Restoration Capacity Research Articles

Circulating Endothelial Progenitor Cells and Their Relation to Thrombosis in Paroxysmal Nocturnal Hemoglobinuria

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder. Chronic intravascular hemolytic anemia, bone marrow failure and thrombophilia are the main clinical findings. Thrombosis is one of the most important cause of morbidity and mortality of this disease. Multiple factors are held responsible for thrombotic tendency in these patients. Endothelial progenitor cells (EPCs) originate from primitive hematopoietic stem cells and are able to turn into endothelial cells. There are extremely small numbers of EPCs in the circulation under normal conditions. The level of EPCs is considered to be indicative of restoration capacity in case of vascular disease and potential damage. Lower EPC levels are also considered as a risk factor in cardiovascular diseases. In this study, our aim was to investigate circulating EPCs in PNH and their relationship with thrombosis. Seventeen patients with PNH, 18 patients with aplastic anemia and 10 healthy volunteers were included in the study. CD309, CD133 and CD34 antibodies were used in order to determine circulating EPCs by flow cytometry and cells which expressed all three antibodies were analyzed as EPC. Prepared samples were read using a prepared list mode software for endothelial progenitor cells on FACS Diva software in BD FACS Canto II device with 6 color lasers and a total of 1,000,000 cells per analysis were evaluated. EPC levels were compared between untreated PNH patients and who were on eculizumab therapy. Statistical analysis was performed using SPSS 22.0 software. The distribution of variables was evaluated by Kolmogorov-Smirnov test, the analysis of quantitative data was evaluated by ANOVA, Kruskal-Wallis, Mann-Whitney U tests and the analysis of the qualitative data was evaluated by chi-square test.Findings and Discussion: The thrombotic complications were observed in five PNH patients. All of these patients had a history of portal vein thrombosis. One of them also had a history of peripheral arterial disease and amputation related to this. There was not a significant difference in EPC levels between patients with and without a history of thrombosis (p>0,05). We also did not find any significant difference between levels of EPC's in PNH groups with or without eculizumab therapy (p˃0,05). There was no significant difference in levels of EPC between aplastic anemia and PNH groups (p ˃ 0,05). However, we found a significant positive correlation between the levels of EPC and LDH in multivariate analysis (p < 0,05). This finding suggests that hemolysis causes vascular endothelium and promotes new blood vessel formations. Increased EPCs in PNH might be an indirect indicator for vascular endothelium damage in PNH.TableGeneral Features and Rates of EPC of PNH, AA, Healthy Volunteers GroupsAplastic Anemia groupPNH groupControl grouppAgemean±s.smedian (min-max)40.0±14.7 37.5 (20.0-67.0)41.9±13.9 43.0 (19.0-78.0)29.3±3.5 29.5(24.0-34.0)0.047SexFemale n-% Male n-%7 38,9% 11 61.1%9 52.9% 8 47.1%5 50% 5 50%0.687EPC(%)mean±s.s median (min-max)0.2% 0.2% 0.1% (0.0-0.6%)0.3%±0.3% 0.1% (0.0-0.9%)0.1%±0.0% %0,0(%0,0-0,2)0.393All Events (x1000)mean±s.s median (min-max)617±172* 565 (360-914)588±255* 471 (250-1000)878±143 950(655-1000)0.003CD309 and CD34mean±s.s median (min-max)0.003±0.002 0.002 (0.001-0.007)0.005±0.004 0.000-0.011)0.001±0.001 0.001 (0.000-0.002)0.009CD133mean±s.s median (min-max)45.8±36.3 58.3 (0.0-88.2)45.8±39.6 60 (0.0-94.7)42.0±19.4 46.4 (11.1-81.3)0.867ANOVA / Kruskal-Wallis / Mann-Whitney U test / Chi-square test*The difference with the control group, p <0.05EPCs: Endothelial progenitor cells DisclosuresYenerel:Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Effect of omega-3 polyunsaturated fatty acid treatment over mechanical allodynia and depressive-like behavior associated with experimental diabetes

