bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of an Antibacterial Envelope is Associated with Reduced Cardiac Implantable Electronic Device Infections in High‐Risk Patients
Authors: KOLEK MATTHEW J. , DRESEN WILLIAM F. , WELLS QUINN S. , ELLIS CHRISTOPHER R.
Published: December 2012

Introduction

The incidence of cardiac implantable electronic device (CIED) infections has risen rapidly since 2004. A commercially available minocycline and rifampin impregnated antibacterial envelope has been associated with a low CIED infection rate. We performed a retrospective cohort study analyzing CIED infection rates in patients receiving an antibacterial envelope.

Methods

Prospectively applied criteria for use of the antibacterial envelope included ≥2 of the following: diabetes, renal insufficiency, anticoagulation, chronic corticosteroid use, fever or leukocytosis at the time of implantation, prior CIED infection, ≥3 leads (cardiac resynchronization therapy or abandoned leads), pacemaker dependence, or early pocket reentry. CIED infection rate was compared to a cohort of patients with matched risk factors and a CIED implanted prior to use of the antibacterial envelope.

Results

A total of 260 antibacterial envelopes were implanted from November 1, 2009 to April 30, 2012. The mean number of CIED infection risk factors was 2.8 ± 1.2. The control cohort (N = 639) was matched for mean number of CIED infection risk factors (2.8 ± 1.2), though individual risk factors differed. After a minimum of 90 days of follow‐up, there was one CIED infection among patients who received an antibacterial envelope (0.4%), compared to 19 (3%) in controls (odds ratio [95% confidence interval] 0.13 [0.02–0.95], P = 0.04). This difference persisted after adjustment for covariates (0.09 [0.01–0.73], P = 0.02) and propensity score matching (0.11 [0.01–0.85], P = 0.04).

Conclusions

In patients prospectively identified at high risk for CIED infection, use of a commercially available antibacterial envelope was associated with a marked reduction in CIED infections when compared to a matched control cohort.
Senescence evasion in melanoma progression: uncoupling of DNA‐damage signaling from p53 activation and p21 expression
Authors: MacKenzie Ross Alastair D. , Cook Martin G. , Chong Heung , Hossain Mehnaz , Pandha Hardev S. , Bennett Dorothy C.
Published: December 2012

The best‐established function of the melanoma‐suppressor p16 is mediation of cell senescence, a permanent arrest following cell proliferation or certain stresses. The importance of p16 in melanoma suggests indolence of the other major senescence pathway through p53. Little or no p53 is expressed in senescent normal human melanocytes, but p16‐deficient melanocytes can undergo p53‐mediated senescence. As p16 expression occurs in nevi but falls with progression toward melanoma, we here investigated whether p53‐dependent senescence occurs at some stage and, if not, what defects were detectable in this pathway, using immunohistochemistry. Phosphorylated checkpoint kinase 2 (CHEK2) can mediate DNA‐damage signaling, and under some conditions senescence, by phosphorylating and activating p53. Remarkably, we detected no prevalent p53‐mediated senescence in any of six classes of lesions. Two separate defects in p53 signaling appeared common: in nevi, lack of p53 phosphorylation by activated CHEK2, and in melanomas, defective p21 upregulation by p53 even when phosphorylated.
A Comparative Pilot Study of Symptom Improvement Before and After Phototherapy in Korean Patients with Perennial Allergic Rhinitis
Authors: Lee Heung‐Man , Park Man Sik , Park Il Ho , Lee Seung Hoon , Lee Seong Keon , Kim Kyu‐Sung , Choi Hyuk
Published: December 2012

Although allergic rhinitis is not life threatening, it significantly influences the quality of a patient's life. This study is intended to evaluate the safety and efficacy of phototherapy with low‐level energy of a 650 nm laser irradiation system in perennial allergic rhinitis patients. This clinical trial was an open‐label, single‐center study with 42 perennial allergic rhinitis subjects. Following laser irradiation in the nasal cavity with a laser irradiation system, the efficacy at weeks 1 through 4 was determined. The symptoms were scored with four parameters (nasal obstruction, rhinorrhea, sneezing and itching) before and after illumination of the laser, and the total score was recorded. A survey of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was conducted by patients before and after treatment. Following treatment, significant improvement in the clinical symptoms of nasal obstruction (P < 0.001), rhinorrhea (P = 0.005), sneezing (P = 0.001) and itching (P = 0.003) was reported by 68% of perennial allergic rhinitis patients. The overall RQLQ scores significantly improved by 45% from the baseline with the treatment after 4 weeks. These results indicate that phototherapy is an effective modality for treating perennial allergic rhinitis and is another option in the steroid‐free management of immune‐mediated mucosal diseases.
An autopsy case of clinically un‐diagnosed autosomal recessive polycystic kidney disease in 77‐year‐old male
Authors: Taneda Sekiko , Honda Kazuho , Aoki Asuka , Nitta Kosaku , Tamura Takashi , Yoshioka Yoko , Oda Hideaki
Published: December 2012

