bluuebunny/crossref_metadata_2025 huggingface dataset:
Healing of Iatrogenic Skeletal Muscle Wounds Is Affected by Incision Device
Authors: Rubino L. Joseph , Konstantakos Emmanuel K. , Stills Harold F. , Dudley Emily S. , Grunden Beverly K. , Malaviya Prasanna
Published: May 2010

Orthopedic joint procedures frequently require extensive dissection of skeletal muscles resulting in tissue injury, formation of scar tissue, pain, and potentially, functional impairment. The authors hypothesized that using a low-temperature ultrasonic cutting and coagulating device (Harmonic Blade, Ethicon Endo-Surgery, Cincinnati, OH) would result in reduction in tissue trauma in terms of reducing acute and chronic inflammation during healing. Bilateral longitudinal incisions were made into the tibialis cranialis muscles of rabbits with either a Harmonic Blade or a standard monopolar electrosurgical scalpel. At 3, 7, and 21 days postoperatively, necropsy and histological evaluations indicated a significant attenuation of acute inflammation ( P = .011) for the Harmonic incisions compared with electrosurgery. No significant differences were observed for chronic inflammation, necrosis, or fibrosis. Use of a Harmonic scalpel during dissection of skeletal muscle in orthopedic surgery may result in reduced influx of neutrophils, reducing acute inflammation, and potentially aid in reducing postoperative pain and functional impairment.
A New Fine-Needle Aspiration System
Authors: Glehr Mathias , Leithner Andreas , Gruber Gerald , Wretschitsch Paul , Zacherl Maximilian , Kroneis Thomas , Quehenberger Franz , Windhager Reinhard
Published: May 2010

Background. The main reasons for fine needle aspiration (FNA) failure are insufficient number of cells in the sample, nonrepresentative samples, and contamination of samples. The aim of this study was to measure the number of cells harvested by a new needle system with an aeration aperture (Thyrosampler) in comparison with a conventional FNA system (C-FNA). Methods. Under a double-blind setting, 30 aspirations, 15 with each system (C-FNA, Thyrosampler), were done in randomized order and recorded. Results. The median total number of cells was 59 680 cells/mL with C-FNA and 396 400 cells/mL with Thyrosampler. The needle system with the aeration aperture led to a significantly higher cell amount (564% more cells than the conventional system; P < .005) in needle aspiration biopsy. Conclusion. The new system with the vacuum release feature leads to a significantly higher cell amount in needle aspiration biopsy, which is a well-defined benefit.
Hydroperitoneum-Facilitated EUS-Guided Peritoneal Entry and Closure of Alternate Access Sites for NOTES
Authors: Elmunzer B. Joseph , Chak Amitabh , Taylor Jason R. , Trunzo Joseph A. , Piraka Cyrus R. , Schomisch Steve J. , Rising Gail M. , Elta Grace H. , Scheiman James M. , Ponsky Jeffrey L. , Marks Jeffrey M. , Kwon Richard S.
Published: May 2010

Background: Access sites other than the anterior gastric wall may provide improved ergonomics for natural orifice transluminal endoscopic surgery (NOTES). Endoscopic ultrasound (EUS) guidance significantly reduces, but does not eliminate, risk of access through these alternate sites. This study evaluates the utility of hydroperitoneum as an adjunct to EUS-guided access and closure of alternate access sites for NOTES. Methods: Access and closure procedures were initially performed with EUS guidance alone, and subsequently, because of complications resulting from this technique, the procedures were performed with the aid of a transabdominal hydroperitoneum. Results: In this nonrandomized study, 6 access and closure procedures performed with EUS guidance alone resulted in 4 complications. After modifying the technique to incorporate pre-access hydroperitoneum, 7 EUS-guided access and closure procedures were performed without significant complications. Conclusions: Hydroperitoneum appears to be an effective adjunct to ensure the safety of EUS-guided peritoneal entry and closure of alternate access sites for NOTES.
Is There a Role for a Strict Incision Length Criterion for Determining Conversions During Laparoscopic Colorectal Resection?
Authors: Offodile Anaeze C. , Balik Emre , Hoffman Aviad , Moon Victor , Baxter Raymond , Grieco Michael , Moradi Dovid , Kim Ik-yong , Nasar Abu , Cekic Vesna , Feingold Daniel L. , Arnell Tracey D. , Huang Emina , Whelan Richard L.
Published: May 2010

Purpose There’s no consensus about what defines a conversion for laparoscopic-assisted colorectal resection (LACR). This study’s goal was to assess the utility of a strict incision length (IL) definition of conversion (incision > 7 cm) and compare it with results obtained when the surgeon determined (SD) if a LACR had been successfully completed. Methods. The demographic and perioperative data for 580 elective LACRs were reviewed. The short-term outcomes for each conversion definition were determined and compared. Results. Conversion rates were 22% using the IL definition and 16% via the SD method. Both methods detected significant differences between completed and converted groups regarding the following: incision size, hospital stay, time to flatus, bowel movement, and regular diet as well as rate of wound infection and ileus. The IL method alone detected significant differences in the rate of pulmonary complications and BMI between the completed and converted groups. Conclusions . The 2 methods yielded similar results for most parameters. The IL method better separated the patients in regard to 2 parameters. This method is objective and easy to apply; however, it may discriminate against obese patients whose extraction incisions are often longer. A conversion definition that considers BMI and IL is needed.
Antithrombin-III Attenuates Hepatocyte Apoptosis in Bile Duct Ligated Rat: A Striking Cellular Change
Authors: Huang Chun-Ying , Sheen-Chen Shyr-Ming , Ho Hsin-Tsung , Tang Rei-Ping , Eng Hock-Liew
Published: May 2010

