Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model.

BACKGROUND: Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. METHODS: The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular architecture (corrosion casting) and wound healing (digital planimetry) are studied in a murine tail lymphedema model. RESULTS: Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization mainly from the proximal wound margin. The application of PRP induced a significantly increased lymphangiogenesis while the application of ASC did not induce any significant change in this regard. CONCLUSIONS: PRP and ASC affect lymphangiogenesis and lymphedema development and might represent a promising approach to improve regeneration of lymphatic vessels, restore disrupted lymphatic circulation and treat or prevent lymphedema alone or in combination with currently available lymphedema therapies.

Effect of humeral stem design on humeral position and range of motion in reverse shoulder arthroplasty.

PURPOSE: The impacts of humeral offset and stem design after reverse shoulder arthroplasty (RSA) have not been well-studied, particularly with regard to newer stems which have a lower humeral inclination. The purpose of this study was to analyze the effect of different humeral stem designs on range of motion and humeral position following RSA. METHODS: Using a three-dimensional computer model of RSA, a traditional inlay Grammont stem was compared to a short curved onlay stem with different inclinations (155°, 145°, 135°) and offset (lateralised vs medialised). Humeral offset, the acromiohumeral distance (AHD), and range of motion were evaluated for each configuration. RESULTS: Altering stem design led to a nearly 7-mm change in humeral offset and 4 mm in the AHD. Different inclinations of the onlay stems had little influence on humeral offset and larger influence on decreasing the AHD. There was a 10° decrease in abduction and a 5° increase in adduction between an inlay Grammont design and an onlay design with the same inclination. Compared to the 155° model, the 135° model improved adduction by 28°, extension by 24° and external rotation of the elbow at the side by 15°, but led to a decrease in abduction of 9°. When the tray was placed medially, on the 145° model, a 9° loss of abduction was observed. CONCLUSIONS: With varus inclination prostheses (135° and 145°), elevation remains unchanged, abduction slightly decreases, but a dramatic improvement in adduction, extension and external rotation with the elbow at the side are observed.

Universal Service Policies in Europe & Latam: Evidence on Bridging the Divide in Rural Areas

Broadband access is a key factor for economic and social development. However, providing broadband to rural areas is not attractive to private telecommunications operators due its low or zero investment return. To deal with broadband provision in rural areas, different governance systems based on private and public cooperation have appeared. This paper not only identifies and defines public and private cooperation models but also assesses their impact on overcoming the digital divide in rural areas. The results show that public ownership infrastructure under private management policy has had positive effects on reducing the broadband digital divide and being applied to areas with higher digital divide; subsides to private operators providers only positive effects on reducing broadband digital divide; but public infrastructure with public management programs did not. The results, obtained using quasi-experimental methods, suggest the importance of incentives and control mechanisms in broadband universal service provision plans.

Distinct contributions of Brodmann areas 1 and 2 to body ownership.

Although body ownership-i.e. the feeling that our bodies belong to us-modulates activity within the primary somatosensory cortex (S1), it is still unknown whether this modulation occurs within a somatotopically defined portion of S1. We induced an illusory feeling of ownership for another person's finger by asking participants to hold their palm against another person's palm and to stroke the two joined index fingers with the index and thumb of their other hand. This illusion (numbness illusion) does not occur if the stroking is performed asynchronously or by the other person. We combined this somatosensory paradigm with ultra-high field functional magnetic resonance imaging finger mapping to study whether illusory body ownership modulates activity within different finger-specific areas of S1. The results revealed that the numbness illusion is associated with activity in Brodmann area (BA) 1 within the representation of the finger stroking the other person's finger and in BA 2 contralateral to the stroked finger. These results show that changes in bodily experience modulate the activity within certain subregions of S1, with a different finger-topographical selectivity between the representations of the stroking and of the stroked hand, and reveal that the high degree of somatosensory specialization in S1 extends to bodily self-consciousness.

