bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation
Authors: Kendrick Agnieszka A. , Choudhury Mahua , Rahman Shaikh M. , McCurdy Carrie E. , Friederich Marisa , Van Hove Johan L. K. , Watson Peter A. , Birdsey Nicholas , Bao Jianjun , Gius David , Sack Michael N. , Jing Enxuan , Kahn C. Ronald , Friedman Jacob E. , Jonscher Karen R.
Published: November 2010

Acetylation has recently emerged as an important mechanism for controlling a broad array of proteins mediating cellular adaptation to metabolic fuels. Acetylation is governed, in part, by SIRTs (sirtuins), class III NAD+-dependent deacetylases that regulate lipid and glucose metabolism in liver during fasting and aging. However, the role of acetylation or SIRTs in pathogenic hepatic fuel metabolism under nutrient excess is unknown. In the present study, we isolated acetylated proteins from total liver proteome and observed 193 preferentially acetylated proteins in mice fed on an HFD (high-fat diet) compared with controls, including 11 proteins not previously identified in acetylation studies. Exposure to the HFD led to hyperacetylation of proteins involved in gluconeogenesis, mitochondrial oxidative metabolism, methionine metabolism, liver injury and the ER (endoplasmic reticulum) stress response. Livers of mice fed on the HFD had reduced SIRT3 activity, a 3-fold decrease in hepatic NAD+ levels and increased mitochondrial protein oxidation. In contrast, neither SIRT1 nor histone acetyltransferase activities were altered, implicating SIRT3 as a dominant factor contributing to the observed phenotype. In Sirt3−/− mice, exposure to the HFD further increased the acetylation status of liver proteins and reduced the activity of respiratory complexes III and IV. This is the first study to identify acetylation patterns in liver proteins of HFD-fed mice. Our results suggest that SIRT3 is an integral regulator of mitochondrial function and its depletion results in hyperacetylation of critical mitochondrial proteins that protect against hepatic lipotoxicity under conditions of nutrient excess.
Surprising toxicity and assembly behaviour of amyloid β-protein oxidized to sulfone
Authors: Maiti Panchanan , Piacentini Roberto , Ripoli Cristian , Grassi Claudio , Bitan Gal
Published: November 2010

Aβ (amyloid β-peptide) is believed to cause AD (Alzheimer's disease). Aβ42 (Aβ comprising 42 amino acids) is substantially more neurotoxic than Aβ40 (Aβ comprising 40 amino acids), and this increased toxicity correlates with the existence of unique Aβ42 oligomers. Met35 oxidation to sulfoxide or sulfone eliminates the differences in early oligomerization between Aβ40 and Aβ42. Met35 oxidation to sulfoxide has been reported to decrease Aβ assembly kinetics and neurotoxicity, whereas oxidation to sulfone has rarely been studied. Based on these data, we expected that oxidation of Aβ to sulfone would also decrease its toxicity and assembly kinetics. To test this hypothesis, we compared systematically the effect of the wild-type, sulfoxide and sulfone forms of Aβ40 and Aβ42 on neuronal viability, dendritic spine morphology and macroscopic Ca2+ currents in primary neurons, and correlated the data with assembly kinetics. Surprisingly, we found that, in contrast with Aβ-sulfoxide, Aβ-sulfone was as toxic and aggregated as fast, as wild-type Aβ. Thus, although Aβ-sulfone is similar to Aβ-sulfoxide in its dipole moment and oligomer size distribution, it behaves similarly to wild-type Aβ in its aggregation kinetics and neurotoxicity. These surprising data decouple the toxicity of oxidized Aβ from its initial oligomerization, and suggest that our current understanding of the effect of methionine oxidation in Aβ is limited.
Lidocaine‐induced apoptosis of gingival fibroblasts: participation of cAMP and PKC activity
Authors: Villarruel Emmanuel Quinteros , Borda Enri , Sterin‐Borda Leonor , Orman Betina
Published: November 2010

Local anaesthetics are drugs that prevent or relieve pain by interrupting nervous conduction and are the most commonly used drugs in dentistry. Their main targets of action are voltage‐dependent Na+ channels. The Na+ channel is modulated by phosphorylation of two enzymes: PKA (protein kinase A) and PKC (protein kinase C). We studied the ability of lidocaine to modulate programmed cell death of human gingival fibroblasts and the mechanisms involved in this process. Lidocaine (10−5 to 10−7 M) stimulated apoptosis in primary cultures and the caspase‐3 activity in a concentration‐dependent manner. The stimulatory effect of lidocaine on apoptosis was attenuated in the presence of HA 1004 (PKA inhibitor) and stimulated by staurosporine and Go 6976 (PKC inhibitors). Lidocaine‐induced apoptotic nuclei correlated positively with cAMP accumulation and negatively with PKC activity. These results show that lidocaine promotes apoptosis in human gingival fibroblasts at concentrations used for local anaesthesia. The mechanism involves PKA stimulation and PKC inhibition, which in turn stimulates caspase‐3 and leads to programmed cell death.
Swallow Syncope
Authors: SRIVATHSAN KOMANDOOR , LEE RICHARD W.
Published: November 2010

