bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast
Authors: Liao Shaoxi , Desouki Mohamed M. , Gaile Daniel P. , Shepherd Lori , Nowak Norma J. , Conroy Jeffrey , Barry William T. , Geradts Joseph
Published: August 2012

Only a minority of intraductal carcinomas of the breast give rise to stromally invasive disease. We microdissected 206 paraffin blocks representing 116 different cases of low‐grade ductal carcinoma in situ (DCIS). Fifty‐five were pure DCIS (PD) cases without progression to invasive carcinoma. Sixty‐one cases had a small invasive component. DNA was extracted from microdissected sections and hybridized to high‐density bacterial artificial chromosome arrays. Array comparative genomic hybridization analysis of 118 hybridized DNA samples yielded data on 69 samples that were suitable for further statistical analysis. This cohort included 20 pure DCIS cases, 25 mixed DCIS (MD), and 24 mixed invasive carcinoma samples. PD cases had a higher frequency of DNA copy number changes than MD cases, and the latter had similar DNA profiles compared to paired invasive carcinomas. Copy number changes on 13 chromosomal arms occurred at different rates in PD versus MD lesions. Eight of 19 candidate genes residing at those loci were confirmed to have differential copy number changes by quantitative PCR. NCOR2/SMRT and NR4A1 (both on 12q), DYNLRB2 (16q), CELSR1, UPK3A, and ST13 (all on 22q) were more frequently amplified in PD. Moreover, NCOR2, NR4A1, and DYNLRB2 showed more frequent copy number losses in MD. GRAP2 (22q) was more often amplified in MD, whereas TAF1C (16q) was more commonly deleted in PD. A multigene model comprising these candidate genes discriminated between PD and MD lesions with high accuracy. These findings suggest that the propensity to invade the stroma may be encoded in the genome of intraductal carcinomas. © 2012 Wiley Periodicals, Inc.
Does religiousness and spirituality moderate the relations between physical and mental health among aging prisoners?
Authors: Allen Rebecca S. , Harris Grant M. , Crowther Martha R. , Oliver JoAnn S. , Cavanaugh Ronald , Phillips Laura L.
Published: August 2012

Objective

We examined positive and negative religious coping as moderators of the relation between physical limitations, depression, and desire for hastened death among male inmates incarcerated primarily for murder.

Methods

Inmates over the age of 45 years who passed a cognitive screening completed face‐to‐face interviews (N = 94; mean age = 57.7 years; SD = 10.68). Multiple regression analyses included age, race/ethnicity, parole belief, physical health, positive or negative religious coping, and all two‐way interactions represented by the product of health and a religious coping variable.

Results

Older inmates and those who reported greater levels of positive religious coping endorsed fewer symptoms of depression, whereas those who reported greater levels of negative religious coping endorsed more symptoms of depression. Inmates who reported higher levels of depression endorsed a greater desire for hastened death. The effect of physical functioning on desire for hastened death is moderated by negative religious coping such that those who endorsed higher levels of negative religious coping reported a greater desire for hastened death.

Conclusions

Examinations of religious/spiritual practices and mindfulness‐based interventions in prison research have assumed a positive stance with regard to the potential impact of religious/spiritual coping on physical and mental health. The current findings provide cautionary information that may further assist in selection of inmates for participation in such interventions. Copyright © 2012 John Wiley & Sons, Ltd.
Lubricin in human breast tissue expander capsules
Authors: Cheriyan Thomas , Guo Lifei , Orgill Dennis P. , Padera Robert F. , Schmid Thomas M. , Spector Myron
Published: August 2012

Capsular contraction is the most common complication of breast reconstruction surgery. While presence of the contractile protein alpha smooth muscle actin (α‐SMA) is considered among the causes of capsular contraction, the exact etiology and pathophysiology is not fully understood. The objective of this study was to investigate the possible role of lubricin in capsular formation and contraction by determining the presence and distribution of the lubricating protein lubricin in human breast tissue expander capsules. Related aims were to evaluate select histopathologic features of the capsules, and the percentage of cells expressing α‐SMA, which reflects the myofibroblast phenotype. Capsules from tissue expanders were obtained from eight patients. Lubricin, at the tissue‐implant interface, in the extracellular matrix, and in cells, and α‐SMA‐containing cells were evaluated immunohistochemically. The notable finding was that lubricin was identified in all tissue expander capsules: as a discrete layer at the tissue‐implant interface, extracellular, and intracellular. There was a greater amount of lubricin in the extracellular matrix in the intimal‐subintimal zone when compared with the tissue away from the implant. Varying degrees of synovial metaplasia were seen at the tissue‐implant interface. α‐SMA‐containing cells were also seen in all but one patient. The findings might help us better understand factors involved in capsule formation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Vitamin D binding protein is a key determinant of 25-hydroxyvitamin D levels in infants and toddlers
Authors: Carpenter Thomas O , Zhang Jane H , Parra Esteban , Ellis Bruce K , Simpson Christine , Lee William M , Balko Jody , Fu Lei , Wong Betty Y-L , Cole David EC
Published: August 2012