Background and purpose: Retention and accumulation of toxic hydrophobic bile salts within hepatocyte may cause hepatocyte toxicity by inducing apoptosis. This study was designed with the purpose of evaluating the possible effect of antithrombin-III on hepatocyte apoptosis in bile duct ligated rat. Materials and methods: The rats were randomized to 3 groups: group 1 (control, C) underwent sham operation; group 2 (obstructive jaundice, OB) underwent common bile duct ligation; and group 3 (obstructive jaundice with antithrombin-III, OBAT-III) underwent common bile duct ligation and simultaneously were treated with antithrombin-III. Liver tissues were harvested on the fifth postoperative day. Results: Hepatocyte apoptosis was significantly increased in bile duct ligated group when compared with the sham operation group. The administration of antithrombin-III effectively attenuates such phenomenon in obstructive jaundice with antithrombin-III group. Conclusion: Bile duct ligation significantly increased hepatocyte apoptosis and the administration of antithrombin-III effectively attenuates such phenomenon.
Transanal Single Port Microsurgery (TSPM) as a Modified Technique of Transanal Endoscopic Microsurgery (TEM)
Authors: Lorenz Cornelia , Nimmesgern Thomas , Back Melanie , Langwieler Thomas E.
Published: May 2010

Background: Single port access (SPA) surgery is a new procedure for minimal invasive surgery using one multichannel port. The authors adapted this technique for transanal surgery as an improvement of the transanal endoscopic microsurgery (TEM). Methods: A total of 3 patients underwent SPA modified TEM using the SILS port (Covidien) under CO2 insufflation. This port allows insertion of 2 laparoscopic instruments and a telescope. Results: The operation was completed successfully in all cases. The transanal placement of the SILS port was easy to perform; a prior dilatation of the anal sphincter was not necessary. There were no perioperative or postoperative complications as verified by postoperative observation, rectoscopy, and anal ultrasound. Conclusions : Transanal single port microsurgery is a feasible and new technique for less invasive and more gentle transanal surgery. By using this new multichannel device TEM surgery was changed in a modified way while preserving the anal sphincter.
International Multicenter Trial on Clinical Natural Orifice Surgery—NOTES IMTN Study: Preliminary Results of 362 Patients
Authors: Zorron Ricardo , Palanivelu Chinnusamy , Galvão Neto Manoel Passos , Ramos Almino , Salinas Gustavo , Burghardt Jens , DeCarli Luis , Henrique Sousa Luiz , Forgione Antonello , Pugliese Raffaele , Branco Alcides J , Balashanmugan T.S. , Boza Camilo , Corcione Francesco , D'Ávila Avila Fausto , Arturo Gómez Néstor , Galvão Ribeiro Paulo Ayrosa , Martins Susana , Filgueiras Marcos , Gellert Klaus , Wood Branco Anibal , Kondo William , Inacio Sanseverino Jose , de Sousa José Américo G. , Saavedra Lil , Ramírez Edwin , Campos Josemberg , Sivakumar K. , Pidigu Seshiyer Rajan  , Priyadarshan Anand Jategaonkar  , Ranagrajan Muthukumaran , Parthasarathi Ramakrishnan , Senthilnathan Palanisamy , Prasad Mohan , Cuccurullo Diego , Müller Verena
Published: May 2010

Objectives: Natural orifice translumenal endoscopic surgery (NOTES) is evolving as a promising alternative for abdominal surgery. IMTN Registry was designed to prospectively document early results of natural orifice surgery among a large group of clinical cases. Methods: Sixteen centers from 9 countries were approved to participate in the study, based on study protocol requirements and local institutional review board approval. Transgastric and transvaginal endoscopic natural orifice surgery was clinically applied in 362 patients. Intraoperative and postoperative parameters were prospectively documented. Results: Mean operative time for transvaginal cholecystectomy was 96 minutes, compared with 111 minute for transgastric cholecystectomy. A general complication rate of 8.84% was recorded (grade I-II representing 5.8%, grade III-IV representing 3.04%). No requirement for any analgesia was found in one fourth of cholecystectomy and appendectomy patients. Conclusions: Results of clinical applications of NOTES in the IMTN Study showed the feasibility of different methods of this new minimally invasive alternative for laparoscopic and open surgery.
Performances of highly insulated compact zinc roofs under a humid-moderate climate - Part I: hygrothermal behavior
Authors: Zheng R. , Janssens A. , Carmeliet J. , Bogaerts W. , Hens H.
Published: May 2010

