bluuebunny/crossref_metadata_2025 huggingface dataset:
A Short History of Posterior Dynamic Stabilization
Authors: Gomleksiz Cengiz , Sasani Mehdi , Oktenoglu Tunc , Ozer Ali Fahir
Published: December 2012

Interspinous spacers were developed to treat local deformities such as degenerative spondylolisthesis. To treat patients with chronic instability, posterior pedicle fixation and rod-based dynamic stabilization systems were developed as alternatives to fusion surgeries. Dynamic stabilization is the future of spinal surgery, and in the near future, we will be able to see the development of new devices and surgical techniques to stabilize the spine. It is important to follow the development of these technologies and to gain experience using them. In this paper, we review the literature and discuss the dynamic systems, both past and present, used in the market to treat lumbar degeneration.
The Flexner Report of 1910 and Its Impact on Complementary and Alternative Medicine and Psychiatry in North America in the 20th Century
Authors: Stahnisch Frank W. , Verhoef Marja
Published: December 2012

America experienced a genuinely vast development of biomedical science in the early decades of the twentieth century, which in turn impacted the community of academic psychiatry and changed the way in which clinical and basic research approaches in psychiatry were conceptualized. This development was largely based on the restructuring of research universities in both of the USA and Canada following the influential report of Johns Hopkins-trained science administrator and politician Abraham Flexner (1866–1959). Flexner’s report written in commission for the Carnegie Foundation for the Advancement of Teaching in Washington, DC, also had a major influence on complementary and alternative medicine (CAM) in psychiatry throughout the 20th century. This paper explores the lasting impact of Flexner’s research published on modern medicine and particularly on what he interpreted as the various forms of health care and psychiatric treatment that appeared to compete with the paradigm of biomedicine. We will particularly draw attention to the serious effects of the closing of so many CAM-oriented hospitals, colleges, and medical teaching programs following to the publication of the Flexner Report in 1910.
Nonlinear Dynamics of an Electrorheological Sandwich Beam with Rotary Oscillation
Authors: Wei Kexiang , Zhang Wenming , Xia Ping , Liu Yingchun
Published: December 2012

The dynamic characteristics and parametric instability of a rotating electrorheological (ER) sandwich beam with rotary oscillation are numerically analyzed. Assuming that the angular velocity of an ER sandwich beam varies harmonically, the dynamic equation of the rotating beam is first derived based on Hamilton′s principle. Then the coupling and nonlinear equation is discretized and solved by the finite element method. The multiple scales method is employed to determine the parametric instability of the structures. The effects of electric field on the natural frequencies, loss factor, and regions of parametric instability are presented. The results obtained indicate that the ER material layer has a significant effect on the vibration characteristics and parametric instability regions, and the ER material can be used to adjust the dynamic characteristics and stability of the rotating flexible beams.
Influence of Weight Loss, Body Composition, and Lifestyle Behaviors on Plasma Adipokines: A Randomized Weight Loss Trial in Older Men and Women with Symptomatic Knee Osteoarthritis
Authors: Miller Gary D. , Jenks Monica Z. , Vendela Mandolyn , Norris James L. , Muday Gloria K.
Published: December 2012

Objective. To investigate effects of weight loss on adipokines and health measures in obese older adults with symptomatic knee osteoarthritis.Methods. Participants were randomly assigned to either weight loss (WL) (men: 12, women: 14) or weight stable (WS) group (men: 12, women: 13). WL intervention included meal replacements and structured exercise training. Measurements of leptin, adiponectin, soluble leptin receptor, lifestyle behaviors, and body composition were collected at baseline and 6 months. Univariate analysis of covariance was performed on 6 month variables, and Spearman and partial correlations were made between variables.Results. Weight loss was 13.0% and 6.7% in WL for men and women, respectively. Women in WL had lower whole body and trunk fat than WS. The leptin : adiponectin ratio was lower for women in WL than WS at 6 months, with no group differences in adipokines for men. Leptin and free leptin index correlated with body fat in both genders at baseline. Interestingly, only women showed reductions in leptin (P<0.100) and correlations between the percentage change leptin and trunk fat and the percentage changes in free leptin index with total fat and trunk fat. Partial correlations between 6 month adipokines after adjustments for covariates and group/time period show potential multivariate influences.Conclusions. In the presence of an effective weight loss intervention in older obese adults, there are significant relationships between weight and fat loss and leptin in women, but not men, suggesting gender-specific features of adipokine metabolism in this age group.
Eicosapentaenoic Acid Supplementation Changes Fatty Acid Composition and Corrects Endothelial Dysfunction in Hyperlipidemic Patients
Authors: Yamakawa Ken , Shimabukuro Michio , Higa Namio , Asahi Tomohiro , Ohba Kageyuki , Arasaki Osamu , Higa Moritake , Oshiro Yoshito , Yoshida Hisashi , Higa Tohru , Saito Taro , Ueda Shinichiro , Masuzaki Hiroaki , Sata Masataka
Published: December 2012