SRIVATHSAN, K., et al.: Swallow Syncope.
Swallow syncope is a rare disorder caused by hypersensitive vagotonic reflex in response to deglutition. A 26‐year‐old man complained of recurrent light‐headedness and near syncope on swallowing was hospitalized for monitoring and evaluation. Continuous electrocardiographic and invasive arterial pressure monitoring showed ingestion of a solid meal evoked light‐headedness and complete AV block without an escape rhythm that lasted for 5.6 seconds. This patient received a Medtronic Kappa (401B) DDDR pacemaker with the rate drop feature. The patient has remained asymptomatic on follow‐up for the past 2 years. (PACE 2003; 26:781–782)
High-current diode with ferroelectric plasma source-assisted hollow anode
Authors: Vekselman V. , Gleizer J. Z. , Yatom S. , Gurovich V. Tz. , Krasik Ya. E.
Published: November 2010

The operation of a ferroelectric plasma source-assisted hollow anode (HA) electron source in a vacuum diode powered by an ∼200 kV and ∼400 ns pulsed generator was studied using time- and space-resolved laser induced fluorescence diagnostics. It was found that the plasma ion “temperature” in the vicinity of the HA output grid increases up to ∼15 eV during the accelerating pulse, which is consistent with a model of the potential screening of the grid by the randomly moving ions [Phys. Plasmas 13, 073506 (2006)]. Also it was shown that the increase in the HA plasma potential up to several kilovolts because of the appearance of a noncompensated ion charge in the HA bulk plasma due to electrons fast extraction, leads to explosive emission centers being generated at the HA grid and to nonuniformity in the cross-sectional electron beam current density. Finally, the plasma prefilled mode of diode operation was studied using a simple one-dimensional model of the plasma erosion and the HA plasma electron heating by energetic ions was considered.
In situ Hall effect measurement on diamond anvil cell under high pressure
Authors: Hu Tingjing , Cui Xiaoyan , Gao Yang , Han Yonghao , Liu Cailong , Liu Bao , Liu Hongwu , Ma Yanzhang , Gao Chunxiao
Published: November 2010

A method for in situ Hall effect measurement under high pressure was developed on a diamond anvil cell. The electrode was accurately integrated on one diamond anvil with regular shape. A uniform and strong magnetic field was introduced into the sample zone. The voltage errors brought by some negative effects during the measurement were well eliminated. The correction factor of the Hall coefficient, brought by the nonpoint contact between the electrode and the sample, was 4.51%. The measurement error of the magnetic field did not exceed 1%. The carrier character of ZnTe powders was studied up to 23 GPa. The evolution of conductivity with pressure was explained based on the variation of the carrier behavior.
Indium nanodeposits: A substrate for metal-enhanced fluorescence in the ultraviolet spectral region
Authors: Dragan Anatoliy I. , Geddes Chris D.
Published: November 2010

We have studied a metallic substrate, composed of indium nanodeposits, for metal-enhanced fluorescence (MEF) in the ultraviolet (UV) spectral region. Indium coated slides were prepared using the thermal vapor deposition technique. Theoretical finite difference time domain simulations and experimental studies show that plasmon enhanced absorption and coupled radiation through the scattering component of the extinction spectra of indium nanoparticles, lie in UV region, and are sensitive to the size and density of the nanoparticles, the thickness of the indium film, and polarity of the medium. The MEF effect, measured for intrinsic protein tryptophan and tyrosine residues, loaded onto indium films of different thickness, changes in a wavelike fashion, reflecting changes in the metal film landscape and, consequently, the chromophores coupling with surface plasmons. Indium films also significantly enhance intrinsic fluorescence of proteins themselves [bovine serum albumin]. In this case the wavelength dependence of MEF shows different emission enhancements of protein Tyr and Trp residues. Subsequently, indium-enhanced intrinsic protein fluorescence in the UV spectral region can be of great potential importance for quantitation assays as well as for the labeless detection of biomolecules in the biosciences.
Seasonal variation in plasma corticosterone concentrations in wild and captive adult Duvaucel's geckos (Hoplodactylus duvaucelii) in New Zealand
Authors: Barry Manuela , Cockrem John F. , Brunton Dianne H.
Published: November 2010

Most of New Zealand’s herpetofauna species are threatened and in decline. Yet, little is known about their basic physiology and endocrinology. This study examined plasma corticosterone (CORT) concentrations in a threatened endemic New Zealand reptile, the Duvaucel’s gecko, in relation to season, sex, body temperature, body condition and female reproductive condition (pregnant versus non-pregnant). In addition, seasonal plasma CORT concentrations were compared between captive geckos from a breeding facility and a wild population to determine whether concentrations of CORT were chronically elevated in captive lizards. Plasma CORT concentrations showed significant seasonal variation, but were not related to sex, body temperature, body condition or female reproductive condition. Geckos, which successfully bred in captivity each year, did not exhibit chronically elevated plasma CORT levels but showed an elevation of plasma CORT concentrations in summer compared with wild geckos. Information on basal CORT concentrations in species of conservation concern can be beneficial for improving their management and can aid in identifying and evaluating stress-related changes in hormone patterns of individuals and chronic stress, which is particularly relevant for threatened species breeding programs.
Central gating of fly optomotor response
Authors: Haag Juergen , Wertz Adrian , Borst Alexander
Published: November 2010

