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991.
Agostina Puppo Alexander Bello Anna Manfredi Giulia Cesi Elena Marrocco Michele Della Corte Settimio Rossi Massimo Giunti Maria Laura Bacci Francesca Simonelli Enrico Maria Surace Gary P. Kobinger Alberto Auricchio 《PloS one》2013,8(3)
Recombinant adeno-associated viral (AAV) vectors are known to safely and efficiently transduce the retina. Among the various AAV serotypes available, AAV2/5 and 2/8 are the most effective for gene transfer to photoreceptors (PR), which are the most relevant targets for gene therapy of inherited retinal degenerations. However, the search for novel AAV serotypes with improved PR transduction is ongoing. In this work we tested vectors derived from five AAV serotypes isolated from porcine tissues (referred to as porcine AAVs, four of which are newly identified) for their ability to transduce both the murine and the cone-enriched pig retina. Porcine AAV vectors expressing EGFP under the control of the CMV promoter were injected subretinally either in C57BL/6 mice or Large White pigs. The resulting retinal tropism was analyzed one month later on histological sections, while levels of PR transduction were assessed by Western blot. Our results show that all porcine AAV transduce murine and porcine retinal pigment epithelium and PR upon subretinal administration. AAV2/po1 and 2/po5 are the most efficient porcine AAVs for murine PR transduction and exhibit the strongest tropism for pig cone PR. The levels of PR transduction obtained with AAV2/po1 and 2/po5 are similar, albeit not superior, to those obtained with AAV2/5 and AAV2/8, which evinces AAV2/po1 and 2/po5 to be promising vectors for retinal gene therapy. 相似文献
992.
Maria Giné-Garriga Carme Martin-Borràs Anna Puig-Ribera Carlos Martín-Cantera Mercè Solà Antonio Cuesta-Vargas 《PloS one》2013,8(6)
Background
Effective promotion of exercise could result in substantial savings in healthcare cost expenses in terms of direct medical costs, such as the number of medical appointments. However, this is hampered by our limited knowledge of how to achieve sustained increases in physical activity.Objectives
To assess the effectiveness of a Primary Health Care (PHC) based physical activity program in reducing the total number of visits to the healthcare center among inactive patients, over a 15-month period.Research Design
Randomized controlled trial.Subjects
Three hundred and sixty-two (n = 362) inactive patients suffering from at least one chronic condition were included. One hundred and eighty-three patients (n = 183; mean (SD); 68.3 (8.8) years; 118 women) were randomly allocated to the physical activity program (IG). One hundred and seventy-nine patients (n = 179; 67.2 (9.1) years; 106 women) were allocated to the control group (CG). The IG went through a three-month standardized physical activity program led by physical activity specialists and linked to community resources.Measures
The total number of medical appointments to the PHC, during twelve months before and after the program, was registered. Self-reported health status (SF-12 version 2) was assessed at baseline (month 0), at the end of the intervention (month 3), and at 12 months follow-up after the end of the intervention (month 15).Results
The IG had a significantly reduced number of visits during the 12 months after the intervention: 14.8 (8.5). The CG remained about the same: 18.2 (11.1) (P = .002).Conclusions
Our findings indicate that a 3-month physical activity program linked to community resources is a short-duration, effective and sustainable intervention in inactive patients to decrease rates of PHC visits.Trial Registration
ClinicalTrials.gov NCT00714831相似文献993.
Background
The common or brinjal eggplant (Solanum melongena L.) belongs to the Leptostemonum Clade (the “spiny” solanums) of the species-rich genus Solanum (Solanaceae). Unlike most of the genus, the eggplant and its relatives are from the Old World; most eggplant wild relatives are from Africa. An informal system for naming eggplant wild relatives largely based on crossing and other biosystematics data has been in use for approximately a decade. This system recognises several forms of two broadly conceived species, S. incanum L. and S. melongena. Recent morphological and molecular work has shown that species-level differences exist between these entities, and a new species-level nomenclature has been identified as necessary for plant breeders and for the maintenance of accurately named germplasm.Methodology/Principal Findings
We examined herbarium specimens from throughout the wild species ranges as part of a larger revision of the spiny solanums of Africa. Based on these morphological and molecular studies, we delimited species in the group to which the common eggplant belongs and constructed identification keys for the group. We also examined the monophyly of the group considered as the eggplant relatives by previous authors.Conclusions/Significance
We recognise ten species in this group: S. aureitomentosum Bitter, S. campylacanthum A.Rich., S. cerasiferum Dunal, S. incanum L., S. insanum L., S. lichtensteinii Willd., S. linnaeanum Hepper & P.-M.L.Jaeger, S. melongena L., S. rigidum Lam. and S. umtuma Voronts. & S.Knapp. We review the history of naming and provide keys and character lists for all species. Ploidy level differences have not been investigated in the eggplant wild relatives; we identify this as a priority for improvement of crop wild relative use in breeding. The application of species-level names to these entities will help focus new collecting efforts for brinjal eggplant improvement and help facilitate information exchange. 相似文献994.