We investigated the effects of purified eicosapentaenoic acid (EPA) on vascular endothelial function and free fatty acid composition in Japanese hyperlipidemic subjects. In subjects with hyperlipidemia (total cholesterol≥220 mg/dL and/or triglycerides≥150 mg/dL), lipid profile and forearm blood flow (FBF) during reactive hyperemia were determined before and 3 months after supplementation with 1800 mg/day EPA. Peak FBF during reactive hyperemia was lower in the hyperlipidemic group than the normolipidemic group. EPA supplementation did not change serum levels of total, HDL, or LDL cholesterol, apolipoproteins, remnant-like particle (RLP) cholesterol, RLP triglycerides, or malondialdehyde-modified LDL cholesterol. EPA supplementation did not change total free fatty acid levels in serum, but changed the fatty acid composition, with increased EPA and decreased linoleic acid,γ-linolenic acid, and dihomo-γ-linolenic acid. EPA supplementation recovered peak FBF after 3 months. Peak FBF recovery was correlated positively with EPA and EPA/arachidonic acid levels and correlated inversely with dihomo-γ-linolenic acid. EPA supplementation restores endothelium-dependent vasodilatation in hyperlipidemic patients despite having no effect on serum cholesterol and triglyceride patterns. These results suggest that EPA supplementation may improve vascular function at least partly via changes in fatty acid composition.
Evolutionary Optimization of Electronic Circuitry Cooling Using Nanofluid
Authors: Mital Manu
Published: December 2012

Liquid cooling electronics using microchannels integrated in the chips is an attractive alternative to bulky aluminum heat sinks. Cooling can be further enhanced using nanofluids. The goals of this study are to evaluate heat transfer in a nanofluid heat sink with developing laminar flow forced convection, taking into account the pumping power penalty. The proposed model uses semi-empirical correlations to calculate effective nanofluid thermophysical properties, which are then incorporated into heat transfer and friction factor correlations in literature for single-phase flows. The model predicts the thermal resistance and pumping power as a function of four design variables that include the channel diameter, velocity, number of channels, and nanoparticle fraction. The parameters are optimized with minimum thermal resistance as the objective function and fixed specified value of pumping power as the constraint. For a given value of pumping power, the benefit of nanoparticle addition is evaluated by independently optimizing the heat sink, first with nanofluid and then with water. Comparing the minimized thermal resistances revealed only a small benefit since nanoparticle addition increases the pumping power that can alternately be diverted towards an increased velocity in a pure water heat sink. The benefit further diminishes with increase in available pumping power.
In VivoAnti-Influenza Virus Activity of Japanese Herbal (Kampo) Medicine, “Shahakusan,” and Its Possible Mode of Action
Authors: Hokari Rei , Nagai Takayuki , Yamada Haruki
Published: December 2012

Background. A Kampo medicine, Shahakusan (SHS), has been prescribed in late phase of infection that causes inflammations in the lung. But effect of SHS on viral infection in respiratory tract has never been reported.Objectives. To evaluate anti-influenza virus activity of SHS and its mode of actions through immune systems.Methods. SHS (0.3 g/kg/day) was orally administered to BALB/c miceforupper (URI) or lower respiratory tract infection (LRI) of influenza virus A/PR/8/34. The virus titer of nasal lavage fluid (NLF) at 5 or 2 day postinfection (p.i.) and cytokine mRNA expressions in mandibular lymph node or lung at 5 or 4 day p.i. were evaluated for URI or LRI, respectively. The histopathological examinations of lung tissue and NK cell activity in the splenocytes were also evaluated at 4 day p.i. on LRI.Results. When SHS was administered from 7 days before to 4 days p.i. for URI, the virus titer was significantly decreased in comparison with water-treated control, and IL-4, IL-1β, and IL-10 mRNA expression was decreased, but IL-12A mRNA expression was increased. Administration of SHS from one day before to one day p.i. for LRI significantly decreased the virus titer. SHS also decreased infiltration of inflammatory cells in the bronchoalveolar spaces and damage of desquamated mucosal epithelia of bronchiole, decreased IP-10 mRNA expression, and increased NK cell activity.Conclusion. SHS has no direct effect on influenza virus infection but exerts antiviral effect in mice by its immunomodulating activity through action of NK cells and anti-inflammatory activity in the lung.
Prevention of Lysosomal Storage Diseases and Derivation of Mutant Stem Cell Lines by Preimplantation Genetic Diagnosis
Authors: Altarescu Gheona , Beeri Rachel , Eiges Rachel , Epsztejn-Litman Silvina , Eldar-Geva Talia , Elstein Deborah , Zimran Ari , Margalioth Ehud J. , Levy-Lahad Ephrat , Renbaum Paul
Published: December 2012

Preimplantation genetic diagnosis (PGD) allows birth of unaffected children for couples at risk for a genetic disorder. We present the strategy and outcome of PGD for four lysosomal storage disorders (LSD): Tay-Sachs disease (TSD), Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (HS), and subsequent development of stem cell lines. For each disease, we developed a family-specific fluorescent multiplex single-cell PCR protocol that included the familial mutation and informative markers surrounding the mutation. Embryo biopsy and PGD analysis were performed on either oocytes (polar bodies one and two) or on single blastomeres from a six-cell embryo. We treated twenty families carrying mutations in these lysosomal storage disorders, including 3 couples requiring simultaneous analysis for two disorders (TSD/GD, TSD/balanced Robertsonian translocation 45XYder(21;14), and HS/oculocutaneus albinism). These analyses led to an overall pregnancy rate/embryo transfer of 38% and the birth of 20 unaffected children from 17 families. We have found that PGD for lysosomal disorders is a safe and effective method to prevent birth of affected children. In addition, by using mutant embryos for the derivation of stem cell lines, we have successfully established GD and HS hESC lines for use as valuable models in LSD research.
Fatal Hepatocellular Carcinoma in a Patient with Occult Hepatitis B Virus Infection following the Administration of R-CHOP for Diffuse Large B-Cell Lymphoma
Authors: Pitini Vincenzo , Rizzo Massimo , Arrigo Carmela , Mondello Patrizia , Altavilla Giuseppe
Published: December 2012