Neuropathic pain and depression are very common comorbidities in diabetic patients. As the pathophysiological mechanisms are very complex and multifactorial, current treatments are only symptomatic and often worsen the glucose control. Thus, the search for more effective treatments are extremely urgent. In this way, we aimed to investigate the effect of chronic treatment with fish oil (FO), a source of omega-3 polyunsaturated fatty acid, over the mechanical allodynia and in depressive-like behaviors in streptozotocin-diabetic rats. It was observed that the diabetic (DBT) animals, when compared to normoglycemic (NGL) animals, developed a significant mechanical allodynia since the second week after diabetes induction, peaking at fourth week which is completely prevented by FO treatment (0.5, 1 or 3g/kg). Moreover, DBT animals showed an increase of immobility frequency and a decrease of swimming and climbing frequencies in modified forced swimming test (MFST) since the second week after diabetes injection, lasting up at the 4th week. FO treatment (only at a dose of 3g/kg) significantly decreased the immobility frequency and increased the swimming frequency, but did not induce significant changes in the climbing frequency in DBT rats. Moreover, it was observed that DBT animals had significantly lower levels of BDNF in both hippocampus and pre frontal cortex when compared to NGL rats, which is completely prevented by FO treatment. In conclusion, our study demonstrates that FO treatment was able to prevent the mechanical allodynia and the depressive-like behaviors in DBT rats, which seems to be related to its capacity of BDNF level restoration.

Conotoxin Interactions with α9α10-nAChRs: Is the α9α10-Nicotinic Acetylcholine Receptor an Important Therapeutic Target for Pain Management?

The α9α10-nicotinic acetylcholine receptor (nAChR) has been implicated in pain and has been proposed to be a novel target for analgesics. However, the evidence to support the involvement of the α9α10-nAChR in pain is conflicted. This receptor was first implicated in pain with the characterisation of conotoxin Vc1.1, which is highly selective for α9α10-nAChRs and is an efficacious analgesic in chronic pain models with restorative capacities and no reported side effects. Numerous other analgesic conotoxin and non-conotoxin molecules have been subsequently characterised that also inhibit α9α10-nAChRs. However, there is evidence that α9α10-nAChR inhibition is neither necessary nor sufficient for analgesia. α9α10-nAChR-inhibiting analogues of Vc1.1 have no analgesic effects. Genetically-modified α9-nAChR knockout mice have a phenotype that is markedly different from the analgesic profile of Vc1.1 and similar conotoxins, suggesting that the conotoxin effects are largely independent of α9α10-nAChRs. Furthermore, an alternative mechanism of analgesia by Vc1.1 and other similar conotoxins involving non-canonical coupling of GABAB receptors to voltage-gated calcium channels is known. Additional incongruities regarding α9α10-nAChRs in analgesia are discussed. A more comprehensive characterisation of the role of α9α10-nAChRs in pain is crucial for understanding the analgesic action of conotoxins and for improved drug design.

Availability of Large Seed-Dispersers for Restoration of Degraded Tropical Forest

An estimated 63% of Southeast Asian forests are classed as disturbed and secondary as a result of human activity. Many of these forests remain important for biodiversity conservation and ecosystem services so there is much interest in their capacity for restoration. The role of larger animals as seed dispersers in natural regeneration is well-attested since they are often the only agent by which large-seeded trees can effectively disperse. This is especially important for late successional shade-tolerant species which might otherwise be excluded from disturbed sites. However, many larger animals are sensitive to habitat degradation so may be lost from the very areas that require them. We investigated the persistence of a suite of large mammals that are known seed-dispersers and are also threatened species, in a degraded site in lowland south-central Sumatra. We used camera traps and field observations to relate their distributions to prevailing vegetation conditions. Although most species were more frequently detected in the more intact areas, most were able to occupy habitats with high levels of disturbance and population densities were relatively high. It is clear that severe habitat degradation does not necessarily lead to the immediate loss of large-bodied seed dispersers, so ensuring adequate protection for these species from external threats, such as hunting, must be built into management plans for restoration concessions.

