bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mujer Mas Segura(Safer Women): a combination prevention intervention to reduce sexual and injection risks among female sex workers who inject drugs
Authors: Vera Alicia , Abramovitz Daniela , Lozada Remedios , Martinez Gustavo , Rangel M Gudelia , Staines Hugo , Patterson Thomas L , Strathdee Steffanie A 
Published: August 2012

Abstract

Background
Female sex workers who inject drugs (FSW-IDUs) are at risk of acquiring HIV, sexually transmitted infections (STI) and blood-borne infections through unprotected sex and sharing injection equipment. We conducted a 2×2 factorial randomized controlled trial to evaluate combination interventions to simultaneously reduce sexual and injection risks among FSW-IDUs in Tijuana and Ciudad Juarez, Mexico.

Methods/design
FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month were randomized to one of four conditions based on an a priori randomization schedule, blinding interviewer/counselors to assignment. Due to the extreme vulnerability of this population, we did not include a control group that would deny some women access to preventive information. All women received similar information regardless of group allocation; the difference was in the way the information was delivered and the extent to which women had an interactive role. Each condition was a single 60-minute session, including either an interactive or didactic version of an injection risk intervention and sexual risk intervention. Women underwent interviewer-administered surveys and testing for HIV, syphilis, gonorrhea, Chlamydia, and Trichomonas at baseline and quarterly for 12 months. Combined HIV/STI incidence will be the primary outcome. Secondary outcomes are proportionate reductions in sharing of injection equipment and unprotected sex with clients.

Discussion
Of 1,132 women, 548 (48.4%) were excluded (88.9% were ineligible; 11.1% refused to participate or did not return); 584 eligible women enrolled (284 in Tijuana; 300 in Ciudad Juarez). All 584 participants completed the baseline interview, provided biological samples and were randomized to one of the four groups. During follow-up, 17 participants (2.9%) were lost to follow-up, of whom 10 (58.8%) had died, leaving 567 participants for analysis. This study appears to be the first intervention to attempt to simultaneously reduce injection and sexual risk behaviors among FSW-IDUs. The factorial design will permit analysis to determine whether the combination of the two interactive interventions and/or its respective components are effective in reducing injection and/or sexual risks, which will have direct, tangible policy implications for Mexico and potentially other resource-poor countries.

Trial registration
NCT00840658
Periodic cohort health examinations in the TAMRISK study show untoward increases in body mass index and blood pressure during 15 years of follow-up
Authors: Kunnas Tarja , Määttä Kirsi , Palmroos Pirjo , Nikkari Seppo T 
Published: August 2012

Abstract

Background
Obesity is a significant risk factor for hypertension and diabetes. A cohort of 50-year-old voluntary periodic health examination (PHE) participants was analyzed 15 years retrospectively. Our aim was to evaluate changes in body mass index (BMI) and blood pressure in subjects diagnosed with hypertension and/or diabetes in comparison with healthy controls.

Methods
Voluntary periodic health examinations (PHE) of the citizens have been carried out by the city of Tampere, Finland. Health data, including body mass index (BMI) and blood pressure, were recorded every five years, starting at the age of 35 (baseline). A total of 339 subjects from the 50-year-old cohort having hypertension and/or diabetes were chosen to the study group. The control group included 604 subjects from the 50-year-old cohort who had the same follow-up information but were not diagnosed with hypertension and/or diabetes.

Results
In the study group the mean BMI had increased from 26.1 at baseline to 28.5 at the final 15-year follow-up examination. The corresponding increase in the control group was from 23.8 at baseline to 25.5 at the final follow-up. The difference in change with time between the groups was statistically significant (p = 0.04). On the average, the controls gained 4.9 kilograms, whereas subjects in the study group gained 7.0 kilograms over the 15 years of follow-up. Systolic and diastolic blood pressures were also higher in the study group already at baseline and systolic blood pressure increased with time more in the study group than in the control group (p = 0.004).

Conclusions
BMI and blood pressure were higher in the study group in comparison with the controls already at baseline at 35 years, and the differences were not favorably changed during the follow-up. Apparently, the effect of PHE had not been as efficient as planned on subjects in the study group, who were already slightly overweight at baseline.
Comparison of efficacy of different route of administration of chemotherapy on unresectable, advanced gastric cancer
Authors: Zhang Caihua , Li Guoli , Fan Chaogang , Xu Jian , Cao Jianmin , Liu Shen , Li Ning 
Published: August 2012

Abstract

Background
The aim of this study was to compare the efficacy of two neoadjuvant chemotherapies (FLEEOX and XELOX) with different routes of administration for unresectable gastric cancer.