Circulating 25-hydroxyvitamin D (25-OHD) levels vary among human populations. Only limited information regarding determinants of these measures is available for infants and children, particularly in minority groups at greatest risk for vitamin D deficiency. We identified demographic determinants of circulating 25-OHD in a large cohort of minority children, and now extend our studies to examine potential roles of vitamin D binding protein (DBP) as a determinant of 25-OHD levels. Serum DBP level and common single nucleotide polymorphisms (SNPs) at positions 432 and 436 in the GC gene, encoding DBP, were examined. We confirmed self-reported ancestry using ancestry informative markers (AIMs), and included quantitative AIMs scores in the analysis. The multivariate model incorporated previously identified demographic and nutritional determinants of 25-OHD in this cohort, as well as GC SNPs and circulating DBP. Genetic variants in GC differed by self-reported ancestry. The 1f allele (D432/T436) was enriched in African Americans, occurring in 71%. Homozygosity for the 1f allele (DDTT) occurred in 53% of African Americans but only 6% of Caucasians and 13% of Hispanics. Circulating DBP was significantly correlated with 25-OHD. GC SNPs were associated with both circulating DBP and 25-OHD. It appears that progressive substitution of lysine for threonine at the 436 position results in lower circulating 25-OHD. Multivariate analysis revealed that genetic variance in GC significantly contributes to circulating DBP as well as 25-OHD. Moreover, the effect of GC SNPs on 25-OHD are evident after adjusting for their effects on circulating DBP. Thus in young children genetic variance of the common GC T436K SNP affects circulating levels of the DBP protein, which in turn affects circulating 25-OHD. However, the GC genotype also affects circulating 25-OHD independently of its effect on circulating DBP. These findings provide data that may be important in the interpretation of vitamin D status in children of varying ancestral backgrounds. © 2013 American Society for Bone and Mineral Research
In vivo impact of Dlx3 conditional inactivation in neural crest‐derived craniofacial bones
Authors: Duverger Olivier , Isaac Juliane , Zah Angela , Hwang Joonsung , Berdal Ariane , Lian Jane B. , Morasso Maria I.
Published: August 2012

Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activities related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. J. Cell. Physiol. 228: 654–664, 2013. © 2012 Wiley Periodicals, Inc.
Cysteine‐linked aromatic nitriles as UV resonance Raman probes of protein structure
Authors: Weeks Colin L. , Jo Hyunil , Kier Brandon , DeGrado William F. , Spiro Thomas G.
Published: August 2012

Nitriles introduced into peptides and proteins can serve as useful vibrational spectroscopic probes, because the nitrile C ≡ N stretch is well isolated from backbone and sidechain vibrational bands. Aromatic nitriles offer large νC ≡ N absorption intensity in infrared spectra and resonance enhancement in Raman spectra with ultraviolet excitation. We report the ultraviolet resonance Raman spectra of cyanophenylalanine attached to cysteine, through linkage reactions that are applicable to cysteine residues in proteins. Excitation profiles are reported, and the νC ≡ N detection limit is estimated to be 5 µ m. The band position is sensitive to solvent polarity and especially to strong H‐bonding. The derivatization of mastoparan X peptide at introduced cysteine residues demonstrated the effectiveness of a cyanophenylcysteine probe in reporting the lowered environmental polarity when the peptide was incorporated into liposomes. For an asymmetrical cyanophenyl derivative, 2‐CBCys, the intensity ratio of asymmetric and symmetric ring modes, ν8b and ν8a, was found to respond to solvent polarity and not to H‐bonding. Copyright © 2012 John Wiley & Sons, Ltd.
Multispectroscopic studies for the identification of archaeological frankincense excavated in the underground palace of Bao'en Temple, Nanjing: near infrared, midinfrared, and Raman spectroscopies
Authors: Zhou Lei , Shen Dawa , He Junquan , Wei Yuhui , Ma Qinglin , Hu Zhide
Published: August 2012

Five resinous incense materials excavated from the underground palace of Bao'en Temple, Nanjing, were studied by a multianalytical approach of near infrared, midinfrared, and Fourier transform Raman spectroscopies. By comparing the multispectroscopic features of five specimens, these incense materials were identified to the same substance. Subsequent analysis and comparison of the ancient incense materials and three modern reference specimens were carried out, and the results indicated that the excavated incense materials were frankincense, with its major component of triterpenoids. This work performs, for the first time, a comprehensive spectroscopic study for the Chinese excavated incense materials, demonstrating that a combined use of near infrared, midinfrared, and Fourier transform Raman spectroscopies is an efficient technique to identify an excavated incense. Copyright © 2012 John Wiley & Sons, Ltd.
Selective intraoperative stimulation of the human larynx
Authors: Broniatowski Michael , Grundfest‐Broniatowski Sharon , Hahn Elizabeth C. , Hadley Aaron J. , Tyler Dustin J. , Tucker Harvey M.
Published: August 2012

Objectives/Hypothesis:

Laryngeal contraction normally entails activation of mutually cooperative intrinsic laryngeal muscles (ILMs). Unfortunately, standard stimulating methods do not completely mimic the normal ongoing synchrony between the muscles. We submit that this problem can be addressed by modifying the stimulating waveform.

Study Design:

This study extends prior canine research to the human using quasitrapezoidal (QT) currents instead of standard square waves, which while valuable incompletely express normal ILM interactions.

