Single stage reconstruction of complex head and neck defects involving the skin with a single ALT flap: A ten year review

Background: Multicomponent defects of the head and neck involving the cervical skin pose a reconstructive challenge for microsurgeons and usually requires two flaps. However, many patients who undergo such surgical treatment had prior treatment with radiotherapy and the availability of recipient vessels for free flap reconstruction may be limited. The purpose of this study was to review our experience in the reconstruction of these extensive head and neck defects using a single ALT free flap. Methods: A total of 21 patients with complex defects of the head and neck involving multiple anatomical subunits, including the overlying cervical skin, underwent reconstruction with a single ALT flap. The clinical, functional, and aesthetic outcomes of these patients were reviewed. Results: The mean hospital stay was 24 days. There was one total flap loss due to pedicle thrombosis. The patient underwent a further ALT reconstruction with no postoperative complications. Cervical fistulas occurred in three patients, and all fistulas were healed by simple wound packing. Three patients with tracheal defect had a functional tracheostoma with adequate stomal patency. A modified barium swallowing study was performed on each patient, and all of them achieved total oral intake. Among them, two patients tolerated only a pureed diet. Conclusions: Complex neck reconstruction can be accomplished with a single ALT flap with good clinical and functional results, minimal morbidity and quick recovery

Prognostic value of CXCL12 expression in 40 low-grade oligodendrogliomas and oligoastrocytomas.

Both clinical and biological features have been reported as prognostic factors in low-grade gliomas. Among these, histotype, tumor size, enhancement, age and genetic pattern. Microvessel density (MVD) has been correlated to clinical outcome in astrocytomas, but its impact in oligodendrogliomas and mixed tumors is not sure. The pro-angiogenic chemokine stromal cell-derived factor (SDF-1/CXCL12) and its receptor CXC chemokine receptor 4 (CXCR4) have been described in low-grade gliomas, with a correlation between CXCL12 expression and shorter time to progression (TTP). The intermediate filament Nestin is expressed in proliferating vessels. Platelet-derived growth factor B (PDGF-B) and its receptor PDGFR-beta are also involved in angiogenesis and malignant progression in gliomas

Normative Autonomy and Normative Co-ordination: Declarative Power, Representation, and Mandate

In this paper we provide a formal analysis of the idea of normative co-ordination. We argue that this idea is based on the assumption that agents can achieve flexible co-ordination by conferring normative positions to other agents. These positions include duties, permissions, and powers. In particular, we explain the idea of declarative power, which consists in the capacity of the power-holder of creating normative positions, involving other agents, simply by "proclaiming" such positions. In addition, we account also for the concepts of representation, namely the representative's capacity of acting in the name of his principal, and of mandate, which is the mandatee's duty to act as the mandator has requested. Finally, we show how the framework can be applied to represent the contract-net protocol. Some brief remarks on future research and applications conclude this contribution

The vascular side of chronic bed rest: when a therapeutic approach becomes deleterious

The interplay between chronic constraint and advanced aging on blood flow, shear-rate, vascular function, nitric oxide (NO)-bioavailability, microcirculation, and vascular inflammation factors is still a matter of debate. Ninety-eight individuals (Young, n=28, 23\ub13yrs; Old, n=36, 85\ub17yrs; Bedridden, n=34, 88\ub16yrs) were included in the study. The bedridden group included old individuals chronically confined to bed (3.8\ub12.3yrs). A blood sample was collected and analyzed for plasma nitrate, and vascular inflammatory markers. Hyperemic response ( 06peak) during the single passive leg movement (sPLM) test was used to measure vascular function. Skeletal muscle total hemoglobin was measured at the vastus lateralis during the sPLM test, by means of near infrared spectroscopy (NIRS). Bedridden subjects revealed a depletion of plasma nitrates compared with Old (-23.8%) and Young (-31.1%). Blood flow was lower in the Bedridden in comparison to Old (-20.1%) and Young (-31.7%). Bedridden presented lower sPLM 06peak compared Old (-72.5%) and the Young (-83.3%). 06peak of NIRS total hemoglobin was lower in the Bedridden compared to that in the Young (-133%). All vascular inflammatory markers except IL-6 were significantly worse in the Bedridden compared to Old and Young. No differences were found between the Old and Young in inflammatory markers. Results of this study confirm that chronic physical constraint induces an exacerbation of vascular disfunction and differential regulation of vascular-related inflammatory markers. The mechanisms involved in these negative adaptations seems to be associated with endothelial dysfunction and consequent diminished NO-bioavailability likely caused by the reduced shear-rate consequential to long-term reduction of physical activity