Occult hepatitis B (OBI) is caused by a persistent low-level replication of HBV. Like overt HBV infection, OBI can be associated with the integration of HBV sequences into the host genome and has a substantial clinical relevance for patients who are severely immunosuppressed for long durations. We present the case of a patient with a diffuse large B-cell non-Hodgkin lymphoma and OBI who developed a hepatocellular carcinoma with a fulminant clinical course following the administration of rituximab plus CHOP.
Motor Control and Neural Plasticity through Interhemispheric Interactions
Authors: Takeuchi Naoyuki , Oouchida Yutaka , Izumi Shin-Ichi
Published: December 2012

The corpus callosum, which is the largest white matter structure in the human brain, connects the 2 cerebral hemispheres. It plays a crucial role in maintaining the independent processing of the hemispheres and in integrating information between both hemispheres. The functional integrity of interhemispheric interactions can be tested electrophysiologically in humans by using transcranial magnetic stimulation, electroencephalography, and functional magnetic resonance imaging. As a brain structural imaging, diffusion tensor imaging has revealed the microstructural connectivity underlying interhemispheric interactions. Sex, age, and motor training in addition to the size of the corpus callosum influence interhemispheric interactions. Several neurological disorders change hemispheric asymmetry directly by impairing the corpus callosum. Moreover, stroke lesions and unilateral peripheral impairments such as amputation alter interhemispheric interactions indirectly. Noninvasive brain stimulation changes the interhemispheric interactions between both motor cortices. Recently, these brain stimulation techniques were applied in the clinical rehabilitation of patients with stroke by ameliorating the deteriorated modulation of interhemispheric interactions. Here, we review the interhemispheric interactions and mechanisms underlying the pathogenesis of these interactions and propose rehabilitative approaches for appropriate cortical reorganization.
Analysis of the Impact of Intraoperative Margin Assessment with Adjunctive Use of MarginProbe versus Standard of Care on Tissue Volume Removed
Authors: Rivera Ronald J. , Holmes Dennis R. , Tafra Lorraine
Published: December 2012

Breast conserving surgery has been accepted as the optimal local therapy for women with early breast cancer, emphasizing the necessity to balance oncologic goals with patient satisfaction and cosmetic outcomes. In the move to enhance a surgeon's ability to achieve histologically clear margins intraoperatively at the initial surgery, the MarginProbe (Dune Medical Devices, Caesarea, Israel) has emerged as an effective tool to accomplish that task. Based on previously reported success using the device, we assessed cosmesis and tissue resection volumes among participants in a randomized-controlled trial comparing the standard of care lumpectomy performed with and without the MarginProbe. The use of the MarginProbe device resulted in a 57% reduction in reexcision rates compared to the control group with a small increase in tissue volume removed at the primary lumpectomy. When total tissue volumes removed were analyzed, the device and control groups were still very similar after normalization to bra cup size. We concluded that the MarginProbe is an effective device to assist surgeons in determining margin status intraoperatively while allowing for better patient cosmetic outcomes due to the smaller volumes of tissue resected and the reduction in patient referrals for second surgeries due to positive margins.
Luminescence and Structure of ZnO Grown by Physical Vapor Deposition
Authors: García-Gutiérrez R. , Barboza-Flores M. , Berman-Mendoza D. , Rangel-Segura R. , Contreras-López O. E.
Published: December 2012

Nanostructured ZnO was deposited on different substrates (Si, SiO2, and Au/SiO2) by an enhanced physical vapor deposition technique that presents excellent luminescent properties. This technique consists in a horizontal quartz tube reactor that uses ultra-high purity Zn and UHP oxygen as precursors. The morphology and structure of ZnO grown in this work were studied by electron microscopy and X-ray diffraction. The XRD patterns revealed the highly crystalline phase of wurtzite polycrystalline structure, with a preferred (1011) growth direction. Room temperature cathodoluminescence studies revealed two features in the luminescence properties of the ZnO obtained by this technique, first a high-intensity narrow peak centered at 390 nm (~3.2 eV) corresponding to a near band-to-band emission, and secondly, a broad peak centered around 517 nm (2.4 eV), the typical green-yellow luminescence, related to an unintentionally doped ZnO.
Pulsar-Driven Jets in Supernovae, Gamma-Ray Bursts, and the Universe
Authors: Middleditch John
Published: December 2012