Methods:

In two patients undergoing laryngectomy for cancer, the recurrent laryngeal nerve on the uninvolved side received QT pulses (4 Hz, 60–2,000 μA, 100–500 μs width, 0–500‐μs decay) via a bipolar cuff electrode. Pairs of needle electrodes placed into the posterior cricoarytenoideus (PCA), lateral cricoarytenoideus (LCA), and thyroarytenoideus (TA) were used to record electromyography amplitudes, and waveforms were analyzed by a specially designed computer program.

Results:

With activity from square waves serving as control, we observed statistically significant (P < .05) shifts in mutual relationships among PCA, LCA, and TA for an array of specific QT configurations.

Conclusions:

Our preliminary data on selective ILM manipulation offer promise for improved dynamic control of faulty laryngeal contraction patterns.
Analysis of protein isoforms: Can we do it better?
Authors: Stastna Miroslava , Van Eyk Jennifer E.
Published: August 2012

Protein isoforms/splice variants can play important roles in various biological processes and can potentially be used as biomarkers or therapeutic targets/mediators. Thus, there is a need for efficient and, importantly, accurate methods to distinguish and quantify specific protein isoforms. Since protein isoforms can share a high percentage of amino acid sequence homology and dramatically differ in their cellular concentration, the task for accuracy and efficiency in methodology and instrumentation is challenging. The analysis of intact proteins has been perceived to provide a more accurate and complete result for isoform identification/quantification in comparison to analysis of the corresponding peptides that arise from protein enzymatic digestion. Recently, novel approaches have been explored and developed that can possess the accuracy and reliability important for protein isoform differentiation and isoform‐specific peptide targeting. In this review, we discuss the recent development in methodology and instrumentation for enhanced detection of protein isoforms as well as the examples of their biological importance.
Embelin inhibits growth and induces apoptosis through the suppression of Akt/mTOR/S6K1 signaling cascades
Authors: Kim Seong Won , Kim Sung‐Moo , Bae Hang , Nam Dongwoo , Lee Jun‐Hee , Lee Seok‐Geun , Shim Bum Sang , Kim Sung‐Hoon , Ahn Kyoo Seok , Choi Seung‐Hoon , Sethi Gautam , Ahn Kwang Seok
Published: August 2012

BACKGROUND

Akt/mTOR/S6K1 signaling cascades play an important role both in the survival and proliferation of tumor cells.

METHODS

In the present study, we investigated the effects of embelin (EB), identified primarily from the Embelia ribes plant, on the Akt/mTOR/S6K1 activation, associated gene products, cellular proliferation, and apoptosis in human prostate cancer cells.

RESULTS

EB exerted significant cytotoxic and suppressive effects on Akt and mTOR activation against androgen‐independent PC‐3 cells as compared to androgen‐dependent LNCaP cells. Moreover, EB suppressed the constitutive activation of Akt/mTOR/S6K1 signaling cascade, which correlated with the induction of apoptosis as characterized by accumulation of cells in subG1 phase, positive Annexin V binding, down‐regulation of anti‐apoptotic (Bcl‐2, Bcl‐xL, survivin, IAP‐1, and IAP‐2) and proliferative (cyclin D1) proteins, activation of caspase‐3, and cleavage of PARP. We also observed that EB can significantly enhance the apoptotic effects of a specific pharmacological Akt inhibitor when used in combination and also caused broad inhibition of all the three kinases in Akt/mTOR/S6K1 signaling axis in PC‐3 cells.

CONCLUSIONS

EB inhibits multiple signaling cascades involved in tumorigenesis and can be used as a potential therapeutic candidate for both the prevention and treatment of prostate cancer. Prostate 73: 296–305, 2013. © 2012 Wiley Periodicals, Inc.
Current management of aspirin‐exacerbated respiratory disease
Authors: Scadding Glenis
Published: August 2012

The diagnosis of aspirin and NSAID hypersensitivity can help the patient avoid further exacerbations. Dr Scadding describes the respiratory reactions seen in aspirin‐exacerbated respiratory disease and the various approaches to management.
Oxygen isotope exchange with quartz during pyrolysis of silver sulfate and silver nitrate
Authors: Schauer Andrew J. , Kunasek Shelley A. , Sofen Eric D. , Erbland Joseph , Savarino Joel , Johnson Ben W. , Amos Helen M. , Shaheen Robina , Abaunza Mariana , Jackson Terri L. , Thiemens Mark H. , Alexander Becky
Published: August 2012

RATIONALE

Triple oxygen isotopes of sulfate and nitrate are useful metrics for the chemistry of their formation. Existing measurement methods, however, do not account for oxygen atom exchange with quartz during the thermal decomposition of sulfate. We present evidence for oxygen atom exchange, a simple modification to prevent exchange, and a correction for previous measurements.

METHODS

Silver sulfates and silver nitrates with excess 17O were thermally decomposed in quartz and gold (for sulfate) and quartz and silver (for nitrate) sample containers to O2 and byproducts in a modified Temperature Conversion/Elemental Analyzer (TC/EA). Helium carries O2 through purification for isotope‐ratio analysis of the three isotopes of oxygen in a Finnigan MAT253 isotope ratio mass spectrometer.