Four flat compact zinc roofs with a U-value less than 0.25 W/(m2 K) were investigated under a humid-moderate climate. Two roofs had a heavyweight deck, the other two a lightweight deck. The heavyweight roofs exhibited a satisfactory thermal behavior. The small amount of moisture accumulation in the insulation did not result in a measurable degradation of thermal quality of the zinc roofs. It was found that the moisture situation at the sheeting underside was much better in the heavyweight roofs than in the lightweight roofs. However, in the heavyweight roof with a perfect air-vapor retarder, a large number of wetting/drying cycles at the sheeting underside were measured in winter. Strong sheeting undercooling was also observed in the four roofs during the test period. The results show that it is possible to build low U-value compact zinc roofs with a perfect thermal performance.
Structural and genetic characterization of the closely related O-antigens of Escherichia coli O85 and Salmonella enterica O17
Authors: Perepelov Andrei V. , Dan Li  , Bin Liu  , Senchenkova Sof'ya N. , Dan Guo  , Shashkov Alexander S. , Lu Feng  , Knirel Yuriy A. , Lei Wang
Published: May 2010

O-Antigen is a part of the lipopolysaccharide present in the outer membrane of Gram-negative bacteria, which confers major antigenic variability to the cell surface. In this study, we report on a previously undefined pair of Escherichia coli and Salmonella enterica with closely related O-antigens. The O-polysaccharides were isolated from the lipopolysaccharides of E. coli O85 and S. enterica O17 by mild acid degradation and studied by sugar analysis and NMR spectroscopy. The following structure was established for the O-unit of the E. coli O85-polysaccharide: The S. enterica O17-polysaccharide has the same carbohydrate backbone and, in addition, contains an O-acetyl group at position 2 of ~80% β-Galf residues. The O-antigen gene cluster of E. coli O85 was found to be closely related to that of S. enterica O17. Screening of type strains of all E. coli and S. enterica O-serogroups revealed two genes specific to the E. coli O85 O-antigen gene cluster, which can be used for development of PCR-based assays for identification and detection of E. coli O85 strains.
Factors determining the spontaneous activation of splenic dendritic cells in culture
Authors: Vremec David , O'Keeffe Meredith , Wilson Anne , Ferrero Isabel , Koch Ute , Radtke Freddy , Scott Bernadette , Hertzog Paul , Villadangos Jose , Shortman Ken
Published: May 2010

Dendritic cells (DCs) serve as a link between the innate and adaptive immune systems. The activation state of DCs is crucial in this role. However, when DCs are isolated from lymphoid tissues, purified and placed in culture they undergo ‘spontaneous’ activation. The basis of this was explored, using up-regulation of DC surface MHC II, CD40, CD80 and CD86 as indicators of DC activation. No evidence was found for DC damage during isolation or for microbial products causing the activation. The culture activation of spleen DCs differed from that of Langerhans cells when released from E-cadherin-mediated adhesions, since E-cadherin was not detected and activation still occurred with β-catenin null DCs. Much of the activation could be attributed to DC—DC interactions. Although increases in surface MHC II levels occurred under all culture conditions tested, the increase in expression of CD40, CD80 and CD86 was much less under culture conditions where such interactions were minimised. DC-to-DC contact under the artificial conditions of high DC concentration in culture induced the production of soluble factors and these, in turn, induced the up-regulation of co-stimulatory molecules on the DC surface.
Dare to Compare: The Next Challenge in Assessing Emotional Cultures
Authors: Stearns Peter N.
Published: May 2010

The need for more comparative analyses in emotions research is increasingly obvious. Recent discussions of fear raise clear issues of “national” patterns and expressions versus standard societal or at least modern responses, and only explicit comparison can clarify. The same applies to current impacts on emotions from contemporary media or broader processes of globalization. Happily, there are some good examples of comparison to build upon, though the challenges of dealing with the complexity of different cultures, and potential causes of differences remain very real. The agenda and the potential for additional understanding of emotional experience through comparison are rich and stimulating.
Understanding the evolutionary relationships and major traits of Bacillus through comparative genomics
Authors: Alcaraz Luis David , Moreno-Hagelsieb Gabriel , Eguiarte Luis E , Souza Valeria , Herrera-Estrella Luis , Olmedo Gabriela
Published: May 2010

Background

The presence of Bacillus in very diverse environments reflects the versatile metabolic capabilities of a widely distributed genus. Traditional phylogenetic analysis based on limited gene sampling is not adequate for resolving the genus evolutionary relationships. By distinguishing between core and pan-genome, we determined the evolutionary and functional relationships of known Bacillus.

Results

Our analysis is based upon twenty complete and draft Bacillus genomes, including a newly sequenced Bacillus isolate from an aquatic environment that we report for the first time here. Using a core genome, we were able to determine the phylogeny of known Bacilli, including aquatic strains whose position in the phylogenetic tree could not be unambiguously determined in the past. Using the pan-genome from the sequenced Bacillus, we identified functional differences, such as carbohydrate utilization and genes involved in signal transduction, which distinguished the taxonomic groups. We also assessed the genetic architecture of the defining traits of Bacillus, such as sporulation and competence, and showed that less than one third of the B. subtilis genes are conserved across other Bacilli. Most variation was shown to occur in genes that are needed to respond to environmental cues, suggesting that Bacilli have genetically specialized to allow for the occupation of diverse habitats and niches.