The bipolarity of Supernova 1987A can be understood through its very early light curve from the CTIO 0.4 m telescope and IUE FES and following speckle observations of the “Mystery Spot”. These indicate a beam/jet of light/particles, with initial collimation factors >104and velocities >0.95 c, involving up to 10−5 M⊙interacting with circumstellar material. These can be produced by a model of pulsar emission from polarization currents induced/(modulated faster than c) beyond the pulsar light cylinder by the periodic electromagnetic field (supraluminally induced polarization currents (SLIP)). SLIP accounts for the disruption of supernova progenitors and their anomalous dimming at cosmological distances, jets from Sco X-1 and SS 433, the lack/presence of pulsations from the high-/low-luminosity low-mass X-ray binaries, and long/short gamma-ray bursts, and it predicts that their afterglows are thepulsedoptical-/near-infrared emission associated with these pulsars. SLIP may also account for the TeV e+/e−results from PAMELA and ATIC, the WMAP “Haze”/Fermi “Bubbles,” and ther-process. SLIP jets from SNe of the first stars may allow galaxies to form without dark matter and explain the peculiar nongravitational motions between pairs of distant galaxies observed by GALEX.
Strong Truncation Approximation in Tandem Queues with Blocking
Authors: Adel-Aissanou Karima , Abbas Karim , Aïssani Djamil
Published: December 2012

Markov models are frequently used for performance modeling. However most models do not have closed form solutions, and numerical solutions are often not feasible due to the large or even infinite state space of models of practical interest. For that, the state‐space truncation is often demanded for computation of this kind of models. In this paper, we use the strong stability approach to establish analytic error bounds for the truncation of a tandem queue with blocking. Numerical examples are carried out to illustrate the quality of the obtained error bounds.
Imaging Findings of Pelvic Tumor Thrombosis Extending from Sacral Bone Metastasis of Adrenocortical Carcinoma
Authors: Ishida Kenichiro , Inoue Yusuke , Woodhams Reiko , Asano Yuji , Hara Toshimasa
Published: December 2012

We report the imaging findings of a patient with adrenocortical carcinoma who showed pelvic tumor thrombosis extending from sacral bone metastasis. Contrast-enhanced computed tomography demonstrated extensive intraluminal filling defects in the pelvic veins. A lytic lesion in the sacrum was also noted and continuity between the sacral lesion and the filling defect in the branch of pelvic veins was indicated. The filling defects showed increased uptake on positron emission tomography with18F-fluorodeoxyglucose and single-photon emission computed tomography with131I-iodomethylnorcholesterol, and fusion images with computed tomography aided the localization of the increased uptake areas. Multimodality imaging may be beneficial for the characterization and localization of lesions in patients suspected of having metastatic adrenocortical carcinoma.
Dependence of Pin Surface Roughness for Friction Forces of Ultrathin Perfluoropolyether Lubricant Film on Magnetic Disks by Pin-on-Disk Test
Authors: Tani H. , Mitsuya Y. , Kitagawa T. , Tagawa N.
Published: December 2012

We fabricated supersmooth probes for use in pin-on-disk sliding tests by applying gas cluster ion beam irradiation to glass convex lenses. In the fabrication process, various changes were made to the irradiation conditions; these included one-step irradiation of Ar clusters or two-step irradiation of Ar and N2clusters, with or without Ar cluster-assisted tough carbon deposition prior to N2irradiation, and the application of various ion doses onto the surface. We successfully obtained probes with a centerline averaged surface roughness that ranged widely from 1.08 to 4.30 nm. Using these probes, we measured the friction forces exerted on magnetic disks coated with a molecularly thin lubricant film. Perfluoropolyether lubricant films with different numbers of hydroxyl end groups were compared, and our results indicated that the friction force increases as the surface roughness of the pin decreases and that increases as the number of hydroxyl end groups increases.
Recent Developments in Neutrino/Antineutrino-Nucleus Interactions
Authors: Morfín Jorge G. , Nieves Juan , Sobczyk Jan T.
Published: December 2012

Recent experimental results and developments in the theoretical treatment of neutrino-nucleus interactions in the energy range of 1–10 GeV are discussed. Difficulties in extracting neutrino-nucleon cross sections from neutrino-nucleus scattering data are explained and significance of understanding nuclear effects for neutrino oscillation experiments is stressed. Detailed discussions of the status of two-body current contribution in the kinematic region dominated by quasielastic scattering and specific features of partonic nuclear effects in weak DIS scattering are presented.
A Multistage Decision-Feedback Receiver Design for LTE Uplink in Mobile Time-Variant Environments
Authors: Deng Juinn-Horng , Liao Shu-Min
Published: December 2012

Single-carrier-frequency division multiple access (SC-FDMA) has recently become the preferred uplink transmission scheme in long-term evolution (LTE) systems. Similar to orthogonal frequency division multiple access (OFDMA), SC-FDMA is highly sensitive to frequency offsets caused by oscillator inaccuracies and Doppler spread, which lead to intercarrier interference (ICI). This work proposes a multistage decision-feedback structure to mitigate the ICI effect and enhance system performance in time-variant environments. Based on the block-type pilot arrangement of the LTE uplink type 1 frame structure, the time-domain least squares (TDLS) method and polynomial-based curve-fitting algorithm are employed for channel estimation. Instead of using a conventional equalizer, this work uses a group frequency-domain equalizer (GFDE) to reduce computational complexity. Furthermore, this work utilizes a dual iterative structure of group parallel interference cancellation (GPIC) and frequency-domain group parallel interference cancellation (FPIC) to mitigate the ICI effect. Finally, to optimize system performance, this work applies a novel error-correction scheme. Simulation results demonstrate the bit error rate (BER) performance is markedly superior to that of the conventional full-size receiver based on minimum mean square error (MMSE). This structure performs well and is a flexible choice in mobile environments using the SC-FDMA scheme.
A Platelet Acquired Storage Pool Disorder Associated with Tamoxifen Therapy
Authors: Nayak Lalitha , Schmaier Alvin H.
Published: December 2012

