 95% CI, 0.06 to 1.59). In the observational cohort, both overall AKI (OR, 0.61; 95% CI, 0.45 to 0.81) and AKI requiring RRT (OR, 0.54; 95% CI, 0.40 to 0.73) were significantly less in the OPCAB group. RCTs were noted to be underpowered and biased toward recruiting low-risk patients. Sensitivity analysis restricted to good-quality studies showed a significant reduction in AKI. Lack of uniform AKI definition in the included studies, heterogeneity for overall AKI outcome. Analysis of the current evidence suggests a reduction in AKI using the OPCAB technique; however, studies lack consistency in defining AKI. Available RCTs are underpowered to detect a difference in AKI requiring RRT; evidence from observational studies suggests a reduction in RRT requirement. Future studies should apply a standard definition of AKI and target a high-risk population.


Local recurrence of breast cancer after skin-sparing mastectomy following core needle biopsy: case reports and review of the literature.
The latest advances in diagnostic and therapeutic procedures for breast cancer have provided valuable technological breakthroughs. Yet the long-term consequences of these modern methods are still quite unclear. Such is the case for stereotactic or ultrasound-guided histologic needle biopsy and skin-sparing mastectomy. We report on three patients who presented with multicentric breast cancer diagnosed by stereotactic needle biopsy and treated by skin-sparing mastectomy. All three patients developed recurrence at the core needle entry site. Records of 58 patients with breast cancer who were treated by skin-sparing mastectomy followed by immediate reconstruction (with transverse rectus abdominis muscle [TRAM] flap or tissue expander) at the Breast Diseases Division of Buenos Aires British Hospital between December 1999 and December 2003 were reviewed retrospectively. Eleven of these patients were diagnosed by histologic needle biopsy. The mean follow-up was 28 months (range 5-60 months). Three (skin or subcutaneous) local recurrences at the needle entry site, diagnosed in a mean time of 23.6 months (16, 22, and 23 months), were reported. The three patients underwent complete resection with clear margins, radiation therapy to the "neobreast," and tamoxifen. All three patients are disease free with a mean postrecurrence follow-up of 24.3 months (30, 23, and 22 months). Based on the evidence of displacement of tumor cells and the potential nonresection of such tumor seeding at the time of skin-sparing mastectomy, as well as the poor probability of postoperative radiation therapy, we recommend surgical resection of the needle biopsy tract, including the dermal entry site, at the time of mastectomy.


No sex-related pharmacokinetic and pharmacodynamic differences of captopril.
Captopril is an angiotensin-converting enzyme inhibitor (ACEI) used in the treatment of hypertension and congestive heart failure and has demonstrated its cardiovascular effects in experimental animal models, healthy volunteers and patients. The aim of this study was to find out whether or not differences in the pharmacokinetic profile and the haemodynamic response of a 100-mg single oral dose of captopril appeared between subjects of both sexes. Twenty-four young healthy volunteers (12 males and 12 females) took part in the trial. Blood samples to assess captopril plasma concentrations, determined by reverse phase high performance liquid chromatography (HPLC), as well as haemodynamic variables, were obtained before and at different times following drug intake. Pharmacokinetic parameters did not show significant sex differences. Systolic and diastolic blood pressure exhibited a statistically significant decrease between 0.5 and 8 h in both sexes. No significant sex-related differences were found. The drug exhibited a good tolerability.


Secondary rhinoplasty following open rhinoplasty.
On the basis of 56 cases of secondary rhinoplasty following an initial open rhinoplasty, I conclude that secondary surgery is safe and effective. Either an open or closed approach can be used in most cases with little risk of skin necrosis or poor scar formation. The decision as to which approach to use depends on numerous factors. In general, a closed technique is favored when augmentation is the solution, while an open technique is favored when structural correction is required. Reopening the nose was done consistently without problems but was avoided in two patients because of severe thinning following previous defatting. However, certain "stigmata" were seen following open primary rhinoplasty and should be avoided: (1) a depressed, visible scar, (2) destruction of the soft-tissue facets and nostril apices, (3) columella deformities with associated nostril asymmetry, and (4) excessive tip or supratip defatting.


