Chip electrospray mass spectrometry for carbohydrate analysis.
Currently two types of chip systems are used in conjunction with MS: out-of-plane devices, where hundreds of nozzles, nanospray emitters are integrated onto a single silicon substrate from which electrospray is established perpendicular to the substrate, and planar microchips, embedding a microchannel at the end of which electrospray is generated in-plane, on the edge of the microchip. In the last two years, carbohydrate research greatly benefited from the introduction and implementation of the chip-based MS. In two laboratories the advantages of the chip electrospray in terms of ionization efficiency, sensitivity, reproducibility, quality of data in combination with high mass accuracy, and resolution of detection were systematically explored for several carbohydrate classes: O- and N-glycopeptides, oligosaccharides, gangliosides and glycoprotein-derived O- and N-glycans, and glycopeptides. The current state-of-the-art in interfacing the chip electrospray devices to high-performance MS for carbohydrate analysis, and the particular requirements for method optimization in both positive and negative ion modes are reviewed here. The recent applications of these miniaturized devices and their general potential for glycomic-based surveys are highlighted.


Postural orthostatic tachycardia syndrome: anesthetic implications in the obstetric patient.
We report the anesthetic management of a parturient with postural orthostatic tachycardia syndrome. This syndrome is associated with hemodynamic instability, which can be worsened by the physiology of labor and delivery. We discuss anesthetic concerns with this disease in the parturient and suggest approaches for management of this disease.


[An excessive diagnosis of constipation in children complaining of abdominal pain in a pediatric emergency department: an example of practice patterns].
Prescriptions of abdominal x-ray and diagnosis of constipation seemed too frequent in children evaluated for abdominal pain (AP) in a paediatric emergency unit. To evaluate the prevalence of constipation in children with AP, to determine clinical and radiological signs related to this diagnosis, and to compare frequencies of clinical criteria of functional chronic constipation (FCC) in children with AP with those of controls (children with mild traumatisms without AP). This prospective observational study included children older than 4 years of age consulting for AP. Among 196 patients with AP, 53% had a diagnosis of constipation on discharge (28% isolated and 25% associated with an other diagnosis), and 88% had a plain abdominal x-ray. A faecal retention was considered by emergency practitioners in 92% of children with the diagnosis of constipation vs 22% with other diagnosis (OR=38; CI 95%: 15-101). Clinical criteria of FCC were associated with the diagnosis of constipation (OR=2.7; CI 95%: 1.4-5.2). A FCC was as prevalent in the control population as in AP population (32 vs 34%). An excessive prevalence of diagnosis of constipation was mainly associated with contestable x-ray diagnosis of faecal retention secondary to inappropriate indications of abdominal x-ray.


Oxygenation of Simple Olefins through Selective Allylic C-C Bond Cleavage: A Direct Approach to Cinnamyl Aldehydes.
A novel metal-free allylic C-C σ-bond cleavage of simple olefins to give valuable cinnamyl aldehydes is reported. 1,2-Aryl or alkyl migration through allylic C-C bond cleavage occurs in this transformation, which is assisted by an alkyl azide reagent. This method enables O-atom incorporation into simple unfunctionalized olefins to construct cinnamyl aldehydes. The reaction features simple hydrocarbon substrates, metal-free conditions, and high regio- and stereoselectivity.


The cytoplasmic isoenzyme of horse liver aldehyde dehydrogenase. Relationship to the corresponding human isoenzyme.
The structural divergence between the cytoplasmic isoenzymes of aldehyde dehydrogenase from different species was investigated by analysis of peptides from the horse protein, and correlation of the results with the complete primary structure of the human isoenzyme. The amino acid sequences of these two proteins show a high degree of homology (91% of residues compared are identical). The differences observed are spread over the entire polypeptide chains, with only one cluster, which is close to a reactive cysteine residue and also adjacent to the most conserved region (covering 68 residues) in the primary structures of the whole enzymes. The secondary structure predicted for the human isoenzyme is mainly unaffected by the residue differences in the horse isoenzyme, although limited conformational changes might be compatible with an unexpected overrepresentation of differences involving isoleucine (12 of 43 exchanges represent a loss of Ile in the horse protein). Two cysteine residues that correlate with catalytic activity are identically positioned in the enzyme from the two species.


HPLC characterization of betalains from plants in the amaranthaceae.
HPLC characterization of reversed-phase (RP) high-performance liquid chromatography (HPLC) has been widely used in separation and identification of plant pigments. An effective RP-HPLC-based method is established to systematically isolate, identify, and quantitate the betalain pigments in the plants of 37 species of eight genera in the Amaranthaceae. A total of 16 betacyanins and three betaxanthins are characterized mainly using the RP-HPLC method and also with the aid of mass spectroscopy. The identified betacyanins include eight amaranthine-types, six gomphrenin-types, and two betanin-types. They are also divided into six simple (nonacylated) betacyanins and 10 acylated betacyanins. Acylated betacyanins are identified as betanidin 5-O-beta-glucuronosylglucoside or betanidin 6-O-beta-glucoside acylated with ferulic, p-coumaric, or 3-hydroxy-3-methylglutaric acids. Three betaxanthins were separated from Celosia species in the Amaranthaceae and identified to be immonium conjugates of betalamic acid with dopamine, 3-methoxytyramine, and (S)-tryptophan; the latter two are found to be new betaxanthins from plants.


Characterization of Bacillus subtilis mutants with carbon source-independent glutamate biosynthesis.
Bacillus subtilis synthesizes glutamate from 2-oxoglutarate and glutamine using the glutamate synthase, encoded by the gltAB operon. Glutamate degradation involves the catabolic glutamate dehydrogenase (GDH) RocG. Expression of both gltAB and rocG is controlled by the carbon and nitrogen sources. In the absence of glucose or other well-metabolizable carbon sources, B. subtilis is unable to grow unless provided with external glutamate. In this work, we isolated mutations that suppressed this growth defect of B. subtilis on minimal media (sgd mutants). All mutations enabled the cells to express the gltAB operon even in the absence of glucose. The mutations were all identified in the rocG gene suggesting that the catabolic GDH is essential for controlling gltAB expression in response to the availability of sugars.


Roger Ward Crosskey-The Life and Contributions of an Entomologist par Excellence (1930-2017).
The life of Roger Ward Crosskey stands as a paragon of scholarly dedication to the profession of entomology. His early interests in natural history prepared him for a diverse entomological career of about 65 years. He began as a medical entomologist working on the onchocerciasis problem with the Colonial Service in Northern Nigeria, and officially transitioned to dipterology, first studying the Tachinidae as a taxonomist with the Commonwealth Institute of Entomology, and later the Simuliidae as a Senior Principal Scientific Officer (Merit) with The Natural History Museum in London. His contributions to the fight against onchocerciasis (river blindness) and to the study of Diptera, particularly the Simuliidae, are an enduring legacy. An indexed chronological listing of his 247 publications is provided, in addition to lists of the taxa that he named and the taxa named in his honor.


Penetrating colon trauma.
Of 56 patients with penetrating colon injuries over 6 years, 15% underwent exteriorized repair, 21% received a colostomy, and 64% were treated with primary repair. Of the eight exteriorized repairs, four required conversion to colostomies. In the entire group of 12 colostomies, there were two deaths, four abscesses, and one empyema. Thirty-six patients (64%) underwent primary repair. In this group there was one superficial wound infection, one empyema, but no intra-abdominal abscesses. Eighty per cent had associated injuries. All laparotomy incisions in the primary repair group except two were closed primarily. Large amounts of saline irrigant were used in all cases. All patients received broad spectrum antibiotics pre- and postoperatively. Primary repair of colon injuries can be done safely in many cases. Proper attention must be given to the associated injuries, the patient's general condition, and the time interval between injury and repair. We now find few indications for exteriorization of injured colons. Colostomies are done if our criteria for safe primary repair are not fulfilled.


Range of movement in ray I of manus and pes and the prehensility of the autopodia in the Early Permian to Late Cretaceous non-anomodont Synapsida.
The mobility of ray I was analysed in seventy-eight Early Permian to Late Cretaceous specimens of non-mammalian Synapsida and one extant mammal. In all non-mammaliamorph Synapsida investigated, ray I formed a digital arcade. The first phalanx was maximally extendable to the zero position in the metapodiophalangeal joint I. Metapodiale I was the functional equivalent to a basal phalanx of digits II-V. In contrast, there was no digital arcade in ray I in Mesozoic Mammaliamorpha. Phalanx 1 I was dorsally extendable and metapodiale I was functionally part of the metapodium. During the propulsion phase, autopodial rotation occurred in the majority of Synapsida with abducted limb posture. Regarding ray I, the reduction of autopodial rotation can be estimated, e.g., from the decrease of lateral rotation and medial abduction of the first phalanx in the metapodiophalangeal joint I. Autopodial rotation was high in Titanophoneus and reduced in derived Cynodontia. In Mammaliamorpha the mobility of the first ray suggests autopodial rolling in an approximately anterior direction. Most non-mammaliamorph Therapsida and probably some Mesozoic Mammaliamorpha had prehensile autopodia with an opposable ray I. In forms with a pronounced relief of the respective joints, ray I could be opposed to 90° against ray III. A strong transverse arch in the row of distalia supported the opposition movement of ray I and resulted in a convergence of the claws of digits II-V just by flexing those digits. A tight articular coherence in the digital joints of digits II-V during strong flexion supported a firm grip capacity. Usually the grip capacity was more pronounced in the manus than in the pes. Prehensile autopodia of carnivorous Therapsida may have been utilized to hold prey while biting, thus helping to avoid fractures of the laterally compressed fangs.


Dabigatran etexilate versus low-molecular weight heparin to control consumptive coagulopathy secondary to diffuse venous vascular malformations.
Diffuse venous malformations can be associated with a consumptive coagulopathy characterized by a reduction of fibrinogen level, platelet count and elevated D-dimer level. We report a case of a patient with extensive venous malformations, hemorrhagic symptoms and biological signs of intravascular coagulopathy. She was initially treated effectively with low-molecular weight heparin (LMWH) (enoxaparin 1 mg/kg, bid) and switched to low-dose dabigatran etexilate (110 mg bid) for more than 2 years. Both treatments showed a similar clinical efficacy with the absence of bleeding or thrombotic complications. Compared with LMWH, dabigatran etexilate provided a similar correction of the fibrinogen level and platelet count but was less effective to reduce the D-dimer level. Although dabigatran etexilate can be safely used to control the consumptive coagulopathy secondary to venous malformation and provides a practical alternative to LMWH, its efficacy in vivo at a low dose to reduce the D-dimer level was lower than that of LMWH.


