bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction of the biosynthetic pathway for the core fungal polyketide scaffold rubrofusarin in Saccharomyces cerevisiae
Authors: Rugbjerg Peter , Naesby Michael , Mortensen Uffe H , Frandsen Rasmus JN
Published: April 2013

Background

Fungal polyketides include commercially important pharmaceuticals and food additives, e.g. the cholesterol-lowering statins and the red and orange monascus pigments. Presently, production relies on isolation of the compounds from the natural producers, and systems for heterologous production in easily fermentable and genetically engineerable organisms, such as Saccharomyces cerevisiae and Escherichia coli are desirable. Rubrofusarin is an orange polyketide pigment that is a common intermediate in many different fungal biosynthetic pathways.

Results

In this study, we established a biosynthetic pathway for rubrofusarin in S. cerevisiae. First, the Fusarium graminearum gene encoding polyketide synthase 12 (PKS12) was heterologously co-expressed with the Aspergillus fumigatus gene encoding phosphopantetheinyl transferase (npgA) resulting in production of YWA1. This aromatic heptaketide intermediate was converted into nor-rubrofusarin upon expression of the dehydratase gene aurZ from the aurofusarin gene cluster of F. graminearum. Final conversion into rubrofusarin was achieved by expression of the O-methyltransferase encoding gene aurJ, also obtained from the aurofusarin gene cluster, resulting in a titer of 1.1 mg/L. Reduced levels of rubrofusarin were detected when expressing PKS12, npgA, and aurJ alone, presumably due to spontaneous conversion of YWA1 to nor-rubrofusarin. However, the co-expression of aurZ resulted in an approx. six-fold increase in rubrofusarin production.

Conclusions

The reconstructed pathway for rubrofusarin in S. cerevisiae allows the production of a core scaffold molecule with a branch-point role in several fungal polyketide pathways, thus paving the way for production of further natural pigments and bioactive molecules. Furthermore, the reconstruction verifies the suggested pathway, and as such, it is the first example of utilizing a synthetic biological “bottom up” approach for the validation of a complex fungal polyketide pathway.
Grip and load force coordination in cyclical isometric manipulation task is not affected by the feedback type
Authors: Pedão Sabrina Tiago , Barela José Angelo , Lima Kauê Carvalho de Almeida , de Freitas Paulo Barbosa
Published: April 2013

Background

The relationship between normal and tangential force components (grip force – GF and load force – LF, respectively) acting on the digits-object interface during object manipulation reveals neural mechanisms involved in movement control. Here, we examined whether the feedback type provided to the participants during exertion of LF would influence GF-LF coordination and task performance.

Methods

Sixteen young (24.7 ±3.8 years-old) volunteers isometrically exerted continuously sinusoidal FZ (vertical component of LF) by pulling a fixed instrumented handle up and relaxing under two feedback conditions: targeting and tracking. In targeting condition, FZ exertion range was determined by horizontal lines representing the upper (10 N) and lower (1 N) targets, with frequency (0.77 or 1.53 Hz) dictated by a metronome. In tracking condition, a sinusoidal template set at similar frequencies and range was presented and should be superposed by the participants’ exerted FZ. Task performance was assessed by absolute errors at peaks (AEPeak) and valleys (AEValley) and GF-LF coordination by GF-LF ratios, maximum cross-correlation coefficients (rmax), and time lags.

Results

The results revealed no effect of feedback and no feedback by frequency interaction on any variable. AEPeak and GF-LF ratio were higher and rmax lower at 1.53 Hz than at 0.77 Hz.

Conclusion

These findings indicate that the type of feedback does not influence task performance and GF-LF coordination. Therefore, we recommend the use of tracking tasks when assessing GF-LF coordination during isometric LF exertion in externally fixed instrumented handles because they are easier to understand and provide additional indices (e.g., RMSE) of voluntary force control.
Is human cytomegalovirus associated with breast cancer progression?
Authors: Utrera-Barillas Dolores , Valdez-Salazar Hilda-Alicia , Gómez-Rangel David , Alvarado-Cabrero Isabel , Aguilera Penélope , Gómez-Delgado Alejandro , Ruiz-Tachiquin Martha-Eugenia
Published: April 2013

Background

It has been hypothesized that human cytomegalovirus (HCMV) may be associated with breast cancer progression. However, the role of HCMV infection in breast cancer remains controversial. We aimed to assess whether HCMV genes (UL122 and UL83) could be detected in breast carcinomas and reinvestigated their possible association with breast cancer progression. DNA from paraffin-embedded tissues was analyzed by real-time PCR. We investigated 20 fibroadenomas and 27 primary breast carcinomas (stages II, III, and IV).

Findings

Two carcinomas were positive for HCMV, one was positive for two TaqMan viral detection probes, and one was positive for a sole TaqMan viral detection probe (UL83), whereas the remainder of the samples was negative.

Conclusions

Samples studied showed no association between HCMV infection and breast cancer progression.
Draft genome of Ochrobactrum intermedium strain M86 isolated from non-ulcer dyspeptic individual from India
Authors: Kulkarni Girish , Dhotre Dhiraj , Dharne Mahesh , Shetty Sudarshan , Chowdhury Somak , Misra Vatsala , Misra Sriprakash , Patole Milind , Shouche Yogesh
Published: April 2013

Background

Ochrobactrum intermedium is an emerging opportunistic pathogen of humans that is closely related to members of the genus Brucella. Earlier, we reported the case of an Indian subject with non-ulcer dyspeptic symptoms whose urease positive gastric biopsy revealed the presence of Helicobacter pylori along with non-Helicobacter like bacteria, eventually cultured and identified as O. intermedium strain M86.