We study the integration of multisensory and central input at the level of an identified fly motoneuron, the ventral cervical nerve motoneuron (VCNM) cell, which controls head movements of the animal. We show that this neuron receives input from a central neuron signaling flight activity, from two identified wide-field motion-sensitive neurons, from the wind-sensitive Johnston organ on the antennae, and from the campaniform sensillae of the halteres. We find that visual motion alone leads to only subthreshold responses. Only when it is combined with flight activity or wind stimuli does the VCNM respond to visual motion by modulating its spike activity in a directionally selective way. This nonlinear enhancement of visual responsiveness in the VCNM by central activity is reflected at the behavioral level, when compensatory head movements are measured in response to visual motion. While head movements of flies have only a small amplitude when flies are at rest, the response amplitude is increased by a factor of 30–40 during flight.
Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells
Authors: Blasius Amanda L. , Arnold Carrie N. , Georgel Philippe , Rutschmann Sophie , Xia Yu , Lin Pei , Ross Charles , Li Xiaohong , Smart Nora G. , Beutler Bruce
Published: November 2010

Despite their low frequency, plasmacytoid dendritic cells (pDCs) produce most of the type I IFN that is detectable in the blood following viral infection. The endosomal Toll-like receptors (TLRs) TLR7 and TLR9 are required for pDCs, as well as other cell types, to sense viral nucleic acids, but the mechanism by which signaling through these shared receptors results in the prodigious production of type I IFN by pDCs is not understood. We designed a genetic screen to identify proteins required for the development and specialized function of pDCs. One phenovariant, which we named
feeble
, showed abrogation of both TLR-induced type I IFN and proinflammatory cytokine production by pDCs, while leaving TLR responses intact in other cells. The
feeble
phenotype was mapped to a mutation in
Slc15a4
, which encodes the peptide/histidine transporter 1 (PHT1) and has not previously been implicated in pDC function. The identification of the
feeble
mutation led to our subsequent observations that AP-3, as well as the BLOC-1 and BLOC-2 Hermansky-Pudlak syndrome proteins are essential for pDC signaling through TLR7 and TLR9. These proteins are not necessary for TLR7 or TLR9 signaling in conventional DCs and thus comprise a membrane trafficking pathway uniquely required for endosomal TLR signaling in pDCs.
Magnetic interaction in exchange-biased bilayers: a first-order reversal curve analysis
Authors: Alonso L , Peixoto T R F , Cornejo D R
Published: November 2010

The distributions of coercivities and magnetic interactions in a set of polycrystalline Ni0.8Fe0.2/FeMn bilayers have been determined using the first-order reversal curve (FORC) formalism. The thickness of the permalloy (Py) film was fixed at 10 nm (nominal), while that of the FeMn film varied within the range 0–20 nm. The FORC diagrams of each bilayer displayed two clearly distinguishable regions. The main region was generated by Py particles whose coercivities were enhanced in comparison with those in which the FeMn film was absent (sample O). The minor region was produced by Py particles with coercivities similar to or slightly higher than those of particles in the Py film of sample O. Each sample presented two distributions of interaction fields, one for each region, and both were centred slightly below the exchange-bias field, thus indicating a prevalence of magnetizing interactions. These results are consistent with a grain size distribution in the Py layer and the presence of uncompensated antiferromagnetic moments.
A method of computing electric field parameters on boundaries between two media
Authors: Rizhov Alexander
Published: November 2010

Many problems of electric field strength on a boundary between two media require
college-level mathematical analysis. However, when the boundary between media is
represented by a sphere or a flat plane, these types of problems can be solved algebraically,
placing them within reach of high school students. This article presents a solution analysis
of the typical problems utilizing the well-known principle of superposition, which allows
simple and precise calculations of electric field parameters.
Vascular function and cardiovascular risk factors in women with severe flushing
Authors: Sassarini J. , Fox H. , Ferrell W. , Sattar N. , Lumsden M. A.
Published: November 2010

Background  Seventy per cent of postmenopausal women suffer from hot flushes causing significant morbidity in 25%. Oestrogen replacement provides symptom relief, but its use has declined following safety issues and there is, as yet, no good alternative. Pathophysiology is poorly understood, but one proposed mechanism is altered peripheral vascular reactivity. It has recently been suggested that the presence of flushing may be a marker of underlying cardiovascular risk.

Aim  To measure (i) peripheral vascular reactivity in subcutaneous vessels (ii) routine and novel cardiovascular risk factors in postmenopausal women who flush, and compare results to a matched group of women who do not flush.

Methods  Thirty‐two postmenopausal women with at least 20 flushes/week and 14 nonflushing postmenopausal women were recruited. Cutaneous microvascular perfusion was measured using laser Doppler imaging, and endothelial function was assessed by iontophoresis (administration of vasoactive agents through the skin by an electric current) of acetylcholine [Ach] (endothelial‐dependent) and sodium nitroprusside [SNP] (endothelial independent). Blood samples for risk factors were taken following vascular assessment.

Results  Both study groups were well matched demographically. The response of the subcutaneous vessels was greater in women who flushed than those who did not, following administration of both the endothelium‐dependent and independent vasodilators, (ACh, P ≤ 0·001, SNP, P = 0·001, 2‐way anova). By contrast, levels of High Density Lipoprotein (HDL)‐cholesterol and ApoA1 were significantly lower in the flushing women compared with the control women (P = 0·02 and 0·002, respectively), and levels of inter‐cellular adhesion molecule‐1 (ICAM‐1) were higher (P = 0·03), findings robust to adjustment for confounders, suggesting an adverse cardiovascular risk profile.