JNK controls the onset of mitosis of planarian stem cells and triggers apoptotic cell death required for regeneration and remodeling

Regeneration of lost tissues depends on the precise interpretation of molecular signals that control and coordinate the onset of proliferation, cellular differentiation and cell death. However, the nature of those molecular signals and the mechanisms that integrate the cellular responses remain largely unknown. The planarian flatworm is a unique model in which regeneration and tissue renewal can be comprehensively studied in vivo. The presence of a population of adult pluripotent stem cells combined with the ability to decode signaling after wounding enable planarians to regenerate a complete, correctly proportioned animal within a few days after any kind of amputation, and to adapt their size to nutritional changes without compromising functionality. Here, we demonstrate that the stress-activated c-jun-NH2-kinase (JNK) links wound-induced apoptosis to the stem cell response during planarian regeneration. We show that JNK modulates the expression of wound-related genes, triggers apoptosis and attenuates the onset of mitosis in stem cells specifically after tissue loss. Furthermore, in pre-existing body regions, JNK activity is required to establish a positive balance between cell death and stem cell proliferation to enable tissue renewal, remodeling and the maintenance of proportionality. During homeostatic degrowth, JNK RNAi blocks apoptosis, resulting in impaired organ remodeling and rescaling. Our findings indicate that JNK-dependent apoptotic cell death is crucial to coordinate tissue renewal and remodeling required to regenerate and to maintain a correctly proportioned animal. Hence, JNK might act as a hub, translating wound signals into apoptotic cell death, controlled stem cell proliferation and differentiation, all of which are required to coordinate regeneration and tissue renewal.

Predicting the future effectiveness of protected areas for bird conservation in Mediterranean ecosystems under climate change and novel fire regime scenarios

AimGlobal environmental changes challenge traditional conservation approaches based on the selection of static protected areas due to their limited ability to deal with the dynamic nature of driving forces relevant to biodiversity. The Natura 2000 network (N2000) constitutes a major milestone in biodiversity conservation in Europe, but the degree to which this static network will be able to reach its long-term conservation objectives raises concern. We assessed the changes in the effectiveness of N2000 in a Mediterranean ecosystem between 2000 and 2050 under different combinations of climate and land cover change scenarios. LocationCatalonia, Spain. MethodsPotential distribution changes of several terrestrial bird species of conservation interest included in the European Union's Birds Directive were predicted within an ensemble-forecasting framework that hierarchically integrated climate change and land cover change scenarios. Land cover changes were simulated using a spatially explicit fire-succession model that integrates fire management strategies and vegetation encroachment after the abandonment of cultivated areas as the main drivers of landscape dynamics in Mediterranean ecosystems. ResultsOur results suggest that the amount of suitable habitats for the target species will strongly decrease both inside and outside N2000. However, the effectiveness of N2000 is expected to increase in the next decades because the amount of suitable habitats is predicted to decrease less inside than outside this network. Main conclusionsSuch predictions shed light on the key role that the current N2000may play in the near future and emphasize the need for an integrative conservation perspective wherein agricultural, forest and fire management policies should be considered to effectively preserve key habitats for threatened birds in fire-prone, highly dynamic Mediterranean ecosystems. Results also show the importance of considering landscape dynamics and the synergies between different driving forces when assessing the long-term effectiveness of protected areas for biodiversity conservation.

Areas of high conservation value in Georgia: present and future threats by invasive alien plants

Georgia is known for its extraordinary rich biodiversity of plants, which may now be threatened due to the spread of invasive alien plants (IAP). We aimed to identify (i) the most prominent IAP out of 9 selected potentially invasive and harmful IAP IAP by predicting thetheir distribution of 9 selected IAP under current and future climate conditions in Georgia as well as in its 43 Protected Areas, as a proxy for areas of high conservation value and (ii) the Protected Areas most at risk due to these IAP. We used species distribution models based on 6 climate variables and then filtered the obtained distributions based on maps of soil and vegetation types, and on recorded occurrences, resulting into the predicted ecological distribution of the 9 IAP's at a resolution of 1km2. We foundOur habitat suitability analysis showed that Ambrosia artemisiifolia, (24% and 40%) Robinia pseudoacaia (14% and 19%) and Ailanthus altissima (9% and 11%) have the largest potential distribution are the most abundant (predicted % area covered)d) IAP, with Ailanthus altissima the potentially most increasing one over the next fifty years (from 9% to 13% and from 11% to 25%), for Georgia and the Protected Areas, respectively. Furthermore, our results show indicate two areas in Georgia that are under specifically high threat, i.e. the area around Tbilisi and an area in the western part of Georgia (Adjara), both at lower altitudes. Our procedure to identify areas of high conservation value most at risk by IAP has been applied for the first time. It will help national authorities in prioritizing their measures to protect Georgia's outstanding biodiversity from the negative impact of IAP.

