Inherited photoreceptor degenerations are not treatable diseases and a frequent cause of blindness in working ages. In this study we investigate the safety, integration and possible rescue effects of ...intravitreal and subretinal transplantation of adult human bone-marrow-derived mononuclear stem cells (hBM-MSCs) in two animal models of inherited photoreceptor degeneration, the P23H-1 and the Royal College of Surgeons (RCS) rat. Immunosuppression was started one day before the injection and continued through the study. The hBM-MSCs were injected in the left eyes and the animals were processed 7, 15, 30 or 60 days later. The retinas were cross-sectioned, and L- and S- cones, microglia, astrocytes and Müller cells were immunodetected. Transplantations had no local adverse effects and the CD45+ cells remained for up to 15 days forming clusters in the vitreous and/or a 2-3-cells-thick layer in the subretinal space after intravitreal or subretinal injections, respectively. We did not observe increased photoreceptor survival nor decreased microglial cell numbers in the injected left eyes. However, the injected eyes showed decreased GFAP immunoreactivity. We conclude that intravitreal or subretinal injection of hBM-MSCs in dystrophic P23H-1 and RCS rats causes a decrease in retinal gliosis but does not have photoreceptor neuroprotective effects, at least in the short term. However, this treatment may have a potential therapeutic effect that merits further investigation.
Abstract
In prokaryotes, the centromere is a specialized segment of DNA that promotes the assembly of the segrosome upon binding of the Centromere Binding Protein (CBP). The segrosome structure ...exposes a specific surface for the interaction of the CBP with the motor protein that mediates DNA movement during cell division. Additionally, the CBP usually controls the transcriptional regulation of the segregation system as a cell cycle checkpoint. Correct segrosome functioning is therefore indispensable for accurate DNA segregation. Here, we combine biochemical reconstruction and structural and biophysical analysis to bring light to the architecture of the segrosome complex in Type III partition systems. We present the particular features of the centromere site, tubC, of the model system encoded in Clostridium botulinum prophage c-st. We find that the split centromere site contains two different iterons involved in the binding and spreading of the CBP, TubR. The resulting nucleoprotein complex consists of a novel double-ring structure that covers part of the predicted promoter. Single molecule data provides a mechanism for the formation of the segrosome structure based on DNA bending and unwinding upon TubR binding.
To evaluate survival after stereotactic body radiotherapy (SBRT) as radical treatment for metastases of colorectal cancer (CRC) and to identify prognostic factors after treatment.
Patients with ...metastatic CRC treated with SBRT on metastatic lesions were retrospectively analyzed between February 2012 and August 2016 at the General University Hospital of Valencia. The follow-up was carried out until July 15, 2018. The data have been collected in a database. Patients may have received prior systemic therapy and/or resection of metastatic disease. Endpoints were timed from end of SBRT and included overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors.
A total of 49 patients were identified. Before SBRT, 77.5% of the patients have received systemic therapy and 65.2% surgery for metastatic disease. Of metastatic lesions treated with SBRT 53.1% were located in the lung, 30.6% in the liver and 16.3% in other locations. Median survival were: PFS after treatment with SBRT was 9.9 months (95% CI: 4.64-15.1) and the median OS was 28.9 months (95% CI: 19.0-38.7). No relapses were observed in 20% of the patients after SBRT. The treatment was well tolerated and no patient had grade 3 or 4 adverse effects. Right colon HR 16.53 (95% CI: 3.11-87.87), P value 0.001 and higher tumor stage (III-IV) HR 12.30 (95% CI: 2.10-71.92), P value 0.005 showed a lower OS in a multivariate analysis.
SBRT for oligometastatic disease is an effective option for patients with advanced CRC, with encorauging survival outcomes. However, a definitive validation in large randomized studies is required.