995.
Savino di Lernia Mary Anne Tafuri Marina Gallinaro Francesca Alhaique Marie Balasse Lucia Cavorsi Paul D. Fullagar Anna Maria Mercuri Andrea Monaco Alessandro Perego Andrea Zerboni 《PloS one》2013,8(2)
Cattle pastoralism is an important trait of African cultures. Ethnographic studies describe the central role played by domestic cattle within many societies, highlighting its social and ideological value well beyond its mere function as ‘walking larder’. Historical depth of this African legacy has been repeatedly assessed in an archaeological perspective, mostly emphasizing a continental vision. Nevertheless, in-depth site-specific studies, with a few exceptions, are lacking. Despite the long tradition of a multi-disciplinary approach to the analysis of pastoral systems in Africa, rarely do early and middle Holocene archaeological contexts feature in the same area the combination of settlement, ceremonial and rock art features so as to be multi-dimensionally explored: the Messak plateau in the Libyan central Sahara represents an outstanding exception. Known for its rich Pleistocene occupation and abundant Holocene rock art, the region, through our research, has also shown to preserve the material evidence of a complex ritual dated to the Middle Pastoral (6080–5120 BP or 5200–3800 BC). This was centred on the frequent deposition in stone monuments of disarticulated animal remains, mostly cattle. Animal burials are known also from other African contexts, but regional extent of the phenomenon, state of preservation of monuments, and associated rock art make the Messak case unique. GIS analysis, excavation data, radiocarbon dating, zooarchaeological and isotopic (Sr, C, O) analyses of animal remains, and botanical information are used to explore this highly formalized ritual and the lifeways of a pastoral community in the Holocene Sahara. 相似文献
996.
Beatriz Grinsztejn Paula M. Luz Antonio G. Pacheco Desiree V. G. Santos Luciane Velasque Ronaldo I. Moreira Maria Regina C. Guimar?es Estev?o P. Nunes Alberto S. Lemos Sayonara R. Ribeiro Dayse P. Campos Marco A. A. Vitoria Valdilea G. Veloso 《PloS one》2013,8(4)
Introduction
We describe temporal trends in the mortality rates and factors associated with AIDS and non-AIDS related mortality at the Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ).Methods
Adult patients enrolling from 1986 through 2009 with a minimum follow up of 60 days were included. Vital status was exhaustively checked using patients’ medical charts, through active contact with individuals and family members and by linkage with the Rio de Janeiro Mortality database using a previously validated algorithm. The CoDe protocol was used to establish the cause of death. Extended Cox proportional hazards models were used for multivariate modeling.Results
A total of 3530 individuals met the inclusion criteria, out of which 868 (24.6%) deceased; median follow up per patient was 3.9 years (interquartile range 1.7–9.2 years). The dramatic decrease in the overall mortality rates was driven by AIDS-related causes that decreased from 9.19 deaths/100PYs n 1986–1991 to 1.35/100PYs in 2007–2009. Non-AIDS related mortality rates remained stable overtime, at around 1 death/100PYs. Immunodeficiency significantly increased the hazard of both AIDS-related and non-AIDS-related causes of death, while HAART use was strongly associated with a lower hazard of death from either cause.Conclusions
Our results confirm the remarkable decrease in AIDS-related mortality as the HIV epidemic evolved and alerts to the conditions not traditionally related to HIV/AIDS which are now becoming more frequent, needing careful monitoring. 相似文献997.