Прогнозирование субклинического атеросклероза сонных артерий на основании параметров отрицательного в отношении ишемии нагрузочного теста

to elucidate relationship between parameters of negative ischemic stress test and subclinical atherosclerosis of carotid arteries.Electrocardiographic stress test on treadmill and ultrasound study of carotid arteries (CA) were carried out in 204 patients (100 women and 104 men, mean age 54.16±8.07 years without verified ischemic heart disease and with ≥ 1 traditional factors of cardiovascular risk). Measurements of intima media thickness (IMT) in three extracranial CA segments and identification of atherosclerotic plaques (AP) were used for detection of subclinical atherosclerosis. CA total atherosclerotic plaque area (TAPA) was calculated when appropriate.Multifactorial regression analysis revealed the following predictors of increased IMT and TAPA: physical working capacity, increment and reserve of heart rate (HR), HR restoration, and increment of systolic arterial pressure (SAP). Presence of atherosclerotic plaque was associated with SAP rise > 42% during exercise test and slow HR restoration (≤42 bpm at 2-nd minute of recovery period).Analysis of nonelectrocardiographic parameters of negative relative to ischemia induction exercise test allows predicting severity of atherosclerotic changes in CA. The information obtained can supplement assessment of traditional factors of cardiovascular risk.

An Experimental Study on Hybrid Noncompression CF Bracing and GF Sheet Wrapping Reinforcement Method to Restore Damaged RC Structures

We describe a novel technique for restoration of reinforced concrete (RC) structures that have sustained damage during an earthquake. The reinforcement scheme described here is a hybrid seismic retrofitting technique that combines noncompression X-bracing using CF with externally bonded GF sheets to strengthen RC structures that have sustained damage following an earthquake. The GF sheet is used to improve the ductility of columns, and the noncompression CF X-bracing system, which consists of CF bracing and anchors to replace the conventional steel bracing and bolt connections, is used to increase the lateral strength of the framing system. We report seismic restoration capacity, which enables reuse of the damaged RC frames via the hybrid CF X-bracing and GF sheet wrapping system. Cyclic loading tests were carried out to investigate hysteresis of the lateral load-drift relations, as well as the ductility. The GF sheet significantly improved the ductility of columns, resulting in a change in failure mode. The strengthening effect of conventional CF sheets used in columns is not sufficient with respect to lateral strength and stiffness. However, this study results in a significant increase in the strength of the structure due to the use of CF X-bracing and inhibited buckling failure of the bracing. This result can be exploited to develop guidelines for the application of the reinforcement system to restore damaged RC structures.

Quantitative assessment of disaster resilience: An empirical study on the importance of post-disaster recovery costs

Recovery costs are as important as losses for decision-making in disaster mitigation given that recovery costs reflect the restorative capacity of affected regions. Hence, this study analyses recovery costs. Results show that the total post-disaster recovery costs in Korea are on average one and a half times the actual losses, mainly because of the private sector. This ratio depends on the hazard type. In Korea, the highest ratio (almost four) arises after heavy rains because of the weak restorative capacity of river systems to heavy rains. The study introduces the community resilience cost index (CRCI), obtained by adding recovery costs and losses and dividing the resultant sum by the magnitude of exposure levels to quantify national and regional resilience. Results show that the recovery cost is an essential component for assessing resilience. In particular, the high ratio of recovery costs to losses owing to heavy rains changes the priorities determined by losses only. The key contribution of this work is that the ratios between losses and recovery costs can estimate the recovery costs based on losses given the high correlation. The study ascertains the most vulnerable system and explains why this is so through analyzing the recovery costs. The importance of recovery costs in quantitative resilience assessments is exemplified. Last, the CRCI is transferrable to other countries to assess their resilience and to establish their priorities and vulnerabilities.