Conclusion  These results confirm a better vascular response in women but paradoxically, such women appear to have worse (not better) cardiovascular disease risk factors in particular lower HDL‐cholesterol but also higher non‐HDL‐c to HDL‐c ratio and increased ICAM‐1. Further studies are needed to assess vascular risk factors in women who flush.
Cardiomyocytes develop from anterior primitive streak cells induced by β‐catenin activation and the blockage of BMP signaling in hESCs
Authors: Yamauchi Kaori , Sumi Tomoyuki , Minami Itsunari , Otsuji Tomomi G. , Kawase Eihachiro , Nakatsuji Norio , Suemori Hirofumi
Published: November 2010

Cardiomyocytes arise from cells that migrate to the mid‐to‐anterior region of the primitive streak (PS) during embryogenesis. We previously showed that canonical Wnt/β‐catenin pathway signaling leads to the development of nascent PS populations from human embryonic stem cells (hESCs) and that synergistic activation of the Wnt/β‐catenin pathway and inhibition of bone morphogenetic protein (BMP) signaling by Noggin induced the formation of anterior PS cells. We herein demonstrate that anterior PS cells induced by the activation of β‐catenin with Noggin differentiate into functional cardiomyocytes when cultured in suspension with BMP4 and fibroblast growth factor 2 (FGF2). All aggregates generated from the anterior PS cells developed into contracting cells demonstrating their cardiac potential. More than 30% of the cells in each aggregate were α‐actinin‐positive cardiomyocytes. In addition, these cardiomyocytes could be easily purified up to 80% by simple size fractionation. In contrast, the posterior PS cells induced by β‐catenin activation without Noggin showed poor cardiac potential. These results show that the commitment to a cardiac lineage in vitro occurs through similar cellular and molecular signaling pathways involved in cardiac development in vivo, thus providing a valuable culture model for studying early cardiac developmental events in hESCs.
Capecitabine for skin cancer prevention in solid organ transplant recipients
Authors: Jirakulaporn Tanawat , Endrizzi Bart , Lindgren Bruce , Mathew Josy , Lee Peter K. , Dudek Arkadiusz Z.
Published: November 2010

Jirakulaporn T, Endrizzi B, Lindgren B, Mathew J, Lee PK, Dudek AZ. Capecitabine for skin cancer prevention in solid organ transplant recipients. Clin Transplant 2011: 25: 541–548. © 2010 John Wiley & Sons A/S.

Abstract:  Skin cancers are the most common malignancies in solid organ transplant recipients (SOTR). A case‐observational, retrospective study was performed to determine the efficacy of low‐dose capecitabine in the secondary prevention of skin cancers in SOTRs treated at a single institution. SOTRs with recurrent squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC) were given low‐dose capecitabine 1 g/m2 daily, days 1–14 of a 21‐d treatment cycle. Skin surveillance was performed by dermatologists every 1–3 months. Cumulative incidence rates of SCC, BCC, and actinic keratosis (AK) before and after treatment were scored and statistically compared for each patient using a non‐parametric Wilcoxon signed rank test. Fifteen patients (13 men and two women) with a median age of 57 yr (range 40–73) were treated. Incidence rates as measured by mean number of events per month declined by 0.33 for SCC, 0.04 for BCC, and 2.45 for AK (p < 0.05). The most common grade 3 and 4 toxicities included fatigue (40.0%), hand‐foot syndrome (20.0%), and diarrhea (20.0%). The discontinuation rate at one yr was approximately 33.3%. We conclude that oral capecitabine significantly decreases the incidence rates of recurrent SCC, BCC, and AK in SOTRs and is associated with manageable toxicity.
Reproductive division of labour and thelytoky result in sympatric barriers to gene flow in honeybees (Apis melliferaL.)
Authors: NEUMANN P. , HÄRTEL S. , KRYGER P. , CREWE R. M. , MORITZ R. F. A.
Published: November 2010

Determining the extent and causes of barriers to gene flow is essential for understanding sympatric speciation, but the practical difficulties of quantifying reproductive isolation remain an obstacle to analysing this process. Social parasites are common in eusocial insects and tend to be close phylogenetic relatives of their hosts (= Emery’s rule). Sympatric speciation caused by reproductive isolation between host and parasite is a possible evolutionary pathway. Socially parasitic workers of the Cape honeybee,Apis mellifera capensis, produce female clonal offspring parthenogenetically and invade colonies of the neighbouring subspeciesA. m. scutellata. In the host colony, socially parasitic workers can become pseudoqueens, an intermediate caste with queenlike pheromone secretion. Here, we show that over an area of approximately 275.000 km2, all parasitic workers bear the genetic signature of a clone founded by a single ancestral worker genotype. Any gene flow from the host to the parasite is impossible because honeybee workers cannot mate. Gene flow from the parasite to the host is possible, as parasitic larvae can develop into queens. However, we show that despite sympatric coexistence for more than a decade, gene flow between host and social parasite (Fst = 0.32) and hybridizations (0.71%) are rare, resulting in reproductive isolation. Our data suggest a new barrier to gene flow in sympatry, which is not based on assortative matings but on thelytoky and reproductive division of labour in eusocial insects, thereby suggesting a new potential pathway to Emery’s rule.
Quantitative demonstration of comparable architectonic areas within the ventromedial and lateral orbital frontal cortex in the human and the macaque monkey brains
Authors: Mackey Scott , Petrides Michael
Published: November 2010