Conclusions

The aquatic Bacilli are defined here for the first time as a group through the phylogenetic analysis of 814 genes that comprise the core genome. Our data distinguished between genomic components, especially core vs. pan-genome to provide insight into phylogeny and function that would otherwise be difficult to achieve. A phylogeny may mask the diversity of functions, which we tried to uncover in our approach. The diversity of sporulation and competence genes across the Bacilli was unexpected based on previous studies of the B. subtilis model alone. The challenge of uncovering the novelties and variations among genes of the non-subtilis groups still remains. This task will be best accomplished by directing efforts toward understanding phylogenetic groups with similar ecological niches.
Characterization of hemin-binding protein 35 (HBP35) in Porphyromonas gingivalis: its cellular distribution, thioredoxin activity and role in heme utilization
Authors: Shoji Mikio , Shibata Yasuko , Shiroza Teruaki , Yukitake Hideharu , Peng Benjamin , Chen Yu-Yen , Sato Keiko , Naito Mariko , Abiko Yoshimitsu , Reynolds Eric C , Nakayama Koji
Published: May 2010

Background

The periodontal pathogen Porphyromonas gingivalis is an obligate anaerobe that requires heme for growth. To understand its heme acquisition mechanism, we focused on a hemin-binding protein (HBP35 protein), possessing one thioredoxin-like motif and a conserved C-terminal domain, which are proposed to be involved in redox regulation and cell surface attachment, respectively.

Results

We observed that the hbp35 gene was transcribed as a 1.1-kb mRNA with subsequent translation resulting in three proteins with molecular masses of 40, 29 and 27 kDa in the cytoplasm, and one modified form of the 40-kDa protein on the cell surface. A recombinant 40-kDa HBP35 exhibited thioredoxin activity in vitro and mutation of the two putative active site cysteine residues abolished this activity. Both recombinant 40- and 27-kDa proteins had the ability to bind hemin, and growth of an hbp35 deletion mutant was substantially retarded under hemin-depleted conditions compared with growth of the wild type under the same conditions.

Conclusion

P. gingivalis HBP35 exhibits thioredoxin and hemin-binding activities and is essential for growth in hemin-depleted conditions suggesting that the protein plays a significant role in hemin acquisition.
Regulation of Arabidopsis defense responses against Spodoptera littoralisby CPK-mediated calcium signaling
Authors: Kanchiswamy Chidananda Nagamangala , Takahashi Hirotaka , Quadro Stefano , Maffei Massimo E , Bossi Simone , Bertea Cinzia , Zebelo Simon Atsbaha , Muroi Atsushi , Ishihama Nobuaki , Yoshioka Hirofumi , Boland Wilhelm , Takabayashi Junji , Endo Yaeta , Sawasaki Tatsuya , Arimura Gen-ichiro
Published: May 2010

Background

Plant Ca2+ signals are involved in a wide array of intracellular signaling pathways after pest invasion. Ca2+-binding sensory proteins such as Ca2+-dependent protein kinases (CPKs) have been predicted to mediate the signaling following Ca2+ influx after insect herbivory. However, until now this prediction was not testable.

Results

To investigate the roles CPKs play in a herbivore response-signaling pathway, we screened the characteristics of Arabidopsis CPK mutants damaged by a feeding generalist herbivore, Spodoptera littoralis. Following insect attack, the cpk3 and cpk13 mutants showed lower transcript levels of plant defensin gene PDF1.2 compared to wild-type plants. The CPK cascade was not directly linked to the herbivory-induced signaling pathways that were mediated by defense-related phytohormones such as jasmonic acid and ethylene. CPK3 was also suggested to be involved in a negative feedback regulation of the cytosolic Ca2+ levels after herbivory and wounding damage. In vitro kinase assays of CPK3 protein with a suite of substrates demonstrated that the protein phosphorylates transcription factors (including ERF1, HsfB2a and CZF1/ZFAR1) in the presence of Ca2+. CPK13 strongly phosphorylated only HsfB2a, irrespective of the presence of Ca2+. Furthermore, in vivo agroinfiltration assays showed that CPK3-or CPK13-derived phosphorylation of a heat shock factor (HsfB2a) promotes PDF1.2 transcriptional activation in the defense response.

Conclusions

These results reveal the involvement of two Arabidopsis CPKs (CPK3 and CPK13) in the herbivory-induced signaling network via HsfB2a-mediated regulation of the defense-related transcriptional machinery. This cascade is not involved in the phytohormone-related signaling pathways, but rather directly impacts transcription factors for defense responses.
Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population
Authors: Cui Lian-Hua , Shin Min-Ho , Kweon Sun-Seog , Kim Hee Nam , Song Hye-Rim , Piao Jin-Mei , Choi Jin-Su , Shim Hyun Jeong , Hwang Jun Eul , Kim Hyeong-Rok , Park Young-Kyu , Kim Soo-Hyun
Published: May 2010

Background

This study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population.

Methods

We conducted a population-based large-scale case-control study involving 2,213 patients with newly diagnosed gastric cancer, 1,829 patients with newly diagnosed colorectal cancer, and 1,700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. The statistical significance was estimated by logistic regression analysis.

Results

The MTHFR C677T frequencies of CC, CT, and TT genotypes were 35.2%, 47.5%, and 17.3% among stomach cancer, 34%, 50.5%, and 15.5% in colorectal cancer, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677TT genotype showed a weak opposite association with colorectal cancer compared to the homozygous CC genotype [adjusted age and sex odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.638-0.984,P= 0.035]. Subjects with the MTHFR 677CT showed a significantly reduced risk of gastric cancer compared whose with the 677CC genotype (age- and sex-adjusted OR = 0.810; 95% CI = 0.696-0.942,P= 0.006). We also observed no significant interactions between the MTHFR C677T polymorphism and smoking or drinking in the risk of gastric and colorectal cancer.