The restorative capacities of victim impact statements: analysis of the victim—judge communication dyad in the sentencing of homicide offenders

ABSTRACTVictim impact statements (VISs) are said to introduce restorative elements into the sentencing hearing for the benefit of victims. Roberts and Erez (2004) argue that a key restorative feature of VISs is their potential to generate reciprocal communication between judge and victim: victims have the opportunity to speak about the impact of the crime and the court has the opportunity to acknowledge the harm suffered and validate victims' experiences. Drawing from the findings of a small qualitative study of VISs in homicide sentencing hearings in New South Wales (NSW), Australia, this paper examines the communicative potential of VISs. While the institutional context of VISs in common law jurisdictions constrains their communicative capacities, nonetheless oral VISs provide victims with a valuable opportunity to speak and be heard. Furthermore, while in the hearings studied there was little direct communication between judge and victim, this study reveals that VISs provide a context in which other, m...

In vivo functional analysis of a nuclear restorer PPR protein.

BackgroundNuclear restorers of cytoplasmic male fertility (CMS) act to suppress the male sterile phenotype by down-regulating the expression of novel CMS-specifying mitochondrial genes. One such restorer gene is Rfo, which restores fertility to the radish Ogura or ogu CMS. Rfo, like most characterized restorers, encodes a pentatricopeptide repeat (PPR) protein, a family of eukaryotic proteins characterized by tandem repeats of a 35 amino acid motif. While over 400 PPR genes are found in characterized plant genomes and the importance of this gene family in organelle gene expression is widely recognized, few detailed in vivo assessments of primary structure-function relationships in this protein family have been conducted.ResultsIn contrast to earlier studies, which identified 16 or 17 PPR domains in the Rfo protein, we now find, using a more recently developed predictive tool, that Rfo has 18 repeat domains with the additional domain N-terminal to the others. Comparison of transcript sequences from pooled rfo/rfo plants with pooled Rfo/Rfo plants of a mapping population led to the identification of a non-restoring rfo allele with a 12 bp deletion in the fourth domain. Introduction into ogu CMS plants of a genetic construct in which this deletion had been introduced into Rfo led to a partial loss in the capacity to produce viable pollen, as assessed by vital staining, pollen germination and the capacity for seed production following pollination of CMS plants. The degree of viable pollen production among different transgenic plants roughly correlated with the copy number of the introduced gene and with the reduction of the levels of the ORF138 CMS-associated protein. All other constructs tested, including one in which only the C-terminal PPR repeat was deleted and another in which this repeat was replaced by the corresponding domain of the related, non-restoring gene, PPR-A, failed to result in any measure of fertility restoration.ConclusionsThe identification of the additional PPR domain in Rfo indicates that the protein, apart from its N-terminal mitochondrial targeting presequence, consists almost entirely of PPR repeats. The newly identified rfo allele carries the same 4 amino acid deletion as that found in the neighboring, related, non-restoring PPR gene, PPR-A. Introduction of this four amino acid deletion into a central domain the Rfo protein, however, only partially reduces its restoration capacity, even though this alteration might be expected to alter the spacing between the adjoining repeats. All other tested alterations, generated by deleting specific PPR repeats or exchanging repeats with corresponding domains of PPR-A, led to a complete loss of restorer function. Overall we demonstrate that introduction of targeted alterations of Rfo into ogu CMS plants provides a sensitive in vivo readout for analysis of the relationship between primary structure and biological function in this important family of plant proteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-014-0313-4) contains supplementary material, which is available to authorized users.

Fragile audio watermarking with perfect restoration capacity based on an adapted integer transform

We propose a novel audio watermarking scheme which can recover the original audio carrier perfectly if the watermarked audio is modified. Besides, we can adjust the maximum tampered rate allowed and the quality of watermarked audio flexibly as required. In the scheme, an efficient generalized integer transform is improved to embed watermark data which are composed of least significant bits(LSBs) of averages in each patch, reference-bits and check-bits. LSBs are needed in the inverse transform. Then, by comparing the extracted check-bits and calculated ones, the modified area can be localized. Finally, reliable reference-bits and samples data help us reconstruct the original audio without errors. The efficiency of the proposed method is theoretically and experimentally verified.