Fertilizing Methods and Nutrient Balance at the End of Traditional Organic Agriculture in the Mediterranean Bioregion: Catalonia (Spain) in the 1860s

By reconstructing the nutrient balance of a Catalan v illage circa 1861-65 we examine the sustainability of organic agricultural sy stems in the northwest Mediterranean bioregion prior to the green rev olution and the question of whether the nutrients extracted f rom the soil were replenished. With a population density of 59 inhabitants per square km, similar to other northern European rural areas at that time, and a lower liv estock density per cropland unit, this v illage experienced a manure shortage. The gap was f illed by other labour-intensiv e way s of transf erring nutrients f rom uncultiv ated areas into the cropland. Key elements in this agricultural sy stem were v iney ards because they hav e f ew nutrient requirements, and woodland and scrublands as sources of relev ant amounts of nutrients collected in sev eral ways.

HouSI: Heuristic for delimitation of housing submarkets and price homogeneous areas

This paper seeks to address the problem of the empirical identification of housing market segmentation,once we assume that submarkets exist. The typical difficulty in identifying housing submarkets when dealing with many locations is the vast number of potential solutions and, in such cases, the use of the Chow test for hedonic functions is not a practical solution. Here, we solve this problem by undertaking an identification process with a heuristic for spatially constrained clustering, the"Housing Submarket Identifier" (HouSI). The solution is applied to the housing market in the city of Barcelona (Spain), where we estimate a hedonic model for fifty thousand dwellings aggregated into ten groups. In order to determine the utility of the procedure we seek to verify whether the final solution provided by the heuristic is comparable with the division of the city into ten administrative districts.

Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas.

Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds. The associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6-72 months). Associations between antibody levels and risk of malaria were assessed using Cox regression models adjusting for covariates. There was a significant association between GLURP R2 IgG3 and reduced risk of malaria after adjusting age of children in both the Burkinabe (hazard ratio 0.82; 95 % CI 0.74-0.91, p < 0.0001) and the Ghanaian (HR 0.48; 95 % CI 0.25-0.91, p = 0.02) cohorts. MSP1 hybrid IgM was associated (HR 0.85; 95 % CI 0.73-0.98, p = 0.02) with reduced risk of malaria in Burkina Faso cohort while IgG against AS202.11 in the Ghanaian children was associated with increased risk of malaria (HR 1.29; 95 % CI 1.01-1.65, p = 0.04). These findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity.

Smoked cocaine in socially-depressed areas

Background: The main objectives of this study are to describe the smoked cocaine user's profile in socially-depressed areas and their needs from a harm-reduction perspective, to investigate their use of smoking crack and compare the acute effects between injecting and smoking consumption. Methods: The study took place in SAPS, Barcelona, Spain. Two focus group sessions were undertaken with a total of 8 drug users. Secondly, the 8 participants answered a structured questionnaire and in the course of the sessions, as a snowball activity, were trained to survey 6 other crack smokers. Results: We obtained 56 questionnaires. The majority of participants were from non-European Community countries (62.69%), 70.2% of participants referred to sharing the smoking equipment. The most frequent symptoms reported during smoked cocaine were mydriasis (83.33%)), perspiration (72.92%) and compulsive object search (70.83%) During the group sessions, participants said that smoked cocaine is much more addictive than injected cocaine and causes more anxiety. Participants also reported the difficulty of changing from injected use to smoked use, due to the larger amount of cocaine needed to reach the same effects as when having injected. Conclusions We can conclude that the research, focused on achieving greater knowledge of the smoked cocaine user's profile, their usage of smoking crack, consumption patterns and acute effects, should be incorporated into substance misuse interventions.

Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells.

Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions.