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BACKGROUNDA long-held goal of vision therapy is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists.METHODSWe implanted an intracortical microelectrode array consisting of 96 electrodes in the visual cortex of a 57-year-old person with complete blindness for a 6-month period. We measured thresholds and the characteristics of the visual percepts elicited by intracortical microstimulation.RESULTSImplantation and subsequent explantation of intracortical microelectrodes were carried out without complications. The mean stimulation threshold for single electrodes was 66.8 ± 36.5 μA. We consistently obtained high-quality recordings from visually deprived neurons and the stimulation parameters remained stable over time. Simultaneous stimulation via multiple electrodes was associated with a significant reduction in thresholds (P < 0.001, ANOVA) and evoked discriminable phosphene percepts, allowing the blind participant to identify some letters and recognize object boundaries.CONCLUSIONSOur results demonstrate the safety and efficacy of chronic intracortical microstimulation via a large number of electrodes in human visual cortex, showing its high potential for restoring functional vision in the blind.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02983370.FUNDINGThe Spanish Ministerio de Ciencia Innovación y Universidades, the Generalitat Valenciana (Spain), the Europan Union’s Horizon 2020 programme, the Bidons Egara Research Chair of the University Miguel Hernández (Spain), and the John Moran Eye Center of the University of Utah.  相似文献   
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Studying the cellular composition and morphological changes of cells lining the central canal during Xenopus laevis metamorphosis could contribute to understand postnatal development and spinal cord regeneration. Here we report the analysis of central canal cells at different stages during metamorphosis using immunofluorescence for protein markers expression, transmission and scanning electron microscopy and cell proliferation assays. The central canal was regionalized according to expression of glial markers, ultrastructure, and proliferation in dorsal, lateral, and ventral domains with differences between larvae and froglets. In regenerative larvae, all cell types were uniciliated, have a radial morphology, and elongated nuclei with lax chromatin, resembling radial glial cells. Important differences in cells of nonregenerative froglets were observed, although uniciliated cells were found, the most abundant cells had multicilia and revealed extensive changes in the maturation and differentiation state. The majority of dividing cells in larvae corresponded to uniciliated cells at dorsal and lateral domains in a cervical‐lumbar gradient, correlating with undifferentiated features. Neurons contacting the lumen of the central canal were detected in both stages and revealed extensive changes in the maturation and differentiation state. However, in froglets a very low proportion of cells incorporate 5‐ethynyl‐2′‐deoxyuridine (EdU), associated with the differentiated profile and with the increase of multiciliated cells. Our work showed progressive changes in the cell types lining the central canal of Xenopus laevis spinal cord which are correlated with the regenerative capacities.  相似文献   
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Purpose

Exclusive breastfeeding and longer breastfeeding reduce women’s breast cancer risk but Mexico has one of the lowest breastfeeding rates worldwide. We estimated the lifetime economic and disease burden of breast cancer in Mexico if 95% of parous women breastfeed each child exclusively for 6 months and continue breastfeeding for over a year.

Methods

We used a static microsimulation model with a cost-of-illness approach to simulate a cohort of Mexican women. We estimated breast cancer incidence, premature mortality, disability-adjusted life years (DALYs), medical costs, and income losses due to breast cancer and extrapolated the results to 1.116 million Mexican women of age 15 in 2012. Costs were expressed in 2015 US dollars and discounted at a 3% annual rate.

Results

We estimated that 2,186 premature deaths (95% CI 2,123–2,248), 9,936 breast cancer cases (95% CI 9,651–10,220), 45,109 DALYs (95% CI 43,000–47,217), and $245 million USD (95% CI 234–256) in medical costs and income losses owing to breast cancer could be saved over a cohort’s lifetime. Medical costs account for 80% of the economic burden; income losses and opportunity costs for caregivers account for 15 and 5%, respectively.

Conclusions

In Mexico, the burden of breast cancer due to suboptimal breastfeeding in women is high in terms of morbidity, premature mortality, and the economic costs for the health sector and society.
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Introduction and objective

Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates.

Methodology

Prospective study of all NTM isolated in Asturias from 2005 to 2012. Samples were processed following internationally accepted guidelines. Statistical analysis was based on Fisher's exact test for 2 × 2 contingency tables.

Results

A total of 3,284 mycobacteria were isolated: 1,499 Mycobacterium tuberculosis complex (MTB) and 1,785 NTM. During the study, NTM isolation rates increased while MTB isolation decreased. NTM were more frequent in men (P < .001). M. gordonae was the most frequently isolated species but did not cause disease in any case. NTM isolates from 212 patients were associated with clinically significant disease (17.1%). M. kansasii and M. avium were most commonly associated with disease. The number of M. kansasii isolates from men was statistically significant (P < .01).

Conclusions

In our study, NTM isolates increased by 35%, compared with a 21% decline in cases of MTB. Both isolation of NTM and clinically significant cases were more common in men. Only 17.1% of NTM isolates were associated with disease, most commonly M. avium complex and M. kansasii.  相似文献   
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On 13 July 2011 the European Commission issued a marketing authorisation valid throughout the European Union (EU) for ipilimumab for the treatment of advanced (unresectable or metastatic) melanoma in adults who have received prior therapy. Ipilimumab is a monoclonal antibody that specifically blocks the inhibitory signal of cytotoxic T lymphocyte antigen 4 (CTLA-4), resulting in T cell activation, proliferation and lymphocyte infiltration into tumours, leading to tumour cell death. The recommended induction regimen of ipilimumab is 3mg/kg administered intravenously over a 90 min period every 3 weeks for a total of four doses. In a phase 3 trial in patients with advanced melanoma, median overall survival for ipilimumab was 10 months versus 6 months for gp100, an experimental melanoma vaccine (Hazard ratio (HR) 0.66; 95% confidence interval (CI): 0.51, 0.87; p = 0.0026). Ipilimumab was most commonly associated with adverse reactions resulting from increased or excessive immune activity. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of ipilimumab. The most common side-effects (affecting more than 10% of patients) were diarrhoea, rash, pruritus, fatigue, nausea, vomiting, decreased appetite and abdominal pain. The objective of this paper is to summarise the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics (SmPC), are available on the European Medicines Agency (EMA) website (www.ema.europa.eu).  相似文献   
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