Marta Elena álvarez-Argüelles Santiago Melón Maria Luisa Junquera Jose Antonio Boga Laura Villa Sonia Pérez-Castro María de O?a 《PloS one》2013,8(1)
Objective
Human Papillomavirus (HPV) infection in men may produce cancer and other major disorders. Men play an important role in the transmission of the virus and act as a reservoir. The aim of this study was to determine the HPV-genotypes and their prevalence in a group of men attending a Sexually Transmitted Infection service.Patients and Samples
Between July 2002 and June 2011, 1392 balanopreputial, 435 urethral, 123 anal, and 67 condyloma lesions from 1551 men with a mean age of 35.8±11.3 years old (range: 17–87) were collected for HPV-DNA testing.Methods
A fragment of the L1-gene and a fragment of the E6/E7-genes were amplified by PCR. Positive samples were typed by hybridization.Results
The HPV genome was detected in 36.9% (486/1318) balanopreputial and in 24.9% (101/405) urethral (p<0.0001) swabs from 38.1% (538) of 1469 men. Co-infections were present in 5.4% (80/1469) of cases. HPV was found in 43.9% (373/850) of men younger than 35 vs. 31.7% (187/589) of men aged >35. HPV was found in 59.4% (104) of 165 men with lesions (macroscopic or positive peniscopy), and in 22.8% (61/267) without clinical alterations. HPV was also detected in 71.4% (40/56) men with condylomata and in 58.7% (64/109) of men with positive peniscopy.Conclusions
HPV prevalence in men was high and decreased with age. HPV was found more frequently in balanopreputial than in urethral swabs. There was a low rate of co-infections. Low-risk HPV vaccine genotypes were the most recurrent especially in younger. Although HPV has been associated with clinical alterations, it was also found in men without any clinical presentation. Inclusion of men in the national HPV vaccination program may reduce their burden of HPV-related disease and reduce transmission of the virus to non-vaccinated women. 相似文献998.
Giovanna Poce Robert H. Bates Salvatore Alfonso Martina Cocozza Giulio Cesare Porretta Lluís Ballell Joaquin Rullas Fátima Ortega Alessandro De Logu Emanuela Agus Valentina La Rosa Maria Rosalia Pasca Edda De Rossi Baojie Wae Scott G. Franzblau Fabrizio Manetti Maurizio Botta Mariangela Biava 《PloS one》2013,8(2)
1,5-Diphenyl pyrroles were previously identified as a class of compounds endowed with high in vitro efficacy against M. tuberculosis. To improve the physical chemical properties and drug-like parameters of this class of compounds, a medicinal chemistry effort was undertaken. By selecting the optimal substitution patterns for the phenyl rings at N1 and C5 and by replacing the thiomorpholine moiety with a morpholine one, a new series of compounds was produced. The replacement of the sulfur with oxygen gave compounds with lower lipophilicity and improved in
vitro microsomal stability. Moreover, since the parent compound of this family has been shown to target MmpL3, mycobacterial mutants resistant to two compounds have been isolated and characterized by sequencing the mmpL3 gene; all the mutants showed point mutations in this gene. The best compound identified to date was progressed to dose-response studies in an acute murine TB infection model. The resulting ED99 of 49 mg/Kg is within the range of commonly employed tuberculosis drugs, demonstrating the potential of this chemical series. The in vitro and in vivo target validation evidence presented here adds further weight to MmpL3 as a druggable target of interest for anti-tubercular drug discovery. 相似文献
999.
Maria Antonella Burza Stefano Romeo Anna Kotronen Per-Arne Svensson Kajsa Sj?holm Jarl S. Torgerson Anna-Karin Lindroos Lars Sj?str?m Lena M. S. Carlsson Markku Peltonen 《PloS one》2013,8(3)
Background and Aim
Obesity is associated with elevated serum transaminase levels and non-alcoholic fatty liver disease and weight loss is a recommended therapeutic strategy. Bariatric surgery is effective in obtaining and maintaining weight loss. Aim of the present study was to examine the long-term effects of bariatric surgery on transaminase levels in obese individuals.Methods
The Swedish Obese Subjects (SOS) study is a prospective controlled intervention study designed to compare the long-term effects of bariatric surgery and usual care in obese subjects. A total of 3,570 obese participants with no excess of alcohol consumption at baseline (1,795 and 1,775 in the control and surgery group, respectively) were included in the analyses. Changes in transaminase levels during follow-up were compared in the surgery and control groups.Results
Compared to usual care, bariatric surgery was associated with lower serum ALT and AST levels at 2- and 10- year follow up. The reduction in ALT levels was proportional to the degree of weight loss. Both the incidence of and the remission from high transaminase levels were more favorable in the surgery group compared to the control group. Similarly, the prevalence of ALT/AST ratio <1 was lower in the surgery compared to the control group at both 2- and 10-year follow up.Conclusions
Bariatric surgery results in a sustained reduction in transaminase levels and a long-term benefit in obese individuals. 相似文献1000.
Sam Nordfeldt Teresia ?ngarne-Lindberg Maria Nordwall Joakim Ekberg Carina Berter? 《PloS one》2013,8(6)