Size does matter: an integrative in vivo-in silico approach for the treatment of critical size bone defects.

Although bone has a unique restorative capacity, i.e., it has the potential to heal scarlessly, the conditions for spontaneous bone healing are not always present, leading to a delayed union or a non-union. In this work, we use an integrative in vivo - in silico approach to investigate the occurrence of non-unions, as well as to design possible treatment strategies thereof. The gap size of the domain geometry of a previously published mathematical model was enlarged in order to study the complex interplay of blood vessel formation, oxygen supply, growth factors and cell proliferation on the final healing outcome in large bone defects. The multiscale oxygen model was not only able to capture the essential aspects of in vivo non-unions, it also assisted in understanding the underlying mechanisms of action, i.e., the delayed vascularization of the central callus region resulted in harsh hypoxic conditions, cell death and finally disrupted bone healing. Inspired by the importance of a timely vascularization, as well as by the limited biological potential of the fracture hematoma, the influence of the host environment on the bone healing process in critical size defects was explored further. Moreover, dependent on the host environment, several treatment strategies were designed and tested for effectiveness. A qualitative correspondence between the predicted outcomes of certain treatment strategies and experimental observations was obtained, clearly illustrating the model's potential. In conclusion, the results of this study demonstrate that due to the complex non-linear dynamics of blood vessel formation, oxygen supply, growth factor production and cell proliferation and the interactions thereof with the host environment, an integrative in silico-in vivo approach is a crucial tool to further unravel the occurrence and treatments of challenging critical sized bone defects.

Eco-existential positive psychology: Experiences in nature, existential anxieties, and well-being.

Numerous scholars have explored the notion that our relationship with nature is essential to our well-being, and some have suggested that we have an evolved inclination to affiliate with nature. A substantial body of research supports these hypotheses, and demonstrates both the restorative and additive capacity of affiliating with nature. This article posits that experiences with the natural environment play a fundamentally important role in addressing the 6 existential anxieties of identity, happiness, isolation, meaning in life, freedom, and death—a perspective that we call Eco-Existential Positive Psychology. Moreover, we propose that affiliating with nature affords us the opportunity to be fully flourishing human beings. This article provides supporting evidence for Eco-Existential Positive Psychology via an interdisciplinary literature review.

Reversible Data Hiding for DNA Sequences and Its Applications

As the blueprint of vital activities of most living things on earth, DNA has important status and must be protected perfectly. And in current DNA databases, each sequence is stored with several notes that help to describe that sequence. However, these notes have no contribution to the protection of sequences. In this paper, the authors propose a reversible data hiding method for DNA sequences, which could be used either to embed sequence-related annotations, or to detect and restore tampers. When embedding sequence annotations, the methods works in low embedding rate mode. Only several bits of annotations are embedded. When used for tamper detection and tamper restoration, all possible embedding positions are utilized to assure the maximum restoration capacity.

ANÁLISE DE CORPOS HÍDRICOS CONSTITUINTES DO RIACHO DAS PIABAS EM CAMPINA GRANDE/PB

Renewable natural resources are considered inexhaustible arising from to capacity for restoration after use by man , when used appropriately. In this context, this research was carried out in the catchment of the creek Piabas aiming to assess the water quality constituents of water bodies from the creek minnows for various purposes . Eight (8 ) water samples were collected in shallow natural sources such as streams , ponds and spring ; and sub - surface sources such as wells and ponds and analyzed the hydrogen potential ( pH ) , electrical conductivity (EC) , turbidity and dissolved oxygen ( DO) . The Electrical Conductivity parameter of irrigation water ( EC w ) has no degree of restriction ( < 0.70 dS m - 1 ) mild and moderate ( 0.70 to 3.00 dS m - 1 ) , with a minimum value of 0 29 dS m-1 and a maximum of 2.23 dS m- 1. Turbidity in the highest value was 1.9 and the lowest 1.3 NTU . In all samples the dissolved oxygen values are greater than 5 mg / L recommended by the MS 2914/2011.As samples can be used for animals , but there restrictions with regard for human consumption and irrigation.