The orbital and ventromedial frontal cortical regions of the human and the macaque monkey brains include several spatially discrete areas which are defined histologically by their distinctive laminar architecture. Although considerable information has been collected on the function and anatomical connections of specific architectonic areas within the orbital and ventromedial frontal cortex of the macaque monkey, the location of comparable areas in the human brain remains controversial. We re‐examined the comparability of orbital and ventromedial frontal areas across these two species and provide the first quantitative demonstration of architectonically comparable cortical areas in the human and the macaque brains. Images of Nissl‐stained sections of the cortex were obtained at low magnification. Differences in the typical size of neurons in alternating pyramidal and granule cell layers were exploited to segregate the cortical layers before sampling. Profiles of areal neuronal density were sampled across the width of the cortex. The location of individual cortical layers was identified on each profile by sampling a set of equally sized images on which the cortical layers had been manually traced. The rank order of sampled architectonic features in comparable architectonic areas in the two species was significantly correlated. The differences in measured features between gyral and sulcal parts of the same architectonic area are at a minimum 3–4 times smaller than the differences between architectonic areas for the areas examined. Furthermore, the quantified architectonic features arrange areas within the orbital and ventromedial frontal cortex along two dimensions: an anterior‐to‐posterior and a medial‐to‐lateral dimension. On the basis of these findings, and in light of known anatomical connections in the macaque, this region of the human cortex appears to comprise at least two hierarchically structured networks of areas.
Irreversible electroporation (IRE): a novel method for renal tissue ablation
Authors: Tracy Chad R. , Kabbani Wareef , Cadeddu Jeffrey A.
Published: November 2010

What’s known on the subject? and What does the study add?

IRE has been used in liver and prostate models before, confirming appropriate cell death with sharp margins of ablation. The current study confirms that this technology may also provide an effective treatment in the kidney, which provides a unique environment due to electrolyte differences, renal blood flow, and collecting system anatomy. The advantage of IRE may be that its athermal nature limits common problems with percutaneous ablation, including heat sink and destruction of the urothelium.

OBJECTIVE

• To evaluate the effects of irreversible electroporation (IRE) on renal parenchyma and the renal collecting system in a porcine model.

MATERIALS AND METHODS

• Eight female Yorkshire pigs underwent a series of laparoscopic ablations using either monopolar or bipolar IRE (Angiodynamics, Queensbury, NY, USA).

• The pigs were killed between 10 min and 14 days after IRE, and the kidneys were harvested for gross and histological analysis, including NADH staining for cellular viability.

RESULTS

• In all, 24 ablations were performed and all the pigs survived without complications.

• Initial gross lesions were diffusely haemorrhagic, decreasing progressively in size (30–40%) to small white scars over the 14‐day period.

• Immediately after IRE, ablated tissue was characterized by diffuse tubular desquamation, eosinophilia, and nuclear pyknosis, with absence of cellular viability by NADH.

• At 7 days after IRE, there was diffuse cellular necrosis with early peripheral granulation changes, and by 14 days there was marked tissue granulation, chronic inflammation, and dystrophic calcification with early fibrosis and cellular contraction.

• Initial patchy urothelial injury and ulceration showed signs of repair and viability by 14 days after IRE.

CONCLUSIONS

• Renal IRE in the porcine kidney leads to predictable histological changes characteristic of cellular death within 1 h of ablation, with relative urothelial sparing.

• Further animal studies are warranted to determine safety and efficacy of this novel ablation technology.
Multiparametric magnetic resonance imaging for the detection and localization of prostate cancer: combination of T2‐weighted, dynamic contrast‐enhanced and diffusion‐weighted imaging
Authors: Delongchamps Nicolas Barry , Rouanne Mathieu , Flam Thierry , Beuvon Frédéric , Liberatore Mathieu , Zerbib Marc , Cornud François
Published: November 2010

Study Type – Diagnostic (exploratory cohort)  Level of Evidence 2b

What’s known on the subject? and What does the study add?

Dynamic contrast enhanced (DCE) and diffusion weighted (DW) MRI have demonstrated their potential value in distinguishing malignant from benign prostate tissue, but none of them used alone is capable of optimally characterizing tumours in the prostate.

The combination of DW, DCE and T2W imaging increased significantly MRI performance for cancer detection in the peripheral zone.

OBJECTIVE

• To evaluate the combination of multiple magnetic resonance imaging (MRI) techniques, including T2‐weighted imaging (T2W), dynamic contrast‐enhanced imaging (DCE) and diffusion‐weighted imaging (DWI), for the detection and localization of prostate cancer.

PATIENTS AND METHODS

• In all, 57 patients underwent endorectal MRI at 1.5 T before radical prostatectomy (RP) for localized prostate cancer.

• On T2W images and histological whole‐mount analysis, the peripheral zone (PZ) and transition zone (TZ) were divided into upper and lower glands, as well as left and right halves, thus yielding four quadrants for each zone.

• On histological analysis, the total number of tumour foci, their location and larger diameter were recorded. T2W alone, T2W + DWI, T2W + DCE and all three techniques combined were scored for the likelihood of tumour in each area and results were compared with whole‐mount analysis.

• The area under the receiver operating characteristic curve (Az) was used to evaluate accuracy for tumour detection. The association between MR accuracy and Gleason score was statistically assessed.

RESULTS

• Of the 456 prostate octants analysed, 145 showed cancer on whole‐mount analysis, 120 (83%) of them with a diameter assumed to correspond to a volume >0.2 cm3. Gleason score was ≥7 in 68 (47%) tumours.

• In the PZ, the Az value was significantly higher for T2W + DWI, T2W + DCE and all three techniques combined than for T2W alone (P < 0.05).

• In the TZ, the Az value was higher for T2W + DWI than for T2W alone, but the difference was not significant.

• The Az value for T2W + DWI was significantly higher than that for T2W + DCE or for the three sequences combined.

• Gleason score was significantly associated with cancer detection in the PZ.

CONCLUSIONS

• Adding DWI and DCE to T2W imaging increased MRI performance in cancer detection in the PZ significantly.

• However, this multiparametric model failed to improve performance in the TZ.

• Gleason score significantly influenced cancer detection in the PZ but not in the TZ.
Periprostatic fat correlates with tumour aggressiveness in prostate cancer patients
Authors: van Roermund Joep G.H. , Hinnen Karel A. , Tolman Christine J. , Bol Gijsbert H. , Witjes J. Alfred , Bosch J.L.H. Ruud , Kiemeney Lambertus A. , van Vulpen Marco
Published: November 2010

Study Type – Prognostic (case series) Level of Evidence 4

What’s known on the subject? and What does the study add?

Nowadays more and more publications have been published about the topic prostate cancer aggressiveness and obesity with mixed results. However, most of the publications used the BMI as a marker for obesity, while the most metabolic active fat is the visceral fat. To learn more about these relations we measured and used the visceral fat in our paper.

OBJECTIVE

• To examine if the periprostatic fat measured on computed tomography (CT) correlates with advanced disease we examined patients who received radiotherapy for localized prostate cancer. Several USA reports found a positive association between obesity and prostate cancer aggressiveness. However, in recent European studies these conclusions were not confirmed. Studies concerning this issue have basically relied on body mass index (BMI), as a marker of general obesity. Visceral fat, however, is the most metabolically active and best measured on CT.

PATIENTS AND METHODS

• In 932 patients, who were treated with external radiotherapy (N= 311) or brachytherapy (N= 621) for their T1‐3N0M0 prostate cancer, different fat measurements (periprostatic fat, subcutaneous fat thickness) were performed on a CT.

• Associations between the different fat measurements and risk of having high‐risk (according to Ash et al., PSA > 20 or Gleason score ≥8 or T3) disease was measured.

RESULTS

• The median age (IQR) was 67.0 years (62.0–71.0) and median BMI (IQR) was 25.8 (24.2–28.3). Logistic regression analyses, adjusted for age, revealed a significant association between periprostatic fat density (PFD) and risk of having a high risk disease. (Odds ratio [95% CI] 1.06 [1.04–1.08], P < 0.001)

CONCLUSION

• Patients with a higher PFD had more often aggressive prostate cancer.
Prostate‐specific antigen velocity based risk‐adapted discontinuation of prostate cancer screening in elderly men
Authors: Tang Ping , Sun Leon , Uhlman Matthew A. , Robertson Cary N. , Polascik Thomas J. , Moul Judd W.
Published: November 2010

Study Type – Prognostic (cohort)  Level of Evidence 2b

What’s known on the subject? and What does the study add?

Currently, the U.S. Preventive Services Task Force (USPSTF) recommends against PSA screening for prostate cancer in men aged ≥75 years as it concluded that “the harm of screening for prostate cancer in men age ≥75 years may outweigh the potential benefits”. Our findings suggest that elderly men with a PSA velocity of ≥0.45 ng/ml/year have higher risk of death from prostate cancer. Continuing PSA testing may be beneficial for these men.

OBJECTIVE

• To evaluate weather prostate‐specific antigen (PSA) velocity could be used to stratify patients at risk of death from prostate cancer (PCa) and be useful in aiding decision making regarding PSA screening in elderly men, as previous studies have shown that PSA velocity can predict PCa risk.

PATIENTS AND METHODS

• The cohort included 3,525 patients aged ≥ 75 years with two or more PSA tests before a diagnosis of PCa. Cox proportional hazard model was used to evaluate which variables at time of last PSA measurement were associated with death from PCa.

• The rates of death from PCa after diagnosis in different PSA velocity groups were calculated. Kaplan‐Meier and log rank test were used to assess the significant difference in death from PCa after diagnosis, stratified by PSA velocity cutoff.

RESULTS

• On multivariate analysis, men with a PSA velocity of PSA velocity ≥0.45 ng/mL/year had a 4.8‐fold higher risk of death from PCa as compared to men with a PSA velocity of <0.45 ng/mL/year (p value = 0.013). After a median 6.5 (up to 16.9) years of follow‐up from diagnosis, 1.4% of the men with a PSA velocity <0.45 ng/mL/year had died of PCa as compared to 8.7% of those with a PSA velocity ≥0.45 ng/mL/year.

• The cumulative rate of death from PCa after diagnosis, stratified by a PSA velocity of 0.45 ng/mL/year, was statistically different (log rank test, P < 0.001).

CONCLUSION

• Men age ≥ 75 years old with a PSA velocity of <0.45 ng/mL/year are unlikely to die of PCa. It may be safe to discontinue PSA screening in these men.
Defecation disturbances after cystectomy for urinary bladder cancer
Authors: Thulin Helena , Kreicbergs Ulrika , Onelöv Erik , Ahlstrand Christer , Carringer Malcolm , Holmäng Sten , Ljungberg Börje , Malmström Per‐Uno , Robinsson David , Wijkström Hans , Wiklund N. Peter , Steineck Gunnar , Henningsohn Lars
Published: November 2010

Study Type – Preference (prospective cohort)

Level of Evidence 4

What’s known on the subject? and What does the study add?

Functional gastrointestinal symptoms and problems are common after radical cystectomy with urinary diversion. This study adds new important epidemiological data on this group of symptoms.

OBJECTIVE

To describe and compare long‐term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non‐continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions.

PATIENTS AND METHODS

During their follow‐up we attempted to contact all men and women aged 30–80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals.

During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study‐specific questionnaire together with free‐hand comments. The patients completed the questionnaire at home.

Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval.

RESULTS

The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability).

A sense of decreased straining capacity was reported by 20% of the men and women with non‐continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively.

CONCLUSIONS

Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability).

Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool‐emptying problems, and asking about them after surgery.
LES QUASI‐MARCHES DANS L’AIDE A DOMICILE: UNE MISE EN PERSPECTIVE EUROPEENNE
Authors: Gardin Laurent , Nyssens Marthe , Minguzzi Paolo
Published: November 2010

RESUME**: L’aide à domicile est emblématique d’importantes mutations à l’œuvre dans les sociétés européennes. L’objet de l’article est d’analyser les enjeux sous‐jacents à l’évolution des modes de régulation vers les quasi‐marchés. Dans la première partie, nous rappelons la nature des modes de régulations historiques de l’aide à domicile dans chacun des pays qui façonnent ainsi des régimes de care. Ensuite, nous analysons comment l’introduction de régulations quasi‐marchandes vient se greffer et ainsi infléchir les régimes de care. Enfin, nous analysons en quoi la présence d’échecs du marché soulève des questions toutes particulières en terme de régulation publique.
Primary Elections for Britain
Authors: McSWEENEY DEAN
Published: November 2010

The coalition's programme for government promises to fund 200 open postal primaries during the current Parliament, targeted at seats which have not changed hands for many years. The lessons from the two open postal primaries used in 2009 are that they will change the numbers and characteristics of those involved in choosing candidates, the criteria for selection and the type of candidates chosen. Much will remain unchanged. Primaries are unlikely to affect the controlling influence of party in the House. The limits to their number and duration will leave most safe seats unaffected and prevent the development of any new form of accountability. Primaries will provide some voters with intra‐party competition but inter‐party uncompetitiveness will remain the norm.
Social inequality and health: the role of social capital
Authors: Dahl Espen , Malmberg‐Heimonen Ira
Published: November 2010

The aim of the article is to examine whether and to what degree the unequal distribution of social capital in the population explains the relationship between socioeconomic position and health in Norway. Theoretical insight and empirical evidence seem to suggest that social capital mediates the effect of socioeconomic position on health outcomes. However, only a few studies have addressed this question and those that have done so have used few and simple indicators of social capital. This study is based on a nationwide cross‐sectional survey (N = 3190) commissioned by Statistics Norway. The survey was designed to cover a comprehensive set of variables measuring different aspects of the theoretical construct of social capital. Two health outcomes, self‐perceived health and longstanding illness, were analysed. The results showed that the mediating role of social capital between socioeconomic position and health was negligible for both health outcomes. After controlling for socio‐demographic variables and socioeconomic position, only neighbourhood satisfaction and generalised trust showed a significant association with self‐perceived health, whereas none of the social capital variables had any significant association with longstanding illness. Some theoretical and methodological implications of the results are discussed.
Releasing the Vindicated Eve
Authors: Kaley Harriette
Published: November 2010

The Woman Within: A Psychoanalytic Essay on Femininity. RAFAEL E. LOPEZ-CORVO. London: Karnac Books, 2009. 144 pp., $26.95 (paperback) ISBN: 9781855756946.
Experimentally elevated testosterone levels enhance courtship behaviour and territoriality but depress acquired immune response in Red Bishops Euplectes orix
Authors: EDLER RALF , GOYMANN WOLFGANG , SCHWABL INGRID , FRIEDL THOMAS W. P.
Published: November 2010

The immunocompetence handicap hypothesis (ICHH) posits that the hormone testosterone mediates a trade‐off between investment in reproduction and immunological condition. In this study, we tested the ICHH in the Red Bishop Euplectes orix, a polygynous weaverbird. Males of this strongly sexually dimorphic species show an elaborate courtship display to attract females and compete aggressively with other males for nesting sites in breeding colonies. We experimentally elevated testosterone levels in breeding male Red Bishops kept in an aviary with a subcutaneous implantation of testosterone‐releasing pellets. We then compared behaviour, development of territory size and immunological condition (as assessed through a white blood cell count) of the experimental group with a control group treated with placebos. In addition, we measured the primary and secondary response to phytohaemagglutinin (PHA) to investigate the effect of testosterone on both innate and acquired immunity. Males with elevated levels of testosterone enlarged their territories and conducted more courtship behaviour, while showing a decrease in health, expressed by an increased heterophil/lymphocyte ratio compared with the control group. Males of the control group showed an increase of the secondary response to PHA, as expected under the assumption that repeated exposure to an antigen enhanced the immune response due to acquired immunity. However, males with experimentally increased testosterone levels did not show such an enhanced immune response in the secondary PHA test (although sample size and power of the statistical tests were low), indicating that testosterone treatment might directly or indirectly suppress some component of the acquired immune response.
Exosomal‐like vesicles with immune‐modulatory features are present in human plasma and can induce CD4+ T‐cell apoptosis in vitro
Authors: Ren Yana , Yang Jie , Xie Rufeng , Gao Li , Yang Yiming , Fan Huahua , Qian Kaicheng
Published: November 2010

BACKGROUND: Exosomes are small membrane vesicles that are secreted from many cell types into various body fluids. These vesicles are thought to play a role in cell–cell interactions.