The antiestrogenic drug tamoxifen, used in patients with breast cancer, is associated with an increase in arterial and venous thrombotic events, the mechanism of which is not clearly understood. We report a case of a lady who presented with new bruising and prolonged bleeding following a tooth extraction 4–6 weeks after starting tamoxifen. Investigations were consistent with an acquired platelet storage pool disorder. Repeat platelet function analysis was normal, performed 3 months after discontinuation of tamoxifen. We present a previously clinically unreported effect of tamoxifen on platelet function.
Brain Temperature: Physiology and Pathophysiology after Brain Injury
Authors: Mrozek Ségolène , Vardon Fanny , Geeraerts Thomas
Published: December 2012

The regulation of brain temperature is largely dependent on the metabolic activity of brain tissue and remains complex. In intensive care clinical practice, the continuous monitoring of core temperature in patients with brain injury is currently highly recommended. After major brain injury, brain temperature is often higher than and can vary independently of systemic temperature. It has been shown that in cases of brain injury, the brain is extremely sensitive and vulnerable to small variations in temperature. The prevention of fever has been proposed as a therapeutic tool to limit neuronal injury. However, temperature control after traumatic brain injury, subarachnoid hemorrhage, or stroke can be challenging. Furthermore, fever may also have beneficial effects, especially in cases involving infections. While therapeutic hypothermia has shown beneficial effects in animal models, its use is still debated in clinical practice. This paper aims to describe the physiology and pathophysiology of changes in brain temperature after brain injury and to study the effects of controlling brain temperature after such injury.
HOXA4Gene Promoter Hypermethylation as an Epigenetic Mechanism Mediating Resistance to Imatinib Mesylate in Chronic Myeloid Leukemia Patients
Authors: Elias Marjanu Hikmah , Baba Abdul Aziz , Husin Azlan , Sulong Sarina , Hassan Rosline , Sim Goh Ai , Abdul Wahid S. Fadilah , Ankathil Ravindran
Published: December 2012

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation ofHOXA4could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status ofHOXA4in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, theHOXA4hypermethylation level was significantly higher (P=0.002) in IM-resistant CML patients. On comparing the risk,HOXA4hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673–12.971;P=0.003). Thus, it is reasonable to suggest that promoter hypermethylation ofHOXA4gene could be an epigenetic mechanism mediating IM resistance in CML patients.
Multimolecular Salivary Mucin Complex Is Altered in Saliva of Cigarette Smokers: Detection of Disulfide Bridges by Raman Spectroscopy
Authors: Taniguchi Motoe , Iizuka Junko , Murata Yukari , Ito Yumi , Iwamiya Mariko , Mori Hiroshi , Hirata Yukio , Mukai Yoshiharu , Mikuni-Takagaki Yuko
Published: December 2012

Saliva contains mucins, which protect epithelial cells. We showed a smaller amount of salivary mucin, both MG1 and MG2, in the premenopausal female smokers than in their nonsmoking counterparts. Smokers' MG1, which contains almost 2% cysteine/half cystine in its amino acid residues, turned out to be chemically altered in the nonsmoker’s saliva. The smaller acidic glycoprotein bands were detectable only in smoker’s saliva in the range of 20–25 kDa and at 45 kDa, suggesting that degradation, at least in part, caused the reduction of MG1 mucin. This is in agreement with the previous finding that free radicals in cigarette smoke modify mucins in both sugar and protein moieties. Moreover, proteins such as amylase and albumin are bound to other proteins through disulfide bonds and are identifiable only after reduction with DTT. Confocal laser Raman microspectroscopy identified a disulfide stretch band of significantly stronger intensity per protein in the stimulated saliva of smokers alone. We conclude that the saliva of smokers, especially stimulated saliva, contains significantly more oxidized form of proteins with increased disulfide bridges, that reduces protection for oral epithelium. Raman microspectroscopy can be used for an easy detection of the damaged salivary proteins.
IROme, a New High-Throughput Molecular Tool for the Diagnosis of Inherited Retinal Dystrophies
Authors: Schorderet Daniel F. , Iouranova Alexandra , Favez Tatiana , Tiab Leila , Escher Pascal
Published: December 2012

The molecular diagnosis of retinal dystrophies is difficult because of the very important number of genes implicated and is rarely helped by genotype-phenotype correlations. This prompted us to develop IROme, a custom designed in solution-based targeted exon capture assay (SeqCap EZ Choice library, Roche NimbleGen) for 60 retinitis pigmentosa-linked genes and three candidate genes (942 exons). Pyrosequencing was performed on a Roche 454 GS Junior benchtop high-throughput sequencing platform. In total, 23 patients affected by retinitis pigmentosa were analyzed. Per patient, 39.6 Mb were generated, and 1111 sequence variants were detected on average, at a median coverage of 17-fold. After data filtering and sequence variant prioritization, disease-causing mutations were identified inABCA4,CNGB1,GUCY2D,PROM1,PRPF8,PRPF31,PRPH2,RHO,RP2, andTULP1for twelve patients (55%), ten mutations having never been reported previously. Potential mutations were identified in 5 additional patients, and in only 6 patients no molecular diagnosis could be established (26%). In conclusion, targeted exon capture and next-generation sequencing are a valuable and efficient approach to identify disease-causing sequence variants in retinal dystrophies.
MDR Gene Expression Analysis of Six Drug-Resistant Ovarian Cancer Cell Lines
Authors: Januchowski Radosław , Wojtowicz Karolina , Sujka-Kordowska Patrycja , Andrzejewska Małgorzata , Zabel Maciej
Published: December 2012

Ovarian cancer is the leading cause of death among gynaecological malignancies. Multiple drug resistance makes cancer cells insensitive to chemotherapy. In this study, we developed six primary ovarian cancer cell lines (W1MR, W1CR, W1DR, W1VR, W1TR, and W1PR) resistant to drugs such as methotrexate, cisplatin, doxorubicin, vincristine, topotecan, and paclitaxel. A chemosensitivity assay MTT test was performed to assess drug cross-resistance. Quantitative real-time polymerase chain reaction and Western blot were also performed to determine mRNA and protein expression of genes involved in chemoresistance. We observed high cross-resistance to doxorubicin, vincristine, and paclitaxel in the cell lines resistant to these agents. We also found a significant correlation between resistance to these drugs and increased expression of P-gp. Two different mechanisms of topotecan resistance were observed in the W1TR and W1PR cell lines. We did not observe any correlation between MRP2 transcript and protein levels. Cell lines resistant to agents used in ovarian cancer treatment remained sensitive to methotrexate. The main mechanisms of drug resistance were due to P-gp expression in the doxorubicin, vincristine, and paclitaxel resistant cell lines and BCRP expression in the topotecan resistant cell line.
Bodyweight Assessment of Enamelin Null Mice
Authors: Chan Albert H.-L. , Lertlam Rangsiyakorn , Simmer James P. , Wang Chia-Ning , Hu Jan C. C.
Published: December 2012

TheEnamnull mice appear to be smaller than wild-type mice, which prompted the hypothesis that enamel defects negatively influence nutritional intake and bodyweight gain (BWG). We compared the BWG ofEnam−/−and wild-type mice from birth (D0) to Day 42 (D42). Wild-type (WT) andEnam−/−(N) mice were given either hard chow (HC) or soft chow (SC). Four experimental groups were studied: WTHC, WTSC, NHC, and NSC. The mother’s bodyweight (DBW) and the average litter bodyweight (ALBW) were obtained from D0 to D21. After D21, the pups were separated from the mother and provided the same type of food. Litter bodyweights were measured until D42. ALBW was compared at 7-day intervals using one-way ANOVA, while the influence of DBW on ALBW was analyzed by mixed-model analyses. The ALBW ofEnam−/−mice maintained on hard chow (NHC) was significantly lower than the two WT groups at D21 and the differences persisted into young adulthood. The ALBW ofEnam−/−mice maintained on soft chow (NSC) trended lower, but was not significantly different than that of the WT groups. We conclude that genotype, which affects enamel integrity, and food hardness influence bodyweight gain in postnatal and young adult mice.
Glucose Toxic Effects on Granulation Tissue Productive Cells: The Diabetics’ Impaired Healing
Authors: Berlanga-Acosta Jorge , Schultz Gregory S. , López-Mola Ernesto , Guillen-Nieto Gerardo , García-Siverio Marianela , Herrera-Martínez Luis
Published: December 2012

Type 2 diabetes mellitus is a metabolic noncommunicable disease with an expanding pandemic magnitude. Diabetes predisposes to lower extremities ulceration and impairs the healing process leading to wound chronification. Diabetes also dismantles innate immunity favoring wound infection. Amputation is therefore acknowledged as one of the disease’s complications. Hyperglycemia is the proximal detonator of systemic and local toxic effectors including proinflammation, acute-phase proteins elevation, and spillover of reactive oxygen and nitrogen species. Insulin axis deficiency weakens wounds’ anabolism and predisposes to inflammation. The systemic accumulation of advanced glycation end-products irreversibly impairs the entire physiology from cells-to-organs. These factors in concert hamper fibroblasts and endothelial cells proliferation, migration, homing, secretion, and organization of a productive granulation tissue. Diabetic wound bed may turn chronically inflammed, procatabolic, and an additional source of circulating pro-inflammatory cytokines, establishing a self-perpetuating loop. Diabetic fibroblasts and endothelial cells may bear mitochondrial damages becoming prone to apoptosis, which impairs granulation tissue cellularity and perfusion. Endothelial progenitor cells recruitment and tubulogenesis are also impaired. Failure of wound reepithelialization remains a clinical challenge while it appears to be biologically multifactorial. Ulcer prevention by primary care surveillance, education, and attention programs is of outmost importance to reduce worldwide amputation figures.
The Role of Canonical and Noncanonical Pre-mRNA Splicing in Plant Stress Responses
Authors: Dubrovina A. S. , Kiselev K. V. , Zhuravlev Yu. N.
Published: December 2012