RESULTS

The Δ17O results show clear oxygen atom exchange from non‐zero 17O‐excess reference materials to zero 17O‐excess quartz cup sample containers. Quartz sample containers lower the Δ17O values of designer sulfate reference materials and USGS35 nitrate by 15% relative to gold or silver sample containers for quantities of 2–10 µmol O2.

CONCLUSIONS

Previous Δ17O measurements of sulfate that rely on pyrolysis in a quartz cup have been affected by oxygen exchange. These previous results can be corrected using a simple linear equation (Δ17Ogold = Δ17Oquartz * 1.14 + 0.06). Future pyrolysis of silver sulfate should be conducted in gold capsules or corrected to data obtained from gold capsules to avoid obtaining oxygen isotope exchange‐affected data. Copyright © 2012 John Wiley & Sons, Ltd.
Practical considerations for the use of pollen δ13C value as a paleoclimate indicator
Authors: King D. Caleb , Schubert Brian A. , Jahren A. Hope
Published: August 2012

RATIONALE

Workers have shown a correlation between temperature and the pollen δ13C value, and therefore suggested using pollen δ13C values to reconstruct paleotemperature. To evaluate the potential for pollen δ13C values to be used as a paleotemperature proxy, it is essential to quantify the variability in pollen δ13C values and to evaluate the effect of temperature on pollen δ13C values, in isolation, under controlled environmental conditions.

METHODS

Pollen was isolated from 146 Hibiscus flowers from 26 plants within a single climate environment to evaluate isotopic variability in pollen δ13C values. The nearest leaf (n = 82) and flower phloem (n = 30) were also sampled to measure the δ13C variability in carbon providing the raw material for new growth. To evaluate the correlation between temperature and pollen δ13C values, we isolated pollen from 89 Brassica rapa plants grown in controlled growth chambers with temperatures ranging from 17 to 32°C.

RESULTS

The range in pollen δ13C values collected from different flowers on the same Hibiscus plant was large (average = 1.6‰), and could be as much as 3.2‰. This amount of variability was similar to that seen between flower‐adjacent leaves, and phloem extracted from styles of individual flowers. In controlled growth chamber experiments, we saw no correlation between temperature and the pollen (R2 = 0.005) or leaf (R2 = 0.10) δ13C values.

CONCLUSIONS

We measured large variability in pollen δ13C values. When temperature was isolated from other environmental parameters, temperature did not correlate with the pollen δ13C value. These results complicate the supposed relationship between temperature and pollen δ13C values and caution against using nanogram isotope analytical techniques for characterizing whole‐plant individuals. Copyright © 2012 John Wiley & Sons, Ltd.
Core–shell structure of fly ash particles ‐ SIMS depth profile analysis
Authors: Konarski P. , Zawada A. , Kowalczyk D. , Juda‐Rezler K.
Published: August 2012

Depth profile analysis in secondary ion mass spectrometry (SIMS) is applied for fly ash particles collected from three electrostatic precipitators in coal combustion type Thermoelectric Power Plant in Warsaw, Poland. Prior to analysis, particles of the collected material were size separated in nine stage cascade impactor with rotating substrate plates. Bulk analysis of the chosen size fractions was performed by atomic absorption spectroscopy. For SIMS depth profile analysis, particles were deposited on indium foils of high purity. Sputtering with 5 keV Ar+, 100 µm diameter ion beam was performed over 1.2 × 1.8 mm area of the indium foil in SIMS system (SAJW‐05 model) equipped with Physical Electronics ion gun and QMA‐410 Balzers quadrupole analyzer. SIMS data are quantified based on bulk concentration values of: carbon, sodium, aluminium, silicon, calcium, chromium, manganese, iron and nickel. Core–shell structure, and also cenosphere structure, is found. Depth profile analysis shows that shell layers of particles are enriched in carbon, calcium, chromium and nickel. Inner parts of particles or their cores are enriched in sodium and aluminium. Copyright © 2012 John Wiley & Sons, Ltd.
P2Y receptors and kidney function
Authors: Vallon Volker , Stockand James , Rieg Timo
Published: August 2012

Cellular release of nucleotides is of physiological importance to regulate and maintain cell function and integrity. Also in the tubular and collecting duct system of the kidney, nucleotides are released in response to changes in cell volume or luminal flow rate and act in a paracrine and autocrine way on basolateral and luminal P2Y receptors. Recent studies using gene knockout mice assigned a prominent role to G protein‐coupled P2Y2 receptors, which are activated by both ATP and UTP. The antidiuretic hormone, arginine‐vasopressin (AVP), and possibly an increase in collecting duct cell volume induce ATP release. The subsequent activation of P2Y2 receptors inhibits AVP‐induced cAMP formation and water reabsorption, which stabilizes cell volume and facilitates water excretion. An increase in NaCl intake enhances luminal release of ATP and UTP in the aldosterone‐sensitive distal nephron which by activating apical P2Y2 receptors and phospholipase C lowers the open probability of the epithelial sodium channel ENaC, thereby facilitating sodium excretion. Thus, the renal ATP/UTP/P2Y2 receptor system not only serves to preserve cell volume and integrity but is also regulated by stimuli that derive from body NaCl homeostasis. The system also inhibits ENaC activity during aldosterone escape, i.e., when sodium reabsorption via ENaC is inappropriately high. The P2Y2 receptor tone inhibits the expression and activity of the Na–K–2Cl cotransporter NKCC2 in the thick ascending limb and mediates vasodilation. While the role of other P2Y receptors in the kidney is less clear, the ATP/UTP/P2Y2receptor system regulates NaCl and water homeostasis and blood pressure. WIREs Membr Transp Signal 2012, 1:731–742. doi: 10.1002/wmts.61