STUDY DESIGN AND METHODS: Vesicles were isolated from human plasma of healthy donors by differential ultracentrifugation and ultrafiltration. The vesicles were identified by transmission electron microscopy, and their biochemical characteristics were analyzed by Western blot and flow cytometry. The immune‐modulatory ability of exosomal‐like vesicles was examined by incubating them with CD4+ T cells for CD4+ T‐cell proliferation and apoptosis assays in vitro.

RESULTS: Vesicles purified from human plasma displayed shapes and sizes similar to those of previously described exosomes and contained exosomes marker proteins CD63 and CD81. They also expressed molecules such as MHC Class II molecules, CD80, CD86, and the cell signal transduction molecules Wnt3a, Wnt5a, and FasL. Furthermore, functional analysis showed that allogeneic plasma exosomes restrained the survival of CD4+ T cells. Plasma exosomes can induce dose‐dependent suppression of proliferation of activated CD4+ T cells, with the strongest responses induced by 500 µg/mL exosomes in vitro. Antibodies against exosomes FasL can block the activity of exosomes on CD4+ T‐cell apoptosis. Moreover, three different concentrations of CD4+ T cells were inhibited by plasma exosomes and the suppressive function was not dependent on interleukin‐2.

CONCLUSION: Exosomes present in human plasma contain immunity‐associated molecules and can induce CD4+ T‐cell apoptosis in vitro. Plasma exosomes have the capacity to influence immune responses.
Expansion of adipose tissue mesenchymal stromal progenitors in serum‐free medium supplemented with virally inactivated allogeneic human platelet lysate
Authors: Shih Daniel Tzu‐Bi , Chen Jung‐Cheu , Chen Wan‐Yu , Kuo Ya‐Po , Su Chen‐Yao , Burnouf Thierry
Published: November 2010

BACKGROUND:Single‐donor or pooled platelet lysates (PL) can substitute for fetal bovine serum (FBS) for mesenchymal stromal cell (MSC) expansion. However, for clinical applications of MSCs, the use of virally inactivated PL would be desirable. Recently, we have developed a solvent/detergent (S/D)‐treated human PL preparation (S/D‐PL) rich in growth factors. The capacity to use this virally inactivated preparation for MSC expansion needs to be evaluated.

STUDY DESIGN AND METHODS:Platelet concentrates were treated by S/D (1% tri‐n‐butyl phosphate and 1% Triton X‐45), extracted by oil, purified by C18 hydrophobic interaction chromatography, and sterile filtered. S/D‐PL was compared to FBS as a medium supplement (10% vol/vol) for isolating, maintaining, and expanding adipose tissue–derived MSCs (AT‐MSCs). Cell morphology; proliferation kinetics; immunophenotype; differentiation capacity toward the chondrogenic, osteogenic, and osteogenic lineages; and cytokine antibody array were assessed.

RESULTS:AT‐MSCs had a typical spindle morphology and proliferated in S/D‐PL at least as well as in FBS. Immunophenotype at Passage 7 was characteristic of MSCs and similar for both culture conditions. Differentiation capacity into the three lineages was maintained and chondrogenesis was enhanced by S/D‐PL. In a 120 human cytokine antibody array analysis, 73 cytokines were detected in S/D‐PL, including 22 with a concentration higher than in FBS.

CONCLUSION:S/D‐PL is an alternative to FBS for AT‐MSC maintenance and expansion, does not compromise the differentiation capacity nor the immunophenotype, and may accelerate chondrogenesis. S/D‐PL protocols for MSC clinical scale‐up may represent a major step toward challenging new use in stem cell therapies.
Tailored Management of Atrial Fibrillation Using a LGE‐MRI Based Model: From the Clinic to the Electrophysiology Laboratory
Authors: VERGARA GASTON R. , MARROUCHE NASSIR F.
Published: November 2010

Tailored Management of Atrial Fibrillation with LGE‐MRI. Ablation provides a good therapeutic alternative for atrial fibrillation (AF) management; however, its effectiveness relies in adequate patient selection. Late gadolinium enhancement‐magnetic resonance imaging (LGE‐MRI) allows for atrial arrhythmic substrate, as well as postablation scarring visualization. In this article, we describe a new staging system for AF based on the amount of left atrial enhancement on LGE‐MRI (Utah I ≤ 5%, Utah II >5–20%, Utah III > 20–35%, and Utah IV > 35%). On the basis of patient stage, a more tailored approach to AF management can be taken. This includes triaging appropriate candidates for ablation (Utah stages I–III), as well as anticoagulation management based on an increase on the predictive statistics of the CHADS2. LGE‐MRI also allows for ablation lesion characterization. Acute edema, defined as enhancement on T2‐weighted MRI images immediately post‐AF ablation correlates with low voltage areas but not with LGE‐MRI‐defined scar. Post‐AF ablation LGE‐MRI scans show significant heterogeneity in the atrial wall on portions subject to radiofrequency (RF). We have postulated that some of these areas correspond to no‐reflow type phenomenon. Postablation LGE‐MRI can also help identify breaks in lesion sets and its correlation with conduction recovery has been used successfully to guide redo procedures. Real‐time MRI‐based ablation system has the potential advantage of tissue lesion visualization during RF delivery. To that end, we have developed a 3‐Tesla‐based real‐time MRI ablation system. We demonstrated the feasibility to safely navigate, pace, and record intracardiac EGMs in the atrial chambers, as well as applying RF energy while directly visualizing lesion formation in real time. (J Cardiovasc Electrophysiol, Vol. 22, pp. 481‐487)