Plants are sessile organisms capable of adapting to various environmental constraints, such as high or low temperatures, drought, soil salinity, or pathogen attack. To survive the unfavorable conditions, plants actively employ pre-mRNA splicing as a mechanism to regulate expression of stress-responsive genes and reprogram intracellular regulatory networks. There is a growing evidence that various stresses strongly affect the frequency and diversity of alternative splicing events in the stress-responsive genes and lead to an increased accumulation of mRNAs containing premature stop codons, which in turn have an impact on plant stress response. A number of studies revealed that some mRNAs involved in plant stress response are spliced counter to the traditional conception of alternative splicing. Such noncanonical mRNA splicing events includetrans-splicing, intraexonic deletions, or variations affecting multiple exons and often require short direct repeats to occur. The noncanonical alternative splicing, along with common splicing events, targets the spliced transcripts to degradation through nonsense-mediated mRNA decay or leads to translation of truncated proteins. Investigation of the diversity, biological consequences, and mechanisms of the canonical and noncanonical alternative splicing events will help one to identify those transcripts which are promising for using in genetic engineering and selection of stress-tolerant plants.
Preparation of ACE Inhibitory Peptides fromMytilus coruscusHydrolysate Using Uniform Design
Authors: Wu Jin-Chao , Cheng Jie , Shi Xiao-lai
Published: December 2012

The angiotensin-I-converting enzyme (ACE) inhibitory peptides from mussel,Mytilus coruscus, were investigated and the variable factors, protease concentration, hydrolysis time, pH, and temperature, were optimized using Uniform Design, a new statistical experimental method. The results proved that the hydrolysate of alkali proteases had high ACE-inhibitory activity, especially the alkali protease E1. Optimization by Uniform Design showed that the best hydrolysis conditions for preparation of ACE-inhibitory peptides fromMytilus coruscuswere protease concentration of 36.0 U/mL, hydrolysis time of 2.7 hours, pH 8.2, and Temperature at 59.5°C, respectively. The verification experiments under optimum conditions showed that the ACE-inhibitory activity (91.3%) were agreed closely with the predicted activity of 90.7%. The amino acid composition analysis ofMytilus coruscusACE-inhibitory peptides proved that it had high percent of lysine, leucine, glycine, aspartic acid, and glutamic acid.
In Silico Studies of C3Metabolic Pathway Proteins of Wheat (Triticum aestivum)
Authors: Naeem Muhammad Kashif , Rauf Sobiah , Iqbal Hina , Nawaz Shah Muhammad Kausar , Mir Asif
Published: December 2012

Photosynthesis is essential for plant productivity and critical for plant growth. More than 90% of plants have a C3metabolic pathway primarily for carbon assimilation. Improving crop yields for food and fuel is a major challenge for plant biology. To enhance the production of wheat there is need to adopt the strategies that can create the change in plants at the molecular level. During the study we have employed computational bioinformatics and interactomics analysis of C3metabolic pathway proteins in wheat. The three-dimensional protein modeling provided insight into molecular mechanism and enhanced understanding of physiological processes and biological systems. Therefore in our study, initially we constructed models for nine proteins involving C3metabolic pathway, as these are not determined through wet lab experiment (NMR, X-ray Crystallography) and not available in RCSB Protein Data Bank and UniProt KB. On the basis of docking interaction analysis, we proposed the schematic diagram of C3metabolic pathway. Accordingly, there also exist vice versa interactions between 3PGK and Rbcl. Future site and directed mutagenesis experiments in C3plants could be designed on the basis of our findings to confirm the predicted protein interactions.
Estradiol Synthesis and Release in Cultured Female Rat Bone Marrow Stem Cells
Authors: Zhang Dalei , Yang Bei , Zou Weiying , Lu Xiaying , Xiong Mingdi , Wu Lei , Wang Jinglei , Gao Junhong , Xu Sifan , Zou Ting
Published: December 2012

Bone marrow stem cells (BMSCs) have the capacity to differentiate into mature cell types of multiple tissues. Thus, they represent an alternative source for organ-specific cell replacement therapy in degenerative diseases. In this study, we demonstrated that female rat BMSCs could differentiate into steroidogenic cells with the capacity forde novosynthesis of Estradiol-17β(E2) under high glucose culture conditions with or without retinoic acid (RA). The cultured BMSCs could express the mRNA and protein for P450arom, the enzyme responsible for estrogen biosynthesis. Moreover, radioimmunoassay revealed that BMSCs cultured in the present culture system produced and secreted significant amounts of testosterone, androstenedione, and E2. In addition, RA promoted E2 secretion but did not affect the levels of androgen. These results indicate that BMSCs can synthesize and release E2 and may contribute to autologous transplantation therapy for estrogen deficiency.
The Importance of the Nurse Cells and Regulatory Cells in the Control of T Lymphocyte Responses
Authors: Reyes García María Guadalupe , García Tamayo Fernando
Published: December 2012

T lymphocytes from the immune system are bone marrow-derived cells whose development and activities are carefully supervised by two sets of accessory cells. In the thymus, the immature young T lymphocytes are engulfed by epithelial “nurse cells” and retained in vacuoles, where most of them (95%) are negatively selected and removed when they have an incomplete development or express high affinity autoreactive receptors. The mature T lymphocytes that survive to this selection process leave the thymus and are controlled in the periphery by another subpopulation of accessory cells called “regulatory cells,” which reduce any excessive immune response and the risk of collateral injuries to healthy tissues. By different times and procedures, nurse cells and regulatory cells control both the development and the functions of T lymphocyte subpopulations. Disorders in the T lymphocytes development and migration have been observed in some parasitic diseases, which disrupt the thymic microenvironment of nurse cells. In other cases, parasites stimulate rather than depress the functions of regulatory T cells decreasing T-mediated host damages. This paper is a short review regarding some features of these accessory cells and their main interactions with T immature and mature lymphocytes. The modulatory role that neurotransmitters and hormones play in these interactions is also revised.
Intestinal Stem Cells: Common Signal Pathways, Human Disease Correlation, and Implications for Therapies
Authors: Dalal Jignesh , Radhi Mohamed
Published: December 2012