Background Antibiotic prescription for respiratory tract infections (RTIs) in children attending primary care centres is almost double that predicted according to bacterial prevalence. Delayed ...antibiotic prescription (DAP) is designed to deploy a more rational use of antibiotics. While studies have evaluated DAP efficacy and safety for children with RTIs, little research has been conducted on the economic implications. Methods Our trial compared cost-effectiveness for DAP, immediate antibiotic prescription (IAP), and no antibiotic prescription (NAP) for children aged 2-14 years with acute uncomplicated RTIs attended to in 39 primary care centres in Spain. The main outcome was the incremental cost-effectiveness ratio (ICER), measured in euros per gained quality-adjusted life days (QALDs). Net monetary benefit (NMB) was also calculated as a tool for decision making. The analysis was performed from a societal perspective for a time horizon of 30 days, and included healthcare direct costs, non-healthcare direct and indirect costs, and the antimicrobial resistance (AMR) cost. Results DAP was the most cost-effective strategy, even when the cost of AMR was included. QALD values for the three strategies were very similar. IAP compared to DAP was more costly (109.68 vs 100.90 euros) and similarly effective (27.88 vs 27.94 QALDs). DAP compared to NAP was more costly (100.90 vs 97.48 euros) and more effective (27.94 vs. 27.82 QALDs). The ICER for DAP compared to NAP was 28.84 euros per QALD. The deterministic sensitivity analysis indicated that non-healthcare indirect costs had the greatest impact on the ICER. The cost-effectiveness acceptability curve showed that DAP was the preferred option in approximately 81.75% of Monte Carlo iterations, assuming a willingness-to-pay value of 82.2 euros per gained QALD. Conclusions When clinicians are in doubt about whether an antibiotic is needed for children with RTIs attending PC centres, those treated with the DAP strategy will have slightly better efficiency outcomes than those treated with IAP because its costs are lower than those of IAP. DAP is also the most cost-effective strategy over a time horizon of 30 days if AMR is considered, despite higher short-term costs than NAP. However, if in the long term the costs of AMR are larger than estimated, NAP could also be an alternative strategy. Trial registration This trial has been registered at www.clinicaltrials.gov (identifier NCT01800747; Date: 28/02/2013 (retrospectively registered). Keywords: Cost effectiveness, Delayed antibiotic prescription, Respiratory tract infections, Primary care, Paediatrics
Abstract Eleven thousand two hundred seventy-two Escherichia coli , 1109 Klebsiella pneumoniae , 1124 Salmonella enterica , and 602 Klebsiella oxytoca unrelated clinical isolates were obtained ...between 2001 and 2004 in a university hospital in Salamanca, Spain. One hundred thirteen E. coli (1%), 32 K. pneumoniae (2.9%), 4 K. oxytoca (0.66%), and 5 S. enterica (0.44%) isolates produced extended-spectrum β-lactamases (ESBLs). We obtained 42.2% of the ESBL-producing isolates from outpatients and 57.8% from inpatients. The most commonly detected ESBLs were CTX-M 14 (43.5% of ESBL-producing isolates), TEM-116 (22.1%), and SHV-2 (15.6%). A CTX-M 27–producing E. coli is 1st reported in Spain in this study. Two (20 isolates, 13%) or 3 (7 isolates, 4.5%) ESBLs were produced by 17.5% of ESBL-producing isolates (27 isolates). The most frequent combinations were CTX-M 14 + TEM-116 (5.7%), SHV-12 + TEM-116 (2.6%), and SHV-2 + CTX-M 14 + TEM-116 (2.6%). Clonal diversity was high even between isolates producing the same combinations of 2 or 3 β-lactamases.
Antibiotic resistance is an old problem with new face as the rate of infections due to multidrug resistant bacteria is higher everyday and the number of new antibiotics to overwhelm the problem is ...becoming smaller. E. coli is the most frequent agent causing nosocomial or community-acquired bacteraemia being in our country 10% of them extended-spectrum beta-lactamases (ESBL) producing E. coli isolates. Nowadays the number of community- acquired or health-related infections caused by these ESBL producing E. coli is increasing. CTX-M has also become the most frequent ESBL compared to other enzymes. The role of these enzymes as a virulence factor increasing mortality in patients with bacteraemia due to E. coli is not well defined. The relevance of ESBL-E. coli seems to be related with the higher frequency of inadequate treatment and therefore the importance of identifying factors or features that might predict that the patient's infection is due to one of these isolates. In terms of prevention and control of infection measures, the role of patient's isolation is not clear but a proper prescription of antibiotics and antibiotic control policies are probably important to reduce the problem.
Tracing Orpheus Miguel Herrero de Jáuregui, Ana Isabel Jiménez San Cristóbal, Eugenio R. Luján Martínez, Raquel Martín Hernández, Marco Antonio Santamaría Álvarez, Sofía Torallas Tovar / Miguel Herrero de Jáuregui, Ana Isabel Jiménez San Cristóbal, Eugenio R. Luján Martínez, Raquel Martín Hernández, Marco Antonio Santamaría Álvarez, Sofía Torallas Tovar
2011
eBook
There is hardly a more controversial issue in the study of ancient religion than Orphism. More than two centuries of debate have not closed the subject, since new evidence and divergent approaches ...have kept appearing regularly. This volume sheds light on the most relevant pieces of evidence for ancient Orphism, collected in the recent edition by Alberto Bernabé. It contains 65 short new studies on Orphic fragments by leading international scholars who comment one of the most controversial phenomena in Antiquity from a plurality of perspectives. Readers will acquire a global vision of the multiple dimensions of the Orphic tradition, as well as many new insights into particular Orphic fragments.
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