For further resources related to this article, please visit the WIREs website.
Shedding light on nanomedicine
Authors: Tong Rong , Kohane Daniel S.
Published: August 2012

Light is an electromagnetic radiation that can convert its energy into different forms (e.g., heat, chemical energy, and acoustic waves). This property has been exploited in phototherapy (e.g., photothermal therapy and photodynamic therapy (PDT)) and optical imaging (e.g., fluorescence imaging) for therapeutic and diagnostic purposes. Light‐controlled therapies can provide minimally‐ or noninvasive spatiotemporal control as well as deep tissue penetration. Nanotechnology provides numerous advantages, including selective targeting of tissues, prolongation of therapeutic effect, protection of active payloads, and improved therapeutic indices. This review explores the advances that nanotechnology can bring to light‐based therapies and diagnostics, and vice versa, including photo‐triggered systems, nanoparticles containing photoactive molecules, and nanoparticles that are themselves photoactive. Limitations of light‐based therapies such as photic injury and phototoxicity are discussed. WIREs Nanomed Nanobiotechnol 2012, 4:638–662. doi: 10.1002/wnan.1188

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Modelling Cerebrovascular Reactivity: A Novel Near-Infrared Biomarker of Cerebral Autoregulation?
Authors: Highton David , Panovska-Griffiths Jasmina , Ghosh Arnab , Tachtsidis Ilias , Banaji Murad , Elwell Clare , Smith Martin
Published: August 2012

Understanding changes in cerebral oxygenation, haemodynamics and metabolism holds the key to individualised, optimised therapy after acute brain injury. Near-infrared spectroscopy (NIRS) offers the potential for non-invasive, continuous bedside measurement of surrogates for these processes. Interest has grown in applying this technique to interpret cerebrovascular pressure reactivity (CVPR), a surrogate of the brain’s ability to autoregulate blood flow. We describe a physiological model-based approach to NIRS interpretation which predicts autoregulatory efficiency from a model parameter k_aut. Data from three critically brain-injured patients exhibiting a change in CVPR were investigated. An optimal value for k_aut was determined to minimise the difference between measured and simulated outputs. Optimal values for k_aut appropriately tracked changes in CVPR under most circumstances. Further development of this technique could be used to track CVPR providing targets for individualised management of patients with altered vascular reactivity, minimising secondary neurological insults.
Oscillations in Cerebral Haemodynamics in Patients with Falciparum Malaria
Authors: Kolyva Christina , Kingston Hugh , Tachtsidis Ilias , Mohanty Sanjib , Mishra Saroj , Patnaik Rajya , Maude Richard J. , Dondorp Arjen M. , Elwell Clare E.
Published: August 2012

Spontaneous oscillations in cerebral haemodynamics studied with near-infrared spectroscopy (NIRS), become impaired in several pathological conditions. We assessed the spectral characteristics of these oscillations in 20 patients with falciparum malaria admitted to Ispat General Hospital, Rourkela, India. Monitoring included continuous frontal lobe NIRS recordings within 24 h of admission (Day 0), together with single measurements of a number of clinical and chemical markers recorded on admission. Seven patients returned for follow-up measurements on recovery (FU). A 2,048 sampling-point segment of oxygenated haemoglobin concentration ([ΔHbO2]) data was subjected to Fourier analysis per patient, and power spectral density was derived over the very low frequency (VLF: 0.02–0.04 Hz), low frequency (LF: 0.04–0.15 Hz) and high frequency (HF: 0.15–0.4 Hz) bands. At Day 0, VLF spectral power was 21.1 ± 16.4, LF power 7.2 ± 4.6 and HF power 2.6 ± 5.0, with VLF power being statistically significantly higher than LF and HF (P < 0.005). VLF power tended to decrease in the severely ill patients and correlated negatively with heart rate (r = 0.57, P < 0.01), while LF power correlated positively with aural body temperature (r = 0.49, P < 0.05). In all but one of the patients who returned for FU measurements, VLF power increased after recovery. This may be related to autonomic dysfunction in severe malaria, a topic of little research to date. The present study demonstrated that application of NIRS in a resource-poor setting is feasible and has potential as a research tool.
Discrete flavour groups, θ
13 and lepton flavour violation
Authors: Altarelli Guido , Feruglio Ferruccio , Merlo Luca , Stamou Emmanuel
Published: August 2012

Abstract

Discrete flavour groups have been studied in connection with special patterns of neutrino mixing suggested by the data, such as Tri-Bimaximal mixing (groups A
4, S
4…) or Bi-Maximal mixing (group S
4…) etc. We review the predictions for sin θ
13 in a number of these models and confront them with the experimental measurements. We compare the performances of the different classes of models in this respect. We then consider, in a supersymmetric framework, the important implications of these flavour symmetries on lepton flavour violating processes, like μ → eγ and similar processes. We discuss how the existing limits constrain these models, once their parameters are adjusted so as to optimize the agreement with the measured values of the mixing angles. In the simplified CMSSM context, adopted here just for indicative purposes, the small tan β range and heavy SUSY mass scales are favoured by lepton flavour violating processes, which makes it even more difficult to reproduce the reported muon g − 2 discrepancy.
Pancreatic cancer stem cells: regulatory networks in the tumor microenvironment and targeted therapy
Authors: Takao Sonshin , Ding Qiang , Matsubara Shyuichiro
Published: August 2012