Sustainable Process for the Preparation of High-Performance Thin-Film Composite Membranes using Ionic Liquids as the Reaction Medium.
A new form of interfacial polymerization to synthesize thin-film composite membranes realizes a more sustainable membrane preparation and improved nanofiltration performance. By introducing an ionic liquid (IL) as the organic reaction phase, the extremely different physicochemical properties to those of commonly used organic solvents influenced the top-layer formation in several beneficial ways. In addition to the elimination of hazardous solvents in the preparation, the m-phenylenediamine (MPD) concentration could be reduced 20-fold, and the use of surfactants and catalysts became redundant. Together with the more complete recycling of the organic phase in the water/IL system, these factors resulted in a 50 % decrease in the mass intensity of the top-layer formation. Moreover, a much thinner top layer with a high ethanol permeance of 0.61 L m(-2) h(-1) bar(-1) [99 % Rose Bengal (RB, 1017 Da) retention; 1 bar=0.1 MPa] was formed without the use of any additives. This EtOH permeance is 555 and 161 % higher than that for the conventional interfacial polymerization (without and with additives, respectively). In reverse osmosis, high NaCl retentions of 97 % could be obtained. Finally, the remarkable decrease in the membrane surface roughness indicates the potential for reduced fouling with this new type of membrane.


Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis.
The Mycobacterium tuberculosis (Mtb) gene product encoded by open reading frame Rv1657 is an arginine repressor (ArgR). All genes involved in the L-arginine (hereafter arginine) biosynthetic pathway are essential for optimal growth of the Mtb pathogen, thus making MtbArgR a potential target for drug design. The C-terminal domains of arginine repressors (CArgR) participate in oligomerization and arginine binding. Several crystal forms of CArgR from Mtb (MtbCArgR) have been obtained. The X-ray crystal structures of MtbCArgR were determined at 1.85 A resolution with bound arginine and at 2.15 A resolution in the unliganded form. These structures show that six molecules of MtbCArgR are arranged into a hexamer having approximate 32 point symmetry that is formed from two trimers. The trimers rotate relative to each other by about 11 degrees upon binding arginine. All residues in MtbCArgR deemed to be important for hexamer formation and for arginine binding have been identified from the experimentally determined structures presented. The hexamer contains six regular sites in which the arginine molecules have one common binding mode and three sites in which the arginine molecules have two overlapping binding modes. The latter sites only bind the ligand at high (200 mM) arginine concentrations.


Discovery of Enzymatic Targets of Transcriptional Activators via in Vivo Covalent Chemical Capture.
The network of activator protein-protein interactions (PPIs) that underpin transcription initiation is poorly defined, particularly in the cellular context. The transient nature of these contacts and the often low abundance of the participants present significant experimental hurdles. Through the coupling of in vivo covalent chemical capture and shotgun LC-MS/MS (MuDPIT) analysis, we can trap the PPIs of transcriptional activators in a cellular setting and identify the binding partners in an unbiased fashion. Using this approach, we discover that the prototypical activators Gal4 and VP16 target the Snf1 (AMPK) kinase complex via direct interactions with both the core enzymatic subunit Snf1 and the exchangeable subunit Gal83. Further, we use a tandem reversible formaldehyde and irreversible covalent chemical capture approach (TRIC) to capture the Gal4-Snf1 interaction at the Gal1 promoter in live yeast. Together, these data support a critical role for activator PPIs in both the recruitment and positioning of important enzymatic complexes at a gene promoter and represent a technical advancement in the discovery of new cellular binding targets of transcriptional activators.


Local regional stimulation of single isolated ventricular myocytes using microfluidics.
The regional manipulation of the microenvironment surrounding single adult cardiac myocytes in a microfluidic structure is described. The flow rates of laminar streams were adjusted such that the fluid interface between an injection flow and a perfusion flow was manipulated laterally to stimulate regions of the cell surface. Using this general principle, we were able to selectively expose defined regions of the cell to test solutions, with predefined pulse durations and frequencies. We demonstrate the transient depolarisation of the cardiomyocyte through the regional chemical stimulation of localized areas of the cell with elevated potassium concentrations (100 mM). The results show that chemical stimulation at frequencies < or = 0.25 Hz evoked Ca(2+) transients and cell shortening, comparable to those induced by electrical (field) stimulation. At higher frequencies the membrane potential failed to recover sufficiently from the depolarisation with the high K(+) solution, possibly because of the slow clearance of the ion from the t-tubular system. To test this hypothesis, the clearance of fluorescently labeled 10 kDa dextran from the t-system was measured and found to be approximately 0.5 s delayed compared to that of the bulk extracellular space, indicating the slow diffusion inside the confined space of the tubular membrane invaginations.