Results

Here, we describe the unclosed draft genome of the strain M86 with a length of 5,188,688 bp and mean G+C content of 57.9%. We have also identified many putative gene clusters that might be responsible for its persistence in the gastric mucosa.Comparative analysis of genomic features of Ochrobactrum intermedium strain M86 and Ochrobactrum intermedium LMG 3301T was also done.

Conclusions

This paper attempts to gain whole-genome based insights into the putative gene determinants of O. intermedium for survival in the highly acidic stomach lumen environment .Identification of genes putatively involved in the various metabolic pathways may lead to a better understanding of the survival of O. intermdedium in acidic condition.
Nonlinear seismic vulnerability evaluation of irregular steel buildings with cumulative damage indices
Authors: Gerami Mohsen , Sharbati Yahya , Sivandi-Pour Abbas
Published: April 2013

Measuring structural damage during earthquakes has always been a challenging problem for earthquake engineers. Various damage indices are proposed with the objective of quantifying the structural damage in prototype and model structures subjected to seismic excitation. In this study, seismic vulnerability of irregular steel buildings is assessed in three dimensions considering effects of the panel zone, which has not been considered in recent studies of the field of seismic vulnerability. The buildings are modeled with different storeys and irregular plans. Seismic performance of buildings was assessed in life-safety and collapse-prevention levels. Cumulative functions of damage indices are applied in the nonlinear dynamic analysis of buildings in the near-field ground motions. It is concluded that participation rates of deformation and energy in the damage of irregular buildings are 74.5% and 25.5%, respectively. Severe damage and collapse due to seismic dissipated energy occurred in the initial storeys of low-rise buildings and in the middle storeys of high-rise buildings.
Difficult-to-detect carbapenem-resistant IMP13-producing P. aeruginosa: experience feedback concerning a cluster of urinary tract infections at a surgical clinic in France
Authors: Milan Odile , Debroize Laurent , Bertrand Xavier , Plesiat Patrick , Valentin Anne-Sophie , Quentin Roland , Van der Mee-Marquet Nathalie
Published: April 2013

Background

We report a carbapenem-resistant P. aeruginosa clone responsible for a cluster of urinary tract infections in elderly surgery patients, diagnosed during a three-month period in a 59-bed surgical clinic.

Findings

The clonal nature of the cluster was established by molecular study of the P. aeruginosa isolates (PFGE and MLST). Despite an MIC of imipenem in the susceptibility range for two isolates, all were metallo-β-lactamase-producers (IMP13-type, clone ST621). We conducted a review of the medical and surgical procedures. We tested water delivered into the clinic and urological devices for the presence of the epidemic strain. The hygiene nurse observed hygiene practices. A week after the implementation of barrier precautions around the fourth infected patient, we studied the extent to which the patients hospitalised were colonised to assess whether the spread of the epidemic strain had been controlled.

Conclusions

1/ Our findings indicate the difficulties in the detection of the metallo-β-lactamase in this clone, that resulted in the alert being delayed. 2/ Unlike most investigations of UTI outbreaks described in urology wards, we did not detect any contaminated urological devices or water colonisation. 3/ Consistent with outbreaks involving the IMP-13 clone in critical care units, the observation of inadequate application of standard precautions argued for patient-to-patient transmission during urinary management of the urology patients. 4/ The implementation of barrier precautions around infected patients resulted in control of the spread of the epidemic clone. This report serves as an alert concerning a difficult-to-detect multidrug-resistant P. aeruginosa clone in elderly urology patients.
Microwave-assisted Synthesis of NaA Zeolite Membrane with High Separating Performance by Seeding Using VPT Method
Authors: Cheng Zhilin , Sun Wei , Han Shuai , Qin Xixi
Published: April 2013

A novel synthesis process was developed for synthesis of NaA zeolite membrane with high quality. The method involved two steps, i.e., the seeding with crystal size of ca. 60 nm formed by vapor-phase transformation and the secondary growth by using microwave heating.
Nitrogen-doped Carbon Nanofibers as Highly Active Metal-free Electrocatalysts for Oxygen Reduction Reactions in Acidic Media
Authors: Yin Jing , Qiu Yejun , Yu Jie
Published: April 2013

Polyacrylonitrile (PAN)-based nitrogen-doped carbon nanofibers (NCNFs) were fabricated by electrospinning. Their electrocatalytic activity for oxygen reduction reactions (ORRs) in 0.5 M H2SO4 solution was greatly enhanced by surface modification by oxidation in a concentrated H2SO4/HNO3 mixture and then NH3 etching at high temperature. The modification treatment resulted in a unique porous structure, fiber diameter reduction, more exposed edge planes, a higher proportion of pyridinic-N, and thus enhancement of ORR activity. The modified NCNF electrocatalysts are highly promising for ORRs in acidic electrolytes.
An Increase in Energy Conversion Efficiency by Decreasing Cobalt Redox Electrolyte Diffusion Resistance in Dye-sensitized Solar Cells
Authors: Uchiyama Takayuki , Murakami Takurou N , Yoshii Nobuhiro , Uemura Yu , Koumura Nagatoshi , Masaki Naruhiko , Kimura Mutsumi , Mori Shogo
Published: April 2013

Cobalt complex redox electrolytes are known to possess high electrolyte diffusion resistances in dye-sensitized solar cells. High resistance was observed not only in the TiO2 pores but also in the bulk of the electrolyte. Therefore, the distance between a dyed TiO2 electrode and a Pt counter electrode was decreased, resulting in increases in the fill factor and short-circuit current. With a carbazole dye, MK-34, an efficiency of 9.3% was obtained under one-sun conditions.
Substituent Effects for Perylenedicarboxylic Anhydrides on the Performance of Dye-sensitized Solar Cells: The Simpler, the Better
Authors: Otsuki Joe , Takaguchi Yusho , Takahashi Daichi , Sugawa Kosuke , Kalimuthu Palanisamy , Islam Ashraful , Han Liyuan
Published: April 2013

The effects of substituents at the bay positions for push–pull-type perylenedicarboxylic anhydride dyes on the performance of dye-sensitized solar cells were investigated. The substituents fine-tune the optical and redox properties of the dyes. It turned out that the simplest dye without any substituent results in highest-efficiency cells because of its broadened IPCE spectrum due to intermolecular interactions, which implies that aggregation may not always be detrimental to the performance of the solar cell.
Statin-Induced Lung Injury; Colchicine-Induced Rhabdomyolysis Caused by Interaction with Clarithromycin; Disulfiram Ethanol Reaction Mimicking Anaphylactic, Cardiogenic, and Septic Shock; Weight Gain with Abdominal Enlargement in a Patient Receiving Tocilizumab; Nilotinib-Associated Acute Pancreatitis
Authors: Mancano Michael A.
Published: April 2013

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Impact of a Pharmacist-Driven Protocol to Improve Drug Allergy Documentation at a University Hospital
Authors: Burrell Christopher , Tsourounis Candy , Quan David , Jue Vicki , Tam Eunice , Guglielmo B. Joseph
Published: April 2013

Background

An internal evaluation of the inpatient pharmacy order entry database ( WORx) at a university hospital revealed that the nature of the reaction was documented for only 47% of patients with reported drug allergies/intolerance. Insufficient documentation of drug allergy/intolerance may result in administration of drugs that should not be prescribed. Similarly, valuable agents that should be used may not be prescribed due to an unnecessary fear of adverse drug reaction. More complete description of drug allergy/intolerance may result in more correct prescribing of medications.

Objective

Evaluate the impact of a pharmacist-driven protocol on the quality of drug allergy/intolerance documentation.

Methods

Four pre-intervention evaluations were conducted every 2 weeks documenting the completeness of drug allergy/intolerance information in the pharmacy order entry database. One week following the implementation of a pharmacist-driven protocol intended to improve the completeness of drug allergy/intolerance information, a series of 4 postintervention evaluations was repeated. Proportional analysis of pre- and postinterventional data was performed to evaluate the effectiveness of the intervention.

Results

A total of 1,686 allergies from 2,174 patients were reviewed pre and post intervention. The frequency of complete drug allergy/intolerance documentation pre intervention was 52% to 62%. Following implementation of the hospitalwide, pharmacist-driven protocol, this rate increased to 60% to 76%. Pediatric services demonstrated the most substantial improvement, increasing from 53% to 79% to 67% to 93%. Blank reaction fields decreased by 10% in both age groups.

Conclusion

A pharmacy-driven initiative intended to improve the completeness of drug allergy/intolerance documentation was associated with modest success. Other mechanisms, including electronic health record systems with computerized physician order entry and decision support, are needed to improve the completeness of drug allergy/intolerance information.
Crys tal struc ture of [Nd2(nba)2(Hnba)2(H2O)6]·2H2O, C32H30N4Nd2O32
Authors: Gao Fan , Yao Lin , Liu Jie , Ma De-Liang , Niu De-Zhong
Published: April 2013

Abstract C32H30N4Nd2O32, triclinic, P1̄ (no. 2), a = 8.137(3) Å, b = 8.800(3) Å, c = 15.184(5) Å, α = 100.201(7)°, β = 91.400(8)°, γ = 104.336(7)°, V = 1034.1 Å3, Z = 1, Rgt(F) = 0.0431, wRref(F2) = 0.1155, T = 296 K.
Improving Reservoir Characterization and Simulation With Near-Wellbore Modeling
Authors: Chandra V.. , Corbett P.W.M.. W.M. , Geiger S.. , Hamdi H..
Published: April 2013

New reservoir characterization methods are needed to integrate multiscale exploration and development data, particularly at the interface between well and field models. In this paper, we illustrate a novel workflow involving high-resolution near-wellbore modeling (NWM), which allows us to accurately include seismic, wireline data, image logs, and well core logs from highly heterogeneous reservoirs in field-scale reservoir simulations. We demonstrate that an NWM-enhanced geoengineering workflow has the potential to improve reservoir characterization by applying it to a realistic clastic reservoir with high variance at small scale. We have performed a number of sensitivities comparing conventional local grid refinement (LGR) in the near-wellbore region with that involving NWM, and we obtained a significant increase in the accuracy of reservoir characterization and the calibration of dynamic models. Centimeter-scale models, containing several million cells, representing the fine geological details of the near-wellbore region, were constructed with available data from core and openhole well-log suits. The resulting well models were upscaled into regular grids with the highest resolution possible through the NWM software and incorporated into a field-scale simulation model to evaluate the dynamic behavior of the reservoir with a static-model transient test. Our results show that the use of NWM tools for reservoir modeling yields more precise flow calculations and improves our fundamental understanding of the interactions between the reservoir and the wellbore.
Enhanced oil–mineral aggregation with modified bentonite
Authors: Chen Li , Zhou Yanbo , Wang Xiaoqian , Zwicker Thomas , Lu Jun
Published: April 2013

The application of modified-bentonite-enhanced oil dispersion in water and oil–mineral aggregate (OMA) formation was studied in the laboratory. The effect of modification on the surface properties of bentonite was characterized. The hydrophobicity and surface electric properties of bentonite were significantly improved by attaching cetyltrimethyl ammonium bromide to its surface. The results showed that surface properties of bentonite played an important role in OMA formation. Spherical droplets of OMAs were formed with natural bentonite and elongated solid OMAs and flake OMAs were formed with modified bentonite as observed by fluorescence microscopy. The effects of shaking time, oil concentration and mineral content were also studied. It was suggested that oil concentration and mineral content were critical factors and OMA formed rapidly with both types of bentonite. Modified bentonite had better performance on OMA formation than hydrophilic natural bentonite.
Effect of wastewater chlorination on endocrine disruptor removal
Authors: Noutsopoulos C. , Mamais D. , Samaras V. , Bouras T. , Marneri M. , Antoniou K.
Published: April 2013

Endocrine disrupting chemicals (EDCs) are compounds of mainly anthropogenic origin that interfere with the endocrine system of animals and humans thus causing a series of disorders. Wastewater treatment plants are one of the major routes for transporting such chemicals to the water courses. In the context of this study, several chlorination batch tests were performed in order to assess the effectiveness of chlorination to remove bisphenol A (BPA), triclosan (TCS), nonylphenol (NP) and its ethoxylates (NP1EO and NP2EO) from secondary effluent. According to the results, an appreciable removal of NP, BPA and TCS to the order of 60–84% was observed as an effect of moderate chlorination doses. This was not the case for NP1EO and NP2EO as even at high chlorine doses, removal efficiencies were lower (37% for NP1EO and 52% for NP2EO). Removal efficiencies of NP, BPA and TCS are practically independent of contact time, although this was not the case for NP1EO and NP2EO. Based on toxicity experiments, it is anticipated that following chlorination of the target chemicals, production of more toxic metabolites is taking place. Therefore the effectiveness of chlorination to remove EDCs is questionable and more research is needed to guarantee safe wastewater reuse.
On the generating function e
xt+yϕ(t) and its fractional calculus
Authors: Ansari Alireza , Sheikhani Amirhossein , Kordrostami Sohrab
Published: April 2013

In this article, we derive the coefficient set {H
m(x,y)}m=1∞ using the generating function ext+yϕ(t). When the complex function ϕ(t) is entire, using the inverse Mellin transform, and when ϕ(t) has singular points, using the inverse Laplace transform, the coefficient set is obtained. Also, bi-orthogonality of this set with its associated functions and its applications in the explicit solutions of partial fractional differential equations is discussed.
Oral financial reporting: A rhetorical analysis of earnings calls
Authors: Crawford Camiciottoli Belinda
Published: April 2013

Earnings calls are a key form of voluntary financial reporting through which companies seek to proactively engage investors. Although now quite routine, little is known about their rhetorical dimension. Inspired by Aristotlean classical rhetoric, this paper offers an exploratory analysis of the language of a small sample of earnings calls to identify expressions of logos (reason), ethos (credibility) and pathos (emotion). Text analysis software was used to generate descriptive data for follow-up qualitative analysis to interpret strategic usage. Results indicate a strong presence of persuasive language that is skillfully juxtaposed by company executives with financial information to emphasize success and instill confidence. The findings can be applied towards developing state-of-the-art courses for students of financial communication and towards enhancing the effectiveness of financial reporting.
Giustizia organizzativa, supporto sociale e burnout tra lavoratori della Sanità: effetti diretti e di moderazione
Authors: Loera Barbara , Gattino Silvia , Converso Daniela
Published: April 2013

Il contributo illustra i risultati di una ricerca sul ruolo che la giustizia organizzativa e il supporto sociale - da parte di colleghi e superiori - hanno in ambito lavorativo sull'insorgere del burnout. Obiettivo è evidenziare gli effetti di queste dimensioni organizzative sull'insorgere della sindrome e, nel dettaglio, identificare gli eventuali effetti di moderazione del supporto sociale sulla relazione tra giustizia organizzativa e burnout. Lo studio è stato condotto nell'Azienda Sanitaria Ospedaliera più grande del Piemonte e ha coinvolto 503 operatori che lavorano in tre reparti molto diversi dal punto di vista delle caratteristiche dei pazienti e dell'intensità del sistema di cure (ICU e non-ICU): medicina d'urgenza, medicina interna e radiodiagnostica. I risultati hanno messo in luce sia la presenza di effetti diretti della giustizia e del supporto sociale sul burnout, sia effetti di moderazione del supporto sociale sulla relazione tra giustizia e dimensioni del burnout, diversificati sulla base dei reparti coinvolti nell'indagine. .
Reazioni psicologiche in soggetti con amputazione di arto: una rassegna della letteratura
Authors: Luchetti Martina , Cutti Andrea Giovanni , Montebarocci Ornella , Verni Gennaro , Rossi Nicolino Cesare Franco
Published: April 2013

L'obiettivo di questo lavoro è fornire un quadro aggiornato sull'attuale stato delle conoscenze relative all'adattamento psicologico post-amputazione, fornendo un'analisi critica degli aspetti metodologici e illustrando alcuni strumenti specificatamente allestiti per indagare le problematiche psicosociali dei soggetti amputati. I risultati delle ricerche evidenziano la presenza di sintomi ansioso-depressivi significativi nel breve periodo dopo il trauma, così come a distanza di numerosi anni. Tuttavia, restano poco indagate alcune fasi potenzialmente critiche, come il periodo immediatamente successivo alla dimissione dai centri di riabilitazione in cui il supporto delle terapie si riduce. Data la complessità del processo di adattamento alla perdita di un arto, diversi autori hanno sottolineato la necessità di ulteriori studi longitudinali, al fine di esplorare l'evoluzione delle reazioni psicologiche nelle diverse fasi del percorso riabilitativo/protesico, nel breve e lungo periodo post-amputazione. Considerare aspetti di natura psicosociale, oltre che medico-riabilitativa, è di rilevanza centrale sia per la ricerca che per la pratica clinica.
Il conflitto lavoro-famiglia e il sense of entitlement: una ricerca in un'azienda svedese
Authors: Ricotta Simona , Ghislieri Chiara , Colombo Lara , Piccardo Claudia
Published: April 2013

Il conflitto lavoro-famiglia, dovuto all'incompatibilità tra le richieste associate al ruolo lavorativo e a quello familiare, rappresenta un tema oggetto di crescente attenzione per le sue possibili conseguenze negative a livello individuale, familiare e organizzativo. La presente ricerca ha coinvolto 641 dipendenti di un'azienda svedese, con l'obiettivo di valutare l'influenza di alcune variabili (il carico di lavoro e il numero di ore lavorative, la qualità delle relazioni, il supporto organizzativo alla conciliazione) sul conflitto lavoro-famiglia e di osservare eventuali differenze nelle determinanti del conflitto lavoro-famiglia in relazione alla percezione di legittimità del supporto organizzativo (sense of entitlement). Le risposte evidenziano la presenza di un elevato sense of entitlement e mostrano che il conflitto lavorofamiglia aumenta al crescere del carico di lavoro e diminuisce in presenza di buone relazioni con il management e di supporto organizzativo. Quest'ultimo aspetto, però, riduce la percezione di conflitto solo per coloro con alto sense of entitlement.
Donne e tumore al seno: effetti del protocollo guidato di scrittura sui sintomi associati al disturbo post-traumatico da stress
Authors: Martino Maria Luisa , Onorato Raffaella , D'Oriano Veronica , Freda Maria Francesca
Published: April 2013

La malattia tumorale al seno si configura come un evento traumatico in grado di compromettere il senso di continuità ed integrazione della propria storia di vita dando luogo, spesso, ad esiti psicopatologici. Entro il paradigma della scrittura espressiva, il presente contribuito valuta l'effetto del Guided Written Disclosure Protocol sui sintomi associati al Disturbo posttraumatico da stress di 40 donne affette da neoplasia mammaria in trattamento farmacologico post-operatorio - 20 trattate con chemioterapia e 20 trattate con terapia biologica - attraverso rilevazioni testologiche, ripetute nel tempo, del test IES-R. È stata effettuata una serie di Anova per Misure Ripetute. I risultati mostrano, nel confronto tra gruppi, sperimentale/controllo, al trascorrere del tempo, una diminuzione significativa dei punteggi delle sottoscale intrusione e irritabilità entro il gruppo sperimentale. Al contrario, l'andamento crescente delle sottoscale intrusione e irritabilità, entro il gruppo di controllo, lascia ipotizzare come il trascorrere del tempo, in assenza di uno spazio di sostegno, non sia un "rimedio naturale" contro il disagio psicologico. Inoltre l'analisi evidenzia che i vissuti connessi ai diversi momenti terapeutici non influenzano la possibilità di beneficiare della scrittura. Entro il presente studio il protocollo di scrittura si è configurato, quindi, come uno strumento di sostegno utile durante le diverse fasi della terapia, che in sinergia con le cure mediche consente di contenere gli effetti del trauma e a svolgere, in tal modo, una funzione di prevenzione. Promuovere salute, non solo dopo la guarigione ma fin dall'esordio della malattia. .
Steroidal Triterpenes of Cholesterol Synthesis
Authors: Ačimovič Jure , Rozman Damjana
Published: April 2013

Cholesterol synthesis is a ubiquitous and housekeeping metabolic pathway that leads to cholesterol, an essential structural component of mammalian cell membranes, required for proper membrane permeability and fluidity. The last part of the pathway involves steroidal triterpenes with cholestane ring structures. It starts by conversion of acyclic squalene into lanosterol, the first sterol intermediate of the pathway, followed by production of 20 structurally very similar steroidal triterpene molecules in over 11 complex enzyme reactions. Due to the structural similarities of sterol intermediates and the broad substrate specificity of the enzymes involved (especially sterol-Δ24-reductase; DHCR24) the exact sequence of the reactions between lanosterol and cholesterol remains undefined. This article reviews all hitherto known structures of post-squalene steroidal triterpenes of cholesterol synthesis, their biological roles and the enzymes responsible for their synthesis. Furthermore, it summarises kinetic parameters of enzymes (Vmax and Km) and sterol intermediate concentrations from various tissues. Due to the complexity of the post-squalene cholesterol synthesis pathway, future studies will require a comprehensive meta-analysis of the pathway to elucidate the exact reaction sequence in different tissues, physiological or disease conditions. A major reason for the standstill of detailed late cholesterol synthesis research was the lack of several steroidal triterpene standards. We aid to this efforts by summarizing commercial and laboratory standards, referring also to chemical syntheses of meiosis-activating sterols.
Breast Cancer Survivorship and South Asian Women: Understanding about the Follow-Up Care Plan and Perspectives and Preferences for Information Post Treatment
Authors: Singh–Carlson S. , Wong F. , Martin L. , Nguyen S.K.A.
Published: April 2013

Background and Objectives: As more treatment options become available and supportive care improves, a larger number of people will survive after treatment for breast cancer. In the present study, we explored the experiences and concerns of female South Asian (sa) breast cancer survivors (bcss) from various age groups after treatment to determine their understanding of follow-up care and to better understand their preferences for a survivorship care plan (scp). Methods: Patients were identified by name recognition from BC Cancer Agency records for sa patients who were 3–60 months post treatment, had no evidence of recurrence, and had been discharged from the cancer centre to follow-up. Three focus groups and eleven face-to-face semistructured interviews were audio-recorded, transcribed verbatim, cross-checked for accuracy, and analyzed using thematic and content analysis. Participants were asked about their survivorship experiences and their preferences for the content and format of a scp. Results: Fatigue, cognitive changes, fear of recurrence, and depression were the most universal effects after treatment. “Quiet acceptance” was the major theme unique to sa women, with a unique cross-influence between faith and acceptance. Emphasis on a generalized scp with individualized content echoed the wide variation in breast cancer impacts for sa women. Younger women preferred information on depression and peer support. Conclusions: For sa bcss, many of the psychological and physical impacts of breast cancer diagnosis and treatment may be experienced in common with bcss of other ethnic backgrounds, but the present study also suggests the presence of unique cultural nuances such as spiritual and language-specific support resource needs. The results provide direction for designing key content and format of scps, and information about elements of care that can be customized to individual patient needs.
Case Report of Very Late Gastric Cancer Recurrence
Authors: Blanchette P. , Lipton J.H. , Barth D. , Mackay H.
Published: April 2013

Very late recurrence of gastric cancer is rare. Here, we report a dramatic recurrence of gastric cancer, with isolated skeletal metastasis and bone marrow carcinomatosis, 22 years after the patient’s initial presentation. Gastric cancer recurrence involving bone or bone marrow is also uncommon and associated with poor prognosis. Pathology from a bone marrow biopsy showed signet ring cell morphology. The patient in this case demonstrated a surprising response—lasting 11 months—to palliative chemotherapy with cisplatin and capecitabine. This case report and literature review describes the characteristics of late gastric cancer recurrence and an approach to the diagnosis and management of patients with bone metastasis or bone marrow carcinomatosis.
Perceptions of Survivorship Care among South Asian Female Breast Cancer Survivors
Authors: Singh–Carlson S. , Nguyen S.K.A. , Wong F.
Published: April 2013

Background and Objectives: To explore the perceptions of South Asian (sa) breast cancer survivors concerning their follow-up care, and to determine the optimal content and format of a survivorship care plan (scp) for this population, according to various life stages. Methods: A survey was mailed to 259 sa women with a diagnosis of nonmetastatic breast cancer who were 18–85 years of age, 3–60 months post-discharge, and not on active treatment. Descriptive statistics and content analysis were applied to the responses. The data were cross-tabulated by age: group A (64 years). Results: We received 64 completed surveys. The compliance rate for adjuvant hormonal therapy was high (86.3%). Most of the respondents (n = 61, 95.4%) had visited their family doctor within several months (0.5–24 months) after discharge. Their main physical effects concern was fatigue, and anxiety concerning health was the main psychosocial impact. Groups A and B were more concerned about physical appearance, depression, and the impact of cancer on family members. Women in the older groups were concerned about family obligations and work issues. Several women (n = 9, 14.1%) described strain on their marriage and on their relationships with family and friends as significant issues. Slightly more than one third (n = 24, 37.5%) experienced a deepening of faith, and almost as many (n = 23, 35.9%) felt that their illness was something that was meant to happen. Conclusions: Many of the impacts of breast cancer treatment are shared by women of all ethnic backgrounds. Others—such as high levels of compliance, little reported strain on spousal and family relationships, and the importance of faith—reflect specific cultural variations. These universal and culture-specific themes should all be kept in mind when developing a scp tailored to sa women. The developmental life stage of a woman affects how she views the cancer diagnosis, especially with respect to family, reproduction, and work issues.
Role of Endolaryngeal Surgery (with or without Laser) Compared with Radiotherapy in the Management of Early (T1) Glottic Cancer: A Clinical Practice Guideline
Authors: Yoo J. , Lacchetti C. , Hammond J.A. , Gilbert R.W.
Published: April 2013

Aims: To provide evidence-based practice guideline recommendations concerning the role of endolaryngeal surgery (with or without laser) compared with radiation therapy for patients with early (T1) glottic cancer, assessing survival, locoregional control, laryngeal preservation rates, and voice outcomes. Methods: The MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies from 1996 to 2011. Recommendations were formulated based on that evidence and on the expert opinion of Cancer Care Ontario’s Head and Neck Cancer disease site group. The systematic review and practice guideline were externally reviewed by practitioners in Ontario, Canada. Results: The available evidence was of a level insufficient to demonstrate a clear difference between treatment options when considering the likelihood of local control or overall survival. Although the evidence was mainly retrospective, there was a suggestion that, compared with surgery, radiotherapy might be associated with less measureable perturbation of voice without a significant difference in patient perception. The likelihood of laryngeal preservation may be higher when surgery can be offered as initial treatment. Conclusions: For patients with early (T1) glottic cancer, the evidence is insufficient to demonstrate a difference between endolaryngeal surgery (with or without laser) and external-beam radiation therapy. The choice between treatment modalities has been based on patient and clinician preferences and general medical condition.
Assessing Fitness to Drive in Brain Tumour Patients: A Grey Matter of Law, Ethics, and Medicine
Authors: Louie A.V. , Chan E. , Hanna M. , Bauman G.S. , Fisher B.J. , Palma D.A. , Rodrigues G.B. , Warner A. , D’Souza D.P.
Published: April 2013