A global lake and reservoir volume analysis using a surface water dataset and satellite altimetry

Lakes and reservoirs are crucial elements of the hydrological and biochemical cycle and are a valuable resource for hydropower, domestic and industrial water use, and irrigation. Although their monitoring is crucial in times of increased pressure on water resources by both climate change and human interventions, publically available datasets of lake and reservoir levels and volumes are scarce. Within this study, a time series of variation in lake and reservoir volume between 1984 and 2015 were analysed for 137 lakes over all continents by combining the JRC Global Surface Water (GSW) dataset and the satellite altimetry database DAHITI. The GSW dataset is a highly accurate surface water dataset at 30&thinsp;m resolution compromising the whole L1T Landsat 5, 7 and 8 archive, which allowed for detailed lake area calculations globally over a very long time period using Google Earth Engine. Therefore, the estimates in water volume fluctuations using the GSW dataset are expected to improve compared to current techniques as they are not constrained by complex and computationally intensive classification procedures. Lake areas and water levels were combined in a regression to derive the hypsometry relationship (dh&thinsp;∕&thinsp;dA) for all lakes. Nearly all lakes showed a linear regression, and 42&thinsp;% of the lakes showed a strong linear relationship with a R2&thinsp;&gt;&thinsp;0.8, an average R2 of 0.91 and a standard deviation of 0.05. For these lakes and for lakes with a nearly constant lake area (coefficient of variation &lt;&thinsp;0.008), volume variations were calculated. Lakes with a poor linear relationship were not considered. Reasons for low R2 values were found to be (1) a nearly constant lake area, (2) winter ice coverage and (3) a predominant lack of data within the GSW dataset for those lakes. Lake volume estimates were validated for 18 lakes in the US, Spain, Australia and Africa using in situ volume time series, and gave an excellent Pearson correlation coefficient of on average 0.97 with a standard deviation of 0.041, and a normalized RMSE of 7.42&thinsp;%. These results show a high potential for measuring lake volume dynamics using a pre-classified GSW dataset, which easily allows the method to be scaled up to an extensive global volumetric dataset. This dataset will not only provide a historical lake and reservoir volume variation record, but will also help to improve our understanding of the behaviour of lakes and reservoirs and their representation in (large-scale) hydrological models.</p

Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats.

Abstract Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3–L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3–L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS

Effects of platelet-rich plasma in a model of bovine endometrial inflammation in vitro

Background: Endometritis reduces fertility and is responsible for major economic losses in beef and dairy industries. The aim of this study was to evaluate an alternative therapy using platelet-rich plasma (PRP). PRP was tested in vivo, after bovine intrauterine administration, and in vitro on endometrial cells. Methods: Bovine endometrial cells were cultured until passage (P) 10 with 5% or 10% PRP. Effect of PRP on endometrial cell proliferation and on the expression of genes [prostaglandin-endoperoxide synthase 2 (COX2), tumor protein p53 (TP53), oestrogen receptors (ER-\u3b1 and ER-\u3b2), progesterone receptor (PR) and c-Myc] involved in the regulation of oestrus cycle and fetal-maternal interaction were evaluated. Moreover, to evaluate the ability of PRP to counteract inflammation, 10 and 100 ng/ml of bacterial endotoxin lipopolysaccharide (LPS) were used to inflame endometrial cells in vitro for 1, 6, 12, 24 and 48 h. The expression of genes such as interleukin 1\u3b2 (IL-1\u3b2), interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), and the release of PGE-2, IL-1\u3b2 and IL-8 were evaluated. Results: In vivo treatment with PRP increased the detection of PR. In vitro, 5% PRP at passage 5 increased proliferation rate and induced a significant increase in the expression of all studied genes. Furthermore, the results revealed that 10 ng/ml of LPS is the most effective dose to obtain an inflammatory response, and that PRP treatment significantly down regulated the expression of pro-inflammatory genes. Conclusion: This study lays the foundations for the potential treatment of endometritis with PRP in vivo