Autosomal recessive polycystic kidney disease (ARPKD) is caused by genetic mutations of the gene encoding fibrocystin, and is characterized by the collecting duct cysts and congenital hepatic fibrosis. We report an autopsy‐proven case of ARPKD in a 77‐year‐old male who presented with rapidly progressive renal and liver dysfunction. He had refused hemodialysis, and died 4 months later. At autopsy, both kidneys were enlarged with numerous small cysts throughout the cortex, which were revealed immunohistochemically to be the collecting ducts. Liver involvement was characterized by ductal plate malformation accompanied with portal fibrosis. The morphological appearances were compatible with ARPKD and the negative immunostaining for fibrocystin in the collecting ducts and bile ducts confirmed the diagnosis. ARPKD is known to occur in the neonatal period or in infancy with a high mortality rate. Although some patients who survive infancy are expected to live longer into young adulthood, most patients with ARPKD die of renal and hepatic failure in their childhood. The present case is extremely exceptional, in that no clinical symptoms suggestive of ARPKD were noticed until old age, and suggests that the disease spectrum of ARPKD is variable, and that a slowly progressive form of ARPKD may not be diagnosed until old age.
Fascin expression is related to poor survival in gastric cancer
Authors: Kim Su Jin , Kim Dae Cheol , Kim Min Chan , Jung Ghap Joong , Kim Ki Han , Jang Jin Seok , Kwon Hyuk Chan , Kim Yu Mi , Jeong Jin Sook
Published: December 2012

Fascin is an actin‐binding protein that provides mechanical support and cell motility, and involves cancer cell metastasis. We investigated fascin protein expression in gastric cancer and assessed their relationship with clinicopathologic parameters and survival rates. In addition, we researched galectin‐3 protein expression to study fascin action mechanisms. We performed immunohistochemisty with fascin and galectin‐3 antibodies in 471 gastric carcinomas, using tissue microarrays. Fascin was positive in 14.9% (70/471) of the samples, and fascin expression was related to worse survival rates (P < 0.001), high clinical stage (P < 0.001), high T stage (P < 0.001), nodal metastasis (P < 0.001), lymphovascular invasion (P= 0.001) and the intestinal type of Lauren classification (P= 0.015). Galectin‐3 protein expression was positive in 83.9% (395/471) of the samples and was reversely correlated with fascin protein expression (P= 0.020). Galectin‐3 expression was related to low clinical stage (P < 0.001), but not to survival rates in multivariate analysis. In multivariate analysis, fascin expression was related to worse survival rates (HR = 1.56, P= 0.036), and can be an independent poor prognostic factor in gastric cancer.
Primary pulmonary myxoid sarcoma with EWSR1‐CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: Case report with a review of Literature
Authors: Matsukuma Susumu , Hisaoka Masanori , Obara Kiyohaya , Kono Takako , Takeo Hiroaki , Sato Kimiya , Hata Yoshinobu
Published: December 2012

Reported herein is an extremely rare case of primary pulmonary myxoid sarcoma (PPMS). A 31‐year‐old man presented with a 2.7 cm‐sized pulmonary tumor surrounded by capsule‐like fibrosis. The patient has been free of disease for 5.8 years after surgery. This tumor focally showed endobronchial features, and consisted of reticular cords of oval, short spindle, or polygonal cells with swollen vesicular nuclei accompanied by an abundant myxoid stroma, closely resembling extraskeletal myxoid chondrosarcoma. Tumor cells were diffusely positive for vimentin and focally positive for epithelial membrane antigen, but were negative for cytokeratin, TTF‐1, Napsin A, S‐100 protein, CD34, desmin, smooth‐muscle actin, CD10, p63, calponin, h‐caldesmon, c‐kit, HMB‐45, synaptophysin, or glial fibrillary acid protein. Our reverse transcription‐polymerase chain reaction using the formalin‐fixed, paraffin‐embedded tumor tissues detected EWSR1‐CREB1 fusion transcript, but could not demonstrate EWSR1‐ATF1 fusion or EWSR1/TAF15/TFG‐NR4A3 fusion. These findings indicate that the current tumor is an additional case of PPMS with EESR1‐CREB1 fusion, recently reported by Thway et al. Some cases of PPMS can behave in an indolent manner.
Immunohistochemical analysis of aromatase in metastatic lymph nodes of breast cancer
Authors: Shibahara Yukiko , Miki Yasuhiro , Ishida Takanori , Nakamura Yasuhiro , Suzuki Takashi , Ohuchi Noriaki , Sasano Hironobu
Published: December 2012

Aromatase is the key enzyme in intratumoral estrogen production in postmenopausal breast cancer and third generation aromatase inhibitors suppress this enzymatic reaction effectively. Aromatase inhibitor is administered to metastatic breast cancer patients customarily in which estrogen receptor had been demonstrated only in the primary tumor, not the metastatic sites. The status of aromatase in metastatic sites has not been well‐characterized to date. We immunolocalized aromatase in 46 estrogen receptor positive primary breast cancers and paired metastatic lymph nodes, using immunohistochemistry. Immunoreactivity was detected in 44/46 primary tumors and 40/46 metastatic lymph nodes. A significant correlation was detected between the status of aromatase in primary and metastatic sites. Aromatase immunoreactivity was correlated with age, size of primary tumor and Ki‐67 index. Aromatase immunoreactivity was also detected in adipose tissue surrounding the lymph nodes. In conclusion, aromatase status in primary tumors generally represents its status in metastatic lymph nodes. This indicates that the endocrine environment of estrogen receptor positive tumors remain stable during the metastatic process.
Ingestion of sodium plus water improves cardiovascular function and performance during dehydrating cycling in the heat
Authors: Hamouti N. , Fernández‐Elías V. E. , Ortega J. F. , Mora‐Rodriguez R.
Published: December 2012

We studied if salt and water ingestion alleviates the physiological strain caused by dehydrating exercise in the heat. Ten trained male cyclists ( : 60 ± 7 mL/kg/min) completed three randomized trials in a hot‐dry environment (33 °C, 30% rh, 2.5 m/s airflow). Ninety minutes before the exercise, participants ingested 10 mL of water/kg body mass either alone (CON trial) or with salt to result in concentrations of 82 or 164 mM Na+ (ModNa+ or HighNa+ trial, respectively). Then, participants cycled at 63% of for 120 min immediately followed by a time‐trial. After 120 min of exercise, the reduction in plasma volume was lessened with ModNa+ and HighNa+ trials (−11.9 ± 2.1 and −9.8 ± 4.2%) in comparison with CON (−16.4 ± 3.2%; P < 0.05). However, heat accumulation or dissipation (forearm skin blood flow and sweat rate) were not improved by salt ingestion. In contrast, both salt trials maintained cardiac output (∼1.3 ± 1.4 L/min; P < 0.05) and stroke volume (∼10 ± 11 mL/beat; P < 0.05) above CON after 120 min of exercise. Furthermore, the salt trials equally improved time‐trial performance by 7.4% above CON (∼289 ± 42 vs 269 ± 50 W, respectively; P < 0.05). Our data suggest that pre‐exercise ingestion of salt plus water maintains higher plasma volume during dehydrating exercise in the heat without thermoregulatory effects. However, it maintains cardiovascular function and improves cycling performance.
Wheat centromeric retrotransposons: the new ones take a major role in centromeric structure
Authors: Li Baochun , Choulet Frédéric , Heng Yanfang , Hao Weiwei , Paux Etienne , Liu Zhao , Yue Wei , Jin Weiwei , Feuillet Catherine , Zhang Xueyong
Published: December 2012

The physical map of the hexaploid wheat chromosome 3B was screened using centromeric DNA probes. A 1.1‐Mb region showing the highest number of positive bacterial artificial chromosome (BAC) clones was fully sequenced and annotated, revealing that 96% of the DNA consisted of transposable elements, mainly long terminal repeat (LTR) retrotransposons (88%). Estimation of the insertion time of the transposable elements revealed that CRW (also called Cereba) and Quinta are the youngest elements at the centromeres of common wheat (Triticum spp.) and its diploid ancestors, with Quinta being younger than CRW in both diploid and hexaploid wheats. Chromatin immunoprecipitation experiments revealed that both CRW and Quinta families are targeted by the centromere‐specific histone H3 variant CENH3. Immuno colocalization of retroelements and CENH3 antibody indicated that a higher proportion of Quinta than CRWs was associated with CENH3, although CRWs were more abundant. Long arrays of satellite repeats were also identified in the wheat centromere regions, but they lost the ability to bind with CENH3. In addition to transposons, two functional genes and one pseudogene were identified. The gene density in the centromere appeared to be between three and four times lower than the average gene density of chromosome 3B. Comparisons with related grasses also indicated a loss of microcollinearity in this region. Finally, comparison of centromeric sequences of Aegilops tauschii (DD), Triticum boeoticum (AA) and hexaploid wheat revealed that the centromeres in both the polyploids and diploids are still undergoing dynamic changes, and that the new CRWs and Quintas may have undertaken the core role in kinetochore formation.
Novel Systems for Dynamically Assessing Insulin Action in Live Cells Reveals Heterogeneity in the Insulin Response
Authors: Burchfield James G. , Lu Jinling , Fazakerley Daniel J. , Tan Shi‐Xiong , Ng Yvonne , Mele Katarina , Buckley Michael J. , Han Weiping , Hughes William E. , James David E.
Published: December 2012

Regulated GLUT4 trafficking is a key action of insulin. Quantitative stepwise analysis of this process provides a powerful tool for pinpointing regulatory nodes that contribute to insulin regulation and insulin resistance. We describe a novel GLUT4 construct and workflow for the streamlined dissection of GLUT4 trafficking; from simple high throughput screens to high resolution analyses of individual vesicles. We reveal single cell heterogeneity in insulin action highlighting the utility of this approach – each cell displayed a unique and highly reproducible insulin response, implying that each cell is hard‐wired to produce a specific output in response to a given stimulus. These data highlight that the response of a cell population to insulin is underpinned by extensive heterogeneity at the single cell level. This heterogeneity is pre‐programmed within each cell and is not the result of intracellular stochastic events.
Replaced platelet concentrates containing a new additive solution, M‐sol: safety and efficacy for pediatric patients
Authors: Yanagisawa Ryu , Shimodaira Shigetaka , Kojima Shunsuke , Nakasone Nobuhiko , Ishikawa Shinsuke , Momose Kayo , Honda Takayuki , Yoshikawa Kentaro , Saito Shoji , Tanaka Miyuki , Nakazawa Yozo , Sakashita Kazuo , Shiohara Masaaki , Akino Mitsuaki , Hirayama Junichi , Azuma Hiroshi , Koike Kenichi
Published: December 2012

Background

Allergic transfusion reactions (ATRs), particularly those caused by plasma‐rich platelet concentrates (P‐PCs), are an important concern in transfusion medicine. Replacing P‐PCs with PCs containing M‐sol (M‐sol‐R‐PCs) is expected to prevent ATRs. However, this has not yet been verified by sufficient clinical evidence.

Study Design and Methods

A retrospective cohort study was performed between 2008 and 2011. Pediatric patients with hematologic disorders, solid tumors, primary immunodeficiency disorders, or inherited metabolic disorders were transfused with M‐sol‐R‐PCs between 2010 and 2011; the transfusions of P‐PCs administered between 2008 and 2011 were compared in terms of frequency and severity of ATRs, corrected count increment (CCI), and occurrence of bleeding. Data were collected for 6 consecutive months on a per‐patient basis.

Results

Data obtained during 2008 to 2011 showed that of the 78 patients receiving 515 P‐PC transfusions, 14 (17.9%) had 17 ATRs (3.3%); 14 and three ATRs were of Grades 1 and 2, respectively. In 2010 to 2011, 49 patients received 620 transfusions of M‐sol‐R‐PCs, and two patients (4.1%) had Grade 1 ATRs (0.3%). Thus, the frequency of ATRs per bag and per patient differed significantly between the two transfusions. No steroid agents were used for the prevention or treatment of ATRs in the M‐sol‐R‐PC group. The CCI (24 hr) for M‐sol‐R‐PCs did not differ from that for P‐PCs.

Conclusion

M‐sol‐R‐PCs were found to be effective in preventing ATRs without loss of transfusion efficiency in children; however, its efficacy should be further evaluated in prospective clinical trials.
Prion removal capacity of plasma protein manufacturing processes
Authors: Cai Kang , Gröner Albrecht , Dichtelmüller Herbert O. , Fabbrizzi Fabrizio , Flechsig Eckhard , Gajardo Rodrigo , von Hoegen Ilka , Jorquera Juan I. , Kempf Christoph , Kreil Thomas R. , Lee Douglas C. , Moscardini Mila , Pölsler Gerhard , Roth Nathan J.
Published: December 2012

Background

The variant Creutzfeldt‐Jakob disease incidence peaked a decade ago and has since declined. Based on epidemiologic evidence, the causative agent, pathogenic prion, has not constituted a tangible contamination threat to large‐scale manufacturing of human plasma‐derived proteins. Nonetheless, manufacturers have studied the prion removal capabilities of various manufacturing steps to better understand product safety. Collectively analyzing the results could reveal experimental reproducibility and detect trends and mechanisms driving prion removal.

Study Design and Methods

Plasma Protein Therapeutics Association member companies collected more than 200 prion removal studies on plasma protein manufacturing steps, including precipitation, adsorption, chromatography, and filtration, as well as combined steps. The studies used a range of model spiking agents and bench‐scale process replicas. The results were grouped based on key manufacturing variables to identify factors impacting removal. The log reduction values of a group are presented for comparison.

Results

Overall prion removal capacities evaluated by independent groups were in good agreement. The removal capacity evaluated using biochemical assays was consistent with prion infectivity removal measured by animal bioassays. Similar reduction values were observed for a given step using various spiking agents, except highly purified prion protein in some circumstances. Comparison between combined and single‐step studies revealed complementary or overlapping removal mechanisms. Steps with high removal capacities represent the conditions where the physiochemical differences between prions and therapeutic proteins are most significant.

Conclusion

The results support the intrinsic ability of certain plasma protein manufacturing steps to remove prions in case of an unlikely contamination, providing a safeguard to products.
Learning to be economical: the energy cost of walking tracks motor adaptation
Authors: Finley James M. , Bastian Amy J. , Gottschall Jinger S.
Published: December 2012

Key points

Neuroscientists often suggest that we adapt our movements to minimize energy use; however, recent studies have provided conflicting evidence in this regard.

In the present study, we show that motor learning robustly increases the economy of locomotion during split‐belt treadmill adaptation.

We also demonstrate that reductions in metabolic power scale with the magnitude of adaptation and are also associated with a reduction in muscle activity throughout the lower limbs.

Our results provide strong evidence that increasing economy may be a key criterion driving the systematic changes in co‐ordination during locomotor adaptation.

These findings may also facilitate the design of novel interventions to improve locomotor learning in stroke survivors.

Abstract  Many theories of motor control suggest that we select our movements to reduce energy use. However, it is unclear whether this process underlies short‐term motor adaptation to novel environments. Here we asked whether adaptation to walking on a split‐belt treadmill leads to a more economical walking pattern. We hypothesized that adaptation would be accompanied by a reduction in metabolic power and muscle activity and that these reductions would be temporally correlated. Eleven individuals performed a split‐belt adaptation task where the belt speeds were set at 0.5 and 1.5 m s‐1. Adaptation was characterized by step length symmetry, which is the normalized difference in step length between the legs. Metabolic power was calculated based on expired gas analysis, and surface EMG was used to record the activity of four bilateral leg muscles (tibialis anterior, lateral gastrocnemius, vastus lateralis and biceps femoris). All participants initially walked with unequal step lengths when the belts moved at different speeds, but gradually adapted to take steps of equal length. Additionally, net metabolic power was reduced from early adaptation to late adaptation (early, 3.78 ± 1.05 W kg−1; and late, 3.05 ± 0.79 W kg−1; P < 0.001). This reduction in power was also accompanied by a bilateral reduction in EMG throughout the gait cycle. Furthermore, the reductions in metabolic power occurred over the same time scale as the improvements in step length symmetry, and the magnitude of these improvements predicted the size of the reduction in metabolic power. Our results suggest that increasing economy may be a key criterion driving locomotor adaptation.
Dosimetric accuracy of a deterministic radiation transport based 192Ir brachytherapy treatment planning system. Part III. Comparison to Monte Carlo simulation in voxelized anatomical computational models
Authors: Zourari K. , Pantelis E. , Moutsatsos A. , Sakelliou L. , Georgiou E. , Karaiskos P. , Papagiannis P.
Published: December 2012

Purpose:

To compare TG43‐based and Acuros deterministic radiation transport‐based calculations of the BrachyVision treatment planning system (TPS) with corresponding Monte Carlo (MC) simulation results in heterogeneous patient geometries, in order to validate Acuros and quantify the accuracy improvement it marks relative to TG43.

Methods:

Dosimetric comparisons in the form of isodose lines, percentage dose difference maps, and dose volume histogram results were performed for two voxelized mathematical models resembling an esophageal and a breast brachytherapy patient, as well as an actual breast brachytherapy patient model. The mathematical models were converted to digital imaging and communications in medicine (DICOM) image series for input to the TPS. The MCNP5 v.1.40 general‐purpose simulation code input files for each model were prepared using information derived from the corresponding DICOM RT exports from the TPS.

Results:

Comparisons of MC and TG43 results in all models showed significant differences, as reported previously in the literature and expected from the inability of the TG43 based algorithm to account for heterogeneities and model specific scatter conditions. A close agreement was observed between MC and Acuros results in all models except for a limited number of points that lay in the penumbra of perfectly shaped structures in the esophageal model, or at distances very close to the catheters in all models.

Conclusions:

Acuros marks a significant dosimetry improvement relative to TG43. The assessment of the clinical significance of this accuracy improvement requires further work. Mathematical patient equivalent models and models prepared from actual patient CT series are useful complementary tools in the methodology outlined in this series of works for the benchmarking of any advanced dose calculation algorithm beyond TG43.
Monte Carlo simulations of adult and pediatric computed tomography exams: Validation studies of organ doses with physical phantoms
Authors: Long Daniel J. , Lee Choonsik , Tien Christopher , Fisher Ryan , Hoerner Matthew R. , Hintenlang David , Bolch Wesley E.
Published: December 2012

Purpose:

To validate the accuracy of a Monte Carlo source model of the Siemens SOMATOM Sensation 16 CT scanner using organ doses measured in physical anthropomorphic phantoms.

Methods:

The x‐ray output of the Siemens SOMATOM Sensation 16 multidetector CT scanner was simulated within the Monte Carlo radiation transport code, MCNPX version 2.6. The resulting source model was able to perform various simulated axial and helical computed tomographic (CT) scans of varying scan parameters, including beam energy, filtration, pitch, and beam collimation. Two custom‐built anthropomorphic phantoms were used to take dose measurements on the CT scanner: an adult male and a 9‐month‐old. The adult male is a physical replica of the University of Florida reference adult male hybrid computational phantom, while the 9‐month‐old is a replica of the University of Florida Series B 9‐month‐old voxel computational phantom. Each phantom underwent a series of axial and helical CT scans, during which organ doses were measured using fiber‐optic coupled plastic scintillator dosimeters developed at the University of Florida. The physical setup was reproduced and simulated in MCNPX using the CT source model and the computational phantoms upon which the anthropomorphic phantoms were constructed. Average organ doses were then calculated based upon these MCNPX results.

Results:

For all CT scans, good agreement was seen between measured and simulated organ doses. For the adult male, the percent differences were within 16% for axial scans, and within 18% for helical scans. For the 9‐month‐old, the percent differences were all within 15% for both the axial and helical scans. These results are comparable to previously published validation studies using GE scanners and commercially available anthropomorphic phantoms.

Conclusions:

Overall results of this study show that the Monte Carlo source model can be used to accurately and reliably calculate organ doses for patients undergoing a variety of axial or helical CT examinations on the Siemens SOMATOM Sensation 16 scanner.
IGFBP7 Binds to the IGF-1 Receptor and Blocks Its Activation by Insulin-Like Growth Factors
Authors: Evdokimova Valentina , Tognon Cristina E. , Benatar Tania , Yang Wenyi , Krutikov Konstantin , Pollak Michael , Sorensen Poul H. B. , Seth Arun
Published: December 2012

By inactivating the insulin-like growth factor receptor, IGFBP7 suppresses growth and promotes cell death.
c-FLIP Maintains Tissue Homeostasis by Preventing Apoptosis and Programmed Necrosis
Authors: Piao Xuehua , Komazawa-Sakon Sachiko , Nishina Takashi , Koike Masato , Piao Jiang-Hu , Ehlken Hanno , Kurihara Hidetake , Hara Mutsuko , Van Rooijen Nico , Schütz Günther , Ohmuraya Masaki , Uchiyama Yasuo , Yagita Hideo , Okumura Ko , He You-Wen , Nakano Hiroyasu
Published: December 2012

The antiapoptotic protein c-FLIP blocks multiple cell death pathways in mice.
Spots to Remember
Authors: Vignieri Sacha N.
Published: December 2012

A male sex pheromone rapidly stimulates learning of place preference that is remembered for about 2 weeks.
Gonad–Life-Span Coupling
Authors: VanHook Annalisa M.
Published: December 2012

A developmental timing program is redeployed to extend life span in the absence of a germ line.
Disrupting the Endothelial Barrier
Authors: Gough Nancy R.
Published: December 2012

A noncanonical pathway involving the adaptor MyD88 may contribute to the disruption of endothelial barrier function associated with inflammation.
Population Pharmacokinetic Analysis of Fluconazole To Predict Therapeutic Outcome in Burn Patients with Candida Infection
Authors: Han Seunghoon , Kim Jimyon , Yim Haejun , Hur Jun , Song Wonkeun , Lee Jongtae , Jeon Sangil , Hong Taegon , Woo Heungjeong , Yim Dong-Seok
Published: December 2012

The pharmacokinetic (PK) property of fluconazole might be significantly altered in major burn patients by medical interventions and physiologic changes. In this study, our aims were to investigate fluconazole PK in burn patients using a population approach and to recommend the optimal fluconazole regimen based upon the predicted therapeutic outcome. At steady state, blood samples for PK analysis were obtained from 60 burn patients receiving between 100 and ∼400 mg fluconazole daily. A mixed-effect modeling was performed and the therapeutic outcome of antifungal therapy was predicted for 10,000 virtual patients using NONMEM (version 7.2). MIC values were sampled from the MIC distribution at the study site. An area under the free drug concentration-time curve (fAUC)/MIC measurement of >25 h was used as the criterion for therapeutic success. When the same dose was given, the plasma concentration of fluconazole was predicted to be lower in burn patients compared to the nonburn population because of the large PK parameter (clearance, volume of distribution) estimates and continuous renal replacement therapy (CRRT). This tendency was particularly predominant when the patients were within 30 postburn days. Based upon our findings, 400 mg/day fluconazole is recommended to obtain therapeutic successes in major burn patients.
KPC Presence in Pseudomonas aeruginosa Has Minimal Impact on the
In Vivo
Efficacy of Carbapenem Therapy
Authors: Hagihara Mao , Crandon Jared L. , Urban Carl M. , Nicolau David P.
Published: December 2012

While reports of
Klebsiella pneumoniae
carbapenemase (KPC) production among
Pseudomonas aeruginosa
strains have emerged from a number of countries worldwide, outcome data are lacking. This is the first report evaluating how KPC production in
P. aeruginosa
impacts the efficacy of carbapenems by using the murine thigh infection model. Our findings suggest that the impact of KPC-2
in vivo
is less pronounced than would be anticipated based on the
in vitro
potency.
Correlation of Cell Membrane Lipid Profiles with Daptomycin Resistance in Methicillin-Resistant Staphylococcus aureus
Authors: Mishra Nagendra N. , Bayer Arnold S.
Published: December 2012

We compared the cell membrane (CM) lipid composition among nine well-characterized daptomycin-susceptible (Dap
s
)/Dap-resistant (Dap
r
) methicillin-resistant
Staphylococcus aureus
(MRSA) strain pairs. Compared to the 9 Dap
s
parental strains, Dap
r
strains (with or without
mprF-yycFG
mutations) exhibited significantly reduced phosphatidylglycerol (PG) content (
P
< 0.01), significantly increased total synthesis of lysyl-PG (LPG) (
P
< 0.01), and reduced carotenoid content (
P
< 0.05 for 5/9 strains). There were no significant changes in LPG flipping, cardiolipin content, or fatty acid composition among strain pairs.
Use of a Human-Like Low-Grade Bacteremia Model of Experimental Endocarditis To Study the Role of Staphylococcus aureus Adhesins and Platelet Aggregation in Early Endocarditis
Authors: Veloso Tiago Rafael , Chaouch Aziz , Roger Thierry , Giddey Marlyse , Vouillamoz Jacques , Majcherczyk Paul , Que Yok-Ai , Rousson Valentin , Moreillon Philippe , Entenza José Manuel
Published: December 2012

Animal models of infective endocarditis (IE) induced by high-grade bacteremia revealed the pathogenic roles ofStaphylococcus aureussurface adhesins and platelet aggregation in the infection process. In humans, however,S. aureusIE possibly occurs through repeated bouts of low-grade bacteremia from a colonized site or intravenous device. Here we used a rat model of IE induced by continuous low-grade bacteremia to explore further the contributions ofS. aureusvirulence factors to the initiation of IE. Rats with aortic vegetations were inoculated by continuous intravenous infusion (0.0017 ml/min over 10 h) with 106CFU ofLactococcus lactispIL253 or a recombinantL. lactisstrain expressing an individualS. aureussurface protein (ClfA, FnbpA, BCD, or SdrE) conferring a particular adhesive or platelet aggregation property. Vegetation infection was assessed 24 h later. Plasma was collected at 0, 2, and 6 h postinoculation to quantify the expression of tumor necrosis factor (TNF), interleukin 1α (IL-1α), IL-1β, IL-6, and IL-10. The percentage of vegetation infection relative to that with strain pIL253 (11%) increased when binding to fibrinogen was conferred onL. lactis(ClfA strain) (52%;P= 0.007) and increased further with adhesion to fibronectin (FnbpA strain) (75%;P< 0.001). Expression of fibronectin binding alone was not sufficient to induce IE (BCD strain) (10% of infection). Platelet aggregation increased the risk of vegetation infection (SdrE strain) (30%). Conferring adhesion to fibrinogen and fibronectin favored IL-1β and IL-6 production. Our results, with a model of IE induced by low-grade bacteremia, resembling human disease, extend the essential role of fibrinogen binding in the initiation ofS. aureusIE. Triggering of platelet aggregation or an inflammatory response may contribute to or promote the development of IE.
Excellent response of malignant peripheral nerve sheath tumour of retroperitoneum to radiation therapy
Authors: Akhavan Ali , Binesh Fariba , Ghannadi Fazlollah , Navabii Hossein
Published: December 2012

Malignant peripheral nerve sheath tumours are high-grade sarcomas originating from Schwann cells or nerve sheath cells. Most of these tumours are associated with major nerves of the body wall and extremities. The lower extremity and the retroperitoneum are the most common sites. Surgery is the cornerstone of treatment, however, radiation therapy is usually used as an adjuvant treatment. In this paper we present a 57-year-old Iranian woman with malignant peripheral nerve sheath tumour of retroperitoneum who was operated subtotally and then underwent radiation therapy which led to disappearance of all gross residual disease.
Acute gluteal compartment syndrome: superior gluteal artery rupture following a low energy injury
Authors: Smith Aubrey , Chitre Vivek , Deo Hersh
Published: December 2012

Acute compartment syndrome affecting the gluteal region is rare when compared to the same condition in the forearm or calf. When it does occur, it is usually due to prolonged immobilisation in those with altered consciousness. Gluteal compartment syndrome resulting from injury to the superior gluteal artery is extremely rare and to our knowledge has been described only twice—both after high-energy road traffic accidents (RTA). Other cases have described profound hypotension with superior gluteal artery injury after an RTA and falling off a horse, without acute gluteal compartment syndrome. We present a case of gluteal compartment syndrome due to rupture of the superior gluteal artery following a relatively minor fall. The patient required an emergency fasciotomy, which was performed within 4 h of the injury. This case highlights the importance of early diagnosis and treatment of this rare condition.
Potential effects of stock enhancement with hatchery-reared seed on genetic diversity and effective population size
Authors: Hold Natalie , Murray Lee G. , Kaiser Michel J , Hinz Hilmar , Beaumont Andrew R. , Taylor Martin I.
Published: December 2012

The present study investigated the genetic efficiency of enhancing populations of wild scallops using hatchery-produced seed scallops. Scallops from the Isle of Man (IOM), Irish Sea, and from a scallop hatchery were genotyped using 15 microsatellite markers. Hatchery scallops had equivalent heterozygosity to wild scallops, but rare alleles were likely to be lost in hatchery scallops as represented by lower allelic richness. The effective number of breeders (Nb) of the hatchery scallops was estimated at 32.4 (95% CI: 24.4–44.9). The confidence intervals for the estimates of Nbfor the IOM included infinity. When Nbbecomes large the genetic signal is weak compared with the sampling noise; therefore, while we can be confident that the Nbof IOM scallops is larger than that of the hatchery, the precise difference is uncertain. Simulations showed it is possible, in some scenarios, that stock enhancement with hatchery seed can lead to an increase in the wild population's effective size; however, in the majority of scenarios a decrease in the effective size of the wild population is more likely. A precautionary approach to stock enhancement with hatchery seed is advised.
Use of a varying turn-density coil (VTDC) to generate a constant-gradient magnetic field and to demonstrate the magnetic force on a permanent magnet
Authors: Friedman Benjamin M.C. , Abraham Michael G. , Paetkau Mark , Taylor S. Richard , Ross Friedman Cynthia
Published: December 2012

In this study, we proposed that a constant gradient magnetic field could be generated by the construction of a current-carrying coil possessing a turn-density (number of turns per unit length) that varies linearly with axial position (i.e., a varying turn-density coil, VTDC). A VTDC is easily constructed and could be used to demonstrate how a ferromagnet placed in a magnetic field experiences a net force. Using the Biot–Savart law, we predicted that a ferromagnetic dipole suspended in a VTDC experiences a force proportional to the length of the dipole. We designed and executed an experiment to test our prediction. A coil with a turn-density varying at a rate of 0.11 cm−2 was constructed. Rare-earth magnets were suspended along the centre of the VTDC using a string that was attached to a mass resting on a scale. The scale reading measured the force experienced by the hanging magnet. The procedures were also carried out in a constant turn-density solenoid (control). A direct linear relationship between force and magnet length was observed in the VTDC, whereas no force was detected in the zero-gradient field solenoid (p < 0.000 001). Linear regressions suggested that the observed data matched the predicted values (95% certainty). The magnetic moment of 0.56 ± 0.21 J/T is in reasonable agreement with remnant magnetization for neodymium magnets of ∼1 T. We found that our easily-built VTDC produced a uniform gradient as no significant differences were observed when magnets were hung at different axial positions. Overall, the results were supportive of the theory. Our VTDC could be readily constructed and used in a physics classroom to demonstrate basic principles of electromagnetism.
History of the pharmaceutical use of pumice
Authors: Duffin Christopher J.
Published: December 2012

Pumice has been used as an abrasive with medical applications for over 2000 years. Introduced into traditional Chinese medicine in the mid-eighteenth century, it has been employed as part of a decoction (tea) in combination with a range of herbs and other geopharmaceuticals (including amber, cinnabar, mica and the bones of fossil vertebrates) in the treatment of gall bladder cancer, urinary conditions, dry and hacking coughs, and anxiety disorders. Pumice has had a relatively stable literary history in Western medicine. ‘Spuma maris’ (sea foam) has been a source of some confusion in classical literature, a situation exacerbated by some medieval revisionist texts. In a medical context, the term most commonly refers to pumice. Pumice has been employed since classical times in preparations acting as dentifrices, cleansers for ulcers (particularly of the skin and cornea), cicatrizing agents to help wounds scar efficiently, an active ingredient in eye ointments and powders in both farriery and human medicine, sneeze-inducing powders, and abrasives for removing body hair and assisting in the production of fine powders of resistant pharmaceutical ingredients.
Comparison of Surface Area across the Allograft-Host Junction Site Using Conventional and Navigated Osteotomy Technique
Authors: Lall Ajay , Hohn Eric , Kim Mimi Y. , Gorlick Richard G. , Abraham John A. , Geller David S.
Published: December 2012

Bulk allograft reconstruction plays an important role in limb-salvage surgery; however, non-union has been reported in up to 27% of cases. The purpose of this study is to quantify average surface contact areas across simulated intraoperative osteotomies using both free-hand and computer-assisted navigation techniques. Pressure-sensitive paper was positioned between two cut ends of a validated composite sawbone and compression was applied using an eight-hole large fragment dynamic compression plate. Thirty-two samples were analyzed for surface area contact to determine osteotomy congruity. Mean contact area using the free-hand osteotomy technique was equal to 0.21 square inches. Compared with a control of 0.69 square inches, average contact area was found to be 30.5% of optimal surface contact. Mean contact area using computer-assisted navigation was equal to 0.33 square inches. Compared with a control of 0.76 square inches, average contact area was found to be 43.7% of optimal surface contact. Limited contact achieved using standard techniques may play a role in the high rate of observed non-union, and an increase in contact area using computer-assisted navigation may improve rates of bone healing. The development of an oncology software package and navigation hardware may serve an important role in decreasing non-union rates in limb salvage surgery.
Copper Deficiency in Sheep with High Liver Iron Accumulation
Authors: Sousa Isadora Karolina Freitas de , Hamad Minervino Antonio Humberto , Sousa Rejane dos Santos , Chaves Dowglish Ferreira , Soares Herbert Sousa , Barros Isabella de Oliveira , Araújo Carolina Akiko Sato Cabral de , Júnior Raimundo Alves Barrêto , Ortolani Enrico Lippi
Published: December 2012

An outbreak of enzootic ataxia among sheep raised in the northeastern region of Brazil is described. Copper (Cu) deficiency was diagnosed in a herd of 56 sheep, among which five presented characteristic clinical symptoms of enzootic ataxia. The symptoms began 30 days after birth, with a clinical condition that included locomotion difficulty, limb ataxia, tremors, and continual falls. Liver biopsies were performed and blood was collected to determine hepatic and plasmatic Cu, iron (Fe), and zinc (Zn) concentration, respectively. The laboratory results showed that the animals presented low copper concentrations in the plasma and liver, without difference between the clinically healthy animals and those affected by enzootic ataxia. Even after supplementation with adequate Cu levels had been recommended, it was found on a new visit to the farm four months later that one animal still presented a clinical condition and that the hepatic Cu levels of the herd had not risen. Despite the low copper content of the diet, the high hepatic Fe levels found suggest that antagonism due to this element may have been an important factor in triggering copper deficiency in these animals, and thus, additional copper supplementation may be necessary for these animals.
Effects of Somatothermal Far-Infrared Ray on Primary Dysmenorrhea: A Pilot Study
Authors: Ke Yu-Min , Ou Ming-Chiu , Ho Cheng-Kun , Lin Yung-Sheng , Liu Ho-Yen , Chang Wen-An
Published: December 2012

The purpose of this study was to assess the beneficial effects of using a far-infrared (FIR) belt on the management of patients with primary dysmenorrhea. This is the first study to determine the efficacy of somatothermal FIR using a parallel-arm randomized sham-controlled and double-blinded design with objective physical evidence and psychometric self-reports. Fifty-one Taiwanese women with primary dysmenorrhea were enrolled in the study. Results indicate that there was an increased abdominal temperature of 0.6°C and a 3.27% increase in abdominal blood flow in the FIR group (wearing FIR belt) compared to those in the control group (wearing sham belt). Verbal rating scale and numeric rating scale scores in the FIR group were both lower than those in the control group. Compared to the blank group (wearing no belt), the average dysmenorrhea pain duration of the FIR group was significantly reduced from 2.5 to 1.8 days, but there was no significant difference in the control group. These results demonstrate that the use of a belt made of far-infrared ceramic materials can reduce primary dysmenorrhea.
Primary Malignant Melanoma of the Rectum: Report of Two Cases
Authors: Tomioka Kodai , Ojima Hitoshi , Sohda Makoto , Tanabe Akiko , Fukai Yasuyuki , Sano Akihiko , Fukuda Takahiro , Murakami Masahiko
Published: December 2012

We report two cases of rectal malignant melanomas. The patients were an 84-year-old male and a 66-year-old female who had blood in their stools. They were preoperatively diagnosed with poorly differentiated adenocarcinoma of the rectum. The clinical diagnosis for each was rectal carcinoma at stage IIIc according to the tumor-node-metastasis classification (6th edition), and the patients underwent abdominoperineal resection with dissection of lymph nodes. Pathological examination of the resected specimens revealed a malignant melanoma. Immunohistochemical analysis results were positive for HMB-45 and negative for cytokeratin AE1/AE3, CD45, and synaptophysin. Primary anorectal melanoma is an uncommon and aggressive disease that carries a poor prognosis. Therefore, it is necessary to provide systemic treatment. To improve prognosis, it is important to detect anorectal melanoma at an early stage.
The Prorenin and (Pro)renin Receptor: New Players in the Brain Renin-Angiotensin System?
Authors: Li Wencheng , Peng Hua , Seth Dale M. , Feng Yumei
Published: December 2012

It is well known that the brain renin-angiotensin (RAS) system plays an essential role in the development of hypertension, mainly through the modulation of autonomic activities and vasopressin release. However, how the brain synthesizes angiotensin (Ang) II has been a debate for decades, largely due to the low renin activity. This paper first describes the expression of the vasoconstrictive arm of RAS components in the brain as well as their physiological and pathophysiological significance. It then focus on the (pro)renin receptor (PRR), a newly discovered component of the RAS which has a high level in the brain. We review the role of prorenin and PRR in peripheral organs and emphasize the involvement of brain PRR in the pathogenesis of hypertension. Some future perspectives in PRR research are heighted with respect to novel therapeutic target for the treatment of hypertension and other cardiovascular diseases.