On Signaling-Free Failure Dependent Restoration in All-Optical Mesh Networks

Failure dependent protection (FDP) is known to achieve optimal capacity efficiency among all types of protection, at the expense of longer recovery time and more complicated signaling overhead. This particularly hinders the usage of FDP in all-optical mesh networks. As a remedy, this paper investigates a new restoration framework that enables all-optical fault management and device configuration via state-of-the-art failure localization techniques, such as the FDP restoration process. It can be implemented without relying on any control plane signaling. With the proposed restoration framework, a novel spare capacity allocation problem is defined and is further analyzed on circulant topologies for any single link failure, aiming to gain a solid understanding of the problem. By allowing reuse of monitoring resources for restoration capacity, we are particularly interested in the monitoring resource hidden property, where less or even no monitoring resources are consumed as more working traffic is in place. To deal with general topologies, we introduce a novel heuristic approach to the proposed spare capacity allocation problem, which comprises a generic FDP survivable routing scheme followed by a novel monitoring resource allocation method. Extensive simulation is conducted to examine the proposed scheme and verify the proposed restoration framework.

Planning Restoration of Vital Infrastructure Services Following Hurricane Sandy: Lessons Learned for Energy and Transportation

Hurricane Sandy arrived on October 29, 2012 with enormous adverse impacts on one of the largest metropolitan areas in the world, the New York region, including its electric power and transportation systems that disrupted the social and economic fabric of a wide geographic area. How these services were restored is an important basis for proactively designing robust public services not only in areas affected by Hurricane Sandy but also for many similar areas and events worldwide. Recovery rates are one important indicator of consequences of disaster. Selected physical and social measures of recovery are analyzed for New York City electricity and rail transit services following Hurricane Sandy to capture the ability of these services to be restored over various time periods, and to illustrate the use of indicators of restoration for infrastructure service resilience analyses for disaster management and planning. Electricity impacts and recovery are presented in user-oriented terms as the ratio of customers affected and restored to both customers without service and total customers served in the period following the hurricane. Results showed that restoration rates varied among the boroughs of NYC potentially reflecting differences in infrastructure resilience and exposure conditions. Rail transit impacts and recovery were analyzed in terms of both the restoration of the two dozen subway lines as a physical measure and ridership by station as a user or social measure. Line recovery analyses showed that within about a couple of weeks of the storm almost 80 percent of the lines were fully restored, almost 20 percent were partially restored, and complete suspensions were rare indicating a high degree of restoration capacity. Ridership measured at stations was compared to levels and rates of change over various time periods around the storm period, as well as from the previous year. High correlations in ridership between single days before and after the storm indicated little redistribution of ridership across stations between those time periods, however, rates of change indicated about a 14–16 percent decline in ridership system-wide within a two week period following the storm relative to the same time period the year before, recovering later, possibly reflecting slower rates of social recovery relative to the recovery of the physical transit systems. A longer period of service quality effects occurred due to lingering equipment damage potentially attributed for example to water damage and corrosion from saltwater. These findings point to the importance of recovery time as at least an initial guide to ways of systematizing service restoration measures and are a foundation for physical, social, and institutional adaptation strategies some of which are already being put in place. Larger considerations remain however in interpreting recovery restoration goals and who decides them.

The interactive effects of climate change, riparian management, and a nonnative predator on stream-rearing salmon.