Recent evidence has demonstrated that the existence of a cancer stem cell (CSC) subset in a solid tumor is responsible for the progression and relapse of cancer as well as its resistance to current therapies. Over the past decade, CSC research on pancreatic cancer has progressed. A fundamental understanding of pancreatic CSCs may improve therapies and deepen insight into the role of cell—cell interactions within a tumor microenvironment in pancreatic cancer progression. This review focuses on the impact of pancreatic CSCs on the regulatory networks in the tumor microenvironment, and the implications of targeting CSCs to treat pancreatic cancer.
Co-fermentation of xylose and cellobiose by an engineered Saccharomyces cerevisiae
Authors: Aeling Kimberly A , Salmon Kirsty A , Laplaza José M , Li Ling , Headman Jennifer R , Hutagalung Alex H , Picataggio Stephen
Published: August 2012

We have integrated and coordinately expressed in Saccharomyces cerevisiae a xylose isomerase and cellobiose phosphorylase from Ruminococcus flavefaciens that enables fermentation of glucose, xylose, and cellobiose under completely anaerobic conditions. The native xylose isomerase was active in cell-free extracts from yeast transformants containing a single integrated copy of the gene. We improved the activity of the enzyme and its affinity for xylose by modifications to the 5′-end of the gene, site-directed mutagenesis, and codon optimization. The improved enzyme, designated RfCO*, demonstrated a 4.8-fold increase in activity compared to the native xylose isomerase, with a Km for xylose of 66.7 mM and a specific activity of 1.41 μmol/min/mg. In comparison, the native xylose isomerase was found to have a Km for xylose of 117.1 mM and a specific activity of 0.29 μmol/min/mg. The coordinate over-expression of RfCO* along with cellobiose phosphorylase, cellobiose transporters, the endogenous genes GAL2 and XKS1, and disruption of the native PHO13 and GRE3 genes allowed the fermentation of glucose, xylose, and cellobiose under completely anaerobic conditions. Interestingly, this strain was unable to utilize xylose or cellobiose as a sole carbon source for growth under anaerobic conditions, thus minimizing yield loss to biomass formation and maximizing ethanol yield during their fermentation.
Novel image cytometric method for detection of physiological and metabolic changes in Saccharomyces cerevisiae
Authors: Chan Leo L , Kury Alexandria , Wilkinson Alisha , Berkes Charlotte , Pirani Alnoor
Published: August 2012

The studying and monitoring of physiological and metabolic changes in Saccharomyces cerevisiae (S. cerevisiae) has been a key research area for the brewing, baking, and biofuels industries, which rely on these economically important yeasts to produce their products. Specifically for breweries, physiological and metabolic parameters such as viability, vitality, glycogen, neutral lipid, and trehalose content can be measured to better understand the status of S. cerevisiae during fermentation. Traditionally, these physiological and metabolic changes can be qualitatively observed using fluorescence microscopy or flow cytometry for quantitative fluorescence analysis of fluorescently labeled cellular components associated with each parameter. However, both methods pose known challenges to the end-users. Specifically, conventional fluorescent microscopes lack automation and fluorescence analysis capabilities to quantitatively analyze large numbers of cells. Although flow cytometry is suitable for quantitative analysis of tens of thousands of fluorescently labeled cells, the instruments require a considerable amount of maintenance, highly trained technicians, and the system is relatively expensive to both purchase and maintain. In this work, we demonstrate the first use of Cellometer Vision for the kinetic detection and analysis of vitality, glycogen, neutral lipid, and trehalose content of S. cerevisiae. This method provides an important research tool for large and small breweries to study and monitor these physiological behaviors during production, which can improve fermentation conditions to produce consistent and higher-quality products.
Is there a role for routine pelvic magnetic resonance imaging in intermediate risk prostate cancer?
Authors: Pal Raj P , Wild Benn , Mayer Nick J , Khan Masood A
Published: August 2012

Objectives

To determine the role of staging pelvic magnetic resonance imaging (MRI) in men with intermediate risk prostate cancer.

Patients and methods

We identified all patients diagnosed with intermediate risk (NICE definition: PSA 10-20 ng/ml, or Gleason score 7, or clinical stage T2b/T2c) prostate cancer between 1st January 2007 and 31st December 2008. Through retrospective case note review, we determined the number of patients who had undergone a pelvic MRI and whether such an investigation had altered the patient's management by increasing tumour stage.

Results

A total of 222 men (mean age 66 years; range: 48-88) were diagnosed with intermediate risk prostate cancer during our study period. The mean PSA was 11.8 ng/ml (range: 3-20 ng/ml). Of these, 112 (50.5%) underwent an MRI. Overall, in 25/112 (22.3%) patients, pelvic MRI findings impacted significantly upon patient treatment by demonstrating either extra-prostatic extension of cancer, lymph node involvement or bone metastases.