Quantum Chemical Modeling of Cycloaddition Reaction in a Self-Assembled Capsule.
Dispersion-corrected density functional theory is used to study the cycloaddition reaction between phenyl acetylene and phenyl azide inside a synthetic, self-assembled capsule. The capsule is first characterized computationally and a previously unrecognized structure is identified as being the most stable. Next, an examination of the free energies of host-guest complexes is conducted, considering all possible reagent, solvent, and solvent impurity combinations as guests. The experimentally observed relative stabilities of host-guest complexes are quite well reproduced, when the experimental concentrations are taken into account. Experimentally, the presence of the host capsule has been shown to accelerate the cycloaddition reaction and to yield exclusively the 1,4-regioisomer product. Both these observations are reproduced by the calculations. A detailed energy decomposition analysis shows that reduction of the entropic cost of bringing together the reactants along with a geometric destabilization of the reactant supercomplex are the major contributors to the rate acceleration compared to the background reaction. Finally, a sensitivity analysis is conducted to assess the stability of the results with respect to the choice of methodology.


[Microsatellite analysis of the 3p13-p25 region in renal cell carcinoma in humans].
Interstitial and terminal deletions of different regions of the chromosome 3 have been associated with the development of human nonpapillary renal cell carcinomas. We performed a microsatellite analysis at the region 3p13-p25 to study the role of the short arm of chromosome 3 in the pathogenesis of Renal Cell Carcinomas. Renal tumor specimens and normal kidney tissue from 57 patients were obtained after radical nephrectomy and immediately snap-frozen. Blood samples were also obtained from each patient, immediately processsed and used as normal DNA. To detect allelic loss, we used 8 microsatellite markers covering the region 3p13-p25. Genetic alterations have been correlated with histology, nuclear grade, pathological stage and stromal cell infiltration. A total of 41 cases (71.9%) were clear cell renal cell carcinomas (CCRCC), 7 (12.3%) were chromophobe renal cell carcinomas, 5 (8.8%) were papillary renal cell carcinomas, and 4 (7%) oncocytic tumors. Microsatellite analysis showed loss of heterozigosity (LOH) in 73.2% of the CCRCCs, and in none of the remaining histologic types. Terminal deletions were detected in 53.3% of the nonpapillary RCCs with LOH, and the remaining nonpapillary RCCs showed multiple interstitial deletions (46.6%). A common region of deletion in 3p14.2 has been observed. Due to contamination with normal DNA, when stromal cell infiltration increases, less losses of heterozigosity are detected. We did not find a correlation between LOH at 3p and the nuclear grade, nor between LOH at 3p and the pathological stage. 1. Microsatellite analysis of LOH at 3p can be used for the differential diagnosis of renal tumors. 2. The evidence of multiple interstitial deletions in a great number of nonpapillary RCCs suggests that more than one gene should be involved in the development of nonpapillary RCC, and already present in early stages of oncogenesis. 3. The common region of deletion 3p14.2 suggests the presence of unstable sequences of DNA that play an important role in the pathogenesis of nonpapillary RCC. 4. LOH at 3p in most nonpapillary RCCs irrespective of the grade and stage, proves that these molecular alterations do not mark a more aggressive behaviour of the tumor.