Predicting how climate change is likely to interact with myriad other stressors that threaten species of conservation concern is an essential challenge in aquatic ecosystems. This study provides a framework to accomplish this task in salmon-bearing streams of the northwestern United States, where land-use-related reductions in riparian shading have caused changes in stream thermal regimes, and additional warming from projected climate change may result in significant losses of coldwater fish habitat over the next century. Predatory, nonnative smallmouth bass have also been introduced into many northwestern streams, and their range is likely to expand as streams warm, presenting an additional challenge to the persistence of threatened Pacific salmon. The goal of this work was to forecast the interactive effects of climate change, riparian management, and nonnative species on stream-rearing salmon and to evaluate the capacity of restoration to mitigate these effects. We intersected downscaled global climate forecasts with a local-scale water temperature model to predict mid- and end-of-century temperatures in streams in the Columbia River basin. We compared one stream that is thermally impaired due to the loss of riparian vegetation and another that is cooler and has a largely intact riparian corridor. Using the forecasted stream temperatures in conjunction with fish-habitat models, we predicted how stream-rearing chinook salmon and bass distributions would change as each stream warmed. In the highly modified stream, end-of-century warming may cause near total loss of chinook salmon-rearing habitat and a complete invasion of the upper watershed by bass. In the less modified stream, bass were thermally restricted from the upstream-most areas. In both systems, temperature increases resulted in higher predicted spatial overlap between stream-rearing chinook salmon and potentially predatory bass in the early summer (two- to fourfold increase) and greater abundance of bass. We found that riparian restoration could prevent the extirpation of chinook salmon from the more altered stream and could also restrict bass from occupying the upper 31 km of salmon-rearing habitat. The proposed methodology and model predictions are critical for prioritizing climate-change adaptation strategies before salmonids are exposed to both warmer water and greater predation risk by nonnative species.

Synthesis of the 18th ArgoSpine Symposium.

The subject of this 18th Symposium of ArgoSpine Association was the space of the intervertebral discs. Space of the intervertebral discs must be initially defined anatomically and histologically. A geometrical rebuilding in 3D is possible and must allow a modeling of the intervertebral discs. The physiology of the disc, its nutrition, must be known, in particular that of the center of the disc. The disc constitutes the base of the balance of the rachis, balances which can be only dynamic. The degenerative cascade by the loss of the proteoglycans involves the loss of the biomechanical properties of the disc. The consequences of this degenerative cascade are the base of all the vertebral pathology of origin of the intervertebral discs and even of the posterior articular facets. The origin of the pains and the diagnosis, especially at the lumbar level, are studied by the speakers. Traumatology of the intervertebral discs is the object of a particular chapter. Finally, the average therapeutic ones, that is, decompression of the intervertebral discs, fusion of the intervertebral discs, the recovery of mobility of the intervertebral discs, and the capacity of restoration of space of the intervertebral discs, are studied in detail. The infection of the disc is studied in detail.

Invited Commentary

Invited Commentary

Candesartan Induces a Prolonged Proangiogenic Effect and Augments Endothelium-Mediated Neuroprotection after Oxygen and Glucose Deprivation: Role of Vascular Endothelial Growth Factors A and B

Angiogenesis is a key component of recovery after stroke. Angiotensin II receptor blocker (ARB) treatment improves neurobehavioral outcome and is associated with enhanced angiogenesis after stroke. The purpose of this study is to investigate the temporal pattern of the ARB proangiogenic effect in the ischemic brain and its association with vascular endothelial growth factors VEGF-A and VEGF-B. Wistar rats were exposed to 90-minute middle cerebral artery occlusion and treated with candesartan (1 mg/kg) at reperfusion. The proangiogenic potential of the cerebrospinal fluid was determined at 8, 24, 48, and 72 hours using an in vitro Matrigel tube formation assay. In addition, the expression of VEGF-A and VEGF-B was measured in brain homogenates using Western blotting at the same time points. A single candesartan dose induced a prolonged proangiogenic effect and a prolonged upregulation of VEGF-A and VEGF-B in vivo. In the ischemic hemisphere, candesartan treatment was associated with stabilization of hypoxia-inducible factor-1α and preservation of angiopoietin-1. The effect of ARB treatment on endothelial cells was studied in vitro. Our results identified brain endothelial cells as one target for the action of ARBs and a source of the upregulated VEGF-A and VEGF-B, which exerted an autocrine angiogenic response, in addition to a paracrine neuroprotective effect. Taken together, this study highlights the potential usefulness of augmenting the endogenous restorative capacity of the brain through the administration of ARBs.