Conclusions

The T allele was found to provide a weak protective association with gastric cancer and colorectal cancer.
A population study on the association between leisure time physical activity and self-rated health among diabetics in Taiwan
Authors: Li Chia-Lin , Lai Yi-Chang , Tseng Chin-Hsiao , Lin Jen-Der , Chang Hsing-Yi
Published: May 2010

Background

There is strong evidence for the beneficial effects of physical activity in diabetes. There has been little research demonstrating a dose-response relationship between physical activity and self-rated health in diabetics. The aim of this study was to explore the dose-response association between leisure time physical activity and self-rated health among diabetics in Taiwan.

Methods

Data came from the 2001 Taiwan National Health Interview Survey (NHIS). Inclusion criteria were a physician confirmed diagnosis of diabetes mellitus and age 18 years and above (n = 797). Self-rated health was assessed by the question "In general, would you say that your health is excellent, very good, good, fair, or poor?" Individuals with a self perceived health status of good, very good, or excellent were considered to have positive health status.

Results

In the full model, the odds ratio (OR) for positive health was 2.51(95% CI = 1.53-4.13), 1.62(95% CI = 0.93-2.84), and 1.35(95% CI = 0.77-2.37), for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. Those with duration over 10 years (OR = 0.53, 95%CI = 0.30-0.94), heart disease (OR = 0.50, 95%CI = 0.30-0.85), and dyslipidemia (OR = 0.65, 95% CI = 0.43-0.98) were less likely to have positive health than their counterparts. After stratified participants by duration, those with a duration of diabetes < 6 years, the adjusted OR for positive health was 1.95(95% CI = 1.02-3.72), 1.22(95% CI = 0.59-2.52), and 1.19(95% CI = 0.58-2.41) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. In participants with a duration of diabetes ≥ 6 years, total energy expenditure showed a gradient effect on self-perceived positive health. The adjusted OR for positive health was 3.45(95% CI = 1.53-7.79), 2.77(95% CI = 1.11-6.92), and 1.90(95% CI = 0.73-4.94) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals.

Conclusions

Our results highlight that regular leisure activity with an energy expenditure ≧ 500 kcal per week is associated with better self-rated health for those with longstanding diabetes.
Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasis
Authors: Ganapathy Vidya , Ge Rongrong , Grazioli Alison , Xie Wen , Banach-Petrosky Whitney , Kang Yibin , Lonning Scott , McPherson John , Yingling Jonathan M , Biswas Swati , Mundy Gregory R , Reiss Michael
Published: May 2010

Background

Transforming Growth Factor β (TGF-β) plays an important role in tumor invasion and metastasis. We set out to investigate the possible clinical utility of TGF-β antagonists in a human metastatic basal-like breast cancer model. We examined the effects of two types of the TGF-β pathway antagonists (1D11, a mouse monoclonal pan-TGF-β neutralizing antibody and LY2109761, a chemical inhibitor of TGF-β type I and II receptor kinases) on sublines of basal cell-like MDA-MB-231 human breast carcinoma cells that preferentially metastasize to lungs (4175TR, 4173) or bones (SCP2TR, SCP25TR, 2860TR, 3847TR).

Results

Both 1D11 and LY2109761 effectively blocked TGF-β-induced phosphorylation of receptor-associated Smads in all MDA-MB-231 subclonesin vitro. Moreover, both antagonists inhibited TGF-β stimulatedin vitromigration and invasiveness of MDA-MB-231 subclones, indicating that these processes are partly driven by TGF-β. In addition, both antagonists significantly reduced the metastatic burden to either lungs or bonesin vivo, seemingly independently of intrinsic differences between the individual tumor cell clones. Besides inhibiting metastasis in a tumor cell autonomous manner, the TGF-β antagonists inhibited angiogenesis associated with lung metastases and osteoclast number and activity associated with lytic bone metastases. In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer.

Conclusions

In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer.
Wound trauma mediated inflammatory signaling attenuates a tissue regenerative response in MRL/MpJ mice
Authors: Zins Stephen R , Amare Mihret F , Anam Khairul , Elster Eric A , Davis Thomas A
Published: May 2010

Background

Severe trauma can induce pathophysiological responses that have marked inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound healing, multi-system organ failure and increased mortality.

Methods

In this study, we examined the impact of thermal injury-induced systemic inflammation on the healing response of a secondary wound in the MRL/MpJ mouse model, which was anatomically remote from the primary site of trauma, a wound that typically undergoes scarless healing in this specific strain. Ear-hole wounds in MRL/MpJ mice have previously displayed accelerated healing and tissue regeneration in the absence of a secondary insult.