Clinical pharmacology of human growth hormone and its secretagogues.
The regulation of the synthesis and secretion of human growth hormone (hGH), its biologic activity, and its therapeutic use are reviewed. Both the production and secretion of GH are stimulated by hypothalamic GH-releasing hormone (GHRH) and by the endogenous GH secretagogue (GHS) ghrelin, a product of the oxyntic cells located within the fundus of the stomach. Ghrelin and GHRH act synergistically to stimulate GH secretion when administered in vivo, but they act additively when incubated with somatotrophs in vitro. Ghrelin is also found within the hypothalamic arcuate nucleus where it may enhance the release of GHRH and impair that of somatostatin (SRIH) thus contributing to its synergism with GHRH; ghrelin is an orexigenic peptide as well as a GHS and appears to play an important role in energy metabolism. SRIH inhibits the secretion but not the synthesis of GH and more effectively that stimulated by GHRH than that by ghrelin. The action of GH is mediated by the GH receptor, a straight chain protein of 620 amino acids with extracellular, transmembrane and cytoplasmic domains. GH has two specific receptor binding sites, (I, II) that bind sequentially to similar acceptor sequences of two GHRs. Activation of the GHR signal transduction pathway begins with attachment of two Janus kinase 2 (JAK2) molecules to the intracellular domains of the GHRs leading to phosphorylation of the tyrosine residues of JAK2 and the GHRs; thereafter the signal transduction and activators of transcription (STAT) and Ras mitogen-activated-protein kinase pathways are enhanced. GHRH, SRIH, and ghrelin act through G-protein coupled receptors (GPCR); GHRH activates adenylyl cyclase, cyclic AMP, and protein kinase A pathways, while ghrelin stimulates phospholipase C activity leading to production of inositol 1,4,5-trisphophate and diacylglycerol, increase in cytosolic calcium levels, and GH release; SRIH acts though an inhibitory GPCR to prevent depolarization of the somatotroph thus blocking GH secretion. GH has long been used to stimulate linear growth in children with GH deficiency (GHD); it has also been demonstrated to be effective in adults with GHD. The availability of large quantities of recombinant hGH has broadly increased the number of children with short stature being treated with this agent--not always with marked effectiveness. Synthesis of the GHR antagonist pegvisomant has provided another agent with which to treat patients with acromegaly. GHRH also enhances linear growth rate effectively in children with GHD but is less effective than hGH. The discovery of peptidyl and non-peptidyl GH secretagogues (that preceded and led to the identification of ghrelin itself) presents yet other agents for stimulation of endogenous GH secretion that have been useful in diagnostic studies for GHD and for its treatment in small groups of subjects. It is likely that hGH and its secretagoguess will become of increasing clinical usefulness in future decades.


[Benchmarks for surgical gynecology: results of the German Society of Gynecology and Obstetrics Quality Assurance Study].
Profiling of performance and quality in gynecological surgery is discussed. Unfortunately, most report cards miss valid clinical benchmarks. Within the German study on quality assurance in gynecological surgery we explored whether indicators of quality were suitable as clinical benchmarks. Using a factor analytic approach, we reduced the number of indicators and obtained in a set of 13 indicators of clinical quality. On the basis of the study data on post operative infections we show that these indicators are suitable as clinical benchmarks: the clinical benchmarks are able to make health care quality transparent and demonstrate opportunities for improvement of the processes of gynecological care.


A role for the mu opioid receptor in the antidepressant effects of buprenorphine.
Buprenorphine (BPN), a mixed opioid drug with high affinity for mu (MOR) and kappa (KOR) opioid receptors, has been shown to produce behavioral responses in rodents that are similar to those of antidepressant and anxiolytic drugs. Although recent studies have identified KORs as a primary mediator of BPN's effects in rodent models of depressive-like behavior, the role of MORs in BPN's behavioral effects has not been as well explored. The current studies investigated the role of MORs in mediating conditioned approach behavior in the novelty-induced hypophagia (NIH) test, a behavioral measure previously shown to be sensitive to chronic treatment with antidepressant drugs. The effects of BPN were evaluated in the NIH test 24h post-administration in mice with genetic deletion of the MOR (Oprm1-/-) or KOR (Oprk1-/-), or after pharmacological blockade with the non-selective opioid receptor antagonist naltrexone and selective MOR antagonist cyprodime. We found that behavioral responses to BPN in the NIH test were blocked in Oprm1-/- mice, but not in Oprk1-/- mice. Both cyprodime and naltrexone significantly reduced approach latency at doses experimentally proven to antagonize the MOR. In contrast the selective MOR agonist morphine and the selective KOR antagonist nor-BNI were both ineffective. Moreover, antinociceptive studies revealed persistence of the MOR antagonist properties of BPN at 24h post-administration, the period of behavioral reactivity. These data support modulation of MOR activity as a key component of BPN's antidepressant-like effects in the NIH paradigm.


A practical approach to the management of high-output stoma.
The development of a high-output stoma (HOS) is associated with water, electrolyte and nutritional complications. Prompt, careful assessment and management is required to avoid rapid clinical deterioration in this patient population. A multidisciplinary approach to management ensures the best possible outcome and quality of life for patients who experience HOS. This article outlines the important considerations in the identification and pathophysiology of HOS. A systematic approach to the management of the condition is outlined, considering fluid and electrolyte requirements, nutrient deficiencies and manipulation of gastrointestinal absorption, motility and secretions using medical and surgical therapies.