Methods
A total of 85 patients with unresectable gastric cancer hospitalized from January 2007 to December 2009 received neoadjuvant chemotherapy. The FLEEOX group (48 patients) received the FLEEOX regimen(fluorouracil, leucovorin, epirubicin, epotoside, and oxaliplatin), which combined arterial with venous administration for one or two cycles, while the XELOX group (37 patients) received XELOX (capecitabine plus oxaliplatin) via venous administration for two to four cycles. The clinical response and overall survival of the two groups were compared.

Results
In the FLEEOX group, the clinical response rate (RR) of chemotherapy was 85.4% (41 of 48 patients) and the median survival time was 25 months. The 1-year and 2-year disease-free survival (DFS) rates were 85.4% and 45.8%, respectively. In the XELOX group, the clinical RR was 59.5% and the median survival time was 9 months, while the 1-year and 2-year survival rates were 35.2% and 8.3%, respectively. The clinical RR, the R0 resection rate, the median survival time, and the 1-year and 2-year DFS rates were significantly better (P < 0.05) in the FLEEOX group than in the XELOX group. In addition, there were no significant differences in the rates of toxic and adverse reactions or post-operative complications between the two groups.

Conclusions
For patients with a preoperative diagnosis of unresectable gastric cancer, the efficacy of the FLEEOX regimen, which combines arterial with venous administration, was better than that of the XELOX regimen, using venous administration only. This combination of arterial and venous administration could be useful for improving the efficacy of neoadjuvant chemotherapy for gastric cancer.
Treatment with MOG-DNA vaccines induces CD4+CD25+FoxP3+ regulatory T cells and up-regulates genes with neuroprotective functions in experimental autoimmune encephalomyelitis
Authors: Fissolo Nicolás , Costa Carme , Nurtdinov Ramil N , Bustamante Marta F , Llombart Victor , Mansilla María J , Espejo Carmen , Montalban Xavier , Comabella Manuel 
Published: August 2012

Abstract

Background
DNA vaccines represent promising therapeutic strategies in autoimmune disorders such as multiple sclerosis (MS). However, the precise mechanisms by which DNA vaccines induce immune regulation remain largely unknown. Here, we aimed to expand previous knowledge existing on the mechanisms of action of DNA vaccines in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), by treating EAE mice with a DNA vaccine encoding the myelin oligodendrocyte glycoprotein (MOG), and exploring the therapeutic effects on the disease-induced inflammatory and neurodegenerative changes.

Methods
EAE was induced in C57BL6/J mice by immunization with MOG35-55 peptide. Mice were intramuscularly treated with a MOG-DNA vaccine or vehicle in prophylactic and therapeutic approaches. Histological studies were performed in central nervous system (CNS) tissue. Cytokine production and regulatory T cell (Treg) quantification were achieved by flow cytometry. Gene expression patterns were determined using microarrays, and the main findings were validated by real-time PCR.

Results
MOG-DNA treatment reduced the clinical and histopathological signs of EAE when administered in both prophylactic and therapeutic settings. Suppression of clinical EAE was associated with dampening of antigen (Ag)-specific proinflammatory Th1 and Th17 immune responses and, interestingly, expansion of Treg in the periphery and upregulation in the CNS of genes encoding neurotrophic factors and proteins involved in remyelination.

Conclusions
These results suggest for the first time that the beneficial effects of DNA vaccines in EAE are not limited to anti-inflammatory mechanisms, and DNA vaccines may also exert positive effects through hitherto unknown neuroprotective mechanisms.
Small duct autoimmune sclerosing cholangitis and Crohn colitis in a 10-year-old child. A case report and review of the literature
Authors: Larsen Erling Peter , Bayat Allan , Vyberg Mogens 
Published: August 2012