Results

Severe thermal injury in addition to distal ear-hole wounds induced marked local and systemic inflammatory responses in the lungs and significantly augmented the expression of inflammatory mediators in the ear tissue. By day 14, 61% of the ear-hole wounds from thermally injured mice demonstrated extensive inflammation with marked inflammatory cell infiltration, extensive ulceration, and various level of necrosis to the point where a large percentage (38%) had to be euthanized early during the study due to extensive necrosis, inflammation and ear deformation. By day 35, ear-hole wounds in mice not subjected to thermal injury were completely closed, while the ear-hole wounds in thermally injured mice exhibited less inflammation and necrosis and only closed partially (62%). Thermal injury resulted in marked increases in serum levels of IL-6, TNFα, KC (CXCL1), and MIP-2α (CXCL2). Interestingly, attenuated early ear wound healing in the thermally injured mouse resulted in incomplete tissue regeneration in addition to a marked inflammatory response, as evidenced by the histological appearance of the wound and increased transcription of potent inflammatory mediators.

Conclusion

These findings suggest that the observed systemic inflammatory response of a severe thermal injury undoubtedly has an adverse effect on wound healing and tissue regeneration.
Measuring physical activity-related environmental factors: reliability and predictive validity of the European environmental questionnaire ALPHA
Authors: Spittaels Heleen , Verloigne Maïté , Gidlow Christopher , Gloanec Julien , Titze Sylvia , Foster Charlie , Oppert Jean-Michel , Rutter Harry , Oja Pekka , Sjöström Michael , De Bourdeaudhuij Ilse
Published: May 2010

Background

A questionnaire to assess physical activity related environmental factors in the European population (a 49-item and an 11-item version) was created as part of the framework of the EU-funded project "Instruments for Assessing Levels of PHysical Activity and fitness (ALPHA)". This paper reports on the development and assessment of the questionnaire's test-retest stability, predictive validity, and applicability to European adults.

Methods

The first pilot test was conducted in Belgium, France and the UK. In total 190 adults completed both forms of the ALPHA questionnaire twice with a one-week interval. Physical activity was concurrently measured (i) by administration of the long version of the International Physical Activity Questionnaire (IPAQ) by interview and (ii) by accelerometry (Actigraph™ device). After adaptations, the second field test took place in Belgium, the UK and Austria; 166 adults completed the adapted questionnaire at two time points, with minimum one-week interval. In both field studies intraclass correlation coefficients (ICC) and proportion of agreement were computed to assess the stability of the two test scores. Predictive validity was examined in the first field test by correlating the results of the questionnaires with physical activity data from accelerometry and long IPAQ-last 7 days.

Results

The reliability scores of the ALPHA questionnaire were moderate-to good in the first field testing (ICC range 0.66 - 0.86) and good in the second field testing (ICC range 0.71 - 0.87). The proportion of agreement for the ALPHA short increased significantly from the first (range 50 - 83%) to the second field testing (range 85 - 95%). Environmental scales from both versions of the ALPHA questionnaire were significantly associated with self-reported minutes of transport-related walking, and objectively measured low intensity physical activity levels, particularly in women. Both versions were easily administered with an average completion time of six minutes for the 49-item version and less than two minutes for the short version.

Conclusion

The ALPHA questionnaire is an instrument to measure environmental perceptions in relation to physical activity. It appears to have good reliability and predictive validity. The questionnaire is now available to other researchers to investigate its usefulness and applicability across Europe.
A genomics-informed, SNP association study reveals FBLN1 and FABP4 as contributing to resistance to fleece rot in Australian Merino sheep
Authors: Smith Wendy JM , Li Yutao , Ingham Aaron , Collis Eliza , McWilliam Sean M , Dixon Tom J , Norris Belinda J , Mortimer Suzanne I , Moore Robert J , Reverter Antonio
Published: May 2010

Background

Fleece rot (FR) and body-strike of Merino sheep by the sheep blowfly Lucilia cuprina are major problems for the Australian wool industry, causing significant losses as a result of increased management costs coupled with reduced wool productivity and quality. In addition to direct effects on fleece quality, fleece rot is a major predisposing factor to blowfly strike on the body of sheep. In order to investigate the genetic drivers of resistance to fleece rot, we constructed a combined ovine-bovine cDNA microarray of almost 12,000 probes including 6,125 skin expressed sequence tags and 5,760 anonymous clones obtained from skin subtracted libraries derived from fleece rot resistant and susceptible animals. This microarray platform was used to profile the gene expression changes between skin samples of six resistant and six susceptible animals taken immediately before, during and after FR induction. Mixed-model equations were employed to normalize the data and 155 genes were found to be differentially expressed (DE). Ten DE genes were selected for validation using real-time PCR on independent skin samples. The genomic regions of a further 5 DE genes were surveyed to identify single nucleotide polymorphisms (SNP) that were genotyped across three populations for their associations with fleece rot resistance.

Results

The majority of the DE genes originated from the fleece rot subtracted libraries and over-representing gene ontology terms included defense response to bacterium and epidermis development, indicating a role of these processes in modulating the sheep's response to fleece rot. We focused on genes that contribute to the physical barrier function of skin, including keratins, collagens, fibulin and lipid proteins, to identify SNPs that were associated to fleece rot scores.

Conclusions

We identified FBLN1 (fibulin) and FABP4 (fatty acid binding protein 4) as key factors in sheep's resistance to fleece rot. Validation of these markers in other populations could lead to vital tests for marker assisted selection that will ultimately increase the natural fleece rot resistance of Merino sheep.
The multiple faces of CXCL12 (SDF-1α) in the regulation of immunity during health and disease
Authors: Karin Nathan
Published: May 2010

Review discusses the role of CXCL12 (SDF1α) as a regulatory chemokine that drives Foxp3- regulatory T cells (Tr1), and its therapeutic implications.

Chemokines are a group of small, structurally related molecules that regulate the trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane G-protein-coupled receptors. As key chemoattractants of inflammatory leukocytes, chemokines have been marked as potential targets for neutralization in autoimmune diseases. Cancer cells also express chemokines, where they function as survival/growth factors and/or angiogenic factors that promote tumor development and angiogenesis. Accordingly, these functions make them attractive targets for therapy of these diseases. Recently, we reported that one of these chemokines CXCL12 (SDF-1α) functions as an anti-inflammatory chemokine during autoimmune inflammatory responses and explored the mechanistic basis of this function. As a pleiotropic chemokine, CXCL12 participates in the regulation of tissue homeostasis, immune surveillance, autoimmunity, and cancer. This chemokine is constitutively expressed in the BM and various tissues, which enables it to regulate the trafficking and localization of immature and maturing leukocytes, including BM stem cells, neutrophils, T cells, and monocytic cells. We have shown recently that CXCL12 increases immunological tolerance in autoimmune diseases by polarizing Tregs and by doing so, restrains the progression of these diseases. This finding suggests a possible use of stabilized rCXCL12 as a potential drug for therapy of these diseases and targeted neutralization of CXCL12 for therapy of cancer diseases. The current review explores the different biological properties of CXCL12 and discusses the implications of CXCL12-based therapies for autoimmunity and cancer diseases.
FoxO1 Links Hepatic Insulin Action to Endoplasmic Reticulum Stress
Authors: Kamagate Adama , Kim Dae Hyun , Zhang Ting , Slusher Sandra , Gramignoli Roberto , Strom Stephen C. , Bertera Suzanne , Ringquist Steven , Dong H. Henry
Published: May 2010

Forkhead box O1 (FoxO1) is a transcription factor that mediates the inhibitory effect of insulin on target genes in hepatic metabolism. Hepatic FoxO1 activity is up-regulated to promote glucose production during fasting and is suppressed to limit postprandial glucose excursion after meals. Increased FoxO1 activity augments the expression of insulin receptor (IR) and IR substrate (IRS)2, which in turn inhibits FoxO1 activity in response to reduced insulin action. To address the underlying physiology of such a feedback loop for regulating FoxO1 activity, we delivered FoxO1-ADA by adenovirus-mediated gene transfer into livers of adult mice. FoxO1-ADA is a constitutively active allele that is refractory to insulin inhibition, allowing us to determine the metabolic effect of a dislodged FoxO1 feedback loop in mice. We show that hepatic FoxO1-ADA production resulted in significant induction of IR and IRS2 expression. Mice with increased FoxO1-ADA production exhibited near glycogen depletion. Unexpectedly, hepatic FoxO1-ADA production elicited a profound unfolded protein response, culminating in the induction of hepatic glucose-regulated protein 78 (GRP78) expression. These findings were recapitulated in primary human and mouse hepatocytes. FoxO1 targeted GRP78 gene for trans-activation via selective binding to an insulin responsive element in the GRP78 promoter. This effect was counteracted by insulin. Our studies underscore the importance of an IR and IRS2-dependent feedback loop to keep FoxO1 activity in check for maintaining hepatic glycogen homeostasis and promoting adaptive unfolded protein response in response to altered metabolism and insulin action. Excessive FoxO1 activity, resulting from a dislodged FoxO1 feedback loop in insulin resistant liver, is attributable to hepatic endoplasmic reticulum stress and metabolic abnormalities in diabetes.
The Endogenous Selective Estrogen Receptor Modulator 27-Hydroxycholesterol Is a Negative Regulator of Bone Homeostasis
Authors: DuSell Carolyn D. , Nelson Erik R. , Wang Xiaojuan , Abdo Jennifer , Mödder Ulrike I. , Umetani Michihisa , Gesty-Palmer Diane , Javitt Norman B. , Khosla Sundeep , McDonnell Donald P.
Published: May 2010

Osteoporosis is an important clinical problem, affecting more than 50% of people over age 50 yr. Estrogen signaling is critical for maintaining proper bone density, and the identification of an endogenous selective estrogen receptor (ER) modulator, 27-hydroxycholesterol (27HC), suggests a mechanism by which nutritional/metabolic status can influence bone biology. With its levels directly correlated with cholesterol, a new possibility emerges wherein 27HC links estrogen and cholesterol signaling to bone homeostasis. In these studies, we found that increasing concentrations of 27HC, both by genetic and pharmacological means, led to decreased bone mineral density that was associated with decreased bone formation and increased bone resorption. Upon manipulation of endogenous estrogen levels, many of the responses to elevated 27HC were altered in such a way as to implicate ER as a likely mediator. In a model of postmenopausal bone loss, some pathologies associated with elevated 27HC were exacerbated by the absence of endogenous estrogens, suggesting that 27HC may act both in concert with and independently from classic ER signaling. These data provide evidence for interactions between estrogen signaling, cholesterol and metabolic disease, and osteoporosis. Patients with high cholesterol likely also have higher than average 27HC, perhaps putting them at a higher risk for bone loss and fracture. More studies are warranted to fully elucidate the mechanism of action of 27HC in bone and to identify ways to modulate this pathway therapeutically.
On Medicaid — Looking Back in New York and Ahead across the Nation: A Conversation with Deborah Bachrach
Authors: Birnbaum Michael
Published: May 2010