Background: Neurocognitive deficits from brain tumours may impair the ability to safely operate a motor vehicle. Although certain jurisdictions in Canada legally require that physicians report patients who are unfit to drive, criteria for determining fitness are not clearly defined for brain tumours. Methods: Patients receiving brain radiotherapy at our institution from January to June 2009 were identified using the Oncology Patient Information System. In addition to descriptive statistics, details of driving assessment were reviewed retrospectively. The Fisher exact test was used to determine factors predictive of reporting a patient to the Ontario Ministry of Transportation (MTO) as unfit to drive. A logistic regression model was constructed to further determine factors predictive of reporting. Results: Of the 158 patients available for analysis, 48 (30%) were reported to the MTO, and 64 (41%) were advised to stop driving. With respect to the 53 patients with seizures, a report was submitted to the MTO for 30 (57%), and a documented discussion about the implications of driving was held with 35 (66%). On univariate analysis, younger age, a central nervous system primary, higher brain radiotherapy dose, unifocal disease, and the presence of seizures were predictive of physician reporting (p < 0.05). On logistic regression modelling, the presence of seizures (odds ratio: 3.9) and a higher radiotherapy dose (odds ratio: 1.3) remained predictive of reporting. Interpretation: Physicians frequently do not discuss the implications of driving with brain tumour patients or are not properly documenting such advice (or both). Clear and concise reporting guidelines need to be drafted given the legal, medical, and ethical concerns surrounding this public health issue.
A Real-Life Experience Using Panitumumab in Chemo-Refractory Metastatic Colorectal Cancer Patients: A Retrospective Analysis at the Jewish General Hospital, 2009–2012
Authors: Mamo A. , Nogueira M. Cardoso , Batist G. , Palumbo M. , Panasci L. , Ferrario C. , Chaudhury P. , Metrakos P. , Kavan P.
Published: April 2013

Background: Panitumumab is a fully human monoclonal antibody, directed against the epidermal growth factor receptor, that was shown to be effective in third-line metastatic colorectal cancer. We performed a retrospective analysis of patients with chemo-refractory non-KRAS-mutated metastatic colorectal cancer, who received panitumumab at the Jewish General Hospital in Montreal, Canada, between 2009 and 2012. Methods: This chart review included 44 patients (median age: 60 years; performance status: 0–3), of whom 50% had already received three lines of treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival and safety. Tumour progression was determined by radiologic assessments performed once every 3 months per clinical guidelines or by clinical deterioration as determined by the clinician–investigator. Results: In our sample, median PFS was 21.86 ± 5.23 weeks (95% confidence interval: 12.9 to 36.9 weeks) and overall survival was 35.14 ± 7.75 weeks (95% confidence interval: 25.6 to 73.4 weeks) with a median of 5 cycles of panitumumab treatment. The most frequently reported toxicities with panitumumab were skin toxicity (16.2% grade 3) and hypomagnesemia (10.8% grade 3). No infusion reactions were reported. Conclusions: Despite a small sample size from a single institution, our survival and efficacy data are encouraging and comparable to results obtained from the registration panitumumab trial. Our findings suggest that panitumumab can be effective and tolerable in a real-world setting.
Impact of a Single-Day Multidisciplinary Clinic on the Management of Patients with Liver Tumours
Authors: Zhang J. , Mavros M.N. , Cosgrove D. , Hirose K. , Herman J.M. , Smallwood–Massey S. , Kamel I. , Gurakar A. , Anders R. , Cameron A. , Geschwind J.F.H. , Pawlik T.M.
Published: April 2013

Purpose: Multidisciplinary cancer clinics may improve patient care. We examined how a single-day multidisciplinary liver clinic (MDLC) affected care recommendations for patients compared with the recommendations provided before presentation to the MDLC. Methods: We analyzed the demographic and clinicopathologic data of 343 patients assessed in the Johns Hopkins Liver Tumor Center from 2009 to 2012, comparing imaging and pathology interpretation, diagnosis, and management plan between the outside provider (OSP) and the MDLC. Results: Most patients were white (n = 259, 76%); median age was 60 years; and 146 were women (43%). Outside providers referred 182 patients (53%); the rest were self-referred. Patients travelled median of 83.4 miles (interquartile range: 42.7–247 miles). Most had already undergone imaging (n = 338, 99%) and biopsy (n = 194, 57%) at the OSP, and a formal management plan had been formulated for about half (n = 168, 49%). Alterations in the interpretation of imaging occurred for 49 patients (18%) and of biopsy for 14 patients (10%). Referral to the MDLC resulted in a change of diagnosis in 26 patients (8%), of management plan in 70 patients (42%), and of tumour resectability in 7 patients (5%). Roughly half the patients (n = 174, 51%) returned for a follow-up, and 154 of the returnees (89%) received treatment, primarily intraarterial therapy (n = 88, 57%), systemic chemotherapy (n = 60, 39%), or liver resection (n = 32, 21%). Enrollment in a clinical trial was proposed to 34 patients (10%), and 21 of the 34 (62%) were accrued. Conclusions: Patient assessment by our multidisciplinary liver clinic had a significant impact on management, resulting in alterations to imaging and pathology interpretation, diagnosis, and management plan. The MDLC is an effective and convenient means of delivering expert opinion about the diagnosis and management of liver tumours.
The Current Oncology Scholar’s Forum and Workshop
Authors: Cai Y.
Published: April 2013

To promote and support the development of cancer research worldwide, Current Oncology facilitates dialogue and builds a valuable body of work through publications, conferences, and Web sites, among other initiatives. [...]
Pharmacokinetic Interactions between Lersivirine and Zidovudine, Tenofovir Disoproxil Fumarate/ Emtricitabine and Abacavir/Lamivudine
Authors: Vourvahis Manoli , Davis John , Langdon Grant , Layton Gary , Fang Juanzhi , Choo Heng Wee , Hansson Arne G , Tawadrous Margaret
Published: April 2013

Background

To investigate pharmacokinetic interactions associated with coadministration of lersivirine with zidovudine, tenofovir disoproxil fumarate (DF)/emtricitabine (Truvada®) or abacavir/lamivudine (Epzicom®/Kivexa®).

Methods

Three Phase I, open, crossover studies with two (studies 1 and 3) or three (study 2) treatment periods were conducted in healthy individuals. In study 1, individuals received zidovudine and placebo or zidovudine and lersivirine on days 1–14. In study 2, individuals received lersivirine and tenofovir DF/emtricitabine, lersivirine and placebo or tenofovir DF/emtricitabine and placebo on days 1–10. In study 3, individuals received abacavir/ lamivudine only in period 1 (5 days) and abacavir/lamivudine and lersivirine in period 2 (10 days). Blood samples were taken on days 1–14 (study 1) or day of final dose (studies 2 and 3) and analysed using high performance liquid chromatography/dual mass spectrometry. Pharmacokinetic parameters were calculated by standard non-compartmental methods.

Results

When coadministered with lersivirine, zidovudine exposure increased by 35%, and exposure of its metabolite zidovudine-glucuronide decreased by 19%. Following coadministration of lersivirine and tenofovir DF/emtricitabine, tenofovir exposure increased by 30%, and lersivirine exposure decreased by 12%. Coadministration of lersivirine and abacavir/lamivudine increased abacavir exposure by 27% and decreased lamivudine exposure by 8%. Adverse events were predominantly mild in these Phase I studies.

Conclusions

Coadministration of lersivirine with zidovudine, tenofovir DF/emtricitabine or abacavir/lamivudine influenced the systemic exposure of all nucleoside reverse transcriptase inhibitor agents investigated (except for lamivudine; emtricitabine pharmacokinetics were not assessed). Changes were not considered clinically meaningful for zidovudine and abacavir. The clinical relevance of the effect on tenofovir pharmacokinetics is currently unknown.
Faldaprevir (Bi 201335), Deleobuvir (Bi 207127) and Ribavirin Oral Therapy for Treatment-Naive HCV Genotype 1: Sound-C1 Final Results
Authors: Zeuzem Stefan , Asselah Tarik , Angus Peter , Zarski Jean-Pierre , Larrey Dominique , Müllhaupt Beat , Gane Ed , Schuchmann Marcus , Lohse Ansgar W , Pol Stanislas , Bronowicki Jean-Pierre , Roberts Stuart , Arasteh Keikawus , Zoulim Fabien , Heim Markus , Stern Jerry O , Nehmiz Gerhard , Kukolj George , Böcher Wulf O , Mensa Federico J
Published: April 2013

Background

Faldaprevir (BI 201335) and deleobuvir (BI 207127) are direct-acting antiviral agents under development for the treatment of chronic HCV infection. This article describes the final results of the Phase Ib SOUND-C1 study that evaluated the interferon-free oral combination of faldaprevir, deleobuvir and ribavirin in 32 treatment-naive patients infected with HCV genotype 1.

Methods

Patients were randomized to receive deleobuvir 400 mg ( n=15) or 600 mg ( n=17) three times daily plus faldaprevir 120 mg once daily and weight-based ribavirin for 4 weeks. Interferon-free therapy was followed by response-guided faldaprevir plus pegylated interferon-α2a/ribavirin to week 24 or 48.

Results

At week 4, 73% (11/15) and 100% (17/17) of patients in the deleobuvir 400 mg and 600 mg groups achieved HCV RNA<25 IU/ml, respectively. During interferon-free treatment, virological breakthrough was reported in one patient and re-increase of HCV RNA in one patient. Both patients were successfully treated with interferon-containing therapy. The rate of sustained virological response 24 weeks after completion of treatment was 73% (11/15) in the deleobuvir 400 mg group and 94% (16/17) in the 600 mg group. During faldaprevir plus pegylated interferon-α2a/ ribavirin treatment, the most common adverse events were pruritus (38% of patients), rash (31%) and asthenia (31%); these were severe in approximately 3% of patients.

Conclusions

Potent antiviral activity and favourable safety of the treatment regimen were demonstrated. Furthermore, the results suggest that patients with breakthrough at week 4 may be rescued with an interferon-containing regimen. Clinical trials.gov number NCT01132313.
La guerre : un stimulant économique ? Bordeaux et la guerre de la Ligue d'Augsbourg, 1688-1697
Authors: Le Mao Caroline
Published: April 2013

Si l’on mesure assez bien les effets néfastes qu’a pu avoir la guerre de la Ligue d’Augsbourg sur le commerce bordelais, on ignore généralement le fait qu’à la même époque, la marine de guerre, dont les consommations allèrent croissant, s’approvisionna dans la cité de Guyenne, par l’intermédiaire du commissaire général de la marine, Lombard. L’étude de 191 contrats passés par celui-ci, au nom du roi, entre 1688 et 1697 nous permet d’esquisser le rôle que Bordeaux a pu jouer dans l’approvisionnement de la marine de guerre durant ce conflit et de préciser la structuration de ce commerce, la nature des marchandises échangées et les intervenants.