Conclusions

Our retrospective study has demonstrated that a pelvic MRI in men diagnosed with intermediate risk prostate cancer may influence treatment decision in approximately a quarter of patients. Routine pelvic MRI is indicated in men with intermediate risk prostate cancer where radical treatment is contemplated.
Bilberry ingestion improves disease activity in mild to moderate ulcerative colitis — An open pilot study
Authors: Biedermann Luc , Mwinyi Jessica , Scharl Michael , Frei Pascal , Zeitz Jonas , Kullak-Ublick Gerd A. , Vavricka Stephan R. , Fried Michael , Weber Achim , Humpf Hans-Ulrich , Peschke Simone , Jetter Alexander , Krammer Gerhard , Rogler Gerhard
Published: August 2012

Background and aims: A significant fraction of patients with ulcerative colitis (UC) is not sufficiently controlled with conventional therapy or suffers from therapy related side effects. Anthocyanins, highly abundant in bilberries (Vaccinium myrtillus), were shown to have antioxidative and anti-inflammatory effects. We aimed to explore the therapeutic potential of bilberries in active UC.

Methods: In an open pilot trial with a total follow-up of 9 weeks the effect of a daily standardized anthocyanin-rich bilberry preparation was tested in 13 patients with mild to moderate UC. Clinical, biochemical, endoscopic and histologic parameters were assessed.

Results: At the end of the 6 week treatment interval 63.4% of patients achieved remission, the primary endpoint, while 90.9% of patients showed a response. In all patients a decrease in total Mayo score was detected (mean: 6.5 and 3.6 at screening and week 7, respectively; p < 0.001). Fecal calprotectin levels significantly decreased during the treatment phase (baseline: mean 778 μg/g, range 192–1790 μg/g; end of treatment: mean 305 μg/g, range < 30–1586 μg/g; p = 0.049), including 4 patients achieving undetectable levels at end of treatment. A decrease in endoscopic Mayo score and histologic Riley index confirmed the beneficial effect. However, an increase of calprotectin levels and disease activity was observed after cessation of bilberry intake. No serious adverse events were observed.

Conclusions: This is the first report on the promising therapeutic potential of a standardized anthocyanin-rich bilberry preparation in UC in humans. These results clearly indicate a therapeutic potential of bilberries in UC. Further studies on mechanisms and randomized clinical trials are warranted.
Determination of cathepsin V activity and intracellular trafficking by N‐glycosylation
Authors: Niwa Yuki , Suzuki Takehiro , Dohmae Naoshi , Umezawa Kazuo , Simizu Siro
Published: August 2012

Cathepsin V (L2), a lysosomal cysteine protease, is a member of cathepsin family, relating to cancer invasion and metastasis. Cathepsin V contains two predicted N‐glycosylation sites, but it has not been reported whether cathepsin V is glycosylated or not. In this study, we clarified the role of N‐glycosylation of cathepsin V for its functions. We demonstrated that cathepsin V is N‐glycosylated at both Asn221 and Asn292 using mass spectrometry and site‐directed mutagenesis. N‐glycosylation of cathepsin V was important for transportation to lysosome, secretion, and activity in HT1080 cells. These data demonstrated that functions of cathepsin V are controlled by N‐glycosylation.
FIGO Saving Mothers and Newborns Initiative 2006–2011
Authors: Lalonde André B. , Grellier Rachel
Published: August 2012

Reduction in maternal mortality is a key Millennium Development Goal (MDG 5). In an effort to contribute toward achievement of MDG 5, FIGO's Safe Motherhood and Newborn Health Committee worked with associations of obstetricians, gynecologists, and midwives in 10 low‐ and middle‐income countries between 2006 and 2011. Contributions were made by professional associations in high‐income countries through a structured north–south mentoring program. Each project focused on identified needs within each country and resulted in varied approaches and targets, ranging from clinical training, protocol development, and implementation of clinical audit through to legislative and policy change. Significant and largely sustainable results were achieved, particularly in relation to the relatively small‐scale funding available. This resulted in direct improvements to maternal and newborn health outcomes. The capacity of both FIGO and national professional associations was also substantially strengthened in project design, management, and implementation, leading to opportunities to further support international development efforts in the future.
Meeting the emerging challenge of breast and cervical cancer in low‐ and middle‐income countries
Authors: Knaul Felicia M. , Bhadelia Afsan , Gralow Julie , Arreola‐Ornelas Héctor , Langer Ana , Frenk Julio
Published: August 2012

Cancer, particularly when it affects women and reproductive health, epitomizes the complexities and inequities of the epidemiological challenge faced by low‐ and middle‐income countries. Women in resource‐poor settings face a double cancer burden: the backlog of preventable cancer, and the emerging challenge of cancers that cannot be prevented but whose impact could be dramatically reduced through early detection and treatment. Disparities in cancer incidence, mortality, and other health and non‐health outcomes are exacerbated by gender inequity and compounded by discrimination and stigma. The combination of these barriers implies a multiplicative challenge for women who face cancer, particularly when the disease is associated with reproduction. The horizons of maternal and reproductive health should extend to include the life cycle of healthy changes and illness that are embodied in longer life for women. Numerous opportunities exist to strengthen health systems through sexual and reproductive and women and health platforms and better meet the challenge of cancer.
Reducing maternal, newborn, and infant mortality globally: An integrated action agenda
Authors: Bhutta Zulfiqar A. , Cabral Sergio , Chan Chok‐wan , Keenan William J.
Published: August 2012