Enterocytes originating from gastrointestinal stem cells are basic building blocks of villi and crypts in human intestine. Little is known about intestinal stem cells (ISCs), their interaction with niche, and key pathways in their regulation. In this paper, we have reviewed the characteristics of ISC, its interaction with niche, and the understanding of key signaling pathways like Wnt. A better understanding of all of this will help to better utilize novel therapies like mesenchymal stromal cells (MSCs), R-spondin1, and sulindac in various disorders like colon cancer, graft-versus-host disease, intestinal polyposis, and radiation-related bowel injuries.
Paired Ductal CarcinomaIn Situand Invasive Breast Cancer Lesions in the D-Loop of the Mitochondrial Genome Indicate a Cancerization Field Effect
Authors: Maggrah Andrea , Robinson Kerry , Creed Jennifer , Wittock Roy , Gehman Ken , Gehman Teresa , Brown Helen , Harbottle Andrew , Froberg M. Kent , Klein Daniel , Reguly Brian , Parr Ryan
Published: December 2012

Alterations in the mitochondrial genome have been chronicled in most solid tumors, including breast cancer. The intent of this paper is to compare and document somatic mitochondrial D-loop mutations in paired samples of ductal carcinomain situ(DCIS) and invasive breast cancer (IBC) indicating a potential breast ductal epithelial cancerization field effect. Paired samples of these histopathologies were laser-captured microdissected (LCM) from biopsy, lumpectomy, and mastectomy tissues. Blood samples were collected as germplasm control references. For each patient, hypervariable region 1 (HV1) in the D-loop portion of the mitochondrial genome (mtGenome) was sequenced for all 3 clinical samples. Specific parallel somatic heteroplasmic alterations between these histopathologies, particularly at sites 16189, 16223, 16224, 16270, and 16291, suggest the presence of an epithelial, mitochondrial cancerization field effect. These results indicate that further characterization of the mutational pathway of DCIS and IBC may help establish the invasive potential of DCIS. Moreover, this paper indicates that biofluids with low cellularity, such as nipple aspirate fluid and/or ductal lavage, warrant further investigation as early and minimally invasive detection mediums of a cancerization field effect within breast tissue.
Cognitive Performance in Men and Women Infected with HIV-1
Authors: Faílde Garrido José María , Lameiras Fernández María , Foltz Marika , Rodríguez Castro Yolanda , Carrera Fernández María Victoria
Published: December 2012

Introduction. Very few studies have examined the neuropsychological performance of HIV-positive women, and even fewer have attempted a comparison of cognitive functioning by gender. The aim of this study was to describe the nature of the neuropsychological performance of HIV seropositive patients by gender.Methods. A clinical sample made up of 151 subjects was recruited to participate in this study. All of the subjects underwent the same assessment process, consisting of a neuropsychological evaluation and an interview to gather sociodemographic, toxicological, and clinical data.Results and Discussion. Despite the fact that men obtained higher scores in visual memory, attention/psychomotor speed, and abstract reasoning/verbal intelligence, these differences were not statistically significant. In contrast, significant differences were found depending on subjects’ serological status. Seropositive participants’ neuropsychological performance was significantly lower than that of the seronegative participants in all of the areas assessed as follows: (1) visual memory; (2) attention/psychomotor speed; (3) abstract reasoning/verbal intelligence; (4) verbal memory for texts; (5) verbal memory for digits and words.Conclusions. The results from this study reveal no significant gender differences in the cognitive performance of patients infected with HIV-1.
History, Pathogenesis, and Management of Familial Gastric Cancer: Original Study of John XXIII's Family
Authors: Corso Giovanni , Roncalli Fabrizio , Marrelli Daniele , Carneiro Fátima , Roviello Franco
Published: December 2012

Background. Hereditary diffuse gastric cancer is associated with the E-cadherin germline mutations, but genetic determinants have not been identified for familial intestinal gastric carcinoma. The guidelines for hereditary diffuse gastric cancer are clearly established; however, there are no defined recommendations for the management of familial intestinal gastric carcinoma.Methods. In this study we describe Pope John XXIII's pedigree that harboured gastric cancer as well as six other family members. Family history was analysed according to the International Gastric Cancer Linkage Consortium criteria, and gastric tumours were classified in accord with the last Japanese guidelines.Results. Seven out of 109 members in this pedigree harboured gastric cancer, affecting two consecutive generations. John XXIII's clinical tumour (cTN) was classified as cT4bN3a (IV stage). In two other cases, gastric carcinomas were classified as intestinal histotype and staged as pT1bN0 and pT2N2, respectively.Conclusions. Pope John XXIII's family presents a strong aggregation for gastric cancer affecting almost seven members; it spreads through two consecutive generations. In absence of defined genetic causes and considering the increased risk of gastric cancer’s development in these families, as well as the high mortality rates and advanced stages, we propose an intensive surveillance protocol for asymptomatic members.