Editorial: fluid resuscitation in acute pancreatitis: striking the right balance.
Fluid resuscitation is a key component of the early management of acute pancreatitis. Current clinical practice guidelines recommend aggressive fluid resuscitation despite limited prospective data. In this month's issue of the American Journal of Gastroenterology, de-Madaria et al. present findings from a prospective cohort study that evaluate the relationship between early resuscitation parameters and several important outcome measures. Their findings challenge several of our long held beliefs regarding the benefits of vigorous fluid resuscitation in the early phase of acute pancreatitis. Findings from this study along with several others now suggest that a more tailored approach to resuscitation is needed.


Correlates of Calcidiol Deficiency in Adults-Cross-Sectional, Observational, Population-Based Study.
The prevalence, determinants, and clinical significance of vitamin D deficiency in the population are debated. The population-based study investigated the cross-sectional associations of several variables with serum 25-hydroxyvitamin D (calcidiol) measured using standardized calibrators. The study cohort consisted of 979 persons of the Moli-sani study, both sexes, ages ≥35 years. The correlates in the analyses were sex, age, education, local solar irradiance in the month preceding the visit, physical activity, anthropometry, diabetes, kidney function, albuminuria, blood pressure, serum cholesterol, smoking, alcohol intake, calorie intake, dietary vitamin D intake, and vitamin D supplement. The serum calcidiol was log transformed for linear regression because it was positively skewed (skewness = 1.16). The prevalence of calcidiol deficiency defined as serum calcidiol ≤12 ng/mL was 24.5%. In multi-variable regression, older age, lower solar irradiance, lower leisure physical activity, higher waist/hip ratio, higher systolic pressure, higher serum cholesterol, smoking, lower alcohol intake, and no vitamin D supplement were independent correlates of lower serum calcidiol (95% confidence interval of standardized regression coefficient ≠ 0) and of calcidiol deficiency (95% confidence interval of odds ratio > 1). The data indicate that low serum calcidiol in the population could reflect not only sun exposure, age, and vitamin D supplementation but also leisure physical activity, abdominal obesity, systolic hypertension, hypercholesterolemia, smoking, and alcohol intake.


Golden tracheal secretions and bronchoalveolar fluid during acute chest syndrome in sickle cell disease.
Acute chest syndrome (ACS) is the leading cause of ICU admission in patients with sickle cell disease and is characterized by golden sputum, which is commonly attributed to the presence of bilirubin. Three young consecutive patients with homozygous sickle cell disease were admitted for severe acute respiratory syndrome due to ACS. In all 3 patients, tracheal secretions and bronchoalveolar lavage fluid (BALF) showed a yellowish plasma-like stain. After normalization for the plasma-to-BAL urea ratio, BALF protein and lactate dehydrogenase levels were consistent with an exudative process. BALF bilirubin concentrations were very low, implying that the yellowish stain was not related to bilirubin content. The yellowish coloration of tracheal secretions and BALF observed during ACS appears to be related to an intense exudative process rather than to the presence of bilirubin.


A 0/1h-algorithm using cardiac myosin-binding protein C for early diagnosis of myocardial infarction.
Cardiac myosin-binding protein C (cMyC) demonstrated high diagnostic accuracy for the early detection of non-ST-elevation myocardial infarction (NSTEMI). Its dynamic release kinetics may enable a 0/1h-decision algorithm that is even more effective than the ESC hs-cTnT/I 0/1 h rule-in/rule-out algorithm. In a prospective international diagnostic study enrolling patients presenting with suspected NSTEMI to the emergency department, cMyC was measured at presentation and after 1 h in a blinded fashion. Modelled on the ESC hs-cTnT/I 0/1h-algorithms, we derived a 0/1h-cMyC-algorithm. Final diagnosis of NSTEMI was centrally adjudicated according to the 4th Universal Definition of Myocardial Infarction. Among 1495 patients, the prevalence of NSTEMI was 17%. The optimal derived 0/1h-algorithm ruled-out NSTEMI with cMyC 0 h concentration below 10 ng/L (irrespective of chest pain onset) or 0 h cMyC concentrations below 18 ng/L and 0/1 h increase <4 ng/L. Rule-in occurred with 0 h cMyC concentrations of at least 140 ng/L or 0/1 h increase ≥15 ng/L. In the validation cohort (n = 663), the 0/1h-cMyC-algorithm classified 347 patients (52.3%) as 'rule-out', 122 (18.4%) as 'rule-in', and 194 (29.3%) as 'observe'. Negative predictive value for NSTEMI was 99.6% [95% confidence interval (CI) 98.9-100%]; positive predictive value 71.1% (95% CI 63.1-79%). Direct comparison with the ESC hs-cTnT/I 0/1h-algorithms demonstrated comparable safety and even higher triage efficacy using the 0h-sample alone (48.1% vs. 21.2% for ESC hs-cTnT-0/1 h and 29.9% for ESC hs-cTnI-0/1 h; P < 0.001). The cMyC 0/1h-algorithm provided excellent safety and identified a greater proportion of patients suitable for direct rule-out or rule-in based on a single measurement than the ESC 0/1h-algorithm using hs-cTnT/I. ClinicalTrials.gov number, NCT00470587.


The work motivations of mothers with preschool children.
This article provides a qualitative and quantitative analysis of the motivations for employment among a sample of 166 Sydney mothers, each of whom had at least 1 preschool-aged child. Mothers with high and moderate work attachment indicated a multiplicity of motives, of both an extrinsic (financial) and intrinsic (personal satisfaction, sense of achievement) nature. In contrast, the majority of women with low work attachment cited extreme financial need as the only possible reason that would impel them to enter the labor force. When asked which was, or would be, their most important reason for working, women with high work attachment endorsed more nonfinancial than financial reasons, women with moderate work attachment were about equally likely to give either reason, and women with low work attachment predominantly gave financial reasons. Husbands' perceptions of the reasons their wives were working, or would work, showed some, but not complete, agreement with those of their wives.


[Dana swimming crab growth Callinectes danae (Decapoda: Portunidae) from Margarita Island, Venezuela].
Callinectes danae is a common species captured with crab traps in nearby areas of coastal lagoons in Margarita Island. Although its considerable economic importance as a fishery resource, few studies have been done on population dynamics and its fishery potential in local coastal environments to support decision making in fishery administration. We present growth pattern details of Callinectes danae to better estimate its population size and exploitation feasibility. For this, we analyzed a total of 3 623 specimens that were monthly captured in crab pots by artisanal fishermen in Las Marites lagoon, from October 2007 to September 2008. The length-weight ratio was determined, and growth parameters estimated from both length and weight curves of the von Bertalanffy model. The general sex ratio showed no significant difference between males and females (chi2 = 0.04, p > 0.05). However, values of slopes b between males and females were significantly different (t(s) = 2.75, p < 0.05), as well as intercepts a (t(s) = 2.44, p < 0.05). Thus, the length-weight ratio was determined separately: W = 7.48e(-5)*L(2.98) for males and W = 1.21e(-4)*L(2.87) for females, indicating a negative allometric growth in both sexes. Growth parameters were established as: L(infinity) =134.80mm, W(infinity) = 166.04g and k = 0.86/yr for males; L(infinity) = 122.35mm, W(infinity) = 118.45g and k = 0.63/yr for females. Lifespan was estimated at 3.05 years for males and 4.24 years for females. We concluded that Callinectes danae is a species with short lifespan and moderately rapid growth. The coefficient of variation values (CV), of the phi-prime growth performance index (Ø'), showed a different growth pattern compared to those obtained in other regions. We propose that a management strategy will be the periodical review of the minimum capture size for fishing area, after the great variability found in growth parameters.