There has been increasing awareness over recent years of the persisting burden of worldwide maternal, newborn, and child mortality. The majority of maternal deaths occur during labor, delivery, and the immediate postpartum period, with obstetric hemorrhage as the primary medical cause of death. Other causes of maternal mortality include hypertensive diseases, sepsis/infections, obstructed labor, and abortion‐related complications. Recent estimates indicate that in 2009 an estimated 3.3 million babies died in the first month of life and that overall, 7.3 million children under 5 die each year. Recent data also suggest that sufficient evidence‐ and consensus‐based interventions exist to address reproductive, maternal, newborn, and child health globally, and if implemented at scale, these have the potential to reduce morbidity and mortality. There is an urgent need to put elements in place to promote integrated interventions among healthcare professionals and their associations. What is needed is the political will and partnerships to implement evidence‐based interventions at scale.
Comparison of methotrexate, actinomycin D, and etoposide for treating low‐risk gestational trophoblastic neoplasia
Authors: Baptista Angela M. , Belfort Paulo
Published: August 2012

Objective

To compare the efficacy and toxicity of 3 single agent chemotherapeutic regimens in low‐risk gestational trophoblastic neoplasia (LRGTN).

Methods

A prospective study was conducted at a referral center in Rio de Janeiro, Brazil. Patients presenting with metastatic or non‐metastatic LRGTN (risk score ≤ 6) in non‐probabilistic sampling were assigned to 1 of 3 treatments: methotrexate with folinic acid rescue (MTX‐CF; n = 20); actinomycin D (n = 20); and etoposide (n = 20). Women with less than 1 year of disease‐free follow‐up after the first normal human chorionic gonadotropin (hCG) value were excluded. Outcome measures included primary remission rate; resistance to primary and sequential chemotherapy; period between treatment initiation and remission (hCG response); and prevalence of toxic effects.

Results

Primary remission was achieved by 48 patients (80.0%). The remission rate with etoposide was 100.0%, while the rates with actinomycin D and MTX‐CF were 90.0% and 50.0%, respectively. Efficacy of etoposide was significantly greater than the other 2 agents (P < 0.001). Alopecia was the most frequent adverse effect caused by etoposide. Common to all protocols were stomatitis, nausea, and vomiting. Mean time intervals between beginning treatment and remission were similar and all 60 participants survived.

Conclusion

Etoposide was the most effective regimen for treating metastatic and non‐metastatic LRGTN.
The burden of health associated with benign gynecological disorders in low‐resource settings
Authors: Black Kirsten I. , Fraser Ian S.
Published: August 2012

Benign gynecological conditions impact on women's lives in a myriad of ways. Many of these conditions exert their burden on women's health because they remain undiagnosed, unacknowledged, or unreported for many years. Some of these conditions cause debilitating primary symptoms, especially of heavy menstrual bleeding, the lethargy of iron deficiency, and of persistent pelvic pain, with substantial impact on quality of life and ability to function on a day‐to‐day basis. The distressing quality of life impact of pelvic floor prolapse or of local vulval lesions should not be overlooked. Many also have secondary health consequences with adverse effects on fertility and reproductive outcome.
Postpartum hemorrhage management in 2012: Predicting the future
Authors: Onwuemene Oluwatoyosi , Green David , Keith Louis
Published: August 2012

Transfusion therapy in postpartum hemorrhage (PPH) traditionally has been modeled after precedents set in the Vietnam and Korean wars. However, data from recent military combat casualties suggest a different transfusion strategy. Transfusion of packed red blood cells, fresh frozen plasma, and platelets in a ratio of 1:1:1 improves dilutional coagulopathy and survival. Women who present with low fibrinogen at the time of diagnosis of PPH have poorer outcomes and might benefit from early fibrinogen replacement. The antifibrinolytic agent, tranexamic acid, decreases bleeding and progression to severe PPH, but its role in PPH management is evolving. Observational data suggest that the use of recombinant factor VIIa should be limited to bleeding that has not responded to an optimal transfusion strategy. Point‐of‐care testing using thromboelastography is helpful in guiding the selection of blood products to be transfused. Additionally, massive transfusion protocols can decrease the overall number of products transfused and improve outcomes.
A problem of Chief and Indian—The role of the supervisory authority BaFin and the ministry of finance in German financial market policy
Authors: Handke Stefan
Published: August 2012

The financial market crisis put the spotlight on the performance of two main German government bodies in financial market policy, the German Ministry of Finance (BMF) and the German Supervisory Authority (BaFin). The problem of delegation between the BMF as the principal of the agent BaFin is the focus of this article. During the crisis a lack of personnel in the BMF and the structural asymmetry between BaFin and the ministry caused problems in the formulation of crisis policies and in the handling of the subordinate authority. However, the crisis showed only the tip of an iceberg, because the BMF suffers from fundamental deficits in coping with the daily business of financial market policy and the control of an agency which gained more autonomy than politically intended. The overarching question is whether the BMF or BaFin controls German financial market policy.