Michael Birnbaum interviews Deborah Bachrach about her three-year tenure as director of the nation's largest Medicaid program. Bachrach, who served under Governors Spitzer and Paterson, had previously spent over a decade as a partner in a New York law firm, navigating and shaping health policy for clients whose patients depended on Medicaid. Reviewing the ambitious Medicaid agenda that she helped lead, Bachrach reflects on expanding eligibility and increasing enrollment, designing and implementing payment reforms, and struggling with how best to rationalize program administration. Enactment of national health reform, finalized shortly after the interview was conducted, makes Bachrach's experiences and insights particularly timely and relevant: Medicaid in New York is now less of an outlier and more of a model for states across the nation as they face implementation of major coverage expansions for their low-income residents.
Multifunctional Spin-carrying Anthraquinone Derivatives
Authors: Shibata Yuuki , Akutsu Hiroki , Yamada Jun-ichi , Satoh Masaharu , Hiremath Uma S , Yelamaggad Channabasaveshwar V , Nakatsuji Shin’ichi
Published: May 2010

Several nitroxide radicals derived from 2,3,6,7-tetraalkoxy-9,10-anthraquinone core have been prepared and their magnetic, redox as well as battery properties are studied. Notably, one of the derivatives with a mono-PROXYL-radical substituent exhibits a fairly stable multistep charge–discharge process and a heat-responsive magnetic behavior.
Cation-specific Transition from Vesicle to Lamella for an Aromatic Diamine Lipid in Aqueous Solutions
Authors: Nishimura Tomoki , Masunaga Hiroyasu , Ogawa Hiroki , Akiba Isamu , Sakurai Kazuo
Published: May 2010

Addition of Cu2+ or Pd2+ into a novel aromatic diamine lipid in water induced vesicle–lamella transition. Combining scattering and calorimetry revealed that the metals first coordinated on the vesicle surface and then induced flattening and stacking of the bilayer to form highly ordered lamellae. This is the first report of the Pd2+-induced structural transition of micelles.
External ophthalmomyiasis caused by Oestrus ovis in Istanbul
Authors: Arslan Ferhat , Mete Birgül , Öztürk Recep , Samasti Mustafa
Published: May 2010

Ophthalmomyiasis externa is mainly caused by the sheep botfly Oestrus ovis; therefore, it is usually seen in rural areas. We report here a case of ophthalmomyiasis externa in a young man from Istanbul. The patient had no known history of exposure to farm animals or rural areas.
Estimating Nonparametric Random Utility Models with an Application to the Value of Time in Heterogeneous Populations
Authors: Bastin Fabian , Cirillo Cinzia , Toint Philippe L.
Published: May 2010

The estimation of random parameters by means of mixed logit models is now current practice for the analysis of transportation behaviour. One of the most straightforward applications is the derivation of willingness-to-pay distribution over a heterogeneous population, an important element for dynamic tolling strategies on congested networks. In numerous practical cases, the underlying discrete choice models involve parametric distributions that are a priori specified and whose parameters are estimated. This approach can however lead to many problems for realistic interpretation, such as negative value of time, etc.

In this paper, we propose to capture the randomness present in the model by using a new nonparametric estimation method, based on the approximation of inverse cumulative distribution functions. This technique is applied to simulated data, and the ability to recover both parametric and nonparametric random vectors is tested. The nonparametric mixed logit model is also used on real data derived from a stated preference survey conducted in the region of Brussels (Belgium). The model presents multiple choices and is estimated on repeated observations. The obtained results provide a more realistic interpretation of the observed behaviours.
The Prophylactic Role for the Human Papillomavirus Quadrivalent Vaccine in Males
Authors: Yancey Abigail M , Pitlick Jamie M , Forinash Alicia B
Published: May 2010

Objective:

To determine the role of human papillomavirus (HPV) quadrivalent vaccine in males.

Data Source:

PubMed (1966–March 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, quadrivalent, males, cancer, and genital warts. Reference citations were reviewed for relevant information.

Study Selection and Data Extraction:

All studies including humans and published in English with data describing HPV quadrivalent vaccine administration in males were evaluated.

Data Synthesis:

The HPV quadrivalent vaccine is currently recommended in females, but its role in males is still being defined. Three clinical trials evaluated the immunogenicity and tolerability of the vaccine in more than 1100 males 9–26 years of age. Greater than 99.5% of males seroconverted for HPV 6, 11, 16, and 18 at 1 month post-completion and titers were found to be numerically higher than those in females 16–26 years old. One study found that immune response persisted in >92.5% of males at 1 year. The results show high efficacy against detection of new anogenital lesions in males 29 months after receiving the quadrivalent HPV vaccine. In addition, the quadrivalent HPV vaccine appears to be well tolerated, with the most common adverse effects being syncope, fever, local site reactions, dizziness, nausea, and headache.

Conclusions:

The HPV quadrivalent vaccine appears to be safe and induces an effective immune response in males. It may also decrease the incidence of anogenital and penile cancer, although current data are limited in number and duration of follow-up. Further analysis of the long-term immunogenicity and effects on HPV-associated complications is needed.