Intraspecies Transmission of BASE Induces Clinical Dullness and Amyotrophic Changes

The disease phenotype of bovine spongiform encephalopathy (BSE) and the molecular/ biological properties of its prion strain, including the host range and the characteristics of BSE-related disorders, have been extensively studied since its discovery in 1986. In recent years, systematic testing of the brains of cattle coming to slaughter resulted in the identification of at least two atypical forms of BSE. These emerging disorders are characterized by novel conformers of the bovine pathological prion protein (PrPTSE), named high-type (BSE-H) and low-type (BSE-L). We recently reported two Italian atypical cases with a PrPTSE type identical to BSE-L, pathologically characterized by PrP amyloid plaques and known as bovine amyloidotic spongiform encephalopathy (BASE). Several lines of evidence suggest that BASE is highly virulent and easily transmissible to a wide host range. Experimental transmission to transgenic mice overexpressing bovine PrP (Tgbov XV) suggested that BASE is caused by a prion strain distinct from the BSE isolate. In the present study, we experimentally infected Friesian and Alpine brown cattle with Italian BSE and BASE isolates via the intracerebral route. BASE-infected cattle developed amyotrophic changes accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. This study provides clear evidence of BASE as a distinct prion isolate and discloses a novel disease phenotype in cattle

Neurosphere-Derived Cells Exert a Neuroprotective Action by Changing the Ischemic Microenvironment

BACKGROUND: Neurosphere-derived cells (NC), containing neural stem cells, various progenitors and more differentiated cells, were obtained from newborn C57/BL6 mice and infused in a murine model of focal ischemia with reperfusion to investigate if: 1) they decreased ischemic injury and restored brain function; 2) they induced changes in the environment in which they are infused; 3) changes in brain environment consequent to transient ischemia were relevant for NC action. METHODOLOGY/PRINCIPAL FINDINGS: NC were infused intracerebroventricularly 4 h or 7 d after 30 min middle cerebral artery occlusion. In ischemic mice receiving cells at 4 h, impairment of open field performance was significantly improved and neuronal loss significantly reduced 7–14 d after ischemia compared to controls and to ischemic mice receiving cells at 7 d. Infusion of murine foetal fibroblast in the same experimental conditions was not effective. Assessment of infused cell distribution revealed that they migrated from the ventricle to the parenchyma, progressively decreased in number but they were observable up to 14 d. In mice receiving NC at 7 d and in sham-operated mice, few cells could be observed only at 24 h, indicating that the survival of these cells in brain tissue relates to the ischemic environment. The mRNA expression of trophic factors such as Insulin Growth Factor-1, Vascular Endothelial Growth Factor-A, Transforming Growth Factor-β1, Brain Derived Neurotrophic Factor and Stromal Derived Factor−1α, as well as microglia/macrophage activation, increased 24 h after NC infusion in ischemic mice treated at 4 h compared to sham-operated and to mice receiving cells at 7 d. CONCLUSIONS/SIGNIFICANCE: NC reduce functional impairment and neuronal damage after ischemia/reperfusion injury. Several lines of evidence indicate that the reciprocal interaction between NC and the ischemic environment is crucial for NC protective actions. Based on these results we propose that a bystander control of the ischemic environment may be the mechanism used by NC to rapidly restore acutely injured brain function