Mesenchymal stem cells may ameliorate inflammation in an ex vivo model of extracorporeal membrane oxygenation.
Mesenchymal stem cells exhibit immunomodulatory properties which are currently being investigated as a novel treatment option for Acute Respiratory Distress Syndrome. However, the feasibility and efficacy of mesenchymal stem cell therapy in the setting of extracorporeal membrane oxygenation is poorly understood. This study aimed to characterise markers of innate immune activation in response to mesenchymal stem cells during an ex vivo simulation of extracorporeal membrane oxygenation. Ex vivo extracorporeal membrane oxygenation simulations (n = 10) were conducted using a commercial extracorporeal circuit with a CO2-enhanced fresh gas supply and donor human whole blood. Heparinised circuits (n = 4) were injected with 40 × 106-induced pluripotent stem cell-derived human mesenchymal stem cells, while the remainder (n = 6) acted as controls. Simulations were maintained, under physiological conditions, for 240 minutes. Circuits were sampled at 15, 30, 60, 120 and 240 minutes and assessed for levels of interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tumour necrosis factor-α, transforming growth factor-β1, myeloperoxidase and α-Defensin-1. In addition, haemoglobin, platelet and leukocyte counts were performed. There was a trend towards reduced levels of pro-inflammatory cytokines in mesenchymal stem cell-treated circuits and a significant increase in transforming growth factor-β1. Blood cells and markers of neutrophil activation were reduced in mesenchymal stem cell circuits during the length of the simulation. As previously reported, the addition of mesenchymal stem cells resulted in a reduction of flow and increased trans-oxygenator pressures in comparison to controls. The addition of mesenchymal stem cells during extracorporeal membrane oxygenation may cause an increase in transforming growth factor-β1. This is despite their ability to adhere to the membrane oxygenator. Further studies are required to confirm these findings.


Metabolism of n-3 and n-6 fatty acids in Atlantic salmon liver: stimulation by essential fatty acid deficiency.
Oxidation, esterification, desaturation, and elongation of [1-14C]18:2n-6 and [1-14C]18:3n-3 were studied using hepatocytes from Atlantic salmon (Salmo salar L.) maintained on diets deficient in n-3 and n-6 polyunsaturated fatty acids (PUFA) or supplemented with n-3 PUFA. For both dietary groups, radioactivity from 18:3n-3 was incorporated into lipid fractions two to three times faster than from 18:2n-6, and essential fatty acids (EFA) deficiency doubled the incorporation. Oxidation to CO2 was very low and was independent of substrate or diet, whereas oxidation to acid-soluble products was stimulated by EFA deficiency. Products from 18:2n-6 were mainly 18:3n-6, 20:3n-6, and 20:4n-6, with minor amounts of 20:2n-6 and 22:5n-6. Products from 18:3n-3 were mainly 18:4n-3, 20:5n-3, and 22:6n-3, with small amounts of 20:3n-3. The percentage of 22:6n-3 in the polar lipid fraction of EFA-deficient hepatocytes was fourfold higher than in n-3 PUFA-supplemented cells. This correlated well with our other results obtained after abdominal injection of [1-14C]18:3n-3 and [1-14C]18:2n-6. In hepatocytes incubated with [4,5-3H]-22:6n-3, 20:5n-3 was the main product. This retroconversion was increased by EFA deficiency, as was peroxisomal betaoxidation activity. This study shows that 18:2n-6 and 18:3n-3 can be elongated and desaturated in Atlantic salmon liver, and that this conversion and the activity of retroconversion of very long chain PUFA is markedly enhanced by EFA deficiency.


The effect of aurothiomalate on the oxidative burst of polymorphonuclear leukocytes varies with the quantity of drug in myocrisin ampoules.
The antirheumatic drug, sodium aurothiomalate (GSTM), is not a well defined substance and chemical changes occur in the heat sterilization of the commercial ampoules (Myocrisin). In a comparison of the pharmacological properties of Myocrisin with freshly prepared solutions of GSTM, their effects on the chemiluminescence of polymorphonuclear leukocytes (PMN) activated by phorbol myristate acetate (PMA) were studied. Chemiluminescence was measured in the presence of GSTM from solid material and from Myocrisin ampoules. Myocrisin from 1 and 5 mg ampoules and GSTM in fresh solutions heated at 95 degrees C for 30 min inhibited chemiluminescence, whereas Myocrisin from the higher strength (10-50 mg) ampoules and GSTM in unheated solutions showed no effect at low concentrations and enhancement of chemiluminescence at higher concentrations. Since the gold complexes present in the different strength Myocrisin ampoules do not have identical biological effects, the use of GSTM in investigational studies should involve consideration of its source.


Tachycardiomyopathy: a diagnosis not to be missed.
The prognosis of dilated cardiomyopathy is generally poor. In the vast majority of cases the cause of the ventricular dysfunction is irreversible but occasionally potentially curable causes are identified. Tachycardiomyopathy is a rare and potentially treatable cause of heart failure. A patient with a particularly severe case who had an excellent outcome is presented.