Proteomic analysis of heat stress resistance of cucumber leaves when grafted onto Momordica rootstock.
Various biotic and abiotic stresses threaten the cultivation of future agricultural crops. Among these stresses, heat stress is a major abiotic stress that substantially reduces agricultural productivity. Many strategies to enhance heat stress tolerance of crops have been developed, among which is grafting. Here, we show that Momordica-grafted cucumber scions have intrinsically enhanced chlorophyll content, leaf area, and net photosynthetic rate under heat stress compared to plants grafted onto cucumber rootstock. To investigate the mechanisms by which Momordica rootstock enhanced cucumber scions heat stress tolerance, comparative proteomic analysis of cucumber leaves in response to rootstock-grafting and/or heat stress was conducted. Seventy-seven differentially accumulated proteins involved in diverse biological processes were identified by two-dimensional electrophoresis (2-DE) in conjunction with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF MS). The following four main categories of proteins were involved: photosynthesis (42.8%), energy and metabolism (18.2%), defense response (14.3%), and protein and nucleic acid biosynthesis (11.7%). Proteomic analysis revealed that scions grafted onto Momordica rootstocks upregulated more proteins involved in photosynthesis compared to scions grafted onto cucumber rootstocks under heat stress and indicated enhanced photosynthetic capacity when seedlings were exposed to heat stress. Furthermore, the expression of photosynthesis-related genes in plants grafted onto Momordica rootstocks significantly increased in response to heat stress. In addition, increased high-temperature tolerance of plants grafted onto Momordica rootstock was associated with the accumulation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and oxygen-evolving enhancer protein 1 (OEE1). Taken together, the data indicated that Momordica rootstock might alleviate growth inhibition caused by heat stress by improving photosynthesis, providing valuable insight into enhancing heat stress tolerance in the global warming epoch.


[Management of transplant-associated thrombotic microangiopathy].
The clinical features of transplant-associated thrombotic microangiopathy (TA-TMA) include microangiopathic hemolytic anemia, consumptive thrombocytopenia, and organ dysfunction caused by thrombi in microvessels. The pathogenesis of TA-TMA is based on vascular endothelial insults caused by various factors, including chemotherapy and total-body irradiation used for transplant pre-conditioning, calcineurin inhibitors, cytokines release associated with infection, and complement factors. The incidence of TA-TMA is approximately 15-30% among allogeneic transplant patients, and the mortality rate reaches 100% in severe cases with multi-organ dysfunction. This review describes the current understanding of the pathogenesis, diagnostic criteria, and treatment strategies of this potentially lethal transplant-associated complication.


Diagnosis Codes for Mold Infections and Mold Exposure Before and After Hurricane Harvey Among a Commercially Insured Population-Houston, Texas, 2016-2018.
Indoor mold after flooding poses health risks, including rare but serious invasive mold infections. The purpose of this study was to evaluate use of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes for mold infection and mold exposure in Houston, Texas, during the year before and the year after Hurricane Harvey. This study used data from MarketScan, a large health insurance claims database. The incidence of invasive mold infections remained unchanged in the year after Hurricane Harvey; however, the incidence of diagnosis codes for mold exposure nearly doubled compared with the year before the hurricane (6.3 vs 11.0 per 100 000 enrollees, rate ratio: 1.7, 95% confidence interval 1.0-3.1). Diagnosis codes alone may not be sufficiently sensitive to detect changes in invasive mold infection rates within this population and time frame, demonstrating the need for more comprehensive studies.


COVID-19 severity and outcome in multiple sclerosis: Results of a national, registry-based, matched cohort study.
Risk factors associated with coronavirus disease 2019 (COVID-19) severity in patients with multiple sclerosis (MS) have been described. Recent improvements in supportive care measures and increased testing capacity may modify the risk of severe COVID-19 outcome in MS patients. This retrospective study evaluates the severity and outcome of COVID-19 in MS and characterizes temporal trends over the course of the pandemic in the United States. We conducted a comparative cohort study using de-identified electronic health record (EHR) claims-based data. MS patients diagnosed with COVID-19 between February 2, 2020 and October 13, 2020 were matched (1:2) to a control group using propensity score analysis. The primary outcome was a composite of intensive care unit (ICU) admission, mechanical ventilation, and/or death. A total of 2,529 patients (843 MS and 1,686 matched controls) were included. Non-ambulatory and pre-existing comorbidities were independent risk factors for COVID-19 severity. The risk for the severe composite outcome was lower in the late cohorts compared with the early cohorts. The majority of MS patients actively treated with a disease-modifying therapy (DMT) had mild disease. The observed trend toward a reduction in severity risk in recent months suggests an improvement in COVID-19 outcome.


Ontology-Based Approach to Social Data Sentiment Analysis: Detection of Adolescent Depression Signals.
Social networking services (SNSs) contain abundant information about the feelings, thoughts, interests, and patterns of behavior of adolescents that can be obtained by analyzing SNS postings. An ontology that expresses the shared concepts and their relationships in a specific field could be used as a semantic framework for social media data analytics. The aim of this study was to refine an adolescent depression ontology and terminology as a framework for analyzing social media data and to evaluate description logics between classes and the applicability of this ontology to sentiment analysis. The domain and scope of the ontology were defined using competency questions. The concepts constituting the ontology and terminology were collected from clinical practice guidelines, the literature, and social media postings on adolescent depression. Class concepts, their hierarchy, and the relationships among class concepts were defined. An internal structure of the ontology was designed using the entity-attribute-value (EAV) triplet data model, and superclasses of the ontology were aligned with the upper ontology. Description logics between classes were evaluated by mapping concepts extracted from the answers to frequently asked questions (FAQs) onto the ontology concepts derived from description logic queries. The applicability of the ontology was validated by examining the representability of 1358 sentiment phrases using the ontology EAV model and conducting sentiment analyses of social media data using ontology class concepts. We developed an adolescent depression ontology that comprised 443 classes and 60 relationships among the classes; the terminology comprised 1682 synonyms of the 443 classes. In the description logics test, no error in relationships between classes was found, and about 89% (55/62) of the concepts cited in the answers to FAQs mapped onto the ontology class. Regarding applicability, the EAV triplet models of the ontology class represented about 91.4% of the sentiment phrases included in the sentiment dictionary. In the sentiment analyses, "academic stresses" and "suicide" contributed negatively to the sentiment of adolescent depression. The ontology and terminology developed in this study provide a semantic foundation for analyzing social media data on adolescent depression. To be useful in social media data analysis, the ontology, especially the terminology, needs to be updated constantly to reflect rapidly changing terms used by adolescents in social media postings. In addition, more attributes and value sets reflecting depression-related sentiments should be added to the ontology.


Time-resolved quantitative proteomic analysis of the developing Xenopus otic vesicle reveals putative congenital hearing loss candidates.
Over 200 genes are known to underlie human congenital hearing loss (CHL). Although transcriptomic approaches have identified candidate regulators of otic development, little is known about the abundance of their protein products. We used a multiplexed quantitative mass spectrometry-based proteomic approach to determine protein abundances over key stages of Xenopus otic morphogenesis to reveal a dynamic expression of cytoskeletal, integrin signaling, and extracellular matrix proteins. We correlated these dynamically expressed proteins to previously published lists of putative downstream targets of human syndromic hearing loss genes: SIX1 (BOR syndrome), CHD7 (CHARGE syndrome), and SOX10 (Waardenburg syndrome). We identified transforming growth factor beta-induced (Tgfbi), an extracellular integrin-interacting protein, as a putative target of Six1 that is required for normal otic vesicle formation. Our findings demonstrate the application of this Xenopus dataset to understanding the dynamic regulation of proteins during otic development and to discovery of additional candidates for human CHL.


[Set up of in vitro methods able to detect the safety of astringent liquids].
Most of dental operators agree about a gengival retraction impregnated cord in order to obtain an accurate and overwide dental impression. Hemostatic agents allow the formation of the primary coagulum that determines/causes the retraction of gum connective. Sometimes these astringent liquids cause local inflammation reaction as reported in literature. Aim of this work was the evaluation of the cytotoxic and inflammatory action of the most common astringent liquid on human gum primary cells by in vitro tests. For this purpose primary cultures of normal human oral keratinocytes were established, following used either as monolayer or as reconstituted model. All dental preparations were dissolved in CEC medium, diluted to the designed concentrations and applied to the cultured cells. The cytotoxicity was determined by using MTT test, able to evaluate the succinate dehydrogenase activity and therefore the cell viability. Control cultures were treated with CED alone, whereas sodium dodecyl sulphate (SDS) was used as a positive control. Furthermore, the inflammatory response, determined by measuring TNF-alpha and IFN-gamma release, was evaluated on a reconstituted multilayer human oral epidermis model. All agents tested showed a dose-dependent increase in the cytotoxicity to normal human gingival keratinocytes over the dose range examined. In particular the results obtained suggest the higher toxicity of the Astringedent X compound. The results obtained from the present studies not only provide useful estimates of relative toxicities of these preparations to human oral mucose, but also can be useful as a standard for cytotoxic and inflammatory assessment of newly developed dental preparations to be topically applied to the oral mucosa. It is important to note, however, that the interpolation of these findings to in vivo conditions remains to be done.


Psychometric evaluation of the social experience questionnaire in adolescents: descriptive data, reliability, and factorial validity.
This study evaluated the psychometric properties of the Social Experience Questionnaire (SEQ) in a sample of 1158 adolescents aged 13-17 years. Confirmatory factor analysis fit indices supported the hypothesized three-factor model of the SEQ that assesses overt and relational victimization, and prosocial behaviors from peers. Analyses of gender differences revealed that boys reported being overtly victimized more than girls, and girls reported greater receipt of prosocial behaviors from peers than boys. No gender differences in relational victimization were found. The internal consistency was adequate across gender, and test-retest stability over 12 months was modest. Intercorrelations among overt and relational victimization subscales suggest that these subscales assess related, but relatively independent constructs of peer victimization. These findings support the use of the SEQ with adolescents.


Sociodemographic disparities in epilepsy care: Results from the Houston/New York City health care use and outcomes study.
The purpose of this study was to identify sociodemographic disparities in health care use among epilepsy patients receiving care at different sites and the extent to which the disparities persisted after adjusting for patient characteristics and site of care. Three months of health care use data were obtained from baseline interviews of approximately 560 patients at four sites. One-half of the patients were from a Houston site and two NYC sites that serve predominantly low-income, minority, publicly insured, or uninsured patients. The other half were at the remaining site in Houston that serves a more balanced racial/ethnic and higher sociodemographic population. Differences in general and specialist visits, hospital emergency room (ER) care, and hospitalizations were associated with race/ethnicity, income, and coverage. Logistic regression was used to assess the extent to which the differences persisted when adjusting for individual patient characteristics and site of care. Compared to whites, blacks and Hispanics had higher rates of generalist visits [odds ratio (OR) = 5.3 and 4.9, p < 0.05), ER care (OR = 3.1 and 2.9, p < 0.05) and hospitalizations (OR = 5.4 and 6.2, p < 0.05), and lower rates of specialist visits (OR = 0.3 and 0.4, p < 0.05). A similar pattern was found related to patient income and coverage. The magnitude and significance of the disparities persisted when adjusting for individual characteristics but decreased substantially or were eliminated when site of care was added to the model. There are sociodemographic disparities in health care for people with epilepsy that are largely explained by differences in where patients receive care.


An Overview of Current Alternative Models for Use in the Context of Prostate Cancer Research.
Prostate cancer is one of the most commonly diagnosed cancers worldwide, particularly in elderly populations. To mitigate the expected increase in prostate cancer-related morbidity and mortality as a result of an expanding aged population, safer and more effective therapeutics are required. To this end, plenty of research is focusing on the mechanisms underlying cancer initiation and development, the metastatic process and on the discovery of new therapies. While animal models are used (mainly rats and mice) for the study of prostate cancer, alternative models and methods are increasingly being considered to replace, or at least reduce, the number of animals used in this particular field of research. In this review, we cover some of the alternative models that are currently available for use in the study of prostate cancer, including: mathematical models; 2-D and 3-D cell cultures; microfluidic devices; the chicken egg chorioallantoic membrane-based model; and zebrafish embryo-based models. The main advantages and limitations, as well as some examples of applications, are given for each type of model. According to our analysis, immortalised cell lines are still the most commonly used models in the field of prostate cancer research. However, the use of alternative models for prostate cancer research will likely become more prevalent in the coming years partly because of the increasing societal pressure to reduce the numbers of laboratory animals. In this context, the development and dissemination of effective non-animal alternative models assumes particular relevance and will be instrumental in leveraging their success. Taking these perspectives into account, we believe that technological advances will lead to more effective cell culture systems, namely 3-D cultures or organ-on-a-chip devices, which can be used to replace animal-based models in prostate cancer research.


The Plasma Membrane-Localized Sucrose Transporter IbSWEET10 Contributes to the Resistance of Sweet Potato to Fusarium oxysporum.
SWEET (Sugars Will Eventually be Exported Transporter) proteins, a novel family of sugar transporters, mediate the diffusion of sugars across cell membranes and acts as key players in sucrose phloem loading. Manipulation of SWEET genes in plants leads to various effects on resistance to biotic and abiotic stresses due to disruption of sugar efflux and changes in sugar distribution. In this study, a member of the SWEET gene family, IbSWEET10, was cloned from the sweet potato line ND98. mRNA expression analysis in sweet potato and promoter β-Glucuronidase analysis in Arabidopsis showed that IbSWEET10 is highly expressed in leaves, especially in vascular tissue. Transient expression in tobacco epidermal cells revealed plasma membrane localization of IbSWEET10, and heterologous expression assays in yeast indicated that IbSWEET10 encodes a sucrose transporter. The expression level of IbSWEET10 was significantly up-regulated in sweet potato infected with Fusarium oxysporum Schlecht. f. sp. batatas. Further characterization revealed IbSWEET10-overexpressing sweet potato lines to be more resistant to F. oxysporum, exhibiting better growth after infection compared with the control; conversely, RNA interference (RNAi) lines showed the opposite results. Additionally, the sugar content of IbSWEET10-overexpression sweet potato was significantly reduced, whereas that in RNAi plants was significantly increased compared with the control. Therefore, we suggest that the reduction in sugar content caused by IbSWEET10 overexpression is the major reason for the enhanced F. oxysporum resistance of the transgenic plants. This is the first report that the IbSWEET10 transporter contributes to the resistance of sweet potato to F. oxysporum. The IbSWEET10 gene has the great potential to be used for improving the resistance to F. oxysporum in sweet potato and other plants.


Spindle cell lipoma breast.
Spindle cell lipoma, which usually arises in the soft tissues, is rare in breast and is difficult to differentiate from primary mammary spindle cell tumor. Here, we present the case of a 48-year-old woman with a 3-cm, solitary, well-circumscribed and nontethered mass lying deep within the tissue of left breast, incidentally detected on routine mammography. The spindle cells proved to be immunoreactive to CD 34, but nonreactive to desmin and smooth muscle actin.


Patients' experience of necrotising otitis externa: a qualitative study.
Necrotising otitis externa is a serious infective condition. Patients are typically frail, diagnostic delay is common and severe pain is a key feature. This study aimed to qualitatively analyse patient-centred data to identify key themes in the patient's experience. Open-ended questionnaires were sent to 28 patients. Responses were qualitatively analysed using a grounded theory approach. Iterative cycles were used to develop codes using a constant comparison technique. Emerging categories were refined to identify core themes. Four main themes emerged: severe pain, mental health, quality of life and diagnostic delays. This is the first study to explore patients' perspectives in necrotising otitis externa. It indicates a need to raise awareness of necrotising otitis externa, and to improve symptom management, pain control and quality of life. This valuable information can be used to identify research priorities, guide service improvements, improve clinical care and feed into the development of a Core Outcome Set for necrotising otitis externa.


Hypergravity induces ATP release and actin reorganization via tyrosine phosphorylation and RhoA activation in bovine endothelial cells.
Mechanical stresses regulate physiological and pathological functions of vascular endothelial cells. We examined, in this study, the effects of hypergravity on endothelial functions. Hypergravity (3 G) applied by low speed centrifuge immediately induced a membrane translocation of small G-protein RhoA and tyrosine phosphorylation of 125 kDa FAK in bovine aortic endothelial cells (BAECs). Hypergravity also induced a transient reorganization of actin fibers in 3 min, which was inhibited by Rho-kinase inhibitor (Y27632) and tyrosine kinase inhibitors (herbimycin A and tyrphostin 46). Furthermore, the extracellular ATP concentration ([ATP]o) was increased by 2 G and 3 G hypergravity in 5 min, and the inhibitors of Rho-kinase, tyrosine kinase, and volume-regulated anion channels (VRAC; verapamil, tamoxifen and fluoxetine) significantly suppressed [ATP]o elevation. Application of 3 G hypergravity for 1 h increased the nuclear uptake of BrdU, which was inhibited by Rho-kinase inhibitor and VARC inhibitors. Furthermore, intermittent application of 3 G hypergravity for 1 or 2 h/day stimulated endothelial migration in 5 days, and this was inhibited by suramin, a P2 antagonist. Collectively, these results indicate that hypergravity induces ATP release and actin reorganization via RhoA activation and FAK phosphorylation, thereby activating cell proliferation and migration in BAECs. These also suggest that gravity can be regarded as an extracorporeal signal that could significantly affect endothelial functions.


In vitro engineering of human skin-like tissue.
Coverage of large, full-thickness burns presents a challenge for the surgeon due to the lack of availability of the patient's own skin. Currently, tissue engineering offers the possibility of performing a suitable therapeutic wound coverage after early burn excision by using cultured keratinocyte sheets supported by a dermal layer. The aim of this study was to develop and characterize a skin substitute composed of both epidermal and dermal elements. For this purpose we grew keratinocytes and fibroblasts separately for 15 days within two different types of biomaterials. Cells then were co-cultured for an additional period of 15 days, after which samples were taken and processed with either classic or immunohistochemical stainings. Results showed that (1) human fibroblasts and keratinocytes can be cultured on hyaluronic acid-derived biomaterials and that (2) the pattern of expression of particular dermal-epidermal molecules is similar to that found in normal skin. The data from this study suggest that our skin equivalent might be useful in the treatment of both burns and chronic wounds.


Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague-Dawley rats.
Initiation and intensification of insulin therapy commonly causes weight gain, a barrier to therapy. A contrasting body of evidence indicates that insulin functions as an adiposity negative feedback signal and reduces food intake, weight gain and adiposity via action in the central nervous system. Basal insulin analogs, detemir (Det) and glargine (Glar), have been associated with less hypoglycemia compared with neutral protamine hagedorn insulin, and Det with less weight gain, especially in patients with higher body mass index (BMI). We sought to determine whether insulin therapy per se causes body weight and fat mass gain when delivered via a clinically relevant subcutaneous (SC) route in the absence of hypoglycemia and glycosuria in non-diabetic lean and diet-induced obese rats. Rats were exposed to either a low-fat diet (LFD; 13.5% fat) or high-fat diet (HFD; 60% fat), and received Det (0.5 U kg(-1)), Glar (0.2 U kg(-1)) or vehicle (Veh) SC once daily for 4 weeks. These dosages of insulin were equipotent in rats with respect to blood-glucose concentration and did not induce hypoglycemia. As predicted by current models of energy homeostasis, neither insulin Det nor Glar therapy affected food intake and weight gain in LFD rats. Det treatment significantly attenuated food intake, body weight gain and fat mass gain relative to the Glar and Veh in high-fat fed animals, mirroring observations in humans. That neither insulin group gained excess weight, suggests weight gain with SC basal insulin therapy may not be inevitable. Our data further suggest that Det possesses a unique property to attenuate the development of obesity associated with a HFD.


MDM2 inhibitors for pancreatic cancer therapy.
MDM2 protein negatively regulates p53 and is found to be elevated in cancer cells. An attractive approach towards targeting MDM2 is the use of small molecule inhibitors that bind to MDM2 and disrupt the MDM2-p53 interaction. Our laboratory has been at the forefront in testing MDM2 inhibitors in pancreatic adenocarcinoma (PaCa), a deadly disease with approximately 50% wild-type p53 population. Emerging evidence suggests that apart from regulating p53, MDM2 can influence other key molecules involved in cancer. This review summarizes recent advancements in the development of MDM2 inhibitors, their novel primary and secondary targets and highlights their potential as therapeutics for PaCa.


Potential and caveats of TRAIL in cancer therapy.
Induction of apoptosis in tumor cells is a major goal for chemotherapy and radiation treatment strategies. However, disordered gene expression often leads to apoptosis resistance rendering tumor cells insensitive to various conventional treatments. TNF-related apoptosis-inducing ligand (TRAIL) is a recently identified cytokine of the TNF superfamily that induces apoptosis in tumor cells upon binding to different receptors. Remarkably, the majority of tumor cell lines are sensitive to TRAIL-induced apoptosis, while most nontransformed cell types are TRAIL-resistant. Furthermore, a combination treatment of TRAIL with ionizing irradiation or chemotherapeutic agents induces apoptosis in a highly synergistic manner, particularly in those cells that are otherwise resistant to a sole treatment. In contrast to other TNF members, TRAIL apparently does not exert overt systemic toxicity in murine and primate models, although unexpected concerns about a potential hepatotoxicity of TRAIL have been recently raised. While the molecular mechanisms of TRAIL sensitivity and resistance are poorly understood, TRAIL seems to be a promising biological agent for combination therapy with chemotherapeutic drugs or irradiation.


What factors influence the average length of stay among stroke patients in a Nigerian tertiary hospital?
Increased emphasis is being laid on ensuring that health resources are efficiently utilized, especially in resource-constrained settings such as in Nigeria. One of the main indices of how efficiently a health institution is being run is Length of Stay (LOS), which is likely to be higher in chronic diseases such as stroke and diabetes. Stroke is a chronic disease that is currently on the rise in Low and Middle income countries (LMICs) who are also characterized by constraint of health resources. This study seeks to determine the LOS of stroke patients as well as factors that affect it. A retrospective analysis of health records of stroke victims admitted into the medical wards of the University College Hospital, Ibadan between January 2012 and December 2014 was conducted. Data on sociodemographic information, comorbidities and risk factors were extracted while LOS was calculated by counting the number of days the patient was admitted. Analysis was carried to using SPSS. A total of 143 records were used in the final analysis with 53.1% of them being males and having a mean age of 61.5 ± 14.2 years. More than half (53.8%) of the cases were ischemic strokes. The average length of stay was 13.7 ± 8.9 days while bivariate analysis showed that a greater proportion of cases who consumed alcohol, had diabetes and hypertension had LOS of over 7 days than those who did not. However, these differences in proportions were not statistically significant (0.310<p<0.883). LOS of stroke patients in Nigeria was shown to be prolonged especially when compared to similar settings in West Africa. The high prevalence of some of the risk factors of stroke such as diabetes mellitus indicates that policy and advocacy to drive changes in lifestyle are necessary to reduce the incidence of stroke and its consequent burden on health systems.


Designing Robust Hierarchically Textured Oleophobic Fabrics.
Commercially available woven fabrics (e.g., nylon- or PET-based fabrics) possess inherently re-entrant textures in the form of cylindrical yarns and fibers. We analyze the liquid repellency of woven and nanotextured oleophobic fabrics using a nested model with n levels of hierarchy that is constructed from modular units of cylindrical and spherical building blocks. At each level of hierarchy, the density of the topographical features is captured using a dimensionless textural parameter D(n)*. For a plain-woven mesh comprised of chemically treated fiber bundles (n = 2), the tight packing of individual fibers in each bundle (D2* ≈ 1) imposes a geometric constraint on the maximum oleophobicity that can be achieved solely by modifying the surface energy of the coating. For liquid droplets contacting such tightly bundled fabrics with modified surface energies, we show that this model predicts a lower bound on the equilibrium contact angle of θ(E) ≈ 57° below which the Cassie–Baxter to Wenzel wetting transition occurs spontaneously, and this is validated experimentally. We demonstrate how the introduction of an additional higher order micro-/nanotexture onto the fibers (n = 3) is necessary to overcome this limit and create more robustly nonwetting fabrics. Finally, we show a simple experimental realization of the enhanced oleophobicity of fabrics by depositing spherical microbeads of poly(methyl methacrylate)/fluorodecyl polyhedral oligomeric silsesquioxane (fluorodecyl POSS) onto the fibers of a commercial woven nylon fabric.


Continuous Glucose Monitoring in Endurance Athletes: Interpretation and Relevance of Measurements for Improving Performance and Health.
Blood glucose regulation has been studied for well over a century as it is intimately related to metabolic health. Research in glucose transport and uptake has also been substantial within the field of exercise physiology as glucose delivery to the working muscles affects exercise capacity and athletic achievements. However, although exceptions exist, less focus has been on blood glucose as a parameter to optimize training and competition outcomes in athletes with normal glucose control. During the last years, measuring glucose has gained popularity within the sports community and successful endurance athletes have been seen with skin-mounted sensors for continuous glucose monitoring (CGM). The technique offers real-time recording of glucose concentrations in the interstitium, which is assumed to be equivalent to concentrations in the blood. Although continuous measurements of a parameter that is intimately connected to metabolism and health can seem appealing, there is no current consensus on how to interpret measurements within this context. Well-defined approaches to use glucose monitoring to improve endurance athletes' performance and health are lacking. In several studies, blood glucose regulation in endurance athletes has been shown to differ from that in healthy controls. Furthermore, endurance athletes regularly perform demanding training sessions and can be exposed to high or low energy and/or carbohydrate availability, which can affect blood glucose levels and regulation. In this current opinion, we aim to discuss blood glucose regulation in endurance athletes and highlight the existing research on glucose monitoring for performance and health in this population.


[Therapeutic strategies in cases of septicemia caused by gram-negative bacteria].
Septic shock is the most severe manifestation of infection and appears to be increasingly common, especially in the intensive care units. Lipopolysaccharides (LPS, endotoxin) are known to be responsible for the initiation of septic shock, therefore they can be targets for new preventive and therapeutic strategies. This review focuses on endotoxin-based molecular strategies for the prevention and treatment of Gram-negative sepsis and septic shock.


A new age to an old site: the earliest Tupiguarani settlement in Rio de Janeiro State?
This paper presents unexpectedly early dates for a Tupiguarani settlement in Southeastern Brazil. One radiocarbon dating of 1740 +/- 90 yr BP (1820-1390 cal yr BP) was already available for the Morro Grande site (Araruama, southeastern coast of Rio de Janeiro State). Two new dates, obtained from charcoal samples, are reported here. An age of 2920 +/- 70 yr BP (3220-2790 cal yr BP) was obtained from a specialized hearth, probably used for cooking ceramics; a funerary hearth at the same archaeological locus was dated at 2600 +/- 160 yr BP (3000-2150 cal yr BP). Both measurements were made independently, indifferent laboratories, arguing for their validity. These results considerably age the arrival time of Tupiguarani populations to the coastal region of Southeastern Brazil. They may have important implications to the hypotheses about the origin and dispersion of these populations from Amazonia, supporting the claim of recent authors who consider that their expansion must have begun well before 2000 yrs BP.


Esthesioneuroblastoma. Intermediate filaments, neuroendocrine, and tissue-specific antigens.
Esthesioneuroblastoma (EN), a malignant neuroblastic tumor arising in the superior portion of the nasal cavity, shares histologic similarities with a number of primary malignant tumors that arise in this region, including rhabdomyosarcoma, lymphoepithelioma, and lymphoma. To establish an antigenic profile of EN as an aid in the differential diagnosis of these histologically similar nasal tumors, immunostaining was performed for the following intermediate filaments: keratin, neurofilament, glial fibrillary acidic protein, and desmin; neuron-specific enolase (NSE), S-100 protein, chromogranin, human common leukocyte antigen (HLE), epithelial membrane antigen (EMA), myoglobin, and carcinoembryonic antigen (CEA) on 21 primary nasal tumors: eight EN, five lymphoepitheliomas, two small cell carcinomas, three lymphomas, and three rhabdomyosarcomas. Keratin and CEA stained only the carcinomas (6/7+, 4/7+), respectively; desmin and myoglobin only rhabdomyosarcoma (3/3+, 1/3+); and HLE only lymphomas (3/3+). Chromogranin and neurofilament staining occurred exclusively in one case each of EN. S-100 and NSE commonly stained EN (5/8+, 6/8+), but carcinomas (1/7+, 2/7+) and rhabdomyosarcomas (1/3+, 3/3+) were also positive. Despite the apparent nonspecificity of NSE and S-100, an antigenic profile of positive NSE of S-100 staining with negative epithelial, muscle, and lymphoid antigens uniquely identified six of eight EN. Chromogranin and neurofilament positivity was further evidence for EN in two cases. This antigenic profile is a helpful adjunct in the diagnosis of EN and other primary malignant nasal tumors.


Association of low age at menarche with increased all-cause mortality: a 37-year follow-up of 61,319 Norwegian women.
Little is known about the impact of age at menarche on later mortality. In a cohort of 61,319 Norwegian women interviewed in 1956-1959, the authors analyzed associations between age at menarche and all-cause mortality. A total of 36,114 women died during the 37 years of follow-up. An inverse association was found between age at menarche and the all-cause mortality rate (p < 0.001), with an approximately 2.4% (95% confidence interval: 1.6, 3.1) reduced mortality per year increase in age at menarche. The association was stronger in women with an attained age of less than 70 years (3.9% reduction in mortality) than in women aged 80 years and above (1.5%). The inverse association could not be explained by extreme mortality rates in women with very early (10 years) or late (19 years) menarche or by possible confounding variables such as birth cohort, place of residence, occupational category (own or husband's occupation), body mass index, age at first delivery, or parity. Because of lack of data, residual confounding by physical activity or cigarette smoking could not be ruled out. Women with a menarche at age 18 years or later had, however, a slightly higher mortality rate than was predicted by the linear association.


Immunohistological examination on the distribution of collagen types I, III, IV and V in bovine post partum placentomes.
This paper describes the in situ presence and distribution of collagen types I, III, IV and V in the bovine placenta. The objective was to determine whether there are qualitative and/or quantitative differences in the collagen content of placentomes originating from cows with retained placenta and cows with normal discharge of placenta. Twelve h post partum discharge of the placenta or the incidence of retained placenta was monitored. From 57 cows one placentome per cow was collected within 1 h post partum. The cows were divided into three groups: retained placenta after caesarean section (Group 1), retained placenta after spontaneous calving (Group 2) and normal discharge of placenta within 12 h post partum after spontaneous calving (Group 3). A pilot study was conducted to establish the technique of collecting the placentomes and to verify the applied immunohistological methods used in this work. In the following study, 32 placentomes were used to determine the amount of collagen (types I, III, IV and V) with qualitative and semi-quantitative methods using immunohistochemical techniques. Collagen types I, III, IV and V were found in large quantities in the maternal tissue. In the fetal connective tissue the amount of these collagen types was smaller. In the placentomes of the three groups, no qualitative or quantitative differences could be detected.


Prolonged empirical antibiotic therapy is correlated with bloodstream infections and increased mortality in a tertiary care hospital in Ethiopia: bacteriology testing matters.
Hospital-associated infection (HAI) and antimicrobial resistance (AMR) are major health threats in low- and middle-income countries (LMICs). Because diagnostic capacity is lacking throughout most of Africa, patients are commonly managed with prolonged empirical antibiotic therapy. Our goal was to assess mortality in relation to HAI and empirical therapy in Ethiopia's largest referral hospital. Cohort study of patients with suspected HAI at Tikur Anbessa Specialized Hospital from October 2016 to October 2018. Blood culture testing was performed on an automated platform. Primary outcomes were proportion of patients with bloodstream infection (BSI), antibiotic resistance patterns and 14 day mortality. We also assessed days of therapy (DOT) pre- and post-blood culture testing. Of 978 enrolled patients, 777 had blood culture testing; 237 (30%) had a BSI. Enterobacteriaceae were isolated in 49%; 81% of these were cephalosporin resistant and 23% were also carbapenem resistant. Mortality at 14 days was 31% and 21% in those with and without BSI, respectively. Ceftriaxone resistance was strongly correlated with mortality. Patients with BSI had longer DOT pre-blood culture testing compared with those without BSI (median DOT 12 versus 3 days, respectively, P < 0.0001). After testing, DOT were comparable between the two groups (20 versus 18 days, respectively). BSI are frequent and fatal among patients with suspected HAI in Ethiopia. Highly resistant blood isolates are alarmingly common. This study provides evidence that investing in systematic blood culture testing in LMICs identifies patients at highest risk of death and that empirical management is frequently inappropriate. Major investments in laboratory development are critical to achieve better outcomes.


Benefit of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy and Bidirectional Chemotherapy for Patients with Gastric Cancer with Peritoneal Carcinomatosis Considering Cytoreductive Surgery.
Comprehensive treatment comprising neoadjuvant laparoscopic HIPEC (L-HIPEC) and bidirectional intraperitoneal and systemic induction chemotherapy (BISIC) followed by cytoreductive surgery (CRS) for gastric cancer with peritoneal carcinomatosis (PC) has been developed. However, its benefits and patient selection criteria have not been thoroughly investigated. We retrospectively reviewed 113 patients, with 25 having received comprehensive treatment (L-HIPEC, BISIC, and then CRS-HIPEC; the BISIC group) and 88 having received direct CRS-HIPEC (the CRS group). The BISIC group showed greater tumor clearance in terms of post-CRS peritoneal cancer index ((PCI) 6 vs. 14, p = 0.002) compared to CRS group. The median survival was 20.0 months in the BISIC group and 8.6 months in the CRS group (p = 0.031). Multivariable analysis revealed that the factors associated with increased survival were the BISIC protocol, age, and post-CRS tumor clearance. BISIC significantly improved survival in cases of moderate severity (PCI 11-20) and severe cases (PCI 21-39) without increasing the morbidity rate. We recommend the use of this neoadjuvant strategy for patients with gastric cancer-associated PC and an initial PCI of >10 to provide superior survival outcomes.


Primary Culture of Human Cumulus Cells Requires Stearoyl-Coenzyme A Desaturase 1 Activity for Steroidogenesis and Enhancing Oocyte In Vitro Maturation.
Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in lipid metabolism and is expressed in cumulus cells. The objective of the present study was to evaluate the effect of SCD1 inhibition in human cumulus cells on triglyceride content, steroidogenesis, and oocyte in vitro maturation. Human cumulus cells were exposed to SCD1 inhibitor CAY10566 (SCDinhib) alone or in combination with oleic acid in primary culture. The SCDinhib markedly suppressed triglyceride accumulation (-47%, P = .01), aromatase gene expression (-36%, P = .02), and estradiol production (-49%, P = .01) even at a dose not affecting cell viability and apoptosis. Human immature oocytes at the germinal vesicle (GV) stage were cocultured with pretreated cumulus cells. The rate of oocytes reaching the metaphase II stage was significantly lower in coculture with SCDinhib-treated cumulus cells than with control cumulus cells (-18%, P < .01), which recovered by oleic acid supplementation. This finding on in vitro maturation rate was also reproducible with mouse GV oocytes. The results suggest that SCD1 activity is required for cumulus cell lipid storage and steroidogenesis. In addition, oocyte maturation is negatively affected by SCD1 inhibition in cumulus cells, possibly due to a deficient lipid-mediated paracrine support.


Ergonomic analysis of the surgical position in functional endoscopic sinus surgery.
Ergonomics is the methodologic study of people's efficiency in their work environment and is based on anatomy, physiology, psychology, and engineering. Although highly studied in other work environments, little attention has been paid to surgeons until the landmark survey by Park et al in 2010. Many unique aspects of endoscopic surgery amplify task-related physical discomfort, and, because of these issues, we aimed to study the physical fatigue effects of functional endoscopic sinus surgery (FESS) performed in the standing and sitting positions. Bilateral FESS was performed in 8 cadaver heads (4 in the standing position, 4 in the sitting position), following established ergonomic principles. Physical fatigue was assessed using a 27-point physical discomfort questionnaire, surface electromyography (EMG), and the NASA Task Load Index Survey. Paired and unpaired t tests were used for statistical analysis. Physical fatigue was noted after FESS performed in both positions. An overall similar task burden was seen when comparing the 2 positions, although the sitting position was more "frustrating" (p < 0.05). Discomfort after FESS in the standing position was worse in the legs and low back, whereas, in the sitting position, it was seen predominantly in the upper back and arms (p < 0.05). Mean power frequency EMG measurements demonstrated fatigue of major muscle groups in both positions. Significant physical fatigue is reported after a single FESS operation, with measurable EMG changes. Surgeons should be aware of the short- and long-term physical implications of their daily tasks, and should use this information to be proactive in decision-making for their longevity.


Field information management systems for DNA barcoding.
Information capture pertaining to the "what?", "where?", and "when?" of biodiversity data is critical to maintain data integrity, interoperability, and utility. Moreover, DNA barcoding and other biodiversity studies must adhere to agreed upon data standards in order to effectively contextualize the biota encountered. A field information management system (FIMS) is presented that locks down metadata associated with collecting events, specimens, and tissues. Emphasis is placed on ease of use and flexibility of operation. Standardized templates for data entry are validated through a flexible, project-oriented validation process that assures adherence to data standards and thus data quality. Furthermore, we provide export functionality to existing cloud-based solutions, including Google Fusion Tables and Flickr to allow sharing of these data elements across research collaboration teams and other potential data harvesters via API services.


Emerging Prevention and Treatment Strategies to Control COVID-19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention therapy exists for COVID-19. The unprecedented rise of this pandemic has rapidly fueled research efforts to discover and develop new vaccines and treatment strategies against this novel coronavirus. While hundreds of vaccines/therapeutics are still in the preclinical or early stage of clinical development, a few of them have shown promising results in controlling the infection. Here, in this review, we discuss the promising vaccines and treatment options for COVID-19, their challenges, and potential alternative strategies.


Observations on attempted leprosy cultures in two media.
Suspensions of skin tissue material collected from lepromatous leprosy patients and material from mouse foot-pad harvests were inoculated into two media, viz., a biphasic medium and a minimal basal medium. The cultures were incubated at 37 degrees C and 15 degrees C. Small oval (or round) cells appeared in these cultures around the tenth day along with a few cystic structures; and they increased in number later, reaching the maximum around six-seven weeks. The above cells appeared acid-fast in some cultures and some of them appeared to split into pairs of acid-fast bacilli. The cells were most often seen in the biphasic medium at 37 degrees C. The identity of these structures is not known at this stage.


The β 2-Adrenergic Agonist Salbutamol Inhibits Migration, Invasion and Metastasis of the Human Breast Cancer MDA-MB- 231 Cell Line.
Breast cancer is the most diagnosed and the major cause of cancer death in women worldwide. Metastasis is the main cause of these deaths. The metastatic cascade involves multiple steps and it has been described that adrenergic receptors can modulate this process at multiple levels. However, β -adrenergic action in breast cancer is controversial. We have previously shown that β-adrenergic agonists inhibit cell proliferation and tumor growth of numerous breast cancer models. The purpose of the present investigation was to evaluate adrenergic effect in parameters related to tumor progression (migration, invasion and metastases) in two human breast cancer cell lines. Migration was assessed in IBH-6 and MDA-MB-231 cells by time-lapse videomicroscopy and modified Boyden chambers. Invasion was evaluated by Transwells coated with Matrigel and expression of pro-metastatic genes was determined by RT-qPCR. Experimental metastases studies were performed by injection of the cells in the tail vein of NSG immuno-deficient mice. In both cell lines, salbutamol (β2-agonist) and propranolol (β-blocker) significantly diminished cell migration while epinephrine exerted opposite effects. Moreover, salbutamol inhibited invasion of both breast cancer cell lines and enhanced adhesion to extracellular matrix. Salbutamol treatment was also able to decrease the expression of pro-metastatic genes in MDA-MB-231 cells. Finally, this compound decreased the number and size of MDA-MB-231 lung experimental metastases in NSG immuno- deficient mice. No effect on the establishment of IBH-6 metastases was observed. Our results suggest that salbutamol could be an effective adjuvant drug for the treatment of metastatic breast cancer.


Describing costs related to nursing.
There is limited financial evidence describing the relationship between nursing staffing and patient care costs. In this analysis, the body of knowledge relating costs to nursing practice is described and critiqued. An improved method of describing costs of patient care is presented, and a comparison of costs using each approach illustrates how the magnitude of cost variation between 2 patients differs based on the approach used.


Association of a Surgical Task During Training With Team Skill Acquisition Among Surgical Residents: The Missing Piece in Multidisciplinary Team Training.
The human patient simulators that are currently used in multidisciplinary operating room team training scenarios cannot simulate surgical tasks because they lack a realistic surgical anatomy. Thus, they eliminate the surgeon's primary task in the operating room. The surgical trainee is presented with a significant barrier when he or she attempts to suspend disbelief and engage in the scenario. To develop and test a simulation-based operating room team training strategy that challenges the communication abilities and teamwork competencies of surgeons while they are engaged in realistic operative maneuvers. This pre-post educational intervention pilot study compared the gains in teamwork skills for midlevel surgical residents at Wake Forest Baptist Medical Center after they participated in a standardized multidisciplinary team training scenario with 3 possible levels of surgical realism: (1) SimMan (Laerdal) (control group, no surgical anatomy); (2) "synthetic anatomy for surgical tasks" mannequin (medium-fidelity anatomy), and (3) a patient simulated by a deceased donor (high-fidelity anatomy). Participation in the simulation scenario and the subsequent debriefing. Teamwork competency was assessed using several instruments with extensive validity evidence, including the Nontechnical Skills assessment, the Trauma Management Skills scoring system, the Crisis Resource Management checklist, and a self-efficacy survey instrument. Participant satisfaction was assessed with a Likert-scale questionnaire. Scenario participants included midlevel surgical residents, anesthesia providers, scrub nurses, and circulating nurses. Statistical models showed that surgical residents exposed to medium-fidelity simulation (synthetic anatomy for surgical tasks) team training scenarios demonstrated greater gains in teamwork skills compared with control groups (SimMan) (Nontechnical Skills video score: 95% CI, 1.06-16.41; Trauma Management Skills video score: 95% CI, 0.61-2.90) and equivalent gains in teamwork skills compared with high-fidelity simulations (deceased donor) (Nontechnical Skills video score: 95% CI, -8.51 to 6.71; Trauma Management Skills video score: 95% CI, -1.70 to 0.49). Including a surgical task in operating room team training significantly enhanced the acquisition of teamwork skills among midlevel surgical residents. Incorporating relatively inexpensive, medium-fidelity synthetic anatomy in human patient simulators was as effective as using high-fidelity anatomies from deceased donors for promoting teamwork skills in this learning group.


Fast EEG spike detection via eigenvalue analysis and clustering of spatial amplitude distribution.
In the current study, we tested a proposed method for fast spike detection in electroencephalography (EEG). We performed eigenvalue analysis in two-dimensional space spanned by gradients calculated from two neighboring samples to detect high-amplitude negative peaks. We extracted the spike candidates by imposing restrictions on parameters regarding spike shape and eigenvalues reflecting detection characteristics of individual medical doctors. We subsequently performed clustering, classifying detected peaks by considering the amplitude distribution at 19 scalp electrodes. Clusters with a small number of candidates were excluded. We then defined a score for eliminating spike candidates for which the pattern of detected electrodes differed from the overall pattern in a cluster. Spikes were detected by setting the score threshold. Based on visual inspection by a psychiatrist experienced in EEG, we evaluated the proposed method using two statistical measures of precision and recall with respect to detection performance. We found that precision and recall exhibited a trade-off relationship. The average recall value was 0.708 in eight subjects with the score threshold that maximized the F-measure, with 58.6 ± 36.2 spikes per subject. Under this condition, the average precision was 0.390, corresponding to a false positive rate 2.09 times higher than the true positive rate. Analysis of the required processing time revealed that, using a general-purpose computer, our method could be used to perform spike detection in 12.1% of the recording time. The process of narrowing down spike candidates based on shape occupied most of the processing time. Although the average recall value was comparable with that of other studies, the proposed method significantly shortened the processing time.


[Treatment of pulmonary embolism. Current status and future prospects].
Although still severe, the prognosis of pulmonary embolism has recently improved due to considerable progress in the therapeutic field. This paper concerns the various therapeutic tools, both pharmacologic and surgical, which are already available or under evaluation. Despite the introduction of thrombolytic drugs, heparin remains an indispensable drug. The rationale for its use comes from the need of preventing further clot formation, while endogenous fibrinolysis or thrombolytic drugs are dissolving the already existing clots. Thrombolytic drugs, such as streptokinase, urokinase or rt-PA, have changed the therapeutic strategy of pulmonary embolism, due to their ability to accelerate the normal fibrinolytic mechanisms and to facilitate pulmonary reperfusion. This often allows an early disappearance of symptoms and a reduced incidence of invalidating complications involving the respiratory function. rt-PA seems to be most effective and fast in inducing reperfusion (angiographic signs of clot dissolution are obtained in 82% of the patients within 2 hours). The administration of rt-PA by intravenous bolus has recently been proposed, which would induce an even faster thrombolysis and fewer hemorrhagic complications. The role of surgical therapy has declined after the diffusion of thrombolytic drugs, being reserved only for the most serious cases. When anticoagulation is counter-indicated or not effective, the prevention of embolic relapses can be achieved by percutaneous insertion of caval filters of different types. Some new catheters provided with rotating metallic tips, which allow the mechanical fragmentation of the emboli, are presently under evaluation. Although some improvements are needed, this technique is expected to become soon of general use, especially in cases in which thrombolytic therapy is counter-indicated.


[Contrast induced nephropathy : myth or reality ?]
Contrast induced nephropathy has long been considered as the third cause of inpatients acute renal insufficiency after functional renal insufficiency and acute tubular necrosis. This entity is now controversial. Numerous studies failed to show a direct link between intravenous iodinated contrast injection and a worsening of renal function after injected scanners in patients with normal renal function. The notion of contrast induced nephropathy remains integrated in the practice of the majority of physicians, who often overestimate this risk.


Clinically relevant concentrations of olprinone reverse attenuating effect of propofol on isoproterenol-induced cyclic adenosine monophosphate accumulation in cardiomyocytes.
Propofol has been shown to attenuate beta-adrenoreceptor-mediated signal transduction in cardiomyocytes. Cyclic adenosine monophosphate (cAMP) is an essential second messenger of beta-signal transduction, while olprinone, a phosphodiesterase-III inhibitor, improves poor cardiac performance by increasing cAMP levels. In the present study, we investigated the effects of olprinone toward the reducing effect of propofol on beta-adrenoreceptor-mediated increases in cAMP production. First, suspensions of rat ventricular myocytes were incubated with isoproterenol or olprinone and the effects on cAMP concentrations were assessed. Next, propofol was added prior to the addition of isoproterenol or olprinone. Finally, following preincubation with propofol, isoproterenol with or without olprinone was added. Both isoproterenol and olprinone increased cAMP production in a dose-dependent manner. However, clinically relevant concentrations of olprinone (up to 10(-7) M) did not cause a significant increase. Propofol (10(-7)-10(-4) M) attenuated isoproterenol-stimulated increases in cAMP production (decrease of 2 +/- 4% approximately 43 +/- 1%, as compared to the isoproterenol-stimulated state). However, the agent did not alter olprinone (10(-7) M)-stimulated cAMP production. Olprinone (10(-8)-10(-6) M) reversed the attenuating effect of propofol (10(-5) M) toward isoproterenol (10(-7) M)-stimulated cAMP production dose-dependently (increase of 10 +/- 5% approximately 79 +/- 4% as compared to the propofol-attenuated state). Our results suggest that an improvement in cardiac function is provided by olprinone when the beta-adrenoreceptor-mediated signaling pathway is inhibited by propofol.


Effect of perivascular electromagnetic flow probes on pulmonary hemodynamics.
We determined the effect of perivascular electromagnetic flow probes (EMF) on pulmonary hemodynamics in acute experiments. In seven dogs placement of the EMF on the main pulmonary artery (MPA) increased pulmonary arterial pulse pressure by 25% (17.8-21.9 cmH2O, P less than 0.005) and mean right ventricular pressure by 12% (23.2-25.9 cmH2O, P less than 0.001) but did not alter heart rate, systemic blood pressure, mean pulmonary arterial pressure, or right ventricular end-diastolic pressure. This response was not abolished by local application of lidocaine to the MPA. In three cats input impedance was calculated from measurements of pressure and flow in the MPA. Impedance was calculated with flow measured using an EMF and ultrasonic volume flow probe (USF), which avoids the constraining effect of the EMF. When flow was measured with an EMF rather than a USF, there was a significant difference in the impedance spectra (P less than 0.001), but it was only apparent in the moduli greater than six harmonics. We conclude that the EMF does affect right ventricular afterload in acute experiments and alters the measured input impedance.


Synthesis and cytotoxicity studies of novel [1,2,4]triazolo[1,5-a]pyrimidine-7-amines.
A series of novel N-anilino-5-methyl-2-(3-(5-(alkylaminomethyl)furan-2-yl-methylthio)propyl)-[1,2,4]triazolo-[1,5-a]pyrimidine-7-amine derivatives were synthesized and evaluated for their in vitro cytotoxicity against two cancer cell lines, Bel-7402 and HT-1080. Compounds 9, 14, 19 and 23 possessed marked cytotoxicity, especially 23 (with IC(50) values of 15.0 microM and 7.8 microM against Bel-7402 and HT-1080 cell lines, respectively), which had emerged as lead compound. The activity was found to depend strongly on substitution pattern of the side chains at C-2 position, and 4-triflouromethylanilino substituent at C-7 position was an option for anticancer potency.


Impact of safe community program on motorcyclists' safety with focus on helmet usage in 14 cities of IR Iran.
The aim of this study was to evaluate the effectiveness of safe community interventions on motorcyclists' safety. Two cross sectional observations were conducted in 14 cities (five safe community practicing and nine safe community non-practicing cities) independently on 2005 and 2007. Ten percent of registered motorcycles were observed and interviewed (n=1114 in each observation). 87.9% used motorcycle for commercial purposes. All motorcyclists were male and mostly aged 18-29 years old. Death rate significantly rose from 122 to 254 per 100000 motorcyclists in Fars province since the first observation (p < 0.0001). Helmet usage rate was constant (13%). Recorded crashes increased from 16.4% to 23.1% in safe community setting (p < 0.0001). 11% carried more than one pillion. Heat disturbances, embarrassment, hearing blockage, and negligence were the most mentioned excuses for not using helmet. Law enforcement, public education, accessibility to helmets on discount rate, new legislation and, finally, access to new designed helmet were the most suggestions made by motorcyclists to promote helmet usage. No significant effect was noticed between two settings except in injury registration system in safe community. Community involvement in the safety programs could ensure sustainability of initiatives and continuity of interventions in safe communities.


Clinical history in management of suspected syncope: A powerful diagnostic tool.
In this paper, the role of history taking as a diagnostic tool in patients with transient loss of consciousness (TLOC) is addressed. From a literature review it can be demonstrated that, if properly performed, the history is a powerful diagnostic tool, which in the majority of cases proves to be the only 'test' necessary to establish a diagnosis other than physical examination and electrocardiogram in patients with TLOC. In order to substantiate this conclusion, we examine the different levels of history taking according to the skills and training of the physician involved, the diagnostic yield of each level, the methodology, and the influence of the venue and urgency of the case.


The characteristics of optics polished with a polyurethane pad.
The effect of polishing an optical workpiece with a polyurethane pad was studied in this paper, including material removal rate, surface roughness and subsurface damage. Usually, optical polishing pitch is applied to polish optical workpieces, but the material removal rate (MRR) of pitch is quite low, and polyurethane foam is thus substituted for polishing pitch. With the polyurethane pad a much higher MRR was obtained. Surface roughness and subsurface damage of workpieces were also examined. We were gratified to find that there was almost no subsurface damage in the workpieces manufactured with pad polishing and surface roughness was comparable to the result of pitch polishing. Finally, a hypothesis was proposed in an attempt to explain the result that workpieces were defect-free.


Myomectomy at time of cesarean delivery: a retrospective cohort study.
BACKGROUND: Myomectomy at time of cesarean delivery is traditionally discouraged because of the risk of hemorrhage. A retrospective cohort study was performed to determine whether myomectomy at time of cesarean delivery leads to an increased incidence of intrapartum and short-term postpartum complications. METHODS: A computer search of medical records from May 1991 to April 2001 identified a total of 111 women who underwent myomectomy at time of cesarean delivery and 257 women with documented fibroids during the index pregnancy who underwent cesarean delivery alone. Charts were reviewed for the following outcome variables: change in hematocrit from preoperative to postoperative period, length of operation, length of postpartum stay, incidence of postpartum fever, and incidence of hemorrhage. Hemorrhage was defined as a change in hematocrit of 10 points or the need for intraoperative blood transfusion. RESULTS: The incidence of hemorrhage in the study group was 12.6% as compared with 12.8% in the control group (p = 0.95). There was also no statistically significant increase in the incidence of postpartum fever, operating time, and length of postpartum stay. No patient in either group required hysterectomy or embolization. Size of fibroid did not appear to affect the incidence of hemorrhage. After stratifying the procedures by type of fibroid removed, intramural myomectomy was found to be associated with a 21.2% incidence of hemorrhage compared with 12.8% in the control group, but this difference was not statistically significant (p = 0.08). This study had 80% power to detect a two-fold increase in the overall incidence of hemorrhage. CONCLUSION: In selected patients, myomectomy during cesarean delivery does not appear to result in an increased risk of intrapartum or short-term postpartum morbidity.


Tamoxifen Pharmacogenetics and Metabolism: Results From the Prospective CYPTAM Study.
Tamoxifen is widely prescribed as adjuvant therapy in patients with early-stage breast cancer. It has been postulated that concentrations of endoxifen, the active metabolite of tamoxifen, are a better predictor of tamoxifen efficacy than CYP2D6 genotypes. Although in a retrospective study, an endoxifen threshold of 5.9 ng/mL for efficacy was described, confirmation based on prospective studies is lacking. The objective of the prospective CYPTAM (The Netherlands National Trial Register: NTR1509) study was to associate endoxifen concentrations and CYP2D6 genotypes with clinical outcome in patients with early-stage breast cancer receiving tamoxifen. From February 2008 to December 2010, patients with breast cancer treated with adjuvant tamoxifen were included. Patients could be enrolled up to a maximum of 12 months after tamoxifen initiation. Blood samples were retrieved for CYP2D6 genotyping and endoxifen measurements by Amplichip (Roche Diagnostics, Indianapolis, IN) and high-performance liquid chromatography-tandem mass spectrometry, respectively. Endoxifen concentrations were analyzed as a continuous variable, classifying patients into quartiles and using an endoxifen threshold of 5.9 ng/mL. Endoxifen concentrations and CYP2D6 genotypes were associated with relapse-free survival (censored at the time of tamoxifen discontinuation; RFSt) by Cox regression analysis. A total of 667 pre- and postmenopausal patients were enrolled and had received tamoxifen for a median time of 0.37 years (range, 0.23 to 0.6 years) before study entry. No association was found between endoxifen concentrations and RFSt (adjusted hazard ratio, 0.991; 95% CI, 0.946 to 1.038; P = .691). Also, neither categorizing endoxifen concentrations into quartiles nor using 5.9 ng/mL as threshold altered these results. In addition, no association was found between CYP2D6 genotype and RFSt (adjusted hazard ratio, 0.929; 95% CI, 0.525 to 1.642; P = .799). This prospective clinical study shows no association between endoxifen concentrations or CYP2D6 genotypes and clinical outcome in patients with early-stage breast cancer receiving adjuvant tamoxifen.


Treatment of hypotension in pigs with an inspiratory impedance threshold device: a feasibility study.
An inspiratory impedance threshold device was evaluated in spontaneously breathing animals with hypotension to determine whether it could help improve systemic arterial pressures when fluid replacement was not immediately available. Prospective, randomized. Animal laboratory. Thirty-nine female farm pigs (weight, 28-33 kg). A total of 39 anesthetized spontaneously breathing pigs were treated with an impedance threshold device, with cracking pressures from 0 to -20 cm H2O. Four separate experimental protocols were performed: protocol A, in which the hemodynamics of seven pigs were examined during application of an impedance threshold device at various levels of inspiratory impedance (-5, -10, -15, and -20 cm H(2)O), both before and after a severe, controlled hemorrhage to a systolic blood pressure of 50 - 55 mm Hg; protocol B, in which nine pigs bled to systolic blood pressure of 50 -55 mm Hg were treated with an impedance threshold device set at -12 cm H2O and were compared with nine others treated with a sham device; protocol C, in which the effects of the impedance threshold device on mixed venous gases were measured in seven hemorrhaged pigs; and protocol D, in which the effects of the impedance threshold device on cardiac output in seven hemorrhaged pigs were measured. During initial studies with both normovolemic and hypovolemic pigs, sequential increases in inspiratory impedance resulted in a significant increase in systolic blood pressure, whereas diastolic left ventricular and right atrial pressures decreased significantly and proportionally to the level of impedance. When comparing the sham vs. active impedance threshold device (-12 cm H(2)O) in hypotensive pigs, systolic blood pressure (mean +/- sem) with active impedance threshold device treatment increased from 70 +/- 2 mm Hg to 105 +/- 4 mm Hg (p <.01). Pressures in the control group remained at 70 +/- 4 mm Hg (p <.01). Cardiac output increased by nearly 25% (p <.01) with the active impedance threshold device when calculated using the mixed gas equation and when determined by thermodilution. These studies demonstrate that it is feasible to use a device that creates inspiratory impedance in spontaneously breathing normotensive and hypotensive pigs to increase blood pressure and enhance cardiopulmonary circulation in the absence of immediate fluid resuscitation. Further studies are needed to evaluate the potential long-term effects and limitations of this new approach to treat hypovolemic hypotension.


Potential therapeutic targets for the treatment of opioid abuse and pain.
Although μ-opioid peptide (MOP) receptor agonists are effective analgesics available in clinical settings, their serious adverse effects put limits on their use. The marked increase in abuse and misuse of prescription opioids for pain relief and opioid overdose mortality in the past decade has seriously impacted society. Therefore, safe analgesics that produce potent analgesic effects without causing MOP receptor-related adverse effects are needed. This review highlights the potential therapeutic targets for the treatment of opioid abuse and pain based on available evidence generated through preclinical studies and clinical trials. To ameliorate the abuse-related effects of opioids, orexin-1 receptor antagonists and mixed nociceptin/MOP partial agonists have shown promising results in translational aspects of animal models. There are several promising non-opioid targets for selectively inhibiting pain-related responses, including nerve growth factor inhibitors, voltage-gated sodium channel inhibitors, and cannabinoid- and nociceptin-related ligands. We have also discussed several emerging and novel targets. The current medications for opioid abuse are opioid receptor-based ligands. Although neurobiological studies in rodents have discovered several non-opioid targets, there is a translational gap between rodents and primates. Given that the neuroanatomical aspects underlying opioid abuse and pain are different between rodents and primates, it is pivotal to investigate the functional profiles of these non-opioid compounds compared to those of clinically used drugs in non-human primate models before initiating clinical trials. More pharmacological studies of the functional efficacy, selectivity, and tolerability of these newly discovered compounds in non-human primates will accelerate the development of effective medications for opioid abuse and pain.


Survival, healing, and swim performance of juvenile migratory sea lamprey (Petromyzon marinus) implanted with a new acoustic microtransmitter designed for small eel-like fishes.
Little is known about the transformer stage of the parasitic lampreys, a brief but critical period that encompasses juvenile out-migration from rivers to lakes or oceans to begin parasitic feeding. Information about this life stage could have significant conservation implications for both imperiled and invasive lampreys. We investigated tag retention, survival, wound healing, and swim performance of newly transformed sea lamprey (Petromyzon marinus) implanted with a new micro-acoustic transmitter, the eel-lamprey acoustic transmitter (ELAT), in a controlled laboratory environment. The 61-day survival of our tagged subjects was 71%, within the range reported in similar studies of juvenile lampreys. However, survival was significantly lower in the tagged animals (vs control), with no effect statistically attributable to measures of animal length, mass, condition, or population of origin (Great Lakes vs. Atlantic drainage). Mortality in tagged fish was concentrated in the first four days post-surgery, suggesting injury from the surgical process. An unusually long recovery time from anesthesia may have contributed to the increased mortality. In a simple burst swim assay, tagged animals swam significantly slower (- 22.5%) than untagged animals, but were not significantly different in endurance swim tests. A composite wound healing score at day four was a significant predictor of maximum burst swim speed at day 20, and wound condition was related to animal mass, but not length, at the time of tagging. Impairments to survival and swim performance of juvenile sea lamprey implanted with the ELAT transmitter were within currently reported ranges for telemetry studies with small, difficult to observe fishes. Our results could be improved with more refined anesthesia and surgical techniques. The ability to track migratory movements of imperiled and pest populations of parasitic lampreys will improve our ability to estimate vital rates that underlie recruitment to the adult population (growth, survival) and to investigate the environmental factors that regulate the timing and rates of movement, in wild populations.


Bacterial Community Shifts Driven by Nitrogen Pollution in River Sediments of a Highly Urbanized City.
Effects of nitrogen pollution on bacterial community shifts in river sediments remain barely understood. Here, we investigated the bacterial communities in sediments of urban and suburban rivers in a highly urbanized city, Shanghai. Sediment nitrate (NO3-) and ammonia (NH4+) were highly accumulated in urban river. Operation Taxonomic Units (OTUs), Abundance-based Coverage Estimators (ACEs) and Chao 1 estimator in urban rivers were slightly lower than those in suburban rivers, while Shannon and Simpson indices were higher in urban rivers than those in suburban rivers. Proteobacteria, Firmicutes, and Bacteroidetes were the dominant bacterial phylum communities, accounting for 68.5-84.9% of all communities. In particular, the relative abundances of Firmicutes and Nitrospirae were significantly higher in suburban rivers than in urban rivers, while relative abundances of Bacteroidetes, Verrucomicrobia, and Spirochaetes were significantly lower in suburban rivers than in urban rivers. NH4+ was significantly and negatively correlated with abundances of Firmicutes, Nitrospirae, and Actinobacteria. Importantly, the significant and negative effects of sediment NH4+ on bacterial richness and diversity suggested that nitrogen pollution likely contribute to the decrease in the bacterial richness and diversity. The results highlight that nitrogen enrichment could drive the shifts of bacterial abundance and diversity in the urban river sediments where are strongly influenced by human activities under the rapid urbanization stress.


Local responses to the Maharashtra gutka and pan masala ban: a report from Mumbai.
The Maharashtra government has banned the production, sale, distribution and storage of gutka, and pan masala in the Maharashtra State due to the increasing burden of cancer and reproductive health problems attributable to the use of these products. In view of this, it is important to understand the way producers', sellers' and users' are adapting to the ban. During the two months following the ban (July 19 th through Sept 30, 2012), a research team studying smokeless tobacco use and promotion in a low income community of Mumbai conducted rapid surveillance to assess the impact of the ban in the study community. Assessment involved documenting new points of sale, informal observations of tobacco use, and interviews with thirteen shop owners and eight gutka users'. Overall changes in accessibility, availability, patterns of use of tobacco products, perception of ban, social norms and surveillance activities were assessed. Tobacco companies were marketing new products that resembled gutka, under similar brand logos. Surveillance, financial and social cost of selling gutka or using it in public have had an immediate effect on reducing local supply, demand and use and increasing stigma associated with its use. There was an increased recognition of ill-effects of gutka on cancer among sellers' but not overall. To reduce the overall consumption of tobacco in the community, it is critical to include programs that create awareness about effects of smokeless tobacco on health and sustain surveillance levels. This would maintain requirements of the ban, and sustain limits on accessibility, availability and use of these products in the community and other similar communities.


Investigating the mechanisms underlying affective priming effects using a conditional pronunciation task.
Recently, using a conditional pronunciation task, De Houwer and Randell (2004) reported evidence of affective priming effects only when pronunciation depended on the semantic category of targets. Although these findings support the notion that spreading of activation is the mechanism underlying affective priming effects, an explanation in terms of postlexical mechanism could not be ruled out. To clarify this point, we conducted two experiments in which nouns for both the to-be-pronounced as well as the not-to-be pronounced targets were used and all stimuli were affectively valenced words. In Experiment 1, the to-be-pronounced targets were object-words, and the not-to-be-pronounced targets were person-words, whereas in Experiment 2, the instructions were reversed. Results of experiment 1 showed affective priming effects only when pronunciation of target words was conditional upon their semantic category. Most importantly, affective priming effects were observed for both object-words (Experiment 1) and person-words (Experiment 2). These results are compatible with a spreading activation account, but not with a postlexical mechanism account of affective priming effects in the pronunciation task.


Lyme borreliosis: laboratory considerations.
The laboratory is frequently the primary source for making the diagnosis of Lyme borreliosis when the symptoms are vague and the clinical hallmarks are missing. However, the temptation to interpret the laboratory results out of context from the clinical history and presentation should be avoided since the laboratory tests for evidence of B. burgdorferi infection can also be problematic. These problems have included sensitivity/specificity problems, lack of standardization of both methology and interpretation, and lack of routine direct evidence (ie culture) testing. These problems are discussed as well as possible solutions. It should be noted that meaningful results can usually be obtained from these tests if caution is used in their interpretation and the clinical symptomatology, history, and examination are integrated with the laboratory results.


Hydrolysis of Ionic Phthalic Acid Based Polyesters by Wastewater Microorganisms and Their Enzymes.
Water-soluble polyesters are used in a range of applications today and enter wastewater treatment plants after product utilization. However, little is known about extracellular enzymes and aquatic microorganisms involved in polyester biodegradation and mineralization. In this study, structurally different ionic phthalic acid based polyesters (the number-average molecular weights (Mn) 1770 to 10 000 g/mol and semi crystalline with crystallinity below 1%) were synthesized in various combinations. Typical wastewater microorganisms like Pseudomonas sp. were chosen for in-silico screening toward polyester hydrolyzing enzymes. Based on the in-silico search, a cutinase from Pseudomonas pseudoalcaligenes (PpCutA) and a putative lipase from Pseudomonas pelagia (PpelaLip) were identified. The enzymes PpCutA and PpelaLip were demonstrated to hydrolyze all structurally different polyesters. Activities on all the polyesters were also confirmed with the strains P. pseudoalcaligenes and P. pelagia. Parameters identified to enhance hydrolysis included increased water solubility and polyester hydrophilicity as well as shorter diol chain lengths. For example, polyesters containing 1,2-ethanediol were hydrolyzed faster than polyesters containing 1,8-octanediol. Interestingly, the same trend was observed in biodegradation experiments. This information is important to gain a better mechanistic understanding of biodegradation processes of polyesters in WWTPs where the extracellular enzymatic hydrolysis seems to be the limiting step.


A mixed methods study of the impact of consultant overnight working in an English Emergency Department.
There is a growing expectation that consultant-level doctors should be present within an ED overnight. However, there is a lack of robust evidence substantiating the impact on patient waiting times, safety or the workforce. To evaluate the impact of consultant-level doctors overnight working in ED in a large university hospital. We conducted a controlled interrupted time series analysis to study ED waiting times before and after the introduction of consultant night working. Adverse event reports (AER) were used as a surrogate for patient safety. We conducted interviews with medical and nursing staff to explore attitudes to night work. The reduction seen in average time in department relative to the day, following the introduction of consultant was non-significant (-12 min; 95% CI -28 to 4, p=0.148). Analysis of hourly arrivals and departures indicated that overnight work was inherited from the day. There were three (0.9%) moderate and 0 severe AERs in 1 year. The workforce reported that night working had a negative impact on sleep patterns, performance and well-being and there were mixed views about the benefits of consultant night presence. Additional time off during the day acted as compensation for night work but resulted in reduced contact with ED teams. Our single-site study was unable to demonstrate a clinically important impact of consultant night working on total time patients spend in the department. Our analysis suggests there may be more potential to reduce total time in department during the day, at our study site. Negative impacts on well-being, and likely resistance to consultant night working should not be ignored. Further studies of night working are recommended to substantiate our results.


Association between depression and tinnitus in a nationally representative sample of US older adults.
Few population-based studies examining the association between tinnitus and depression among older adults have been conducted. Therefore, the purpose of this study was to examine the association between tinnitus and depression among a nationally representative sample of US older adults. Data from the 2005-2006 National Health and Nutrition Examination Survey was used. 696 older adults (70-85 yr) completed questionnaires on tinnitus and depression, with depression assessed using the Patient Health Questionnaire-9. After controlling for firearm use, age, gender, race-ethnicity, cardiovascular/stroke history, diabetes, smoking status, body mass index, physical activity, noise exposure and elevated blood pressure, there was a significant positive association (beta coefficient: 1.28, 95% CI: 0.26-2.29, p = 0.01) between depression and tinnitus being at least a moderate problem, suggesting that those who perceived their tinnitus to be a moderate problem were more likely to be depressed than those perceiving it to be a small or no problem. Additionally, after adjustments, those who were bothered by tinnitus when going to bed were 3.06 times more likely to be depressed than those who were not bothered by tinnitus when going to bed (OR = 2.44, 95% CI: 1.03-5.76, p = 0.04). These findings suggest that individuals who perceive their tinnitus to be a problem or have problems with tinnitus when going to bed may be in need of intervention to prevent or reduce their depression symptoms so as to ensure that other areas of their life are not negatively influenced.