AbstractAbstractAutoimmune sclerosing cholangitis is an overlap syndrome characterized by features of both autoimmune hepatitis and primary sclerosing cholangitis, the latter usually involving the large bile ducts. Autoimmune sclerosing cholangitis occurs more often in children than in adults and is frequently associated with inflammatory bowel disease, predominantly ulcerative colitis. We report a unique case of a 10-year-old Danish boy with severe small duct autoimmune sclerosing cholangitis and synchronic Crohn colitis. He was referred with a history of weight loss, abdominal pain, vomiting and diarrhea. Biochemical anomalies included elevated alanine aminotransferase, γ-glutamyl transferase and immunoglobulin G levels and the presence of smooth muscle antibodies and perinuclear antineutrophil cytoplasmic antibodies but normal alkaline phosphatase. Liver biopsy specimen revealed features of both autoimmune hepatitis and sclerosing cholangitis, the latter characterized by acute, hyperplastic and destructive inflammation – granulocytic epithelial lesion – of the small ducts. Magnetic resonance cholangiography was normal. Colonoscopic biopsies showed chronic inflammatory changes of the caecum and the ascending and transverse colon compatible with Crohn disease. Ursodeoxycholic acid and immunosuppressive treatment was initiated and within four weeks of treatment the general condition improved. Normalization of aminotransferase was seen at 21 weeks and γ-glutamyl transferase at 72 weeks after first admittance, while immunoglobulin G remained slightly increased.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1418596609736470
Synthesis and preliminary in vivo evaluations of polyurethane microstructures for transdermal drug delivery
Authors: Borcan Florin , Soica Codruta M , Ganta Srinivas , Amiji Mansoor M , Dehelean Cristina A , Munteanu Melania F 
Published: August 2012

Abstract

Background
Polymers have been considered as important materials in fabrication of microstructures for various medical purposes including drug delivery. This study evaluates polyurethane as material for hollow microstructures preparation.

Results
Polyurethane microstructures were obtained by interfacial polyaddition combined with spontaneous emulsification and present slightly acid pH values. Scanning electron microscopy revealed the existence of irregular shapes and agglomerated microstructures. The material is heat resistant up to 280°C. Good results were recorded on murine skin tests in case of polyurethane microstructures based on isophorone diisocyanate. Mesenchymal stem cells viability presents good results for the same sample after 48 hours based on the Alamar Blue test.

Conclusions
The research revealed the reduced noxiousness of this type of microstructures and consequently the possibility of their use for therapeutic purposes.
A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis
Authors: Zheng Shuqiu , Ghitani Nima , Blackburn Jessica S , Liu Jeh-Ping , Zeitlin Scott O 
Published: August 2012

Abstract

Background
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ) stretch within Huntingtin (htt), the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR) in modulating HD mouse model pathogenesis is currently unknown.

Results
We describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh) encoding N-terminal hemaglutinin (HA) or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt) and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt). Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q) htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt’s polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis.

Conclusion
In mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes.
The international effort: building the bridge for Translational Medicine: Report of the 1st International Conference of Translational Medicine (ICTM)
Authors: Chen Xiaoming , Andersson Roland , Cho William CS , Christiani David , Coico Richard , Drazen Jeffery , Ege Markus , Fehniger Thomas , Gao Hongwei , Jin Kunlin , Liebman Michael N , Lopez Elena , Marraro Giuseppe , Marko‐Varga Gyorgy , Marincola Francesco M , Popescu Laurentiu M , Spada Claudio , Shahzad Aamir , Wang Ena , Wang Wei , Wang Xiangdong , Wang Yong‐Xiao , Xia Jinglin , Qu Jia 
Published: August 2012

AbstractBackgroundSupported by the International Society for Translational Medicine (ISTM), Wenzhou Medical College and the First Affiliated Hospital of Wenzhou Medical College, the International Conference on Translational Medicine (ICTM) was held on October 22–23, 2011 in Wenzhou, China. Nearly 800 registrants attended the meeting, primarily representing institutes and hospitals in Europe, The United States of America, And Asia, and China. The meeting was chaired and organized by Dr. Xiangdong Wang, Xiaoming Chen, Richard Coico, Jeffrey M. Drazen, Richard Horton, Francesco M. Marincola, Laurentiu M. Popescu, Jia Qu and Aamir Shahzad.FindingsThe meeting focused on the communication of the need to foster translational medicine (TM) by building and broadening bridges between basic research and clinical studies at the international level. The meeting included distinguished TM experts from academia, the pharmaceutical and diagnostics industries, government agencies, regulators, and clinicians and provided the opportunity to identify shared interests and efforts for collaborative approaches utilizing cutting edge technologies, innovative approaches and novel therapeutic interventions. The meeting defined the concept of TM in its two‐way operational scheme and emphasized the need for bed to bench efforts based directly on clinical observation.ConclusionsIt was the meeting participants’ realization that the shared main goals of TM include breaking the separation between clinic practice and basic research, establishing positive feedback by understanding the basis of expected and unexpected clinical outcomes and accelerating basic research relevant to human suffering. The primary objectives of the meeting were two‐fold: to accelerate the two‐way translation by informing the participants representing the different disciplines about the state of art activities around TM approaches; and to identify areas that need to be supported by redirecting limited resources as well as identifying new sources of funding. This report summarizes key concepts presented during the meeting representing the state‐of‐art translational research and salient aspects of the ensuing discussions.
Precision medicine: an approach to R&D for delivering superior medicines to patients
Authors: Dolsten Mikael , Søgaard Morten 
Published: August 2012

AbstractPharmaceutical R&D productivity has declined over the last decade despite increasing investments. Recent trends, however, indicate a potential reversal of this trend fueled by a wave of new biologics, vaccines and highly selective NCEs directed against targets validated by human genetics, focus on new disease areas including orphan and genetic diseases and more precise tailoring of medicines to their target populations.
Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
Authors: Abdulahad Deena A , Westra Johanna , Bijzet Johannes , Dolff Sebastian , van Dijk Marcory C , Limburg Pieter C , Kallenberg Cees GM , Bijl Marc 
Published: August 2012

Abstract

Introduction

Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE. Urinary excretion of HMGB1 might reflect renal inflammatory injury. To assess whether urinary HMGB1 reflects renal inflammation we determined serum levels of HMGB1 simultaneously with its urinary levels in SLE patients with and without LN in comparison to healthy controls (HC). We also analyzed urinary HMGB1 levels in relation with clinical and serological disease activity.

Methods

The study population consisted of 69 SLE patients and 17 HC. Twenty-one patients had biopsy proven active LN, 15 patients had a history of LN without current activity, and 33 patients had non-renal SLE. Serum and urine levels of HMGB1 were both measured by western blotting. Clinical and serological parameters were assessed according to routine procedures. In 17 patients with active LN a parallel analysis was performed on the expression of HMGB1 in renal biopsies.

Results

Serum and urinary levels of HMGB1 were significantly increased in patients with active LN compared to patients without active LN and HC. Similarly, renal tissue of active LN patients showed strong expression of HMGB1 at cytoplasmic and extracellular sites suggesting active release of HMGB1. Serum and urinary levels in patients without active LN were also significantly higher compared to HC. Urinary HMGB1 levels correlated with SLEDAI, and showed a negative correlation with complement C3 and C4.

Conclusion

Levels of HMGB1 in urine of SLE patients, in particular in those with active LN, are increased and correlate with SLEDAI scores. Renal tissue of LN patients shows increased release of nuclear HMGB1 compared to control renal tissue. HMGB1, although at lower levels, is, however, also present in the urine of patients without active LN. These data suggest that urinary HMGB1 might reflect both local renal inflammation as well as systemic inflammation.
Modulation of phenotypic and functional maturation of dendritic cells by intestinal bacteria and gliadin: relevance for celiac disease
Authors: De Palma G , Kamanova J , Cinova J , Olivares M , Drasarova H , Tuckova L , Sanz Y 
Published: August 2012

AbstractBifidobacteria and enterobacteria influence phenotypic and functional maturation of DCs differently, which together with gliadin, could define the role of DCs in celiac disease progression.DC maturation and functions are influenced by microbial and environmental stimuli, which could contribute to immune dysfunction. Here, we have investigated the role of enterobacteria (Escherichia coli CBL2 and Shigella CBD8) isolated from CD patients, bifidobacteria (Bifidobacterium longum CECT 7347 and Bifidobacterium bifidum CECT 7365), and gliadins on phenotypic and functional features of MDDCs and in coculture with Caco-2 cells. The ultimate goal of our study is to understand the roles played by specific components of the gut microbiota in CD. Enterobacteria induced marked alterations in MDDC morphology, inducing podosome dissolution and dendrites, and activated MDDC adhesion and spreading. Enterobacteria also induced inflammatory cytokine production (IFN-γ, TNF-α, and IL-12), partially resembling the gliadin-induced Th1-type cytokine profile. B. longum CECT 7347 and B. bifidum CECT 7365 induced minor MDDC morphological changes and activated adhesion and spreading and inflammatory cytokine production to a lesser extent compared with enterobacteria. B. longum CECT 7347 also induced lower CD86 and CD40 expression on MDDCs than the two enterobacteria. The aforementioned bifidobacterial strain also reduced gliadin-induced IFN-γ production and increased IL-10 secretion when both stimuli were combined. Similar trends were detected for MDDCs cocultured with Caco-2 cells. B. longum CECT 7347 reversed the gliadin-reduced ZO-1 expression in Caco-2 cells. Thus, our results suggest that specific components of the gut microbiota may influence phenotypic and functional maturation of DCs differently and their interactions with epithelial cells. This could ultimately define the role of DCs in CD progression.